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Pancreas-preserving total duodenectomy technique. A: The duodenum is separated from the head of the pancreas by cutting the branches of the pancreaticoduodenal arcade vessels. The choledochal trunk is saved and only the membrane of the major papilla is shaved sharply. The accessory pancreatic duct is ligated and cut; B: Papillotomy is performed on the major papilla at 0, and then a catheter is inserted into the main pancreatic duct for stenting; C: Bilio-jejunal reconstruction. The edge of the common bile duct is sewn to a small opening on the jejunum with 4-0 absorbable knotted sutures; D:The final reconstruction schema of the alimentary tract.
Source publication
To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1.
Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome (ZES) underwent resection of both gastrinomas and duodenopancreatic neuroendocrine t...
Context in source publication
Context 1
... was performed using a new technique described elsewhere [20] ; briefly, when resecting the entire duodenum, only a mucosectomy is performed on the duodenal major papilla portion, retaining the structure of the major pa- pilla, and after an 8 mm long sphincterotomy, the opened papilla is anastomosed to the incisional opening of the jejunum [20] . Details of the procedure are shown in Figure 1. ...
Similar publications
Learning Objectives
Compare the approaches to management of sporadic and MEN-1 associated Zollinger-Ellison syndrome variants. Discuss the controversies in surgical and medical management of Zollinger-Ellison syndrome.
Citations
... SASI testing is performed to localize pancreatic neuroendocrine tumors, including insulinoma [9] and gastrinoma [22]. This method is useful in guiding surgical decisions, especially for small tumors that remain elusive on imaging examinations, such as CT, MRI, scintigraphy, and endoscopic ultrasound. ...
Patient: Male, 64-year-old
Final Diagnosis: Tumor-induced osteomalacia
Symptoms: Arthralgia • bone fractures • bone pain • gait disturbance
Clinical Procedure: —
Specialty: Endocrinology and Metabolic • Oncology • Orthopedics and Traumatology
Objective
Rare disease
Background
Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by aberrant fibroblast growth factor-23 (FGF-23)-producing tumors. Early surgical resection is the optimal strategy for preventing TIO progression. Thus, tumor localization is a priority for successful treatment. A simple and safe examination method to identify functional endocrine tumors is essential to achieve better outcomes in patients with TIO.
Case Report
A 64-year-old Japanese man with recurrent fractures, hypophosphatemia, and elevated alkaline phosphatase and FGF-23 levels (109 pg/mL) was admitted to our university hospital and was diagnosed with FGF23-related hypophosphatemic osteomalacia. Notably, the superficial dorsal vein in the patient’s left foot exhibited a high FGF-23 level (7510 pg/mL). Octreotide and ¹⁸F-fluorodeoxyglucose (FDG) scintigraphy and systemic venous sampling revealed that the tumor in the third basal phalanx of the left foot was responsible for FGF-23 overproduction. Tumor resection resulted in a rapid decrease in serum FGF-23 levels and an increase in serum phosphorus levels.
Conclusions
Octreotide scintigraphy, FDG-positron emission tomography, and systemic venous sampling are the standard methods for localizing functional endocrine tumors. However, the limited availability and invasive nature of these examinations hinder effective treatment. Here, we highlight the importance of peripheral superficial blood sampling as an alternative to conventional systemic methods for confirming the presence of FGF-23-producing tumors. Clinicians should consider TIO as a potential cause of acquired hypophosphatemic osteomalacia. Furthermore, peripheral superficial vein blood sampling may be useful for confirming the localization of FGF-23-producing tumors.
... In patients with multiple endocrine neoplasia type 1 syndrome (MEN1) and Zollinger-Ellison syndrome (ZES), gastrinomas usually arise from the submucosal layer of the duodenum. About 60% of these gastrinomas are multiple and about 15% of patients have pancreatic gastrinomas [1][2][3][4][5][6]. These gastrinomas have the potential to metastasize to the regional lymph nodes and liver, even if the primary tumors are less than 5 mm in diameter (Table 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. ...
... About 60% of these gastrinomas are multiple and about 15% of patients have pancreatic gastrinomas [1][2][3][4][5][6]. These gastrinomas have the potential to metastasize to the regional lymph nodes and liver, even if the primary tumors are less than 5 mm in diameter (Table 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The guidelines (GLs) of the Japanese Neuroendocrine Tumor Society (JNETS) recommend resection for functioning duodenopancreatic neuroendocrine tumors (NET) in MEN1 patients (Grade A, 100% agreement among members) [6]. ...
... Gastrinomas must be considered malignant since most eventually metastasize to the liver or intraperitoneal cavity [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. This is not prevented by PPIs; therefore, it seems more logical to perform resection for the gastrinomas instead of using PPIs alone in patients. ...
In patients with multiple endocrine neoplasia type 1 syndrome (MEN 1) and Zollinger–Ellison syndrome (ZES), gastrinomas arise from the duodenum, about 60% are multiple, and about 15% of patients have coexisting pancreatic gastrinomas, which can be localized by the selective arterial secretagogue injection test (SASI test). The guidelines (GLs) by the Japanese Neuroendocrine Tumor Society (JNETS) recommend surgical resection for functioning duodenopancreatic neuroendocrine tumors (NETs), including gastrinomas, in patients with MEN1 (Grade A, 100% agreement among members). Conversely, the GLs of the National Comprehensive Cancer Network (NCCN) in the USA recommend observation and treatment with proton pump inhibitors (PPIs) or exploratory surgery for occult gastrinomas. An international Consensus Statement (ICS) from the European Union (EU) also does not recommend resection of gastrinomas in patients with MEN1, despite some surgeons having reported surgery being curative for gastrinomas in MEN1 patients. In this review, we discuss the serious side effects and tumorigenic effects of the prolonged use of PPIs and the safety and curability of surgery, supported by our results of curative surgery for gastrinomas in 20 patients with MEN1 over 30 years. We conclude that surgery should be the first-line treatment for gastrinomas in MEN1 patients.
... Second, as part of the PD, the radical excision of the peripancreatic lymph nodes and pNEN in the head of the pancreas is performed, thus clearing the whole gastrinoma triangle. Although PD provides a cure rate of 60-100% of MEN1-ZES in small series [16,[21][22][23][24][25][26][27], this procedure might have an increased perioperative mortality and morbidity and lead to reduced quality of life compared to non-PD resections in the long term. Therefore, the present study evaluated the long-term outcomes of PD versus non-PD resections in MEN1-ZES with regard to biochemical cure and quality of life. ...
... Although PD is potentially associated with a higher ZES cure rate, a major concern regarding PD as a primary surgical procedure is the potentially higher rate of complications as compared to non-PD resections. This fear is based on the fact that young MEN1 patients have a soft pancreatic tissue and often a small diameter (<3 mm) of the pancreatic and biliary ducts, which are proven risk factors for anastomotic complications [24][25][26]28,38]. In the presented series, the rate of patients with clinically relevant complications (Clavien-Dindo ≥ 3) was 36% (four of 11) after PD, which is in line with the reported 26% (eight of 31), 37% (6/16) and 64% (nine of 14) from PD series conducted in France, Italy, and the Netherlands [16,25,39]. ...
Aim:
The aim of this research was to evaluate the long-term outcome of pancreaticoduodenectomy (PD) versus other duodenopancreatic resections (non-PD) for the surgical treatment of the Zollinger-Ellison syndrome (ZES) in patients with multiple endocrine neoplasia type 1 (MEN1).
Methods:
Prospectively recorded patients with biochemically confirmed MEN1-ZES who underwent duodenopancreatic surgery were retrospectively analyzed in terms of clinical characteristics, complications, cure rate, and long-term morbidity, including quality of life assessment (EORTC QLQ-C30).
Results:
35 patients (16 female, 19 male) with MEN1-ZES due to duodenopancreatic gastrinomas with a median age of 42 (range 30-74) years were included. At the time of diagnosis, 28 (80%) gastrinomas were malignant, but distant metastases were only present in one (3%) patient. Eleven patients (31.4%) underwent pancreatoduodenectomy (PD) as the initial procedure, whereas 24 patients underwent non-PD resections involving duodenotomy with gastrinoma excision, enucleation of the pNEN from the head of the pancreas, and peripancreatic lymphadenectomy, either with or without distal pancreatectomy (i.e., either Thompson procedure, n = 12, or DUODX, n = 12). There was no significant difference in perioperative morbidity and mortality between the two groups (p ≥ 0.05). One (9%) patient of the PD group required reoperation for recurrent or metastatic ZES compared to eight (22.8%) patients of the non-PD resection groups. After a median follow-up time of 134 months (range 6-480) nine of 11 (82%) patients in the PD group, two of 12 (16%) patients in the Thompson procedure group, and three of 12 (25%) patients in the DUODX group had normal serum gastrin levels. In addition, the global health QoLScore was better in the PD group (76.9) compared to the Thompson procedure (57.4) and DUODX (59.5) groups.
Conclusions:
Initial PD seems to be the superior surgical procedure for MEN1-ZES, resulting in a long-term cure rate of about 80%, fewer duodenopancreatic reoperations, and an acceptable quality of life.
... Tumor size is strongly correlated with the detection sensitivity of any examination modality, and tumors of <1 cm in diameter are often difficult to detect (1,2). Therefore, the selective arterial calcium agent injection (SACI) test was developed as an effective method to detect small gastrinomas (2,6,7). In the SACI test, calcium gluconate is injected via a microcatheter into selected arterial branches to stimulate gastrin secretion from the gastrinoma located in the corresponding arterial territory. ...
... Although biochemical cure is uncommon with this procedure (<38% at 5 years), distant metastases are rarely observed during longterm follow-up (0-13% during follow-up period of 18-136 months in various studies). Some groups perform duodenectomy (pancreas-preserving or as part of partial pancreatoduodenectomy) with good results in terms of biochemical cure and distant metastases in expert centres 77,78 . The Whipple procedure is reserved for patients with large pancreatic head tumours that cannot be enucleated. ...
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.
... www.nature.com/scientificreports/ The SACI test is a method for the identification and differentiation of insulinomas or gastrinomas among multiple NETs that are essentially impossible to identify on imaging techniques alone, and it is useful for planning the surgical strategy preoperatively [3][4][5] . In patient no. 3 and 7 in group B, the SACI test revealed accurate localization among multiple NETs, and we performed the surgical procedure according to the result of the SACI test. ...
The selective arterial calcium injection (SACI) test is useful for patients with functional pancreatic neuroendocrine tumors (F-PNETs). This study evaluated which patients with F-PNETs would benefit from the SACI test. We retrospectively analyzed the preoperative findings of patients on computed tomography (CT), magnetic resonance imaging (MRI), CT angiography (CTA), and the SACI test. Fourteen patients who underwent pancreatectomy between January 1997 and September 2016 for F-PNETs were evaluated. We classified these patients into groups A, B, and C; group A, one tumor detected by either CT or MRI; group B, multiple tumors detected; and group C, the tumor location was accordant on CT, MRI, and CTA, but the SACI test revealed another tumor. In group A, the tumor was also detected by CTA and the SACI test was positive on calcium injection. In group B, the focus tumor among the multiple tumors was detected by the SACI test. In group C, another tumor was identified by the SACI test, whose location was different from that detected using CT and MRI. The SACI test is more useful for multiple F-PNETs on CT or MRI. If CT or MRI detects a single tumor, the SACI test or CTA may be unnecessary.
... First, MEN1-associated tumors, with the exception of pituitary NET, are usually multiple, thereby making it difficult to achieve a successful surgical cure. For example, MEN1 patients often develop multiple submucosal duodenal gastrinomas, thereby reducing surgical cure rates compared with similar sporadic solitary tumors, such that only approximately 15% of MEN1 patients, compared with 45% of non-MEN1 patients, are free of disease immediately after surgery, and at 5 yr this decreased to approximately 5% in MEN1 patients, compared with 40% in non-MEN1 patients [6,[11][12][13][14]. MEN1 patients also develop multiple parathyroid tumors, and subtotal parathyroidectomy has resulted in persistent or recurrent hypercalcemia within 10 yr in 20 -60% of MEN1 patients, as opposed to 4% in non-MEN1 patients [6,15,16]. ...
... PD with tumor-free margins and lymphadenectomy appears to be the best choice for lesions of the pancreatic head, in an attempt to completely remove all NETs. Conversely, partial duodenectomy or pancreas-preserving total duodenectomy have been associated with risk of recurrence and persistent postoperative hypergastrinemia [31,34]. In this patient, considering the preoperative assessment, the MEN1 syndrome and the imperative need for a definitive withdrawal of PPIs, the probability that biochemical cure could not be obtained by surgery alone was high. ...
We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.
... Surgery represents the treatment of choice also in case of functional GEP NETs. However, treatment outcomes of these tumors in MEN1 syndrome are less successful than sporadic tumors for different reasons (150): (22,151,152). 2) Occult metastatic disease is more frequent in MEN1 patients with NETs than in patients with sporadic endocrine tumors. For instance, a metastatic disease is present in up to 50% of subjects with MEN1-related insulinomas, whereas less than 10% of sporadic insulinomas are malignant (57). ...
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited tumor syndrome, associated with parathyroid, pituitary, and gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs). MEN1 is usually consequent to different germline and somatic mutations of the MEN1 tumor suppressor gene, although phenocopies have also been reported. This review analyzed main biomedical databases searching for reports on MEN1 gene mutations and focused on aggressive and aberrant clinical manifestations to investigate the potential genotype-phenotype correlation. Despite efforts made by several groups, this link remains elusive to date and evidence that aggressive or aberrant clinical phenotypes may be related to specific mutations has been provided by case reports and small groups of MEN1 patients or families. In such context, a higher risk of aggressive tumor phenotypes has been described in relation to frameshift and non-sense mutations, and predominantly associated with aggressive GEP NETs, particularly pancreatic NETs. In our experience a novel heterozygous missense mutation at c.836C>A in exon 6 was noticed in a MEN1 patient operated for macro-prolactinoma, who progressively developed recurrent parathyroid adenomas, expanding gastrinomas and, long after the first MEN1 manifestation, a neuroendocrine uterine carcinoma. In conclusion, proof of genotype-phenotype correlation is limited but current evidence hints at the need for long-term interdisciplinary surveillance in patients with aggressive phenotypes and genetically confirmed MEN1.
... Sampling Arterial calcium stimulation with hepatic vein catheterization can be used in selected patients when F-DP-NENs such as insulinomas (selective arterial calcium injection [SACI]) or gastrinomas (selective arterial calcium or secretin injection) are undetected on cross-sectional imaging [94,95]. However, this very invasive technique is only able to regionalize but not to localize hormone excess. ...
The better understanding of the biological behavior of MEN1 organ manifestations and the in-crease in clinical experience warrant a revision of previously published guidelines. DP-NENs are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to re-evaluate recommendations for their diagnosis and treatment. Especially over the last two years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syn-drome in an effort to further standardize and improve treatment and follow-up, as well as to es-tablish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guide-lines of 2001 and 2012 and attempts to supplement the recommendations issued by various na-tional and international societies.
