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Utility of the Sendai Consensus Guidelines for Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Systematic Review
Abstract
The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN.
Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG-ve.
Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24 % were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG-ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52 % and the NPV of SCG-ve neoplasms ranged from 90 to 100 %. Overall, there were 150/501 (29.9 %) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90 %) of benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99 %) of SCG-ve BD-IPMNs were benign.
The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.
... However, numerous surgical studies published subsequently demonstrated that the SCG had a low positive predictive value (PPV) whereby many patients with benign BD-IPMNs had undergone unnecessary surgical resection according to the guidelines. 7,8 Hence, a new revised guideline termed the Fukuoka Consensus Guidelines (FCG) was proposed in 2012. 5 These new guidelines classified patients with IPMNs into 3 categories-high risk, worrisome risk and low risk. ...
... 8 EUS was recommended for IPMNs with worrisome risk features. 7 Two recent systematic reviews 7,8 which evaluated the utility of the SCG and FCG found that both guidelines had a low PPV and high NPV. The FCG seemed to have a better PPV than the SCG but a lower NPV. ...
... The FCG seemed to have a better PPV than the SCG but a lower NPV. 7,8 The aim of the present study was to perform an updated systematic review to assess the clinical utility of the SCG and FCG for the management of IPMNs. ...
Background:
This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN).
Methods:
A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs.
Results:
Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign.
Conclusion:
The FCG had a higher PPV compared to the SCG. However, the NPV of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines.
... It was also recommended that only branch duct (BD) IPMNs [ 30 mm in size should be resected, whereas smaller lesions without associated symptoms, mural nodules, or MD dilatation could be followed. However, the positive predictive value (PPV) of the 2006 guidelines for malignant BD-IPMN was low, and recommending resection was unsatisfactory [5]. Hence, the 2006 guidelines were updated in 2012. ...
... However, these guidelines are based on expert opinion rather than clinical evidence [5,7]. Although several studies attempted to validate these guidelines, their utility and safety remain controversial [8][9][10][11][12][13]. ...
... In 2006, international consensus guidelines were published for managing IPMN, and surgical indications were proposed [4]. The diagnostic value of each individual factor in the 2006 guidelines has been validated in recent systematic reviews [5,9,17]. Goh et al. [5] demonstrated that the 2006 guidelines had a low PPV (11-52%), which led to the resection of a large number of benign IPMNs. ...
Background:
International consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) were revised in 2012.
Aims:
We aimed to evaluate the clinical utility of each predictor in the 2006 and 2012 guidelines and validate the diagnostic value and surgical indications.
Methods:
Forty-two patients with surgically resected IPMNs were included. Each predictor was applied to evaluate its diagnostic value.
Results:
The 2012 guidelines had greater accuracy for invasive carcinoma than the 2006 guidelines (64.3 vs. 31.0%). Moreover, the accuracy for high-grade dysplasia was also increased (48.6 vs. 77.1%). When the main pancreatic duct (MPD) size ≥8 mm was substituted for MPD size ≥10 mm in the 2012 guidelines, the accuracy for high-grade dysplasia was 80.0%.
Conclusions:
The 2012 guidelines exhibited increased diagnostic accuracy for invasive IPMN. It is important to consider surgical resection prior to invasive carcinoma, and high-risk stigmata might be a useful diagnostic criterion. Furthermore, MPD size ≥8 mm may be predictive of high-grade dysplasia.
... [3] This guidelines seemed highly sensitive to detect malignant or premalignant BD-IPMNs; under this guideline, the most suspicious BD-IPMNs (i.e., highgrade dysplasia [HGD] or invasive cancer [IC]) would be resected. [4][5][6][7] However, the low specificity of lesions with HGD or IC on final pathology reports indicate a limitation of the 2006 Sendai guideline. [4,6,7] Some patients had undergone unnecessary operations because of the Sendai guideline, including complicated pancreaticoduodenectomies. Thus, the revised 2012 Sendai consensus guideline (i.e., Fukuoka guideline) leans toward a relatively conservative approach for pancreatic IPMNs. ...
... [4][5][6][7] However, the low specificity of lesions with HGD or IC on final pathology reports indicate a limitation of the 2006 Sendai guideline. [4,6,7] Some patients had undergone unnecessary operations because of the Sendai guideline, including complicated pancreaticoduodenectomies. Thus, the revised 2012 Sendai consensus guideline (i.e., Fukuoka guideline) leans toward a relatively conservative approach for pancreatic IPMNs. The Fukuoka guideline proposed "worrisome features" and "highrisk stigmata" categories in an attempt for further stratify patients regarding risk of malignancy. ...
... For predicting malignancy, many studies reported a low PPV (11%-52%) but a high NPV (90%-100%) using the Sendai guideline for BD-IPMN, for mucinous CLPs, and even for all CLPs. [4,6,7,19,20] However, some studies reported a missed malignancy using the Sendai guidelines. [4,21,22] According to our study results, the PPV of the highrisk group under the Sendai and Fukuoka guidelines were 35.1% and 43.3%, respectively, indicating a slightly better predictive value for the "Fukuoka high-risk" group. ...
This study aimed to evaluate the utility of the 2006 Sendai and 2012 Fukuoka guidelines for differentiating malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas from benign IPMN.
Between January 2000 and March 2015, a total of 138 patients underwent surgery and had a pathologically confirmed pancreatic IPMN. Clinicopathological parameters were reviewed, and all patients were classified according to both the 2006 Sendai and 2012 Fukuoka guidelines. Univariate and multivariate analyses were used for identifying significant factors associated with malignancy in IPMN.
There were 9 high-grade dysplasia (HGD) and 37 invasive cancers (ICs) in the 138 patients. The positive predictive value (PPV) and negative predictive value (NPV) of the Sendai and Fukuoka guidelines for HGD/IC was 35.1%, 43.3%, 100%, and 85.4%, respectively. Of the 36 patients with worrisome features using the Fukuoka guideline, 7 patients had HGD/IC in their IPMNs. According to the multivariate analysis, jaundice, tumors of ≥3 cm, presence of mural nodule on imaging, and aged <65 years were associated with HGD/IC in patients with IPMN.
The Sendai guideline had a better NPV, but the Fukuoka guideline had a better PPV. We suggest that patients with worrisome features based on the Fukuoka guideline be aggressively managed.
... Imaging is the most common method of diagnosis and follow-up for pancreatic cysts. IPMN management is guided by the presence of features of concern, e.g., the size and growth rate of the cysts [4,5]. When the cysts are < 5 mm in diameter, the likelihood of malignancy is low, and further evaluation may not be necessary. ...
... Moreover, while MCnnU-net appears to have a slightly better performance than the MC3DU-Net, with a Dice score of 0.83 versus 0.80 for all cyst sizes, the difference is not statistically different and is above the manual annotation observer variability. Table 3 Results of the effect of the ROI on the detection of pancreatic cysts with diameter > 10 mm, > 5 mm, and all cysts for the multisequence cascaded 3D U-Net (MC3DU-Net) with five ROIs: (1) pancreas ROI computed from the TSE sequence (Pancreas ROI); (2) pancreas ROI created from the manual pancreas segmentation in the TSE sequence (Pancreas ROI GT ); (3) manual ground truth segmentation of the pancreas (Pancreas GT ); (4) axis-aligned bounding box tightly enclosing the ground truth segmentation of the pancreas (BB Pancreas); (5) Our study has several limitations. First, the method failed for two excluded studies in which there was large patient movement between the MRCP and TSE sequences. ...
Radiological detection and follow-up of pancreatic cysts in multisequence MRI studies are required to assess the likelihood of their malignancy and to determine their treatment. The evaluation requires expertise and has not been automated. This paper presents MC3DU-Net, a novel multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI studies consisting of coronal MRCP and axial TSE MRI sequences.
MC3DU-Net leverages the information in both sequences by computing a pancreas Region of Interest (ROI) segmentation in the TSE MRI scan, transferring it to MRCP scan, and then detecting and segmenting the cysts in the ROI of the MRCP scan. Both the voxel-level ROI of the pancreas and the segmentation of the cysts are performed with 3D U-Nets trained with Hard Negative Patch Mining, a new technique for class imbalance correction and for the reduction in false positives.
MC3DU-Net was evaluated on a dataset of 158 MRI patient studies with a training/validation/testing split of 118/17/23. Ground truth segmentations of a total of 840 cysts were manually obtained by expert clinicians. MC3DU-Net achieves a mean recall of 0.80 ± 0.19, a mean precision of 0.75 ± 0.26, a mean Dice score of 0.80 ± 0.19 and a mean ASSD of 0.60 ± 0.53 for pancreatic cysts of diameter > 5 mm, which is the clinically relevant endpoint.
MC3DU-Net is the first fully automatic method for detection and segmentation of pancreatic cysts in MRI. Automatic detection and segmentation of pancreatic cysts in MRI can be performed accurately and reliably. It may provide a method for precise disease evaluation and may serve as a second expert reader.
... Increased pancreatic cyst detection alone poses a significant cost burden to the healthcare system given the high cost of pancreatic resections and the high rate of complications associated with pancreatectomy 53 . The potential burden is amplified by the low specificity to identify and resect high-grade or invasive cysts in current practice 11,12,51 . Three prior studies evaluated the cost-effectiveness of IPMN management. ...
... Given considerable effort in the field to create diagnostic assays or management nomograms to stratify risk groups, we considered specificity a modifiable variable and calculated that a 52% and 67% specificity are required for Surveillance to be favored over Surgery and Do Nothing, respectively. Current surgical consensus guidelines achieve only 22-38% specificity 11,51 , however, there is no superior alternative. The American Gastroenterological Association guidelines, which evaluate many of the same clinical characteristics with a more stringent criteria for resection shows higher specificity, 64% in a pooled analysis, but the sensitivity is only 35-62% [60][61][62] . ...
Background
Detection of cystic lesions of the pancreas has outpaced our ability to stratify low-grade cystic lesions from those at greater risk for pancreatic cancer, raising a concern for overtreatment.
Methods
We developed a Markov decision model to determine the cost-effectiveness of guideline-based management for asymptomatic pancreatic cysts. Incremental costs per quality-adjusted life year gained and survival were calculated for current management guidelines. A sensitivity analysis estimated the effect on cost-effectiveness and mortality if overtreatment of low-grade cysts is avoided, and the sensitivity and specificity thresholds required of methods of cyst stratification to improve costs expended.
Results
“Surveillance” using current management guidelines had an incremental cost-effectiveness ratio of $171,143/quality adjusted life year compared with no surveillance or operative treatment (“do nothing”). An incremental cost-effectiveness ratio for surveillance decreases to $80,707/quality adjusted life year if the operative overtreatment of low-grade cysts was avoided. Assuming a societal willingness-to-pay of $100,000/quality adjusted life year, the diagnostic specificity for high-risk cysts must be >67% for surveillance to be preferred over surgery and “do nothing.” Changes in sensitivity alone cannot make surveillance cost-effective. Most importantly, survival in surveillance is worse than “do nothing” for 3 years after cyst diagnosis, although long-term survival is improved. The disadvantage is eliminated when overtreatment of low-grade cysts is avoided.
Conclusion
Current management of pancreatic cystic lesions is not cost-effective and may increase mortality owing to overtreatment of low-grade cysts. The specificity for risk stratification for high-risk cysts must be greater than 67% to make surveillance cost-effective.
... 13 Although the sensitivity, specificity, and overall accuracy of the IAP guidelines have been reported, the influence of these guidelines on clinical practice over time has not been fully analyzed. 8,9,[14][15][16][17][18][19][20] If guidelines are helpful in identifying patients with high risk disease, then their implementation and utilization (resecting only patients within guideline recommendations) should correlate with the percentage of patients with high risk disease on final pathology. We, therefore, hypothesized that the development and implementation of these guidelines should have increased the percentage of patients who had undergone resection for an IPMN with high-risk clinical and radiographic features. ...
... However, in addition to radiological features, new biological markers for high-risk disease are urgently needed to improve the management of these patients, particularly in those with BD-IPMN. (21) 97 (25) 57 (20) 101 (19) 0.041 (20) 45 (25) 10 (7) 64 (22) <0.001 Unknown 28 (5) 2 (1) 15 (11) 11 (4) Wall thickening, n (%) Yes 38 (6) 11 (6) 8 (6) 19 (7) 0.89 Unknown 44 (7) 3 (2) 15 (11) 26 (9) At least 1 radiological feature, n (%) ...
Objective:
To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes.
Background:
Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease.
Methods:
Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000-2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006-2012), Fukuoka (FCG, after 2012)].
Results:
The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63).
Conclusion:
Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed.
... 4 This approach generated a high rate of resections for IPMNs that exhibited only low-grade dysplasia at final histology. 5 In time, as risk factors for malignancy were more carefully identified, guidelines evolved. The 2012 and 2017 International Guidelines were more conservative and identified "high-risk stigmata" (HRS), which are strongly associated with malignancy and warrant pancreatectomy, and "worrisome features" (WF), which represent an intermediate-risk level. ...
Background
Surgical resection of intraductal papillary mucinous neoplasms is based on preoperative high-risk stigmata/worrisome features, but the risk of overtreatment remains high. The aim of this study was to evaluate surgical indications and perioperative and long-term complications in patients with low-grade intraductal papillary mucinous neoplasms.
Methods
Patients who underwent surgical resection between 2009 and 2018 with a final histology of low-grade intraductal papillary mucinous neoplasms were included. Surgical indications, type of surgery, and short- and long-term outcomes were evaluated.
Results
A significant decrease in the rate of patients resected for low-grade intraductal papillary mucinous neoplasms was observed (43.6% in 2009–2012 vs 27.8% in 2013–2018; P = .003), and 133 patients were finally included (62 women, median age: 68 years). Of these, 24.1% had 1 worrisome feature, 39.8% had ≥2 worrisome features, 18.8% had ≥1 high-risk stigmata, and 15.8% had ≥1 worrisome features + 1 high-risk stigmata. Overall surgical morbidity was 55.6%, 15.8% had Clavien-Dindo ≥3 complications, reoperation rate was 3.8%, and 90-day postoperative mortality was 1.5%. After a median follow-up of 60 months, 13 patients (11.5%) had a recurrence of benign intraductal papillary mucinous neoplasm in the pancreatic remnant, and 2 patients (1.8%) developed pancreatic ductal adenocarcinoma. After partial pancreatectomy, 51.3% of patients were taking pancreatic enzyme replacement therapy. Among nondiabetics, 26% developed diabetes after partial pancreatectomy, of which 38% were insulin-dependent. Eighteen patients (13.7%) developed incisional hernia.
Conclusion
Given the rates of morbidity and long-term complications after pancreatic resections, surgeons should attentively balance the true risks of intraductal papillary mucinous neoplasm degeneration with the risks of surgical resection in each patient.
... Moreover, our study has shown that among the patients diagnosed with BD-IPMN, a significantly higher percentage has been diagnosed with LGD, while in MD-IPMN and mixed type IPMN patients, a significantly higher percentage of HGD/IC cases was presented. These observations are in accordance with the literature data [25][26][27][28]. Among the 25 patients diagnosed with BD-IPMN, 11 (84.6%) and 12 (92.3%) ...
The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy.
... For example, Fritz et al., reported a risk of malignancy of 24.6% in surgically resected "Sendai Negative" IPMNs [7]. The original Sendai guidelines were also found to result in unnecessary operations in 70% of patients due to high false-positive rate and suboptimal specificity [29]. ...
Background
/Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI.
Methods
Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts.
Results
356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria.
Conclusions
In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.
... This software takes exact input system data like pipe 5 and reservoir elevation, length of pipe, coefficient of friction and demand nodes and sets the cost as function. The output data is the optimized pipe length and diameters such that overall cost of system is minimized [16]. ...
Water is a critical and crucial substance for sustenance all over the world. The need for water distribution systems to satisfy increasing demand and also to satisfy quality requirements has birthed a surging need to model real-life situations in order to access the workability of Water distribution system (WDSs) and their ability to operate efficiently. Through the review of the analysis of modelling software and performance analysis, it was deduced that different licensed software and freeware products are available for design and model of various categories of WDSs, ranging from simple to complex, realistic and even hypothetical. It was discovered that software with licenses offers versatility, flexibility and precision in modeling various categories of hydraulic models with various features over software that are open for all. Therefore, the decision on which software to use for the design of water distribution systems is predicated on software precision, the overall project cost, software - required data, complexity of system, aspect of system to be modelled (quality, demand, valve operation and location etc.) software specificity related to the types of distribution systems that it can manage and computational and hydraulic criterion.
... The recent version (ICG 2017) added mural nodule size as a malignancy predictor [5] . However, these guidelines still result in low positive predictive value (PPV) and miss some malignant IPMNs [6,7] . In addition, we are still unable to know the individual risk of malignancy, thus failing to obtain a patient's risk-benefit profile for resection vs surveillance. ...
Background:
Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking.
Aim:
To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN.
Methods:
A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests.
Results:
Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model.
Conclusion:
The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.
... The recent version (ICG 2017) added mural nodule size as a malignancy predictor [5] . However, these guidelines still result in low positive predictive value (PPV) and miss some malignant IPMNs [6,7] . In addition, we are still unable to know the individual risk of malignancy, thus failing to obtain a patient's risk-benefit profile for resection vs surveillance. ...
... When looking at pooled data from nine study cohorts, these guidelines had a high negative predictive value (71 to 100%) in detecting dysplastic or malignant BD-IPMNs at the expense of a low positive predictive value (11 to 52%) [52]. Thus, the fundamental limitation of the Sendai guidelines is increasing sensitivity at the expense of specificity, resulting in the potential for numerous unnecessary pancreatic resections of benign cysts. ...
Purpose of review:
The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging.
Recent findings:
Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.
... The diagnostic impression based on radiological imaging findings was branch duct type IPMN most likely and serous cystadenoma as a possible differential diagnosis. In thinking of branch duct type IPMN, analyses of imaging findings included the "worrisome features" of contrast-enhancing ductal margin on CT and MRI and mural nodules in dilated duct on EUS [17][18][19] . In addition, FNA suggested intraductal-growing epithelial neoplasm though scant cellularity. ...
Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the pathologic findings of focal inflammatory fibrosis without evidence of tumor in pancreas. A 34-year-old man presented with right upper abdominal pain for a few weeks and slightly elevated bilirubin level on clinical findings. Radiological findings of multidetector-row computed tomography, magnetic resonance (MR) imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed focal branch pancreatic duct dilatation with surrounding delayed enhancing solid component at uncinate process and head of pancreas, suggesting branch duct type intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I would like to report the first case report of mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm.
... Oncotarget, Advance Publications 2017 have been controversial [4,5]. Some articles reported that many mucinous PCNs did not meet these criteria and were still proven to harbor high-grade dysplasia or even invasive cancers, and the validity of the guidelines were doubtful [6,7]. Thus, novel and accurate diagnostic indexes are required to discriminate benign lesions from invasive malignancies. ...
The treatment decision-making of mucinous pancreatic cystic neoplasm (PCN) has become a common clinical problem since the diagnostic accuracy of current tests in identifying malignancies in pancreatic cysts is limited. In this study, we aimed to validate the predictive value of systemic inflammatory factors in detecting malignant PCNs. Two hundred and forty-five patients with pathologically confirmed mucinous PCNs in a single Chinese institution were retrospectively analyzed. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cut-off values and measure the diagnostic value. The results showed that neutrophil count (P = 0.009), lymphocyte count (P = 0.002), neutrophil-to-lymphocyte ratio (NLR, P < 0.001), platelet-to-lymphocyte ratio (PLR, P < 0.001) and lymphocyte-to-monocyte ratio (LMR, P < 0.001) were distributed differently among the various differentiation groups of PCN. The univariate analyses indicated that a neutrophil count ≥ 2.8 × 10⁹/L (P = 0.024), lymphocyte count ≤ 1.9 × 10⁹/L (P < 0.001), PLR ≥ 125 (P < 0.001), NLR ≥ 1.96 (P < 0.001), and LMR ≤ 4.29 (P < 0.001) were significantly associated with invasive carcinomas in PCN patients. In addition, the multivariate analyses demonstrated that PLR ≥ 125 and LMR ≤ 4.29 were independent predictors of invasive malignancies. The ROC curves exhibited the malignant detection utility of the independent factor-based predictive model with an area under the curve (AUC) of 0.858 (P < 0.001). In conclusion, systemic inflammatory markers provide a supportive and easily accessible tool for the preoperative diagnoses of malignant PCNs.
... While great efforts have been made, including international consensus guidelines and follow-up of these patients with MRI and EUS to capture the small fraction of BD-IPMNs that harbor an invasive cancer, the majority of resections (~75%) for radiologically worrisome BD-IPMNs to date have revealed only low to moderate-grade dysplasia. [10][11][12][13][14] The management of these patients remains a significant challenge, and the fact that these lesions are radiologically detectable suggests that a new functional imaging strategy may be the key to progress. One of the greatest success stories in functional imaging is sodium iodide symporter-(NIS-) mediated imaging for thyroid cancer. ...
Objective:
We used transcriptomic profiling and immunohistochemistry (IHC) to search for a functional imaging strategy to resolve common problems with morphological imaging of cystic neoplasms and benign cystic lesions of the pancreas.
Methods:
Resected pancreatic cancer (n = 21) and normal pancreas were laser-capture micro-dissected, and transcripts were quantified by RNAseq. Functional imaging targets were validated at the protein level by IHC on a pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated adenocarcinomas.
Results:
Genes encoding proteins responsible for cellular import of pyruvate, export of lactate, and conversion of pyruvate to lactate were highly upregulated in pancreatic adenocarcinoma compared to normal pancreas. Strong expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma specimens. In IPMNs, the pyruvate-to-lactate signature was significantly elevated in high grade dysplasia (HGD) and IPMN-associated adenocarcinoma. Additionally, cores containing HGD and/or adenocarcinoma exhibited a higher number of peri-lesional stromal cells and a significant increase in peri-lesional stromal cell staining of LDHA and MCT4. Interestingly, the pyruvate-to-lactate signature was significantly upregulated in cores containing only low grade dysplasia (LGD) from patients with histologically confirmed IPMN-associated adenocarcinoma versus LGD cores from patients with non-invasive IPMNs.
Conclusion:
Our results suggest prospective studies with hyperpolarized [1-(13)C]-pyruvate magnetic resonance spectroscopic imaging are warranted. If these IHC results translate to functional imaging findings, a positive pyruvate-to-lactate imaging signature might be a risk factor for invasion that would warrant resection of IPMNs in the absence of other worrisome features.
... It is suggested that these lesions undergo endoscopic evaluation with endoscopic ultrasound with fine needle aspiration (EUS-FNA) despite suboptimal sensitivity and technical complications 5,11 . The guidelines provide an important framework for management, but there is disagreement between the preoperative diagnosis and pathologic examination in a large percentage (30-70%) of cases 10,[12][13][14][15][16] . Novel, noninvasive markers of IPMN pathology are needed, especially for individuals who do not present with HRS. ...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing ‘aggressive/malignant’ IPMNs that warrant surgical removal from ‘indolent/benign’ IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative ‘radiomic’ imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.
... However, a similarly large analysis based on a surgical resection series of 194 patients did not show a significant difference for either PPV (21 vs. 32%) or NPV (92 vs. 88%) between the Sendai and the revised ICG guidelines, respectively [74]. In a systematic review comparing nine separate studies on the Sendai guidelines, including a total of 690 patients, with a separate group of seven studies on the ICG guidelines, including a total of 1372 patients, the overall PPVs (31 vs. 36%) and NPVs (91 vs. 99%) for the Sendai guidelines were not that much lower than that for the revised ICG guidelines [75,76]. However, stratification of the IPMN groups into ''high-risk stigmata'' and ''worrisome feature'' groups did result in a higher PPV in the ''high-risk stigmata'' groups (66%) and a lower PPV in the worrisome features group (27%). ...
Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.
... The management of branch duct-type IPMNs (BD-IPMNs), being either surgery or surveillance, was recommended based on clinical symptoms and imaging [CT, MRI and endoscopic ultrasound (EUS)] features. Subsequent studies assessing the Sendai guidelines reported a high sensitivity (90-100%) but both low specificity (21-31%) and low positive predictive value (PPV) in detecting advanced neoplasia in mucinous cysts [12][13][14][15][16][17]. The reason for the high false-positive rate has been ascribed to the inclusion of cyst size ([3 cm) and clinical symptoms as surgical criteria. ...
With increased utilization and ongoing advancements in cross-sectional abdominal imaging, the identification of a pancreatic cyst has become a frequent finding. While many pancreatic cysts are associated with a benign clinical course, others may transform into pancreatic ductal adenocarcinoma. However, distinguishing a benign from a malignant pancreatic cyst or pancreatic cyst with malignant potential on the basis of standard clinical findings, imaging parameters and ancillary studies can be challenging. Hence, a significant interest within the past decade has been the identification of novel biomarkers to accurately classify and prognosticate a pancreatic cyst. Within this review, we discuss novel DNA, miRNA, protein and metabolite biomarkers, and their relevance in clinical practice. In addition, we focus on future areas of research that have the potential to change pancreatic cyst management.
The management algorithm for pancreatic cystic neoplasms (PCN) has evolved with rapid advancements in the knowledge of the diagnostic features, natural history and biology of these neoplasms together with the introduction of new and improvement in diagnostic modalities and tests. Over time, the management of PCNs has gradually trended from an aggressive resection approach in the past towards a more conservative approach with surveillance at present. Due to controversy in the management of intraductal papillary mucinous neoplasms (IPMN) especially with regards to branch duct (BD)-IPMN over the past 2 decades, several international consensus guidelines have been formulated to guide clinicians on the management of these neoplasms. These guidelines in general serve 2 main objectives: (1) diagnostic workup and clinical decision making and (2) surveillance protocol including methods, interval and duration. The present consensus guidelines’ are useful in in guiding clinicians in decision making for the management of IPMNs by utilizing widely and easily available clinical parameters and morphological features from conventional cross-sectional imaging. Nevertheless, present guidelines remain far from ideal and are still associated with various limitations.KeywordsIntraductal papillary mucinous neoplasmConsensus guidelinesPancreatic cystic neoplasmIPMNFukuoka
Objectives
To assess the diagnostic performance of the 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas and to compare the diagnostic performance and intermodality agreement between contrast-enhanced CT and MRI.Methods
We retrospectively evaluated patients with surgical resection of IPMN of the pancreas who underwent preoperative CT and MRI between 2009 and 2019. Two radiologists evaluated the clinical and imaging features of IPMN of pancreas according to the 2017 international consensus guideline. Univariable and multivariable analyses were performed to identify significant predictors of malignancy in IPMN. The diagnostic abilities of CT and MRI were compared, and their intermodality agreement was determined.ResultsOf 175 patients (mean age, 64 years; 116 males), 88 (50.3%) had malignant IPMN. On multivariable analysis, all three high-risk stigmata (main pancreatic duct [MPD] ≥ 10 mm, mural nodule ≥ 5 mm, and obstructive jaundice) and two worrisome features (MPD 5–9 mm and elevated carbohydrate antigen 19–9) were associated with malignant IPMN on CT and MRI (p < 0.05). A mural nodule < 5 mm on MRI was also associated with malignant IPMN (OR 5.3, p = 0.009). The diagnostic accuracy of high-risk stigmata showed no difference between CT and MRI (73.7% vs. 75.4%, p = 0.505), with good to excellent intermodality agreement.Conclusions
Current high-risk stigmata had the strongest association with malignant IPMN on CT and MRI. Although MRI is superior to CT for identifying mural nodules, diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI.Key Points
• The current high-risk stigmata in the 2017 International Consensus Guidelines had the strongest association with malignant IPMN on CT and MRI.
• MRI is better than CT for identifying enhancing mural nodule.
• Diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI.
Background & Aim
The risk of malignancy is uncertain for of intraductal papillary mucinous neoplasms (IPMNs) with main pancreatic duct (MPD) of 5-9 mm. No study has correlated MPD size and malignancy considering the anatomic site of the gland (head versus body-tail). Our aim was to analyze the significance of MPD in pancreatic head/body-tail as a predictor of malignancy in main-duct/mixed IPMNs.
Methods
Retrospective analysis of resected patients between 2009-2018. Malignancy was defined as high-grade dysplasia and invasive carcinoma. MPD diameter was measured with magnetic resonance imaging. Receiver operating characteristic curve (ROC) analysis was utilized to identify optimal MPD cut-off for malignancy. Independent predictors of malignancy were searched.
Results
Malignancy was detected in 74% of 312 identified patients. 213 patients (68.3%) had IPMNs of the pancreatic head and 99 (31.7%) of the body-tail. ROC analysis identified 9 and 7 mm as the optimal MPD cut-offs for malignancy in IPMNs of head and body-tail of the pancreas, respectively. Multivariate analysis confirmed that MPD ≥9 mm (pancreatic head), and ≥7 mm (body-tail) were independent predictors of malignancy along with macroscopic solid components, positive cytology and elevated CA 19-9. The risk of malignancy was low for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) unless high-risk stigmata or multiple worrisome features were present.
Conclusions
Different thresholds of MPD dilation are associated with malignancy in IPMNs of the head and body-tail of the pancreas. The risk of malignancy for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) lacking high-risk stigmata or multiple worrisome features is low.
Objectives
To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs).Methods
Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis.ResultsAmong MR findings, enhancing mural nodule size ≥ 5 mm, main pancreatic duct (MPD) ≥ 10 mm or MPD of 5 to 9 mm, and abrupt change of MPD were significant predictors for malignant IPMNs (p < 0.05). Among texture variables, significant predictors were effective diameter, surface area, sphericity, compactness, entropy, and gray-level co-occurrence matrix entropy (p < 0.05). At multivariate analysis, enhancing mural nodule ≥ 5 mm (odds ratios (ORs), 6.697 and 6.968, for reviewers 1 and 2, respectively), MPD ≥ 10 mm or MPD of 5 to 9 mm (ORs, 4.098 and 4.215, and 2.517 and 3.055, respectively), larger entropy (ORs, 1.485 and 1.515), and smaller compactness (ORs, 0.981 and 0.977) were significant predictors for malignant IPMNs (p < 0.05). When adding texture variable to MR findings, diagnostic performance for predicting malignant IPMNs improved from 0.80 and 0.78 to 0.85 and 0.85 in both reviewers (p < 0.05), respectively.ConclusionsMRCP-derived texture features are useful for predicting malignant IPMNs, and the addition of texture analysis to MR features may improve diagnostic performance for predicting malignant IPMNs.Key Points
• Among the MR imaging findings, an enhancing mural nodule size ≥ 5 mm and dilated main pancreatic ducts are independent predictors for malignant IPMNs.
• Greater entropy and smaller compactness on MR texture analysis are independent predictors for malignant IPMNs.
• The addition of MR texture analysis improved the diagnostic performance for predicting malignant IPMNs from 0.80 and 0.78 to 0.85 and 0.85, respectively.
Introduction:
The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice.
Methods:
462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998-2006, 2007-2012 and 2013 to 2018.
Results:
Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HRSG06 and HRFG12 CLP with a corresponding lower proportion of LRSG06 and LRFG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated.
Conclusions:
Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HRSG06 and HRFG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.
Imaging is a key technology in the early detection of cancers, including X-ray mammography, low-dose CT for lung cancer, or optical imaging for skin, esophageal, or colorectal cancers. Historically, imaging information in early detection schema was assessed qualitatively. However, the last decade has seen increased development of computerized tools that convert images into quantitative mineable data (radiomics), and their subsequent analyses with artificial intelligence (AI). These tools are improving diagnostic accuracy of early lesions to define risk and classify malignant/aggressive from benign/indolent disease. The first section of this review will briefly describe the various imaging modalities and their use as primary or secondary screens in an early detection pipeline. The second section will describe specific use cases to illustrate the breadth of imaging modalities as well as the benefits of quantitative image analytics. These will include optical (skin cancer), X-ray CT (pancreatic and lung cancer), X-ray mammography (breast cancer), multiparametric MRI (breast and prostate cancer), PET (pancreatic cancer), and ultrasound elastography (liver cancer). Finally, we will discuss the inexorable improvements in radiomics to build more robust classifier models and the significant limitations to this development, including access to well-annotated databases, and biological descriptors of the imaged feature data.
See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”
Background
Cystic lesions of the pancreas (PCLs) may be inflammatory or proliferative and making an accurate and timely pre‐operative diagnosis remains a significant clinical challenge. This is principally due to the heterogeneity of the pathological processes involved. PCLs constitute an entity with diverse histology and although infrequent, the possible potential for malignant transformation of these lesions and the opportunity for curative surgery mandates that our diagnostic approaches are up to date and evidence based. In addition, improved diagnostic accuracy is crucial to prevent unnecessary surgical procedures with the inevitable associated morbidity.
Methods
This narrative review examines the current diagnostic benchmarks and identifies novel diagnostic techniques that warrant further consideration, a number of which are beginning to be included in routine clinical practice when these PCLs are being investigated. A computerized search was made of MEDLINE, EMBASE and PubMed using the search words ‘diagnostic approaches to pancreatic cystic lesions’. All relevant articles in English language or with an English abstract were retrieved and additionally cross referenced.
Conclusion
The increasing accuracy of available imaging techniques together with the wider availability of endoluminal ultrasound and the development of additional novel methods to assess PCLs presents an opportunity to significantly improve the pre‐operative diagnosis rate. This is essential to classify the type of PCL and hence guide the management particularly with lesions where there is a likelihood of progression to more serious pathology. We have highlighted the need for a comprehensive and standardized algorithm for the diagnosis and management of PCLs.
Introduction
Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the (Sendai-06), Fukuoka-122, Fukuoka-17and European-18 guidelines.in predicting malignancy of mPCN.
Methods
One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma.
Results
Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indication (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively.
Conclusions
All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.
Background
The management of Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) is still controversial. Our objective was to assess the long-term follow-up (FU) of patients with “low-risk” BD-IPMN according to the Sendai-International Consensus Guidelines (ICG-I).
Methods
We retrospectively analyzed a cohort of patients with BD-IPMN and Negative Sendai-Criteria (NSC) from January 2004 to October 2019. A univariate analysis was performed to determine factors associated with conversion to Positive Sendai-Criteria (PSC) and malignancy. Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the IGC-I were assessed for the development of malignancy.
Results
A total of 219 patients were selected and underwent a median 58-month FU. Thirty-seven (17%) patients developed PSC during FU including 12 (5.5%) with malignant lesions. Conversely, 182 patients (83%) did not develop malignancy. The NPV and PPV of ICG-I for malignancy were 100% and 32.4%, respectively. Among patients who developed PSC, those with cancer were >65years (OR = 3.57;p = 0.015) and had significantly higher serum CA-19-9 levels (OR = 5.27;p = 0.007).
Conclusion
The ICG-I is a safe strategy for FU of patients with BD-IPMN. The absence of PSC exclude malignancy. Among patients who develops PSC, the risk of cancer remains low and surgery should be decided according to their surgical risk and life expectancy.
Body
Introduction
Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to increased CT and MRI usage. EUS is an emerging tool that can differentiate between benign and malignant features of pancreatic cysts. We hoped to identify the specific cross-sectional imaging findings and patient characteristics that warrant EUS referral.
Methods
We conducted a retrospective case-control chart review, evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS between January 1, 2010 and December 31, 2017.
Results
EUS was found to change management when CT imaging found cyst size > 4 cm (OR = 4.07, p < 0.01), cyst size > 3 cm (OR = 3.79, p < 0.001) and associated solid component to the cyst (OR = 5.95, p < 0.01). Additionally, patient characteristics, including age less than 50 years, male sex and 10-pack year smoking history were significantly associated with EUS change in management.
Discussion
Our findings suggest that EUS referral should be coordinated based on the findings of specific HRFs, with support from high risk patient characteristics, rather than the accumulation of multiple HRFs, as suggested by existing guidelines.
Owing to increased detection rates, the diagnosis and management of incidental pancreatic cysts has become a common predicament. Up to 13% of patients undergoing cross-sectional imaging studies for other indications are found to have pancreatic cystic lesions. Although most cystic lesions are benign, the malignant potential of several types of pancreatic cysts makes accurate classification vital to directing therapy. To this end, advances in the last decade led to better characterization of pancreatic cyst morphology and hence enhanced the ability to predict underlying histopathology, and biological behavior. Although accurate classification remains a challenge, the utilization of complementary diagnostic tools is the optimal approach to dictate management. The following review includes a description of pancreatic cysts, a critical review of current and emerging diagnostic techniques and a review of recent guidelines in the management of incidental pancreatic cysts.
Background
A differential diagnosis of advanced pancreatic cystic neoplasms (PCNs) is critical to determine optimal treatment. The Fukuoka and American Gastroenterological Association (AGA) guidelines are the most widely accepted criteria for the management of PCNs.
Objective
This study aimed to evaluate the diagnostic value of these guidelines in predicting advanced neoplasia (AN).
Methods
A comprehensive electronic search of the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases was conducted to identify all relevant studies evaluating the Fukuoka and AGA guidelines in surgically resected and histologically confirmed PCNs. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated as compound measures of diagnostic accuracy using the random-effects model. Summary of receiver operating characteristic (SROC) curves and the area under the curve (AUC) were also performed.
Results
A total of 21 studies with 3723 patients were included in this meta-analysis. Of these studies, 15, 4, and 2 evaluated the Fukuoka guidelines, the AGA guidelines, and both guidelines, respectively. For AN prediction, the Fukuoka guidelines had a pooled sensitivity of 0.67 (95% confidence interval [CI] 0.64–0.70), pooled specificity of 0.64 (95% CI 0.62–0.66), and pooled DOR of 6.28 (95% CI 4.38–9.01), with an AUC of the SROC of 0.78. AGA guidelines showed a pooled sensitivity of 0.59 (95% CI 0.52–0.65), pooled specificity of 0.77 (95% CI 0.74–0.80), and pooled DOR of 5.84 (95% CI 2.60–13.15), with an AUC of 0.79 (95% CI 0.70–0.88).
Conclusion
When used alone, the Fukuoka and AGA guidelines showed similar but unsatisfactory diagnostic accuracy in the risk stratification of malignant potential of PCN. Thus, we recommend that they be applied only as a broad framework in clinical practice.
Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted mass spectrometry demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers.
Background:
The aim of this systematic review is to assess the role of 18-fluorodeoxyglucose positron emission tomography in the preoperative evaluation of intraductal papillary mucinous neoplasms and cystic lesions of the pancreas.
Methods:
A computerized PubMed search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies evaluating positron emission tomography in the preoperative evaluation of pancreatic cystic lesions.
Results:
A total of 14 studies evaluated the role of 18-fluorodeoxyglucose positron emission tomography/positron emission tomography-computed tomography, 9 of which evaluated only intraductal papillary mucinous neoplasms and 5 evaluated all pancreatic cystic lesions, including intraductal papillary mucinous neoplasms. Pooled analysis was carried out for studies evaluating intraductal papillary mucinous neoplasms only and studies evaluating all cystic lesions. Imaging with 18-fluorodeoxyblucose positron emission tomography had a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 90%, 91%, 85%, 95%, and 91% in identifying malignancy (defined as either invasive and/or high-grade dysplasia) in intraductal papillary mucinous neoplasms and a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 85%, 81%, 79%, 86%, and 88% in identifying malignancy in other cystic lesions. Pooled analysis reported the positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of Sendai consensus guidelines (SCG) criteria as 69%, 69%, 68%, 55%, and 58%. The Fukuoka consensus guidelines (FCG) only had sensitivity, specificity, and accuracy reported as 61%, 52%, and 52%, respectively.
Conclusion:
The 18-fluorodeoxyblucose positron emission tomography had a high degree of accuracy of detecting malignancy in intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Comparison of the utility of positron emission tomography with the Fukuoka consensus guidelines and the Sendai consensus guidelines suggest that positron emission tomography is superior to present guidelines in detecting malignant intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Further studies in larger patient cohorts may be required to corroborate these findings and to determine the place of positron emission tomography in the management of intraductal papillary mucinous neoplasm and cystic lesions of the pancreas.
Background:
Significant overtreatment of intraductal papillary mucinous neoplasms can be attributed to low specificity of the current International Consensus Guidelines as well as nonconformity with the guidelines. We compare the ability of the 2012 and revised 2017 intraductal papillary mucinous neoplasms International Consensus Guidelines to predict high-grade dysplasia/invasive cancer and to determine the preoperative variables that predict resection of benign or low-grade dysplasia in tertiary care centers.
Methods:
Clinical, radiographic, and pathologic data for resected intraductal papillary mucinous neoplasms at 3 high-volume National Cancer Institute Cancer Centers were reviewed and the 2012 and 2017 consensus criteria were retrospectively applied. When International Consensus Guidelines were not met, clinical decision analysis was used to determine the primary indication for resection. Logistic regression identified variables associated with pathologic grade.
Results:
Records for a total of 251 patients were reviewed, 129 of whom (52%) had low-grade dysplasia. The revised 2017 International Consensus Guidelines had high sensitivity (98.4%) and negative predicted value (96.1%), and all high-risk stigmata predicted high-grade dysplasia/invasive cancer; however, specificity remained low (14.8%). Nonconformity with International Consensus Guidelines was the most powerful predictor of low-grade dysplasia on final pathologic examination (9.5; 2.12-40.78). Independent predictors of low-grade dysplasia included age younger than 50 (2.46; 1.08-5.62), fine-needle aspiration without epithelial cells (2.6; 1.43-4.72), and normal duct diameter (3.07; 1.99-4.75). Diabetes developed in 30% of patients after resection.
Conclusion:
Management of intraductal papillary mucinous neoplasms remains clinically challenging. Low specificity of the International Consensus Guidelines and nonconformity with the guidelines continue to contribute to unnecessary pancreatic resections. Improved tools for disease classification as well as a better understanding of the natural history, biology, and rates of progression of intraductal papillary mucinous neoplasms are needed to avoid surgical overtreatment of low-grade intraductal papillary mucinous neoplasms.
The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.
Background:
This study analyzed the pathologic findings for patients with Fukuoka-negative branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) who theoretically were eligible for surveillance care with follow-up assessment, but instead underwent resection.
Methods:
From January 2005 to December 2012, 820 patients underwent evaluation for IPMN. At initial staging, 319 patients had BD-IPMN, and 89 of these patients presented with Fukuoka-negative criteria. These 89 patients were included in this study.
Results:
Of the 89 patients, 55 (62%) underwent pancreatectomy. After pathologic examination, the ultimate diagnosis was MT-IPMN for 20 (36%) of these patients (the MT group) and BD-IPMN for 35 (64%) of these patients (the BD group). The remaining 34 patients (38%) underwent enucleation. The patients in the MT group were more likely to be male (P = 0.01) and to have a higher rate of recent (< 1 year) diabetes mellitus diagnosis (P = 0.007) than the patients in the BD group. In the multivariate analysis, diabetes mellitus was independently associated with involvement of the main pancreatic duct (P = 0.05). Malignancy was diagnosed for 14 (16%) of the 89 patients. The rate of invasive IPMN was higher in the MT group than in the BD group (20% vs. 0%, P = 0.02). The 5-year overall survival rate was 100% for the BD group and 84% for the MT group (P = 0.02). For the male patients with diabetes mellitus, the rate of malignancy rose to 67%.
Conclusions:
For patients with a diagnosis of Fukuoka-negative BD-IPMN, resection should be considered primarily for male patients with a recent diabetes mellitus diagnosis.
Incidental cystic intrapancreatic lesions are daily findings in abdominal radiology. The discovery of incidental pancreatic lesions is increasingly common with technologic diagnostic advancements. This article provides a perspective and guideline on the clinical management of incidental intraductal papillary mucinous neoplasms and cystic or premalignant lesions of the pancreas.
Background and objectives:
The Sendai consensus guidelines (SCG) and Fukuoka consensus guidelines (FCG) have been examined for their roles in predicting advanced neoplasia (AN) in pancreatic cystic neoplasm (PCN) patients with mixed results. We aim to evaluate the utilities of both guidelines in a Chinese cohort with preoperatively diagnosed mucinous PCNs.
Methods:
One hundred ninety-seven patients who underwent resections from 2008 to 2015 in Zhong Shan Hospital, Fudan University for suspected PCNs were retrospectively reviewed. Receiver operating characteristic (ROC) curves were calculated and compared to measure diagnostic value.
Results:
Fifty-five patients were diagnosed with AN pathologically. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the SCG high-risk (SCG(HR) ) criteria were 87.3%, 28.2%, 32.0%, 85.1%, and 44.7%, respectively, and for the FCG high-risk (FCG(HR) ) criteria, they were 40.0%, 95.8%, 78.6%, 80.5%, and 80.2%, respectively. ROC curve comparison analyses showed that the FCG(HR) were superior to the SCG(HR) (P = 0.02). The performance of the FCG(HR) was enhanced with CA19-9 incorporated (P = 0.004).
Conclusions:
The FCG were superior to the SCG in this retrospective analysis, which could be further improved by the incorporation of CA19-9. However, the practical safety remains uncertain because of missed invasive carcinoma cases.
Objectives:
The aim of this study was to investigate whether MUC1 expression is associated with progression of intraductal papillary mucinous neoplasms with worrisome features during follow-up.
Methods:
Fifteen patients positive for MUC1 and negative for MUC2 (MUC1 group) and 16 patients negative for MUC1 and MUC2 (control group) were followed up and examined for changes in diameters of the main and ectatic branches of pancreatic ducts, enlargement of mural nodules, and appearance of a solid mass, by imaging studies. All of them presented worrisome features, and none had "high-risk stigmata."
Results:
The sizes of the main and ectatic branches of pancreatic ducts increased in 8 (53.3%) and 8 (53.3%) patients, respectively, of the MUC1 group and in 1 (6.3%) and 1 (6.3%) patients, respectively, of the control group (P = 0.0059 and 0.0059, respectively). A solid mass developed in 6 patients (33.3%) of the MUC1 group but in none of the control group patients (P = 0.0373).
Conclusions:
Positive MUC1 expression in cell block cytology specimens may be associated with progressive dilation of the main and ectatic branches of pancreatic ducts and appearance of a solid mass in patients with intraductal papillary mucinous neoplasm with worrisome features during follow-up.
Objective:
The aim of this study was to pool incidences of increased cyst size, malignant branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs), pancreatic malignancy, and pancreatic malignancy-related death during follow-up (FU) of BD-IPMN patients.
Methods:
Searches were performed from January 2010 to April 2016. All hits were checked on inclusion criteria, and outcomes were extracted. Incidences were pooled. Three subgroups were defined: (1) including only BD-IPMN patients, (2) short-interval FU (maximum 6 months), and (3) long-interval FU (>6 months).
Results:
Thirty-one articles were enrolled, including 8455 patients (mean age, 66.4 years). Twenty-two studies included subgroup 1; 10 and 6 studies included, respectively, subgroups 2 and 3. Incidence of increased cyst size was 17.4%. In subgroups 1, 2, and 3, incidences were, respectively, 20.0%, 17.2%, and 31.7%. Incidence of malignant BD-IPMN was 2.5. In subgroups 1, 2, and 3, incidences were, respectively, 3.0%, 2.4%, and 3.3%. Incidence of pancreatic malignancy was 2.6%. In subgroups 1, 2, and 3, incidences were, respectively, 2.3%, 1.2%, and 4.0%. Incidence of death was 0.5%. In subgroups 1, 2, and 3, incidences were, respectively, 0.4%, 0.04%, and 0.12%.
Conclusions:
Although not significant, all incidences on long-interval FU were higher; therefore, short-interval FU seems necessary to find resectable lesions.
Objectives:
Guidelines regarding the surveillance of intraductal papillary mucinous neoplasms (IPMNs) are controversial because of uncertain risk of malignancy, agnosticism regarding the use of endoscopic ultrasound, and their recommendation to stop surveillance after 5 years. We present a systematic review and meta-analysis of the risk of malignancy and other end points and estimate the value of endoscopic ultrasound for surveillance.
Methods:
We systematically searched MEDLINE for studies with a cohort of patients with presumed branch-duct IPMN who initially were managed nonsurgically. Data regarding study characteristics, surveillance, and outcomes were extracted. Incidence rates of morphologic progression, malignancy, surgery, and death were calculated with a random effects model.
Results:
Twenty-four studies with 3440 patients and 13,097 patient-years of follow-up were included. Rates of morphologic progression, surgery, malignancy, and death were 0.0379, 0.0250, 0.0098, and 0.0043 per patient-year, respectively. Endoscopic ultrasound was not associated with significantly different rates of these outcomes.
Conclusions:
The risk of malignancy calculated in this study was low and in line with recent systematic reviews. Endoscopic ultrasound does not have marginal use in surveillance. Given the limitations of a systematic review of nonrandomized studies, further studies are needed to determine the optimal surveillance of branch-duct IPMNs.
Objective
Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/pathology.
Methods
In a cohort of 34 surgically-resected, pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative abdominal computed tomography (CT) images, we calculated body mass index (BMI) and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat ratio (V/S). Measures were compared between groups using Wilcoxon two-sample exact tests and other metrics.
Results
Mean BMI for individuals with malignant IPMNs (28.9 kg/m²) was higher than mean BMI for those with benign IPMNs (25.8 kg/m²) (P=0.045). Mean VFA was higher for patients with malignant IPMNs (199.3 cm²) compared to benign IPMNs (120.4 cm²),P=0.092. V/S was significantly higher (P=0.013) for patients with malignant versus benign IPMNs (1.25vs. 0.69 cm²), especially among females. The accuracy, sensitivity, specificity, and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%, 71%, 76%, 75%, and 72%, respectively.
Conclusions
Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology, acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than BMI. Further investigation of gender-specific associations in larger, prospective IPMN cohorts is warranted to validate and expand upon these observations.
The real prevalence of pancreatic cystic lesions remains unknown. The malignant potential of some of these lesions remains a cause for significant concern. Thus, it is mandatory to develop a strategy to clearly discriminate those cysts with a potential for malignant transformation from those that do not carry any significant risk. Intraductal papillary mucinous neoplasms and mucinous cystadenomas are mucinous cystic neoplasms with a known malignant potential that have gained greater recognition in recent years. However, despite the numerous studies that have been carried out, their differential diagnosis among other cysts subtypes and their therapeutic approach continue to be a challenge for clinicians. This review contains a critical approach of the current recommendations and management strategies regarding intraductal papillary mucinous neoplasms and mucinous cystadenomas, as well as highlighting the limitations exposed in current guidelines.
Backround:
The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection.
Methods:
Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured.
Results:
A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant.
Conclusion:
Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.
Objectives:
This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN.
Background:
Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited.
Methods:
Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded.
Results:
The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test.
Conclusion:
A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
The role of pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts remains unclear.
Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cysts.
Prospective, multicenter study.
Patients with pancreatic cysts presenting for EUS evaluation.
EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic loss analysis, mutational amplitude, and sequence determination.
Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination.
The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cysts. Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points for allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value >148 ng/mL). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio >10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytologic evaluation (10/40) could be diagnosed as malignant by using DNA analysis.
Limited follow-up, selection bias.
Elevated amounts of pancreatic cyst fluid DNA, high-amplitude mutations, and specific mutation acquisition sequences are indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy.
Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are reported to be less aggressive than the main-duct type. Hence, less aggressive treatment has been proposed for the former.
To evaluate the effectiveness of a follow-up protocol for BD-IPMNs.
Prospective study.
An academic tertiary referral centre.
From 2000 to 2003, 109 patients with BD-IPMNs underwent trans-abdominal ultrasound and magnetic resonance cholangiopancreatography with secretin. Patients who presented malignancy-related parameters (size >3.5 cm, nodules, thick walls, carbohydrate antigen 19.9 level >25 U/l, recent-onset or worsened diabetes) and/or complained of symptoms were submitted to surgery (arm A). All asymptomatic patients without suspicion of malignancy were followed up according to a 6-month clinical-radiological protocol (arm B).
The effectiveness of conservative management of BD-IPMNs.
20 (18.3%) patients underwent surgery (arm A); pathological diagnosis of BD-IPMNs was always confirmed. 89 (81.7%) patients were followed up for a median of 32 months (arm B); of these, 57 (64%) patients had multifocal disease. After a mean follow-up of 18.2 months, 5 (5.6%) patients showed an increase in lesion size and underwent surgery. The pathological diagnosis was branch-duct adenoma in three patients and borderline adenoma in two.
Surgery is indicated in <20% of cases of BD-IPMNs, and, in the absence of malignancy-related parameters, careful non-operative management seems to be safe and effective in asymptomatic patients. Although observation for a longer time is needed to confirm these results, our findings support the guidelines recently recommended by the International Association of Pancreatology.
Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.
Hypothesis
Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT).Design
Retrospective study.Setting
University hospital from January 1988 through December 1994.Patients and Intervention
We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT.Results
The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease.Conclusions
Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.
Background
The Sendai Consensus Guidelines(SCG) was formulated in 2006 to guide management of mucinous cystic lesions of the pancreas (CLP)and was updated in 2012 (ICG 2012). This study aims to evaluate the clinical utility of the ICG 2012 with the SCG based on initial cross-sectional imaging findings
Methods
One-hundred and fourteen patients with mucinous CLP were reviewed and classified according to the ICG 2012 as high risk(HRICG2012), worrisome(WICG2012),low risk(LRICG2012) and according to the SCG as high risk(HRSCG) and low risk(LRSCG)
Results
On univariate analysis; symptoms, obstructive jaundice, elevated serum CEA/CA 19-9, solid component, MPD ≥ 10 mm and MPD ≥ 5mm was associated with high grade dysplasia(HGD)/invasive carcinoma in all mucinous CLP. Increasing number of HRSCG or HRICG2012 features was associated with an significantly increased likelihood of malignancy. The PPV of HRSCG and HRICG2012 for HGD/invasive carcinoma was 46% and 62.5% respectively. The NPV of both LRSCG and LRICG2012 was 100%.
Conclusion
Both the guidelines were useful in the initial cross-sectional imaging evaluation of mucinous CLP. The ICG2012 guidelines were superior to the SCG
The aim of this study was to critically analyze the safety of the revised guidelines, with focus on cyst size and worrisome features in the management of BD-IPMN.
The Sendai guidelines for management of branch duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai negative). Revised international consensus guidelines published in 2012 suggest a still more conservative approach, even for lesions of 3 cm or larger. By contrast, 2 recent studies have challenged the safety of both guidelines, describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than 3 cm and in 25% of "Sendai-negative" BD-IPMN.
Review of a prospective database identified 563 patients with BD-IPMN. A total of 240 patients underwent surgical resection (152 at the time of diagnosis and 88 after being initially followed); the remaining 323 have been managed by observation with median follow-up of 60 months. No patient developed unresectable BD-IPMN carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23 patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or developed concurrent pancreatic ductal adenocarcinoma. According to the revised guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD-IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of invasive carcinoma was found.
Expectant management of BD-IPMN following the old guidelines is safe, whereas caution is advised for larger lesions, even in the absence of worrisome features.
Objective:
To systematically determine the imaging findings for distinguishing malignant and benign branch-duct type intraductal papillary mucinous neoplasms (BD-IPMNs), including mixed type, and their diagnostic value through meta-analysis of published studies.
Background:
Management of BD-IPMNs, including mixed type, largely relies on imaging findings. The current knowledge on imaging findings to distinguish malignant and benign BD-IPMNs has weak evidence and is mostly from scattered individual retrospective studies.
Methods:
Thorough literature search in Ovid-MEDLINE and EMBASE databases was conducted to identify studies where findings of computed tomography, magnetic resonance imaging, and endoscopic ultrasonography of BD-IPMNs with or without main pancreatic duct (MPD) dilatation were correlated with surgical/pathological findings. Review of 1128 article candidates, including full-text review of 102 articles, identified 23 eligible articles with a total of 1373 patients for meta-analysis. Dichotomous data regarding distinction between malignant and benign BD-IPMNs were pooled using random effects model to obtain the diagnostic odds ratios (DORs) and their 95% confidence intervals (CIs) of various individual imaging findings for diagnosing malignant BD-IPMN.
Results:
Presence of mural nodules revealed the highest pooled DOR (95% CI) of 6.0 (4.1-8.8) followed by MPD dilatation [3.4 (2.3-5.2)], thick septum/wall [unadjusted, 3.3 (1.5-6.9); publication bias-adjusted, 2.3 (0.9-5.5)], and cyst size greater than 3 cm [2.3 (1.5-3.5)]. Multilocularity and multiplicity of the cystic lesions did not reveal statistically significant association with malignancy.
Conclusions:
Presence of mural nodules should be regarded highly suspicious for malignancy warranting a surgical excision whereas cyst size greater than 3 cm, MPD dilatation (5-9 mm), or thick septum/wall may better be managed by careful observation and/or further evaluation.
Background:
Better pancreatic cyst fluid biomarkers are needed.
Objective:
To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers.
Design:
Retrospective study.
Setting:
Tertiary-care referral center.
Patients:
Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts.
Intervention:
Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed.
Main outcome measurements:
Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve).
Results:
Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts.
Limitations:
Small sample sizes.
Conclusion:
Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.
BACKGROUND & AIMS: International guidelines for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate risk of malignancy associated with each of these features of IPMNs. METHODS: We performed a comprehensive search of MEDLINE from January 1, 1996 to November 11, 2011 for studies that included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Data were analyzed from 41 studies for the following features: cyst size >3 cm, the presence of mural nodules, dilated main pancreatic duct, symptoms, and main duct vs branch duct IPMNs. Malignant IPMNs were defined as those with carcinoma in situ or more advanced histology. A separate meta-analysis was performed for each risk factor to calculate pooled odds ratios (ORs). A random-effects model was used, based on the assumption of variation among study populations. RESULTS: The risks of malignancy associated with individual cyst features were: cyst size >3 cm (OR, 62.4; 95% confidence interval [CI], 30.8-126.3), presence of a mural nodule (OR, 9.3; 95% CI, 5.3-16.1), dilatation of the main pancreatic duct (OR, 7.27; 95% CI, 3.0-17.4), and main vs branch duct IPMN (OR, 4.7; 95% CI, 3.3-6.9]. There was a moderate level of heterogeneity among studies (I(2) range, 34-67). CONCLUSIONS: Based on a meta-analysis, cyst features proposed by the international guidelines for resection of IPMN were highly associated with malignancy. However, based on our findings, not all cyst features should be weighted equally when considering risk of malignancy; cyst size >3 cm was most strongly associated with malignant IPMN.
The aim of this study was to evaluate existing management guidelines for branch-duct intraductal papillary mucinous neoplasms (IPMNs).
According to current treatment guidelines (Sendai criteria), patients with asymptomatic branch-duct type IPMNs of the pancreas less than 3 cm in diameter without suspicious features in preoperative imaging should undergo conservative treatment with yearly follow-up examinations. Nevertheless, the risk of harboring malignancy or invasive cancer remains a significant matter of consequence.
All patients who were surgically resected for branch-duct IPMNs between January 2004 and July 2010 at the University Clinic of Heidelberg were analyzed. Clinical characteristics of the patients and preoperative imaging were examined with regard to the size of the lesions, presence of mural nodules, thickening of the wall, dilation of the main pancreatic duct, and tumor markers. Results were correlated with histopathological features and were discussed with regard to the literature.
Among a total of 287 consecutively resected IPMNs, 123 branch-duct IPMNs were identified analyzing preoperative imaging. Some 69 branch-duct IPMNs were less than 3 cm in size, without mural nodules, thickening of the wall, or other features characteristic for malignancy ("Sendai negative"). Of all the Sendai negative branch-duct IPMNs, 24.6% (17/69) showed malignant features (invasive carcinoma or carcinoma in situ) upon histological examination of the surgical specimen.
Although many branch-duct IPMNs are small and asymptomatic, they harbor a significant risk of malignancy. We believe that both main-duct and branch-duct IPMNs represent premalignant lesions. This should be taken into account for adequate therapeutic management. With regard to these results, the current Sendai criteria for branch-duct IPMNs need to be adjusted.
Malignancy in intraductal papillary mucinous neoplasms (IPMN) of the pancreas may be predicted on the basis of a number of clinical and radiologic features, which have raised sensitivity but result in a specificity as low as 20-50%. We sought to confirm the additional value of (18)F-18-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) in diagnostic accuracy of imaging-based IPMN malignancy assessment.
This prospective uncontrolled case series contained 44 patients with IPMN undergoing comprehensive diagnostic evaluation, including magnetic resonance cholangiopancreatography and (18)FDG-PET. Average follow-up time was 39.3 months (range 3-97 months). Diagnostic performance regarding the diagnosis of malignancy was evaluated for the classic preoperative assessment, including clinical signs, CA 19-9, imaging (computed tomography and magnetic resonance cholangiopancreatography), and International Consensus Guidelines criteria, as well as (18)FDG-PET scan.
Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100, 22, 32, 100, and 43%, and 83, 100, 100, 94, and 96%, respectively, for comprehensive assessment without and with (18)FDG-PET [maximum standardized uptake value (SUV(max)) cutoff of 2.5 MBq]. Elevated CA 19-9 values and positive PET scan were the only independent prognostic factors for malignancy (odds ratio 2.11, 95% confidence interval 1.15-2.74 and 5.49, 95% confidence interval 3.98-21.44, respectively).
(18)FDG-PET is useful for detection of malignancy in IPMN, improving the differential diagnosis with benign cases by functional data. The choice of SUV(max) cutoff should maximize specificity.
The international consensus guidelines for management of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm of the pancreas established in 2006 have increased awareness and improved the management of these entities. During the subsequent 5 years, a considerable amount of information has been added to the literature. Based on a consensus symposium held during the 14th meeting of the International Association of Pancreatology in Fukuoka, Japan, in 2010, the working group has generated new guidelines. Since the levels of evidence for all items addressed in these guidelines are low, being 4 or 5, we still have to designate them "consensus", rather than "evidence-based", guidelines. To simplify the entire guidelines, we have adopted a statement format that differs from the 2006 guidelines, although the headings are similar to the previous guidelines, i.e., classification, investigation, indications for and methods of resection and other treatments, histological aspects, and methods of follow-up. The present guidelines include recent information and recommendations based on our current understanding, and highlight issues that remain controversial and areas where further research is required.
To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs.
Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value ≥2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased.
Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3.
PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy.
Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most common disease producing enzymopathy. People with G6PD deficiency cannot cope with oxidative stressors. These patients are asymptomatic until they develop a haemolytic crisis which presents as anaemia and jaundice. The agents known to cause haemolysis in these patients are: oxidant drugs, (primaquine, chloroquine and other anti-malarials), antibiotics, (chloramphenicol, nitrofurantoin, sulphonamides, and all quinolone antibiotics). Chemicals to be avoided are moth balls (napththalene), aniline dyes, and some Chinese herbal medicine (San Chi, Chuan Lian). The classic presentation of exposure to Fava beans (legumes), causing oxidative haemolysis, has led G6PD deficiency to be also known as Favism. The patient we present here had no exposure to any of the known causes of oxidative haemolysis. Instead his precipitating cause strongly suggests raw fenugreek (T foenum-graecum L), a legume used as a herbal treatment for diabetes and previously not known to be a precipitant of haemolysis in G6PD deficiency.
The purpose of this study was to examine the characteristics of pancreatic intraductal papillary mucinous neoplasm (IPMN) in our institution and the selection for resection. Recent publications, including those from the International Consensus Guidelines and the Mayo Clinic, set forth criteria for resection. However, these criteria differ in the definition of main duct IPMN, which is an indication to resect.
Sixty patients from a single institution were retrospectively reviewed between 2000 and 2009.
Thirteen percent of patients had high-grade dysplasia, and 22% had invasive cancer. In multivariate analysis, factors associated with a lower risk of carcinoma were female sex (P = .039) and size <3 cm (P = .024). Patients were retrospectively evaluated with Mayo and International Consensus Guidelines. Eight patients had a diagnosis that would have changed from main duct to branch duct if the International Consensus Guidelines were used. Of these 8, there were 2 cancers. If the International Consensus Guidelines were applied instead of the Mayo, both cancers would have been resected, but 2 patients without cancer would have been spared an operation.
Twenty-two percent of resected patients had invasive cancer, and they had significantly worse survival (37 vs 85 months, P = .032). In our patient group, application of the International Consensus Guidelines identified all malignant IPMN and would have prevented 2 nontherapeutic resections when compared with the Mayo criteria.
Using Kaplan-Meier curves, a 2006 study illustrated a shorter time interval between development of symptoms and detection of malignant IPMN in the main pancreatic duct versus a side-branch duct location. Of 93 cases, only 62 were confirmed histologically. To support these interesting findings, we examined a larger cohort of cases where the diagnosis was confirmed histologically and asked if symptoms by themselves, as well as main duct location, were associated with malignant detection.
Between 1989 and 2009, 210 IPMN cases meeting international criteria were resected and histologically examined. Actuarial rates of malignant detection over time were calculated from the first clinical symptom to malignant detection (resection). These rates of malignant detection over time were compared for main vs. side-branch duct location and symptomatic vs. asymptomatic cases.
The most common indications for resection were symptoms (88%) and main pancreatic duct location (65%). The actuarial malignant detection rates were significantly shorter for main duct location and also for symptomatic cases, regardless of duct location.
Presence of symptoms followed by main pancreatic duct location had a significantly shorter elapsed time to malignant detection. The visual depiction of these actuarial rates highlights the importance of the clinical history. To determine malignant risk, the primary determinants for resection were either symptoms or main duct location (but not cyst size), confirming the 2006 study with a larger cohort of histologically confirmed cases.
The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan.
We analyzed 349 follow-up BD-IPMN patients who had no MNs on endoscopic ultrasonography at initial diagnosis.
Observation periods ranged from 1 to 16.3 years (median, 3.7 years). Sixty-two (17.8%) patients exhibited disease progression during follow-up. Twenty-two underwent surgery, leading to a pathological diagnosis of carcinoma in 9 and adenoma in 13. Although the remaining 287 (82.2%) showed no changes, 7 underwent surgery because of symptoms (n = 2), choice (n = 2), or development of pancreatic ductal adenocarcinoma (n = 3); all of them were diagnosed pathologically as adenomas. Of the 29 patients undergoing surgery, all 9 with carcinoma exhibited signs of progression, such as increased main pancreatic duct diameter and/or appearance of MNs. Pancreatic ductal adenocarcinomas and additional BD-IPMNs developed in 7 (2.0%) and 13 (3.7%), respectively. Overall, 320 (91.7%) patients were followed without surgery.
Most BD-IPMN patients who had no MNs on endoscopic ultrasonography could be managed without surgery. However, careful attention should be paid to disease progression and the development of pancreatic ductal adenocarcinomas during follow-up.
Several imaging modalities are commonly performed during work-up of intraductal papillary mucinous neoplasm (IPMN), but guidelines do not suggest any one technique. The aim of this study was to evaluate tumour and duct measurements by computed tomography (CT) and endoscopic ultrasound (EUS) and their ability to predict high-grade dysplasia (HGD) and cancer within pancreatic IPMN.
Patients with IPMN who underwent preoperative CT and EUS between 2001 and 2009 were selected. Data were gathered retrospectively from medical records.
The study group was comprised of 52 patients, 33% (17/52) of whom had HGD or cancer. On fine needle aspirate (FNA), neither carcinoembryonic antigen (CEA) >200 nor cytological analysis correlated with malignancy. In multivariate analysis, duct size ≥ 1.0 cm (P= 0.034) was a significant predictor of HGD or cancer, and diameter on CT scan (P= 0.056) approached significance. Lesion diameter of ≥ 2.5 cm on CT scan identified malignancy in 71% (12/17) of patients (P= 0.037). When analysed, all patients with HGD or cancer had a lesion diameter ≥ 2.5 cm and/or a duct diameter ≥ 1.0 cm by CT scan.
The use of radiographic criteria on CT including lesion size ≥ 2.5 cm and/or pancreatic duct diameter ≥ 1.0 cm appears to reliably identify patients with either HGD or invasive cancer. High-resolution CT scanning may obviate the need for EUS and FNA in patients with suspected IPMN.
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has malignant potential. Although serum levels of carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) are known to be raised in pancreatic ductal adenocarcinoma, little has been reported about their significance in IPMN.
Preoperative CA19-9 and CEA levels were measured in consecutive patients undergoing surgical resection for IPMN. Results were correlated with histopathological and clinical features.
In 142 patients, raised CEA and CA19-9 serum levels were significantly associated with invasiveness in both branch-duct and main-duct/mixed-type IPMN. Some 74 per cent of patients with an invasive IPMN had raised levels of CA19-9, compared with only 14 per cent who had non-invasive tumours. With a cut-off level of 37 units/ml, CA19-9 had a specificity of 85·9 per cent, a negative predictive value of 85·9 per cent, a positive predictive value of 74·0 per cent and accuracy of 81·7 per cent. Overall, 80 per cent of patients with an invasive IPMN had raised serum levels of CA19-9 and/or CEA compared with only 18 per cent of those with a non-invasive tumour (P < 0·001).
Serum CA19-9 is a useful non-invasive preoperative tool for differentiating between invasive and benign IPMN, and should be taken into account in the decision to offer surgery. Patients with an IPMN and positive tumour markers have a high risk of malignant disease.
The predictors of malignant intraductal papillary mucinous neoplasm (IPMN) and invasive IPMN were investigated in this study to determine the optimal indicators of surgical resection for IPMN.
Recently, international consensus guidelines have described the standard indicators of resection for IPMN. However, the indicators of surgical resection for IPMN, especially for branch duct IPMN, still remain controversial.
Eighty-two patients with IPMN who underwent surgical resection during April 1998 to January 2009, were retrospectively reviewed and examined with regard to their preoperative factors and pathologic diagnosis.
Multivariate analysis showed that main duct IPMN (P<0.01) and earlier diabetes (P=0.03) were independent predictors of malignant IPMN. In branch duct IPMN, the diameter of the main pancreatic duct (MPD) was found to be significantly associated with malignancy by univariate analysis (P=0.034). An elevated serum CA19-9 level (P<0.01) was an independent predictor of invasive IPMN.
Our observations suggest that main duct IPMN, branch duct IPMN with MPD dilatation, and IPMN with an elevated serum CA19-9 level should be considered as indications for surgical resection.
In branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas, the importance of the cyst size to predict malignancy is still controversial. Our aim was to elucidate the malignant potential of branch duct IPMN without mural nodules (flat branch duct IPMN).
Seventy-three patients with flat branch duct IPMNs were studied in our institution.
There were 6 malignant IPMNs in this series, all of which were 30 mm or more in size, whereas there was no malignancy in IPMNs of less than 30 mm. Statistically significant predictors of malignancy were atypical cytological condition and main pancreatic duct (MPD) diameter of 5 mm or more. The cyst size of 30 mm or more tended to be associated with malignancy. The frequency of malignancy in flat branch duct IPMNs with the size of 30 mm or more and MPD diameter of less than 5 mm was 3.6%, whereas there were 5 malignant cases (26.3%) in flat branch duct IPMNs with the size of 30 mm or more and MPD diameter of 5 mm or more.
We conclude that the size criteria (> or =30 mm) to predict malignancy proposed in the international consensus guidelines is appropriate and resection or meticulous follow-up using cytological examination and MPD dilatation is needed in patients with flat branch duct IPMNs.
International consensus guidelines, aimed at predicting malignancy, are available for surgical resection of mucinous cysts but not for other cystic lesions of the pancreas. We sought to determine whether the consensus guidelines can be applied to all cystic lesions of the pancreas.
We identified all patients who underwent surgical resection of pancreatic cysts from 2001-2007. Pathology analyses of surgical specimens served as the reference standard. Surgical resection criteria proposed by the Sendai Guidelines and 5 modifications of these criteria were tested to determine their accuracy for diagnosis of malignant cysts.
Patients with cystic lesions of the pancreas (n = 154; mean age, 59.8 years; 64% women) underwent resection and met prespecified study criteria. Twenty-one patients had a malignancy. The classification cyst size > or = 3 cm had an accuracy of 56%, negative predictive value of 84%, and identified only 57% of the malignant cysts. The classification cyst size > or = 3 cm or cyst with main pancreatic duct > or = 10 mm had an accuracy of 55%, negative predictive value of 86%, and identified 66% of malignant cysts. The modified criterion of cyst size > or = 3 cm or cyst with main pancreatic duct > 3 mm had an accuracy of 48%, negative predictive value of 94%, and identified 91% (19/21) of the malignancies. Cyst size (odds ratio, 1.05) and pancreatic duct dilation > 3 mm (odds ratio, 10.5) were strong and independent predictors of malignancy.
When applied to all cystic lesions of the pancreas, the international consensus criteria cause some malignant cysts to be missed. Modified criteria could identify most malignant cysts, although overall accuracy remains low.
A consensus conference has recommended close observation of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) smaller than 30 mm, without symptoms or mural nodules. This study investigated whether these recommendations could be validated in a single-centre experience of BD-IPMNs.
Some 190 patients with radiological imaging or histological findings consistent with BD-IPMN were enrolled between 1998 and 2005. Those with less than 6 months' follow-up and no histological confirmation were excluded.
BD-IPMN was diagnosed by computed tomography and pancreatography in 105 patients and pathologically in 85. Eighteen patients had adenoma, 53 borderline malignancy, five carcinoma in situ and nine invasive carcinoma. Findings associated with malignancy were the presence of radiologically suspicious features (P < 0.001) and a cyst size of at least 30 mm (P = 0.001). Had consensus guidelines been applied, 54 patients would have undergone pancreatic resection, whereas only 28 of these patients actually had a resection; 12 of the latter patients had a malignancy compared with none of the 26 patients who were treated conservatively.
A simple increase in cyst size is not a reliable predictor of malignancy. Observation is recommended for patients with a BD-IPMN smaller than 30 mm showing no suspicious features on imaging.
The international consensus guidelines (the guidelines) for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of branch duct IPMNs with any of the following features: cyst size >30 mm, mural nodules, main pancreatic duct diameter >6 mm, positive cytology, and symptoms. The aim of this study was to evaluate the usefulness of these guidelines for resection of branch duct IPMNs.
We reviewed 84 consecutive patients with branch duct IPMNs who underwent surgical resection at our hospital between January 1984 and December 2007.
Sixty-nine patients had indications for resection according to the guidelines. Malignant IPMNs had significantly larger cysts than benign tumors (P = 0.026). Patients with malignant IPMNs had significantly more indications for resection than those with benign IPMNs (2.6 +/- 1.0 vs. 1.7 +/- 0.9, P < 0.001), and 36 of the 37 patients with malignant IPMNs had indications. The sensitivity of the guidelines for predicting malignancy was 97.3%. One of 15 patients without indications had malignancy, and the specificity was low (29.8%).
The guidelines show a high sensitivity for predicting malignancy of branch duct IPMNs, but the specificity is low. The cyst size and the total number of indications in each patient should be taken into account when predicting the risk of malignancy for branch duct IPMNs.
Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT).
Retrospective study.
University hospital from January 1988 through December 1994.
We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT.
The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease.
Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.
Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct. To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied. All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases. In contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group. IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type. Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.
To determine the optimal management of the intraductal papillary mucinous neoplasms (IPMNs) according to the morphologic type based on distinguishing between benign and malignant diseases.
IPMNs are increasingly recognized clinicopathologic entity. Extended pancreatic resection with radical lymph node dissection has been recommended for treatment.
A retrospective clinicopathologic study was carried out of the 57 cases with IPMNs who were treated between 1985 and 2001. Forty-three patients with IPMNs underwent resection, and 14 patients with small IPMNs were observed without resection.
Among the 43 resected IPMNs, 25 were benign and 18 were malignant. Malignant tumors were significantly greater in diameter than benign tumors (52.9 vs. 30.2 mm, P< 0.05). All main duct type tumors with mural nodules were malignant. All branch duct type tumors less than 30 mm in diameter and without mural nodules were benign. Twelve branch duct type IPMNs size less than 30 mm were not resected and have not progressed.
These results suggest that the branch duct type IPMNs less than 30 mm and without mural nodules is benign and might be treatable with limited resection or careful observation.
Preoperative assessment of the likelihood of malignancy in intraductal papillary-mucinous tumour (IPMT) of the pancreas is often difficult. Predictive factors for malignancy and invasive carcinoma in IPMT were analysed.
Sixty-two patients with IPMT underwent surgical treatment, with histological confirmation of adenoma in 28, carcinoma in situ in 14 and invasive carcinoma in 20. Tumours were of the main duct type in 14 patients, branch duct type in 32, and combined type in 16. A multivariate analysis of 17 potential predictive factors, including preoperative clinical and imaging findings, was conducted.
Multivariate analysis identified two independent predictive factors for malignancy: mural nodules and main pancreatic duct diameter of 7 mm or more. Mural nodules in the main duct or combined type, and mural nodules and tumour diameter of 30 mm or more in the branch duct type were particularly indicative of malignancy. Mural nodules, jaundice and main duct or combined type were predictors of invasive carcinoma in the multivariate analysis.
The above factors should be considered in the diagnosis of IPMT to facilitate appropriate management.
The objectives of this analysis were to define the incidence, natural history, and predictors of neoplasia in pancreatic cysts to determine which patients can safely be observed and which should undergo an operation.
With advancements in imaging technology, cystic lesions of the pancreas are being detected with increased frequency. Many of these lesions are small and asymptomatic, but they may be associated with pancreatitis or have malignant potential. Therefore, the management of these patients is complex, and knowledge of pancreatic cyst natural history and predictors of neoplasia are important.
From January 1995 through December 2002, all radiologic, surgical, and pathology records were reviewed for the presence of pancreatic cysts. In determining natural history, only patients with 2 scans more than 1 month apart at our institution were included. Patients with a clinical history and laboratory evidence of pancreatitis and/or pathologic confirmation of a pseudocyst were excluded. Factors analyzed as potential predictors of neoplasia included age, gender, cyst size, and symptoms. Serous cystadenomas, solid and cystic papillary (Hamoudi) tumors, lymphoepithelial cysts and simple cysts were all benign, whereas mucinous cystic neoplasms, intraductal papillary mucinous neoplasm, cystic neuroendocrine tumors, and cystadenocarcinomas were considered to be premalignant or malignant.
Among 24,039 CT or MR scans, 290 patients (1.2%) had pancreatic cysts, and 168 of these patients (0.7%) had no documentation of pancreatitis. Seventy-nine of these patients with 103 cysts had more than 1 scan with an average interval of 16 months. These cysts increased in size in 19%, did not change in 59% and decreased in 22% of patients. Forty-nine patients underwent surgery for 14 benign (serous cystadenomas = 10, Hamoudi = 2, lymphoepithelial = 1, simple = 1) 25 premalignant (mucinous cystic neoplasm =16, intraductal papillary mucinous neoplasm = 5, neuroendocrine tumors = 4), or 10 malignant (intraductal papillary mucinous neoplasm = 7, cystadenocarcinomas = 3) lesions. Gender and cyst size did not predict neoplasia. However, presence of symptoms predicted premalignant or malignant pathology (60% vs. 23%, P < 0.05), and age over 70 years was associated with malignancy (60% vs. 21%, P < 0.02).
These data suggest that cystic pancreatic neoplasms 1) occur in 0.7% of patients, 2) increase in 19% over 16 months, and 3) are likely (60%) to be malignant in patients older than 70 years. Therefore, we recommend surgical excision for pancreatic cysts that are increasing under observation, symptomatic, or detected radiologically in fit older patients.
Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.
To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas.
Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted.
Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003).
IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.
Despite advances in imaging modalities, preoperative diagnosis of pancreatic cystic lesions remains difficult.
To assess the accuracy of endoscopic ultrasound and computer tomography to preoperatively distinguish benign from potentially malignant and malignant pancreatic cystic lesions.
Photograph series obtained from endoscopic ultrasound examinations of 66 patients with cystic pancreatic lesions were blindly reviewed by three endoscopic ultrasonographers. Forty-one of those 66 patients also underwent a computer tomography scan at our institution, which was blindly reviewed by a single radiologist. Computer tomography and endoscopic ultrasound classification into benign and malignant and potentially malignant pancreatic cystic lesions was correlated with the final diagnosis, which was established by surgical pathology (n = 43), diagnostic fine needle aspiration (n = 13) or follow-up imaging (n = 10). Interobserver agreement was measured using kappa statistics.
Endoscopic ultrasound classification by the three examiners into benign versus malignant or potentially malignant cystic lesions was correct in 65-67%. Interobserver agreement was 50%. Kappa values for pairs of endoscopic ultrasound examiners were 0.16, 0.43 and 0.53. Computer tomography classification was correct in 71% and in agreement with the endoscopic ultrasound classification in 56-61% (kappa 0.12 to 0.27).
Endoscopic ultrasound and computer tomography cannot accurately distinguish between benign pancreatic cystic lesions and malignant or potentially malignant ones. There is poor-to-modest interobserver agreement in classifying these lesions.
Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.
Natural history of intraductal papillary mucinous tumors of the pancreas (IPMTs) is unknown. Cross-sectional studies suggest that exclusive branch duct (BD) involvement is associated with a lower risk of carcinoma than main pancreatic duct (MPD) involvement. The aim of our study was to calculate longitudinal risk of malignant transformation of IPMT since the first sign.
All the patients with a diagnosis of highly probable or histologically proven IPMT were included. Actuarial risks of occurrence of at least low-grade dysplasia (>or=LGD), high-grade dysplasia (>or=HGD), or invasive carcinoma (IC) were calculated by Kaplan-Meier method from the first sign attributable to IPMT. The risks according to sex, acute pancreatitis, tumor size, and involvement of MPD were compared by log-rank test.
One hundred six patients were included with a proven (n = 76) or probable (n = 30) IPMT. The tumor was confined to BD in 53 cases. Median duration since the onset of the first sign to the end of follow-up was 21 months (range, 0-241). Ten-year actuarial risk that IPMT grade was >or=LGD, >or=HGD, or IC was 67%, 49%, and 29%, respectively. The only morphologic risk factor of malignant transformation was involvement of MPD, with a 5-year actuarial risk of >or=HGD of 63% in the MPD group compared with 15% in the BD group (P < .001).
Longitudinal risk of at least HGD or IC is time-dependent. Patients with BD IPMT present a much lower risk, justifying a nonoperative surveillance.
Although an aggressive resectional approach toward pancreatic cysts has been advocated in the past, many clinicians now deem this therapeutic strategy impractical given the rapidly increasing incidence of incidentally detected pancreatic cystic lesions. The aim of this study was to review the aggressive resectional policy toward pancreatic cysts adopted at our institution during the past 15 years.
One hundred nine consecutive patients who underwent surgical resection of a cystic lesion of the pancreas during a 15-year period were retrospectively reviewed. To determine subsets of patients at lower risk of having a malignant cyst, the clinicopathologic features (in particular, the malignant potential) of these patients were compared as a function of 3 variables, ie, presence of symptoms, patient age, and cyst size, using univariate analyses. Results were expressed as median and range and P < .05 was considered statistically significant.
Forty-three (39%) of 109 patients were asymptomatic. Incidental cysts were smaller (28 [10 to 240] vs 59 [10 to 200] mm, P < .001) and were found in older patients (55.0 [18 to 77] vs 45.5 [14 to 82] years, P = .003). Overall, 14% of asymptomatic cysts, versus 35% of symptomatic cysts, were malignant (P = .016). Incidental cysts were also less likely to be premalignant or malignant compared with symptomatic cysts (47% vs 70%, P = .015). Twenty (18%) patients were elderly (73.0 [70 to 82] years old). Elderly patients had a more equal sex distribution (45% vs 76% female, P = .005) and had smaller cysts (26 [10 to 200] vs 55 [10 to 240] mm, P = .003) that involved the head of the pancreas more frequently (8 [40%] vs 17 [19%], P = .045) compared with their younger counterparts. The cohort of elderly patients also had a higher median American Society of Anesthesiologists score (2 [1 to 3] vs 1 [1 to 3], P < .001), and a higher proportion had undergone a "more" major procedure (Whipple's or total pancreatectomy) (55% vs 18%, P < .001). Not unexpectedly, surgical morbidity in the elderly was significantly higher (10 [50%] vs 24 [27%], P = .045). The operative mortality in both groups was not significantly different (1 [5%] vs 1 [1%], P = .324). The proportion of premalignant or malignant lesions in elderly patients was also similar to that in younger patients (11 [55%] vs 55 [62%], P = .574). The size of a cyst in asymptomatic patients had no correlation with its potential for malignancy.
Reliance on preoperative characteristics alone such as the presence of symptoms, cyst size, and patient age are not sufficiently reliable in determining the malignant potential and thus management approach toward pancreatic cysts.
Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have advocated an aggressive resectional policy. This approach is no longer appropriate, and the number of PCs detected incidentally has increased. This study reviews the present literature and attempts to provide a management algorithm of pancreatic cysts based on currently available evidence.
A Medline search was conducted to identify studies investigating PC, with particular emphasis placed on studies addressing its diagnosis and management. Additional articles were obtained from the reference lists of key articles and recent reviews.
Based on current evidence, the optimal management of PC remains an art and should be individualized based on the risk-benefit ratio of surgery, which is influenced by multiple factors, such as the patient's potential life expectancy, surgical risk; and malignant potential of the cyst. Our proposed management algorithm is based on an individual's predicted risk-benefit ratio of surgery. Prospective evaluation of the algorithm is needed to determine its integrity.
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations.
A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1990 and 2005 was conducted.
Sixty-six patients (45.5%) had adenoma, 47 (32%) borderline tumors, 16 (11%) carcinoma in situ, and 16 (11%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). Jaundice was more frequent in patients with cancer (12.5% vs 1.8%, respectively, P = .022) and abdominal pain in patients with benign tumors (45% vs 25%, respectively, P = .025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter >or=30 mm (P < .001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100% and, for invasive cancer, was 63%.
This large cohort of resected branch-duct IPMNs shows that cancer is present in 22% of cases and validates the recent guidelines that indicate absence of malignancy in tumors <30 mm, without symptoms or mural nodules.
Recent consensus guidelines suggest that presence of > or =1 of the following is an indication for resection (IR) of branch duct intraductal papillary mucinous neoplasm (IPMN-Br): cyst-related symptoms, main pancreatic duct diameter > or =10 mm, cyst size > or =30 mm, intramural nodules, or cyst fluid cytology suspicious/positive for malignancy. Among a cohort of patients with IPMN-Br we determined if the consensus IR (CIR), presence of multifocal IPMN-Br, or growth of cyst size on follow-up predict malignancy.
We identified 147 patients with IPMN-Br of whom 66 underwent surgical resection at diagnosis and 81 were followed conservatively, of whom 11 were resected during follow-up. Clinical, imaging, histological, and cyst fluid characteristics from all 147 patients with IPMN-Br were obtained from clinical records and/or by contacting the patients. In all cases, presence of CIR at baseline and during follow-up (N = 66), presence of multifocal cysts (N = 57), and increase in cyst size (N = 38) were noted.
Among the 77 resected IPMN-Brs, at initial evaluation 61 had at least one CIR and 16 had none. Malignancy was present in 9/61 (15%) with CIR and 0/16 without IR (P= 0.1). When presence of any one of the CIR was taken as an indicator of malignancy, the CIR had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 23%, 14%, and 100%, respectively. Prevalence of malignancy in those with single versus multifocal IPMN-Br was similar (13%vs 11%). No patient has developed malignancy after a median follow-up of 15 months. So far, none of the 38 patients with increase in cyst size on follow-up has developed malignancy related symptoms.
Suggested consensus indications for resection identify all patients with malignancy; however, their specificity is low. In the short term it would be safe to follow patients without these features.
The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN.
We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea.
Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor </=2 cm without a mural nodule was 9.2%, for a tumor of </=2 cm plus a mural nodule was 25%, and for other conditions such as tumor >2 cm, >25%.
Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of </=2 cm without a mural nodule.
This study aims to determine the use of preoperative clinical, biochemical, and cross-sectional imaging features for predicting malignancy in cystic lesions of the pancreas (CLP).
Two hundred twenty patients who underwent operations for CLP or suspected CLP were reviewed. Patients were divided into two groups, patients undergoing operations for pseudocysts and patients undergoing operations for suspected cystic neoplasms. The predictive effect of various preoperative factors on the malignant potential of CLP was evaluated.
Forty-four patients with a preoperative diagnosis of pseudocysts underwent operations for complications of pseudocyst. Forty-two were confirmed pathologically to have pseudocysts, but two were found, unexpectedly, to harbor malignant lesions. One hundred seventy-six patients underwent operations for suspected pancreatic cystic neoplasms. There were 70 benign, 51 potentially malignant, and 55 malignant CLP. On multivariate analysis, three factors, ie, elevated serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9; cyst size > 3 cm; and presence of one or more of three morphologic features, such as solid component; peripheral calcification; and main duct dilation on cross-sectional imaging were independent predictors of malignancy. Presence of two or three of these factors had a positive predictive value of 88% in predicting a premalignant or malignant CLP.
Most pancreatic pseudocysts can be accurately diagnosed preoperatively. In patients with suspected pancreatic cystic neoplasms, elevated serum CEA or carbohydrate antigen 19-9, cyst size > 3 cm, and presence of suspicious morphologic features on imaging are predictors of potentially malignant or malignant CLP. Patients with a high likelihood of a potentially malignant or malignant lesion based on these three factors should undergo operation without additional investigations.
The 2006 Sendai Consensus Guidelines recommend surgical resection for all suspected branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) greater than 3 cm irrespective of symptoms, and those less than 3 cm with worrisome features. We aimed to evaluate the surgical characteristics of these guidelines retrospectively in pathologically confirmed cases of BD-IPMN.
IPMNs resected at our institution (1995-2006) were classified as main-duct predominant or branch-duct (BD) predominant based on preoperative imaging and postoperative histology. Resected BD-IPMNs were classified histologically: low risk (adenoma, borderline) and high risk (carcinoma in situ or invasive cancer). Clinical data (presence of symptoms, mural nodule, dilated pancreatic duct, and cyst size) were correlated with pathology.
Between 1995 and 2006, there were 204 patients who underwent surgical resection of pancreatic cysts. Sixty-one patients had IPMN including 31 with BD-IPMN. A total of 74.2% (23 of 31) of BD-IPMNs would have been recommended for surgical resection including 69.2% (18 of 26) of low-risk lesions and 100% (5 of 5) of high-risk lesions. All 8 cases of BD-IPMN that would have been recommended for nonsurgical management were low-risk lesions. The positive predictive value of the guidelines is 21.7% (95% confidence interval, 9.7%-41.9%). The negative predictive value is 100% (95% confidence interval, 67.6%-100.0%). Between 2000 and 2007, 351 patients with likely BD-IPMN were evaluated but not resected.
Implementation of the Consensus Guidelines to our single-institution, referral-based, surgical BD-IPMN population would have recommended resection of all histologically high-risk lesions. All lesions recommended for nonsurgical management were histologically low-risk lesions. For presumed BD-IPMNs less than 3 cm, the application of the Consensus Guidelines may reduce the resection rate for low-risk lesions.