Rishabh Sehgal

Dehydration Is the Most Common Indication for Readmission After Diverting Ileostomy Creation

BACKGROUND: Early readmission after discharge from the hospital is an undesirable outcome. Ileostomies are commonly used to prevent symptomatic anastomotic complications in colorectal resections. OBJECTIVE: The aim of this study was to identify factors predictive of readmission after colectomy/proctectomy and diverting loop ileostomy. DESIGN: This study is a retrospective review. PATIENTS: Patients were included who underwent colon and rectal resections with ileostomy at our institution. Sex, age, type of disease, comorbidities, elective vs urgent procedure, type of ileostomy, operative method, steroid use, ASA score, and the use of diuretics were evaluated as potential factors for readmission. MAIN OUTCOME MEASURES: The primary outcomes measured were the need for readmission and the presence of dehydration (ostomy output ≥1500 mL over 24 hours and a blood urea nitrogen/creatinine level ≥20, or physical findings of dehydration). RESULTS: Six hundred three loop ileostomies were created mostly in white (95.3%), male (55.6%) patients undergoing colon or rectal resections. IBD was the most common indication at 50.9%, with rectal cancer at 16.1%, and other at 31.0%. The 60-day readmission rate was 16.9% (n = 102) with the most common cause dehydration (n = 44, 43.1%). Regression analysis demonstrated that the laparoscopic approach (p = 0.02), lack of epidural anesthesia (p = 0.004), preoperative use of steroids (p = 0.04), and postoperative use of diuretics (p = 0.0001) were highly predictive for readmission. Furthermore, regression analysis for readmission for dehydration identified the use of postoperative diuretics as the sole risk factor (p = 0.0001). LIMITATIONS: This study is limited by the retrospective analysis of data, and it does not capture patients that were treated at home or in clinic. CONCLUSION: Readmission after colon or rectal resection with diverting loop ileostomy was high at 16.9%. Dehydration was the major cause for readmission. Patients receiving diuretics are at increased risk for readmission for dehydration. High-risk patients should be treated more cautiously as inpatients and closely monitored in the outpatient setting to help reduce dehydration and readmission.

The NOD2insC polymorphism is associated with worse outcome following ileal pouch-anal anastomosis for ulcerative colitis

Background Inflammatory complications after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are common. Objective To investigate whether genetic factors are associated with adverse pouch outcomes such as chronic pouchitis (CP) and a Crohns disease-like (CDL) phenotype. Design 866 patients were recruited from three centres in North America: Mount Sinai Hospital (Toronto, Ontario, Canada), the Cleveland Clinic (Cleveland, Ohio, USA) and Penn State Milton S Hershey Medical Center (Hershey, Pennsylvania, USA). DNA and clinical and demographic information were collected. Subjects were classified into post-surgical outcome groups: no chronic pouchitis (NCP), CP and CDL phenotype. Results Clinical and genetic data were available on 714 individuals. 487 (68.2%) were classified as NCP, 118 (16.5%) CP and 109 (15.3%) CDL. The presence of arthritis or arthropathy (p=0.02), primary sclerosing cholangitis (p=0.009) and duration of time from ileostomy closure to recruitment (p=0.001) were significantly associated with outcome. The NOD2insC (rs2066847) risk variant was the single nucleotide polymorphism (SNP) most significantly associated with pouch outcome (p=7.4×10−5). Specifically, it was associated with both CP and CDL in comparison with NCP (OR=3.2 and 4.3, respectively). Additionally, SNPs in NOX3 (rs6557421, rs12661812), DAGLB (rs836518) and NCF4 (rs8137602) were shown to be associated with pouch outcome with slightly weaker effects. A multivariable risk model combining previously identified clinical (smoking status, family history of inflammatory bowel disease), serological (anti-Saccharomyces cerevisiae antibody IgG, perinuclear antineutrophil cytoplasmic antibody and anti-CBir1) and genetic markers was constructed and resulted in an OR of 2.72 (p=8.89×10−7) for NCP versus CP/CDL and 3.22 (p=4.11×10−8) for NCP versus CDL, respectively. Conclusion Genetic polymorphisms, in particular, the NOD2insC risk allele, are associated with chronic inflammatory pouch outcomes among patients with UC and IPAA.

Risk Factors for Surgical Site Infections after Colorectal Resection in Diabetic Patients

BACKGROUND Surgical site infections (SSIs) are a well known complication of gastrointestinal surgery and associated with an increased morbidity, mortality and overall cost. Diabetes mellitus (DM) is a risk factor for SSI. However, there is no clear consensus as to which other risk factors play a significant role. The goal of this study was to identify risk factors associated with SSI in patients with DM undergoing colorectal resection. STUDY DESIGN A retrospective review was conducted of DM patients who underwent colorectal resection from June 2000 to June 2009 at Milton S Hershey Medical Center, Division of Colorectal Surgery. Individual measures were analyzed using chi-square, t-test, and Mann-Whitney U tests, and statistical significance was confirmed using a multiple logistical regression model. RESULTS There were 183 DM patients included in the study, 28 (15%) of whom developed SSI. Glucose levels were significantly higher in the SSI group for each time interval, 0 to 6 hours (211 mg/dL, p = 0.03), 0 to 48 hours (176 mg/dL, p = 0.001), and 48 to 96 hours (167 mg/dL, p = 0.012) postoperatively. Other measures significantly associated with SSI included the use of drains (p = 0.05) and the use of prophylactic antibiotics for more than 24 hours (p = 0.02). Body mass index and stoma creation approached statistical significance (p = 0.08, 0.07, respectively). The type of hypoglycemic regimen, immunosuppression, and emergency surgery were not associated with an increased rate of SSI. CONCLUSIONS Higher than normal glucose control at all postoperative time intervals was associated with SSI. The majority of glucose levels were below the American Diabetes Association recommended level of 200 mg/dL, but patients still developed SSI. Type of perioperative glucose control did not affect the incidence of SSI. These data suggest that DM patients undergoing colectomy should have glucose tightly controlled, avoid placement of drains, and receive antibiotics for less than 24 hours.

NOD2/CARD15 Mutations Correlate With Severe Pouchitis After Ileal Pouch-Anal Anastomosis

PURPOSE: Pouchitis and Crohns-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohns disease. We hypothesize that IPAA patients with complications (Crohns disease-like/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS: Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohns-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohns disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohns disease were genotyped using polymerase chain reaction. Groups were compared by use of &khgr;2 with Yates continuity correction. RESULTS: NOD2 mutations were found in 8.5% of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67%) compared with both asymptomatic IPAA (5.4%, P < .001) and IPAA with Crohns disease-like complications (14.3%, P = .008) groups. CONCLUSIONS: 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohns-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.

Infliximab and/or azathioprine in the treatment of Crohn's disease-like complications after IPAA.

PURPOSE: Ileal pouch-anal anastomosis continues to be confounded by Crohns disease-like complications after surgery. Such patients experience significant morbidity and often require either pouch excision or diversion. This study evaluated the effectiveness in our hands of infliximab and/or azathioprine/6-mercaptopurine in treating this patient population. METHODS: We conducted a retrospective chart review of all patients who underwent IPAA who experienced Crohns disease-like complications (pouch fistulas, stricturing small-bowel disease, or pouchitis unresponsive to antibiotics) after ileostomy closure. Patients were segregated according to treatment (azathioprine/6-mercaptopurine only, infliximab only, or both azathioprine/6-mercaptopurine and infliximab) and evaluated for clinical response defined by significant symptomatic improvement and avoidance of stoma. RESULTS: Of 382 IPAAs, 32 (8.4%) patients developed Crohns disease-like complications a mean of 17 months after stoma closure. Of these, 22 were treated with azathioprine/6-mercaptopurine and/or infliximab with one lost to follow-up. Overall mean follow-up was 97 ± 11.8 months. Failure rate (requiring stomas) was highest in the fistula group treated with infliximab and azathioprine/6-mercaptopurine (6/13, 46%). Patients with stricturing disease (6) or severe pouchitis (2) were all effectively treated with azathioprine/6-mercaptopurine (5/6) or infliximab (1 patient allergic to azathioprine/6-mercaptopurine) and none of these patients required stomas. In the group not receiving stomas, bowel frequency improved from 8.3 ± 1 to 5.7 ± 0.5 per day (P < .05). CONCLUSION: Fistulizing disease after IPAA has the highest failure/stoma rate (46%) despite treatment with infliximab and/or azathioprine/6-mercaptopurine. IPAA patients with stricturing disease and/or antibiotic resistant pouchitis were successfully treated without stomas and all had resolution of symptoms, which suggests that fistulous disease after IPAA should be treated with infliximab, but stricturing disease and antibiotic resistant pouchitis may be effectively treated with azathioprine/6-mercaptopurine only. Such a protocol will potentially minimize the risks associated with infliximab in this difficult group of patients.

Mutations in IRGM are associated with more frequent need for surgery in patients with ileocolonic Crohn's disease.

BACKGROUND: There are no clear criteria for judging the severity of disease in patients with Crohns disease. Yet classification of patients into low- and high-risk severity groups would benefit both medical and surgical management. At the time of this study, approximately 80 single-nucleotide polymorphisms within 55 genes had been associated with IBD. OBJECTIVE: The aim of this study was to identify genetic determinants (single-nucleotide polymorphisms) that could be markers of Crohns disease severity by the use of frequency of ileocolic surgery as a surrogate for disease severity. DESIGN: Sixty-six patients (30 male) with ileocolonic Crohns disease who previously underwent ileocolectomy were retrospectively studied. The severity of Crohns disease was quantified by dividing the total number of ileocolectomy procedures by the time between IBD diagnosis and the patients last clinic visit, the rationale being that more severe disease would be associated with a more frequent need for surgery. Genotyping for the 83 single-nucleotide polymorphisms associated with IBD was done on a customized Illumina Veracode genotyping platform. Three genetic models (general, additive, and dominant) were used to statistically quantify the genetic association of the studied single-nucleotide polymorphisms to the frequency of surgery after adjusting for covariates (age, smoking, family history, disease location, and disease behavior). RESULTS: For the entire group the average number of ileocolectomies per patient was 1.7 (range, 1–5) with an average duration of disease of 14.7 years. Single-nucleotide polymorphism rs4958847 in the IRGM gene (immunity-related GTPase family, M) was the most significant single-nucleotide polymorphism in all 3 models tested (p = 0.007) as being associated with ileocolectomy, and it remained significant even after a Benjamini-Hochberg false-discovery correction for multiple observations. Patients carrying the “at-risk” allele for this single-nucleotide polymorphism (n = 20) had an average of 1 surgery every 6.87 ± 1.33 years in comparison with patients carrying the wild-type genotype (n = 46) who averaged 1 surgery in 11.43 ± 1.21 years (p = 0.007, Mann-Whitney U test). CONCLUSIONS: Single-nucleotide polymorphism rs4958847 in the IRGM gene correlated very significantly with frequency of surgery in patients with ileocolonic Crohns disease. IRGM is a mediator of innate immune responses and is involved in autophagy. The presence of this IRGM SNP may be a marker for disease severity and/or early recurrence after ileocolectomy and may assist in surgical and medical decision making.

Genetic risk profiling and gene signature modeling to predict risk of complications after IPAA.

BACKGROUND: Severe pouchitis and Crohns disease-like complications are 2 adverse postoperative complications that confound the success of the IPAA in patients with ulcerative colitis. To date, approximately 83 single nucleotide polymorphisms within 55 genes have been associated with IBD. OBJECTIVE: The aim of this study was to identify single-nucleotide polymorphisms that correlate with complications after IPAA that could be utilized in a gene signature fashion to predict postoperative complications and aid in preoperative surgical decision making. DESIGN: One hundred forty-two IPAA patients were retrospectively classified as “asymptomatic” (n = 104, defined as no Crohns disease-like complications or severe pouchitis for at least 2 years after IPAA) and compared with a “severe pouchitis” group (n = 12, ≥4 episodes pouchitis per year for 2 years including the need for long-term therapy to maintain remission) and a “Crohns disease-like” group (n = 26, presence of fistulae, pouch inlet stricture, proximal small-bowel disease, or pouch granulomata, occurring at least 6 months after surgery). Genotyping for 83 single-nucleotide polymorphisms previously associated with Crohns disease and/or ulcerative colitis was performed on a customized Illumina genotyping platform. The top 2 single-nucleotide polymorphisms statistically identified as being independently associated with each of Crohns disease-like and severe pouchitis were used in a multivariate logistic regression model. These single-nucleotide polymorphisms were then used to create probability equations to predict overall chance of a positive or negative outcome for that complication. RESULTS: The top 2 single-nucleotide polymorphisms for Crohns disease-like complications were in the 10q21 locus and the gene for PTGER4 (p = 0.006 and 0.007), whereas for severe pouchitis it was NOD2 and TNFSF15 (p = 0.003 and 0.011). Probability equations suggested that the risk of these 2 complications greatly increased with increasing number of risk alleles, going as high as 92% for severe pouchitis and 65% for Crohns disease-like complications. CONCLUSION: In this IPAA patient cohort, mutations in the 10q21 locus and the PTGER4 gene were associated with Crohns disease-like complications, whereas mutations in NOD2 and TNFSF15 correlated with severe pouchitis. Preoperative genetic analysis and use of such gene signatures hold promise for improved preoperative surgical patient selection to minimize these IPAA complications.

A detailed appraisal of mesocolic lymphangiology – an immunohistochemical and stereological analysis

Inadequate resection of the adjoining mesentery is associated with adverse outcome for colon cancer. Disruption of the integrity of the mesenteric lymphatic package has been implicated in this, though not proven. Recent studies have determined mesenteric anatomy and histology and now provide an opportunity to determine accurately the distribution of lymphatic vessels. The aim of this study was to characterise the distribution of the lymphatic vessels (LV) within the small intestinal and colonic mesentery, and in Toldts fascia, which lies between the mesocolon and underlying retroperitoneum. Mesenteric samples were harvested from 12 human cadavers. Samples were taken from the small bowel mesentery, ascending, transverse, descending mesocolon and from both apposed and non‐apposed portions of the mesosigmoid. Serial sections were stained immunohistochemically with monoclonal antibody D2‐40 (podoplanin), and Massons Trichrome. Lymphatic vessel (LV) density and radius of diffusion were determined using a stereological approach. A lymphatic network was embedded within the mesenteric connective tissue lattice throughout each mesenteric region. LV were identifiable within the submesothelial connective tissue where they measured 10.2 ± 4.1 μm in diameter and had an average radius of diffusion of 174.72 ± 97.68 μm. Unexpectedly, LV were identified in Toldts fascia, where they measured 4.3 ± 3.1 μm in diameter and had a radius of diffusion of 165.12 ± 66.26 μm. This is the first study systematically to determine and quantify the distribution of lymphatic vessels within the mesenteric organ and to demonstrate the presence of such vessels within Toldts fascia. A rich lymphatic network occupies all levels of the mesenteric connective tissue lattice. Within the latter, they are found within 0.1 mm of peritonealised mesenteric surfaces and are separated by an average distance of 0.17 mm and may be particularly vulnerable during surgery.

Terminology and nomenclature in colonic surgery: universal application of a rule-based approach derived from updates on mesenteric anatomy

Recent developments in colonic surgery generate exciting opportunities for surgeons and trainees. In the first instance, the anatomy of the entire mesenteric organ has been clarified and greatly simplified. No longer is it regarded as fragmented and complex. Rather it is continuous from duodenojejunal flexure to mesorectum, spanning the gastrointestinal tract between. Recent histologic findings have demonstrated that although apposed to the retroperitoneum, the mesenteric organ is separated from this via Toldt’s fascia. These fundamentally important observations underpin the principles of complete mesocolic excision, where the mesocolic package is maintained intact, following extensive mesenterectomy. More importantly, they provide the first opportunity to apply a canonical approach to the development of nomenclature in resectional colonic surgery. In this review, we demonstrate how the resultant nomenclature is entirely anatomic based, and for illustrative purposes, we apply it to the procedure conventionally referred to as right hemicolectomy, or ileocolic resection.

Mesenteric-Based Surgery Exploits Gastrointestinal, Peritoneal, Mesenteric and Fascial Continuity from Duodenojejunal Flexure to the Anorectal Junction--A Review.

Introduction: It is now well established that mesenteric-based colorectal surgery is associated with superior outcomes. Recent anatomic observations have demonstrated that the mesenteric organ is contiguous from the duodenojejunal to the anorectal junction. This led to similar observations in relation to associated peritoneum and fascia. The aim of this review was to demonstrate the relevance of the contiguity principle to resectional colorectal surgery. Methods: All literature in relation to mesenteric anatomy was reviewed from 1873 to the present, without language restriction. Results: Mesenteric-based surgery (i.e. complete mesocolic excision, total mesocolic and mesorectal excision) requires division of the peritoneal reflection (i.e. peritonotomy), and mesenteric mobilisation in the mesofascial plane. These are the fundamental technical elements of mesenterectomy. Mesenteric, peritoneal and fascial contiguity mean that in resectional surgery, these technical elements can be reproducibly applied at all levels from the origin at the superior mesenteric root, to the anorectal junction. Conclusions: The goals of complete mesocolic, total mesocolic and mesorectal excision can be universally achieved at any level from duodenojejunal flexure to anorectal junction, by adopting technical elements based on mesenteric, peritoneal and fascial contiguity.