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Abstract: Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery., Methods: A narrative review of the most recent relevant literature was conducted., Results: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients., Conclusion: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

The average American today undergoes three inpatient and two outpatient surgical procedures during one's life, each of which carries with it a risk of post-operative infection. It has long been known that post-operative infections cause significant morbidity in the immediate peri-operative period, but recent evidence suggests that they can have long-term consequences as well, increasing a patient's risk of infectious complications in unrelated surgeries performed months or even years later. While there are several theories on the origin of this association, including bacterial colonization of a post-operative infectious wound site, antimicrobial resistance from curative courses of antibiotics, subclinical immunosuppression, or the creation of an inflammatory "pathobiome" following an infectious insult, it is ultimately still unclear why patients who experience a single post-operative infection seem to be at a significantly higher risk of experiencing subsequent ones. Regardless, this association has significant implications for the routine use of pre-operative antibiotic prophylaxis. Indeed, while the prescription of antibiotics pre-operatively has dramatically reduced the rate of post-operative infections, the chosen prophylaxis regimens are typically standardized according to national guidelines, are facing increasing antimicrobial resistance patterns, and have been unable to reduce the risk of post-operative infection to acceptably low levels for certain surgeries. As a result, some clinicians have speculated that tailoring pre-operative antibiotic prophylaxis according to a patient's prior infectious and operative history could improve efficacy and further reduce the rate of post-operative infections. The purpose of this review is to describe the evidence for the link between multiple post-operative infections and explore the efficacy of individualized pre-operative prophylaxis.

Objective: To determine the timeframe and associated changes in the microenvironment that promote the development of a diet-induced local-regional recurrence in a mouse model of colorectal surgery., Background: Postoperative recurrence and metastasis occur in up to 30% of patients undergoing attempted resection for colorectal cancer (CRC). The underlying mechanisms that drive the development of postoperative recurrences are poorly understood. Preclinical studies have demonstrated a diet and microbial-driven pathogenesis of local-regional recurrence, yet the precise mechanisms remain undefined., Methods: BALB/C mice were fed a western diet (WD) or standard diet (SD), underwent a colon resection and anastomosis, given an Enterococcus faecalis enema on postoperative day (POD) 1, and subjected to a CT26 cancer cell enema (mimicking shed cancer cells) on POD2. Mice were sacrificed between POD3 and POD7 and cancer cell migration was tracked. Dynamic changes in gene expression of anastomotic tissue that were associated with cancer cell migration was assessed., Results: Tumor cells were identified in mice fed either a SD or WD in both anastomotic and lymphatic tissue as early as on POD3. Histology demonstrated that these tumor cells were viable and replicating. In WD-fed mice, the number of tumor cells increased over the early perioperative period and was significantly higher than in mice fed a SD. Microarray analysis of anastomotic tissue found that WD-fed mice had 11 dysregulated genes associated with tumorigenesis., Conclusions: A WD promotes cancer cells to permeate a healing anastomosis and migrate into anastomotic and lymphatic tissue forming viable tumor nodules. These data offer a novel recurrence pathogenesis by which the intestinal microenvironment promotes a CRC local-regional recurrence., Competing Interests: J.V. received Association for Academic Surgery/Association for Academic Surgery Foundation Resident Research Award. B.D.S. received Cancer Research Foundation Young Investigator Award; NIH NCI 1K08CA248957-01A1. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The conceptual underpinning of carcinogenesis has been strongly influenced by an expanded understanding of the human microbiome. Malignancy risks in diverse organs have been uniquely tied to aspects of the resident microbiota in different organs and systems including the colon, lungs, pancreas, ovaries, uterine cervix, and stomach; other organs are increasingly linked to maladaptive aspects of the microbiome as well. In this way, the maladaptive microbiome may be termed an oncobiome. Microbe-driven inflammation, anti-inflammation, and mucosal protection failure, as well as diet-induced microbiome derangement are all mechanisms that influence malignancy risk. Therefore, they also offer potential avenues of diagnostic and therapeutic intervention to modify malignancy risk, and to perhaps interrupt progression toward cancer in different sites. Each of these mechanisms will be explored using colorectal malignancy as a prototype condition to demonstrate the microbiome's role in carcinogenesis.

Background: Surgeons are often asked to provide a diverting colostomy to enable healing or simplify management of sacral pressure ulcers. However, little evidence exists regarding the safety of a diversion in this often compromised patient population. We hypothesized that malnourished patients with sacral pressure ulcers have poor outcomes with fecal diversion., Methods: ACS-NSQIP (2012-2018) was used to identify patients who underwent elective diverting colostomy for sacral pressure ulcers. Demographics, comorbidities, and perioperative details were recorded. Postoperative complications and 30-day mortality were compared between patients with moderate/severe hypoalbuminemia (< 2.5 g/dL) vs those with albumin > 2.5 g/dL., Results: We identified a total of 863 patients who underwent elective diverting colostomy for sacral pressure ulcer. Mean age was 57.5 years old. Rate of associated comorbidities was high, with most patients classified as ASA class 3 or 4. Over 40% of patients had a preoperative albumin level < 2.5 g/dL. Thirty-day overall postoperative mortality was 6.7%. This was significantly higher in patients with hypoalbuminemia (11.4% vs. 3.5%, p < 0.001). On multivariable regression analysis, preoperative albumin < 2.5 g/dL was independently associated with mortality (OR 1.92, p = 0.039). Other factors associated with mortality included increased age (OR 1.04 per year, p < 0.001), preoperative sepsis (OR 1.66, p = 0.003), and Black race (OR 2.2, p = 0.01)., Conclusions: Diverting colostomy performed for patients with sacral pressure ulcers is associated with a substantial risk of postoperative death. Surgeons should carefully consider risks of diversion in this patient population, especially in malnourished patients with hypoalbuminemia., (© 2022. The Society for Surgery of the Alimentary Tract.)

Purpose: Pelvic recurrence of rectal or anal cancers is associated with considerable morbidity and mortality. We report our initial experience with an aggressive intra-operative radiotherapy (IORT) program., Methods: Patients with locally advanced or recurrent rectal or anal cancers considered to have a high likelihood of R1 or R2 resection after multi-disciplinary review underwent surgical excision and IORT using a high-dose-rate afterloader (Ir-192) and HAM applicator. Endpoints included local or distant recurrence, and acute and late toxicity graded using the American College of Surgeons (ACS) NSQIP and the LENT-SOMA scale., Results: Twenty-one patients, largely with prior history of both pelvic external beam radiotherapy (EBRT, median 50.4 Gy) and surgical resection, underwent excision with IORT (median dose 12.5 Gy, range 10-15). Median follow-up was 20 months. Twelve (57%) patients had failure at the IORT site. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF at 1 year 75% for R0 vs 15% for R1/2, p = 0.0065) but not re-irradiation EBRT or IORT dose (p > 0.05). Twelve, 5, and 13 patients experienced local, regional, and distant failure, respectively; 3 (14%) patients were disease-free at last follow-up. The most frequent acute toxicity was sepsis/abscess (24%). One patient (5%) required a ureteral stent; no patients developed neuropathy attributable to IORT., Conclusions: In patients treated with excision and IORT for locally recurrent cancer, R0 resection is a critical determinant of local control. For patients with R1/2 resection, poor disease-free outcomes warrant consideration of a different treatment strategy., (© 2022. Society of Surgical Oncology.)

The American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) are dedicated to ensuring high-quality innovative patient care for surgical patients by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus as well as minimally invasive surgery. The ASCRS and SAGES society members involved in the creation of these guidelines were chosen because they have demonstrated expertise in the specialty of colon and rectal surgery and enhanced recovery. This consensus document was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. While not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, healthcare workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. This clinical practice guideline represents a collaborative effort between the American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and was approved by both societies., (© 2022. Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and American Society of Colon and Rectal Surgeons (ASCRS).)

Background: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Methods: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test., Results: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05)., Conclusions: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The endoscopic appearance in patients with "pouchitis" after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn's disease (CD) are at high risk of pouch loss., Aims: We aimed to assess how the histopathology of colectomy specimens predicts endoscopic pouch phenotypes in UC., Methods: We retrospectively assessed pouchoscopies from patients with UC who underwent IPAA and classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted ≥ 6 months from ileostomy takedown. We assessed the clinical and pathological data including deep, focal inflammation, granulomas, and terminal ileal involvement in the colectomy specimens. Logistic regression analysis was performed to identify contributing factors to each phenotype., Results: This study included 1,203 pouchoscopies from 382 patients with UC. On multivariable analysis, deep inflammation was significantly associated with pouch fistulas (Odds ratio 3.27; 95% confidence interval 1.65-6.47; P = 0.0007). Of the 75 patients with deep inflammation, only two patients (2.7%) were diagnosed with CD based on pathology review. Terminal ileal involvement significantly increased the risk of afferent limb involvement (Odds ratio 2.96; 95% confidence interval 1.04-8.47; P = 0.04). There were no significant associations between other microscopic features and phenotypes., Conclusions: We identify histologic features of colectomy specimens in UC that predict subsequent pouch phenotypes. Particularly, deep inflammation in the resected colon was significantly associated with pouch fistulas, a pouch phenotype with poor prognosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Infections after abdominal surgery remain a significant problem. Although preoperative antibiotic prophylaxis is a primary strategy used to reduce postoperative infections, it is typically prescribed based on standardized protocols, without attention to previous infection or antibiotic history. Patients with a previous infection after surgery may be at higher risk for infectious complications after subsequent operations owing to antibiotic resistance. We hypothesized that a previous postoperative infection is a significant risk factor for the development of infection after a second unrelated surgery., Study Design: We performed a retrospective study of patients who had undergone 2 unrelated abdominal operations at a tertiary care center from 2012 to 2018. Clinical variables and microbiological culture results were abstracted. Univariate and multivariable regression models were constructed., Results: Of 758 patients, 15.0% (n = 114) developed an infection after the first operation. After the second operation, 22.8% (n = 26) of those with a previous infection developed another infection, whereas the incidence of an infection after the second operation was only 9.5% (n = 61) in patients who did not develop an infection after the first operation. Multivariable analysis demonstrated that previous infection (odds ratio 2.49, 95% CI 1.46 to 4.25) was associated with future infection risk. Microbiological analysis found that infections after the second surgery were significantly more likely to be antibiotic resistant than infections after the first surgery (82.3% vs 64.1%; p = 0.036). Strikingly, 49% of infections after the second surgery were resistant to the antibiotic prophylaxis given at the time of incision., Conclusions: Previous postoperative infection is an independent risk factor for a subsequent postoperative infection and is associated with resistance to standard prophylaxis. Individualization of antibiotic prophylaxis in patients with a previous postoperative infection is warranted., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Intestinal anastomotic tissue follows a similar pattern of healing that is seen in all tissues with characteristic inflammatory, proliferative, and remodeling phases. Several aspects of intestinal healing are distinct from other tissues, however, including its time course and interaction with the environment of the gastrointestinal tract. As the anastomosis progresses through each stage, initial inflammatory cells are replaced by collagen-producing fibroblasts that generate the anastomosis' strength. A complex network of cell-to-cell signaling mediates this process through the release of cytokines and growth factors including platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF). Interventions based on these signaling pathways have been shown to improve anastomotic strength in animals, though methods for improving anastomotic healing in human patients remain unclear. Given the risks associated with anastomotic failure in patients, there is value in monitoring inflammatory markers and cytokines that can indicate the presence of a leak., Competing Interests: Disclosure: The author reports no potential conflicts.

Much about the role of intestinal microbes at the site of colon cancer development and tumor progression following curative resection remains to be understood. We have recently shown that collagenolytic bacteria such as Enterococcus faecalis predominate within the colon postoperatively, particularly at the site of the colon reconnection (i.e. anastomosis) in the early period of post-surgical recovery. The presence of collagenolytic bacteria at this site correlates with the tumor progression in a mouse model of post-surgical tumor development. In the present study we hypothesized, that collagenolytic bacteria, such as E. faecalis, play an important yet to be discovered role in tumor formation and progression. Therefore the aims of this study were to assess the role of collagenolytic E. faecalis on the migration and invasion of a murine colon cancer cell line. Results demonstrated that both migration and invasion were induced by E. faecalis with collagenolytic activity being required for only invasion. Bidirectional signaling in the E. faecalis-cancer cell interaction was observed by the discovering that the expression of gelE in E. faecalis, the gene required for collagenase production, is expressed in response to exposure to CT26 cells. The mechanism by which migration enhancement via E. faecalis occurs appears to be dependent on its ability to activate pro-uPA, a key element of the urokinase-plasminogen system, a pathway that is well - known to be important in cancer cell invasion and migration. Finally, we demonstrated that collagenase producing microbes preferentially colonize human colon cancer specimens., (Copyright © 2022. Published by Elsevier Inc.)

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care., (© 2021 Wiley Periodicals LLC.)

Background & Aims: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype., Methods: We identified 426 patients (384 with ulcerative colitis) treated with proctocolectomy and IPAA who subsequently underwent pouchoscopies at the University of Chicago between June 1997 and December 2019. We retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown. Logistic regression analysis was used to assess factors contributing to each phenotype. Pouch survival was estimated by the log-rank test and the Cox proportional hazards model., Results: Significant contributing factors for afferent limb involvement were a body mass index of 25 or higher and hand-sewn anastomosis, for inlet involvement the significant contributing factor was male sex; for diffuse inflammation the significant contributing factors were extensive colitis and preoperative use of anti-tumor necrosis factor drugs, for cuffitis the significant contributing factors were stapled anastomosis and preoperative Clostridioides difficile infection. Inlet stenosis, diffuse inflammation, and cuffitis significantly increased the risk of pouch excision. Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34-5.41; P = .005)., Conclusions: We describe 7 unique IPAA phenotypes with different contributing factors and outcomes, and propose a new classification system for pouch management and future interventional studies., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the role of bacterial- mediated plasminogen (PLG) activation in the pathogenesis of anastomotic leak (AL) and its mitigation by tranexamic acid (TXA)., Background: AL is the most feared complication of colorectal resections. The pathobiology of AL in the setting of a technically optimal procedure involves excessive submucosal collagen degradation by resident microbes. We hypothesized that activation of the host PLG system by pathogens is a central and targetable pathway in AL., Methods: We employed kinetic analysis of binding and activation of human PLG by microbes known to cause AL, and collagen degradation assays to test the impact of PLG on bacterial collagenolysis. Further, we measured the ability of the antifibrinolytic drug TXA to inhibit this process. Finally, using mouse models of pathogen-induced AL, we locally applied TXA via enema and measured its ability to prevent a clinically relevant AL., Results: PLG is deposited rapidly and specifically at the site of colorectal anastomoses. TXA inhibited PLG activation and downstream collagenolysis by pathogens known to have a causal role in AL. TXA enema reduced collagenolytic bacteria counts and PLG deposition at anastomotic sites. Postoperative PLG inhibition with TXA enema prevented clinically and pathologically apparent pathogen-mediated AL in mice., Conclusions: Bacterial activation of host PLG is central to collagenolysis and pathogen-mediated AL. TXA inhibits this process both in vitro and in vivo. TXA enema represents a promising method to prevent AL in high-risk sites such as the colorectal anastomoses., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC., Methods: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion., Results: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01)., Conclusion: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC., (© 2021 Wiley Periodicals LLC.)

Background: Anastomotic leak is among the most dreaded complications in patients undergoing colorectal surgery. We have discovered that in rodents, collagenase-producing bacteria, particularly Enterococcus faecalis , promotes anastomotic leak by degrading healing anastomotic tissue. Yet, it is unclear if these organisms play a role in humans. Patients and Methods: Patients undergoing colorectal resection at the University of Chicago from July 2014 through June 2019 who developed a post-operative infection were stratified into infections that resulted from an anastomotic leak, a Hartmann pouch stump leak, or a deep infection without an associated staple line leak. Results: Forty-two patients had available culture data. Of these patients, 19 were found to have an anastomotic leak, 7 had a stump leak, and 16 had a deep infection that was not associated with a staple line. Enterococcus faecalis was identified in 24% of all infections and was associated with the development of anastomotic leak (p = 0.029). When the organisms were classified into their known ability to produce collagenase, 74% of patients with an anastomotic leak were colonized with collagenase-producing organisms, compared with only 28% of patients with a deep infection or stump leak (p = 0.022). Antibiotic-resistant organisms were more common in patients with anastomotic leak (p = 0.01). Conclusions: Collagenase-producing and antibiotic-resistant organisms are more prevalent in anastomotic leak infections compared with other deep or organ/space infections. This lends evidence to a bacterial driven pathogenesis of leak and suggests that targeting these organisms may be a novel strategy to reduce this complication.

The microbiome plays a major role in human physiology by influencing obesity, inducing inflammation, and impacting cancer therapies. During the 60th Annual Meeting of the Society of the Alimentary Tract (SSAT) at the State-of-the-Art Conference, experts in the field discussed the influence of the microbiome. This paper is a summary of the influence of the microbiome on obesity, inflammatory bowel disease, pancreatic cancer, cancer therapies, and gastrointestinal optimization. This review shows how the microbiome plays an important role in the development of diseases and surgical complications. Future studies are needed in targeting the gut microbiome to develop individualized therapies., (© 2020. The Society for Surgery of the Alimentary Tract.)

Background: Various reports have now established that postoperative endoscopy to examine and intervene in the process of anastomotic healing is both feasible and safe. Here we present our preliminary experience with serial postoperative endoscopy to determine its feasibility, patient acceptance and the ability to obtain and the utility of perianastomotic material for molecular analysis., Methods: Patients undergoing LAR with ileostomy for rectal cancer were recruited for study to undergo routine serial endoscopic surveillance (SES) at three time points during the course of LAR: intraoperatively, before discharge (postoperative day 3-7) and at follow-up (postoperative day 10-28). At each endoscopy, images were captured, anastomotic tissues were lavaged and lavage fluid was retrieved. Fluid samples were analyzed using proteomics, zymography, ELISA and bacteria via 16S rRNA gene amplicon sequencing and culture of collagenolytic strains., Results: SES is feasible and acceptable to this limited set of patients following LAR. Biologic analysis of perianastomotic fluids was able to detect the presence of proteins, microbiota and inflammatory mediators previously identified at anastomotic sites in animals with pathologic healing., Conclusion: SES can be implemented in patients undergoing LAR with a high degree of patient compliance and capture of biologic information and imaging. Application of this approach has the potential to uncover, for the first time, the natural history of normal versus pathologic anastomotic healing in patients undergoing anastomotic surgery.

Background: Anastomotic leak is a feared complication. The presence of abnormal vital signs is often cited as an important overlooked predictive clue in retrospective settings once the diagnosis of leak has already been established. We aimed to determine the prevalence of abnormal vital signs following colorectal resection and assess its predictive value., Methods: We retrospectively studied patients undergoing colorectal resection. The performance of vital signs in predicting anastomotic leak was assessed using discrete-time survival analysis and receiver operator characteristic curve., Results: 1662 patients (841 laparoscopic, 821 open) were included. Clinical anastomotic leak was diagnosed in 50 patients (3.1%). 96.8% of patients of the entire cohort had at least one abnormal vital sign during their postoperative course. No individual vital sign was a strong predictor of anastomotic leak in either laparoscopic or open cohorts., Conclusion: Vital sign abnormalities are extremely common following open and laparoscopic colorectal surgery and alone are poor predictors of anastomotic leak., Competing Interests: Declaration of competing interest All authors report no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Vitamin D deficiency has been associated with disease activity in Crohn's disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD., Methods: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6-12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied., Results: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of <15, 15-30, and >30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08-0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively)., Conclusion: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence., (© 2021 S. Karger AG, Basel.)

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.

Colorectal cancer is the result of multiple genetic mutations that drive normal cells to adenoma and then carcinoma. Recent technology has evolved to allow for an in-depth examination of the microbiota and it has become clear that many components of the intestinal microbiome play a role in promoting carcinogenesis. This review aims to describe the potential mechanisms that lead to the dysbiosis that initiates tumor formation and that influence the development of cancer recurrence following surgical resection. We further discuss how manipulation of the microbiome may be a future novel strategy to prevent both primary and secondary colorectal cancer. While we discuss how bacterial communities and individual strains can promote cancer, the microbiome is individualized, dynamic, and complex, and our understanding of its role in carcinogenesis is still in its infancy.

Background: This study aims to evaluate sarcopenia defined by skeletal muscle index (SMI) with cutoffs adjusted for sex and body mass index as a predictive marker for postoperative outcomes among individuals with inflammatory bowel disease., Methods: The SMI was measured using the cross-sectional computed tomography images at the lumbar spine. Multivariate logistic regression was performed to identify independent risk factors of postoperative complications., Results: Ninety-one patients were included in the study. In multivariate analysis, sarcopenia (odds ratio = 5.37; confidence interval: 1.04-27.6) was predictive of infectious postoperative complications., Conclusions: Sarcopenia as defined by the SMI is a predictor for 30-day postoperative infection complications in inflammatory bowel disease surgeries., (© The Author(s) 2020. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

The extraordinary spread of the novel coronavirus (COVID-19) has dramatically and rapidly changed the way in which we provide medical care for patients with all diagnoses. Conservation of resources, social distancing, and the risk of poor outcomes in COVID-19-positive cancer patients have forced practitioners and surgeons to completely rethink routine care. The treatment of patients with rectal cancer requires both a multidisciplinary approach and a significant amount of resources. It is therefore imperative to rethink how rectal cancer treatment can be aligned with the current COVID-19 pandemic paradigms. In this review, we discuss evidence-based recommendations to optimize oncological outcomes during the COVID-19 pandemic.

Background: The most common complications after colorectal surgery, postoperative ileus, surgical site infections, and anastomotic leaks continue to occur despite advances in surgical technique and enhanced recovery pathways. Preclinical studies have documented that intestinal bacteria play a role in the development of these complication, yet human data is lacking. Here we hypothesized that patients that develop ileus, surgical site infection, and/or anastomotic leak following colorectal surgery harbor a specific preoperative gut microbiome., Methods: We performed a prospective cohort study on 101 patients undergoing colon or rectal resection at the Mayo Clinic. Rectal samples were collected preoperatively and on the ward on postoperative day two. The bacterial community from each sample was characterized by 16S rRNA and associated with the development of complications., Results: The rectal microbiome collected from patients in the operating room (p = .003) and on postoperative day two (p = .001) was significantly difference in patients whom later developed postoperative ileus compared with patients that had a normal return of bowel function. Patients whom developed ileus showed increased abundance of Bacteroides spp., Parabacteroides spp., and Ruminococcus spp., bacteria that are associated with promoting intestinal inflammation. There were no differences in the microbiome in patients that developed surgical site infections or anastomotic leaks., Conclusions: In this pilot study, patients that develop postoperative ileus harbor a specific gut microbiome during the perioperative period. These findings demonstrate that the preoperative bacterial composition may predispose patients to the development of ileus and that perioperative manipulation of the gut bacteria may provide a novel method to promote normal return of bowel function.

Background: Insufficient data exist for peristomal pyoderma gangrenosum (PPG), which primarily affects patients with inflammatory bowel disease (IBD)., Aims: To evaluate the risk factors and treatment response of PPG in IBD patients in a real-life cohort., Methods: Cases of PPG were identified retrospectively using ICD-9/10 codes in patients with IBD who had an ostomy at a tertiary care centre. Disease-specific characteristics were compared between groups with and without PPG, and response to therapy was evaluated in patients with PPG., Results: The cohort included 41 IBD patients with PPG and 123 IBD controls with an ostomy who never developed PPG. Patients with PPG were more likely to be female (76% vs 51%, P = 0.006), had higher BMIs (29.78 ± 0.89 vs 23.53 ± 0.51, P < 0.0001) and had increased usage of pouch belts (97% vs 71%, P = 0.0008) compared to controls. There were no differences in age at surgery (41.76 ± 2.60 vs 43.49 ± 1.50, P = 0.57) or IBD diagnosis (63% vs 54% Crohn's disease, P = 0.28) between PPG and controls. 85% of PPG patients achieved complete resolution with different treatments, including surgery. Complete resolution with topical corticosteroids and calcineurin inhibitors alone were low (14% and 13% respectively). Higher rates of complete resolution were reported with anti-tumour necrosis factor (TNF) agents (63%) and surgical interventions (80%)., Conclusions: Female gender, higher BMI and pouch belts were associated with increased risk of developing PPG. Most PPG cases resolved after treatment with the highest rates of complete resolution seen with anti-TNF agents and surgical intervention., (© 2020 John Wiley & Sons Ltd.)

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., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis -mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa -mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

Background and Aim: Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy., Methods: Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed., Results: A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy., Conclusions: Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity., Objective: The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis., Design: This is a retrospective case-control study., Settings: This study was conducted at a tertiary-care IBD center., Patients: Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included., Main Outcome Measures: The primary outcome measured was the incidence of pouchitis., Results: Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes., Limitations: The retrospective design was a limitation of this study., Conclusion: In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.

Objective: Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice., Summary: Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion., Methods: Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models., Results: One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 - 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5- 0.9; P = 01)., Conclusions: Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.

Background: Revisional and reconstructive surgery for IPAA is rare given the high success of pouch surgery for chronic ulcerative colitis. Limited data exist on both surgical and functional outcomes in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction., Objective: This study aimed to determine the surgical and functional outcome in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction., Design: A prospectively collected surgical database was accessed for this study., Setting: This study was conducted at an IBD referral center., Patients: Patients with chronic ulcerative colitis who underwent IPAA revision or reconstruction were selected., Main Outcome Measures: The primary outcomes measured were 30-day postoperative outcomes and long-term pouch function., Results: Eighty-one patients were identified. Original IPAA was performed for chronic ulcerative colitis (n = 71; 88%) and indeterminate colitis (n = 11; 12.%), and the most common configuration was a J-pouch (n = 69; 86%) with handsewn anastomosis (n = 41;68%). No independent predictors of 30-day postoperative complications following reconstructive/revisional surgery were identified. Pelvic abscesses and Crohn's disease of the pouch were independently associated with ultimate pouch excision. Median follow-up following revision/reconstruction was 40 months (range, 1-292 months) during which 15 patients (23%) had pouch failure. The 5- and 10-year pouch survival rates following revision were 85 ± 5% and 65 ± 9% by Kaplan-Meier estimation; age <30 years was significantly associated with pouch survival. Long-term function (n = 30; 35%) compared with a matched control cohort of primary IPAA was characterized by significantly increased daytime bowel incontinence (p = 0.0119), liquid stool (p = 0.0062), and medication to thicken stools (p = 0.0452)., Limitations: This was a single-center series, and response rate for functional data was 35%., Conclusions: In properly selected patients with a failing pouch, originally made for chronic ulcerative colitis or indeterminate colitis, revisional and reconstructive surgery is associated with low complication rates, high pouch salvage, and acceptable long-term pouch function. See Video Abstract at http://links.lww.com/DCR/A640.

The microbiome exerts a remarkable effect on human physiology. The study of the human-microbiome relationship is a burgeoning field with great potential to improve our understanding of health and disease. In this review, we address common surgical problems influenced by the human microbiome and explore what is thus far known about this relationship. These include inflammatory bowel disease, colorectal neoplasms, and diverticular disease. We will also discuss the effect of the microbiome on surgical complications, specifically anastomotic leak. We hope that further research in this field will enlighten our management of these and other surgical problems.

The microorganisms that inhabit hospitals may influence patient recovery and outcome, although the complexity and diversity of these bacterial communities can confound our ability to focus on potential pathogens in isolation. To develop a community-level understanding of how microorganisms colonize and move through the hospital environment, we characterized the bacterial dynamics among hospital surfaces, patients, and staff over the course of 1 year as a new hospital became operational. The bacteria in patient rooms, particularly on bedrails, consistently resembled the skin microbiota of the patient occupying the room. Bacterial communities on patients and room surfaces became increasingly similar over the course of a patient's stay. Temporal correlations in community structure demonstrated that patients initially acquired room-associated taxa that predated their stay but that their own microbial signatures began to influence the room community structure over time. The α- and β-diversity of patient skin samples were only weakly or nonsignificantly associated with clinical factors such as chemotherapy, antibiotic usage, and surgical recovery, and no factor except for ambulatory status affected microbial similarity between the microbiotas of a patient and their room. Metagenomic analyses revealed that genes conferring antimicrobial resistance were consistently more abundant on room surfaces than on the skin of the patients inhabiting those rooms. In addition, persistent unique genotypes of Staphylococcus and Propionibacterium were identified. Dynamic Bayesian network analysis suggested that hospital staff were more likely to be a source of bacteria on the skin of patients than the reverse but that there were no universal patterns of transmission across patient rooms., (Copyright © 2017, American Association for the Advancement of Science.)

Even under the most expert care, a properly constructed intestinal anastomosis can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis. The cause of anastomotic leak remains unknown, and its incidence has not changed in decades. We demonstrate that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of anastomotic leak through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were colonized by E. faecalis strains that showed an increased collagen-degrading activity and also an increased ability to activate host MMP9, both of which contributed to anastomotic leakage. We demonstrate that the E. faecalis genes gelE and sprE were required for E. faecalis-mediated MMP9 activation. Either elimination of E. faecalis strains through direct topical antibiotics applied to rat intestinal tissues or pharmacological suppression of intestinal MMP9 activation prevented anastomotic leak in rats. In contrast, the standard recommended intravenous antibiotics used in patients undergoing colorectal surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent leak in our rat model. Finally, we show in humans undergoing colon surgery and treated with the standard recommended intravenous antibiotics that their anastomotic tissues still contained E. faecalis and other bacterial strains with collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the intestinal tissue contributing to anastomotic leak., Competing Interests: Competing interests. The authors declare no competing interests., (Copyright © 2015, American Association for the Advancement of Science.)

Background: When diseased intestine (i.e., from colon cancer, diverticulitis) requires resection, its reconnection (termed anastomosis) can be complicated by non-healing of the newly joined intestine resulting in spillage of intestinal contents into the abdominal cavity (termed anastomotic leakage). While it is suspected that the intestinal microbiota have the capacity to both accelerate and complicate anastomotic healing, the associated genotypes and functions have not been characterized., Results: Using 16S rRNA amplicon sequencing of samples collected on the day of surgery (postoperative day 0 (POD0)) and the 6th day following surgery (postoperative day 0 (POD6)), we analyzed the changes in luminal versus tissue-associated microbiota at anastomotic sites created in the colon of rats. Results indicated that anastomotic injury induced significant changes in the anastomotic tissue-associated microbiota with minimal differences in the luminal microbiota. The most striking difference was a 500-fold and 200-fold increase in the relative abundance of Enterococcus and Escherichia/Shigella, respectively. Functional profiling predicted the predominance of bacterial virulence-associated pathways in post-anastomotic tissues, including production of hemolysin, cytolethal toxins, fimbriae, invasins, cytotoxic necrotizing factors, and coccolysin., Conclusion: Taken together, our results suggest that compositional and functional changes accompany anastomotic tissues and may potentially accelerate or complicate anastomotic healing.

The bacteria that colonize humans and our built environments have the potential to influence our health. Microbial communities associated with seven families and their homes over 6 weeks were assessed, including three families that moved their home. Microbial communities differed substantially among homes, and the home microbiome was largely sourced from humans. The microbiota in each home were identifiable by family. Network analysis identified humans as the primary bacterial vector, and a Bayesian method significantly matched individuals to their dwellings. Draft genomes of potential human pathogens observed on a kitchen counter could be matched to the hands of occupants. After a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota., (Copyright © 2014, American Association for the Advancement of Science.)

We recently demonstrated that Pseudomonas aeruginosa PAO1 undergoes a pronounced phenotypic change when introduced into the intestines of rats during surgical injury. Recovered strains displayed a specific phenotype (termed the P2 phenotype) characterized by altered pyocyanin production, high collagenase activity, high swarming motility, low resistance to chloramphenicol, and increased killing of Caenorhabditis elegans compared to the inoculating strain (termed the P1 phenotype). The aims of this study were to characterize the differences between the P. aeruginosa P1 and P2 phenotypes in quorum sensing and competitiveness. We then determined the presence of the P2 phenotype among PAO1 strains from various laboratories. Results demonstrated that P2 cells display accelerated growth during early exponential phase and early activation of quorum-sensing systems and overcome the growth of P1 cells in a mixed population. Among eight PAO1 strains obtained from different laboratories, four exhibited the P2 phenotype. Of 27 mutants analyzed from the P. aeruginosa MPAO1 transposon library, 25 displayed P2 phenotypes. The P2 phenotype in both cases correlated with a lack of expression of mexE or mexF due to mutations in mexT and mexF genes. In summary, strains possessing the P2 phenotype are distributed among PAO1 strains commonly used across a variety of research laboratories. Genetically, they are characterized by various mutations in mexT or mexF.

Introduction: Colorectal anastomotic leak, a feared complication, results in significantly increased patient morbidity, mortality, and hospital resource utilization. The overall incidence of colorectal anastomotic leak is approximately 11% with increasing rate the closer the anastomosis is to the anal verge. Because surgeons are unable to reliably predict which anastomosis would fail, most will construct a diverting ileostomy for low colorectal anastomosis to circumvent the devastating complications of anastomotic failure. Despite extensive investigations on technical considerations of anastomosis construction, anastomotic leaks continue to occur at an unacceptably high rate., Discussion: In this review, we examine the major known risk factors and technical considerations that have been implicated as factors in leakage. Although surgical technique has evolved over the past several decades with the advent of newer surgical staplers, laparoscopy, and robotics, we have not witnessed a decrease in the incidence of colorectal anastomotic leaks suggesting that the fundamental pathogenesis of anastomotic leak remains unknown. Among the factors contributing to anastomotic healing, intestinal bacteria remains largely overlooked even though compelling evidence exist that intraluminal microbes could play a major role in pathogenesis of anastomotic leak. Further investigation focusing on intestinal microbes could be one such avenue for uncovering the elusive cause of colorectal anastomotic leak.