Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. RESULTS: Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. CONCLUSION: MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes.

Primary colorectal lymphoma - A single centre experience.

PURPOSE: The incidence of primary colorectal lymphoma (PCL) is rare (0.2-0.6% of large bowel malignancy). Up to one third of Non-Hodgkin's lymphoma will present with extra-nodal manifestations only. Extra-nodal lymphomas arise from tissues other than the lymph nodes and even from sites, which contain no lymphoid tissue. The incidence of Non-Hodgkin's lymphoma has increased over the past fifty years. The objective of this study was to examine our experience of PCL. METHODS: A prospectively-compiled database (1988-2012) of patients with colorectal cancer was retrospectively examined for cases of colorectal lymphoma. A retrospective chart review identified cases of PCL based on Dawson's criteria. Clinical information was obtained from case notes. RESULTS: Eleven patients (0.3% of 4219 patients) were identified (6 male, 5 female). The median age at diagnosis was 63 years. Mode of presentation varied; abdominal pain, a palpable mass and per rectal bleeding being the most frequent. The caecum was the most frequently involved site (5/11). Nine patients underwent surgical management, one had chemotherapy alone and one had radiotherapy alone. All cases were non-Hodgkin's lymphoma, with diffuse large B-cell lymphoma in majority. The median event-free survival of those treated with surgery and post-operative chemotherapy was 10 months (range 5-120 months). CONCLUSION: Primary colorectal lymphoma is rare. Management is multidisciplinary and dependent on the subtype of lymphoma. Due to the rarity of diagnosis, there is a paucity of randomised control trials. Most information published is based on individual case reports and there is, thus, no clear treatment algorithm for these cases.

Open versus laparoscopic abdominal rectopexy: an examination of early postoperative outcomes.

BACKGROUND: Abdominal rectopexy is used to treat full thickness rectal prolapse and obstructed defecation syndrome, with good outcomes. Use of a laparoscopic approach may reduce morbidity. The current study assessed short-term operative outcomes for patients undergoing laparoscopic or open rectopexy. METHODS: Rectopexy cases were identified from theater logs in two tertiary referral centers. Patient demographics, intra-operative details and early postoperative outcomes were examined. RESULTS: There were 62 patients included over 10 years, a third of whom underwent laparoscopic rectopexy. Laparoscopy was associated with a longer operative time (195.9 versus 129.6 min, p = 0.003), but this did not affect postoperative outcomes, with no significant differences found for complication rates and length of stay between the two groups. Univariable analysis found no influence of laparoscopic approach on the likelihood of postoperative complications, and no factor achieved significance with multivariable analysis. This study included the first laparoscopic cases performed in the involved institutions, and a "learning curve" existed as seen with a decreasing operative duration per case over time (p = 0.002). CONCLUSIONS: Laparoscopic rectopexy has similar short-term outcomes to open rectopexy.

Management of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC). METHODS: A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed. RESULTS: A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups. CONCLUSIONS: Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.

Management of synchronous rectal and prostate cancer.

PURPOSE: Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution's experience with this and propose a treatment algorithm based on the best available evidence. METHODS: From 2000 to 2011, a retrospective review of institutional databases was performed to identify patients with synchronous prostate and rectal cancers where the rectal cancer lay in the lower two thirds of the rectum. Operative and non-operative outcomes were analysed and a management algorithm is proposed. RESULTS: Twelve patients with prostate and rectal cancer were identified. Three were metachronous diagnoses (>3-month time interval) and nine were synchronous diagnoses. In the synchronous group, four had metastatic disease at presentation and were treated symptomatically, while five were treated with curative intent. Treatment included pelvic radiotherapy (74 Gy) followed by pelvic exenteration (three) and watchful waiting for rectal cancer (one). The remaining patient had a prostatectomy, long-course chemoradiotherapy and anterior resection. There were no operative mortalities and acceptable morbidity. Three remain alive with two patients disease-free. CONCLUSIONS: Synchronous detection of prostate cancer and cancer of the lower two thirds of the rectum is uncommon, but likely to increase with rigorous preoperative staging of rectal cancer and increased awareness of the potential for synchronous disease. Treatment must be individualized based on the stage of the individual cancers taking into account the options for both cancers including EBRT (both), surgery (both), hormonal therapy (prostate), surgery (both) and watchful waiting (both).

A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Locally advanced rectal cancer is frequently treated with neoadjuvant chemoradiotherapy to reduce local recurrence and possibly improve survival. The tumor response to chemoradiotherapy is variable and may influence the prognosis after surgery. This study assessed tumor regression and its influence on survival in patients with rectal cancer treated with chemoradiotherapy followed by curative surgery. METHODS: One hundred twenty-six patients with locally advanced rectal cancer (T3/T4 or N1/N2) were treated with chemoradiotherapy followed by total mesorectal excision. Patients received long-course radiotherapy (50 Gy in 25 fractions) in combination with 5-flourouracil over 5 weeks. By means of a standardized approach, tumor regression was graded in the resection specimen using a 3-point system related to tumor regression grade (TRG): complete or near-complete response (TRG1), partial response (TRG2), or no response (TRG3). RESULTS: The 5-year disease-free survival was 72% (median follow-up 37 months), and 7% of patients had local recurrence. Chemoradiotherapy produced downstaging in 60% of patients; 21% of patients experienced TRG1. TRG1 correlated with a pathological T0/1 or N0 status. Five-year disease-free survival after chemoradiotherapy and surgery was significantly better in TRG1 patients (100%) compared with TRG2 (71%) and TRG3 (66%) (P = .01). CONCLUSION: Tumor regression grade measured on a 3-point system predicts outcome after chemoradiotherapy and surgery for locally advanced rectal cancer.

Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

AIMS: To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression. METHODS AND RESULTS: Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long-course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5-point tumour regression grade (TRG), and a novel 3-point grade. Both scores were evaluated for interobserver variability. A complete or near-complete pathological response (3-point TRG 1) was found in 10 patients (17%). Using the 5-point TRG, there was good agreement between both pathologists (kappa = 0.64). Using the 3-point grade, agreement was excellent (kappa = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3-point TRG 1), after a mean follow-up of 22 months. CONCLUSION: Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3-point grade has the advantage of better reproducibility, with similar prognostic significance.

Diagnosis and treatment of enterovesical fistulae.

OBJECTIVE: Enterovesical fistulae are a recognized complication of a variety of inflammatory and neoplastic conditions. Despite advances in imaging and treatment the diagnosis may be delayed and the management remains diverse. We describe our experience with their diagnosis and management. PATIENTS AND METHODS: This retrospective study encompassed all patients referred over a 10-year period with clinical suspicion of or confirmed enterovesical fistula. Demographics, clinical presentation, aetiology and clinical outcome were evaluated. Mean follow-up was 18 months (range 6-50 months). RESULTS: Thirty patients were studied. The mean age was 63.5 years (range 23-92 years). Fifteen (50%) patients presented with classical urinary symptoms (pneumaturia, faecaluria and recurrent urinary tract infections). The commonest investigations (n, % positive) included CT (15, 80), cystoscopy (16, 87.5), endoscopy (11, 54.5) and barium enema (8, 50). There were 20 inflammatory and 10 neoplastic aetiologies. Five patients were treated conservatively and 25 patients underwent surgery. Surgery resulted in symptomatic cure in the majority of cases (22/25). CONCLUSION: Classical urinary symptoms were only evident in 50% of patients with confirmed fistulae. We advocate CT scanning as the optimum imaging modality before surgical intervention. Surgical treatment in a specialized unit remains the most effective treatment of enterovesical fistulae.

Perianal Crohn's disease and infliximab therapy.

INTRODUCTION: Perianal manifestations occur in almost half of patients with Crohn's disease and often respond poorly to conventional therapies. The introduction of anti-tumour necrosis factor alpha agents (e.g. infliximab) has altered the management of patients who fail first and second line medical and surgical therapies. METHODS: We performed a literature search of the PubMed database using the Medical Search Headings infliximab, perianal Crohn's disease, fistulae, cost and safety. We also performed a manual search using references from these articles, review articles and proceedings from major gastroenterology meetings. RESULTS: Use of infliximab, at a dose of 5mg/kg at intervals of 0, 2 and 6 weeks, results in significant improvement in disease in approximately 70% of patients with fistulae. Prior examination under anaesthesia with placement of non-cutting seton sutures in fistula tracks is a useful adjunct in many patients. Preliminary results show a benefit from maintenance infliximab therapy and from concomitant use of immunosuppressants such as azathioprine. No clinical or biochemical markers have been identified which predict non-response to infliximab, although its use is contraindicated in patients with strictures. Acute infusion reactions are the most common side-effect of infliximab therapy and they are usually mild. Despite initial fears, the incidence of opportunistic infection is low. There is inadequate information, at present, regarding a possible increase in incidence of lymphoma with infliximab therapy. Infliximab is expensive compared with established therapies and its use will increase the lifetime cost of treating Crohn's disease. CONCLUSION: While infliximab is a useful adjunct in selected patients, the cornerstones of management of perianal Crohn's are essentially unchanged.

Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression.

Cathepsin B and Cathepsin L are cysteine proteases important in the process of invasion and metastasis. The aim of our study was to assay antigen and activity levels of these enzymes and to correlate these with established clinical and pathological prognostic parameters including patient survival. 99 patients undergoing operations for colorectal cancer were included in this study. We quantitated cathepsin B and L levels in matched normal mucosa and cancer samples using an enzyme-linked immunosorbent assay (ELISA) and specific activity assays and expressed the results as tumour/normal ratios. Significant correlations were found between tumour/normal cathepsin B and L antigen and activity ratios. Cathepsin B and L tumour/normal activity ratios were greater than 1 in early stage disease and there were gradual reductions in cathepsin B (P = 0.02) and L (P = 0.03) activity ratios with advancing tumour stage. Survival of patients with potentially curative disease was inversely related to both cathepsin B (P = 0.007) and L (P = 0.001) activity ratio, in addition to cathepsin L antigen ratio (P = 0.008). Our findings suggest that cysteine proteases play an important role in colorectal cancer progression.

Peritoneal involvement in stage II colon cancer.

A pathologist (K.S.) reviewed histologic slides for peritoneal involvement by tumor cells for 118 patients with stage II colon cancer. Patients were followed up for a median of 6 years. Tumor cells were found free in the peritoneal space in 16 cases (13.6%). The presence of cancer cells free in the peritoneal space was associated with lymphovascular invasion (P = .001) and neural invasion (P < .001). The overall 5-year survival was 80% in the patient population, but was 39% and 86% for those with and without tumor cells free in the peritoneal space, respectively (P < .0001). Multivariate analysis confirmed that free tumor cells within the peritoneal space (P < .0001) and lymphovascular invasion (P = .007) were related independently to outcome. Peritoneal involvement with tumor cells free in the peritoneal space in stage II colon cancer is a powerful indicator of outcome; patients have a survival similar to that for patients with stage III disease.

Sigmoid volvulus: a 10-year-audit.

BACKGROUND: Chronic constipation in elderly, institutionalised patients is the leading cause of sigmoid volvulus in the developed world. Endoscopic deflation is associated with a 90% recurrence rate and a 35% mortality rate. AIMS: To review a 10-year experience of sigmoid volvulus and encourage more aggressive primary treatment. METHODS: A retrospective study was performed on 16 patients with sigmoid volvulus from 1992 to 1999. Patients were identified using the hospital inpatient enquiry (HIPE) data system. Demographics, clinical course, intervention, complications and outcome were recorded. RESULTS: The male:female ratio was 5:3 and mean age was 78 years (range 39-92). Fifty per cent had at least one risk factor: Parkinson's disease (n=3); multiple sclerosis (n=1); Alzheimer's disease (n=1); and hypokalaemia (n=3). Thirty-seven per cent were managed conservatively and 63% required surgical intervention. Mean time to surgery was 2.4 days. Operations performed were sigmoid colectomy (45%), Hartmann's procedure (33%) and total colectomy (22%). There was one post-operative death from myocardial ischaemia. Mean duration of admission was 21 days. CONCLUSIONS: Endoscopic deflation of a sigmoid volvulus facilitates optimisation of cardiopulmonary co-morbidity in a high-risk group of patients. It converts an emergent to an elective procedure and minimises operative morbidity as a result.