Publications by authors named "Neil H Hyman"

55 Publications

Endoscopic Phenotype of the J Pouch in Patients With Inflammatory Bowel Disease: A New Classification for Pouch Outcomes.

Clin Gastroenterol Hepatol 2021 Feb 5. Epub 2021 Feb 5.

University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cgh.2021.02.010DOI Listing
February 2021

Caring for Patients with Rectal Cancer During the COVID-19 Pandemic.

J Gastrointest Surg 2020 07 15;24(7):1698-1703. Epub 2020 May 15.

Department of Surgery, The University of Chicago Medicine, 5841 S. Maryland Ave., Rm J557F, MC5095, Chicago, IL, 60637, USA.

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.
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http://dx.doi.org/10.1007/s11605-020-04645-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228429PMC
July 2020

Peritoneal Metastases in Colorectal Cancer: Biology and Barriers.

J Gastrointest Surg 2020 03 19;24(3):720-727. Epub 2019 Nov 19.

Department of Surgery, University of Chicago, Chicago, IL, USA.

Background: Advances in the molecular biology of tumor metastasis have paralleled the evolution in the management of metastatic disease from colorectal cancer. In this review, we summarize the current understanding of the mechanism of colorectal cancer metastases, in particular that of peritoneal metastases, as well as clinical data on the treatment of this disease.

Methods: A review of relevant English literature using MEDLINE/PubMed on the biology of colorectal cancer metastases, determinants of oligometastasis, and use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of metastatic colorectal cancer is presented.

Results: Recognition of oligometastasis in the evolution of colorectal peritoneal metastases provides the theoretical framework for which cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy is considered. Clearly, a subset of patients benefit from peritoneal metastasectomy.

Conclusion: Advances in cancer biology and clinical imaging promise to expand the role of cytoreductive surgery with or without intraperitoneal chemotherapy in the management of peritoneal metastases from colorectal cancer.
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http://dx.doi.org/10.1007/s11605-019-04441-4DOI Listing
March 2020

Exposure to Anti-tumor Necrosis Factor Medications Increases the Incidence of Pouchitis After Restorative Proctocolectomy in Patients With Ulcerative Colitis.

Dis Colon Rectum 2019 11;62(11):1344-1351

Department of Surgery, University of Chicago, Chicago, Illinois.

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.
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http://dx.doi.org/10.1097/DCR.0000000000001467DOI Listing
November 2019

Low-Dose Metronidazole is Associated With a Decreased Rate of Endoscopic Recurrence of Crohn's Disease After Ileal Resection: A Retrospective Cohort Study.

J Crohns Colitis 2019 Sep;13(9):1158-1162

Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, USA.

Background And Aims: Recurrence of Crohn's disease after surgical resection and primary anastomosis is an important clinical challenge. Previous studies have demonstrated the benefit of imidazole antibiotics, but have been limited by adverse events and medication intolerance. We evaluated whether administration of low-dose metronidazole [250 mg three times per day] for 3 months reduces endoscopic postoperative recurrence rates.

Methods: We performed a retrospective cohort study of patients with Crohn's disease who underwent ileal resection with a primary anastomosis and subsequently received care at our center. We compared the cases who received low-dose metronidazole for 3 months with control patients who did not receive this therapy. Data collected included demographics, risk factors for recurrence, and medications before and after surgery. The primary end point was the number of patients with ≥i2 [Rutgeerts] endoscopic recurrence by 12 months. Variables found to be predictive in univariate analysis at p < 0.10 were introduced in the Cox model for multivariate analysis.

Results: In all, 70 patients with Crohn's disease [35 cases and 35 controls] met inclusion criteria. Risk factors for Crohn's recurrence were similar between groups. The number of patients with ≥i2 endoscopic recurrence within 12 months following ileal resection was significantly lower in the metronidazole group [7 of 35 patients; 20%] compared with the number in the control group [19 of 35 patients; 54.3%] [p = 0.0058]. Eight participants [22.9%] in the metronidazole group experienced adverse events, and 3 of these patients [8.6%] discontinued the therapy.

Conclusion: Low-dose metronidazole reduces endoscopic recurrence of Crohn's disease postoperatively and is well tolerated. This intervention should be considered as a therapy option following ileocolonic resection.
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http://dx.doi.org/10.1093/ecco-jcc/jjz047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939874PMC
September 2019

Abnormal Pouchogram Predicts Pouch Failure Even in Asymptomatic Patients.

Dis Colon Rectum 2019 04;62(4):463-469

Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois.

Background: Anastomotic complications after restorative total proctocolectomy with IPAA for ulcerative colitis alter functional outcomes and quality of life and may lead to pouch failure. Routine contrast enema of the pouch assesses anastomotic integrity before ileostomy reversal, but its clinical use is challenged.

Objective: The purpose of this research was to assess the relationship among preoperative clinical characteristics, abnormal pouchography, and long-term pouch complications.

Design: This was a retrospective chart review.

Settings: The study was conducted at a tertiary care center between 2000 and 2010.

Patients: Ulcerative colitis patients with IPAA undergoing pouchography before ileostomy closure were included.

Main Outcome Measures: Patient demographics, incidence of pouch-related complications, and findings on pouchogram were recorded. Primary outcome was pouch failure, defined as excision or permanent diversion of the ileoanal pouch. Independent predictors of pouch failure were determined by multivariate regression.

Results: A total of 262 patients with ulcerative colitis were included. Contrast extravasation was seen in 27 patients (10.3%): 14 (51.9%) were clinically asymptomatic at the time of pouchogram. Six (22.2%) of 27 patients with extravasation developed pouch failure despite normalization of the pouchogram before ileostomy closure. Forty patients (15.3%) were found to have pouch-anal anastomotic stenosis; only 1 developed pouch failure. Pre-IPAA serum albumin and hemoglobin levels were inversely associated with contrast extravasation (serum albumin: OR = 0.42; hemoglobin: OR = 0.77; p < 0.05). Contrast extravasation was associated with delayed takedown operation (average = 67 d), increased risk (OR = 5.25; p < 0.01), and shorter time (median = 32.0 vs 72.5 mo; HR = 5.88; p < 0.05) to pouch failure, as well as increased risk of pouch-related complications (p < 0.05).

Limitations: The study was limited by its retrospective nature and small number of patients who developed pouch failure.

Conclusions: Pouchography before ileostomy takedown is useful in identifying patients with ulcerative colitis at risk for postoperative complications. Radiologic resolution of IPAA-related leak does not reliably predict healing; caution is warranted in this subgroup. See Video Abstract at http://links.lww.com/DCR/A818.
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http://dx.doi.org/10.1097/DCR.0000000000001285DOI Listing
April 2019

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

Dis Colon Rectum 2018 Oct;61(10):1146-1155

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.

Objective: The purpose of this study was to analyze disease-free and overall survival.

Design: This was a nonrandomized phase II trial.

Settings: The study was conducted at multiple institutions.

Patients: Four sequential study groups with stage II or III rectal cancer were included.

Intervention: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.

Main Outcome Measures: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.

Results: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03).

Limitations: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients.

Conclusions: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.
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http://dx.doi.org/10.1097/DCR.0000000000001207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130918PMC
October 2018

The New Frontier: the Intestinal Microbiome and Surgery.

J Gastrointest Surg 2018 07 9;22(7):1277-1285. Epub 2018 Apr 9.

Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 5095, Chicago, IL, 60637, USA.

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.
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http://dx.doi.org/10.1007/s11605-018-3744-7DOI Listing
July 2018

Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy.

PLoS One 2018 9;13(3):e0194234. Epub 2018 Mar 9.

Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, Illinois, United States of America.

Background: Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported.

Materials And Methods: 52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded.

Results: Median follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively.

Conclusions: In this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194234PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844568PMC
July 2018

Need a LIFT?

Authors:
Neil H Hyman

Dis Colon Rectum 2017 10;60(10):997-998

Chicago, IL.

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http://dx.doi.org/10.1097/DCR.0000000000000886DOI Listing
October 2017

Implementation of the surgical safety checklist at a tertiary academic center: Impact on safety culture and patient outcomes.

Am J Surg 2017 Aug 30;214(2):193-197. Epub 2016 Nov 30.

Department of Surgery, University of Chicago Medicine, Chicago, IL, USA.

Background: The impact and efficacy of the World Health Organization Surgery Safety Checklist (SSC) is uncertain. We sought to determine if the SSC decreases complications and examined the attitudes of the surgical team members following implementation of the SSC.

Methods: A 28-question survey was developed to assess perspectives of surgical team members at the University of Vermont Medical Center (UVMC). The University Health System Consortium database was examined to compare the rates of nine complications before and after SSC implementation using Chi square analysis and Fisher's exact test.

Results: There was no significant decrease in any of the nine complications 2 years after SSC implementation. There was overall agreement that the SSC improved communication, safety, and prevented errors in the operating room. However, there was disagreement between nursing and surgeons over whether all three parts of the SSC were always completed.

Conclusions: Implementation of the SSC did not result in a significant decrease in perioperative morbidity or mortality. However, it did improve the perception of safety culture by operating room staff.
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http://dx.doi.org/10.1016/j.amjsurg.2016.10.027DOI Listing
August 2017

Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.

Ann Surg 2018 06;267(6):1112-1118

University of Chicago, Department of Surgery, Chicago, IL.

Objective: The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery.

Background: We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth.

Methods: Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration.

Results: PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa.

Conclusions: Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.
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http://dx.doi.org/10.1097/SLA.0000000000002167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540820PMC
June 2018

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

J Gastrointest Surg 2016 12 16;20(12):2035-2051. Epub 2016 Sep 16.

Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA.

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.
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http://dx.doi.org/10.1007/s11605-016-3255-3DOI Listing
December 2016

Prevention of Perioperative Anastomotic Healing Complications: Anastomotic Stricture and Anastomotic Leak.

Adv Surg 2016 09 29;50(1):129-41. Epub 2016 Jun 29.

Department of Surgery, The University of Chicago Medicine, University of Chicago, 5841 South Maryland Avenue, MC 5095, Chicago, IL 60637, USA. Electronic address:

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079140PMC
http://dx.doi.org/10.1016/j.yasu.2016.03.011DOI Listing
September 2016

Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility.

Am J Physiol Gastrointest Liver Physiol 2016 06 14;310(11):G973-88. Epub 2016 Apr 14.

Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois;

Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis (UC) patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self-emptying (SEL) ileal loops using wild-type (WT), IL-10 knockout (KO) (IL-10), TLR4 KO (T4), and IL-10/T4 double KO mice. After 5 wk, loop histology, host gene/protein expression, and bacterial 16s rRNA profiles were examined. SFL exhibit fecal stasis due to directional motility oriented toward the loop end, whereas SEL remain empty. In WT mice, SFL, but not SEL, develop pouchlike microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. The inflammation associated with IL-10 required TLR4, as animals lacking both pathways displayed little disease. Furthermore, germ-free IL-10 mice conventionalized with SFL, but not SEL, microbiota populations develop severe colitis. These data support essential roles of stasis-induced, colon-like microbiota, TLR4-mediated colonic metaplasia, and genetic susceptibility in the development of pouchitis and possibly UC. However, these factors by themselves are not sufficient. Similarities between this model and human UC/pouchitis provide opportunities for gaining insights into the mechanistic basis of IBD and for identification of targets for novel preventative and therapeutic interventions.
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http://dx.doi.org/10.1152/ajpgi.00017.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935476PMC
June 2016

Clostridium Difficile Infection in Ulcerative Colitis: Can Alteration of the Gut-associated Microbiome Contribute to Pouch Failure?

Inflamm Bowel Dis 2016 Apr;22(4):902-11

*Department of Surgery, The University of Chicago Medicine, Chicago, Illinois; †Center for Biomedical Research Informatics, NorthShore University HealthSystem, Evanston, Illinois; ‡Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois; §Section of Colon and Rectal Surgery, Department of Surgery, The University of Chicago Medicine, Chicago, Illinois; and ‖Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois.

Background: Ulcerative colitis is frequently treated with total proctocolectomy and ileal pouch-anal anastomosis reconstruction. Causes of pouch failure and criteria for improved patient selection remain poorly understood. We aimed to identify risk factors for pouch failure.

Methods: We performed a retrospective chart review of patients in a prospectively maintained database. Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease between 2000 and 2010 at our institution were included. The primary outcome was pouch failure, defined as permanent ostomy diversion or pouch excision.

Results: Of 417 total patients, 28 (6.7%) patients developed pouch failure. Pouch failure was associated with female gender, anastomotic leak, Crohn's disease of the pouch and preoperative Clostridium difficile colitis. The use of anti-tumor necrosis factor alpha biologics was not associated with pouch failure. Notably, 14.9% of patients were diagnosed with preoperative C. difficile colitis, a factor independently associated with pouch failure (hazard ratio 3.02; 95% confidence interval, 1.23-7.44; P = 0.016). C. difficile colitis did not contribute to failure by increasing the incidence of anastomotic leak but was associated with a diagnosis of Crohn's disease of the pouch (adjusted hazard ratio 2.27 [1.08-4.79]; P = 0.031). Anastomotic leak (P < 0.001) and pelvic abscess requiring drainage (P = 0.031) were other independent risk factors for pouch failure.

Conclusions: In addition to previously known risk factors, history of preoperative C. difficile colitis was associated with pouch failure after reconstruction, suggesting the need for further study into the role of the gut-associated microbiome in pouch outcomes.
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http://dx.doi.org/10.1097/MIB.0000000000000710DOI Listing
April 2016

Rectal cancer in patients under the age of 50 years: the delayed diagnosis.

Am J Surg 2016 Jun 3;211(6):1014-8. Epub 2015 Nov 3.

Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 5095, Chicago, IL 60637, USA. Electronic address:

Background: The incidence of rectal cancer in younger patients continues to increase. Because most of these patients do not meet criteria for routine colorectal cancer screening, diagnosis may be delayed, potentially resulting in adverse outcomes. The aim of this study was to determine whether patients under the age of 50 years with rectal cancer have a delay in diagnosis and treatment leading to a worse overall prognosis.

Methods: A case control study of patients diagnosed with rectal adenocarcinoma in an academic medical center from 1997 to 2007 under 50 years of age were matched 1:1 to randomly selected patients over the age of 50 years by sex and date of diagnosis. Time to diagnosis, time to treatment, staging of the American Joint Committee on Cancer, and 5-year overall survival were compared.

Results: The overall time to treatment from symptom onset was 217 days for patients under the age of 50 years versus 29.5 days if over 50 years of age (P < .0001). The primary delay occurred between the onset of symptoms and presentation to the initial physician. There was no difference in stage at the time of diagnosis or 5-year survival (64% vs 71%, P = .39 and P = .54, respectively).

Conclusions: Patients with rectal cancer under the age of 50 years have symptoms for a considerable period of time before seeking medical care and are referred in less timely manner to specialists. However, the delay in diagnosis did not adversely impact stage on presentation or 5-year survival.
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http://dx.doi.org/10.1016/j.amjsurg.2015.08.031DOI Listing
June 2016

Can sepsis predict deep venous thrombosis in colorectal surgery?

Am J Surg 2016 Jan 12;211(1):53-8. Epub 2015 Aug 12.

Department of Surgery, Madigan Army Medical Center, 9040 Jackson Avenue, Tacoma, WA 98431, USA.

Background: Little data exist regarding the impact of sepsis on deep venous thrombosis (DVT) in colorectal surgery patients. We sought to elucidate this relationship.

Methods: Current Procedural Terminology codes were used to identify patients who underwent colorectal surgery as reported to the National Surgical Quality Improvement Program in 2010. The relationship between DVT and sepsis was then explored in a matched population.

Results: Of the 26,554 patients who underwent colorectal surgery, 462 (1.7%) developed a DVT. The largest dependent correlations with DVT were malnutrition (33% vs 57%), emergency operation (15% vs 31%), open operation (58% vs 78%), and prolonged ventilator requirement (5% vs 24%; all P < .001). After propensity score matching, urosepsis (.5% vs 1.9%), organ/space sepsis (1.1% vs 4.8%), pneumosepsis (.5% vs 5.8%), and overall perioperative sepsis (18% vs 39%; all P ≤ .04) were associated with DVT. The strongest independent predictor of DVT was pneumosepsis (odds ratio 15.9, 95% confidence interval 3.7 to 67.2, P < .001).

Conclusion: Perioperative sepsis is a significant risk factor for postoperative DVT in the colorectal surgery population.
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http://dx.doi.org/10.1016/j.amjsurg.2015.06.016DOI Listing
January 2016

Parastomal hernia repair.

J Gastrointest Surg 2015 Apr 13;19(4):766-9. Epub 2014 Dec 13.

Division of Gastrointestinal Surgery, Department of Surgery, University of Vermont, Burlington, VT, USA.

Parastomal herniation is a common clinical occurrence. Historically, there has been a high recurrence rate after repair, and conservative management is usually recommended for patients with mild symptoms. When operative intervention is warranted, we opt for a laparoscopic mesh sublay over the fascial defect and lateralization of the stoma limb, or the Sugarbaker technique. In patients who are considered poor risk for laparoscopy/laparotomy requiring repair, we perform a fascial onlay with mesh utilizing an anterior circumstomal approach.
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http://dx.doi.org/10.1007/s11605-014-2717-8DOI Listing
April 2015

Evidence against a systemic arterial defect in patients with inflammatory bowel disease.

J Surg Res 2014 Oct 16;191(2):318-22. Epub 2014 Apr 16.

Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont; Department of Surgery, College of Medicine, University of Vermont, Burlington, Vermont.

Background: Despite increasing interest in local microvascular alterations associated with inflammatory bowel disease (IBD), the potential contribution of a primary systemic vascular defect in the etiology of IBD is unknown. We compared reactivity of large diameter mesenteric arteries from segments affected by Crohn disease (CD) or ulcerative colitis (UC) to an uninvolved vascular bed in both IBD and control patients.

Methods: Mesenteric and omental arteries were obtained from UC, CD, and non-IBD patients. Isometric arterial contractions were recorded in response to extracellular potassium (K(+)) and cumulative additions of norepinephrine (NE). In addition, relaxation in response to pinacidil, an activator of adenosine triphosphate-sensitive K(+) channels was examined.

Results: Contraction to K(+) and sensitivity to NE were not significantly different in arteries from CD, UC, and controls. Relaxation to pinacidil was also similar between groups.

Conclusions: Potassium-induced contractions and sensitivity to NE and pinacidil were not significantly different in large diameter mesenteric and omental arteries obtained from IBD patients. Furthermore, there was no significant difference in the sensitivity to K(+), NE, and pinacidil between mesenteric and omental arteries of CD and UC patients and those from non-IBD patients. Our results suggest an underlying vascular defect systemic to CD or UC patients is unlikely to contribute to the etiology of IBD.
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http://dx.doi.org/10.1016/j.jss.2014.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160373PMC
October 2014

Abnormal vital signs are common after bowel resection and do not predict anastomotic leak.

J Am Coll Surg 2014 Jun 28;218(6):1195-9. Epub 2014 Feb 28.

Department of Surgery, University of Vermont College of Medicine, Burlington, VT.

Background: Anastomotic leak is a serious complication of gastrointestinal surgery. Abnormal vital signs are often cited in retrospective peer review and medicolegal settings as evidence of negligence in the failure to make an early diagnosis. We aimed to profile the postoperative courses of patients who undergo intestinal anastomosis and determine how reliably abnormal vital signs predict anastomotic leaks.

Study Design: Consecutive patients undergoing bowel resection with anastomosis at an academic medical center from July 2009 through July 2011 were identified from a prospective complication database. The electronic medical record was queried for postoperative vital signs and laboratory studies, which were digitally abstracted. Abnormal values were defined as temperature >38°C, white blood cell count ≤4,000 or ≥12,000 cells/uL, systolic blood pressure ≤80 mmHg or diastolic blood pressure ≤50 mmHg, pulse ≥100 beats per minute, and respiratory rate ≥20 breaths per minute. Patients who developed an anastomotic leak were compared with those with an uncomplicated postoperative course.

Results: Of the 452 patients, 141 (31.2%) suffered a total of 271 complications, including 19 anastomotic leaks. Even in "uncomplicated" recoveries, tachycardia and tachypnea were almost routine, occurring in more than half of the patients frequently throughout the postoperative period. Hypotension, fever, and leukocytosis were also remarkably common. The positive predictive value of any aberrant vital sign or white blood cell count ranged between 4% and 11%.

Conclusions: Abnormal vital signs are extremely common after bowel resection with anastomosis. Even sustained aberrant vital signs and/or leukocytosis are not necessarily suggestive of a leak or other postoperative complication.
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http://dx.doi.org/10.1016/j.jamcollsurg.2013.12.059DOI Listing
June 2014

Anastomotic leak after low anterior resection: a spectrum of clinical entities.

JAMA Surg 2013 Feb;148(2):177-82

Department of Surgery, University of Vermont College of Medicine, Fletcher Room 301, 111 Colchester Ave, Burlington, VT 05401, USA.

Importance: Anastomotic leak is a potentially devastating complication of bowel surgery, yet a leak can refer to a range of clinical problems, with disparate treatment and outcomes.

Objectives: To qualitatively categorize the spectrum of anastomotic leaks that occur after low anterior resection for rectal cancer and to describe their effect on outcomes.

Design And Setting: Retrospective review of a prospective database at an academic teaching hospital.

Participants: Two hundred ten patients with at least 1 year of follow-up data.

Intervention: Low anterior resection for rectal cancer.

Main Outcome Measures: Anastomotic leak, associated treatment, and need for permanent stoma creation.

Results: Of 198 study patients, 168 had no demonstrated anastomotic leak, free fluid, or abscess at any time after surgery. Of the remaining 30 patients, 17 had extravasation of contrast medium into the peritoneal cavity or the presacral space on a postoperative imaging study, some long after surgery. Six to 9 of these patients seemed to meet usual clinical criteria for anastomotic leak. Ten patients had only free or simple pelvic fluid collection without extravasation of contrast medium, and 3 patients had an abscess near the anastomotic site without extravasation of contrast medium. Male sex, diabetes mellitus, and radiation therapy (but not cigarette smoking) increased the risk for anastomotic leak. Anastomotic leak was correlated with the requirement for permanent stoma creation, while only free anastomotic leak was associated with an increased incidence of irregular bowel function. Notably, simple fluid without extravasation of contrast medium also correlated with irregular bowel function.

Conclusions And Relevance: A spectrum of clinical entities may be considered to represent an anastomotic leak after low anterior resection, with differing consequences. Presacral and free extravasation of contrast medium led to an increased need for permanent diversion, but even simple pelvic fluid collections were associated with irregular bowel function.
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http://dx.doi.org/10.1001/jamasurgery.2013.413DOI Listing
February 2013

A comparison of the quality of life of ulcerative colitis patients after IPAA vs ileostomy.

Dis Colon Rectum 2012 Nov;55(11):1131-7

University of Vermont College of Medicine, Burlington, Vermont, USA.

Background: Total proctocolectomy with IPAA is frequently considered the procedure of choice for surgical patients with ulcerative colitis, presumably owing to an expectation of improved quality of life in comparison with an ileostomy.

Objective: The goal of our study was to determine whether long-term quality of life among patients with a pelvic pouch is better than those who chose a permanent stoma.

Design: This investigation is a cross-sectional observational study using a prospective database.

Setting: This study was conducted at an academic medical center.

Patients: Consecutive patients who had undergone IPAA or a permanent ileostomy for ulcerative colitis by a single surgeon, presenting for their annual follow-up visit from July through September 2011, were offered participation in the study. A randomly chosen group of subjects who did not have scheduled appointments during the study period were sent a letter inviting them to participate in the study.

Main Outcome Measures: The primary outcome measures used were EQ-5D-3L, the Short Quality of Life in Inflammatory Bowel Disease questionnaire, the Cleveland Global Quality of Life instrument, the Fecal Incontinence Quality of Life scale, and the Stoma Quality of Life scale.

Results: Thirty-five patients with a pelvic pouch and 24 ostomates were accrued and comprehensively studied. Global quality-of-life scores were virtually identical for the 2 groups. Patients with a pelvic pouch had better subscores in current quality of health and energy level, Fazio score, sexuality/body image, and work/social function.

Limitations: This study was limited by its small sample size, and some of our patients were enrolled through mailed surveys and, hence, nonresponse bias may be present. The follow-up time since surgery was longer in the pelvic pouch group than in the ileostomy group.

Conclusion: Informed patients with ulcerative colitis choosing an ileostomy have a health-related global quality of life very similar to patients with a pelvic pouch. Better outcomes in patients with an ileal pouch were most evident in the areas of sexuality/body image and work/social function.
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http://dx.doi.org/10.1097/DCR.0b013e3182690870DOI Listing
November 2012

Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation.

Am J Gastroenterol 2010 May 15;105(5):1173-80. Epub 2009 Dec 15.

Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.

Objectives: Changes in mucosal serotonin (5-HT) signaling have been detected in a number of functional and inflammatory disorders of the gastrointestinal (GI) tract. This study was undertaken to determine whether chronic constipation (CC) is associated with disordered 5-HT signaling and to evaluate whether constipation caused by opiate use causes such changes.

Methods: Human rectal biopsy samples were obtained from healthy volunteers, individuals with idiopathic CC, and individuals taking opiate medication with or without occurrence of constipation. EC cells were identified by 5-HT immunohistochemistry. 5-HT content and release levels were determined by enzyme immunoassay, and mRNA levels for the synthetic enzyme tryptophan hydroxylase-1 (TpH-1) and serotonin-selective reuptake transporter (SERT) were assessed by quantitative real-time reverse transcription PCR.

Results: CC was associated with increases in TpH-1 transcript, 5-HT content, and 5-HT release under basal and stimulated conditions, whereas EC cell numbers and SERT transcript levels were not altered. No changes in these elements of 5-HT signaling were detected in opiate-induced constipation (OIC).

Conclusions: These findings demonstrate that CC is associated with a pattern of altered 5-HT signaling that leads to increased 5-HT availability but does not involve a decrease in SERT expression. It is possible that increased 5-HT availability due to increased synthesis and release contributes to constipation due to receptor desensitization. Furthermore, the finding that elements of 5-HT signaling were not altered in the mucosa of individuals with OIC indicates that constipation as a condition does not lead to compensatory changes in 5-HT synthesis, release, or signal termination.
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http://dx.doi.org/10.1038/ajg.2009.683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872481PMC
May 2010

The effects of daikenchuto (DKT) on propulsive motility in the colon.

J Surg Res 2010 Nov 3;164(1):84-90. Epub 2009 May 3.

Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont 05401, USA.

Background: The purpose of this study is to examine the use of daikenchuto (DKT), a traditional Japanese medicine, as a potential treatment for opiate-induced slowing of intestinal transit in an isolated guinea pig colon model of motility.

Methods: Isolated segments of distal guinea pig colon were mounted in a perfusion chamber and imaged with a digital video camera interfaced with a computer. Fecal pellets were inserted into the oral end of the colonic segment and the rates of propulsive motility over a 3 to 4 cm segment of colon were determined in the presence and absence of test compounds. In addition, intracellular recordings were obtained from intact circular muscle, and the responsiveness of inhibitory and excitatory junction potentials to DKT was evaluated.

Results: The addition of D-Ala2, N-Me-Phe4, Gly-ol5 (DAMGO), a selective μ-receptor agonist, caused a concentration dependent decrease in colon motility. Naloxone did not affect basal activity, but partially restored motility in the DAMGO treated preparations. DKT (1 × 10(-4)-3 × 10(-4)g/mL) also reversed the inhibitory effect of DAMGO treated colon in a concentration dependent manner. At higher concentrations (1 × 10(-3)-3 × 10(-3)g/mL), however, this effect was lost. Motility slowed even further when naloxone and DKT were combined with noticeable disruptions in spatiotemporal patterns. Interestingly, when added alone, DKT resulted in reverse peristalsis of the pellet. In electrophysiologic studies DKT inhibited both excitatory and inhibitory junction potentials.

Conclusions: DKT appears to be as effective as naloxone in restoring motility in DAMGO treated colon. These two agents, however, do not appear to have an additive effect. When used on untreated colon segments, DKT appears to cause disruptions in the intrinsic reflex circuit of the gut resulting in a disruption of neuromuscular communication.
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http://dx.doi.org/10.1016/j.jss.2009.03.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945404PMC
November 2010

Anastomotic leaks after bowel resection: what does peer review teach us about the relationship to postoperative mortality?

J Am Coll Surg 2009 Jan 7;208(1):48-52. Epub 2008 Nov 7.

Department of Surgery, University of Vermont College of Medicine, Fletcher Allen Health Care, Burlington, VT, USA.

Background: Anastomotic leak is a dreaded complication of intestinal surgery and has been associated with a high mortality rate. But it is uncertain exactly which patient populations are at risk of death from the leak. We sought to assess the impact of surgeon volume on leak rate and to better understand the relationship of a leak to postoperative mortality.

Study Design: All adult patients having a small or large bowel resection with anastomosis at a university hospital from July 2003 to June 2006 were entered into a prospectively maintained quality database; data were entered by a specially trained nurse practitioner who rounded daily with housestaff. Patients with a postoperative leak based on standardized criteria were identified. Patient characteristics, surgical procedure, and operating surgeon were noted. Overall complication and leak rates by surgeon were compared using Fisher's exact test. Individual case review by a group of peers was performed for all patients with a leak who died, to determine the relationship to mortality.

Results: Five hundred fifty-six patients underwent resection with anastomosis during the study period. There were 27 patients with leaks (4.9%), 6 of whom died. Leak rate for the highest-volume surgeons ranged from 1.6% to 9.9% (p <0.01), and overall complication rate varied from 30.5% to 44% (p=0.04). In four of six deaths, leaks occurred in very ill patients undergoing emergency procedures and appeared to be premorbid events. In only one patient did the leak appear to be the primary cause of death.

Conclusions: The variability in leak rate by surgeons doing similar operations suggests that many leaks may be preventable. But death after a leak is most often a surrogate for a critically ill patient and was infrequently the actual cause of death.
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http://dx.doi.org/10.1016/j.jamcollsurg.2008.09.021DOI Listing
January 2009

Attending work hour restrictions: is it time?

Authors:
Neil H Hyman

Arch Surg 2009 Jan;144(1):7-8

Department of Surgery, Medical Center Hospital of Vermont, Fletcher 465, University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401, USA.

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http://dx.doi.org/10.1001/archsurg.2008.518DOI Listing
January 2009

Crohn's disease: drug therapy or surgery?

Authors:
Neil H Hyman

Expert Rev Gastroenterol Hepatol 2007 Dec;1(2):187-92

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http://dx.doi.org/10.1586/17474124.1.2.187DOI Listing
December 2007

Death after bowel resection: patient disease, not surgeon error.

J Gastrointest Surg 2009 Jan 8;13(1):137-41. Epub 2008 Aug 8.

Department of Surgery, University of Vermont College of Medicine, Fletcher Allen Health Care, Fletcher House 301, 111 Colchester Avenue, Burlington, VT 05401, USA.

Introduction: Although bowel resection is associated with a significant mortality rate, little is known about the demographics of the patients and how often surgical error is the primary cause of death. We sought to use a rigorous prospective quality database incorporating standardized peer review, to define how often patients die from provider-related causes.

Materials And Methods: All patients undergoing bowel resection with anastomosis at a university hospital from July 2003 to June 2006 were entered into a prospectively maintained quality database. Patients were seen daily with house staff by a specially trained nurse practitioner who recorded demographics and complications. Clinical case reviews were conducted monthly. Five hundred sixty-six patients underwent bowel resection with anastomosis during the study period.

Discussion: One hundred ninety-three patients suffered at least one complication (34.1%) and there were 20 deaths (3.5%). In 17 cases, death was deemed unavoidable due to patient disease; most occurred in patients who developed ischemic bowel while hospitalized for a serious concomitant illness. In only one case did death appear clearly related to a surgical complication (0.17%). Death after bowel resection typically reflects the need for urgent surgery in extreme circumstances and not surgeon error. Postoperative mortality rate in this population appears to be poor indicator of surgical quality.
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http://dx.doi.org/10.1007/s11605-008-0609-5DOI Listing
January 2009