Is treatment in certified cancer centers related to better survival in patients with pancreatic cancer? Evidence from a large German cohort study.

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 ).

Oral antibiotic bowel decontamination in open and laparoscopic sigmoid resections for diverticular disease.

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.

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study.

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.

Prognostic relevance of preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 in a multicenter subset analysis of 179 patients with distal cholangiocarcinoma.

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.

Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.

Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study.

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.

Prognosis of rectal cancer patients improves with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis.

BACKGROUND: Neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. The present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival. METHODS: A total of 387 patients underwent oncologic resection for rectal cancer in our institution between January 2000 and December 2009. There were 106 patients (27.4%) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). A matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). Matching was carried out in descending order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category of the TNM-system according to the histopathological staging. Follow-up data included local recurrence rate, cancer related and disease free survival. RESULTS: In the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5% (98/106) of these patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an observation period of 4.3 ± 2.55 years. In the control group cancer related and disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an observation period of 3.8 ± 3.05 years revealing no statistical significant difference between the two groups. Moreover, estimated 5-year results of cancer related survival (66.7% vs 67.9% (controls)), the disease free survival (66.7% vs 79.9% (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients showed no difference between the study and control group as well. CONCLUSION: In our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. The resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage.

Scoring of human acute pancreatitis: state of the art.

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.

Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications.

BACKGROUND: Neoadjuvant radiochemotherapy has proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases. The present study aimed at addressing the effects of an intensified protocol of neoadjuvant treatment on the development of postoperative complications. METHODS: A total of 387 patients underwent oncological resection for rectal cancer in our institution between January 2000 and December 2009. 106 patients received an intensified radiochemotherapy. Perioperative morbidity and mortality were analyzed retrospectively with special attention on complication rates after intensified radio-chemotherapy. Therefore, for each patient subjected to neoadjuvant treatment a patient without neoadjuvant treatment was matched in the following order for tumor height, discontinuous resection/exstirpation, T-category of the TNM-system, dividing stoma and UICC stage. RESULTS: Of all patients operated for rectal cancer, 27.4% received an intensified neoadjuvant treatment. Tumor location in the matched patients were in the lower third (55.2%), middle third (41.0%) and upper third (3.8%) of the rectum. Postoperatively, surgical morbidity was higher after intensified neoadjuvant treatment. In the subgroup with low anterior resection (LAR) the anastomosis leakage rate was higher (26.6% vs. 9.7%) and in the subgroup of patients with rectal exstirpations the perineal wound infection rate was increased (42.2% vs. 18.8%) after intensified radiochemotherapy. CONCLUSIONS: In rectal cancer the decision for an intensified neoadjuvant treatment comes along with an increase of anastomotic leakage and perineal wound infection. Quality of life is often reduced considerably and has to be balanced against the potential benefit of intensifying neoadjuvant radiochemotherapy.

Treatment of Colorectal Cancer in Certified Centers: Results of a Large German Registry Study Focusing on Long-Term Survival.

(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.

The editors of Langenbeck's since 1860.

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.

Enhanced ENA-78 and IL-8 expression in patients with malignant pancreatic diseases.

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.

Duodenum-preserving total pancreatic head resection for cystic neoplasm: a limited but cancer-preventive procedure.

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%.

High compliance with guideline recommendations but low completion rates of adjuvant chemotherapy in resected pancreatic cancer: A cohort study.

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.

Evaluation of procalcitonin for predicting septic multiorgan failure and overall prognosis in secondary peritonitis: a prospective, international multicenter study.

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.

Severe acute pancreatitis: Clinical course and management.

Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (>50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis-Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.

Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer.

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.