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Background: The definition of resection margin (R) status in pancreatic cancer is under debate. Although a margin of at least 1 mm is an independent predictor of survival after resection for pancreatic head cancer, its relevance to pancreatic body and tail cancers remains unclear. This study aimed to validate R status based on a 1‐mm tumour‐free margin as a prognostic factor for resected adenocarcinoma involving the pancreatic body and tail. Methods: Patients who underwent distal or total pancreatectomy for adenocarcinomas of the pancreatic body and tail between January 2006 and December 2014 were identified from a prospective database. Resection margins were evaluated using a predefined cut‐off of 1 mm. Rates of R0, R1 with invasion within 1 mm of the margin (R1 less than 1 mm), and R1 with direct invasion of the resection margin (R1 direct) were determined, and overall survival in each group assessed by Kaplan–Meier analysis. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. Results: R0 resection was achieved in 107 (23·5 per cent) and R1 in 348 (76·5 per cent) of 455 patients. Among R1 resections, invasion within 1 mm of the margin was found in 104 (22·9 per cent) and direct invasion in 244 (53·6 per cent). The R0 rate was 28·9 per cent after distal and 18·6 per cent after total pancreatectomy. In the total cohort, median survival times for patients with R0, R1 (less than 1 mm) and R1 (direct) status were 62·4, 24·6 and 17·2 months respectively, with 5‐year survival rates of 52·6, 16·8 and 13·0 per cent (P < 0·001). In patients who received adjuvant chemotherapy, respective median survival times were 68·6, 32·8 and 21·4 months, with 5‐year survival rates of 56, 22 and 16·0 per cent (P < 0·001). In multivariable analysis, R status was independently associated with survival. Conclusion: A cut‐off of at least 1 mm for evaluation of resection margins is an independent determinant of survival after resection of adenocarcinomas of the pancreatic body and tail. [ABSTRACT FROM AUTHOR]

Mutations in the DJ-1 gene have been identified to cause Parkinson's disease. In humans, nonmutated DJ-1 is expressed in specific brain areas but seems to be expressed by astrocytes rather than by neurons. In contrast, DJ-1 mRNA is mainly found in neurons in the mouse brain. We have investigated the distribution of DJ-1 protein in the mouse brain and found that DJ-1 protein is predominantly expressed by neurons but can also be detected in astrocytes. Consistent with a global role of DJ-1 in the brain, we found immunoreactivity, for example, in cortical areas, hippocampus, basolateral amygdala, the reticular nucleus of the thalamus, zona incerta, and locus coeruleus. Within the substantia nigra, however, DJ-1 is localized in both neuronal and nonneuronal cells, suggesting a distinct role in this area. [ABSTRACT FROM AUTHOR]

Background and aims: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-lr on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. Methods: We assessed the effect of IGF-Ir ligancis on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. Results: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed humorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-I activation induced by IGF-I, IGF-II, and des(1 -3)IGF-I, but not by insulin. IGF-Ir/ dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-lr/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. Conclusions: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer. [ABSTRACT FROM AUTHOR]

Background Emergency surgery for colorectal cancer has become more aggressive and radical over the past decade. This retrospective review analyses the impact on outcome. Methods The results of emergency surgery within 24 h of admission were compared between 1982 and 1987 (77 patients) and 1988 and 1993 (75 patients). Patient and tumour characteristics were similar in both groups. Results Right colonic obstruction or perforation was treated by primary resection and anastomosis in 11 of 12 patients before 1988 and in all 19 patients thereafter. Primary resection was also the treatment of choice for perforated cancer of the left colon and rectum before 18 of 20) and after (20 of 21) 1988. The rate of primary resection for obstructing cancer of the left colon and rectum increased from 17 of 45 to 30 of 35. One-stage resections for obstructing cancer were performed in ten of 45 and 22 of 35 patients before and after 1988 respectively. The overall mortality rate declined from 14 of 77 to three of 75 after 1988 (P<0·01). The rate of radical lymphadenectomy rose from six of 46 patients to 42 of 69 after 1988. The 3-year survival rate increased from 50 to 74 per cent (P<0·05). Conclusion The data support further efforts towards improving the immediate and late outcome of emergency surgery in complicated colorectal cancer. [ABSTRACT FROM AUTHOR]

B Background: b The definitions for R0 and R1 margin status after resection for pancreatic cancer are controversial. B Results: b Of 535 patients with pancreatic adenocarcinoma treated with DP or TP, 122 (22.8%) had R0 and 401 (75.9%) had R1 resections, including 114 (21.3%) R1 (<=1mm) and 286 (53.4%) R1 (direct) resections. With R0, R1 (<=1mm) and R1 (direct) status the median survival times and five-year survival rates were 57.2, 23.2 and 16.9 months and 48.9, 16.2 and 11.5%, respectively (p<0.0001). [Extracted from the article]

B Background: b Postoperative pancreatic fistula (POPF) is the most important complication after pancreatic surgery and is associated with major morbidity, increased use of resources, and prolonged hospital stay. The occurrence and the grade of POPF were significantly associated with increased treatment costs in all cases and in subgroups of different resections (e.g. mean costs of 15,741.51€ without and of 54,023.20€ with POPF after pancreatoduodenectomy; p< 0.0001). POPF resulted in uncovered costs and was associated with a deficit in total, after different resections, and within single DRGs. [Extracted from the article]

B Background: b Postoperative pancreatic fistula (POPF) is the most important complication after pancreatic surgery and is associated with major morbidity, increased use of resources, and prolonged hospital stay. The occurrence and the grade of POPF were significantly associated with increased treatment costs in all cases and in subgroups of different resections (e.g. mean costs of 15,741.51€ without and of 54,023.20€ with POPF after pancreatoduodenectomy; p< 0.0001). POPF resulted in uncovered costs and was associated with a deficit in total, after different resections, and within single DRGs. [Extracted from the article]

Background Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. Methods For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more. Risk factors for chyle leak were assessed by univariable and multivariable analyses. The clinical relevance of chyle leak was evaluated using hospital stay and resolution by 14 days for short-term outcome and overall survival for long-term outcome. Results Chyle leak developed in 346 (10·4 per cent) of 3324 patients. Pre-existing diabetes, resection for malignancy, distal pancreatectomy, duration of surgery 180 min or longer, and concomitant pancreatic fistula or abscess were independent risk factors for chyle leak. Both isolated chyle leak and coincidental chyle leak (with other intra-abdominal complications) were associated with prolonged hospital stay. Some 178 (87·7 per cent) of 203 isolated chyle leaks and 90 (70·3 per cent) of 128 coincidental chyle leaks resolved with conservative management within 14 days. Initial and maximum drainage volumes were associated with duration of hospital stay and success of therapy by 14 days. Impact on survival was restricted to chyle leaks that persisted at 14 days in patients with cancer undergoing palliative surgery. Conclusion Chyle leak is a relevant complication, with an incidence of more than 10 per cent after pancreatic surgery, and has a major impact on hospital stay. Drainage volume is associated with hospital stay and success of therapy. [ABSTRACT FROM AUTHOR]

Background In the recent International Study Group of Pancreatic Surgery ( ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer. Methods A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan-Meier analysis. Results The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival. Conclusion Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable long-term outcome is achieved in some patients. [ABSTRACT FROM AUTHOR]

Background Enucleation is used increasingly for small pancreatic tumours. Data on perioperative outcome after pancreatic enucleation, especially regarding the significance and risk factors associated with postoperative pancreatic fistula ( POPF), are limited. This study aimed to assess risk-dependent perioperative outcome after pancreatic enucleation, with a focus on POPF. Methods Patients undergoing enucleation for pancreatic lesions between October 2001 and February 2014 were identified from a prospective database. A detailed analysis of morbidity was performed. Risk factors for POPF were assessed by univariable and multivariable analyses. Results Of 166 enucleations, 94 (56·6 per cent) were performed for cystic and 72 (43·4 per cent) for solid lesions. Morbidity was observed in 91 patients (54·8 per cent). Severe complications occurred in 30 patients (18·1 per cent), and one patient (0·6 per cent) died. Reoperation was necessary in nine patients (5·4 per cent). POPF was the main determinant of outcome and occurred in 68 patients (41·0 per cent): grade A POPF, 34 (20·5 per cent); grade B, ten (6·0 per cent); and grade C, 24 (14·5 per cent). Risk factors independently associated with POPF were: cystic tumour, localization in the pancreatic tail, history of pancreatitis and cardiac co-morbidity. Only cystic morphology was independently associated with clinically relevant POPF (grade B or C), occurring after enucleation in 25 (27 per cent) of 94 patients with cystic tumours versus nine (13 per cent) of 72 patients with solid tumours. Tumour size and distance to the main duct were not associated with risk of POPF. Conclusion Enucleation is a safe procedure in appropriately selected patients with a low rate of severe complications. POPF is the main determinant of outcome and is more frequent after the enucleation of cystic lesions. [ABSTRACT FROM AUTHOR]

Aim Restorative proctocolectomy with ileal pouch-anal anastomosis for patients with familial adenomatous polyposis ( FAP) and ulcerative colitis ( UC) has been modified from a transanal hand-suture after mucosectomy to a stapled ileal pouch-anal anastomosis (IPAA) without mucosectomy. Better functional results favour stapled anastomosis; however, stapled anastomosis results in higher rates of adenomas in persisting anorectal mucosa. The purpose of this study was to compare the two techniques of pouch-anal anastomosis with respect to early postoperative complications in a collective of FAP patients. Method The study was performed as a matched-pair analysis. Data were obtained from a prospectively collected database. Results The overall rate of postoperative complications was higher after stapled IPAA (31% stapled vs 23% handsewn), with anastomotic stricture occurring in 24.3% (stapled) and 16.2% (handsewn) ( P = 0.22). Any leakage or pelvic abscess formation after stapled anastomosis occurred within 30 days in almost all patients, whereas these were mainly diagnosed between 30 days and 6 months after handsewn IPAA. A laparoscopic approach was used in 56.7% of patients in the stapled group but in only two patients in the handsewn group. Intra-operative blood loss was significantly higher in the handsewn group (mean ± SD: 699 ± 511 ml vs 369 ± 343 ml; P < 0.0001), as was the volume of blood transfused (mean ± SD: 205 ± 365 ml vs 8 ± 49 ml; P < 0.0001). Function did not differ between the groups. Conclusion There was a nonstatistically significant tendency towards a higher rate of early postoperative complications after stapled IPAA. The timing of anastomotic leakage and abscess formation differed between the groups. [ABSTRACT FROM AUTHOR]

The article discusses a study on the role of serum carbohydrate antigen (CA) 19-9 carcinoembryonic antigen (CEA) in determining the distinction between benign and invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Procedure included the measurement of preoperative CA19-9 and CEA levels in 142 patients who were administered with surgical resection for IPMN. Researchers concluded that patients with positive tumour markers and IPMN face the risk of malignant disease.

Abstract: The organ shortage has driven many transplant centers to accept extended donor criteria and to modify graft allocation policies. This study was designed to analyze the impact of applying extended donor criteria (EDC) in orthotopic liver transplantation (OLT). Between December 2001 and December 2004, we performed 165 primary cadaveric whole OLTs. Up to three EDC, that is, ventilation >7 days; aminotransferases (ALT or AST) >3× normal; bilirubin >3 mg/dL; anti-HBc or HBs Ag positivity; donor age >65 years; liver steatosis >40%; donor body mass index >30; cold ischemia time >14 hours; peak serum Na+ >165 mmol/L; history of extrahepatic malignancy; or previous drug abuse were present in 55% of all grafts. Both univariate and multivariate analysis revealed that EDC status had no effect on graft or patient survival, the necessity for retransplantation, the length of intensive care/intermediate care unit stay, mechanical ventilation, complications, or posttransplant laboratory findings. Recipient age of ≥55 years was the only independent prognostic factor for survival, regardless of EDC. These findings suggested that the use of grafts from EDC donors are safe and expand the donor pool. [Copyright &y& Elsevier]

Background and aims: Conflicting results exist about the presence of Mycobacterium avium subspecies paratuberculosis (MAP) specific IS 900 DNA in Crohn's disease (CD) tissues. Therefore, we examined IS 900 in a large number of gut samples from patients with CD (n = 100) and ulcerative colitis (UC, n = 100), and in non-inflamed control tissues (nIBD, n =100). We hypothesised that IS 900 DNA detection might be associated with distinct clinical phenotypic characteristics in CD. Methods: The prevalence of MAP DNA in surgically resected tissues was examined using a mechanical-enzymatic disruption technique and nested IS 900 specific polymerase chain reaction (PCR). CD patients were stratified according to the criteria of the Vienna classification and other clinical characteristics. Results: IS 900 PCR detection rate was significantly higher in CD tissue samples (52%) than in UC (2%) or nIBD (5%) specimens (p<0.0001). In CD patients, IS 900 DNA was detected in samples from both diseased small bowel (47%) as well as from the colon (61%). No firm association between MAP specific IS 900 detection rates and clinical phenotypic characteristics in CD could be established. However, corticosteroid medication constituted a factor which tended to have a negative influence on IS 900 DNA detection rates in CD (p<0.01). Conclusions: The presence of MAP specific IS 900 DNA is a predominant feature of CD. Therapeutic intervention against MAP might represent a potential target for disease mitigation in Crohn's disease. [ABSTRACT FROM AUTHOR]

Background: Despite the wide range of surgical approaches for pouch salvage, septic complications are among the main causes of pouch failure. Methods: This study analysed the mode and outcome of various therapeutic approaches for pouch salvage and the impact of time of diagnosis, localization and form of septic complications on the risk of pouch failure in 131 patients with septic complications of a total of 706 patients undergoing a J pouch procedure. Results: Septic complications consisted of 76·3 per cent fistulas, 15·3 per cent anastomotic breakdowns and 8·4 per cent pelvic abscesses. A total of 107 patients (81·7 per cent) with septic complications required a mean of 2·2 surgical procedures. The frequency of permanent defunctioning and excision of the pouch in the 131 patients with septic complications was 23·7 and 6·1 per cent respectively. The estimated cumulative 3-, 5- and 10-year rate of pouch failure in patients with septic complications was 19·6, 31·1 and 39·2 per cent respectively. The risk of pouch failure was significantly affected by the site of origin of septic complications (P = 0·02). The 5-year pouch failure rate increased in a subgroup of patients with septic complications at the pouch–anal anastomosis when the anal sphincter was involved (50·1 versus 29·2 per cent; P = 0·18). Conclusion: Pouch failure as a result of septic complications may occur several years after ileal pouch–anal anastomosis. For prevention of pouch failure, surgery for septic complications is required in a high percentage of patients and repeated attempts are justified. Follow-up studies are required for further analysis of pouch failure. [ABSTRACT FROM AUTHOR]

Follow-up data included postoperative tumor-directed therapy, disease status, and survival. By multivariable analysis tumor grading, extent of lymph node metastasis, IPMN context, and vascular resections were independently associated with overall and disease-free 5YS. [Extracted from the article]

Encouraging observed 5-year survival with upfront resection and adjuvant therapy for pancreatic ductal adenocarcinoma in a large contemporary series Follow-up data included postoperative tumor-directed therapy, disease status, and survival. By multivariable analysis tumor grading, extent of lymph node metastasis, IPMN context, and vascular resections were independently associated with overall and disease-free 5YS. [Extracted from the article]

B Background: b Complex liver resection with concomitant biliary or vascular resection is a standard surgical procedure. B Methods: b Records of 1796 patients undergoing liver resection for >1 segment were analyzed. Risk factors for 90-day in-hospital mortality were age >=60 years (OR 3.7), ASA III/IV (OR 2.9 / 15.6), intrahepatic cholangiocarcinoma (OR 3.0), perihilar cholangiocarcinoma (Klatskin tumor) (OR 5.6), right trisectionectomy (OR 2.8), Quick< 85% (OR 2.4), g-GT >60U/L (OR 2.8), plateletcount < 120/nL (OR 5.5) and creatine >2mg/dL (OR 9.8). [Extracted from the article]

B Background: b Complex liver resection with concomitant biliary or vascular resection is a standard surgical procedure. B Methods: b Records of 1796 patients undergoing liver resection for >1 segment were analyzed. Risk factors for 90-day in-hospital mortality were age >=60 years (OR 3.7), ASA III/IV (OR 2.9 / 15.6), intrahepatic cholangiocarcinoma (OR 3.0), perihilar cholangiocarcinoma (Klatskin tumor) (OR 5.6), right trisectionectomy (OR 2.8), Quick< 85% (OR 2.4), g-GT >60U/L (OR 2.8), plateletcount < 120/nL (OR 5.5) and creatine >2mg/dL (OR 9.8). [Extracted from the article]

Hintergrund und Fragestellung: Die Anastomoseninsuffizienz ist nach wie vor die Hauptursache für Mortalität nach Ösophagus- und Kardiaresektion. Da sich in Deutschland die Endoskopie als erste diagnostische Maßnahme beim Verdacht auf eine Insuffizienz etabliert hat, hat die CAES auf der Basis des endoskopischen Befundes eine Definition und Schweregradklassifikation der Insuffizienz nach Ösophagusresektion entwickelt und validiert.Material und Methoden: Der 2010 publizierte und 2013 validierte Vorschlag der internationalen Studiengruppe für die Insuffizienz nach anteriorer Rektumresektion diente als Basis für die intrathorakale Anwendung. Die Schwere der Insuffizienz sollte anhand der Bedeutung für das klinische Management bewertet werden: Typ I konservatives Management, Typ II interventionell radiologisch oder endoskopische Therapie und Typ III chirurgische Revision. Im Unterschied zur Rektumklassifikation wurde eine Unterteilung des Typ III in eine Kategorie ohne (Typ IIIa) und mit Diskontinuitätsresektion (Typ IIIb) vorgenommen. Die Validierung erfolgte anhand eines 10-Jahres-Kollektivs aus den Unikliniken Heidelberg und Tübingen.Ergebnisse: Im Zeitraum 2006 bis 2015 wurden alle 92 Patienten, die nach Ösophagus- und Kardiaresektion eine Insuffizienz entwickelten, in das Kollektiv eingeschlossen. Wir fanden einen signifikanten Anstieg der IMC/ICU-Tage mit aufsteigenden Typen der Klassifikation (p < 0,0143). Weiterhin fand sich eine signifikante Korrelation sowohl mit der allgemeinen Klassifikation postoperativer Komplikationen nach Clavien-Dindo als auch mit der Mortalität (p < 0,001).Diskussion: Standardisierte Parameter sind die Voraussetzung, um Ergebnisse zwischen Kliniken und Studien vergleichen zu können. Die Validierung der hier vorgeschlagenen Klassifikation zeigt, dass die Differenzierung zwischen den Gruppen durch die Korrelationen zu Intensivaufenthalt, Clavien-Dindo und Mortalität untermauert wird und damit in Zukunft zur besseren Vergleichbarkeit der Daten zu Insuffizienz nach Ösophagusresektion beiträgt. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the procedural and clinical outcomes of carotid artery stenting (CAS) in the hands of endovascular trained vascular surgeons. Methods: Between April 2008 to May 2013, 1197 patients were treated for extracranial internal carotid artery (ICA) stenosis. The proportion of endovascular treated patients was 5.0% (CAS n = 60 vs. carotid endarterectomy (CEA) n = 1137). All patients in the CAS group (44 males, median age 70 years) were treated by two senior vascular surgeons experienced in endovascular methods. Restenosis was the indication for CAS in 32 out of 60 patients (53.3%). Further indications were contralateral ICA occlusion ( n = 14, 23.3%), radiogenic ICA stenosis ( n = 5, 8.3%), high-risk candidates for CEA ( n = 4, 6.6%), and the presence of contralateral recurrent paresis ( n = 2, 3.3%). High-risk patients for CEA were defined as patients with history of severe cardiac disease and patients with impaired general condition. 84.4% ( n = 27) of the restenosis were asymptomatic with a mean degree of stenosis of 83.7%, and 12.9% ( n = 4) were symptomatic (degree of stenosis of 90%). Mean procedural and fluoroscopy time were 61 and 14 min. Study endpoints were periprocedural stroke-related mortality and morbidity, restenosis rate, and overall survival. Follow-up was performed by duplex ultrasound with a median follow-up period of 12 months (range 1-55). Results: The periprocedural stroke rate of CAS within 30 days was 3.3% (one ischemic stroke, one intracranial hemorrhage); two additional patients suffered TIA (3.3%). None of the patients had a myocardial infarction perioperatively. The mortality rate was 0. CAS procedures were completed in 90.0% ( n = 54) of cases. Dropout rate was 8.3% ( n = 5) for morphological reasons (e.g., carotid kinking). Intraoperative complication rate was 1.7% ( n = 1) including one patient who suffered intraoperative rupture of access vessels. The conversion rate with subsequent CEA procedure was 6.6% ( n = 4 of 5). The restenosis rate during follow-up was 3.3% after CAS. The reintervention rate during the median follow-up period of 12 months (1-55 months) was 5.5% ( n = 3/54). Two patients received a reintervention with successful balloon angioplasty; in one case, a diagnostic angiography was performed excluding the presence of a relevant restenosis. No additional stent was implanted. The survival rate was 100% at 1 year, 90.4% at 2 years, and 77.7% at 3 years. Conclusion: CAS, in the hands of vascular surgeons, is feasible with a moderate perioperative risk in a highly selected patient cohort. A procedure termination rate of approximately 10% shows that the complementary therapy using CAS procedure is not overused by surgeons. [ABSTRACT FROM AUTHOR]

Background The incidence of pancreatic neuroendocrine neoplasms ( pNEN) is increasing. This study aimed to evaluate predictors of overall survival and the indication for surgery. Methods Data collected between October 2001 and December 2012 were analysed. Histological grading and staging was based on the classifications of the World Health Organization, the International Union Against Cancer and the European Neuroendocrine Tumour Society. Results Some 310 patients (150 female, 48·4 per cent) underwent surgical resection. The final survival analysis included 291 patients. Five-year overall survival differed according to tumour grade (G): 91·0 per cent among 156 patients with pancreatic neuroendocrine tumours ( pNET) G1, 70·8 per cent in 111 patients with pNET G2, and 20 per cent in 24 patients with pancreatic neuroendocrine carcinomas ( pNEC) G3 ( P < 0·001). Tumours graded G3 (hazard ratio ( HR) 6·96, 95 per cent confidence interval 3·67 to 13·21), the presence of distant metastasis ( HR 2·41, 1·32 to 4·42) and lymph node metastasis ( HR 2·10, 1·07 to 4·16) were independent predictors of worse survival ( P < 0·001, P = 0·004 and P = 0·032 respectively). Eight of 61 asymptomatic patients with pNEN smaller than 2 cm had tumours graded G2 or G3, and six of 51 patients had lymph node metastasis. Among patients with pNEC G3, the presence of distant metastasis had a significant impact on the 5-year overall survival rate: 0 per cent versus 43 per cent in those without distant metastasis ( P = 0·036). Conclusion Neuroendocrine tumours graded G3, lymph node and distant metastasis are independent predictors of worse overall survival in patients with pNEN. [ABSTRACT FROM AUTHOR]

Background Autoimmune pancreatitis ( AIP) is characterized by diffuse or focal swelling of the pancreas. AIP has been divided into types 1 and 2. The aim of the study was to evaluate and compare the clinicopathological characteristics, therapy and outcome of patients with AIP. Methods The medical records of patients diagnosed with AIP between January 2003 and July 2011 were reviewed. Characteristics of patients with AIP types 1 and 2 were compared with those of patients with pancreatic ductal adenocarcinoma ( PDAC). Results AIP was classified as type 1 in 40 patients and type 2 in 32 according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria. Patients with histologically confirmed AIP type 2 were younger than those with type 1 ( P = 0·005). Some 30 of 32 patients with AIP type 2 were found to have a localized tumour-like pancreatic mass and underwent pancreatectomy, compared with only 16 of 40 with type 1 ( P < 0·001). Three of 25 patients with AIP type 2 presented with raised serum levels of IgG4 compared with 21 of 38 with type 1 ( P < 0·001). There was no difference in symptoms and involvement of other organs between AIP types 1 and 2. Presentation with weight loss was more common among patients with PDAC than those with AIP, but there was no difference in pain or jaundice between the groups. Raised serum carbohydrate antigen 19-9 levels were more prevalent in patients with PDAC. Conclusion Patients with AIP type 2 frequently present with abdominal pain and a tumour-like mass. Differentiating AIP from PDAC is difficult, so making the clinical decision regarding operative versus conservative management is challenging. [ABSTRACT FROM AUTHOR]

Background. Pharmacokinetic monitoring of calcineurin inhibitors (CNIs) is unsatisfactory because, at comparable blood concentrations, side effects vary considerably. We recently confirmed the applicability of a pharmacodynamic (PD) assay that measures the suppression of CNI target genes, specifically the suppression of nuclear factor of activated T cells (NFAT)-regulated genes in liver transplant (LT) recipients. The aim of this prospective study was to prove the clinical reliability of this assay. Therefore, we quantified the residual gene expression (RGE) of NFAT-regulated genes and evaluated the association between the RGE of NFATregulated genes and the incidence of cytomegalovirus (CMV) infection. Patients and methods. In 20 LT recipients, 10 patients on cyclosporine (CsA) and 10 patients on tacrolimus (Tac) therapy, who presented with CMV infection, the RGEs of interleukin-2, interferon-γ (IFNγ), and granulocyte-monocyte colony-stimulating factor were measured and compared with the RGEs of these cytokines in 40 healthy dose-matched LT controls. Results. CsA-treated CMV patients demonstrated a lower RGE of all NFAT-regulated genes compared with controls (30 ± 17 vs. 44 ± 20, P = 0.067). For IFNγ, the level of significance was reached (26 ± 17 vs. 43 ± 17, P = 0.0125). Daily CsA dosage, CsA baseline (C0) and 2 h (C2) concentrations were comparable (CsA dosage 169 mg/day vs. 165 mg/day; CsA C0 94 µg/L vs. 85 µg/L; CsA C2 389 µg/L vs. 381 µg/L). In addition, Tac-treated CMV patients demonstrated a lower RGE of all NFAT-regulated genes compared with controls (68 ± 25 vs. 84 ± 22, P = 0.0769). Analogous to CsA-treated CMV patients, the level of significance was reached for IFNγ (61 ± 24 vs. 88 ± 29, P = 0.0154). Daily Tac dosage and Tac 1.5 h concentrations (C1.5) were comparable in both groups (Tac dosage 4 mg/day vs. 4 mg/day; Tac C1.5 8 µg/L vs. 10 µg/L), whereas Tac C0 concentrations were significantly higher in controls (Tac C0 4 µg/L vs. 6 µg/L, P = 0.0276). Conclusion. Measuring the RGE of NFAT-regulated genes is appropriate to assess the risk of infections in LT recipients. Measuring the RGE of IFNγ is particularly suitable to assess the risk of CMV infection. PD monitoring of CNIs in LT recipients is an approach to individualize immunosuppression, which may help to reduce infectious complications. [ABSTRACT FROM AUTHOR]

Aims: Postoperative morbidity and mortality after liver resection is closely related to the degree of intraoperative blood loss; the majority of which occurs during transection of the liver parenchyma. Many approaches and devices have therefore been developed to limit bleeding, but none has yet achieved perfect results up to now. The aim of this standardized chronic animal study was to compare the safety and efficacy of the LigaSure™ Vessel Sealing System (LVSS) with the stapler technique, which is one of the modern techniques for transecting the parenchyma in liver surgery. Methods: Sixteen pigs underwent a left liver resection (LLR). Eight pigs received a LLR by means of an Endo GIA, whereas the other eight pigs underwent liver parenchymal transection followed by simultaneous sealing by the LVSS. The operating time, transection time, blood loss during transection, and time of hemostasis were measured on the day of LLR (postoperative day 0/POD 0). Animals were re-explored on postoperative day 7 (POD 7) and the transection surface of remnant liver was observed for fluid collection (hematoma, biloma, and abscess), necrosis, and other pathologies. A biopsy was taken from the area of transection for histopathological examination. Results: All animals survived until POD 7. Operating time and transection time of the liver parenchyma on POD 0 was significantly shorter in the stapler group. There was no significant difference between the two groups in terms of blood loss during transection, time of hemostasis and number of sutures for hemostasis on POD 0, morbidity rate, as well as the histopathological examination on POD 7. Furthermore, the material costs were significantly higher in the stapler group than in the LVSS group. Conclusion: In this standardized chronic animal study concerning transection of the parenchyma in liver surgery, LVSS seems not only to be safe, but also comparable with the stapler technique in terms of morbidity and mortality. Additionally, LVSS significantly reduces material costs. However, the transection time is significantly longer for LVSS than for the stapler resection technique. [ABSTRACT FROM AUTHOR]

Aims: The da Vinci® telemanipulation system offers a wide range of precise movements and 3D visualization with depth perception and magnification effect. Such a system could be useful for improving minimally invasive procedures-as in the case of large hiatal hernia with paraesophageal involvement (PEH) repair. Studies reporting on the robotic-assisted PEH repair are scarce, and a comparison to the standard operation techniques is lacking. Therefore, we decided to investigate the feasibility and safety of robotic-assisted surgery (RAS) compared to conventional laparoscopic (CLS) and open surgery (OS) for the first time. Methods: We investigated 42 patients for the perioperative outcome after PEH repair. Twelve patients were operated on with RAS, 17 with CLS, and 13 with OS. Operating time, intraoperative blood loss, intra- and postoperative complications, mortality, and duration of hospital stay were analyzed in each method. Results: On average, operating time in the RAS group was 38 min longer, and the intraoperative blood was loss 217 ml lower compared to OS. Both results were similar to the CLS group. The intraoperative complication rate was similar in all groups. The postoperative complication rate in the RAS group was significantly lower than the OS group, though again similar to the CLS group. The hospital stay was 5 days shorter in the RAS group than the OS group and once again similar to the CLS group. Conclusion: The results show that RAS is feasible and safe. It appears to be an alternative to OS due to lower intraoperative blood loss and potentially fewer postoperative complications, as well as shorter hospital stay. Though, RAS is not superior to CLS. [ABSTRACT FROM AUTHOR]

The mechanism of therapeutic success of propranolol for severe infantile haemangioma remains unclear. Propranolol was shown to modify matrix metalloproteinase (MMP) levels, which are associated with tumour pathogenesis. We hypothesized that urinary MMP2/9 is higher in patients with infantile haemangioma compared to healthy infants and that propranolol reduces MMP2/9 levels and thus leads to an involution of the haemangioma. In this case, MMP2/9 could be used as a marker of indicated therapy or therapeutic success. Urinary samples were taken before, 2 weeks after, and 2 months after the beginning of propranolol treatment in haemangioma patients and once in healthy controls. Activity of MMP2/9 was determined by commercially available activity kits. Urine of 22 haemangioma patients and 21 control subjects was obtained. Propranolol therapy had significant success in all patients. MMP2/9 was present in most samples, the younger the children the higher the MMP2 levels. Haemangioma patients showed lower levels of MMP2. The MMP2 levels were significantly higher after 2 weeks of propranolol than prior to therapy. There were no differences in MMP9 levels. Conclusions: Presence of MMP2/9 in the urine of infants <1 year can be explained by high rate of physiological tissue remodelling. Unexpectedly, MMP2 was lower in the urine of haemangioma patients and higher 2 weeks after propranolol treatment. Taking this and the diverse results in literature into account, the correlation between MMPs, proliferation, and regression of haemangiomas and propranolol remains unclear. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated the delayed gastric emptying (DGE) definition of the International Study Group of Pancreatic Surgery (ISGPS). It utilized univariable and multivariable analyses to determine the factors such as prolonged hospital stay, longer intensive care unit (ICU) admission, and gender, linked to DGE. It also discusses the feasibility of the ISGPS DGE definition to postoperative complications.

Background: ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported.Methods: In this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters.Results: We could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM.Conclusions: Our findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Restorative proctocolectomy followed by an ileoanal J-pouch procedure is the therapy of choice for patients with familial adenomatous polyposis and ulcerative colitis. After low anterior rectal resection, the authors have reported on a novel, less complex pouch configuration, a transverse coloplasty pouch. The aim of the present work was to apply this new design to the ileal pouch construction, to evaluate feasibility, and to measure functional results in comparison with the J-pouch and the straight ileoanal anastomosis using the pig as an animal model.Methods: Twenty-three pigs underwent restorative proctocolectomy followed by reconstruction with straight ileoanal anastomosis (IAA; n = 5), J-pouch (n = 7), and a transverse ileal pouch (TIP; n = 11). Pigs were followed for 6 days postoperatively. Peristaltic function was assessed by manometry proximal to the pouch, in the reservoir, and at the level of the ileoanal anastomosis. Functional outcome was monitored by semiquantitative assessment of the general condition of the animals, postoperative feeding habits, and stool frequency and consistency. A Fourier analysis was performed in order to compare peristalsis in the ileal reservoirs. The reservoir volume was measured in situ by triple contrast computed tomography scan with 3D reconstruction.Results: Seventeen animals survived for 1 week. There was no difference in the general condition or the feeding habits of the groups. A significant number of pigs with the TIP pouch (7/10) had semisolid or formed stools as opposed to liquid stools after J-pouch (6/6) and IAA (4/5; p = 0.01). TIP animals had a lower stool frequency (3.2 +/- 1.14 per day) on day 6 after the operation than pigs with J-pouch, 5.33 +/- 1,03, and IAA, 4.6 +/- 1.82 (p = 0.0036). The in situ volume of the pouches did not differ significantly. The Fourier analysis demonstrated a disruption of peristalsis by the J-pouch and the TIP reconstruction but not after IAA.Conclusion: The function of ileoanal reservoirs after proctocolectomy may result from the disruption of properistaltic waves after pouch formation. The mechanism of peristalsis disruption is independent of the in situ volume of the pouch. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed the clinical relevance of the 2000 World Health Organization (WHO) classification and the tumour node metastasis (TNM) classifications and examined surgical outcomes and survival of patients with pancreatic neuroendocrine tumours (pNET). The study analyzed data from 118 consecutive patients with a pNET receiving surgical intervention. The study concluded that both classifications accurately reflect the clinical outcome of patients with pNET.

The article highlights a study which evaluated a long-term follow up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple (ppWhipple) procedure for chronic pancreatitis. At 14 years' follow-up, loss of appetite was significantly worse in the ppWhipple group. Meanwhile, diabetes mellitus was observed in 7 of 15 patients under the Beger procedure and 11 of 14 patients in the ppWhipple group.

This study evaluated the role of the acute phase C-reactive protein (CRP) in the postoperative course of a large series of rectal resections on the basis of a prospective database. Main focus of this study was the early identification of complications. Three hundred eighty-three rectal resections with primary anastomosis for rectal cancer were screened for infectious postoperative complications. Forty-eight complicated cases were identified and matched with 48 patients with an uneventful postoperative course. In the postoperative setting, CRP peaked on postoperative day (POD) 2 with a median serum CRP of 140 mg/l and gradually declined thereafter in uncomplicated cases. In complicated cases, CRP elevation generally persisted after POD 2, whereas white blood cells and body temperature were within normal range in the early postoperative period. A cutoff CRP value of 140 mg/dl on PODs 3 and 4 resulted in predictive values of 85.7 and 90.5% (adjusted to the prevalence: 37.6 and 50.3%), sensitivities of 80.0 and 54.3%, and specificities of 81.0 and 92.3% for a complicated postoperative course ( P < 0.001), respectively. Persistent CRP elevation and elevation of serum CRP above 140 mg/dl on PODs 3–4 are predictive of infectious postoperative complications and should prompt intense clinical search for an inflammatory process, especially for an anastomotic leak if pneumonia and wound infection are unlikely or excluded. [ABSTRACT FROM AUTHOR]

Background: Success of chemotherapy and alleviation of pain are frequently less than optimal in pancreatic cancer patients, leading to increasing interest in new pharmacological substances, such as vanilloids. Our study addressed the question of whether vanilloids influence pancreatic cancer cell growth, and if vanilloids could be used for pain treatment via the vanilloid 1 receptor (VR1) in pancreatic cancer patients. Methods: In vitro, the effect of resiniferatoxin (vanilloid analogue) on apoptosis and cell growth in pancreatic cancer cells—either alone, combined with 5-fluorouracil (5-FU), or combined with gemcitabine—was determined by annexin V staining, FACS analysis, and MTT assay, respectively. VR1 expression was evaluated on RNA and protein level by quantitative polymerase chain reaction and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics—especially pain levels—were registered in a prospective database and correlated with VR1 expression. Results: Resiniferatoxin induced apoptosis by targeting mitochondrial respiration and decreased cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 was significantly upregulated in human pancreatic cancer and chronic pancreatitis. VR1 expression was related to the intensity of pain reported by cancer patients but not to the intensity of pain reported by patients with chronic pancreatitis. Conclusions: Resiniferatoxin induced apoptosis in pancreatic cancer cells indicates that vanilloids may be useful in the treatment of human pancreatic cancer. Furthermore, vanilloid might be a novel and effective treatment option for neurogenic pain in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background and aims: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. Methods: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAl) of ⩾4. Retarded release phosphatidyicholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAl towards clinical remission (CAl ⩽ 3) or CAl improvement by ⩾50%. Secondary end points included ⩾50% changes in endoscopic activity index (EAl), histology, and quality of life scores. Results: Induction of clinical remission (CAl ⩽ 3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAl improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAl score (70% improvement) was recorded in the phosphatidylchohine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p=0.00005). Conclusion: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: A defective mucus composition represents a key pathogenetic factor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of hydrophobic mucus layer. For evaluation of PC to the pathogenesis of inflammatory bowel disease, the concentration and composition of PC in the rectal mucus of patients with the ulcerative colitis was determined. Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) allows quantification of PC species and enables analysis of crude extracts. Methods: Lipid extracts of material obtained by light scrapings of the intestinal lumen were analysed quantitatively by nanoESI MS/MS with synthetic internal PC and lysophosphatidylcholine (LPC) standards, PC and LPC species from rectoscopically acquired mucus aliquots of patients with ulcerative colitis were compared to Crohn disease and control subjects. Results: Patients with inactive ulcerative colitis showed significantly less PC and LPC (median 346 [IQR: 230-405] pmol total PC/mg dry weight) in rectal mucus compared to Crohn disease (median 1126 [IQR: 465-1941] pmol total PC/mg dry weight) and control subjects (median 1285 [IQR: 850-1639] pmol total PC/mg dry weight) P < 0.05). The molecular species of PC and LPC were not significantly different between the groups. The most abundant species were PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0; and LPC 18:0. Conclusion: NanoESI MS/MS is a suitable tool for analysing and quantifying small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC molecular species composition pattern. This suggests that a low amount of protective mucus PC is a characteristic feature in ulcerative colitis and explains an increased susceptibility to luminal contents. [ABSTRACT FROM AUTHOR]

UniProtKB/Swiss-Prot, a curated protein database, and dictyBase, the Model Organism Database for Dictyostelium discoideum, have established a collaboration to improve data sharing. One of the major steps in this effort was the ‘Dicty annotation marathon’, a week-long exercise with 30 annotators aimed at achieving a major increase in the number of D. discoideum proteins represented in UniProtKB/Swiss-Prot. The marathon led to the annotation of over 1000 D. discoideum proteins in UniProtKB/Swiss-Prot. Concomitantly, there were a large number of updates in dictyBase concerning gene symbols, protein names and gene models. This exercise demonstrates how UniProtKB/Swiss-Prot can work in very close cooperation with model organism databases and how the annotation of proteins can be accelerated through those collaborations. [ABSTRACT FROM PUBLISHER]