The prevalence and fate of the defunctioning stoma in patients with anal cancer: a regional experience following the ACT II trial.

AIM: UK guidance advises the creation of a defunctioning stoma for anal tumours infiltrating the vagina, impending obstruction or significant faecal incontinence. Other patients may be offered a defunctioning stoma at the discretion of the clinician. The purpose of this study was to establish the prevalence and fate of defunctioning stomas in a regional anal cancer service, with reference to the results from the recent ACT II trial. METHOD: Oncological treatment was standardized as described in the ACT II trial. All patients from 2010 to 2013 inclusive were included. Collected data were correlated with both the IMRT guidelines and the outcomes of the ACT II trial. Kaplan-Meier survival analysis was applied to stoma-free survival to the end of the study period. RESULTS: Seventy-six patients were identified during the study period, of whom 51% had a defunctioning stoma. Twenty were performed for anterior tumours without infiltration into the vagina (Group A), whilst 19 had a stoma for indications as set out by the guidelines (Group B). Stoma reversal was performed in 41% of patients, 13/20 in Group A and 3/19 in Group B. The median time to reversal was 11 months. Eleven deaths were recorded and six patients still had their stomas at time of death. Stoma-free survival was 74%. No new ano-vaginal fistulation occurred as a consequence of treatment. CONCLUSION: The tumour features that are indications for defunctioning as advised by the UK IMRT guidelines are associated with a poorer overall outcome, and these stomas are less likely to be reversed. The majority of stomas, however, were formed for anterior tumours without infiltration into the vagina and were more likely to be successfully reversed.

Early experience with the bioabsorbable anal fistula plug.

PURPOSE: Management of anal fistula represents a balance between curing the condition and maintaining anal continence. Recent reports of the results of the porcine anal fistula plug have demonstrated excellent fistula healing rates without reporting significant complications. METHODS: The outcome of patients who underwent treatment for anal fistula with the Surgisis anal plug was retrospectively reviewed. RESULTS: Twenty patients were treated; three underwent concomitant anal advancement flap at the time of plug placement. Seventeen patients had a trans-sphincteric fistula, and three had an anoperineal fistula. Ten patients had previously undergone failed surgical therapy to cure their fistula, including anal advancement flap in four, muscle interposition flap in two, fistulotomy in two, and cutting seton placement in two. Mean follow-up was 7.4 months. Only 4 of 17 (24%) patients treated with the plug alone had closure of their fistula. Acute postoperative sepsis was seen in 5 of 17 (29%) patients treated with the plug alone. Four developed perianal abscesses that required incision and drainage, and one intersphincteric abscess was treated with antibiotics. Two of the patients who underwent concomitant anal advancement flaps and plug placement healed successfully. CONCLUSIONS: Contrary to other published series, the use of the Surgisis anal plug was associated with a low rate of fistula healing and a high incidence of perianal sepsis. The addition of a transanal advancement flap to the procedure may improve success rates.

The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis.

BACKGROUND: The risk of damage to the bile duct and structures in the hilum of the liver is significant when Calot's triangle cannot be safely dissected during laparoscopic cholecystectomy, and conversion to an open procedure often is performed. This is more common during emergency surgery, but may not render the procedure any easier. Traditionally, open subtotal cholecystectomy was performed, but with the advent of laparoscopic surgery, this has fallen from favor. The authors report their experience using laparoscopic subtotal cholecystectomy to avoid bile duct injury and conversion in difficult cases. METHODS: Laparoscopic subtotal cholecystectomy, performed when the cystic duct cannot be identified safely, consists of resecting the anterior wall of the gallbladder, removing all stones, and placing a large drain into Hartmann's pouch. The notes for all patients who underwent a laparoscopic subtotal cholecystectomy between 1 September 2001 and 31 December 2004 were retrospectively analyzed. RESULTS: Subtotal cholecystectomy was performed in 26 cases including 13 emergency and 13 elective procedures. The median age of the patients (15 women and 11 men) was 68 years (range, 36-86 years). The indications were severe fibrosis in 16 cases, inflammatory mass or empyema in 8 cases, and gangrenous gallbladder or perforation in 2 cases. The median postoperative inpatient stay was 5 days (range, 2-26 days). Five patients underwent postoperative endoscopic retrograde cholangiopancreatography: four for persistent biliary leak and one for a retained common bile duct stone. One patient required laparotomy for subphrenic abscess, and one patient (American Society of Anesthesiology [ASA] grade 4, presenting with biliary peritonitis) died 2 days postoperatively. One patient required a subsequent completion laparoscopic cholecystectomy for a retained gallstone. One patient had a chest infection, and two patients experienced port-site hernias. CONCLUSIONS: Laparoscopic subtotal cholecystectomy is a viable procedure during cholecystectomy in which Calot's triangle cannot be dissected. It averts the need for a laparotomy.

Is MSI-H of value in predicting the development of metachronous colorectal cancer?

Nearly 10% of patients with colorectal cancer (CRC) develop a metachronous cancer after curative resection of their primary malignancy, however identifying these patients is problematic. Although microsatellite instability (MSI) is associated with the development of multiple CRC, this is predominantly seen in those with hereditary non-polyposis colon cancer (HNPCC). This study has examined the value of MSI analysis in identifying patients at risk of developing metachronous cancer from the general population. MSI analysis was performed at the Bat25, Bat26, Bat40, D2S123, D5S346 and D17S250 loci using polymerase chain reaction and single-stranded conformational polymorphism on DNA extracted from 62 specimens taken from 49 patients with metachronous CRC, and from 71 primary single CRCs. MSI status was classified into MSI-H, MSI-L and MSS. MSI-H was more prevalent in metachronous cancers, 34/62 compared to 8/71 single cancers (P < 0.0001). The incidence of MSI-H from proximal colon cancers in index metachronous group, 4/22 was similar to single cancer group, 7/71 (P = 0.28), however MSI-H was more commonly identified in index metachronous cancers located distal to the splenic flexure 9/22 than single cancers 1/71 (P < 0.0001). Patients presenting with MSI-H colorectal cancers distal to the splenic flexure are more likely to develop a metachronous cancer and will benefit from surveillance.

The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers.

There is increased incidence of microsatellite instability (MSI) in patients who develop multiple primary colorectal cancers (CRC), although the association with hereditary nonpolyposis colon cancer (HNPCC) is unclear. This study aims to evaluate the underlying genetic cause of MSI in these patients. Microsatellite instability was investigated in 111 paraffin-embedded CRCs obtained from 78 patients with metachronous and synchronous cancers, and a control group consisting of 74 cancers from patients with a single CRC. Tumours were classified as high level (MSI-H), low level (MSI-L) or stable (MSS). MLH1, MSH2 and MSH6 gene expression was measured by immunohistochemistry. Methylation of the MLH1 promoter region was evaluated in MSI-H cancers that failed to express MLH1, and mutational analysis performed in MSI-H samples that expressed MLH1, MSH2 and MSH6 proteins. The frequency of MSI-H was significantly greater in the multiple, 58 out of 111 (52%), compared to the single cancers, 10 out of 74 (13.5%), P < 0.01. Of the 32 patients from whom two or more cancers were analysed, eight (25%) demonstrated MSI-H in both cancers, 13 (41%) demonstrated MSI-H in one cancer and 11 (34%) failed to demonstrate any MSI-H. MSI-H single cancers failed to express MLH1 or MSH2 in seven out of nine (78%) cases and MSI-L/MSS cancers failed to express MLH1 or MSH2 in one out of 45 (2.2%) cases, all cancers expressed MSH6. MSI-H multiple cancers failed to express MLH1 or MSH2 in 21 out of 43 (48%) cases and MSI-L/MSS cancers failed to express MLH1 or MSH2 in four out of 32 (12.5%) cases. MSH6 expression was lost in five MSI-H multiple cancers, four of which also failed to express MLH1 or MSH2. Loss of expression of the same mismatch repair (MMR) gene was identified in both cancers from six out of 19 (31%) patients. Methylation was identified in 11 out of 17 (65%) multiple and three out of six (50%) single MSI-H cancers that failed to express MLH1. Mutational analysis of 10 MSI-H multiple cancers that expressed MLH1, MSH2 and MSH6 failed to demonstrate mutations in the MLH1 or MSH2 genes. We suggest that, although MSI-H is more commonly identified in those with multiple colorectal cancers, this does not commonly arise from a classical HNPCC pathway.

One year follow up of a randomized trial comparing Ligasure with open haemorrhoidectomy.

BACKGROUND: Ligasure haemorrhoidectomy is an effective treatment for prolapsing haemorrhoids, however, concerns exist regarding potential damage to the anal sphincters. METHODS: Patients previously included into a randomized trial comparing open and Ligasure haemorrhoidectomy were contacted by postal questionnaire to evaluate their overall satisfaction and continence at 12 months post operatively. RESULTS: Thirteen patients who underwent open and 17 who underwent Ligasure haemorrhoidectomy were evaluated. Three patients from the open group and 2 from the Ligasure group were unhappy with the result (P = 0.37) and minor incontinence was reported in 5 Ligasure and 2 open patients (P = 0.42). CONCLUSION: Patient satisfaction and post operative continence scores at 1 year post operatively are comparable for open and Ligasure haemorrhoidectomy.

The use of Ligasure haemorrhoidectomy in patients taking oral anticoagulation therapy.

OBJECTIVES: To assess the safety of Ligasure haemorrhoidectomy in treating patients on long-term anticoagulation therapy. METHOD: Three patients taking warfarin underwent Ligasure haemorrhoidectomy for prolapsing haemorrhoids. RESULTS: Each had a successful procedure without complications. CONCLUSION: Ligasure haemorrhoidectomy can be safely performed in anticoagulated patients and reduces in-patient hospital stay.

The clinical importance and prognostic implications of microsatellite instability in sporadic cancer.

AIMS: The genetic abnormality known as microsatellite instability (MSI), first identified in colorectal cancer in 1993, has subsequently been recognised in other malignancies. These cancers are caused by a defect in the nuclear mismatch repair system, allowing mutations to accumulate with every cellular division. Hereditary Non Polyposis Colon Cancers (HNPCC) and associated malignancies demonstrating MSI have a unique histological appearance, improved prognosis and altered response to chemotherapy and radiotherapy. This review examines the incidence of MSI and its clinical significance in commonly occurring solid malignancies. METHOD: A medline based literature search was performed using the key words 'Microsatellite Instability' and the name of the specific malignancy being investigated. Additional original papers were obtained from citations in those articles identified in the original medline search. RESULTS: MSI has been detected in many solid malignancies although the definition of instability applied has been variable. It is most commonly found in sporadic malignancies that also occur in the HNPCC syndrome such as colorectal, stomach, endometrial and ovarian cancer. MSI may impart a favorable prognosis in colorectal, gastric, pancreatic and probably oesophageal cancers but a poor prognosis in non small cell lung cancer. In clinical studies colorectal cancers demonstrating MSI respond better to chemotherapy while in vitro studies using MSI positive cell lines show resistance to radiotherapy and chemotherapy. CONCLUSION: MSI may be a useful genetic marker in prognosis and could be an influential factor in deciding treatment options. However, in many cancers its significance remains unclear and more evaluation is required.

Pathogenesis and clinical management of hereditary non-polyposis colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited genetic condition associated with microsatellite instability; it accounts for around 5 per cent of all cases of colorectal cancer. This review examines recent data on management strategies for this condition. METHODS: A Medline-based literature search was performed using the keywords 'HNPCC' and 'microsatellite instability'. Additional original papers were obtained from citations in articles identified by the initial search. RESULTS AND CONCLUSION: The Amsterdam criteria identify patients in whom the presence of an inherited mutation should be investigated. Those with a mutation should be offered counselling and screening. The role of prophylactic surgery has been superseded by regular colonoscopy, which dramatically reduces the risk of colorectal cancer. Screening for extracolonic malignancy is also advocated, but the benefits are uncertain. Chemoprevention may be of value in lowering the incidence of bowel cancer in affected patients, but further studies are required.