David K. Driman

Prevention of adhesion formation with use of sodium hyaluronate-based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh--a randomized, controlled study.

BACKGROUNDnThere is a high incidence of adhesions after ventral hernia repair with polypropylene mesh. Hyaluronic acid (HA)-based membrane has been shown to reduce the incidence of adhesions in the absence of prosthetic mesh. The purpose of this study was to determine the effect of HA membrane on the quantity and grade of adhesions and its effect on strength of repair after abdominal wall repair with polypropylene mesh.nnnMETHODSnIn 61 rats a full-thickness abdominal wall defect (excluding skin) was created, and a section of small bowel was abraded. The animals were randomized, receiving either HA membrane to cover the viscera or no membrane. The fascial defect was repaired with polypropylene mesh. Equal numbers of animals from each group were killed at 4 weeks and 8 weeks after surgery. Adhesion severity and percentage of mesh surface covered with adhesions were estimated. Tensile strength between mesh and muscle from each animal was measured. Sections of the mesh-muscle interface were examined histologically and measured for thickness and graded for inflammation and fibrosis.nnnRESULTSnFifty-five animals survived until the end point. Animals in the HA membrane group had a significant reduction in (1) grade of adhesions between small bowel and mesh at 4 weeks (P = .009) and 8 weeks (P = .000001), (2) grade of adhesions between colon and mesh at 8 weeks (P = .00003), and (3) percentage of mesh covered with adhesions at 4 weeks (P = .01) and 8 weeks (P = .0000002). There was no difference between the 2 groups in tensile strength of the repairs, tissue thickness, degree of inflammation, or degree of fibrosis.nnnCONCLUSIONSnHA membrane reduces the quantity and grade of adhesions of both small and large bowel, to polypropylene mesh in a rat model of ventral hernia repair, without compromising strength of the repair.

Gastrointestinal Stromal Tumours: Consensus Statement on Diagnosis and Treatment

In the multidisciplinary management of gastrointestinal stromal tumours (GISTs), there is a need to coordinate the efforts of pathology, radiology, surgery and oncology. Surgery is the mainstay for resectable nonmetastatic GISTs, but virtually all GISTs are associated with a risk of metastasis. Imatinib 400 mg/day with or without surgery is the recommended first-line treatment for recurrent or metastatic GIST; a higher dose may be considered in patients who progress, develop secondary resistance or present with specific genotypic characteristics. Adjuvant or neoadjuvant imatinib is not advised for resectable nonmetastatic GISTs. Neoadjuvant imatinib may be considered when surgery would result in significant morbidity or loss of organ function. Follow-up computed tomography imaging is recommended every three to six months for at least five years. Patients with metastatic disease should be continued on imatinib due to the high risk of recurrence on discontinuation of therapy. Treatment should be continued until there is progression or intolerable adverse effects. If dose escalation with imatinib fails, a clinical trial with novel agents alone or in combination may be considered. The present recommendations were developed at a surgical subcommittee meeting and a subsequent full Advisory Committee meeting held in Toronto, Ontario, in April 2005, under the sponsorship of Novartis Pharmaceuticals Canada Inc.

Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution

Evidence is emerging that sodium phosphate (NaP), a commonly used oral cathartic agent, causes aphthoid ulcers or focal active colitis (FAC) in the colon and rectum. The aims of this study were (1) to assess the incidence of such ulcers diagnosed endoscopically (aphthoid ulcers), (2) to assess the incidence of histologically detected FAC and neutrophilic infiltration overlying lymphoid follicles (aphthoid lesions), and (3) to determine whether this effect of NaP is associated with epithelial cell proliferation. Aphthoid ulcers, unexplained by other diagnoses, were found in 18 of 687 consecutive patients (2.6%) who underwent colonoscopic examination after oral NaP preparation during a 12-month period; biopsy specimens showed FAC or aphthoid lesions. FAC was present in 11 of 316 patients (3.5%) who had biopsies but were endoscopically normal. Eight patients with aphthoid ulcers in the rectosigmoid showed no abnormalities when reexamined by flexible sigmoidoscopy after an interval as short as 7 days (range, 7 to 56 days). Mucosal biopsy specimens from these patients were assessed for apoptosis and epithelial proliferation by determining the MIB-1 labeling index (LI). The LI was increased by 136% after NaP preparation (55 +/- 6) compared with biopsy specimens obtained from the same patients during reexamination without NaP preparation (23 +/- 6, P = .01). This correlated with the number of apoptotic bodies per 10 colonic crypts (1.2 +/- 0.3 v 0.5 +/- 0.2, respectively). To determine whether these proliferative changes represent a response to mucosal ulceration, rectosigmoid biopsy specimens were compared in two additional patient groups: an NaP group in whom no gross lesions were evident and a no-NaP group who were not exposed to NaP. Although more modest, similar changes in the LI (42 +/- 4 and 30 +/- 3, respectively, P = .03) and in the occurrence of apoptotic bodies per 10 colonic crypts (1.3 +/- 0.4 and 0.4 +/- 0.1, respectively) were observed. We conclude that use of NaP is associated with increased colorectal crypt epithelial cell proliferation. This proliferative response to NaP exposure is evident in the absence of colonoscopically or other histologically recognizable abnormalities. In a proportion of patients, aphthoid ulcers, FAC, or aphthoid lesions serve as markers of mucosal damage by NaP.

Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices.

Background:Ulcerative colitis (UC) is an idiopathic inflammatory disorder. Currently, the main goals of treatment are to induce and maintain clinical and/or endoscopic remission. However, evidence indicates that persistent disease activity on colonic biopsies in the setting of clinical or endoscopic remission is an independent predictor of poor outcomes. A number of previous studies have proposed histologic indices for use in specific trials of UC. The aim of this study was to systematically review the existing histological indices for UC and assess their potential use in both patient management and clinical trials. Methods:We performed a systematic review of histological indices evaluating disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Diseases Week (DDW) abstracts of randomized and/or controlled trials clinical trials were searched from inception to February 2013 for applicable studies. Data from these studies were reviewed and analyzed. Results:After systematically applying inclusion criteria, we identified 108 scientific articles including 88 clinical studies and 21 related clinical reviews. Eighteen indices of histological activity in UC were identified and reviewed. Conclusions:Although multiple histological scoring indices for assessment of UC disease activity currently exist, none of these instruments were developed using a formal validation process and their operating properties remain poorly understood. Future studies are needed to address this deficiency.

Development and validation of a histological index for UC

Objective Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument. Design Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatts responsiveness statistic (GRS) using data from a clinical trial of an effective therapy. Results Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively. Conclusions The RHI is a new histopathological index with favourable operating properties.

Outcomes of a 5-year follow-up of patients with sessile serrated adenomas

Abstract Objective. Sessile serrated adenomas (SSAs) are precursors to colorectal cancer (CRC). The purpose of this study is to determine the occurrence of new polyps and CRC in patients with an SSA over a 5-year follow-up interval. Methods. This study is a retrospective chart review of patients with SSAs diagnosed at colonoscopy in 2005. Abstracted information included patient demographics, colonoscopy information, and polyp characteristics. Results. During 2005, 34 SSAs and 5 mixed SSAs were identified in 33 patients. The mean patient age was 66 years and 58% were female. There was a family history of CRC in 45%, prior polyps in 33%, and previous CRC in 15%. The mean SSA size was 11 mm. SSAs were located proximal to the splenic flexure in 70%. Low-grade dysplasia was present in 3% of SSAs and 80% mixed SSAs. Synchronous adenomatous and hyperplastic polyps occurred respectively in 45% and 21%. High-grade dysplasia was present in 12% of the adenomas. Twenty-two patients underwent subsequent colonoscopies with 20 new SSAs and 1 mixed SSA identified. In SSAs low-grade dysplasia occurred in 10% and high-grade dysplasia in 5%. Low-grade dysplasia was present in the mixed SSA. Synchronous adenomatous and hyperplastic polyps occurred respectively in 45% and 37%. High-grade dysplasia was present in 10% of adenomas and CRC occurred in 1 (5%) patient. Conclusions. SSAs occurred more frequently in females and in the right colon. Dysplasia occurred in a small subset of SSAs. There was a high rate of prior and subsequent CRC in patients with SSAs.

Matrilysin (matrix metalloproteinase‐7) expression in ulcerative colitis–related tumorigenesis†

Matrilysin (matrix metalloproteinase‐7) plays a part in the initiation and growth of colorectal tumors; expression of this protein has been implicated in tumor invasion and metastasis. To date, matrilysin expression in ulcerative colitis (UC)–associated tumorigenesis has not been studied. The aim of this study was to assess the immunohistochemical expression of matrilysin at different stages of UC‐associated neoplasia. Paraffin‐embedded specimens from 25 patients with UC without dysplasia, UC‐related low‐grade dysplasia (LGD) and high‐grade dysplasia (HGD), and UC‐associated carcinoma as well as four colon biopsy samples with no abnormality were examined using an anti–human matrilysin monoclonal antibody and standard immunoperoxidase techniques. Matrilysin expression was recorded as the number of positive cases and the percentage of positive crypts as follows: normal: none of four; negative results for dysplasia: seven of 12 (<u200910%); LGD: nine of 15 (<u200910%); HGD: nine of 13 (11–50%); and invasive carcinoma: six of seven (>u200950%). The results indicated an apparent switch from focal expression of matrilysin in UC‐related low‐grade dysplasia to widespread expression in high‐grade dysplasia and invasive cancer, mimicking the pattern of expression in sporadic colorectal cancer. Although the sample size is small and further investigation therefore is required, the results suggest the possible role of anti–matrix metalloproteinase therapy in reducing the risk of progression from LGD to cancer in patients with ulcerative colitis. Published 2002 Wiley‐Liss, Inc.

Mucocele of the appendix secondary to endometriosis. Report of two cases, one with localized pseudomyxoma peritonei.

This report documents 2 cases of obstructive mucocele of the appendix secondary to endometriosis of the appendix. In 1 case, the tip of the mucocele was ruptured and associated with localized pseudomyxoma peritonei. Mucoceles of the appendix usually are associated with hyperplastic or neoplastic mucosal proliferation; obstruction, particularly that due to endometriosis, is an infrequent cause. Occurrence of localized pseudomyxoma peritonei associated with appendiceal endometriosis and mucocele has not been reported previously.

Reproducibility of histological assessments of disease activity in UC.

Objective Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA. Design Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100u2005mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated. Results Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61. Conclusions Although ‘substantial’ to ‘almost perfect’ ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.

Basaloid carcinoma of the colon arising at the splenic flexure

Basaloid carcinomas typically arise in the anal canal and there are only three well‐documented cases of this neoplasm reported outside the anal canal, none more proximally than the sigmoid colon. The first occurrence of a basaloid colonic carcinoma arising outside the sigmoid colon, at the splenic flexure, is presented.