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.

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.

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.

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.

Percentage distribution of fatty acids in subcutaneous adipose tissue of patients with peptic ulcer disease.

Dietary linoleic acid has been implicated in the pathogenesis of peptic ulcer disease because its metabolite arachidonic acid may be converted to cytoprotective prostaglandins. In addition, it has been suggested that the falling incidence and virulence of duodenal ulcer disease is related to increased dietary polyunsaturated essential fatty acid intake. In the present study the percentage content of linoleic acid in subcutaneous adipose tissue microbiopsies were used to see whether changes in percentage of fatty acids correlate with the presence or absence of an ulcer in individual patients. No significant difference in the adipose tissue content of linoleic acid was found, ie, 11.2 +/- 0.7% (n = 15) vs 10.9 +/- 0.5% (n = 15) in patients with peptic ulcer disease and matched control subjects, respectively.

Ulcer recurrence two to twelve years after parietal cell vagotomy for duodenal ulcer.

An analysis is presented of the ulcer recurrence rate following parietal cell vagotomy in 333 patients with duodenal ulcer. The median period of observation for patients without ulcer recurrence was 54 months (range 1 to 128 months). Forty-two patients developed proven recurrent ulcer. The median period of freedom from recurrence was 33 months (range 3 to 113 months). Recurrent ulcer was suspected but not verified in an additional 12 patients. The calculated risk (by the life table method) of recurrence after 5 years was 13% (95% confidence limits 9-17), after 8 years 21% (14-28), and after 10 years 23% (15-31). The rate of recurrence remained constant throughout the study period. The analysis indicates a constant monthly recurrence risk of 0.23%. The patients with ulcer recurrence had a significantly lower reduction of peak pentapeptide acid output and higher rate of positive insulin test than patients without recurrence. The risk of recurrence did not depend on the location of the ulcer (duodenal bulb or pyloric-prepyloric area).

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.

Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria.

Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain. Therefore, the effects of supplementary treatment with iron or folic acid, given together with chloroquine or pyrimethamine-sulfadoxine (Fansidar), has been assessed in 600 Gambian children with uncomplicated falciparum malaria. After one month, haematological recovery was significantly better in the group treated with Fansidar than in the chloroquine-treated group (difference in mean haemoglobin level = 0.54 g/dL, P = 0.01). Children who received iron had a significantly better response than those given placebo (differences in mean haemoglobin level after one month and at dry season follow-up = 0.70 g/dL, P = 0.006, and 0.81 g/dL, P = 0.001, respectively). Iron supplementation was not associated with increased prevalence of malaria. Supplementation with folic acid did not improve the haematological response but, among children who received Fansidar, the treatment failure rate was significantly higher among those given folic acid than among those given placebo. Thus, supplementation with iron, but not folic acid, improves haematological recovery without increasing susceptibility to malaria.

[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.

[Ulcer surgery during 1976-1978 and 1986-1988. Significance of H2 blockaders in surgical training]. / Operation for ulcussygdommen i perioderne 1976-1978 og 1986-1988. H2-blokkernes betydning for den kirurgiske uddannelse.

A retrospective study of all operations done for duodenal or stomach peptic ulcers in 1976-1978 and 1986-1988 was performed so as to evaluate elective and emergency surgery before and after the introduction of H2-receptor antagonists and to evaluate the influence of medical treatment on surgical training in ulcer surgery. The number of elective operations fell by 80%, the number of emergency operations was unchanged. In 1986-1988 the number of elderly patients who underwent emergency surgery increased, no change in age was seen in elective surgery. The rate of complications was unchanged after elective operations, but has increased considerably after emergency surgery in 1986-1988. Surgeons in training performed a greater share of operations, both elective and emergency, but without an increase in complications. The introduction of H2-receptor antagonists has not reduced the number of emergency operations.

[Experiences with microcomputer based registration of esophago-gastro-duodenoscopy]. / Erfaringerne med mikrocomputerbaseret registrering af øsofago-gastro-duodenoskopi.

The development of and the experience with a microcomputer based register of endoscopy is described. The paper work was reduced from nine forms to one. The register provides the information necessary for budgeting the resources for staff and new equipment. The system provides the opportunity for analysing existing and new principles for treatment and provides information about the pattern of diagnoses, thereby supporting the running of clinical controlled studies. During the first 29 months, data from 6,014 endoscopies were collected. The categories of patients and the distribution of diagnoses is presented.

[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.

[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.