Christian Krautz

Nationwide In-hospital Mortality Following Pancreatic Surgery in Germany is Higher than Anticipated.

Objective: We aimed to determine the unbiased mortality rates for pancreatic surgery procedures at the national level through a comprehensive analysis of every inpatient case in Germany. Summary of Background Data: Several studies have proclaimed a general improvement of perioperative outcomes following pancreatic surgery. These results are challenged by recent analyses of large US databases that found strong volume-outcome relationships, with high mortality in low-volume facilities. Methods: All inpatient cases with a pancreatic surgery procedure code in Germany from 2009 to 2013 were identified from nationwide administrative hospital data. We determined the absolute number of patients and the in-hospital death rate for crucial subcategories such as medical indications and types of surgical procedure. Results: A total of 58,003 inpatient episodes of pancreatic surgery were identified between 2009 and 2013. Annual case numbers increased significantly, which was primarily attributed to patients aged 70 years and older. The overall in-hospital mortality rate (10.1%) did not significantly change during the study period. Major pancreatic resections were associated with mortality ranging from 7.3% (distal pancreatectomy) to 22.9% (total pancreatectomy). Postoperative interventions indicative of severe complications were documented frequently (eg, more than 6 blood transfusions in 20% of all patients and relaparotomy in 16%). Their occurrence was associated with a dramatic increase in mortality. Conclusion: At the national level in Germany, perioperative mortality is higher than anticipated from previous studies. The absence of a significant reduction in overall mortality challenges current health policies that aim to improve the outcomes of high-risk surgical procedures in Germany.

Effect of Hospital Volume on In-hospital Morbidity and Mortality Following Pancreatic Surgery in Germany

Objective: We aimed to determine the effect of hospital volume on in-hospital mortality, and failure to rescue following major pancreatic resections using hospital discharge data of every inpatient case in Germany. Summary Background Data: Several studies have found strong volume–outcome relationships in pancreatic surgery, with high mortality in low-volume facilities. However, their datasets were only based on portions of national populations. In addition, these studies did not assess the effect of hospital volume according to other crucial variables such as medical indications, postoperative complications, and failure to rescue. Methods: We studied all inpatient cases of major pancreatic surgery (n = 60,858) in Germany from 2009 to 2014, using national hospital discharge data. We evaluated the association between hospital volume and in-hospital mortality following major pancreatic resections by using multivariate regression methods. In addition, we analyzed rates of major complications and failure to rescue across hospital volume quintiles. Results: Risk-adjusted in-hospital mortality varied widely across hospital volume quintiles, from 6.5% (95% CI 6.0–7.0) in very high volume hospitals to 11.5% (95% CI 10.9–12.1) in very low volume hospitals (OR 0.47, 95% CI 0.41–0.54). Rates of postoperative interventions necessary for complications and failure to rescue were lower in higher volume hospitals [eg, mortality following septic complications in very high volume hospitals: 24.2% (95% CI 22.4–26.1) vs. very low volume hospitals: 36.8% (34.9–38.7)]. Moreover, we estimated that centralization of surgical care to the minimum volume and mortality risk of the medium volume quintile could prevent at least 94 deaths per year. Conclusions: In Germany, patients who are undergoing major pancreatic resections have improved outcomes if they are admitted to higher volume hospitals. As current health policies failed to centralize pancreatic surgery procedures in Germany, new strategies to initiate a sufficient centralization process in the field of pancreatic surgery are needed.

An update on molecular research of pancreatic adenocarcinoma.

INTRODUCTION This review provides an overview of the molecular mechanisms and pathways known to enhance development and progression of pancreatic ductal adenocarcinoma (PDAC). RESULTS Today, the concept that progression of epithelial precursor lesions leads to invasive PDAC as a result of accumulating mutation in K-ras, p16(INK4A), p53 and Smad4 is widely accepted. Multiple signaling pathways that PDAC utilizes to acquire its tumorigenic features have been identified. Recent data suggest that reactivated developmental signaling pathways play a role in oncogenesis of PDAC. Furthermore, it is now clear that the tumor microenvironment actively promotes invasion and tumor growth through a complex of interactions of different cellular components. CONCLUSION PDAC is still a challenging entity for physicians and scientists. Despite of recent advances in understanding its molecular biology, treatment options remain limited. Distinct tumor stroma interactions and apoptotic resistance lead to frequent failure of current chemotherapy. An early and aggressive tumor infiltration in combination with a late diagnosis prevents successful surgical therapy. Thus, our primary goal remains to translate the increasing knowledge of molecular pathogenesis of this disease into successful therapeutic strategies. Apart from tumor cell biology, the complex interactions of PDAC cells with their microenvironment have to be focus of future molecular research.

Impaired insulin turnover in islets from type 2 diabetic patients

Failure of pancreatic β-cells contributes to the development of type 2 diabetes. Besides evidence of reduced glucose-stimulated insulin secretion and β-cell mass, little information is available about the molecular deficits of human diabetic islets. Islets were isolated from macroscopically normal pancreatic tissue from 8 patients with type 2 diabetes and 17 matched non-diabetic patients who underwent pancreatic surgery. Insulin content and insulin secretion were measured before and after islet stimulation with 25 mM glucose for 2 hours. In parallel, we also investigated the subcellular localization of polypyrimidine tract-binding protein 1 (PTBP1), whose nucleocytoplasmic translocation is involved in the rapid posttranscriptional up-regulation of insulin biosynthesis following islet stimulation with glucose and GLP-1. Glucose stimulated insulin secretion was decreased, albeit not significantly, in type 2 diabetic islets compared to non-diabetic islets. Stimulation increased the total amount of insulin (islet insulin content + secreted insulin) in islet preparation from non-diabetic patients, but not from type 2 diabetic subjects. Furthermore, the nuclear levels of PTBP1 were decreased in stimulated non-diabetic islets, but not in type 2 diabetic islets. These results suggest that impairment of rapid insulin increase in response to glucose is a specific trait of type 2 diabetic islets. Nuclear retention of PTBP1 is likely to play a role in this deficit, which in turn can contribute to impaired insulin secretion in type 2 diabetes. Overall, these data highlight the importance of investigating mechanisms of insulin biosynthesis and degradation to gain insight into the pathogenesis of type 2 diabetes.

Functional assessment of automatically sorted pancreatic islets using large particle flow cytometry.

The size composition of human islet preparations has been attributed to functional potency, islet survival and transplantation outcomes. In the early post-transplantation phase islets are supplied with oxygen by diffusion only and are at risk of critical hypoxia. The high rate of early islet graft dysfunction is in part attributed to this condition. It has been presumed that islets with smaller diameter, and therefore smaller diffusion distance, are superior to large islets regarding early survival rate and graft function. In this study we aimed to evaluate Complex Object Parametric Analysis and Sorting (COPAS) as a device for automated sorting of human islets. The use of COPAS was validated for accuracy and sensitivity using polystyrene beads of known diameters. Based on time of flight relative to particle isolated islets were then automatically sorted and analyzed for viability and function using handpicked islets as control. Our results suggest that COPAS enables the automated and accurate sorting of islets with no negative impact on their integrity and viability. Thus, COPAS is an adequate tool for size-specific analysis of pancreatic islets and may be considered as part of a platform for automated high-throughput screening of pancreatic islets.

Influence of Hospital Volume Effects and Minimum Caseload Requirements on Quality of Care in Pancreatic Surgery in Germany

Introduction: Numerous international studies have identified hospital volume as significant independent variable of death following pancreatic surgery. Most of these studies were limited to regions of countries or portions of a national population and did not include data on volume-outcome effects in Germany. Methods: The Medline database was systematically searched to identify studies that analyzed volume-outcome relationships and effects of minimum caseload requirements on outcomes of pancreatic surgery in Germany. Results: Recent observational studies utilizing German hospital discharge data confirmed that patients undergoing pancreatic surgery in Germany also have better outcomes when treated in facilities with high annual caseloads. Besides a decreased risk of in-hospital mortality, there is also a reduced risk of 1-year mortality in high-volume hospitals. In addition, there is evidence that adherence to already existing minimum caseload requirements reduces morbidity and mortality of pancreatic surgery in Germany. As a result of an insufficient centralization in the recent past, however, a large proportion of hospitals that perform pancreatic surgery still do not meet minimum caseload requirements. Conclusions: Specific measures (i.e. sanctions for failure to achieve minimum volumes) that initiate a sufficient centralization process without threatening patient access to surgical care are needed.

Living with severe dysphagia for 10 years: consequence of misdiagnosis.

TO THE EDITOR: A 52-year-old woman with a longstanding history of slowly progressive stenosis of the cervical esophagus had been referred to us in June 2008. Analysis of her previous health record revealed that solid food dysphagia had appeared for the first time 2 years after subtotal thyroidectomy in 1996. Since then she had undergone numerous endoscopic balloon dilations, botulinum toxin injections and an incomplete esophageal myotomy for presumed peptic stricture. External histological examination of several specimens consistently showed distinct fibrosclerosis without evidence of malignancy. The most recent anamnesis pointed out that dysphagia had worsened. At the same time, loss of body weight exceeded 30 kg. Clinical examination and results of laboratory tests were unremarkable. Endoscopy revealed fibrotic stenosis located 19 cm distal from the incisor teeth. These fibrotic alterations had a length of »1 cm and were occupying more than three-quarters of the esophageal circumference. Ultrasonography and computerized tomography detected no evidence of nodal or visceral metastases. Magnetic resonance imaging showed hypointense wall thickening (»9 mm) of the proximal esophagus in T1and T2-weighted images with a protrusion into the tracheal lumen (Figure 1). These results, as well as the longstanding history of slowly progressive esophageal stenosis, were indicative of a benign, submucosal tumor. Therefore, we decided to perform a surgical resection through a collar incision. After mobilization of the esophagus from the prevertebral fascia, a 12-mm stenosis was found and confirmed by intraoperative esophagoscopy. Following complete lateral myotomy, rock-hard fibrotic tissue was removed. After freeing >180 of the circumference we confirmed good endoscopic patency. Histopathological examination of the specimen found a granular cell tumor with periodic acid–Schiff-positive cytoplasmic granules and strong immunoreactivity for S-100. No signs of malignancy were detectable. The postoperative course was uneventful. A follow-up after 6 months revealed no restrictions of food intake. Granular cell tumors (GCTs) of the esophagus are neoplasms that endoscopists rarely have to deal with [1]. Although having a typical macroscopic appearance, their diagnosis can potentially cause difficulties. This case depicts how misdiagnosis of such a lesion can dramatically affect quality of life as well as future clinical management. Because of the intramural location, the epithelium above these tumors is frequently hyperplastic and squamous. If biopsies taken during endoscopic examination are not deep enough, the GCT will be missed by histological examination. Occasionally, hyperplasia of the covering epithelium is pseudo-carcinomatous and may lead to a misdiagnosis of well-differentiated squamous cell carcinoma [2]. Therefore, the typical endoscopic appearance and endoscopic ultrasonography should be included in the diagnostic decision. In our case, the GCT had not been diagnosed for several years, despite the fact that the patient had consulted various physicians from different specialties. At the time the patient presented to us, the typical macroscopic appearance of a GCT could not be seen due to previous therapy. Because previous reports of external histological examination

Continuous or interrupted suture technique for hepaticojejunostomy? A national survey

BackgroundHepaticojejunostomy is commonly used in hepato-bilio-pancreatic surgery and a crucial step in many surgical procedures, including pancreaticoduodenectomy. The most frequently used techniques are the interrupted suture and the continuous suture technique. Currently, there is no data available in regard to the utilization of these techniques.MethodsIn total, 102 hospitals in Germany were invited between September and November 2017 to participate in this survey. Using a paper-based questionnaire, data were collected on surgical technique and complication rates of hepaticojejunostomies.ResultsA total of 77 of the 102 addressed hospitals (76%) participated in the survey. On average, each hospital performed 71 hepaticojejunostomies per year - most often in the context of pancreaticoduodenectomy (71%). 24 (31%) hospitals exclusively use an interrupted suture technique, 7 (9%) hospitals solely a continuous suture technique, 3 (4%) hospitals perform a combination of continuous and interrupted suture technique and 43 (56%) hospitals decide on one of both techniques depending on intraoperative findings. According to the participants in this survey, the continuous suture technique is significantly faster than the interrupted suture technique in hepaticojejunostomy (p = 0,015). There were no significant differences in the overall complication rate (p = 0,902) and insufficiency rate (p = 1,000).ConclusionsIn Germany, there is a heterogeneity in the technique used to create a hepaticojejunostomy. As our survey suggests that the use of continuous suture technique may offer an advantage in time without jeopardizing patient outcomes, the different techniques should be compared in a randomized controlled study.

Peritoneal dissemination of a gastric API2-MALT1-positive MALT lymphoma.

The majority of mucosa-associated lymphoid tissue (MALT) lymphomas arises in the stomach but a variety of extranodal sites inside or outside the gastrointestinal (GI) tract can be afflicted.1 Gastric MALT lymphomas most frequently spread to a GI site, MALT lymphomas of extragastric origin rather disseminate to a non-GI site. Moreover, gastric MALT lymphomas disseminate less frequently (up to 25%) than extragastric MALT lymphomas (up to 46%).2 It has been reported that at diagnosis up to a third of all MALT lymphomas have disseminated with involvement of one or multiple MALT-containing organs or non-MALT-containing organs.1 The lymph nodes, bone marrow, spleen and liver are common non-MALT sites but also dissemination to the pleura has been described.3 However, involvement of the peritoneum has not been reported before. A patient with an unremarkable social and family history was referred to us for therapy of a newly diagnosed rectal tumour suspicious for cancer. Staging confirmed a large, obstructing tumour of the middle rectum, which showed high-grade dysplasia and atypical glands suspicious for invasive cancer on histological examination (category 4.3 of the revised Vienna classification). Although, signs of locoregional lymph node metastases were missing, we found multiple small mesenteric lesions and ascites in addition to a thickening of the entire stomach wall (figure 1A) and suspiciously enlarged retrocrural and upper abdominal lymph nodes on a CT scan. Subsequent oesophagogastroduodenoscopy revealed multiple peptic …