The expression of cMET/hepatocyte growth factor receptor in colorectal cancer

In this study, we estimated the expression of c-MET/Hepatocyte Growth Factor receptor in colorectal cancers by immunohistochemistry. In 118 patients, c-MET wee expressed in 65 patients (55%). About the clinicopathological findings of metastasis, the proportion of c-MET-positive in the patients with liver metastasis, 78% (18/23), was significantly higher than that without liver metastasis, 49% (47/95), but there was no significant difference about lymph node metastasis and peritoneal dissemination. About the pathological findings of primary lesion, the proportion of c-MET-positive in the patients with infiltration into lymphatic vessels, 63% (48/76), was significantly higher than that without infiltration, 40% (17/42), but there was no significant difference about infiltration into veins. The proportion of c-MET-positive increased as the tumor stage proceeded from t1 to t4 and as the histopathological stage proceeded from I to IV. These results suggest that c-MET may play an important role in the growth and scattering of colorectal cancer cells.     

Cholesterolemia in colorectal cancer

BACKGROUND/AIMS: Colorectal cancer incidence is higher in developed countries. High fat intake is one of the risk factors. However, many studies observed lower cholesterol serum levels on diagnosis of colorectal cancer. The aim of this assay was to study the serum cholesterol levels in patients with colorectal cancer and compare these values with individuals of the same age and sex. METHODOLOGY: Cholesterol serum levels of 85 patients with colorectal cancer were determined. Each of the patients with colorectal cancer were matched with an individual without cancer of the same age and sex. Total cholesterol concentrations were determined using an enzymatic colorimetric method. RESULTS: The mean serum of cholesterol was 183.4 for the colorectal group and 209.7 for the control group. This difference was statistically significant. This difference was more evident in patients with colon cancer and older than 60 years of age. There was no difference between the different Dukes' stage. CONCLUSIONS: Our study suggest an association between low blood cholesterol and colorectal cancer. We believe that the lower level of cholesterol observed in these patients is a consequence between the difference of colorectal carcinogenesis.     

Adjuvant intra-arterial chemotherapy with gastrin receptor antagonist after hepatic resection in colorectal cancer metastasis

The aim of this study was to determine whether chemo-endocrine therapy after the resection of liver metastasis from colorectal cancer would prevent recurrence in the remnant liver and prolong survival. Eleven colorectal cancer patients underwent hepatic resection for liver metastasis. Subsequently, they were administered Proglumide gastrin antagonist 1,200 mg/day + 5'-DFUR 800 mg/day for 2 years. In seven of them, MMC 6-10 mg and ADM 20 mg were infused intra-arterially every two weeks alternately for one year. In four of them, 5-FU 250 mg/day was infused for seven days continuously intra-arterially every two weeks for one year. Recurrence in the remnant liver occurred in four of 11 patients. All of these patients underwent repeated hepatectomy. The mean disease-free survival in the remnant liver was 37 months and the five-year survival rate was 91%. These results indicate that intra-arterial chemotherapy with gastrin receptor antagonist might be effective for adjuvant therapy in patients with resectable liver metastasis from colorectal cancer.     

Vitamin D receptor expression as a predictive marker of biological behavior in human colorectal cancer

To date, none of the potential biological markers in colorectal cancer attempts to link the epidemiological data with the molecular biology of the disease. In an attempt to link dietary and epidemiological factors and to obtain a better understanding of the molecular biology of colorectal cancer, we measured vitamin D receptor (VDR) expression in 75 human colorectal cancers as a potential predictive marker of the biological behavior of the disease. Our results showed that a high level of VDR expression was associated with a favorable prognosis. The results of the studies reinforce the potential role that VDR may play in the development of the pathogenesis of colorectal cancer. Larger studies looking exclusively at stage I and stage II disease will hopefully lead to the development of a sensitive hormonal marker that can be used to predict the biological behavior of colorectal cancer, identifying at-risk patients in need of adjuvant treatment.     

Integrated imaging in colorectal cancer

BACKGROUND: Although most aspects of the consultation have been extensively reported there is very little information on the effects of interruptions on the consultation. OBJECTIVE: We wished to discover the patients' view of interruptions. METHODS: In this pilot study the sources and frequency of interruptions to the consultations of a single general practitioner were measured. The effects of interruptions on 102 patients whose consultations were interrupted were then ascertained using a simple questionnaire. RESULTS: The overall interruption rate was found to be 10.2%. The telephone was the commonest source of interruption, accounting for 50% of interruptions. Although most patients did not perceive the interruption as having an important effect on the consultation, 20% of patients did feel that the interruption had a bad effect on the consultation and 40% of patients felt it would have been better not to have been interrupted. A majority of patients (52%) did not feel that the reason for the interruption was important. Although most patients did not feel affected by the interruption, a significant minority (18%) of patients had a strongly negative emotional response to the interruption. CONCLUSIONS: In view of these findings the need for further work has been highlighted.     

Calcium chemoprevention in colorectal cancer

BACKGROUND/AIMS: There are genetic, endoengenous, and exogenous factors responsible for colorectal cancer. Calcium may play a chemopreventive role in high risk groups. Binding fatty and biliary acids and their reduced absorbtion, with a consequent decrease of proliferative stimulation and reduction of secondary carcinogenic compounds, may explain this role. MATERIAL AND METHODS: 175 patients with adenomatous polyps after polypectomy and with calcium chemoprevention were evaluated for polyps recurrence. Another three groups of patients with colorectal cancer without chemoprevention (A,B) and with chemoprevention (group C) were followed concerning survival after surgery. RESULTS: The cumulative survival rate of patients after surgery due to colorectal carcinoma is significantly higher in a calcium chemopreventive group. Adenomatous polyps recurrences after polypectomy are lower (12.9%) in the chemoprevention group than in the group without prevention (55%) with a mean time of follow-up 3.1 yrs. CONCLUSIONS: Calcium is an important chemopreventive agent in adenomatous polyps after polypectomy and after colorectal surgery for colorectal cancer.     

Molecular biology of colorectal cancer and clinical consequences for colorectal cancer syndromes

Because of the accomplishments in biotechnical research in the past few decades our knowledge about the molecular mechanisms of carcinogenesis has grown rapidly. Colorectal cancer has been one of the most intensively investigated tumor entities, and it seems to be well established that colorectal tumor growth is associated with an accumulation of acquired somatic mutational events in tumor suppressor genes and oncogenes. Recent progress in our understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Identification and characterization of the causative genes for these colorectal cancer syndromes have enabled precise presymptomatic detection of mutations in individuals who bear an a priori risk of about 50% of developing colorectal cancer. Genotype-phenotype correlations might further increase the clinical management of hereditary colorectal cancer. Even though developments in cancer research are restricted to the minority of individuals with hereditary cancer syndromes, growing knowledge about the effect of low penetrance variations in tumor suppressor genes may affect the diagnosis and therapy of sporadic colorectal cancer.     

Carcinoembryonic antigen in metastatic colorectal cancer

OBJECTIVE: To determine the reliability and validity of the carcinoembryonic antigen (CEA) level in following the response of tumours to chemotherapy in patients with metastatic colorectal cancer. At present, CEA has an accepted role in detecting recurrence of colorectal cancer following complete resection. DESIGN: Retrospective case series. PATIENTS: Eighty-one patients with metastatic colorectal cancer seen at the Ottawa Regional Cancer Centre in 1992 whose CEA levels were above the upper limit of normal. MAIN OUTCOME MEASURES: Change in CEA levels as compared with the tumour response to chemotherapy (as assessed by radiologic studies, physical examination and surgery) and with survival. RESULTS: Over one-half of the CEA levels measured were not consistent with the tumour responses to chemotherapy. The sensitivity of CEA in following the tumour response was 0.54 (95% confidence interval [CI] 0.37 to 0.75) and the specificity was 0.53 (95% CI 0.42 to 0.63). A sample size of 2258 was calculated as necessary to determine the minimum number for establishing the reliability of CEA in measuring tumour response to chemotherapy. Survival was analyzed using the Kaplan-Meier method. CEA was found to have no statistical value in determining survival in this group of patients (p = 0.09). Sample size was calculated for the survival statistics; an adequate sample size was used in this study (the minimum necessary being 20). CONCLUSION: Neither this study nor a review of the literature supports the use of the CEA level in the setting of metastatic colorectal cancer. Sample size calculations discourage the implementation of a large prospective trial to investigate this topic further.     

Improved tumor staging in colorectal cancer

Paratesticular rhabdomyosarcoma is a highly malignant neoplasm and is exceedingly rare in adults. Thus, its biological behavior is unclear and there is no standard established treatment. The prognosis of recurrent paratesticular rhabdomyosarcoma is dismal in the elderly. Herein we describe a case of locally recurrent paratesticular rhabdomyosarcoma in a 68-year-old patient treated with surgery and radiotherapy.     

Anemia in patients with colorectal cancer

Although anemia is one of the signs of colorectal cancer, the relationships between histological findings and hematological findings other than hemoglobin level have not been adequately investigated. We investigated the relationship between hematological findings, serum iron, and histological findings in 358 patients (207 men and 157 women) with colorectal cancer. Their mean (+/-SD) ages were 64.3 +/- 12.4 and 63.8 +/- 13.3 years. A hemoglobin level of less than 10 g/dl was the criterion for anemia, and 20.8% of the men and 25.8% of the women met this criterion. Univariate analysis showed that carcinoma of the cecum, ascending colon, and transverse colon; large-size carcinoma, invasion beyond the proper muscle layer; positive lymph node metastasis: and clinical stage (Dukes' B, C, and D) were factors associated with high incidence of anemia. Histological type did not affect the hematological findings. Multivariate analysis showed that age, tumor site, and tumor size were significant factors related to anemia. Depth of invasion, the presence or absence of lymph node metastasis, and Dukes' classification were not significant factors. In the presence of these factors, mean corpuscular volume and mean corpuscular hemoglobin concentration values were low, and red blood cells were microcytic and hypochromic. The incidence of a low serum iron level was about twice the frequency of a hemoglobin level of less than 10 g/dl. The results of the multivariate analysis showed that none of the factors were significantly related to iron deficiency.     

Screening for colorectal cancer

Second only to lung cancer in mortality, colon cancer is amenable to cure if detected early. Because fecal occult blood testing and flexible sigmoidoscopy are effective individually but have limitations, both are now recommended for screening. However, after successful polyp removal, surveillance colonoscopy does not need to be performed as often as previously thought.     

Biomodulation of Fluorouracil in colorectal cancer

5-Fluorouracil (5-FU) remains the agent of choice for the treatment of colorectal cancer. Research has focused on the biomodulation of 5-FU in order to attempt to improve the cytotoxity and therapeutic effectiveness of this drug in the treatment of advanced colorectal cancer. Modulation of 5-FU by methotrexate (MTX), trimetrexate (TMTX), interferon-alpha (IFN-alpha), leucovorin (LV), or N-(phosphonacetyl)-L-asparte acid (PALA) has produced higher response rates than those observed with 5-FU alone. Methotrexate may improve the durability of response to or survival with 5-FU, but with inferior results compared with those in trials of 5-FU and leucovorin. Trimetrexate produces a number of responses, and further phase III trials are in progress to confirm the results of promising phase II trials with this drug. IFN-alpha has shown therapeutic efficiency when combined with 5-FU alone or with 5-FU and leucovorin, but latest studies with these combinations have shown increased toxicity. Initial single-institution phase I trials with 5-FU and PALA reported promising responses, but the latter responses with PALA were not substantiated in randomized multicenter trials. Leucovorin enhances the cytotoxic activity of 5-FU in vitro and in vivo, and several clinical trials have shown improved response rates and possible trends in improved survival when such therapy is compared with the use of 5-FU as a single-agent. More recent randomized trials have focused their attention on determining the optimal dose and schedule with this combination for producing a better clinical response with minimal toxicity. Schedules using infusional 5-FU appear to be the most active regimens when 5-FU is used as a single agent, as demonstrated by recent randomized trials. The Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) have performed separate randomized trials and have shown that the optimal regimens employ infusional 5-FU as a single agent, and that these are the least toxic regimens, perhaps more effective, and associated with a better quality of life. Future studies will focus on infusional regimens involving either short-term, high-dose protracted or long-term, low-dose protracted infusion of 5-FU, since these regimens have shown the most favorable toxicity spectrum and produced the longest survival times. Future research will also focus on the evaluation of various methods of delivery of 5-FU, including oral administration of the drug in combination with compounds that can modify its catabolism.     

Ki-ras mutations and prognosis in colorectal cancer

A total of 191 colorectal adenocarcinomas, obtained from consecutive patients with a median follow-up of 6 years, were studied in order to evaluate the possible association of Ki-ras mutations with tumour stage, tumour differentiation and survival time. Resected full-cross tumour samples were screened for Ki-ras mutations in codons 12 and 13 using temporal temperature gradient gel electrophoresis (TTGE). Ki-ras mutations were detected in 62 (32%) of the samples. The most frequent mutation, observed in 21 samples, was from GGT to GAT changing glycine to aspartic acid in codon 12. The study did not show any association between Ki-ras mutations and Dukes' stage or tumour differentiation. Patients with Ki-ras mutations had a marginally shorter survival time (median 50 months) compared with patients without (median 59 months), but the difference was not statistically significant. The results indicate that Ki-ras gene mutations have no relevant prognostic importance in this cohort of colorectal cancer patients.