[Successful pembrolizumab therapy in metastasized adenosquamous carcinoma of the colon]. / Erfolgreiche Pembrolizumab-Therapie bei metastasiertem adenosquamösem Karzinom des Kolons.

Adenosquamous carcinoma (ASqC) is an exceedingly rare subtype of colorectal cancer without any known special guidelines for treatment. The biological behaviour and molecular background are widely unknown, although a few case studies report a worse prognosis compared to ordinary colorectal adenocarcinoma. We herein report for the first time the successful immune checkpoint inhibitor therapy in a 40-year-old patient suffering from metastasized right-sided colonic ASqC with unique molecular features, after having previously progressed under standard chemotherapy.

Minimally Invasive Surgery for Pancreatic Disease - Current Status.

Laparoscopic procedures have advanced to represent the new gold standard in many surgical fields. Although application in pancreatic surgery is hampered by the friable nature of the gland and the difficulty of its exposure, advanced technology and surgeons' experience are leading to an expansion of minimally invasive pancreatic surgery. Addressing the whole range of main operative procedures, this review analyzes the literature data so far to give an overview about the current status of minimally invasive pancreatic surgery, its indications and limitations. In acute pancreatitis, a step-up approach from percutaneous drainage to retroperitoneoscopic necrosectomy seems beneficial. Transgastric necrosectomy also preserves the retroperitoneal compartment in contrast to the laparoscopic approach, which has widely been abandoned. In tumor pathology, laparoscopic access is adequate for small benign lesions in the pancreatic tail and body. Oncological outcome shows to be at least equal to the open procedure. Concerning laparoscopic pancreaticoduodenectomy, there is no evidence for a patients' benefit currently although several studies prove that it can be done.

Volume-outcome relationship in pancreatic surgery.

BACKGROUND: Volume-outcome relationships related to major surgery may be of limited value if observation ends at the point of discharge without taking transfers and later events into consideration. METHODS: The volume-outcome relationship in patients who underwent pancreatic surgery between 2008 and 2010 was assessed using claims data for all inpatient episodes from Germany's largest provider of statutory health insurance covering about 30 per cent of the population. Multiple logistic regression models with random effects were used to analyse the effect of hospital volume (using volume quintiles) on 1-year mortality, adjusting for age, sex, primary disease, type of surgery and co-morbidities. Additional outcomes were in-hospital (including transfer to other hospitals until final discharge) and 90-day mortality. RESULTS: Of 9566 patients identified, risk-adjusted 1-year mortality was significantly higher in the three lowest-volume quintiles compared with the highest-volume quintile (odds ratio 1·73, 1·53 and 1·37 respectively). A similar, but less pronounced, effect was demonstrated for in-hospital and 90-day mortality. The effect of hospital volume on 1-year mortality was comparable to the effect of co-morbid conditions such as renal failure. CONCLUSION: Although mortality related to pancreatic surgery is influenced by many factors, this study demonstrated lower mortality at 1 year in high-volume centres in Germany.

Surgical endoscopic vacuum therapy for anastomotic leakage and perforation of the upper gastrointestinal tract.

INTRODUCTION: Emergency operations for perforations and anastomotic leakage of the upper gastrointestinal tract are associated with a high overall morbidity and mortality rate. An endoscopic vacuum therapy (EVT) has been established successfully for anastomotic leakage after rectal resection but only limited data exist for EVT of the upper GI tract. METHODS: We report on a series of nine patients treated with EVT for defects of the upper intestinal tract between March 2011 and May 2012. In four patients, initial endoscopic sponge placement was performed in combination with open surgical revision. Median follow-up was 189 (range, 51-366) days. RESULTS: In total, 52 vacuum sponges were placed in upper GI defects of nine patients. Indication for EVT were anastomotic leakage after esophageal resection or gastrectomy (n = 5) and iatrogenic or spontaneous esophageal perforations (n = 4). The mean number of sponge insertions was six (range, 1-13) with a mean changing interval of 3.5 days (range, 2-5). A successful vacuum therapy for upper intestinal defects was achieved in eight of nine patients (89 %). CONCLUSION: EVT is a promising approach for postoperative, iatrogenic, or spontaneous lesions of the upper GI tract. If necessary the endoscopic procedure can be combined with operative revision for better control of the local septic focus.

Duodenum-preserving subtotal and total pancreatic head resections for inflammatory and cystic neoplastic lesions of the pancreas.

INTRODUCTION: For treatment of inflammatory and benign neoplastic lesions of the pancreatic head, a subtotal or total pancreatic head resection is a limited surgical procedure with the impact of replacing the application of a Whipple procedure. The objective of this work is to describe the technical modifications of subtotal and total pancreatic head resection for inflammatory and neoplastic lesions of the pancreas. The advantages of this limited surgical procedure are the preservation of the stomach, the duodenum and the extrahepatic biliary ducts for treatment of benign lesions of the pancreatic head, papilla, and intrapancreatic segment of the common bile duct. For chronic pancreatitis with an inflammatory mass complicated by compression of the common bile duct or causing multiple pancreatic main duct stenoses and dilatations, a subtotal pancreatic head resection results in a long-lasting pain control. Performing, in addition, a biliary anastomosis or a Partington Rochelle type of pancreatic main duct drainage, respectively, is a logic and simple extension of the procedure. The rationale for the application of duodenum-preserving total pancreatic head resection for cystic neoplastic lesions are complete exstirpation of the tumor and, as a consequence, interruption of carcinogenesis of the neoplasia preventing development of pancreatic cancer. Duodenum-preserving total head resection necessitates additional biliary and duodenal anastomoses. For mono-centric IPMN, MCN, and SCA tumors, located in the pancreatic head, total duodenum-preserving pancreatic head resection can be performed without hospital mortality and resurgery for recurrency. Based on controlled clinical trials, duodenum-preserving pancreatic head resection is superior to the Whipple-type resection with regard to lower postoperative morbidity, almost no delay of gastric emptying, preservation of the endocrine function, lower frequency of rehospitalization, early professional rehabilitation, and establishment of a predisease level of quality of life. CONCLUSION: The limited surgical procedures of subtotal or total pancreatic head resection are simple, safe, ensures free tumour margins and replace in the authors institution the application of a Whipple-type head resection.

Anti-cytokine strategies in acute pancreatitis: pathophysiological insights and clinical implications.

The clinical presentation of acute pancreatitis varies significantly from mild self-limiting discomfort to a severe life-threatening condition. Once the disease process is initiated, the severity of the disease is largely determined by a complex network of activated inflammatory mediators such as cytokines, proteolytic enzymes, reactive oxygen species, and many more which render the local injury to a systemic disease with multiple organ dysfunction, sepsis, and considerable mortality. Remarkable progress in diagnostic modalities, intensive care technologies, and organ preserving surgical techniques have decreased mortality of severe acute pancreatitis during the past decades. However, the treatment of acute pancreatitis still remains largely supportive and no specific approach exists to prevent evolving complications. A large body of clinical and experimental evidence suggests that cytokines are key factors in the pathomechanism of local and systemic complications of acute pancreatitis. Targeting cytokine activity as therapeutic approach to acute pancreatitis is a challenging concept and the results of modulating activation of TNF-alpha, IL-1beta, IL-2, IL-10, PAF and various chemokines has indeed been promising in the experimental setting even if tested under therapeutic conditions. However, experience from a limited number of clinical trials on anti cytokine strategies in acute pancreatitis has remarkably emphasized that translating successful experimental observations into reproducible clinical associations seems to be difficult.

Surgical treatment of pancreas divisum causing chronic pancreatitis: the outcome benefits of duodenum-preserving pancreatic head resection.

Pancreas divisum (PD) represents a duct anomaly in the pancreatic head ducts, leading frequently leading to recurrent acute pancreatitis (rAP) or chronic pancreatitis (CP). Based on endoscopic retrograde cholangiopancreatography, pancreas divisum can be found in 1% to 6% of patients with pancreatitis. The correlation of this abnormality with pancreatic disease is an issue of continuing controversy. Because of the underlying duct anomalies and major pathomorphological changes in the pancreatic head, duodenum-preserving pancreatic head resection (DPPHR) offers an option for causal treatment. Thirty-six patients with pancreatitis caused by PD were treated surgically. Thirty patients suffered from CP, 6 from rAP. The mean duration of the disease was 47.5 and 49.8 months, respectively. The age at the time of surgery was 39.2 years in the CP group, and 27.6 years in the rAP group. Median hospitalization since diagnosis was 18.8 weeks for CP patients and 24.6 weeks for rAP patients. Previous procedures performed in these patients included endoscopic papillotomy (30%), duct stenting (14%), and surgical treatment (17%). The median preoperative pain score was 8 on a visual analog scale. According to the classification of pancreas divisum, 10 patients demonstrated a complete PD, 25 had a functionally incomplete PD, and 1 had a dorsal duct type. The pain status as well as the endocrine (oral glucose tolerance test) and exocrine (pancreolauryl test) function were evaluated preoperatively and early and late postoperatively with a median follow-up time of 39.3 months. There was no operative-related mortality. The follow-up was 100%; 4 patients died (1 from suicide, 1 from cardiac arrest, and 2 from cancer of the esophagus). Fifty percent of the patients were completely pain-free, 31% had a significant reduction of pain with a median pain score of 2 (P < 0.001). Six patients (5 CP, 1 rAP) had further attacks of acute pancreatitis with a need for hospitalization. DPPHR reduced pain and preserved the endocrine function in the majority of patients with pancreas divisum. Therefore, DPPHR is an alternative to other resective or drainage procedures after failure of interventional treatment.

Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater.

Cancer of the papilla or the ampulla of Vater appears, from a clinical point of view, to be an intraduodenal or ampullary cancer. An adenoma-dysplasia-carcinoma sequence has been established. In 20%-40% of the patients with an adenoma of the papilla, a cancerous lesion in the adenoma is additionally observed. Oncological resection using a Kausch-Whipple technique or a pylorus-preserving partial pancreatico-duodenectomy (PPPD) offers a 5-year survival probability of between 45% and 65%. The hospital mortality after oncological resection at experienced centers is below 5%. The most frequent treatment-related complication is pancreatic fistula, which occurs in around 20% of the patients. In about 10% of the patients with a pT1 cancer and in 25% to 67% with pT2 and pT3 cancer, lymph node involvement has been observed. Lymph nodes in front of and behind the head of the pancreas are the primary targets for cancer cell disseminations. In more than one-third of the patients, lymph nodes in the inter-aortocaval space and the lymph nodes around the superior mesenteric artery and the nodes in the pancreatic segment of the hepatoduodenal ligament are involved. Therefore, tissue dissection, including, selectively, the N2 lymph nodes, is an essential component of radical surgery for cancer of the papilla. A standard Kausch-Whipple resection or PPPD without a selective extended lymph node dissection, including the interaortocaval and superior mesenteric artery nodes, results in about 30% of the patients having an R2-resection, i.e., with cancer left behind. The long-term survival is determined by the tumor biological factors: (1) absence of lymph node involvement and (2) absence of infiltration into the pancreas. The surgeon's contribution to the cure of cancer of the papilla is to perform an R0-resection with low hospital mortality and low postoperative morbidity. Patients without lymph node involvement, and with absence of infiltration into the pancreas, no lymph vessel invasion, and tumor-negative margins have major benefits from oncological resection in regard to curability of the cancer.