Long Term Outcome After Open Abdomen Treatment: Function and Quality of Life.

Background: Open abdomen treatment (OAT) is widely accepted to manage severe abdominal conditions such as peritonitis and abdominal compartment syndrome but can be associated with high morbidity and mortality. The main risks in OAT are (1) entero-atmospheric fistula (EAF), (2) failure of primary fascial closure, and (3) incisional hernias. In this study, we assessed the long-term functional outcome after OAT to understand which factors impacted most on quality of life (QoL)/daily living activities and the natural course after OAT. Materials and Methods: After a retrospective analysis of 165 consecutive OAT patients over a period of 10 years (2002-2012) with over 65 clinical parameters that had been performed at our center (1), we initiated a prospective structured follow-up approach. All survivors were invited for a clinical follow-up. Forty complete datasets including clinical and social follow-up with SF-36 scores were available for full analysis. Results: The patients were dominantly male (75%) with a median age of 52 years. Primary fascial closure (PC) was achieved in 9/40 (23%), while in 77% a planned ventral hernia (PVH) approach was followed. A total of 3/4 of the PVH patients underwent a secondary-stage abdominal wall reconstruction (SSR), but 2/3 of these reconstructed patients developed recurrent hernias. Fifty-five percent of the patients with PC developed an incisional hernia, while 20% of all patients developed significant scarring (Vancouver Scar Score >8). Scar pain was described by 15% of the patients as "moderate" [Visual Analog Scale (VAS) 4-6] and by 10% as "severe" (VAS > 7). While hernia presence, PC or PVH, and scarring showed no impact on QoL, male sex and especially EAF formation significantly reduced QoL. Discussion: Despite many advantages, OAT was associated with relevant mortality and morbidity, especially in the early era before the implementation of a structured concept at our center. Follow-up revealed that hernia incidence after OAT and secondary reconstruction were high and that 25% of patients qualifying for a secondary reconstruction either did not want surgery or were unfit. Sex and EAF formation impacted significantly on QoL, which was lower than in the general population. With regard to hernia incidence, new strategies such as prophylactic mesh implantation upon fascial closure should be discussed analogous to other major abdominal procedures.

Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). / Strukturierte Befundung von soliden und zystischen Pankreasläsionen im CT und MRT: Konsensus-basierte Befundvorlagen der Deutschen Röntgengesellschaft (DRG).

BACKGROUND: Radiological reports of pancreatic lesions are currently widely formulated as free texts. However, for optimal characterization, staging and operation planning, a wide range of information is required but is sometimes not captured comprehensively. Structured reporting offers the potential for improvement in terms of completeness, reproducibility and clarity of interdisciplinary communication. METHOD: Interdisciplinary consensus finding of structured report templates for solid and cystic pancreatic tumors in computed tomography (CT) and magnetic resonance imaging (MRI) with representatives of the German Society of Radiology (DRG), German Society for General and Visceral Surgery (DGAV), working group Oncological Imaging (ABO) of the German Cancer Society (DKG) and other radiologists, oncologists and surgeons. RESULTS: Among experts in the field of pancreatic imaging, oncology and pancreatic surgery, as well as in a public online survey, structured report templates were developed by consensus. These templates are available on the DRG homepage under www.befundung.drg.de and will be regularly revised to the current state of scientific knowledge by the participating specialist societies and responsible working groups. CONCLUSION: This article presents structured report templates for solid and cystic pancreatic tumors to improve clinical staging (cTNM, ycTNM) in everyday radiology. KEY POINTS: · Structured report templates offer the potential of optimized radiological reporting with regard to completeness, reproducibility and differential diagnosis.. · This article presents consensus-based, structured reports for solid and cystic pancreatic lesions in CT and MRI.. · These structured reports are available open source on the homepage of the German Society of Radiology (DRG) under www.befundung.drg.de.. CITATION FORMAT: · Persigehl T, Baumhauer M, Baeßler B et al. Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). Fortschr Röntgenstr 2020; 192: 641 - 655.

Chronic rejection after intestinal transplantation: A systematic review of experimental models.

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.

Delayed gastric emptying following pancreatoduodenectomy with alimentary reconstruction according to Roux-en-Y or Billroth-II.

BACKGROUND: Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD) with published incidences as high as 61%. The present study investigates the impact of bowel reconstruction techniques on DGE following classic PD (Whipple-Kausch procedure) with pancreatogastrostomy (PG). METHODS: We included 168 consecutive patients who underwent PD with PG with either Billroth II type (BII, n = 78) or Roux-en-Y type reconstruction (ReY, n = 90) between 2004 and 2015. Excluded were patients with conventional single loop reconstruction after pylorus preserving procedures. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay and demographic factors. RESULTS: No difference was observed between BII and ReY regarding frequency of DGE. Overall rate for clinically relevant DGE was 30% (ReY) and 26% (BII). BII and ReY did not differ in terms of demographics, morbidity or mortality. DGE significantly prolongs ICU (four vs. two days) and hospital stay (20.5 vs. 14.5 days). Risk factors for DGE development are advanced age, retrocolic reconstruction, postoperative hemorrhage and major complications. CONCLUSIONS: The occurrence of DGE can not be influenced by the type of alimentary reconstruction (ReY vs. BII) following classic PD with PG. Old age and major complications could be identified as important risk factors in multivariate analysis. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00011860 . Registered 14 March 2017.

DNA Methylation of PITX2 and PANCR Is Prognostic for Overall Survival in Patients with Resected Adenocarcinomas of the Biliary Tract.

Biliary tract cancers (BTC) are rare but highly aggressive malignant epithelial tumors. In order to improve the outcome in this lethal disease, novel biomarkers for diagnosis, prognosis, and therapy response prediction are urgently needed. DNA promoter methylation of PITX2 variants (PITX2ab, PITX2c) and intragenic methylation of the PITX2 adjacent non-coding RNA (PANCR) were investigated by methylations-specific qPCR assays in formalin-fixed paraffin-embedded tissue from 80 patients after resection for BTC. Results were correlated with clinicopathologic data and outcome. PITX2 variants and PANCR showed significant hypermethylation in tumor vs. normal adjacent tissue (p < 0.001 and p = 0.015), respectively. In survival analysis, dichotomized DNA methylation of variant PITX2c and PANCR were significantly associated with overall survival (OS). Patients with high tumor methylation levels of PITX2c had a shorter OS compared to patients with low methylation (12 vs. 40 months OS; HR 2.48 [1.38-4.48], p = 0.002). In contrast, PANCR hypermethylation was associated with prolonged survival (25 vs. 19 months OS; HR 0.54 [0.30-0.94], p = 0.015) and qualified as an independent prognostic factor on multivariate analysis. The biomarkers investigated in this study may help to identify BTC subpopulations at risk for worse survival. Further studies are needed to evaluate if PITX2 might be a clinically useful biomarker for an optimized and individualized treatment.

Cyclooxygenase Inhibitors as a New Therapeutic Strategy in Small Bowel Transplantation.

BACKGROUND: The long-term outcome of intestinal transplantations is still not favorable, which is partly due to the intestinal susceptibility to ischemia. There are several indications that the inflammatory response to ischemia-reperfusion injury is mediated by cyclooxygenases and that their inhibition may be associated with improved organ function. The aim of this study was to analyze if cyclooxygenase (COX) inhibitors could improve the early posttransplant outcome after orthotopic small bowel transplantation. METHODS: Small bowel transplantation was performed between rats to test the impact of nonselective (Piroxicam), preferential (Meloxicam), and selective COX-2 inhibitors (Parecoxib). The donor intestines were either perfused and stored with inhibitor or had inhibitor administered intravenously after transplantation. RESULTS: Using COX inhibitors, a sequential increase of posttransplantation intestinal integrity could be shown, with Parecoxib the least effective and Meloxicam the most effective treatment. These differences were in line with the downregulation of COX-2 activity by the inhibitors. Functionally, the same tendency could be seen in diminished expression of proinflammatory molecules, decreased leucocyte inflammation, and significantly improved graft microcirculation. In most cases, the intravenous administration was more effective. However, the COX inhibitors used were shown to cause relevant hepatotoxicity under nearly all conditions, but particularly under intravenous administration. Only Meloxicam in histidine-tryptophan-ketoglutarate was demonstrated to be a safe drug without hepatotoxic side effects. CONCLUSIONS: The activity of COX contributes to ischemia-reperfusion injury after intestinal transplantation. In this comparative study, the administration of the preferential COX-2 inhibitor Meloxicam via histidine-tryptophan-ketoglutarate showed the best graft-protective attributes and the lowest hepatotoxic side effects.

Recombinant HLA-G as Tolerogenic Immunomodulant in Experimental Small Bowel Transplantation.

The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8+ T-cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4+ populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4+/CD25+/FoxP3+Treg-cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8+ T-cell populations either directly or by induction of non-classical Treg populations.

Incidentally Detected Focal Liver Lesions - A Common Clinical Management Dilemma Revisited.

BACKGROUND: Detection of asymptomatic focal liver lesions (FLL) is increasing because of a widespread use of modern radiologic imaging. Most of these lesions are benign, though malignancy often has to be ruled out, which is posing a diagnostic challenge. AIM: To critically evaluate our treatment strategy in the context of recently published American College of Gastroenterology (ACG) guidelines. PATIENTS AND METHODS: The medical records of patients who underwent surgery for asymptomatic, incidentally detected FLL from 2005-2012 were reviewed. Primary end-points were the congruence of suspected diagnosis and final pathology, as well as the identification of predictors of malignancy. A systematic review was undertaken to help define a standardized management. RESULTS: Eighty patients, 37 male and 43 female with a mean age of 57 years (range=16-83) were included, harboring 39 (49%) malignant and 41 (51%) benign, asymptomatic hepatic lesions. Hepatocellular carcinoma (HCC) (n=24) represented most of malignant FLL, followed by cholangiocellular carcinoma (CCC) (n=10), whereas focal nodular hyperplasia (FNH) (n=19) and liver hemangioma (n=7) were the predominant benign entities. Fifty-one patients (64%) had a correct preoperative diagnosis, while patients with FNH were most commonly misdiagnosed (53%). We identified age (p<0.001) and male sex (p=0.013) as risk factors for malignancy in an asymptomatic FLL. CONCLUSION: Despite recent technical advances of the modern radiology setting a correct preoperative diagnosis in an asymptomatic FLL remains challenging. Male gender and old age seem to correlate with malignancy. In the absence of biomarkers and evidence-based guidelines, a multidisciplinary approach in an experienced tertiary referral center is recommended for an optimized individual management.

Impact of Extended Primary Surgery on Suboptimally Operable Patients With Advanced Ovarian Cancer.

OBJECTIVES: Extensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today's criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions. METHODS: All patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study. RESULTS: Fifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates. CONCLUSIONS: Because of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.

Risk factors for delayed gastric emptying following distal pancreatectomy.

PURPOSE: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy and other types of upper gastrointestinal surgery with published incidences as high as 60 %. The present study examines the incidence of DGE following distal pancreatic resection (DPR). METHODS: Between 2002 and 2014, 100 patients underwent conventional DPR at our department. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay, and demographic factors. RESULTS: Overall incidence of DGE was 24 %. No difference in age, gender, or other demographic factors was observed in patients with DGE. Perioperative characteristics (splenectomy rate, closure technique of the pancreatic remnant, operation time, blood loss and transfusion, ICU, ASA score) were comparable. Major complications were associated with DGE (11/24 patients (46 %) vs. 19/76 patients (25 %) without DGE) and the rate of pancreatic fistula was significantly higher in the group of patients with DGE (14/24 patients (58 %) vs. 27/76 patients (36 %), P = 0.047). In multivariate analysis, a periampullary malignancy was shown to be a significant factor for DGE development. DGE significantly prolonged hospital stay (14 vs. 22 days). CONCLUSIONS: DGE is a substantial complication not only after pancreatoduodenectomy, but it also occurs frequently after DPR. Prevention of pancreatic fistula might reduce its incidence, especially in patients with malign pathology.

Current knowledge on regulation and impairment of motility after intestinal transplantation.

PURPOSE OF REVIEW: Understanding the key mechanisms impacting on intestinal graft motility is paramount for successful intestinal transplantation. In this review, we will discuss causes of graft hypomotility and hypermotility, rooted in changes of the intrinsic nervous system, local inflammatory processes, adaptive immune responses, and more. RECENT FINDINGS: Recently, it has been shown that the gut microbiome closely interacts with the structural integrity and rejection processes in the small intestine. After the ischemia/reperfusion injury is overcome, the absence of rejection is important to maintain graft motor function. The interstitial cells of Cajal, with their pacemaker function, play an important role by regulating propulsive intestinal motility in the initial absence of extrinsic signaling. Local inflammatory and immunological changes in the tunica muscularis of transplanted intestines also result in dysmotility, both after ischemia/reperfusion and during rejection. SUMMARY: Motility of the transplanted intestine is crucial for transplant outcome and depends on multiple factors. Extrinsic denervation and changes in the intrinsic intestinal nervous system, local inflammation in the tunica muscularis, acute and chronic rejection, changes in the microbiome with Toll-like receptor activation, stasis of intestinal contents with bacterial translocation, all multifactorially result in impaired graft motility. These factors must be individually acknowledged and addressed to obtain adequate graft function.

Extensive multifocal branch duct IPMN of the pancreas after liver transplantation: is surgery justified?

BACKGROUND: Cystic lesions of the pancreas resembling intraductal papillary mucinous neoplasms (IPMN) have been reported to develop in an increased rate following liver transplantation and immunosuppression. The cause for this possible association is thus far elusive. PRESENTATION OF THE CASE: We report on a 60-year-old male patient who developed an extensive multicystic change of the entire pancreas, suspicious for IPMN, under follow-up after liver transplantation for secondary sclerosing cholangitis. A total pancreaduodenectomy with splenectomy was performed. The postoperative histopathological assessment revealed a multifocal branch duct IPMN of the gastric subtype showing low-grade dysplasia. DISCUSSION: In the absence of evidence-based guidelines for the management of suspected IPMNs in liver transplant recipients, each patient's management should be discussed in detail. CONCLUSION: Prospective studies may help to understand the disease and identify risk factors for malignant transformation in IPMNs after liver transplantation for treatment optimization.

Biliary intraepithelial neoplasia (BilIN) is frequently found in surgical margins of biliary tract cancer resection specimens but has no clinical implications.

Biliary tract cancers are aggressive tumors of which the incidence seems to increase. Resection with cancer-free margins is crucial for curative therapy. However, how often biliary intraepithelial neoplasia (BilIN) occurs in resection margins and what its clinical and therapeutic implications might be is largely unknown. We reexamined margins of resection specimens of adenocarcinoma of the biliary tree including the gallbladder for the presence of BilIN. When present, it was graded. The findings were correlated with clinicopathological parameters and overall survival. Complete examination of the resection margin could be performed on 55 of 78 specimens (71%). BilIN was detected in the margin in 29 specimens (53%) and was mainly low-grade (BilIN-1; N = 14 of 29; 48%). In resection specimens of extrahepatic cholangiocarcinoma, BilIN was most frequent (N = 6 of 8; 75%). BilIN was found in the resection margin more frequently in extrahepatic cholangiocarcinomas (P = 0.007) and in large primary tumors (P = 0.001) with lymphovascular (P = 0.006) and perineural invasion (P = 0.049). Patients with cancer in the resection margin (R1) had a significantly shorter overall survival than those with resection margins free of tumor (R0) irrespective of the presence of BilIN (R0 vs R1; P < 0.001) or BilIN grade (BilIN-positive vs BilIN-negative, P = 0.6, and BilIN-1 + 2 vs BilIN-3, P = 0.58). BilIN is frequently found in the surgical margin of resection specimens of adenocarcinoma of the biliary tract. Hepatopancreatobiliary surgeons will be confronted with this recently defined entity when an intraoperative frozen section of a resection margin is requested. However, this diagnosis does not require additional resection and in the intraoperative evaluation of resection, the emphasis should remain on the detection of residual invasive tumor.

Total or subtotal colectomy in patients undergoing surgery for primary or recurrent epithelial ovarian cancer.

BACKGROUND: There is controversy as to whether performing a total or subtotal colectomy is justified in patients with advanced ovarian cancer, given its potential for morbidity and a negative effect on long-term quality of life. The aim of this study was to assess the perioperative complications, mortality and outcomes of patients who underwent total or subtotal colectomy as part of the surgical procedure for primary or recurrent epithelial ovarian cancer. PATIENTS AND METHODS: All patients who had undergone surgery including a total or subtotal colectomy for advanced or recurrent ovarian cancer between 2005 and 2013 at our institution were retrospectively identified. RESULTS: In this time period, 339 patients underwent surgery for epithelial ovarian cancer, which in 11 (3%) patients included a total or subtotal colectomy. Severe grade 3-4 postoperative complications occurred in 3 (27%) patients, and 1 (9%) patient died within 60 days of surgery. CONCLUSION: A total or subtotal colectomy is associated with increased but acceptable morbidity in selected patients undergoing primary cytoreductive surgery. However, in the recurrent/palliative setting, total or subtotal colectomy should be avoided as the prognosis is poor and the morbidity outweighs the clinical benefit.

Clinical Management of Chronic Portal/Mesenteric Vein Thrombosis: The Surgeon's Point of View.

BACKGROUND: Bleeding from esophageal varices is a life-threatening complication of chronic portal hypertension (PH), occuring in 15% of patients with a mortality rate between 20 and 35%. METHODS: Based on a literature review and personal experience in the therapy of PH, we recommend a therapy strategy for the secondary prophylaxis of variceal bleeding in PH. RESULTS: The main causes for PH in western countries are alcoholic/viral liver cirrhosis and extrahepatic portal/mesenteric vein occlusion, mainly caused by myeloproliferative neoplasms or hypercoagulability syndromes. The primary therapy is medical; however, when recurrent bleeding occurs, a definitive therapy is required. In the case of parenchymal decompensation, liver transplantation is the causal therapy, but in case of good hepatic reserve or without underlying liver disease, a portal decompressive therapy is necessary. Transjugular intrahepatic portosystemic shunt has achieved a widespread acceptance, although evidence is comparable with or better for surgical shunting procedures in patients with good liver function. The type of surgical shunt should be chosen depending on the patent veins of the portovenous system and the personal expertise. CONCLUSION: The therapy decision should be based on liver function, morphology of the portovenous system, and imminent liver transplantation and should be made by an interdisciplinary team of gastroenterologists, interventional radiologists, and visceral surgeons.

Iatrogenic extracellular matrix disruption as a local trigger for postoperative ileus.

BACKGROUND: Active matrix metallopeptidase 9 (MMP-9) disruption of the extracellular matrix (ECM) plays an important role in inflammatory disorders. In this study, we investigated the inflammatory role of MMP-9 and the ECM breakdown product hyaluronan as a trigger for the postoperative intestinal inflammatory response of postoperative ileus. METHODS: We performed a standardized intestinal surgical manipulation on rats to produce ileus assessed by the oral non-digestible fluorescein isothiocyanate-dextran transit assay. We studied isolated intestinal muscularis extracts for mRNA expressions of interleukin 6 (IL-6), MMP-9 and CD44. We quantified peritoneal MMP-9 activity using zymography, and quantified peritoneal fluid and serum for hyaluronan and tissue inhibitor of metalloproteinase 1 levels by enzyme-linked immunosorbent assay (ELISA). We cultured peritoneal macrophages and exposed them to peritoneal fluid or synthetic hyaluronan for ELISA analysis of IL-6 and macrophage inflammatory protein-1α. RESULTS: Transit was significantly delayed after surgical manipulation, and extracts of the isolated jejunal and colonic muscularis demonstrated a significant induction of IL-6, MMP-9, and CD44 mRNAs compared with controls. Zymography confirmed significant MMP-9 activity in peritoneal fluid compared with controls. Enzyme-linked immunosorbent assay measurements showed a significant up-regulation in hyaluronan and tissue inhibitor of metalloproteinase 1 in the peritoneal fluid and serum. In addition, ELISA and reverse transcriptase-polymerase chain reaction measurements of peritoneal macrophages stimulated with postsurgical peritoneal fluid and synthetic hyaluronan resulted in higher expressions of IL-6 and macrophage inflammatory protein-1α in the macrophage supernatant. CONCLUSIONS: Our results confirm that MMP-9 disruption in the ECM with hyaluronan release and muscularis CD44 receptor induction has the potential to trigger muscularis proinflammatory cascades that cause postoperative ileus. Matrix metallopeptidase 9 inhibition may be a novel therapeutic approach to limit postoperative ileus.

Hemin induction of HO-1 protects against LPS-induced septic ileus.

BACKGROUND: Heme oxygenase (HO-1) protects against inflammation. In this study, we investigated the protective function of hemin-induced HO-1 against lipopolysaccharide (LPS)-induced ileus. METHODS: Rats received LPS intraperitoneally 24 h after intraperitoneal hemin pretreatment or placebo. We also injected zinc protoporphyrin (ZnPP, 3rd group), an inhibitor of HO-1, intraperitoneally 2 h before LPS administration. To assess intestinal muscle function, we examined muscularis strip contractility in an organ bath and measured gastrointestinal transit in vivo. We investigated inflammation within the muscularis using polymerase chain reaction (interleukin [IL]-6, inducible nitric oxide synthase (iNOS), HO-1 and IL-10) 6 and 24 h after LPS. RESULTS: Hemin significantly improved in vitro intestinal muscularis contractility (P < 0.001). In addition, hemin prevented LPS-induced dysmotility in vivo (gastrointestinal transit, geometric center: 8.39 ± 0.33 versus 5.68 ± 0.44; P < 0.001). In Zinc protoporphyrin (ZnPP)-treated animals, both parameters were significantly decreased compared with the hemin group. Messenger RNA expression demonstrated a significant reduction in IL-6 (6 h, hemin: 127.6 ± 36.7 versus LPS: 14,431 ± 5407; 24 h: 1.58 ± 0.39 versus 11.15 ± 2.59; P < 0.01) and iNOS (6 h: 2516 ± 985 versus 50,771 ± 13,321; 24 h: 55.11 ± 10.55 versus 257.1 ± 43.18; P < 0.001) in hemin-treated animals. Anti-inflammatory HO-1 messenger RNA levels (6 h, hemin: 116.3 ± 18.55 versus LPS: 26.02 ± 3.64; 24 h: 18.46 ± 2.69 versus 2.80 ± 0.32; P < 0.001) were increased. There was no significant difference in IL-10 levels at 6 and 24 h. ZnPP reversed the anti-inflammatory hemin effects. CONCLUSIONS: Hemin induction of HO-1 diminishes LPS-induced sepsis. Heme oxygenase-1 has a central role in preventing sepsis-induced ileus. This benefit is reversed by HO-1 inhibition with ZnPP.

Survival after accidental extrahepatic distribution of Y90 microspheres to the mesentery during a radioembolization procedure.

We present the acute management and outcome of a patient after an accidental mesenteric distribution of Y90 microspheres during radioembolization (RE). This report describes and highlights: (1) the incidence of a significant reflux during a RE session while injecting into a replaced right hepatic artery from the superior mesenteric artery, (2) the appearance of diffuse mesenteric Y90 distribution in bremsstrahlung-imaging, (3) the management protocol with the radiation protection agent amifostine, (4) the development of typical adverse effects in the expected time window, and (5) survival of the patient without long-term sequelae. This report should sensitize physicians to this particular problem and may help to avoid as well as manage similar radioembolization incidences.

Operative re-intervention following pancreatic head resection: indications and outcome.

BACKGROUND: This study analyzed indication and outcome regarding operative re-intervention following pancreatoduodenectomy (PD) and pancreatogastrostomy (PG) with special emphasis on complications related to redo surgery. PATIENTS AND METHODS: Two hundred eighty-five patients who underwent PD with PG between 1989 and 2008 were identified from a pancreatic resection database and indications for repeat surgery were registered. Patients with and without reoperation were analyzed with regard to gender, age, underlying disease, length of hospital stay, mortality rate, and postoperative complications. RESULTS: Thirty-one patients (11%) underwent operative reintervention. Early intra-abdominal extraluminal postoperative bleeding was the main cause for redo surgery followed by abdominal abscesses. Thirteen percent of patients with and 1.9% without secondary surgery died during the postoperative course. Forty-five percent of reoperated patients had to undergo at least one more operation resulting in doubling of the length of hospital stay. There was no correlation between patients' gender, age, and underlying disease and the need for operative reintervention. However, redo surgery was associated with higher incidence of delayed gastric emptying, pancreatic fistula and bleeding, and non-surgery related complication. Intra-abdominal bleeding and abscesses, insufficiencies of bilio-digestive and gut anastomosis, wound infections, and pancreatitis were observed significantly more often in patients with secondary surgery. CONCLUSIONS: Complications after pancreatic resection that require operative re-intervention are associated with a notably increased mortality, ranging between 13% and 60%. Apart from the surgeon's experience in selecting patients and his/her personal technical skills in performing a pancreaticoduodenectomy, timely anticipation and determined management of postoperative complications is essential for improving the outcome of this operation.