B. P. C. Lin

Aspartate aminotransferase: alanine aminotransferase ratio in chronic hepatitis C infection: is it a useful predictor of cirrhosis?

Background : The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST : ALT ≥ 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non‐cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST : ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis.

Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer

PURPOSE The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O(6)-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. PATIENTS AND METHODS The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation. RESULTS We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. CONCLUSION MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.

Promoter methylation of the mutated in colorectal cancer gene is a frequent early event in colorectal cancer

The mutated in colorectal cancer (MCC) gene is in close linkage with the adenomatous polyposis coli (APC) gene on chromosome 5, in a region of frequent loss of heterozygosity in colorectal cancer. The role of MCC in carcinogenesis, however, has not been extensively analysed, and functional studies are emerging, which implicate it as a candidate tumor suppressor gene. The aim of this study was to examine loss of MCC expression due to promoter hypermethylation and its clinicopathologic significance in colorectal cancer. Correspondence of MCC methylation with gene silencing was demonstrated using bisulfite sequencing, reverse transcription–polymerase chain reaction and Western blotting. MCC methylation was detected in 45–52% of 187 primary colorectal cancers. There was a striking association with CDKN2A methylation (P<0.0001), the CpG island methylator phenotype (P<0.0001) and the BRAF V600E mutation (P<0.0001). MCC methylation was also more common (P=0.0084) in serrated polyps than in adenomas. In contrast, there was no association with APC methylation or KRAS mutations. This study demonstrates for the first time that MCC methylation is a frequent change during colorectal carcinogenesis. Furthermore, MCC methylation is significantly associated with a distinct spectrum of precursor lesions, which are suggested to give rise to cancers via the serrated neoplasia pathway.

Correlates and outcomes of tumor adherence in resected colonic and rectal cancers.

Objectives:The aims of this study were to examine the associations between tumor adherence and other operative findings, postoperative complications, recurrence, and survival after resection of colorectal cancer. Summary Background Data:The prognostic importance of tumor adherence to other organs or structures, either by direct invasion (T4) or simply by inflammatory adhesions, is yet to be clearly defined as earlier studies have been limited in size or have not used contemporary multivariable statistical techniques. Methods:Data were drawn from a comprehensive, prospective hospital registry of all resections for colorectal cancer between January 1971 and December 2000 with follow-up to December 2005. Statistical analysis employed the &khgr;2 test, Kaplan-Meier estimation, and proportional hazards regression with a significance level of <0.05 and 95% confidence intervals (CI). Results:Tumor adherence was identified in 268 of 2504 resections (10.7%). Adherent tumors were more likely than nonadherent tumors to be spontaneously or surgically perforated or transected, to have nodal metastases and to be poorly differentiated. Venous invasion was more frequent in adherent colonic but not rectal tumors. Adherence was associated with only 5 of 16 medical and surgical complications considered. In rectal cancer, adherence was independently associated with pelvic recurrence (hazard ratio 1.8, 95% CI 1.2–2.7) and diminished survival (hazard ratio 1.6, 95% CI 1.3–2.0) after adjustment for other variables. Conclusion:In rectal cancer, tumor adherence indicates a poor prognosis after adjustment for other prognostic factors, regardless of whether actual tumor invasion of the adherent structure has occurred. However, adherence is not associated with survival after resection of colonic cancer.

The significance of involvement of a free serosal surface for recurrence and survival following resection of clinicopathological stage B and C rectal cancer

Objective  To determine whether the presence of tumour at a free serosal surface was independently associated with pelvic recurrence or survival in patients who had a resection for clinicopathological stage B or stage C rectal cancer and who had not received adjuvant therapy.

Assessing the evidence for an association between circumferential tumour clearance and local recurrence after resection of rectal cancer

Objective  Circumferential resection margin involvement (CRMI) after resection of rectal cancer is regarded as a risk factor for local recurrence. We have been able to identify only nine peer‐reviewed English‐language publications which focus primarily on this association, and they report widely differing rates of local recurrence. The aims of this study were to review possible reasons for this variability and to assess the evidence for the micrometrically measured threshold defining CRMI.

Case report: gastrointestinal tuberculosis simulating Crohn's disease.

A male Caucasian presented with abdominal pain and a right iliac fossa mass. There were no risk factors for Mycobacterium tuberculosis infection. He was investigated by upper and lower gastrointestinal endoscopy, chest and small bowel radiology. The latter showed stricturing of the third and fourth parts of the duodenum, mid‐jejunum and terminal ileum. Biopsies were non‐specific and he was thought to have Crohns disease. Subsequent treatment with corticosteroids resulted in improved well being and weight gain; however, the patient demonstrated disease progression with the development of complex fistulae and Escherichia coli septicaemia. At surgery the patient was found to have an ileal inflammatory mass with fistulae to the sigmoid colon. The terminal ileum, fistulae and a segment of colon were resected. Treatment with anti‐tuberculous drugs ensued and the patient is now asymptomatic after 15 months of follow‐up. This case serves to highlight the difficulty in making the diagnosis of gastrointestinal tuberculosis, a disease that may mimic Crohns disease, and the need for caution in the use of corticosteroids in any disease in which tuberculosis enters into the differential diagnosis. The role of surgery in making the diagnosis and managing the complications, in conjunction with anti‐tuberculous drugs, and the prospect of cure are exemplified by this case.

Fascin expression predicts survival after potentially curative resection of node-positive colon cancer.

Fascin, an actin-bundling protein, is expressed in many neoplasms including colorectal cancer. It is considered to be a mediator of tumor cell invasion and an indicator of aggressive phenotype; however, there are few reports on the association between fascin and prognosis in colorectal cancer. The aims of this study were to: (a) investigate the expression of fascin in the central part of the tumor and at the invasive front in patients who had a potentially curative resection for node-positive colonic carcinoma; (b) examine the method of scoring fascin expression; and (c) investigate the association between fascin expression and overall survival and other clinicopathologic features. Fascin expression was assessed by immunostaining of microarrays from archived tissue of 470 patients who were followed for a minimum of 5 years after resection. Other clinicopathologic data had been recorded prospectively according to a standardized protocol. Analysis of overall survival was by the Kaplan-Meier method and Cox regression. For both central tumor tissue and the invasive front, it was found that the percentage of stained cells was a sufficient measure of fascin expression in relation to survival, with staining intensity providing no significant additional information. At both levels, there was a significant independent association between high fascin expression and diminished survival, although this association was much stronger in the central region (adjusted hazard ratio 1.6, P<0.001) than at the invasive front (adjusted hazard ratio 1.1, P=0.044). Fascin expression predicted overall survival but did not displace other routinely collected clinicopathologic predictors.

The 13C-caffeine breath test distinguishes significant fibrosis in chronic hepatitis B and reflects response to lamivudine therapy

Background : The 13C‐caffeine breath test is a non‐invasive, quantitative test of liver function.

Transitional cell carcinoma of the nasolacrimal sac

Tumors in the lacrimal sac are rare yet important due to their malignant and potentially lethal outcomes if there is a misdiagnosis or delay in treatment. Epithelial tumors predominate with squamous cell carcinoma. We report a transitional cell carcinoma of the lacrimal sac and management course for the patient.