Changes in epithelial tight junction protein expression and apoptosis increase epithelial permeability in inflammatory bowel diseases. The effect of the probiotic mixture VSL#3 on the epithelial ...barrier was studied in dextran sodium sulfate (DSS)-induced colitis in mice. Acute colitis was induced in BALB/c mice (3.5% DSS for 7 days). Mice were treated with either 15 mg VSL#3 or placebo via gastric tube once daily during induction of colitis. Inflammation was assessed by clinical and histological scores. Colonic permeability to Evans blue was measured in vivo. Tight junction protein expression and epithelial apoptotic ratio were studied by immunofluorescence and Western blot. VSL#3 treatment reduced inflammation (histological colitis scores: healthy control 0.94 +/- 0.28, DSS + placebo 14.64 +/- 2.55, DSS + VSL#3 8.43 +/- 1.82; P = 0.011). A pronounced increase in epithelial permeability in acute colitis was completely prevented by VSL#3 therapy healthy control 0.4 +/- 0.07 (extinction/g), DSS + placebo 5.75 +/- 1.67, DSS + VSL#3 0.26 +/- 0.08; P = 0.003. In acute colitis, decreased expression and redistribution of the tight junction proteins occludin, zonula occludens-1, and claudin-1, -3, -4, and -5 were observed, whereas VSL#3 therapy prevented these changes. VSL#3 completely prevented the increase of epithelial apoptotic ratio in acute colitis healthy control 1.58 +/- 0.01 (apoptotic cells/1,000 epithelial cells), DSS + placebo 13.33 +/- 1.29, DSS + VSL#3 1.72 +/- 0.1; P = 0.012. Probiotic therapy protects the epithelial barrier in acute colitis by preventing 1) decreased tight junction protein expression and 2) increased apoptotic ratio.
Endoscopic management of leakages and perforations of the upper gastrointestinal tract has gained great importance as it avoids the morbidity and mortality of surgical intervention.In the past ...years,covered selfexpanding metal stents were the mainstay of endoscopic therapy.However,two new techniques are now available that enlarge the possibilities of defect closure:endoscopic vacuum therapy(EVT),and over-the-scope clip(OTSC).EVT is performed by mounting a polyurethane sponge on a gastric tube and placing it into the leakage.Continuous suction is applied via the tube resulting in effective drainage of the cavity and the induction of wound healing,comparable to the application of vacuum therapy in cutaneous wounds.The system is changed every 3-5 d.The overall success rate of EVT in the literature ranges from 84%to 100%,with a mean of 90%;only few complications have been reported.OTSCs are loaded on a transparent cap which is mounted on the tip of a standard endoscope.By bringing the edges of the perforation into the cap,by suction or by dedicated devices,such as anchor or twin grasper,the OTSC can be placed to close the perforation.For acute endoscopy associated perforations,the mean success rate is 90%(range:70%-100%).For other types of perforations(postoperative,other chronic leaks and fistulas)success rates are somewhat lower(68%,and59%,respectively).Only few complications have been reported.Although first reports are promising,further studies are needed to define the exact role of EVT and OTSC in treatment algorithms of upper gastrointestinal perforations.
Background
Perforations and anastomotic leakages of the upper gastrointestinal (GI) tract cause a high morbidity and mortality rate. Only limited data exist for endoscopic vacuum therapy (EVT) in the ...upper GI tract.
Methods
Fifty-two patients (37 men and 15 women, ages 41–94 years) were treated (12/2011–12/2015) with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy (
n
= 39), iatrogenic esophageal perforation (
n
= 9) and Boerhaave syndrome (
n
= 4). After diagnosis, polyurethane sponges were endoscopically positioned with a total of 390 interventions and continuous negative pressure of 125 mm of mercury (mmHg) was applied to the EVT-system. Sponges were changed endoscopically twice per week. Clinical and therapy-related data and mortality were analyzed.
Results
After 1–25 changes of the sponge at intervals of 3–5 days with a mean of 6 sponge changes and a mean duration of therapy of 22 days, the defects were healed in 94.2 % of all patients without revision surgery. In three patients (6 %), EVT failed. Two of these patients died due to hemorrhage related to EVT. Four postinterventional strictures were observed during the follow-up of up to 4 years.
Conclusion
Esophageal wall defects of different etiology in the upper gastrointestinal tract can be treated successfully with EVT, considering that indication for EVT should be weighed carefully. EVT can be regarded as a novel life-saving therapeutic tool.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Temporary loop ileostomy is a routine procedure to reduce the morbidity of restorative proctocolectomy. However, morbidity of ileostomy closure could reduce the benefit of this concept. ...The objective of this systematic review was to assess the risks of ileostomy closure after restorative proctocolectomy for ulcerative colitis or familial adenomatous polyposis.
Materials and Methods
Publications in English or German language reporting morbidity of ileostomy closure after restorative proctocolectomy were identified by Medline search. Two hundred thirty-two publications were screened, 143 were assessed in full-text, and finally 26 studies (reporting 2146 ileostomy closures) fulfilled the eligibility criteria. Weighted means for overall morbidity and mortality of ileostomy closure, rate of redo operations, anastomotic dehiscence, bowel obstruction, wound infection, and late complications were calculated.
Results
Overall morbidity of ileostomy closure was 16.5 %, there was no mortality. Redo operations for complications were necessary in 3.0 %. Anastomotic dehiscence occurred in 2.0 %. Postoperative bowel obstruction developed in 7.6 %, with 2.9 % of patients requiring laparotomy for this complication. Wound infection rate was 4.0 %. Hernia or bowel obstruction as late complications developed in 1.9 and 9.4 %, respectively.
Conclusion
The considerable morbidity of ileostomy reversal reduces the overall benefit of temporary fecal diversion. However, ileostomy creation is still recommended, as it effectively reduces the risk of pouch-related septic complications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF along ...with its potential perioperative clinical risk factors and its effect on tumor recurrence. Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. 340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (pless than or equal to0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Single-incision laparoscopic surgery is a development in the field of minimally invasive surgery that is being increasingly used for colorectal procedures.
OBJECTIVE:We report on the ...short-term results of single-port laparoscopic ileocolic resection in patients with ileocecal Crohnʼs disease.
DESIGN:This investigation is a retrospective matched-pair control study. Data were obtained from a prospectively maintained single-institution inflammatory bowel disease database.
SETTINGS:This study was conducted at a tertiary care university hospital.
PATIENTS:Twenty consecutive patients receiving elective single-port ileocolic resection between April 2010 and May 2011 were included (6 male, 14 female; age, 31.6 ± 10.8 years; BMI, 21.5 ± 2.6 kg/m). Their data were compared with the data of 20 individually matched patients who had undergone standard 3-trocar laparoscopic-assisted ileocolic resection between 2007 and 2010 (6 male, 14 female; age, 31.7 ± 10.7 years; BMI, 21.2 ± 2.5 kg/m). All patients had medically refractory stenosis of the terminal ileum in histologically confirmed Crohnʼs disease.
INTERVENTIONS:Single-port laparoscopic-assisted or standard laparoscopic-assisted ileocolic resection was performed.
MAIN OUTCOME MEASURES:The primary outcomes measured were the surgical details and early outcome.
RESULTS:The mean length of the paraumbilical single-port incision was 3.8 cm (range, 2.5–5.0 cm). Conversion rates were similar in both groups (1/20 vs 2/20, p = 0.55). Additional strictureplasties or short-segment small-bowel resections were performed in both groups. The overall complication rate was 20% (4/20) in both groups. There were no observed differences in postoperative pain scores and hospital stay duration.
LIMITATIONS:The limitations of this study were as followsthis study was a comparison of 2 different time points with possible selection bias, there was no prestudy power calculation, and the study might be underpowered.
CONCLUSIONS:Single-port ileocolic resection is a safe procedure for the surgical treatment of stenotizing Crohnʼs disease of the terminal ileum. Avoidance of additional trocars was the only identified benefit.
Introduction
More than 1.0 million patients worldwide are diagnosed with space-occupying lesions in the liver every year, with the number approaching 0.5 million per year in China, and only 20% of ...the lesions are resectable Due to a lack of available donors, only a limited number of patients underwent allogeneic liver transplantation, the remaining patients simply receive palliative care. Therefore, discovering new options for treating these patients is a high priority. Liver autotransplantation （LAT） is a surgical technique that adopts liver transplantation skills to radically treat spaceoccupying hepatic lesions, benign or malignant,
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or ...oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern.
Gemcitabine-resistant variants of two mutant p53 human PDAC cell lines were established. Survival rates were analyzed by cytotoxicity and apoptosis assays. Expression of 1733 human miRs was investigated by microarray and validated by qRT-PCR. After in-silico analysis of specific target genes and proteins of dysregulated miRs, expression of MRP-1, Bcl-2, mutant p53, and CDK1 was quantified by Western blot.
Both established PDAC clones showed a significant resistance to gemcitabine (p<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone.
Consistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim of the study
To clarify the intestinal cancer risk in Crohn’s disease (CD).
Methods
20 clinical studies (1965–2008) with a total of 40,547 patients with Crohn’s disease-associated cancer (CDAC) ...were included in the meta-analysis (“inverse variance weighted” method).
Results
The incidence of CDAC in any CD patient was 0.8/1,000 person years duration (pyd) (CI, 0.6–1.0). The incidences of different carcinomas were: colorectal cancer 0.5/1,000 pyd (CI, 0.3–0.6), small bowel carcinoma 0.3/1,000 pyd (CI, 0.1–0.5), and cancers arising from CD-associated fistulae 0.2/1,000 pyd (CI, 0.0–0.4). Compared to the incidence in an age-matched standard population, the risk of colorectal cancer was increased by factor 2–3 and of small bowel cancer by factor 18.75, respectively. Mean patient age at diagnosis of CD-associated colorectal cancer was 51.5 years, thus 20 years earlier than in a standard population. The mean duration of CD until diagnosis of CDAC was 18.3 years. Duration of CD, age at diagnosis of CD, and anatomical area of CD involvement had no significant influence on cancer incidence.
Conclusions
CD is a risk factor for colorectal cancer, small bowel cancer, and fistula cancer; however, compared to ulcerative colitis, cancer risk is moderate.
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EMUNI, NUK, SBMB, SBNM, UL, UPUK
Aims The European Senior Program (ESP) aims to avoid waiting list competition between younger and elderly patients applying for renal transplantation. By listing patients ≥65 years on a separate ...waiting list and locally allocating of grafts ≥65 years exclusively to this cohort, waiting and cold ischemia times are predicted to be shortened, potentially resulting in improved kidney transplantation outcomes. This study compared a historic cohort of renal transplant recipients being simultaneously listed on the general and the ESP waiting lists with a collective exclusively listed on the ESP list in terms of surrogates of the transplantation outcome. Methods Total 151 eligible patients ≥ 65 years from Münster transplant Center, Germany, between 1999 and 2014 were included. Graft function, graft and patient survival were compared using surrogate markers of short- and long-term graft function. Patients were grouped according to their time of transplantation. Results Recipients and donors in the newESP (nESP) cohort were significantly older (69.6 ± 3.5 years vs 67.1 ± 2 years, p<0.05; 72.0 ± 5.0 years vs 70.3 ± 5.0 years, p = 0.039), had significantly shorter dialysis vintage (19.6 ± 21.7 months vs 60.2 ± 28.1 months, p<0.001) and suffered from significantly more comorbidities (2.2 ± 0.9 vs 1.8 ± 0.8, p = 0.009) than the historic cohort (HC). Five-year death-censored graft survival was better than in the HC, but 5-year graft and patient survival were better in the ESP cohort. After 2005, cold ischemia time between groups was comparable. nESP grafts showed more primary function and significantly better long-term graft function 18 months after transplantation and onwards. Conclusion nESP recipients received significantly older grafts, but experienced significantly shorter time on dialysis. Cold ischemia times were comparable, but graft function in the nESP cohort was significantly better in the long term.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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