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H&E ·100 specimen of pancreatic tail displaying multifocal high-grade intraductal papillary mucinous neoplasia. H&E, hematoxylin and eosin.
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Background: The risk of developing invasive cancer in the remnant pancreas after resection of multifocal high-grade pancreatic precursor lesions is not well known. We report three patients who were followed up after resection of multifocal high-grade pancreatic intraepithelial neoplasia (PanIN)-3 or intraductal papillary mucinous neoplasia (IPMN),...
Context in source publication
Context 1
... 1 A 68-year-old woman had a laparoscopic distal pancreatectomy for multifocal IPMN-mixed type with two foci of high-grade dysplasia detected on final pathology analysis (Fig. 1). Surgical margins were negative. The patient's remnant pancreas continued to be monitored semiannually through cross-sectional studies and intermittent endoscopic ultrasound (EUS) and fine-needle aspiration (FNA). Eight years from the date of the first surgery, the patient was still symptomatic with intermittent twinges of discomfort ...
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Purpose:
To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC).
Methods:
From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a...
Citations
... Although previous studies have postulated that multifocal PanIN lesions arise separately, our work definitively demonstrates their independent nature through the development of a technique for integrated 3D modeling and genomic analyses. 6,[37][38][39][40] We found that spatially distinct PanINs most often arise from independent genetic events, exemplified by discordant somatic mutations between spatially discrete lesions. Furthermore, we demonstrate that the proximity of LG or HG PanIN to PDAC does not guarantee shared genetic origins -our cohort included 2 examples of PanINs containing HG dysplasia that were genetically distinct from adjacent PDACs, further emphasizing the importance of 3D genomic analyses to ascertain genetic origins. ...
Pancreatic intraepithelial neoplasia (PanIN) is a precursor to pancreatic cancer and represents a critical opportunity for cancer interception. However, the number, size, shape, and connectivity of PanINs in human pancreatic tissue samples are largely unknown. In this study, we quantitatively assessed human PanINs using CODA, a novel machine-learning pipeline for 3D image analysis that generates quantifiable models of large pieces of human pancreas with single-cell resolution. Using a cohort of 38 large slabs of grossly normal human pancreas from surgical resection specimens, we identified striking multifocality of PanINs, with a mean burden of 13 spatially separate PanINs per cm3 of sampled tissue. Extrapolating this burden to the entire pancreas suggested a median of approximately 1000 PanINs in an entire pancreas. In order to better understand the clonal relationships within and between PanINs, we developed a pipeline for CODA-guided multi-region genomic analysis of PanINs, including targeted and whole exome sequencing. Multi-region assessment of 37 PanINs from eight additional human pancreatic tissue slabs revealed that almost all PanINs contained hotspot mutations in the oncogene KRAS, but no gene other than KRAS was altered in more than 20% of the analyzed PanINs. PanINs contained a mean of 13 somatic mutations per region when analyzed by whole exome sequencing. The majority of analyzed PanINs originated from independent clonal events, with distinct somatic mutation profiles between PanINs in the same tissue slab. A subset of the analyzed PanINs contained multiple KRAS mutations, suggesting a polyclonal origin even in PanINs that are contiguous by rigorous 3D assessment. This study leverages a novel 3D genomic mapping approach to describe, for the first time, the spatial and genetic multifocality of human PanINs, providing important insights into the initiation and progression of pancreatic neoplasia.
... Depending on the location of the tumor, the patient might undergo a Whipple procedure (pancreaticoduodenectomy) for the head tumors, left or distal pancreatectomy for the body and tail tumors, or a total pancreatectomy for extended disease [56]. Thus, the occurrence of multifocal lesions spread all over the pancreatic parenchyma is an indication for total pancreatec-tomy [57][58][59]. Nevertheless, the decision on surgery is not always a simple task due to serious complications. ...
... Nevertheless, the decision on surgery is not always a simple task due to serious complications. As both the endocrine and exocrine portions of the pancreas is resected, the patients may suffer not only from postoperative DM, which requires insulin treatment, but also from exocrine pancreatic insufficiency with steatorrhea, weight loss, malabsorption, and dumping syndrome [57,58,60]. ...
... Overall, total pancreatectomy is the surgical procedure of choice for synchronous primary PDAC in the head and tail [57][58][59], and the rates of postoperative mortality and long-term survival have been remarkably improved in recent years, especially when the surgery is performed in high-volume centers by experienced surgeons [59,66,67]. In our case, the patient, despite his age, was a good candidate for total pancreatectomy, as the disease was considered resectable and he was at low surgical risk. ...
Synchronous primary pancreatic ductal adenocarcinoma (PDAC) is very rare and can be formed either through multicentric carcinogenesis or intrapancreatic metastasis. We report the case of an 80-year-old man with a history of type 2 diabetes mellitus who presented with abdominal pain and weight loss. Laboratory tests showed elevated levels of blood glucose and CA 19-9, and Computed Tomography revealed two hypoenhancing lesions in the head and tail of the pancreas. Endoscopic ultrasound, which is the imaging method of choice for pancreatic cancer, was performed with a fine needle biopsy, and the cytological analysis diagnosed PDAC in both lesions. The patient underwent total pancreatectomy, and pathologic evaluation revealed synchronous primary PDAC with moderate to poor differentiation in the head and tail in the setting of IPMN (intraductal papillary mucinous neoplasia) and chronic pancreatitis. After his recovery from postoperative pulmonary embolism, the patient was discharged home with sufficient glycemic control. Multifocal PDAC occurs more often when precursor lesions, such as IPMN, pre-exist. The optimal treatment for multiple lesions spread all over the pancreas is total pancreatectomy. Diabetes mellitus is a serious complication of total pancreatectomy (new-onset or type 3c), but overall, long-term survival has been significantly improved.
... The five-year survival rate for all pancreatic cancer stages combined is just 9%, with incidence rates continuing to rise every year [2]. Pancreatic cancer can be divided into two main subtypes: pancreatic adenocarcinoma, which is responsible for 85-90% of all pancreatic neoplasms and has a five-year survival rate of just 8%, and pancreatic neuroendocrine tumour (PanNET), which is far less common and represents less than 5% of PC [1,3,4]. As pancreatic adenocarcinoma is by far the most prevalent type of pancreatic cancer, it is used synonymously with PC and will be the type of PC referred to throughout this review. ...
... Pancreatic cystic lesions (PCLs) are typically fluid-filled structures that can be found within or on the surface of the pancreas, though some may have a solid appearance [3]. While many PCLs are benign and show no malignant potential, others, such as intraductal papillary mucinous neoplasms (IPMNs) or mucinous cystic neoplasms (MCNs), possess the ability to undergo malignant transformation and can be regarded as precursor lesions of PC [3][4][5]. The risk factors known to be associated with PC are extensive. ...
... Surgical resection is associated with significant morbidity and mortality and should be reserved for those at high risk of malignant transformation or established cancer [24]. Moreover, there is a 20% recurrence rate following surgical resection for IPMN [31], and recent studies have found multiple distinct regions of dysplasia within the pancreas, sometimes with differing mutational status of the same gene, supporting the notion of a multi-focal tumorigenic process of IPMN within the pancreas [4,31,32]. ...
Simple Summary
Pancreatic cancer (PC) is among the most aggressive types of cancer, having caused over 495,000 deaths worldwide in 2020, with increasing annual incidence. Pancreatic cystic lesions (PCLs) are protrusions found within or on the surface of the pancreas, and in many cases have the potential to become malignant. Current methods of characterising PCLs are imperfect and there is a profound need for improved diagnostic algorithms. This review highlights the importance of biological markers in the context of PCLs and PC, with a focus on ‘omics’-related work. Successful integration of different ‘omics’ data could aid in the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC.
Abstract
Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons—so called ‘incidentalomas’. Current methods of characterising PCLs are imperfect and vary hugely between institutions and countries. As such, there is a profound need for improved diagnostic algorithms. This could facilitate more accurate risk stratification of those PCLs that have malignant potential and reduce unnecessary surveillance. As PC continues to have such a poor prognosis, earlier recognition and risk stratification of PCLs may lead to better treatment protocols. This review will focus on the importance of biomarkers in the context of PCLs and PCand outline how current ‘omics’-related work could contribute to the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC.
... Two-thirds of these neoplasms occur in the head or uncinate process of the pancreas. The remaining neoplasms are in the body (15%), tail (10%), or diffusely dispersed throughout the pancreatic gland (multifocal) 2,11,17 . It is important to acknowledge other types of pancreatic tumors as their unique characteristics and genetics can alter their presentation and management. ...
... These series of mutations and polyclonality help to explain the relatively high rate of recurrence after resection (20%) 17 that significantly increases with higher levels of cell dysplasia. The presence of an IPMN and its field defect also increases the risk in which the entire pancreas may be prone to accumulation of distinct genetic mutations that will eventually evolve into cancer 17 . In fact, for patients with BD-IPMN, pancreatic ductal adenocarcinoma is found distal to and distinct from the primary lesion in 3-9% of patients 32 . ...
Robotic surgery is flourishing worldwide. Pancreatic cancer is the fourth leading cause of cancer death in the United States. Most pancreatic operations are undertaken for the management of pancreatic adenocarcinoma. Therefore, it is essential for all physicians caring for patients with cancer to understand the role and importance of molecular tumor markers. This article details our technique and application of the robotic platform to robotic pancreatectomy. The use of the robot does not change the nature of pancreatic operations, but it is our belief that it will improve patient outcomes and, possibly, survival by reducing perioperative complications.
Background. The variety of cystic tumors of the pancreas from benign to malignant, the availability of a large number of modern diagnostic methods, increasingly directs surgeons to systematize already existing experience and to search for new algorithms for the treatment of patients from the standpoint of evidence-based medicine. The purpose of the work is to analyze literary sources related to the results of diagnosis and surgical interventions for patients with various forms of cystic tumors of the pancreas, with the aim of determining the strategy of their surgical treatment. Materials and Methods. The data of full-text publications obtained as a result of a literature search in the Scopus and PubMed databases for the period from 2009 to 2022, which were devoted to the issues of surgical treatment of various morphological forms of cystic tumors of the pancreas, were analyzed and systematized. The search was conducted using the following keywords: «cystic tumor», «mucinous cystadenoma», «cystadenocarcinoma», «pseudocyst of the pancreas», «diagnostics», «surgical treatment». Results. For the diagnosis of cystic tumors of the pancreas, the entire range of known methods of perioperative research is used. The extent of surgical intervention for benign cysts is determined by such factors as the size of the neoplasm, its relationship with the parenchyma of the pancreas, the main pancreatic duct, and the vessels of the organ. Mucinous cystic tumors are an indication for surgical treatment. If the size of the serous cystadenoma is less than 3–4 cm, surgical intervention can be postponed, such patients are subject to dynamic observation. The choice of method of resection of the pancreas depends on the location of the tumor and may include distal pancreatectomy with or without splenectomy, median pancreatectomy, or Whipple pancreatoduodenal resection. When the neoplasm is located proximally, classical pancreatoduodenal resection is performed, and its localization in the body or tail of the gland requires distal resection of the organ. Laparoscopic technology can be an alternative for such damage to the gland by a small or medium-sized tumor. Issues of lymph node dissection and adjuvant chemotherapy currently remain debatable. Conclusions. Thus, the analysis of foreign literature on diagnosis and surgical treatment of cystic tumors of the pancreas showed that the use of modern instrumental examination methods affects the results of treatment of patients with this pathology. Fine-needle aspiration of cyst fluid is a safe, highly accurate diagnostic manipulation when cytological diagnosis of a cystic lesion of the pancreas is required. Multispiral computed tomography with bolus contrast enhancement remains the «gold standard», but the use of magnetic resonance imaging, endoscopic ultrasonography, and positron emission tomography are increasingly used to assess the operability, staging, and resect ability of cystic tumors. Knowledge and interpretation of imaging data are crucial for developing personalized patient treatment algorithms and improving treatment outcomes and patient quality of life.
