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(1) Background: The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. This certification program is provided by the German Cancer Society (GCS) and represents one of the largest oncologic certification programs worldwide. Currently, about 50% of colorectal cancer patients in Germany are treated in certified centers. (2) Methods: All analyses are based on population-based clinical cancer registry data of 47.440 colorectal cancer (ICD-10-GM C18/C20) patients treated between 2009 and 2017. The primary outcome was 5-year overall survival (OAS) after treatment at certified cancer centers compared to treatment at other hospitals; the secondary endpoint was recurrence-free survival. Statistical methods included Kaplan-Meier analysis and multivariable Cox regression. (3) Results: Treatment at certified hospitals was associated with significant advantages concerning 5-year overall survival (HR 0.92, 95% CI 0.89, 0.96, adjusted for a broad range of confounders) for colon cancer patients. Concentrating on UICC stage I-III patients, for whom curative treatment is possible, the survival benefit was even larger (colon cancer: HR 0.89, 95% CI 0.84, 0.94; rectum cancer: HR 0.91, 95% CI 0.84, 0.97). (4) Conclusions: These results encourage future efforts for further implementation of the certification program. Patients with colorectal cancer should preferably be directed to certified centers.

Background: Treatment of cancer patients in certified cancer centers, that meet specific quality standards in term of structures and procedures of medical care, is a national treatment goal in Germany. However, convincing evidence that treatment in certified cancer centers is associated with better outcomes in patients with pancreatic cancer is still missing., Methods: We used patient-specific information (demographic characteristics, diagnoses, treatments) from German statutory health insurance data covering the period 2009-2017 and hospital characteristics from the German Standardized Quality Reports. We investigated differences in survival between patients treated in hospitals with and without pancreatic cancer center certification by the German Cancer Society (GCS) using the Kaplan-Meier estimator and Cox regression with shared frailty., Results: The final sample included 45,318 patients with pancreatic cancer treated in 1,051 hospitals (96 GCS-certified, 955 not GCS-certified). 5,426 (12.0%) of the patients were treated in GCS-certified pancreatic cancer centers. Patients treated in certified and non-certified hospitals had similar distributions of age, sex, and comorbidities. Median survival was 8.0 months in GCS-certified pancreatic cancer centers and 4.4 months in non-certified hospitals. Cox regression adjusting for multiple patient and hospital characteristics yielded a significantly lower hazard of long-term, all-cause mortality in patients treated in GCS-certified pancreatic centers (Hazard ratio = 0.89; 95%-CI = 0.85-0.93). This result remained robust in multiple sensitivity analyses, including stratified estimations for subgroups of patients and hospitals., Conclusion: This robust observational evidence suggests that patients with pancreatic cancer benefit from treatment in a certified cancer center in terms of survival. Therefore, the certification of hospitals appears to be a powerful strategy to improve patient outcomes in pancreatic cancer care., Trial Registration: ClinicalTrials.gov ( NCT04334239 )., (© 2022. The Author(s).)

Purpose: There is an ongoing debate on whether or not to use oral antibiotic bowel decontamination in colorectal surgery, despite the numerous different regimens in terms of antibiotic substances and duration of application. As we routinely use oral antibiotic bowel decontamination (selective decontamination of the digestive tract (SDD) regimen and SDD regimen plus vancomycin since 2016) in surgery for diverticular disease, our aim was to retrospectively analyze the perioperative outcome in two independent centers., Methods: Data from two centers with a routine use of oral antibiotic bowel decontamination for up to 20 years of experience were analyzed for the perioperative outcome of 384 patients undergoing surgery for diverticular disease., Results: Overall morbidity was 12.8%, overall mortality was 0.3%, the overall rate of anastomotic leakage (AL) was 1.0%, and surgical site infections (SSIs) were 5.5% and 7.8% of all infectious complications including urinary tract infections and pneumonia. No serious adverse events were related to use of oral antibiotic bowel decontamination. Most of the patients (93.8%) completed the perioperative regimen. Additional use of vancomycin to the SDD regimen did not show a further reduction of infectious complications, including SSI and AL., Conclusion: Oral antibiotic decontamination appears to be safe and effective with low rates of AL and infectious complications in surgery for diverticular disease., (© 2021. The Author(s).)

Background/objective: The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC., Methods: Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated., Results: 214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients., Conclusion: Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC., Competing Interests: Declaration of competing interest All authors declare to have no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Distal cholangiocarcinoma (DCC) is a rare malignancy and validated prognostic markers remain scarce. We aimed to evaluate the role of serum CA19-9 as a potential biomarker in DCC., Methods: Patients operated for DCC at 6 high-volume surgical centers from 1994 to 2015 were identified from prospectively maintained databases. Patient baseline characteristics, surgical and histopathological parameters, as well as overall survival after resection were assessed for correlation with preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 (CA19-9). Preoperative CA19-9 to bilirubin ratio (CA19-9/BR) was classified as elevated (≥ 25 U/ml/mg/dl) according to the upper serum normal values of CA19-9 (37 U/ml) and bilirubin (1.5 mg/dl) giving a cut-off at ≥ 25 U/ml/mg/dl., Results: In total 179 patients underwent resection for DCC during the study period. High preoperative CA19-9/BR was associated with advanced age and regional lymph node metastases. Median overall survival after resection was 27 months. Elevated preoperative serum CA19-9/bilirubin ratio (HR 1.6, p = 0.025), T3/4 stage (HR 1.8, p = 0.022), distant metastasis (HR 2.5, p = 0.007), tumor grade (HR 1.9, p = 0.001) and R status (HR 1.7, p = 0.023) were identified as independent negative prognostic factors following multivariable analysis., Conclusion: Elevated preoperative bilirubin-adjusted serum CA19-9 correlates with regional lymph node metastases and constitutes a negative independent prognostic factor after resection of DCC., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Adjuvant chemotherapy (adCx) is an integral part of multimodal treatment in resected pancreatic ductal adenocarcinoma (PDAC) and is recommended by the German S3 guideline since 2007 in all patients. We aimed to investigate the impact of this guideline at our institution., Methods: In 151 of 403 pancreatic resections performed histopathology revealed PDAC. Follow-up data were available from 143 patients (95%) representing our study group. The rate of recommended, initiated and fully completed adCx was analyzed for period 1 (09/2003-07/2007) and period 2 (08/2007-08/2014)., Results: Our study group comprised 49 patients in period 1 and 94 patients in period 2. AdCx was recommended, initiated and completed in 42/49 (86%), 34/49 (69%) and 22/49 (45%) patients in period 1 and in 93/94 (99%), 78/94 (83%) and 49/94 (52%) patients in period 2, respectively. Only the increase in recommendations for adCx was statistically significant (p = 0.0024). Overall, only 50% (71/143) of patients fully completed the Cx protocol. Completed adCx resulted in a significantly longer (p = 0.0225) overall survival compared to patients with incomplete or without adCx. Multiple logistic regression revealed adCx (p = 0.0046) as independent factor of survival. The hazard ratio for fully completed adCx was 0.406 and for incomplete adCx 0.567., Conclusion: Our results indicate a high acceptance of the S3-guidline recommendation for adCx in resected PDAC in a routine setting, which, however, is completed in only 50% of all patients. Fully completed adCx had the most powerful effect on improving overall survival.

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m 2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Purpose: Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma., Methods: Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival., Results: N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis., Conclusion: Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

Background: Parenchyma-sparing local extirpation of benign tumors of the pancreatic head provides the potential benefits of preservation of functional tissue and low postoperative morbidity., Methods: Medline/PubMed, Embase, and Cochrane library databases were surveyed for studies performing limited resection of the pancreatic head and resection of a segment of the duodenum and common bile duct or preservation of the duodenum and common bile duct (CBD). The systematic analysis included 27 cohort studies that reported on limited pancreatic head resections for benign tumors. In a subgroup analysis, 12 of the cohort studies were additionally evaluated to compare the postoperative morbidity after total head resection including duodenal segment resection (DPPHR-S) and total head resection conserving duodenum and CBD (DPPHR-T)., Results: Three hundred thirty-nine of a total of 503 patients (67.4%) underwent total head resections. One hundred forty-seven patients (29.2%) of them underwent segmental resection of the duodenum and CBD (DPPHR-S) and 192 patients (38.2%) underwent preservation of duodenum and CBD. One hundred sixty-four patients experienced partial head resection (32.6%). The final histological diagnosis revealed in 338 of 503 patients (67.2%) cystic neoplasms, 53 patients (10.3%) neuroendocrine tumors, and 20 patients (4.0%) low-risk periampullary carcinomas. Severe postoperative complications occurred in 62 of 490 patients (12.7%), pancreatic fistula B + C in 40 of 295 patients (13.6%), resurgery was experienced in 2.7%, and delayed gastric emptying in 12.3%. The 90-day mortality was 0.4%. The subgroup analysis comparing 143 DPPHR-S patients with 95 DPPHR-T patients showed that the respective rates of procedure-related biliary complications were 0.7% (1 of 143 patients) versus 8.4% (8 of 95 patients) (p ≤ 0.0032), and rates of duodenal complications were 0 versus 6.3% (6 of 95 patients) (p ≤ 0.0037). DPPHR-S was associated with a higher rate of delay of gastric emptying compared to DPPHR-T (18.9 vs. 2.1%, p ≤ 0.0001)., Conclusion: Parenchyma-sparing, limited head resection for benign tumors preserves functional pancreatic and duodenal tissue and carries in terms of fistula B + C rate, resurgery, rehospitalization, and 90-day mortality a low risk of postoperative complications. A subgroup analysis exhibited after total pancreatic head resection that preserves the duodenum and CBD an association with a significant increase in procedure-related biliary and duodenal complications compared to total head resection combined with resection of the periampullary segment of the duodenum and resection of the intrapancreatic CBD.

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., (© 2016 S. Karger AG, Basel.)

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., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1μg and 1.0μg VEGF. The in vitro VEGF release kinetics was studied using a Sandwich ELISA. The biological activity of the released VEGF was investigated in vitro using human umbilical vein endothelial cells. The potential of the VEGF-releasing suture material was also studied in vivo 5days after implantation in the hind limb of Wistar rats, when the histological findings were analyzed. The essential results, enhanced cell viability in vitro as well as significantly increased vascularization in vivo, were achieved using PLLA/1.0μg VEGF-coated suture material. Furthermore, ELISA measurements revealed a high reproducibility of the VEGF release behavior. Based on the results achieved regarding the dose-effect relationship of VEGF, the stability during its processing and the release behavior, it can be predicted that a bioactive suture material would be successful in later in vivo studies. Therefore, this knowledge could be the basis for future studies, where bioactive substances with different modes of action are combined for targeted, overall enhancement of wound healing., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background. Breast cancer liver metastasis is a hematogenous spread of the primary tumour. It can, however, be the expression of an isolated recurrence. Surgical resection is often possible but controversial. Methods. We report on 29 female patients treated operatively due to isolated breast cancer liver metastasis over a period of six years. Prior to surgery all metastases appeared resectable. Liver metastasis had been diagnosed 55 (median, range 1-177) months after primary surgery. Results. Complete resection of the metastases was performed in 21 cases. The intraoperative staging did not confirm the preoperative radiological findings in 14 cases, which did not generally lead to inoperability. One-year survival rate was 86% in resected patients and 37.5% in nonresected patients. Significant prognostic factors were R0 resection, low T- and N-stages as well as a low-grade histopathology of the primary tumour, lower number of liver metastases, and a longer time interval between primary surgery and the occurrence of liver metastasis. Conclusions. Complete resection of metastases was possible in three-quarters of the patients. Some of the studied factors showed a prognostic value and therefore might influence indication for resection in the future.

Background: Acute pancreatitis remains as one of the most difficult and challenging digestive disorder to predict in terms of clinical course and outcome. Every case has an individual course and therefore acute pancreatitis remains challenging and fascinating. Due to this variability, many different scoring systems have evolved during the last decades. Every scoring system has advantages and disadvantages. Not every scoring system is capable of assessing the clinical time course of the disease, some are only suitable for the time of initial presentation., Aim: This paper will give an overview on the development of different widely used scoring systems and their performance in assessing severity and prognosis of acute pancreatitis., Conclusion: Severity assessment means objective quantification of overall severity of illness. Early and reliable stratification of severity is required to decide best treatment of the individual patient, preparation for possible evolving complications or for referral to specialist centers. No single scoring system is able to cover the entire range of problems associated with treatment and assessment of acute pancreatitis. In our clinical experience, we recommend hematocrit upon admission, daily sequential organ failure assessment score and procalcitonin, C-reactive protein on day 3 and CT severity index beyond the first week. These scoring tools together with close clinical follow-up of the patient ultimately lead to an optimized treatment of this challenging disease.

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.

Background: The quality of a histopathologic workup after oncologic resection of pancreatic malignancies has changed the central role of surgery substantially for radical tumor clearance over the past years. The development of standardized protocols for pathologic workup increased the rate of R1 resections from around 20% up to 80%. In the present study, we investigated the incidence of R1 and its impact on survival after oncologic pancreatic resections using a standardized pathologic routine protocol., Patients and Methods: We performed 265 pancreatic resections from September 2003 to September 2010. Among 128 patients with malignant neoplasms, histology revealed ductal pancreatic adenocarcinoma in 97, ampullary cancer in 10, and distal bile duct cancer in 21 patients. Resected specimens were analyzed according to this improved standardized pathology protocol introduced in 2000. Follow-up data on overall and cancer-related survival, presence and site of tumor recurrence, and chemotherapy were obtained from 120 patients., Results: Pancreatic resection comprised a pylorus-preserving or classical pancreaticoduodenectomy in 112, a distal pancreatectomy in 8, and a total pancreatectomy in 7 patients. In the overall series, 56 (44%) were classified R1 resections and 68 (43%) R0 resections, 3 patients with R2 resections were excluded, leaving 125 patients for analysis. In pancreatic adenocarcinoma, the rate of R1 was 51% (48/94). R1 resection involved most frequently the circumferential margin in 86% (48/125) of the total group and in 92% (44/48) in pancreatic cancer. Follow-up was performed after a median of 17 months (range, 1-85) postoperatively. Cancer-related death rate in R0 and R1-resected patients was 60% and 83% (P < .02) in all cancers (n = 117) and 66% and 80% in patients with pancreatic adenocarcinoma (n = 88). Median tumor-related survival in R0 and R1 resections was 22 (range, 4-85) vs 14 months (range, 2-48) in all cancers (P < .002), and 19 (range, 4-85) vs 14 months (range, 2-48) in pancreatic adenocarcinoma (P < .04). Kaplan-Meier survival analysis revealed a survival benefit after R0 resection in both all cancers (P = .002) and pancreatic adenocarcinoma (P < .02). The pattern of tumor recurrence had a greater rate of regional metastases in the R1 group (P < .05)., Conclusion: Our 51% rate of R1 resections in ductal pancreatic carcinoma indicates a high quality standard of pathologic evaluation. The vast majority of R1 margins are located at the retroperitoneal dissection surface. Standardization of histopathologic analysis has a clinically relevant impact on survival after oncologic resection of pancreatic cancer and can be achieved by less extensive protocols., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Langenbeck's Archives of Surgery is celebrating its 150th anniversary and accounts to the oldest and most traditional scientific periodical in the field of surgery. This exceptional success and continuity has been mainly driven by the editors, many of them world famous surgeons, opinion leaders, and outstanding researchers. The article presents an overview of all editors since the foundation of the journal by Bernhard von Langenbeck, Theodor Billroth, and E.G. Gurlt in Berlin in 1860.

Background: Cystic neoplastic lesions of the pancreas are found in up to 10% of all pancreatic lesions. A malignant transformation of cystic neoplasia is observed in intraductal papillary mucinous tumor (IPMN) lesions in 60% and in mucinous cystic tumor (MCN) lesions in up to 30%. For cystic neoplasia located monocentrically in the pancreatic head and that do not have an association with an invasive pancreatic cancer, the duodenum-preserving total head resection has been used in recent time as a limited surgical procedure., Patients: An indication to duodenum-preserving total pancreatic head resection is considered for patients who do not have clinical signs of an advanced cancer in the lesion and who have main-duct IPMN and monocentric MCN lesions. In 104 patients with cystic neoplastic lesions in the Ulm series, 32% finally had a carcinoma in situ or an advanced pancreatic cancer. The application of a duodenum-preserving total pancreatic head resection in patients with asymptomatic cystic lesion is based on the size of the tumor and the tumor relation to the pancreatic ducts. For patients who have preoperatively clinical signs of malignancy, a Kausch-Whipple type of oncologic resection is recommended., Results: Duodenum-preserving total pancreatic head resection is used in several modifications. The surgical procedure is a limited pancreatic head resection which necessitates segmental resection of the peripapillary duodenum. Hospital mortality is very low; in most published series it is 0%. The long-term outcome is determined by completeness of resection for both -- benign and malignant -- entities. Careful evaluation of the frozen section results has a pivotal role for intraoperative decision making., Conclusion: A duodenum-preserving total pancreatic head resection is a limited surgical procedure for patients who suffer a local monocentric, cystic neoplastic lesion in the pancreatic head. Absence of an advanced pancreatic cancer and completeness of extirpation of the benign tumor determine the long-term outcome. In regards to the location of the lesion in the pancreatic head, several modifications have been applied with low hospital morbidity and mortality below 1%.

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.

Background/aim: Pancreatic cancer is characterized by perineural invasion, early lymph node and liver metastases, and an extremely dismal prognosis. In the present study we aimed at investigating the expression profile of pro-inflammatory and angiogenic CXC chemokines as potential factors contributing to the aggressive biology of this gastrointestinal malignancy., Methods: Protein expression profiles of the CXC chemokines growth-related oncogene alpha (GRO-alpha/CXCL1), epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5), granulocyte chemoattractant protein-2 (GCP-2/CXCL6), neutrophil-activating protein-2 (NAP-2/CXCL7), and interleukin-8 (IL-8/CXCL8) were assessed by enzyme-linked immunosorbent assay in pancreatic carcinoma, cancer of the papilla of Vater, pancreatic cystadenoma, and chronic pancreatitis specimens., Results: IL-8 and ENA-78 protein expression was most pronounced in pancreatic carcinoma specimens, showing an 11-fold and 17-fold overexpression in comparison with non-affected neighbouring tissues, a 66-fold and 24-fold upregulation compared to pancreatic cystadenoma, and a 6-fold and 9-fold overexpression with respect to chronic pancreatitis, respectively (p < 0.05 between all groups). In addition, a close correlation between IL-8 and ENA-78 protein expression and advanced pancreatic carcinomas in relation to the T category was evident (p < 0.05)., Conclusion: Our results demonstrate that ELR+ CXC chemokines are differentially expressed in malignant and non-malignant human pancreatic specimens, suggesting a potential contribution of these chemokines to the pathogenesis of pancreatic carcinoma., (Copyright 2008 S. Karger AG, Basel.)

Aim: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM)., Methods: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16)., Results: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues. Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found., Conclusion: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

Purpose of Review: New understanding of the dynamic of acute pancreatitis, the clinical impact of local pathology in chronic pancreatitis and cystic neoplastic lesions bearing high potential for malignant transformation has changed the management of pancreatic diseases., Recent Findings: In acute pancreatitis, risk factors independently determining outcome in severe acute pancreatitis are early and persistent multiorgan failure, infected necrosis and extended sterile necrosis. The management of severe acute pancreatitis is based on early intensive-care treatment and late surgical debridement. In chronic pancreatitis, recent data from randomized controlled clinical trials have demonstrated duodenum-preserving pancreatic head resection with an inflammatory mass of the head as superior to pylorus-preserving Whipple resection. Cystic neoplasms are local lesions of the pancreas with high malignant potential. Local organ-preserving resection techniques have been applied with low morbidity and mortality, replacing a Whipple-type resection. Resection of pancreatic cancer is ineffective to cure patients. After an R0-resection, a significant survival benefit has been achieved when adjuvant chemotherapy has additionally been applied., Summary: New knowledge about the nature of inflammatory diseases, cystic neoplastic lesions and malignant pancreatic tumours has changed the indication for surgical treatment and the application of organ-preserving surgical techniques.

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP., Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter., Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of > or =3.5 ng/mL on 2 consecutive days was superior to CRP > or =430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT > or =3.8 ng/mL compared with 36% and 97% for CRP > or =430 mg/L, respectively (P = 0.002)., Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications.

Severity stratification is a critical issue in acute pancreatitis that strongly influences diagnostic and therapeutic decision making. According to the widely used Atlanta classification, "severe" disease comprises various local and systemic complications that are associated with an increased risk of mortality. However, results from recent clinical studies indicate that these complications vary in their effect on outcome, and many are not necessarily life threatening on their own. Therefore, "severe," as defined by Atlanta, must be distinguished from "prognostic," aiming at nonsurvival. In the first week after disease onset, pancreatitis-related organ failure is the preferred variable for predicting severity and prognosis because it outweighs morphologic complications. Contrast-enhanced CT and MRI allow for accurate stratification of local severity beyond the first week after symptom onset. Among the biochemical markers, C-reactive protein is still the parameter of choice to assess attack severity, although prognostic estimation is not possible. Other markers, including pancreatic protease activation peptides, interleukins-6 and -8, and polymorphonuclear elastase are useful early indicators of severity. Procalcitonin is one of the most promising single markers for assessment of major complications and prognosis throughout the disease course.

Hypothesis: Infections and sepsis are major complications in secondary peritonitis and still represent a diagnostic challenge. We hypothesized that the laboratory marker procalcitonin would provide an early and reliable assessment of septic complications., Design: Prospective, international, multicenter inception cohort study., Setting: Five European surgical referral centers., Patients: Eighty-two patients with intraoperatively proven secondary peritonitis were enrolled within 96 hours of symptom onset., Main Outcome Measures: Procalcitonin and the laboratory routine marker C-reactive protein (CRP) were prospectively assessed and monitored for a maximum of 21 consecutive days., Results: Procalcitonin concentrations were most closely correlated with the development of septic multiorgan dysfunction syndrome (MODS), with peak levels occurring early after symptom onset or during the immediate postoperative course. No such correlation was observed for CRP. According to receiver operating characteristic analysis, a procalcitonin value of 10.0 ng/mL or greater on 2 consecutive days was superior to a CRP level of 210 mg/L or greater for predicting septic MODS, with sensitivity, specificity, and positive and negative predictive values of 65%, 92%, 83%, and 81% for procalcitonin and 67%, 58%, 49%, and 74% for CRP, respectively (P<.001). Assessment of septic MODS was already possible on the first 2 postoperative days, with similar sensitivity and specificity. Persisting procalcitonin levels greater than 1.0 ng/mL beyond the first week after disease onset strongly indicated nonsurvival and were significantly better than CRP in assessing overall prognosis (P<.001)., Conclusions: Procalcitonin monitoring is a fast and reliable approach to assessing septic MODS and overall prognosis in secondary peritonitis. This single-test marker improves stratification of patients who will develop clinically relevant complications.

Background & Aims: Infection of necrosis is considered as principal determinant of outcome in necrotizing pancreatitis and as potential complication after operative treatment of sterile necrosis. In this report a new concept is proposed., Methods: Of 392 patients with necrotizing pancreatitis, 135 patients with operatively treated sterile necrosis were stratified into 3 postoperative entities: secondary pancreatic infections (PIN, group I), pancreatic contaminations (group II), and sterile courses (group III). Ninety-five patients with conservatively treated sterile necrosis (group IV) served as controls., Results: Secondary PIN developed in 64 (47%) patients and contaminations in 37 (27%) patients, whereas 34 (25%) patients remained sterile postoperatively. Secondary PIN and contaminations were both diagnosed after a median of 3 weeks after disease onset. Early/preoperative multisystem organ failure (MODS) affecting >2 organs was more frequent in group I (35%) than in group II (5%), group III (12%), and group IV (7%) (P < .003); mortality rates were 38%, 3%, 21%, and 7%, respectively (P < .001). Multiple logistic regression identified early/preoperative MODS and extent of intrapancreatic necrosis as major risk factors to develop secondary PIN in operatively treated sterile necrosis. However, irrespective of operative or conservative treatment, only early onset MODS >2 organs proved to be the predominant risk factor for death., Conclusions: Early MODS and extended intrapancreatic necrosis are risk factors for secondary PIN after operative treatment of sterile necrosis. In contrast, the ultimate outcome strongly depends on early and high systemic illness, whereas local pathology and operative procedure seem to be less important.

Objectives: Acute pancreatitis is associated with substantial alterations of the immunologic host response which has been claimed to promote remote organ dysfunction, septic complications, and mortality. Treatment with immunomodulating substances has been subject of few experimental studies with still conflicting results., Methods: We used the taurocholate-induced model of severe acute pancreatitis (SAP) in rats which were assigned to different treatment regimen: isotonic saline (SAP-S) for nontreated controls, recombinant rat interferon-gamma for immunostimulation (SAP-IFN-gamma), and FK506 for immunosuppression (SAP-FK506). Animals were killed after 3, 6, and 24 hours as well as 3 and 7 days, and parameters of local and systemic severity were assessed., Results: Treatment with IFN-gamma and FK506 attenuated the progression of intrapancreatic necrosis within the first 24 hours after pancreatitis induction along with a substantial reduction of subsequent neutrophil tissue infiltration as shown by decreased myeloperoxidase activity. Enhanced cell death by apoptosis during the postacute course was reduced in FK506-treated animals only. Pancreatic interleukin (IL) 1beta messenger RNA up-regulation occurred early and was slightly suppressed in both treatment groups; tumor necrosis factor alpha (TNF-alpha) and IL-2 messenger RNA expression paralleled the onset of apoptosis and was markedly decreased in IFN-gamma- and FK506-treated rats. The 2 therapeutic regimens had similar effects on intrapancreatic and systemic IL-1beta and TNF-alpha protein release; however, the profiles of both cytokines were differently influenced. Whereas IFN-gamma and FK506 treatment lead to an enhanced intrapancreatic and systemic TNF-alpha protein release during the early course, IL-1beta concentrations were significantly reduced within the late intervals. Seven-day mortality was 44% in saline-, 29% in IFN-gamma-, and 25% in FK506-treated rats (P = not significant)., Conclusions: Severe acute pancreatitis is associated with early alterations of the immune response comprising overt T-cell activation and impaired monocyte/macrophage function alike. Targeting either immunologic derangement improves local pancreatic damage and systemic severity. However, because mortality was not improved, a therapeutic benefit of immunomodulating substances in clinical SAP remains to be defined.

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.

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.

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.