Seamus B. Kelly

Impact of surgeon volume and specialization on short‐term outcomes in colorectal cancer surgery

Several studies have shown a relationship between surgeon volume and outcomes in colorectal cancer surgery. The aim of this study was to determine the impact of surgeon volume and specialization on primary tumour resection rate, restoration of bowel continuity following rectal cancer resection, anastomotic leakage and perioperative mortality.

Volume-outcome analysis of colorectal cancer-related outcomes

Significant associations between caseload and surgical outcomes highlight the conflict between local cancer care and the need for centralization. This study examined the effect of hospital volume on short‐term outcomes and survival, adjusting for the effect of surgeon caseload.

Role of Self-Expanding Metallic Stents in the Management of Malignant Obstruction of the Proximal Colon

PURPOSE: Expandable metal stents have been shown to be effective in the management of malignant large-bowel obstruction. However, right colonic lesions account for less than 5% of all reported cases of colonic stenting. This study was performed to determine the outcomes following stenting for lesions proximal to the splenic flexure. METHODS: The hospital records of patients undergoing stenting for large-bowel obstruction at a district general hospital in northeastern England from 2003 to 2008 were reviewed retrospectively. Data were analyzed to identify patient characteristics, site of obstructing lesion, intent for stenting, and outcomes measured including relief of obstruction, hospital stay, and complications. RESULTS: Stenting was attempted in 97 patients with malignant large-bowel obstruction. Of these, 16 (16.5%) patients had lesions proximal to the splenic flexure: 8 patients had lesions in the ascending colon and 8 patients had lesions in the transverse colon. Self-expanding metal stents were successful in relieving obstruction in 14 (88%) patients with proximal colonic lesions. Stenting was attempted as a bridge to definitive surgery in five patients and for palliation in nine patients. One patient had poststent bleeding that was managed conservatively, and there were no perforations or stent dislodgements. The mean postprocedure hospital stay was 1.6 days. CONCLUSIONS: Self-expanding metal stents are safe and effective in the management of malignant large-bowel obstruction proximal to the splenic flexure. The technical and clinical success rates are comparable with those reported for stenting distal colonic lesions.

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

Objective: This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC), and its potential role in colon cancer prevention. Methods: 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa, and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 (cyclin-dependent kinase 4) and GADD45A (growth arrest and DNA damage-inducible, alpha) were investigated. Results: The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment (3.1 (1.5), mean (SEM)) as compared with OS treatment (13.7 (3.2)) (p = 0.028). However, there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index. There was significant upregulation in expression of CDK4 (p<0.01) and downregulation in expression of GADD45A (p<0.001) in the tumour tissue when compared with macroscopically normal mucosa. Following RS treatment, CDK4 expression in tumours (0.88 (0.15)) was twofold higher than that in the OS group (0.37 (0.16)) (p = 0.02). The expression of GADD45A, which was downregulated in the presence of cancer, was significantly upregulated (p = 0.048) following RS treatment (1.41 (0.26)) as compared with OS treatment (0.56 (0.3)). However, there were no significant differences in the expression of these genes in the normal mucosa following starch treatment. Conclusions: Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS. Trial registration number: ISRCTN93586244.

Involvement of surgical trainees in surgery for colorectal cancer and their effect on outcome

Objective  Surgical training in the UK is undergoing substantial changes. This study assessed: 1) the training opportunities available to trainees in operations for colorectal cancer, 2) the effect of colorectal specialization on training, and 3) the effect of consultant supervision on anastomotic complications, postoperative stay, operative mortality and 5‐year survival.

Effect of the circumferential resection margin on survival following rectal cancer surgery.

The aim was to determine the effect of the circumferential resection margin (CRM) on overall survival following surgical excision of rectal cancer.

Impact of deprivation on short- and long-term outcomes after colorectal cancer surgery

The aim of the study was to determine the association between short‐ and long‐term outcomes and deprivation for patients undergoing operative treatment for colorectal cancer in the Northern Region of England.

Differential Antineoplastic Effects of Butyrate in Cells With and Without a Functioning DNA Mismatch Repair

The aim of this study was to investigate the differential antineoplastic effects of butyrate in cells with and without a functional mismatch repair and to determine the molecular mechanisms underlying these effects. SW48 colon cancer cells in which the MLH1 gene is silenced by promoter hypermethylation and demethylated SW48 cells in which the MLH1 gene is reexpressed were treated with butyrate (0-5mM) for 8 days and the effects on cell number, MLH1 gene promoter methylation, and expression of two cell cycle regulatory genes, CDK4 and GADD45A, were assessed. Butyrate suppressed viable cell number ( P < 0.001) and reduced MLH1 promoter methylation ( P < 0.05) in SW48 cells. However, in demethylated SW48 cells, butyrate caused an increase in viable cells ( P < 0.05) and promoter methylation ( P < 0.05). CDK4 expression was downregulated by butyrate exposure, but the effect was significantly greater for demethylated SW48 cells ( P = 0.025). Butyrate treatment caused upregulation of GADD45A expression in SW48 cells but downregulation of GADD45A expression in demethylated SW48 cells ( P = 0.045). This study supports the hypothesis that butyrate has more potent antineoplastic effects on colon cancer cells with MLH1 dysfunction. Differential expression of key cell cycle regulatory genes may explain some of the molecular mechanisms underlying these effects.

The predictive value of p53 and p33(ING1b) in patients with Dukes'C colorectal cancer.

Objective  Identification of biological markers that may predict response to chemotherapy would allow the individualization of treatment by enabling selection of patients most likely to benefit from chemotherapy. The aims of this study were to determine whether p53 mutation status and p53 and p33ING1b protein expression can predict which patients with Dukes’ C colorectal cancer following curative surgical resection respond to adjuvant chemotherapy with 5‐fluorouracil (5‐FU).

Nurse specialist led flexible sigmoidoscopy in an outpatient setting

Objective  There has been an increasing demand for diagnostic flexible sigmoidoscopy. In order to improve our diagnostic services, we established a nurse specialist led flexible sigmoidoscopy clinic in 1999. The aim of this study was to review the outcomes of this service between 1999 and 2004.