FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Immunoblot analysis of c-Met expression in human colorectal cancer: Overexpression is associated with advanced stage cancer

c-Met, the receptor of hepatocyte growth factor is known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. To investigate the significance of c-Met expression in human colorectal cancer (CRC), total cellular protein, extracted from 130 CRCs were examined by Western blot analysis. The signal was quantitated by ChemiImager™ 4000 Low Light Imaging System. c-Met expression was analyzed as the ratio of tumor to matched normal tissue (T/N) and expressed as fold-increase. The cellular localization of c-Met was assessed by immunohistochemistry. The T/N fold increase of c-Met varied from 0.2 to 10.7 with a mean of 3.41 ± 0.23 (mean ± SE). 69% primary CRC showed overexpression (T/N >2.0) of c-Met. Significantly higher c-Met levels were found in CRC with blood vessel invasion (P = 0.04), and in advanced stage (P = 0.04). No relationship was noted between c-Met expression and age, tumor size, location, differentiation. C-Met immunoreactivity was observed in the membrane and cytoplasm of cancer cells. Positive staining of endothelial cells of blood vessels within normal submucosa and tumor was also evident. C-Met protein is expressed at levels significantly higher than adjacent mucosa in most primary adenocarcinomas of the colon. Our results support an important role for c-Met in human CRC progression and metastasis.     

Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1H MRS study

Hepatic steatosis is a hallmark of chemotherapy‐induced liver injury. We made serial ¹H MRS measurements of hepatic lipids in patients over the time course of a 24‐week chemotherapeutic regimen to determine whether ¹H MRS could be used to monitor the progression of chemotherapy‐induced steatosis. Thirty‐four patients with stage III or IV colorectal cancer receiving 5‐fluorouracil, folinic acid and oxaliplatin (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n = 13) were studied prospectively. ¹H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A ¹H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat + water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty‐seven patients completed baseline, 6‐week and 24‐week ¹H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6‐week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial ¹H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy‐associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks. Copyright © 2012 John Wiley & Sons, Ltd.     

Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.     

Metastatic Epithelioid Gastrointestinal Stromal Tumor: Yet Another Tumor with Anemone Cell Features

Since 1980 when Sibley and coworkers first described a nodal neoplasm of unknown histogenesis with striking surface microvilli for which they introduced the term "anemone cell," a series of reports have appeared in the literature illustrating tumors with similar ultrastructural features. While most reported cases showed differentiation along a particular line, rare cases remained histogenetically unclear. In this report a case is described of epithelioid gastric gastrointestinal stromal tumor metastatic to the liver, showing conspicuous long microvillus-type cell processes partially or circumferentially coating the cell surfaces, thus qualifying as yet another tumor type with anemone cell features.     

The Association between Glomerular Hyperfiltration and Left Ventricular Structure and Function in Patients with Primary Aldosteronism

Background: Glomerular hyperfiltration has been recently noticed as an important issue in primary aldosteronism (PA) patients. However, its effect on the cardiovascular system remains unknown.Methods: We prospectively analyzed 47 PA patients including 11 PA patients with estimated glomerular filtration rate (eGFR) > 130 ml/min per 1.73 m² (group 1), and 36 PA patients with eGFR 90-110 ml/min per 1.73 m² (group 2). Fourteen essential hypertension (EH) patients with eGFR 90-110 ml/min per 1.73 m² were included as the control group (group 3). Echocardiography including left ventricular mass index (LVMI) measurement and tissue Doppler imaging (TDI) was performed. Predicted left ventricular mass (LVM) was calculated. Inappropriate LVM was defined as an excess of > 35% from the predicted value.Results: The value of LVMI decreased significantly in order from groups 1 to 3 (group 1>2>3). While group 2 had a significantly higher percentage of inappropriate LVM than group 3, the percentage of inappropriate LVM were comparable in groups 1 and 2. Group 1 had a higher mitral E velocity, E/A ratio than that of group 2. In the TDI study, the E/E'' ratio also decreased significantly in order from groups 1 to 3 (group 1>2>3). Group 2 had lower E'' than that of group 3, although the E'' of group 1 and 2 were comparable.Conclusions: Although PA patients with glomerular hyperfiltration were associated with higher LVMI, higher mitral E velocity, higher E/E'' ratio, they had comparable E'' with PA patients with normal GFR. This phenomenon may be explained by higher intravascular volume in this patient group.     

Lymph node metastasis in T1 adenocarcinoma of the colon and rectum

The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n = 428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0–18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p = .04) or right colon (3/92, 3%, p = .003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004