Oxathiazinane derivatives display both antineoplastic and antibacterial activity: a structure activity study.

PURPOSE: The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250. METHODS: The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects. RESULTS: The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity. CONCLUSION: Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.

Effect of solar radiation on natural organic matter composition in surface waters and resulting impacts on drinking water treatment.

Solar radiation experiments showed a shift in the composition of natural organic matter (NOM). Due to irradiation, the concentration of high molecular weight (HMW) molecules decreased, and that of the low molecular weight (LMW) fraction increased. Microbiological analyses showed that biodegradation was neglectable. To assess the consequences for water treatment processes, coagulation jar tests were performed by comparing the removal effectivity for NOM fractions from irradiated and unirradiated raw water. The degree of dissolved organic carbon (DOC) removal by coagulation was lower for irradiated waters. As primarily HMW organic compounds are removed by coagulation, the decrease in coagulation performance is attributed to the increase in the LMW concentration due to photochemical reactions induced by solar radiation. Flocs were about 15% larger for irradiated water. Possibilities to adapt water treatment to respond to changes in DOC composition and concentration are outlined. Ozonation-biofiltration is judged as the most promising treatment process to cope with climate change-related challenges in drinking water treatment.

Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

[Diagnostic Imaging of pancreatic carcinoma-Update of the new guideline]. / Diagnostik beim Pankreaskarzinom ­ Update in der neuen Leitlinie.

The new German S3 guidelines on ductal pancreatic adenocarcinoma were published for the first time on the homepage of the Association of the Scientific Medical Societies in Germany (AWMF) in December 2021 as a new update and thus the second update (first update 2013) and contain a large number of innovations in terms of diagnostics and treatment. The guidelines were organized and led by the German Society for Digestive and Metabolic Diseases (DGVS). In this article we would like to present the central content and innovations related to the radiological diagnostics of ductal pancreatic adenocarcinoma. The most important innovations are the highest recommendation strength in favor of computed tomography (CT) when assessing tumor spread as well as the adaptation of the European guidelines for cystic tumors by magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the method of first choice. A further innovation is the implementation of a structured reporting of CT findings for describing the anatomical tumor resectability on the basis of the publication presented by the Abdominal Imaging Working Group and the Oncological Imaging Working Group of the German Radiological Society. There is no evidence for the implementation of radiological imaging in the field of aftercare or in the field of screening.

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial.

PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

Lipomatous pancreas facilitates late onset of renal cell carcinoma metastases.

BACKGROUND: Late metastasizing into pancreatic tissue is a special hallmark of renal cell carcinomas (RCC). A very low prevalence leads to scarce data about therapy, prognosis and spreading pathways. The aim of the study was to analyze whether a high fat content in the pancreas facilitates RCC metastases formation. A model for density measurement of pancreatic tissue has been developed and evaluated. Pancreatic fat content was measured comparing Hounsfield units (HU) of CT scans. METHODS: In a consecutive single centre retrospective database of 3600 patients with pancreatic resections, only 12 patients (0.3%) cases of RCC metastases in the pancreas were found. HU were measured in 3 pancreatic regions: head, body and tail in patients' CT scans. HU values were compared to a control population and results aligned with recent literature. RESULTS: We revealed a prevalence of pancreatic metastases of RCC in 0.3% of cases. The formation of RCC in the pancreas occurred within 14 ± 5.6 years after initial diagnosis of RCC. 83.3% of the patients were alive after a follow-up period of up to 48 months. Clinical data analysis revealed an affinity for metastatic formation to lipomatous pancreas. This could be objectivized by HU analysis in CT scans. CONCLUSION: Pancreatic metastases occur late after the first diagnosis of renal carcinoma and show an affinity for lipomatous pancreatic tissues. Due to its rarity in occurrence, multicentric studies are highly recommended to further analyze this correlation between fatty pancreas and RCC.

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial.

BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).

[Treatment of abdominal tuberculosis : Background, diagnostics and treatment of a global problem]. / Therapie der abdominellen Tuberkulose : Hintergrund, Diagnostik und Therapie einer globalen Problematik.

BACKGROUND: Tuberculosis (TB) is among the 10 leading causes of global deaths and is a special threat to immunocompromised patients with human immunodeficiency virus (HIV). Due to migration from endemic areas cases in central Europe can also increase. OBJECTIVE: This article gives an overview of background information, detection methods, treatment and the role of surgery in abdominal manifestation of a systemic infection. MATERIAL AND METHODS: A PubMed search was carried out using the following keywords: abdominal TB, incidence, symptoms, diagnostics, treatment and surgery. RESULTS: The detection of TB in cases of abdominal manifestation can be carried out via percutaneous biopsy; however, laparoscopy is recommended due to the better detection rate, low complication rate and its ability to differentiate other diseases, such as peritoneal carcinomatosis and lymphomas. Antituberculous drugs are the primary treatment. An acute abdomen can occur in up to approximately 30% of cases. Complications such as strictures and perforations require surgical treatment. CONCLUSION: Although the prevalence of TB is decreasing, the infection causes more than 1 million deaths per year. The correct diagnosis can be impeded by a misleading clinical presentation. A multidisciplinary approach enables rapid and efficient diagnostics and treatment.

Natural organic matter fractions and their removal in full-scale drinking water treatment under cold climate conditions in Nordic capitals.

Drinking water treatment plants (DWTPs) designed to remove natural organic matter (NOM) are challenged as concentrations of NOM in raw waters are increasing. Here, we assess seasonal differences in NOM quality and quantity, from raw waters to the distribution network, at three large DWTPs in Oslo, Stockholm and Helsinki. Samples, collected during stable stratification in both winter and summer and during the autumnal turnover, were analysed for NOM concentrations and composition. The NOM was characterized by common routine parameters, size and content (TFF, LC-OCD, fluorescence) and biodegradability. The NOM concentration decreased to 2.5 mg/L (55%), 4.0 mg/L (48%) and 5.7 mg/L (76%) at the respective DWTPs in Oslo, Stockholm and Helsinki. The NOM in raw waters were predominantly in the largest size fraction (>50 kDa), in particular from Oslo. High MW fractions >50 kDa and humics remained the largest fractions with minimum 30% and maximum 80% of the total NOM. The BDOC in treated water <0.3 mg/L and the conditions in the distribution network imply low probability for bacteria regrowth. The multi-step treatment consisting of coagulation/flocculation, sedimentation, rapid sand filtration, ozonation and biological activated carbon filtration (BAC) was most effective in removing NOM. Coagulation/flocculation followed by sedimentation and sand filtration were critical, especially for the removal of biopolymers and humics, and somewhat for building blocks. The sand filtration provided up to 25% additional removal of biopolymers and below 7% removal of other fractions. The ozonation and BAC was more effective and removed 11% of biopolymers, and about 35% of building blocks and LMW neutrals.

Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort.

BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ2-test, Kaplan-Meier estimator and Cox regression hazard model were used for statistical analysis. RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

Diagnostic double strike in the emergency room - two cases of complete pancreatic ruptures due to bicycle handlebar injuries on two consecutive days.

BACKGROUND: Pancreatic injuries are rare in cases of blunt abdominal trauma and therefore easily misdiagnosed at time of hospital admission. They are associated with a significantly elevated morbidity and lethality. Bicycle handlebar injuries are the most common cause of pancreatic trauma in children and adolescents. CASE PRESENTATION: We report two cases of a 23-year-old Caucasian woman and a 15-year-old Caucasian boy who presented to our clinic with a similar history of a bicycle accident on 2 consecutive days. Both suffered from a fall from a bicycle with bicycle handlebar injury 4 and 6 days prior to admission in our clinic. Emergency distal pancreatectomies were performed in both cases. CONCLUSIONS: Pancreatic injuries must be highly suspected in bicycle handlebar injuries, even if amylase/lipase levels or ultrasound findings seem unremarkable. The best initial strategies are early computed tomography and a quick referral to a level 1 trauma center. Distal pancreatectomy is the treatment of choice in cases of complete rupture of the pancreatic body.

[Severe atypical ketoacidosis due to SGLT2-inhibitor therapy : Two case reports]. / Schwere atypische Ketoazidose durch SGLT2-Inhibitor-Therapie : Zwei Fallberichte.

Two female patients were admitted due to ketoacidosis. Serum glucose was moderately elevated. The patients exhibited abdominal and neurologic symptoms. Treatment consisted of metformin, insulin glargin and empagliflozin, as well as glimepiride, insulin detemir and empagliflozin, respectively. Treatment with intravenous fluid replacement, insulin, glucose, potassium and buffer solution led to a normalisation of pH and serum glucose levels. Our report describes two cases of atypical ketoacidosis with moderately elevated serum glucose during sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy.

Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo.

BACKGROUND: Former studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo. METHODS: The anti-neoplastic potential of substance 2250 as well as its mode of action was demonstrated in extensive in vitro analysis, followed by successful and effective in vivo testings, using xenograft models derived from established pancreatic cancer cell lines as well as patient derived tissue. RESULTS: Our functional analysis regarding the role of oxidative stress (ROS) and caspase activated apoptosis showed, that ROS driven programmed cell death (PCD) is the major mechanisms induced by substance 2250 in pancreatic carcinoma. What is strongly relevant towards clinical practice is especially the observed inhibition of patient derived pancreatic cancer tumor growth in mice treated with this new substance in combination with its sharply higher metabolic stability. CONCLUSION: These encouraging results provide new therapeutical opportunities in pancreatic cancer treatment and build the basis for further functional analysis as well as first clinical studies for this promising agent.

[Evidence-based supportive measures to secure pancreatic anastomoses]. / Evidenzlage zu supportiven Maßnahmen zur Sicherung der Pankreasanastomose.

BACKGROUND: Pancreatic anastomosis is the Achilles heel of pancreatic surgery. Despite substantial progress in surgical techniques the rate of postoperative pancreatic fistulas remains very high. For this reason various supportive measures to secure pancreatic anastomoses are of continuing interest. OBJECTIVE: This review presents the newest evidence-based data on supportive measures designed to secure a pancreatic anastomosis. MATERIAL AND METHODS: The most recent meta-analyses, randomized controlled trials and the largest retrospective studies on the role of pancreatic duct stenting, double loop reconstruction, autologous patches and drainage in pancreaticoduodenectomy were taken into account. The value of somatostatin analogues, perioperative nutrition and fluid management is critically discussed. RESULTS: The existing body of evidence on supportive measures is insufficient and remains controversial. The use of somatostatin analogues, drainages and restrictive perioperative fluid management has proven effective. In contrast, routine stenting of the pancreatic duct cannot be recommended. Other approaches, such as double loop reconstruction and use of autologous patches lack sufficient evidence. CONCLUSION: Meticulous surgical technique and surgeon experience remain the cornerstones of performing a safe pancreatic anastomosis; however, some additional supportive measures seem to have significant potential and should be further investigated in large and well-designed prospective clinical trials.

Circumportal Pancreas-a Must Know Pancreatic Anomaly for the Pancreatic Surgeon.

PURPOSE: Circumportal pancreas is a rare congenital pancreatic anomaly with encasement of the portal vein and/or the superior mesenteric vein by pancreatic tissue. It is often overlooked on cross-sectional imaging studies and can be encountered during pancreatic surgery. Pancreatic head resection with circumportal pancreas is technically difficult and bears an increased risk of postoperative pancreatic fistula. MATERIALS AND METHODS: A retrospective chart review of our data base for all patients who had undergone pancreatic head resection between 2004 and 2015 was performed. RESULTS: We identified six patients out of 1102 patients who had undergone pancreatic head surgery in the study period. CT-scan and MRI were never able to identify circumportal pancreas prior to surgery. The right hepatic an artery derived from the superior mesenteric artery in four cases (67%). Additional resection of the pancreatic body was always performed. Postoperative course was uneventful in all cases without occurrence of pancreatic fistula. CONCLUSIONS: Circumportal pancreas is a rare entity every pancreatic surgeon should be aware of. It is difficult to identify on cross-sectional imaging studies. A right hepatic artery arising from the superior mesenteric artery should raise suspicion of circumportal pancreas. Additional pancreatic tissue resection should be performed during pancreatic head resections to avoid pancreatic fistula.

Integrated oxidation membrane filtration process - NOM rejection and membrane fouling.

The extent and mechanisms by which organic matter in a solution can be retained and foul a membrane largely depends on the molecular weight of the material being filtered and the molecular weight cut-off (MWCO) of the membrane. The present study investigated the effect of the MWCO of a membrane and the molecular weight distribution of natural organic matter (NOM) in a source water on the increase in resistance to the permeate flux over time. Of particular interest was the effect of oxidation, applied prior to membrane filtration, on the predominant fouling mechanism. Oxidation can change the molecular weight distribution of organic matter in raw water, and therefore the ability of a membrane to retain this organic matter. Oxidation, using both ozonation and UV/H2O2, could effectively reduce the extent of fouling for higher MWCO membranes. However, neither oxidation approaches could effectively reduce the extent of fouling for lower MWCO membranes, likely because oxidation could not effectively oxidize lower molecular weight organic matter. Althoug the data indicated that the extent of fouling is increasing with the amount of DOC retained by the membrane, no statistically significant correlation was observed between these parameters. The results suggest that oxidation did not affect the predominant fouling mechanism. However, it did affect the molecular weight distribution of the organic matter retained by the membranes, and as a result, the resistance offered by the foulant cake layer.

[Distal Pancreatectomy with Autologous Fibrin Sealant - Implementation of an Established Concept of Tissue Sealing in Pancreatic Surgery]. / Die Pankreaslinksresektion mit autologem Fibrinkleber ­ Anwendung eines etablierten Versiegelungskonzepts in der Pankreaschirurgie.

Background: Postoperative pancreatic fistulas (POPF) remain a major concern after distal pancreatectomy. Irrespective of the technique to close the pancreatic remnant, pancreatic fistulas will occur in approximately 30 % of patients undergoing distal pancreatectomy. For the first time ever, autologous fibrin sealant (Vivostat®) was used to additionally seal the pancreatic remnant after a distal pancreatectomy. The aim was to analyse whether this changes the postoperative outcome. Patients/Material and Methods: In 2015, a technical case series was performed in 15 patients who underwent distal pancreatectomy. The pancreatic remnant was additionally sealed with autologous fibrin sealant (Vivostat®). Results: A postoperative pancreatic fistula (POPF) occurred in 5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided percutaneous drainage had to be placed only in one case. Conclusion: Autologous fibrin sealant is simple to apply and seems to be well tolerated. However, it does not seem to avoid the development of postoperative pancreatic fistulas after distal pancreatectomy.

[Recurrent hypoglycemia due to an occult insulinoma]. / Okkultes Insulinom als Ursache rezidivierender Hypoglykämien.

A 64-year-old woman presented with a history of recurrent hypoglycemia. A prolonged fasting test revealed an increased "amended" insulin-glucose ratio. Transabdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI) did not show abnormal results. An insulinoma was suspected based on a contrast-enhanced endoscopic US examination as well as a (68)gallium-DOTA-exendin-4 positron-emission tomography (PET)/CT. The diagnosis of an insulinoma was confirmed histologically after surgical removal of the tumor. Hypoglycemia did not occur during the postoperative period. The prolonged fasting test is the gold standard for the diagnosis of an insulinoma. Novel imaging procedures, such as contrast-enhanced endoscopic US or (68)gallium-DOTA-exendin-4 PET/CT are valuable additions to the diagnostic workup.