Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms.

BACKGROUND: The incidence of asymptomatic, sporadic, small non-functioning pancreatic neuroendocrine neoplasms (NF-PNENs) has increased in recent decades. Conservative treatment has been advocated for these tumours. The aim of this study was systematically to evaluate the literature on active surveillance and to compare this with surgical management for asymptomatic sporadic small NF-PNENs. METHODS: PubMed, Embase and the Cochrane Library were searched systematically for studies that compared the active surveillance of asymptomatic, sporadic, small NF-PNENs with surgical management. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 3915 records, five retrospective studies with a total of 540 patients were included. Of these, 327 patients (60·6 per cent) underwent active surveillance and 213 (39·4 per cent) had surgery. There was wide variation in the tumour diameter threshold considered as inclusion criterion (2 cm to any size). The median length of follow-up ranged from 28 to 45 months. Measurable tumour growth was observed in 0-51·0 per cent of patients. Overall, 46 patients (14·1 per cent) underwent pancreatic resection after initial conservative treatment. In most patients the reason was an increase in tumour size (19 of 46). There were no disease-related deaths in the active surveillance group in any of the studies. CONCLUSION: This systematic review suggests that active surveillance of patients affected by sporadic, small, asymptomatic NF-PNENs may be a good alternative to surgical treatment.

Refinement of screening for familial pancreatic cancer.

OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Well-differentiated neuroendocrine neoplasia: relapse-free survival and predictors of recurrence after curative intended resections.

BACKGROUND: Resection with curative intention is the cornerstone of treatment in patients with neuroendocrine tumors. A proportion of patients will relapse after R0 resection, but the factors predictive of recurrence are not well understood. METHODS: A database established 1998 at the University Hospital Marburg was queried for all patients with documented R0 resection. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Uni- and multivariate analyses were performed. RESULTS: 180 patients with a median age of 52 years entered the analysis. We observed 77 recurrences after a median time of 2.9 years. 24% of the recurrences occurred later than 5 years after operation. Median recurrence-free survival of the whole cohort was 101 months. In univariate analysis grade by Ki-67, stage, high lymph node ratio and microangioinvasion were significant predictors of recurrence. On multivariate analysis these parameters were confirmed as independent prognostic parameters with stage and microangioinvasion being the most important predictors. CONCLUSIONS: After R0 resection of neuroendocrine tumors, postoperative surveillance should be extended to at least 10 years. Patients with distant metastases and microangioinvasion are at high risk of recurrence. Clinical trials of adjuvant treatment protocols are indicated in these patients.

Embryonic transcription factors CDX2 and Oct4 are overexpressed in neuroendocrine tumors of the ileum: a pilot study.

BACKGROUND: Neuroendocrine tumors (NETs) of the ileum are rare submucosal tumors that are often diagnosed at advanced stages with metastatic spread to the liver causing a carcinoid syndrome. They present as solitary or multiple tumors. In NETs, loss of sequences on chromosomes 11, 16, 18 and 22 or gain of sequences on chromosomes 17 and 19 has been described. In this study we explored the expression of two novel candidate genes, CDX2 and Oct4, in NETs of the ileum and analyzed whether the molecular expression pattern correlates with the clinical phenotype (solitary/multiple tumors). METHODS: Data from all patients who underwent surgery for a NET of the ileum between 2000 and 2010 were retrieved from a prospective database. For each patient, frozen normal and tumor tissue was used for the comparison of gene expression levels of two putative cancer stem cell markers, CDX2 and Oct4, using real-time PCR (rtPCR). Serial slides from paraffin blocks were used for immunohistochemistry. Gene expression was compared between normal and tumor tissue as well as between solitary and multiple tumors. RESULTS: 78 patients were identified. In rtPCR, a statistically significant higher expression of CDX2 in tumor tissue (p < 0.001) compared to normal tissue was found. The expression of Oct4 was elevated in the tumors, but did not reach the level of significance (p = 0.155). The expression of both candidate genes was confirmed immunohistochemically and showed a nuclear expression pattern. There was no difference in expression between solitary and multiple tumors or between tumors that had already spread to the liver. CONCLUSION: CDX2 is overexpressed in ileum NETs, thus playing a role in the tumorigenesis of these rare tumors. Since expression does not correlate with clinical stage or phenotype, it might be an early event in tumor development.

[Hereditary medullary thyroid cancer]. / Hereditäres medulläres Schilddrüsenkarzinom.

Parafollicular C cells progress via C cell hyperplasia to medullary thyroid cancer (MTC), which can be present even in the first years of life in multiple endocrine neoplasia (MEN) type 2A and 2B patients. Basal calcitonin and carcinoembryonic antigen (CEA) are useful tumor markers for the diagnosis and monitoring. The prognosis depends on the stage when the disease is diagnosed and there is a good genotype-phenotype correlation with the RET proto-oncogene, which can be used for estimation of the risk. The risk-stratified prophylactic thyroidectomy plays a decisive role in the prognosis of known gene mutation carriers.

[Localization diagnostics and operative strategy for the first intervention in sporadic primary hyperparathyroidism]. / Lokalisationsdiagnostik und Operationsstrategie beim Ersteingriff bei sporadischem primärem Hyperparathyreoidismus.

Primary hyperparathyroidism (pHPT) is a frequent endocrine disease, the incidence of which is clearly increasing. In addition to the classical symptoms of bone pain, osteoporosis and renal calculi, nonspecific complaints, such as listlessness and exhaustion, anxiety states and depressive symptoms also often occur. The diagnosis is simple and is carried out by determination of calcium and parathormone (PTH) serum levels. The majority of parathyroid adenomas can be localized by ultrasound and Tc-99m-MIBI scintigraphy. The indications for surgery can normally already be identified by the laboratory biochemical detection. Surgery is the only curative treatment of pHPT and is normally successful. In addition to bilateral exploration, a focused parathyroidectomy can be planned. The success of surgery can be intraoperatively documented by the determination of intraoperative Quick PTH (IOPTH).

Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma.

BACKGROUND: The study was undertaken to determine prognostic factors and the value of systematic lymphadenectomy on survival in sporadic gastrinoma. METHODS: Patients with sporadic gastrinoma who underwent initial surgery during a 21-year period in two tertiary referral centres were analysed retrospectively with respect to clinical characteristics, operative procedures and outcome. RESULTS: Forty-eight patients with a median age of 52 (range 22-73) years were analysed. Some 18 patients had pancreatic and 26 had duodenal gastrinomas, whereas the primary tumour remained unidentified in four patients. After a median postoperative follow-up of 83 (range 3-296) months, 20 patients had no evidence of disease, 13 patients were alive with disease, 11 patients had died from the disease and four had died from unrelated causes. In 41 patients who underwent potentially curative surgery, systematic lymphadenectomy with excision of more than ten lymph nodes resulted in a higher rate of biochemical cure after surgery than no or selective lymphadenectomy (13 of 13 versus 18 of 28 patients; P = 0·017), with a trend towards prolonged disease specific survival (P = 0·062) and disease-free survival (P = 0·120), and a reduced risk of death (0 of 13 versus 7 of 24 patients; P = 0·037). Negative prognostic factors for disease specific survival were pancreatic location (P = 0·029), tumour size equal to or larger than 25 mm (P = 0·003), Ki-67 index more than 5 per cent (P < 0·001), preoperative gastrin level 3000 pg/ml or more (P = 0·003) and liver metastases (P < 0·001). Sex, age, type of surgery and presence of lymph node metastases had no influence on disease free or disease specific survival. CONCLUSION: In sporadic gastrinoma, systematic lymphadenectomy during initial surgery may reduce the risk of persistent disease and improve survival.

Harmonic scalpel versus conventional dissection technique in pylorus-preserving partial duodenopancreatectomy.

BACKGROUND/AIMS: Pancreatic head resection is performed with low mortality, but morbidity remains high. Extensive preparation, long operating times, intraoperative blood loss and the need for blood transfusions are risk factors for postoperative morbidity. The aim of our study was to evaluate the feasibility and safety of the ultrasonic dissection device in pylorus-preserving duodenopancreatectomy (PPPD). METHODS: Fifty consecutive patients who underwent PPPD with an ultrasonic dissection device (group 1) were compared with a match-controlled group of 50 consecutive patients who underwent PPPD with conventional dissection techniques (group 2). Duration of surgery, intraoperative blood loss, blood units, complications, mortality and duration of hospital stay were analyzed. RESULTS: There was no difference in age, gender or BMI between groups. In group 1, mean blood loss (446 ± 281.8 ml, p = 0.008) and number of blood units (0.32 ± 0.86, p = 0.001) were significantly lower than in group 2 (819 ± 915.4 ml; 1.36 ± 2.83 units). Duration of surgery was shorter in group 1 (345.6 vs. 373 min, p = 0.28). The rate of postoperative complications, mortality and hospital stay were not significantly different. CONCLUSIONS: Use of an ultrasonic dissection device in PPPD might significantly reduce intraoperative blood loss and the need for blood transfusions. These results should be verified in a prospective randomized controlled trial.

[The Marburg surgical curriculum - improving the attraction of medical education by teaching central surgical competence]. / Das Marburger chirurgische Curriculum - Attraktivitätssteigerung der studentischen Ausbildung in der Chirurgie durch Vermittlung von chirurgischen Kernkompetenzen.

The quality of medical education is an ongoing challenge due to the continuing changes of the health-care politics and general social conditions. At many German university hospitals the dominating picture is overfilled courses, lack of hands-on practice, reduced patient contact and the dull provision of theoretical, abstract knowledge. The reformed surgical curriculum at the University of Marburg university hospital is used to demonstrate that, in spite of large student numbers, a practice-oriented, small-group training at a high didactic level is possible. The surgical training courses are organized in detail and coordinated. Course contents and structure are media available in print and online versions for both students and teachers and thus fulfill not only transparency needs but also contemporary requirements. The strategy of a practice- and patient-oriented, small-group training is followed strictly in the surgical curriculum. In addition, accompanying tutorial possibilities for individual study in an up-to-date learning center are offered. Here the students have the opportunity to intensify knowledge acquired in previous or future courses with numerous attractive education means. Continuous evaluation of the individual training courses at the end of each semester not only document motivation of the students but also serve to continuously improve the training concepts.

[Hereditary neuroendrocrine tumors. Multiple endocrine neoplasia type 1 and 2]. / Hereditäre neuroendokrine Tumoren. Multiple endokrine Neoplasien Typ 1 und 2.

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal-dominant hereditary disease characterized by the occurrence of tumors of the parathyroids, duodenum and/or pancreas, and anterior pituitary. The syndrome is caused by germline mutations of the MEN1 tumor suppressor gene. The identification of the causative mutations is of paramount importance for the long-term management of affected individuals and their relatives. Multiple endocrine neoplasia type 2 (MEN2) is less frequent than MEN1 and represents a cancer syndrome caused by autosomal-dominant inherited mutations of the RET proto-oncogene, and displays a genotype-phenotype correlation of remarkable clinical relevance. Major components of MEN-2 comprise medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism. Since 25-30% of patients with MTC display a hereditary background, genetic testing is indicated once MTC is diagnosed. Occurrence of MTC can be avoided by prophylactic thyroidectomy in early childhood in gene carriers. Early diagnosis and therapy of simultaneous pheochromocytoma avoids the development of complications caused by acute or chronic hypertension.

[EUROCRINE®: adrenal surgery 2015-2019- surprising initial results]. / EUROCRINE®: Nebennierenoperationen 2015 bis 2019 ­ überraschende erste Ergebnisse.

BACKGROUND: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines. METHODS: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. RESULTS: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. CONCLUSION: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

[Diagnosis and surgical management of neureondocrine pancreatic tumours]. / Diagnostik und operative Therapie des Gastrinoms, Vipoms, Glukagonoms, Somatostatinoms und nichtfunktioneller endokriner Pankreastumoren.

The only chance of cure for patients with pancreatic endocrine tumours (PETs) is complete surgical removal not only of the primary tumour, but also of local or distant metastases. This is true for gastrinomas, vipomas, glucagonomas, somatostatinomas and non-functional pancreatic endocrine tumours. An aggressive surgical approach leads to cure in patients with benign tumours, and may achieve long-term survival in patients with malignant NPTs.

Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer.

OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme. AIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years. METHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography. RESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1). CONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.

[Perineal hernia. A rare complication following abdominoperineal rectal amputation]. / Perineale Hernie : Seltene Komplikation nach abdominoperinealer Rektumamputation.

BACKGROUND: Abdominoperineal excision of the rectum is a standard procedure in deep-lying rectal cancer if the sphincter muscle cannot be preserved. Besides common complications such as impotence, disorders of urinary tract function, and prolonged wound healing, perineal hernia is a rare long-term phenomenon. Surgical repair can be done either through a transabdominal approach or transperineally. Long-term results show that both methods are feasible in this situation. We report the third case of perineal hernia in German literature. CASE REPORT: A 66-year-old man presented with a painful perineal tumor 2 years after abdominoperineal excision for rectal adenocarcinoma. Perineal hernia was confirmed by magnetic resonance imaging, and the patient underwent open mesh repair through a perineal approach. DISCUSSION: A number of surgical techniques have been described for the repair of perineal hernias. These include abdominal, perineal, and combined or laparoscopic approaches with or without mesh repair. The transabdominal route seems to have some advantages over the perineal approach. In cases of small hernias, the latter can however be the option of choice. In the presented case of an uncomplicated hernia, we decided on the perineal approach including mesh implantation to keep the trauma as small as possible.

Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer is among the most dismal of human malignancies. Current therapeutic strategies are virtually ineffective in controlling advanced, metastatic disease. Recent evidence suggests that the Hedgehog signalling pathway is aberrantly reactivated in the majority of pancreatic cancers, and that Hedgehog blockade has the potential to prevent disease progression and metastatic spread. METHODS: Here it is shown that the Hedgehog pathway is activated in the Pdx1-Cre;LsL-Kras(G12D);Ink4a/Arf(lox/lox) transgenic mouse model of pancreatic cancer. The effect of Hedgehog pathway inhibition on survival was determined by continuous application of the small molecule cyclopamine, a smoothened antagonist. Microarray analysis was performed on non-malignant human pancreatic ductal cells overexpressing Gli1 in order to screen for downstream Hedgehog target genes likely to be involved in pancreatic cancer progression. RESULTS: Hedgehog inhibition with cyclopamine significantly prolonged median survival in the transgenic mouse model used here (67 vs 61 days; p = 0.026). In vitro data indicated that Hedgehog activation might at least in part be ascribed to oncogenic Kras signalling. Microarray analysis identified 26 potential Hedgehog target genes that had previously been found to be overexpressed in pancreatic cancer. Five of them, BIRC3, COL11A1, NNMT, PLAU and TGM2, had been described as upregulated in more than one global gene expression analysis before. CONCLUSION: This study provides another line of evidence that Hedgehog signalling is a valid target for the development of novel therapeutics for pancreatic cancer that might be worth evaluating soon in a clinical setting.

Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival.

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

[Early endocrine neoplasia of the pancreas]. / Kleine neuroendokrine Neoplasien des Pankreas.

Pancreatic endocrine neoplasias (pNENs) are uncommon but fascinating tumors with a rising incidence. In accordance to its location, size and grading, the decision to operate the patient should always be made in an interdisciplinary approach. This article provides a comprehensive review of the current literature addressing the current challenges in pNEN surgery and shows that patients with completely resected small pNENs generally have an excellent prognosis, but also that surveillance may be a powerful tool.

Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas.

BACKGROUND: Gastrinomas are functional endocrine duodenopancreatic tumours and are responsible for Zollinger-Ellison syndrome (ZES). Clinical presentation, localization techniques and operative management were reviewed. METHODS: An electronic search of the Medline database was undertaken for articles published in English between January 1987 and May 2007. This timeframe was chosen because of the fundamental changes in operative strategy, antisecretory therapy and localization techniques during this period. RESULTS AND CONCLUSION: Most gastrinomas are located in the 'gastrinoma triangle', comprising the head of the pancreas, and the first and second parts of the duodenum. Some 20 per cent of gastrinomas occur in association with multiple endocrine neoplasia type 1 (MEN1) and 50-60 per cent of tumours are malignant at the time of diagnosis. Biochemical evidence justifies operation of which duodenotomy is an essential part. Only complete tumour resection allows 5- and 10-year survival rates of 90 per cent. Pylorus-preserving pancreaticoduodenectomy may be the procedure of choice for MEN1-ZES.

Pancreatitis in primary hyperparathyroidism-related hypercalcaemia is not associated with mutations in the CASR gene.

BACKGROUND: Primary hyperparathyroidism (pHPT) related hypercalcaemia is considered to represent a risk factor for the development of pancreatitis. We therefore explored whether mutations in the calcium-sensing receptor gene ( CASR) coding for the calcium-sensing receptor (CaR), an essential regulator of the calcium homeostasis in parathyroid chief cells, exist in a cohort of patients with pHPT and pancreatitis. METHODS: Among 826 patients prospectively studied between 1987 and 2002 with pHPT, 38 patients were identified with pancreatitis (4.6%). DNA was available of 25 patients (13 females and 12 males). These individuals were analysed for mutations in the CASR by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. RESULTS: None of the 25 patients with pHPT and pancreatitis carried a CASR mutation and only one had a known heterozygous polymorphism R990G. CONCLUSIONS: Pancreatitis in primary hyperparathyroidism is not associated with mutations in the CASR gene, while it remains to be determined why the polymorphisms A986S, R990G and Q1011E were less often present in that subgroup than in the normal population.