Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?

Purpose

The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.

Methods

A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.

Results

A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (n?=?64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of MSH2 on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.

Conclusions

Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.     

Total Thyroidectomy and Low-Risk Thyroid Cancer: Are We Treating the Surgeon or Patient?

Annals of Surgical Oncology -     

Asymptomatic Colorectal Cancer with Un-Resectable Liver Metastases: Immediate Colorectal Resection or Up-Front Systemic Chemotherapy?

Background About 20% of patients with colorectal cancer have synchronous un-resectable liver metastases. Resection of colorectal cancer in patients with moderate-severe symptoms is mandatory before starting chemotherapy. Surgical treatment of asymptomatic colorectal cancers is still a matter of discussion. Methods From January 2000 to December 2004, we prospectively collected data on 35 consecutive patients who were treated straightaway by chemotherapy without primary tumor resection. All patients underwent FOLFOX6 as first-line chemotherapy. The aim of the study was to evaluate the rate of surgical complications related to un-resected colorectal tumor. Results The mean interval between diagnosis and start of chemotherapy was 23.1 days (95% CI: 17.3–28.8). Fifteen of the 35 patients (42.9%) were down-staged to surgery; the mean interval between chemotherapy start and colon-rectum cancer resection was 6.5 months (95% CI: 5.5–7.5). None of them developed complications related to the primary tumor during chemotherapy. Of the other 20 patients who did not undergo any curative surgery, 16 received a second line chemotherapy and 10 a third line: six patients are alive and without intestinal symptoms (mean follow up 22.5 months, 95% CI: 11.2–33.9). Only one patient (2.8%) developed clinical signs of intestinal occlusion 5.6 months from the start of chemotherapy and required urgent colostomy. Conclusions The rate of complications related to the non-resected colorectal tumor is very low using oxaliplatin as first line chemotherapy. Non-operative management of asymptomatic colorectal cancers with un-resectable liver metastases is a safe approach.     

Should We Replace the Gleason Score with the Amount of High-Grade Prostate Cancer?

OBJECTIVES: The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system. We investigated the predictive value of the amount of high-grade cancer (Gleason growth patterns 4/5) in the biopsy for prostate-specific antigen (PSA) and clinical relapse after radical prostatectomy. METHODS: PSA-tested participants (N=281) of the European Randomized Study of Screening for Prostate Cancer (ERSPC) who underwent radical prostatectomy were analyzed. Besides clinical features, and serum-PSA, histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome. RESULTS: At a median follow-up of 7 yr, 39 (13.9%), 24 (8.5%), and 12 (4.3%) patients had PSA >/=0.1 ng/ml, PSA >/=1.0 ng/ml, and clinical relapse after radical prostatectomy, respectively. Using Cox proportional hazards, PSA level (p=0.002), length of tumour (p=0.040), and length of high-grade cancer (p=0.006) in the biopsy, but not Gleason score, were independent prognostic factors for biochemical relapse (PSA >/=0.1 ng/ml) when assessed as continuous variables. In radical prostatectomies, the proportion of high-grade cancer (p<0.001) was most predictive of relapse (PSA >/=0.1 ng/ml). For PSA >/=1.0 ng/ml and clinical relapse, the amount of high-grade cancer, both in the biopsy specimen (p=0.016 and p=0.004, respectively) and radical prostatectomy specimen (p=0.002 and p=0.005, respectively), but not Gleason score, was an independent predictor. CONCLUSIONS: In biopsy and radical prostatectomy specimens of surgically treated prostate cancer, the amount of high-grade cancer is superior to the Gleason grading system in predicting patient outcome. We propose that, in addition to the Gleason score, the amount of Gleason growth patterns 4/5 in the biopsy (whether absolute length or proportion) should be mentioned in the pathology report.