Long-term follow-up of a randomized clinical trial of open versus laparoscopic appendicectomy.

BACKGROUND: The aim of this study was to assess long-term outcome following open versus laparoscopic appendicectomy. METHODS: A total of 105 patients with suspected acute appendicitis were randomized to LA (51) or OA (54) between 1997 and 1999 at one hospital. Perioperative factors and follow-up data from the outpatient clinic were recorded. Information about symptoms and overall satisfaction was obtained by telephone interview. In addition, appendicectomy data for 2008 were analysed retrospectively for comparison in a contemporary setting. RESULTS: Data from 52 patients who had OA and 47 who had LA were analysed. OA was performed mostly by trainees, but LA was more likely to be undertaken by a consultant. The open procedure was quicker than the laparoscopic operation in the trial period (median 38 versus 65 min respectively; P < 0.001), but the difference was only 10 min in 2008. The OA group returned to work later than the LA group (median 13 versus 8 days; P = 0.013) and had more complications (22 versus 6; P = 0.014). Only one patient (OA) had a reoperation, owing to abdominal adhesions. Among 76 patients available for telephone interview, satisfaction scores were marginally higher for LA than OA. CONCLUSION: LA has some advantages compared with an open approach. REGISTRATION NUMBER: NCT00908804 (http://www.clinicaltrials.gov).

Population-based molecular detection of hereditary nonpolyposis colorectal cancer.

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.

Microsatellite instability in adenomas as a marker for hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common of the well-defined colorectal cancer syndromes, accounting for at least 2% of the total colorectal cancer burden and carrying a greater than 80% lifetime risk of cancer. Significant reduction in cancer morbidity and mortality can be accomplished by appropriate clinical cancer screening of HNPCC patients with mutations in mismatch repair (MMR) genes. Thus, it is desirable to identify individuals who are mutation-positive. In individuals with cancer, mutation detection can be accomplished relatively efficiently by germline mutation analysis of individuals whose cancers show microsatellite instability (MSI). This study was designed to assess the feasibility of screening colorectal adenoma patients for HNPCC in the same manner. Among 378 adenoma patients, six (1.6%) had at least one MSI adenoma. Five out of the six patients (83%) had a germline MMR gene mutation. We conclude that MSI analysis is a useful method of prescreening colorectal adenoma patients for HNPCC.

Prognostic factors in human pancreatic cancer, with special reference to quantitative histology.

A retrospective clinicopathologic study was done on 111 patients with a pancreatic ductal adenocarcinoma. The mean follow-up period was 6 years. By means of interactive morphometry six nuclear morphometric features were measured in biopsy specimens from the primary tumours. Volume-corrected mitotic index (M/V index) was estimated in the same sections. Histologic grading was done in accordance with the WHO. The M/V index (p = 0.002), the nuclear area of the 10 largest nuclei (NA10) (p = 0.025), the histologic grade (p = 0.0956), the nuclear area (NA) (p = 0.038), the standard deviation of the nuclear perimeter (SDPE) (p = 0.033), and the standard deviation of the nuclear area (SDNA) (p = 0.0430) predicted survival in univariate analysis. The type of surgery performed was a significant prognosticator too (p = 0.0131). A multifactor regression analysis of survival including clinical and histologic factors identified the M/V index as the most important prognosticator (p = 0.009), followed by the type of surgery performed (p = 0.022). Other histologic factors had no independent prognostic value. Our results suggest the use of morphometric features instead of the conventional histologic grading in predicting survival of pancreatic ductal adenocarcinoma.