Colonic diverticulosis is associated with abdominal wall hernia.

PURPOSE: Colonic diverticulosis and abdominal wall hernia are common pathologies. Studies have suggested that connective tissue alterations play a role in the formation of both diverticulosis and abdominal wall hernia. The aim of this cohort study was to evaluate the association between diverticulosis and abdominal wall hernia in a large cohort of patients undergoing colonoscopy. METHODS: All consecutive patients who underwent colonoscopy between 2001 and 2013 at Bispebjerg Hospital were eligible for inclusion. The endoscopists prospectively registered the findings of diverticulosis in a database. Data were merged with the Danish Hernia Database identifying patients who underwent groin and ventral hernia repair. Calculated odds ratios (ORs) were used to describe the extent of association and multivariable logistic regression models were utilized to adjust for age and gender. RESULTS: A total of 13,855 patients were included, 3685 (26.6%) of whom were diagnosed with diverticulosis. Diverticulosis was independently associated with direct inguinal, OR 1.33, 95% CI 1.00-1.76, P = 0.049, and umbilical/epigastric hernia repair, OR 1.74, 95% CI 1.16-2.63, P = 0.008. CONCLUSIONS: Colonic diverticulosis was associated with direct inguinal and umbilical/epigastric hernia repair suggesting that connective tissue alterations, herniosis, could be a common etiologic factor of colonic diverticulosis and these abdominal wall hernias.

Induction of endoplasmic reticulum stress by deletion of Grp78 depletes Apc mutant intestinal epithelial stem cells.

Intestinal epithelial stem cells are highly sensitive to differentiation induced by endoplasmic reticulum (ER) stress. Colorectal cancer develops from mutated intestinal epithelial stem cells. The most frequent initiating mutation occurs in Apc, which results in hyperactivated Wnt signalling. This causes hyperproliferation and reduced sensitivity to chemotherapy, but whether these mutated stem cells are sensitive to ER stress induced differentiation remains unknown. Here we examined this by generating mice in which both Apc and ER stress repressor chaperone Grp78 can be conditionally deleted from the intestinal epithelium. For molecular studies, we used intestinal organoids derived from these mice. Homozygous loss of Apc alone resulted in crypt elongation, activation of the Wnt signature and accumulation of intestinal epithelial stem cells, as expected. This phenotype was however completely rescued on activation of ER stress by additional deletion of Grp78. In these Apc-Grp78 double mutant animals, stem cells were rapidly lost and repopulation occurred by non-mutant cells that had escaped recombination, suggesting that Apc-Grp78 double mutant stem cells had lost self-renewal capacity. Although in Apc-Grp78 double mutant mice the Wnt signature was lost, these intestines exhibited ubiquitous epithelial presence of nuclear ß-catenin. This suggests that ER stress interferes with Wnt signalling downstream of nuclear ß-catenin. In conclusion, our findings indicate that ER stress signalling results in loss of Apc mutated intestinal epithelial stem cells by interference with the Wnt signature. In contrast to many known inhibitors of Wnt signalling, ER stress acts downstream of ß-catenin. Therefore, ER stress poses a promising target in colorectal cancers, which develop as a result of Wnt activating mutations.

Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. Main Recommendations: 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).(AU)

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). This Guideline was also reviewed and endorsed by the Governing Board of the American Society for Gastrointestinal Endoscopy (ASGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered as an alternative to emergency surgery in those who have an increased risk of postoperative mortality, I. e. American Society of Anesthesiologists (ASA) Physical Status ≥ III and/or age > 70 years (weak recommendation, low quality evidence). 4 SEMS placement is recommended as the preferred treatment for palliation of malignant colonic obstruction (strong recommendation, high quality evidence), except in patients treated or considered for treatment with antiangiogenic drugs (e. g. bevacizumab) (strong recommendation, low quality evidence).(AU)

NOTES in Europe: summary of the working group reports of the 2012 EURO-NOTES meeting.

The sixth EURO-NOTES workshop (4 - 6 October 2012, Prague, Czech Republic) focused on enabling intensive scientific dialogue and interaction between surgeons, gastroenterologists, and engineers/industry representatives and discussion of the state of the practice and development of natural orifice transluminal endoscopic surgery (NOTES) in Europe. In accordance with previous meetings, five working groups were formed. In 2012, emphasis was put on specific indications for NOTES and interventional endoscopy. Each group was assigned an important indication related to ongoing research in NOTES and interventional endoscopy: cholecystectomy and appendectomy, therapy of colorectal diseases, therapy of adenocarcinoma and neoplasia in the upper gastrointestinal tract, treating obesity, and new therapeutic approaches for achalasia. This review summarizes consensus statements of the working groups.

Colonic stenting as a bridge to surgery in malignant large-bowel obstruction: a report from two large multinational registries.

OBJECTIVES: To date, this is the largest prospective series in patients with malignant colorectal obstruction to evaluate the effectiveness and safety of colonic self-expanding metal stents (SEMSs) as an alternative to emergency surgery. SEMSs allow restoration of bowel transit and careful tumor staging in preparation for elective surgery, hence avoiding the high morbidity and mortality associated with emergency surgery and stoma creation. METHODS: This report is on the SEMS bridge-to-surgery subset enrolled in two multicenter international registries. Patients were treated per standard of practice, with documentation of clinical and procedural success, safety, and surgical outcomes. RESULTS: A total of 182 patients were enrolled with obstructive tumor in the left colon (85%), rectum (11%), or splenic flexure (4%). Of these patients, 86% had localized colorectal cancer without metastasis. Procedural success was 98% (177/181). Clinical success was 94% (141/150). Elective surgery was performed in 150 patients (9 stomas) and emergency surgery in 7 patients for treatment of a complication (3 stomas). The overall complication rate was 7.8% (13/167), including perforation in 3% (5/167), stent migration in 1.2% (2/167), bleeding in 0.6% (1/167), persistent colonic obstruction in 1.8% (3/167), and stent occlusion due to fecal impaction in 1.2% (2/167). One patient died from complications related to surgical management of a perforation. CONCLUSIONS: SEMSs provide an effective bridge to surgery treatment with an acceptable complication rate in patients with acute malignant colonic obstruction, restoring luminal patency and allowing elective surgery with primary anastomosis in most patients.

Natural-orifice transluminal endoscopic surgery (NOTES) in Europe: summary of the working group reports of the Euro-NOTES meeting 2010.

The fourth Euro-NOTES workshop took place in September 2010 and focused on enabling intensive scientific dialogue and interaction between participants to discuss the state of the practice and development of natural-orifice transluminal endoscopic surgery (NOTES) in Europe. Five working groups were formed, consisting of participants with varying scientific and medical backgrounds. Each group was assigned to an important topic: the correct strategy for dealing with bacterial contamination and related complications, the question of the ideal entry point and secure closure, interdisciplinary collaboration and indications, robotics and platforms, and matters related to training and education. This review summarizes consensus statements of the working groups to give an overview of what has been achieved so far and what might be relevant for research related to NOTES in the near future.

Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts.

Endoscopic submucosal dissection (ESD) is the gold standard technique for performing en bloc resection of large superficial tumors in the upper and lower gastrointestinal tract. Experience in Europe, however, is still limited and ESD is only performed in a few selected centers, with low volumes of cases, no description of training programs, and few published reports. In 2008, a panel of experts gathered in Rotterdam to discuss indications, training, and the wider use of ESD. The panel of experts and participants reached a consensus on five general statements: 1) ESD aims at treating mucosal cancer; 2) treatment aims for R0 resection; 3) ESD should meet quality standards; 4) ESD should be performed following national or European Society of Gastrointestinal Endoscopy (ESGE) guidelines or under institutional review board approval; and 5) ESD cases should be registered. Due to the high level of expertise needed to perform the technique safely, ESD should be performed in a step-up approach, starting with lesions presenting in the rectum or in the distal stomach, then colon, proximal stomach, and finally in the esophagus. Registration is advised either at the local site or at a national or ESGE level, and should include information on indication (Paris classification of lesion, location, and histological results prior to treatment), technique used (e. g. type of knife), results (en bloc and R0 resection), complications, and follow-up. The panel also agreed on minimal institutional requirements: good quality imaging, experienced histopathologist following the Japanese criteria (2-mm sections, micrometric invasion, vessel and lymphatic infiltration, etc), and dedicated endoscopic follow-up. Moreover, minimum training requirements were also defined: knowledge in indications and instruments, exposure to experts (currently all in Japan), hands-on experience in a model of isolated pig stomach and in live pigs, and management of complications. The experts did not reach a consensus on a minimum case load, or whether the technique should be restricted to expert centers.

Self-expanding metal stents for gastroduodenal malignancies: systematic review of their clinical effectiveness.

BACKGROUND AND STUDY AIMS: The current standard approach to the management of malignant gastric outlet obstruction mainly involves bypass surgery, which is associated with significant rates of mortality and morbidity. Recently, metal stents have emerged as a new therapeutic option. The aim of the present study was to review the currently published evidence on the effectiveness and safety of this form of endoscopic treatment. MATERIALS AND METHODS: A systematic review of the published data was carried out by searching medline, embase, and abstracts from the major gastroenterological conferences from January 1992 to September 2003. A total of 136 relevant publications were identified (case series, single case reports, letters and editorials, or reviews). The systematic review included 32 case series from a total of 46 publications identified as reporting primary clinical data. Abstracts and single case reports were not taken into account. Analysis of these 32 case series included data on technical success (successful stent placement and deployment), clinical success (relief of symptoms such as nausea and vomiting, and/or improvement of food intake), and complications. Pooled results were calculated from the 32 studies (10 of which were prospective). RESULTS: Stent insertion was attempted in 606 patients with malignant symptomatic gastroduodenal obstruction; 94 % of the patients were unable to take food orally or were mainly ingesting liquids. Stent placement and deployment were successful in 589 of the patients (97 %). Clinical success was achieved in 526 patients in the group in which technical success was reported (89 %; 87 % of the entire group undergoing stenting). Disease-related factors accounted for the majority of clinical failures. Oral intake became possible in all of the patients in whom a successful procedure was carried out, with 87 % taking soft solids or a full diet, with final resolution of symptoms occurring after a mean of 4 days. There was no procedure-related mortality. Severe complications (bleeding and perforation) were observed in seven patients (1.2 %). Stent migration was reported in 31 patients (5 %). Stent obstruction occurred in 104 cases (18 %), mainly due to tumor infiltration. The mean survival period was 12.1 weeks. CONCLUSIONS: Published evidence from case series suggests that gastroduodenal stenting offers good palliation and is a safe and effective treatment option in patients with a short remaining lifespan. However, patient selection for this intervention continues to be an issue requiring thorough consideration, and studies comparing the method with surgery are needed.

A major susceptibility locus for leprosy in India maps to chromosome 10p13.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.

Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans.

Twin and family studies indicate that host genetic factors influence susceptibility to leprosy and, possibly, leprosy type. Murine studies have suggested a role for the natural resistance-associated macrophage protein 1 (Nramp1) gene, which can influence cellular immune responses to intracellular pathogens. We evaluated a variation in the human homolog, NRAMP1, recently associated with tuberculosis susceptibility in West Africa. A total of 273 patients with leprosy and 201 controls from Mali were genotyped for NRAMP1 polymorphisms previously associated with tuberculosis. No association was found with leprosy per se (P = 0.83), but the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism was associated with leprosy type (P = 0.007). Heterozygotes were more frequent among multibacillary than paucibacillary leprosy cases. Thus, variation in or near the NRAMP1 gene may exert an influence on the clinical presentation of leprosy, possibly by influencing cellular immune response type.

Endoscopic placement of self-expanding metal stents for treatment of colorectal obstruction with long-term follow-up.

INTRODUCTION: Relief of colorectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. METHODOLOGY: Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). RESULTS: Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death after median 116 days (33-292 days). CONCLUSION: These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomised trials can be initiated.

[Endoscopic treatment of colorectal obstruction with self-expandable metal endoprosthesis]. / Endoskopisk behandling af kolorektal obstruktion med selvekspanderende metal-endoprotese.

Relief of colo-rectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death (33-175 days, four patients) or are still patent (follow-up 35-80 days). These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomized trials can be initiated.

[Stricture of the colon induced by hyperthermia--in connection with irrigation via sigmoidostomy]. / Hypertermisk induceret colonstriktur--i forbindelse med irrigation via sigmoideostomi.

A case of thermal injury following the introduction of excessively hot tap water into the colon during irrigation of a sigmoid colostomy is described. The radiological proof of a subsequently developed colon stricture made it necessary to remove the injured part and reconstruct the colostomy. Only two other cases of this kind have been reported in English literature. The case emphasizes that care must be taken in selecting the right temperature of the water for irrigation.

The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation.

BACKGROUND: Glucagon-like peptide-1 (GLP-1)(7-36) amide is an intestinal incretin hormone which also inhibits gastric acid secretion in humans. Its mechanism of action is unclear, but it strongly inhibits vagally induced secretion (sham feeding), suggesting that it could influence vagal activity. AIM/METHODS: The effect of intravenous GLP-1 (7-36 amide) (1 pmol/kg/min) was studied on pentagastrin induced acid secretion in otherwise healthy subjects, previously vagotomised for duodenal ulcer (n = 8) and in a group of young (n = 8) and old (n = 6) healthy volunteers. RESULTS: Pentagastrin increased acid secretion significantly in all three groups, but the plateau concentration in the vagotomised subjects was lower than in controls. Infusion of GLP-1 (7-36 amide) significantly inhibited acid secretion in the control groups (to 67 (SEM 6) and 74 (SEM 3)% of plateau concentrations in young and old controls, respectively) but had no effect in the vagotomised subjects. Differences in plasma concentrations of GLP-1 (7-36 amide), recovery of gastric marker, duodenal regurgitation, or Helicobacter pylori status could not explain the lack of effect. Blood glucose was lowered equally by GLP-1 (7-36 amide) in all subjects. CONCLUSION: The inhibitory effect of GLP-1 (7-36 amide) on acid secretion depends on intact vagal innervation of the stomach.

[The validity of data in registration of operations. A quality analysis]. / Datavaliditeten i en operationsregistrering. En kvalitetsanalyse.

In Denmark all operations are registered centrally and identified by a unique number describing the exact operation. The aim of this study has been to validate the data, which are registered. Within a period of four months all registrations were carried out in duplo in two independent registers. The contents of the two registers were compared manually. A total of 1568 operations were registered. In one of the registrations 102 (6.5%) were missing and in the other 112 (7.1%). In 70 cases (4.5%) a discrepancy was found between the registers according to type or date of operation. It is concluded, that about 10% of all registrations in such a register are wrong. A better validity of data might be obtained by a simplification of registration procedures. Double registration is an effective way to locate the mistakes.