Comparing bowel lengthening procedures: which, when, and why?

PURPOSE OF REVIEW: Intestinal failure secondary to short bowel syndrome is still a very serious condition. Treatment consists of parenteral nutrition to provide nutrients and maintain body weight. During the last decades, intestinal lengthening procedures have become more available. The goal of this review is to discuss the results of the literature on the most commonly performed intestinal lengthening procedures. RECENT FINDINGS: Longitudinal Intestinal Lengthening, Serial Transverse Enteroplasty (STEP), and Spiral Intestinal Lengthening and Tailoring (SILT) are currently the most frequently reported intestinal lengthening procedures. The most recent literature of these procedures is described with respect to indication, technical details, complications, short and long-term outcome, and PN independence. SUMMARY: On the basis of indication, surgical complexity, complications, and clinical success, we conclude that the STEP procedure is probably the best choice for most centers.

Involvement of the Commensal Organism Bacillus subtilis in the Pathogenesis of Anastomotic Leak.

Background: It is now well established that microbes play a key and causative role in the pathogenesis of anastomotic leak. Yet, in patients, determining whether a cultured pathogen retrieved from an anastomotic leak site is a cause or a consequence of the complication remains a challenge. The aim of this study was to test a methodology to invoke causality between a retrieved microbe from a leak site and its role in anastomotic leak. Methods: The commensal organism Bacillus subtilis was isolated from an esophagojejunostomy leak site in a 35-year-old patient with a CDH1 mutation after a prophylactic gastrectomy whose body mass index (BMI) was 35 kg/m2. The organism was screened for its ability to degrade collagen, shift human recombinant matrix metalloprotease-9 (MMP9) to its active form, and induce a clinical anastomotic leak when introduced to anastomotic tissues of mice fed their standard diet (SD) of chow or an obesogenic Western-type diet (WD). Results: The Bacillus subtilis strain retrieved from the anastomotic leak site displayed a high degree of collagenolytic activity and was able to activate human MMP9 consistent with other pathogens expressing this characteristic "leak phenotype." Exposure of the Bacillus subtilis to the anastomotic tissues of obese mice fed a WD led to dehiscence of the anastomosis, abscess formation with peritonitis, and mortality in 50% of mice (3/6). When anastomotic healing was evaluated by a validated anastomotic healing score (AHS), substantially worse healing was observed (i.e., higher AHS) in WD-fed mice exposed to Bacillus subtilis compared to SD-fed mice (analysis of variance [ANOVA], p = 0.0006). Conclusions: Microbial strains obtained from patients' anastomotic leak sites can be evaluated for their pathogenic in the leak process by assessing their ability to produce collagenase, activate MMP9 and cause clinical leaks in mice fed a WD. These studies may aid in identifying those bacterial strains that play a causal role in patients with an anastomotic leak.

Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis.

BACKGROUND: Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. DESIGN: BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. RESULTS: Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. CONCLUSIONS: Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis.

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

Mucus Microbiome of Anastomotic Tissue During Surgery Has Predictive Value for Colorectal Anastomotic Leakage.

OBJECTIVE: The aim of the present study is to investigate the association of gut microbiota, depending on treatment method, with the development of colorectal anastomotic leakage (AL). BACKGROUND: AL is a major cause for morbidity and mortality after colorectal surgery, but the mechanism behind this complication still is not fully understood. METHODS: Bacterial DNA was isolated from 123 "donuts" of patients where a stapled colorectal anastomosis was made and was analyzed using 16S MiSeq sequencing. In 63 patients, this anastomosis was covered with a C-seal, a bioresorbable sheath stapled to the anastomosis. RESULTS: In non-C-seal patients, AL development was associated with low microbial diversity (P = 0.002) and correspondingly with a high abundance of the dominant Bacteroidaceae and Lachnospiraceae families (P = 0.008 and 0.010, respectively). In C-seal samples, where AL rates were slightly higher (25% vs 17%), an association with the gut microbiota composition was almost undetectable. Only a few opportunistic pathogenic groups of low abundance were associated with AL in C-seal patients, in particular Prevotella oralis (P = 0.007). CONCLUSIONS: AL in patients without a C-seal can be linked to the intestinal microbiota, in particular with a low microbial diversity and a higher abundance of especially mucin-degrading members of the Bacteroidaceae and Lachnospiraceae families. In C-seal patients, however, it seems that any potential protective benefits or harmful consequences of the gut microbiota composition in regard to wound healing are negated, as progression to AL is independent of the initially dominant bacterial composition.

Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury.

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We therefore developed an ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Postischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation, and maturation. Proliferation of PBG cells increased after 24 hours of oxygenated incubation, reaching a peak after 72 hours. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (homeobox protein Nanog+/ sex-determining region Y-box 9+) to a mature (cystic fibrosis transmembrane conductance regulator+/secretin receptor+) and activated phenotype (increased expression of hypoxia-inducible factor 1 alpha, glucose transporter 1, and vascular endothelial growth factor A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. Conclusion: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behavior of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury.

Intestinal microbiota and anastomotic leakage of stapled colorectal anastomoses: a pilot study.

BACKGROUND: Anastomotic leakage (AL) after colorectal surgery is a severe complication, resulting in morbidity, reinterventions, prolonged hospital stay and, in some cases, death. Some technical and patient-related aetiological factors of AL are well established. In many cases, however, none of these factors seem to explain the occurrence of AL. Recent studies suggest that the intestinal microbiome plays a role in wound healing, diabetes and Crohn's disease. The aim of this study was to compare the intestinal microbiota of patients who developed AL with matched patients with healed colorectal anastomoses. METHODS: We investigated the microbiome in the doughnuts collected from 16 patients participating in the C-seal trial. We selected eight patients who developed AL requiring reintervention and eight matched controls without AL. We analysed the bacterial 16S rDNA of both groups with MiSeq sequencing. RESULTS: The abundance of Lachnospiraceae is statistically higher (P = 0.001) in patient group who did develop AL, while microbial diversity levels were higher in the group who did not develop AL (P = 0.037). Body mass index (BMI) was also positively associated with the abundance of the Lachnospiraceae family (P = 0.022). CONCLUSION: A correlation between the bacterial family Lachnospiraceae, low microbial diversity and anastomotic leakage, possibly in association with the BMI, was found. The relative abundance of the Lachnospiraceae family is possibly explained by the higher abundance of mucin-degrading Ruminococci within that family in AL cases (P = 0.011) as is similarly the case in IBD.