[Individualized approach for MEN1-associated duodenopancreatic neuroendocrine neoplasms]. / Individualisiertes Vorgehen bei MEN1-assoziierten duodenopankreatischen neuroendokrinen Neoplasien.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1)-associated duodenopancreatic neuroendocrine neoplasms (dpNEN) represent the most frequent syndrome-associated cause of death, but the adequate treatment is sometimes considered controversial. OBJECTIVE: Presentation of possible diagnostic and therapeutic options for MEN1-associated dpNENs. MATERIAL AND METHODS: In this review article retrospective case studies, expert recommendations, national and international guidelines as well as personal experiences were analyzed and evaluated. RESULTS: Due to early detection programs and the use of the most modern imaging techniques, dpNEN are nowadays diagnosed much earlier. Nonfunctional pNENs currently represent the most frequent dpNENs with about 70%, followed by gastrinomas and insulinomas. Regardless of their functional activity, dpNENs with a size of > 2 cm are generally an indication for surgery. The choice of the optimal treatment strategy, however, in most cases remains the subject of controversial discussions, although nowadays surgery should always be performed in an organ-preserving and minimally invasive way when feasible. Recurrences or new dpNENs are expected in more than 60% of cases, necessitating a reoperation in up to 40% of these cases. Duodenopancreatic resections and reoperations can be carried out safely by experienced practitioners and with an acceptable level of risk. CONCLUSION: The planning of treatment requires careful consideration of the suitable timing, the extent of the operation, the risk of recurrence and potential morbidities. Furthermore, preserving pancreatic function and the quality of life is of utmost importance. In view of the complexity of the disease, MEN1 patients should be treated in specialized centers.

Multiple Endocrine Neoplasia Type 1: The Current Status of Disease Management.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disease of autosomal dominant inheritance, with an estimated prevalence of 3-20/100 000. Its main feature is neuroendocrine neoplasia in the parathyroid glands, the endocrine pancreas, the duodenum, and the pituitary gland. In this article, we review the diagnostic and therapeutic options for MEN1-associated tumors. METHODS: We present an analysis and evaluation of retrospective case studies retrieved from PubMed, guidelines from Germany and abroad, and our own experience. RESULTS: The disease is caused by mutations in the MEN1 gene. Mutation carriers should participate in a regular, specialized screening program from their twenties onward. The early diagnosis and individualized treatment of MEN1-associated tumors can prevent the development of life-threatening hormonal syndromes and prolong the expected life span of MEN1 patients from 55 to 70 years, as well as improving their quality of life. Surgical treatment is based on the location, size, growth dynamics, and functional activity of the tumors. The evidence for treatment strategies is derived from retrospective studies only (level III evidence) and the optimal treatment is often a matter of debate. This is a further reason for treatment in specialized centers. CONCLUSION: MEN1 is a rare disease, and, consequently, the evidence base for its treatment is limited. Carriers of disease-causing mutations in the MEN1 gene should be cared for in specialized interdisciplinary centers, so that any appreciable tumor growth or hormonal activity can be detected early and organ-sparing treatment can be provided.

Characteristics, therapy, and outcome of rare functioning pancreatic neuroendocrine neoplasms.

Functioning pancreatic neuroendocrine neoplasms other than insulinomas and gastrinomas (rf-pNENs) are exceptionally rare tumours. Thus, their characteristics and long-term prognosis have not been well defined. This article aims to present data and experience from a single institution concerning this topic. Twelve of 216 (5.5%) patients with pNENs operated between 2002 and 2022 in the ENETS Centre of Excellence Marburg had rf-pNENs and their data were retrospectively analysed. We identified three vasoactive intestinal polypeptide producing pNENs, four glucagonomas and five calcitoninomas. The tumour could be visualised by preoperative imaging in all 12 patients, and six patients had distant metastases at the time of diagnosis. The tumour was located in the pancreatic tail in nine patients and the median tumour size was 82 (range 12-220) mm. Eleven patients underwent tumour resections (two robotic, nine conventional), nine of which were R0. After a median follow-up of 75 (range 1-247) months, six patients were alive, five of whom had no evidence of disease. All patients who remained disease-free had an initial R0 resection of the primary tumour and no initial liver involvement. This study sheds light on the distinct characteristics and outcomes of these exceedingly rare tumours, offering insights for improved understanding and management.

Acinar content at pancreatic resection margin is significantly associated with clinically relevant pancreatic fistula after partial pancreatoduodenectomy.

BACKGROUND: This study aimed to evaluate the clinical significance of acinar content at the pancreatic resection margin after partial pancreatoduodenectomy (PD). METHODS: A total of 228 consecutive patients undergoing PD were included for analysis. Resection margins were assessed for acinar, fibrosis, and fat contents by 2 pathologists blinded to the patients' clinical data. Univariate and multivariable analyses of possible predictors for clinically relevant postoperative pancreatic fistula (cr-POPF) were performed. RESULTS: The median acinar, fibrosis, and fat contents were 70% (IQR, 25%-82%), 13% (IQR, 5%-40%), and 15% (IQR, 9.25%-25%), respectively. The rates of cr-POPF were significantly higher in patients with an acinar content of >70% than in patients with an acinar content of ≤70% (26.4% vs 5.5%, respectively; P < .001). In addition, the rates of postoperative hyperamylasemia (POH) were significantly higher in patients with an acinar content of ≥70% than in patients with an acinar content of ≤70% (55.2% vs 13.8%, respectively; P < .001). The median fat content did not differ between patients with and without cr-POPF (13.0% [IQR, 7.5%-20.0%] vs 15.0% [IQR, 10.0%-30.0%], respectively; P = .06). An acinar content of >70% at the pancreatic resection margin (odds ratio [OR], 4.85; 95% CI, 1.61-14.58; P = .005) and a soft pancreatic texture (OR, 2.82; 95% CI, 1.02-7.76; P = .046) were independent predictive factors of cr-POPF in the multivariable analysis. CONCLUSION: An acinar content of ≥70% at the pancreatic resection margin was a significant predictive factor for cr-POPF after PD and was also significantly associated with POH, a precursor of cr-POPF after PD in many cases. Fatty infiltration of the pancreatic resection margin was not associated with cr-POPF.