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PubMed1999

Carcinogenesis of intestinal-type gastric cancer and colorectal cancer is commonly accompanied by expression of brain (fetal)-type glycogen phosphorylase.

Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the role of this molecule in the gastrointestinal carcinogenesis. The only isoform expressed in gastric cancer was brain-type GP (BGP) using polymerase chain reaction (PCR) analysis. The expression of BGP, oncogene products and proliferating cell nuclear antigen in the gastric and colorectal carcinomas, their premalignant lesions, and the normal mucosa were examined using 136 gastric and 96 colorectal surgically resected specimens, and 55 endoscopically resected colorectal adenomas. The BGP visualized by immunohistochemistry was commonly present in intestinal-type gastric (80.6%) and colorectal (83.3%) carcinomas, whereas no BGP expression was seen in the normal human gastric and large intestinal mucosa except in the BGP foci described below. IMs with BGP had close correlation with intestinal-type gastric carcinoma, and some of them coexpressed accumulated p53 protein. The expression of BGP during 'adenoma carcinoma sequence' (ACS) showed excellent correlation with the increased dysplasia and was found prior to p53 expression. Positive staining in overtly normal looking colonic mucosa (BGP foci) was observed mainly around carcinomas without any adenoma component, and frequent p53 mutation (41.2%) was detected in the BGP foci using PCR-single strand conformation polymorphism analysis. It is suggested that BGP is a novel biomarker for carcinogenesis in the intestinal-type gastric carcinoma and in both of the pathways of ACS and the 'de novo' colorectal carcinoma.

Adenocarcinoma↗
PubMed1999

Suspected hereditary nonpolyposis colorectal cancer: International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) criteria and results of genetic diagnosis.

PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (<40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged <50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged <50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.

Age of Onset↗
PubMed2006

[Inflammatory bowel disease and colorectal cancer].

The colorectal cancer is one of the most serious complication of inflammatory bowel disease. Longer duration of the disease, extensive colitis, primary sclerosing cholangitis, family history of colorectal cancer are the main risk factors. The relative risk of colorectal cancer in ulcerative colitis is increased, however, there're marked geographically differences. Relative risk of colorectal cancer is 2.5 and small bowel cancer risk is 31.2 in Crohn's disease. There aren't prospective, randomized, controlled trials that definitively prove the benefit of surveillance of colorectal cancer in IBD. Colonoscopy improve the 5-year survival rate, however, there is no evidence for the reduction of mortality. Meta-analysis showed efficacy of mesalamine in the reduction of risk of colorectal cancer, but prospective trials have been missed. Chemoprotective role of other immunomodulators has not been proven yet.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Clinical characteristics of patients with sporadic colorectal cancer and primary cancers of other organs.

Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up.

Aged↗
PubMedDate not supplied

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.

Adult↗
PubMed1994

High frequency of allelic deletion on chromosome 17p in advanced colorectal cancer.

BACKGROUND: Colorectal cancers often show allelic loss of chromosomes 5q and 17p, regions where the tumor suppressor genes p53 and adenomatous polyposis coli are known to reside. Currently, the inactivation of tumor suppressor genes and the activation of oncogenes are considered major events involved in tumor development. According to a recent genetic model, ras gene mutations and allelic deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q deletions are late changes in colorectal tumorigenesis. It has been shown that 17p and 18q deletions are associated with an increased tendency of disease dissemination in colorectal cancer. Most of the studies on allelic deletion in colorectal cancer were undertaken with Western population cohorts. The authors examined the association of chromosomes 5q and 17p deletions with clinical parameters, including metastasis in a predominantly Chinese population with a high incidence of colorectal cancer. METHOD: Allelic deletion was studied with the restriction fragment length polymorphism technique in tumors from 102 and 100 sporadic colorectal cancer cases for chromosomes 5q and 17p, respectively. Probes pi 227 and ECB27 were used for chromosome 5q, and probe YNZ22.1 was used for chromosome 17p. RESULTS: 5q Deletion was found in 33% of informative cases, whereas 17p deletion was seen in 69% of informative cases. 17p Allelic loss showed significant association with Dukes' Stage D as well as the presence of distant metastasis, whereas 5q deletion showed no such association. CONCLUSION: Allelic loss on chromosome 17p may be a useful prognostic marker in cases of colorectal cancer.

Adult↗
PubMedDate not supplied

Clinical features of second other-site primary cancers among sporadic colorectal cancer patients--a hospital-based study of 3,722 cases.

BACKGROUND/AIMS: Although synchronous and metachronous colorectal cancers are now well known to all colorectal surgeons, second other-site primary cancers following colorectal cancer are unfamiliar to most colorectal physicians. Knowledge of the clinical characteristics of these second other-site primary cancers becomes important especially during their follow-up surveillance. METHODOLOGY: Information from a computer database was retrieved. Medical records were reviewed and all histopathological data were confirmed. RESULTS: Forty-seven (1.26%) patients developed second other-site primary cancers. Of these patients, 22 (46.8%) patients were diagnosed concordantly while 25 (53.2%) patients were discordant cases. Twelve of 25 (45%) discordant cases were found within one year postoperatively. Regarding the clinical features of these 47 patients, male patients more frequently develop discordant cases (p=0.031). A significantly higher proportion of Dukes' B patients developed second other-site primary cancer than that of patients of other stages (p=0.017). Liver, 8 (17%) cases, was the most common site followed by the prostate, 6 (13%), stomach, 6 (13%), lung, 5 (11%), head and neck cancers, 5 (11%), and kidney, 3 (6.4%). However, there was not a significantly increased risk for these sporadic colorectal patients statistically. CONCLUSIONS: We described clinical features of second other-site primary cancers and emphasized that knowledge of these is important for their postoperative surveillance.

Colectomy↗
PubMed2001

Current status of laparoscopic surgery in colorectal cancer.

Laparoscopic colorectal procedures offer several benefits postoperatively, including reduction of pain, minimal impairment of pulmonary and gastrointestinal function, and improved reconvalescence. At present, laparoscopic resections for colorectal cancer are discussed controversially due to oncologic radicality, potential tumor dissemination, and the fundamental problem of port-site metastases. Oncologic standards of open surgery for colorectal cancer are not compromised by the laparoscopic technique. Short-term results of both retrospective and prospective trials comparing open with laparoscopic surgery for colorectal cancer showed comparable oncologic outcomes related to recurrence and survival. Despite extensive research efforts, neither the incidence of port-site recurrence nor its causes have been clarified definitely. However, according to the preliminary results of recently published studies, the problem of port-site metastases may not be an inherited detriment of laparoscopic surgery, but rather an unfortunate sequel to the learning curve of the application of laparoscopic surgery in colorectal cancer. Finally, as long-term results of prospective randomized trials are still missing, the crucial issue whether laparoscopic resection for colorectal cancer is oncologically equivalent to open surgery, cannot be answered definitely. Therefore, in the interim, laparoscopic curative resections in colorectal cancer are only to be offered within prospective randomized trials.

Clinical Trials as Topic↗
PubMed1999

Failure to diagnose hereditary colorectal cancer and its medicolegal implications: a hereditary nonpolyposis colorectal cancer case.

PURPOSE: We describe a patient who had precancerous colonic symptoms and a positive family history of multiple occurrences of early-onset colorectal cancer in her first-degree and second-degree relatives consistent with hereditary nonpolyposis colorectal cancer. Hereditary nonpolyposis colorectal cancer diagnosis had not been made before her diagnosis of carcinoma of the cecum with liver metastasis. She died at age 20, leading to litigation. Controversies about standards of care, their malpractice implications, and pertinent legal issues are discussed. METHODS: Review of the medical and family history was made by the expert witness (HTL) with appropriate documentation of the chronology of symptoms, as derived from depositions. These documents revealed that the patient's mother had repeatedly discussed with the caregivers her concern about the family history of colon cancer and the need for appropriate surveillance. RESULTS: The patient's colonic symptoms progressed for a period of three years. Flexible sigmoidoscopy was performed by a nonphysician. The physician who ordered the procedure considered this appropriate because isolated polyps were reported in the patient's father and paternal uncle, which apparently led him to believe that the diagnosis was familial adenomatous polyposis. During litigation procedures, a pedigree was constructed and found to be consistent with hereditary nonpolyposis colorectal cancer. The case was settled in favor of the plaintiff before trial. CONCLUSION: It is essential to understand the natural history of hereditary nonpolyposis colorectal cancer, inclusive of the need for surveillance colonoscopy in patients at increased risk by virtue of their position in their family pedigree.

Adenomatous Polyposis Coli↗
PubMed1998

National Cancer Institute Clinical Trials Program in Colorectal Cancer.

Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil (5-FU) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer. However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer.

Antimetabolites, Antineoplastic↗
PubMed2000

Surgery for colorectal cancer in elderly patients: a systematic review. Colorectal Cancer Collaborative Group.

BACKGROUND: The effectiveness of surgery for colorectal cancer depends on it being carried out safely, which allows most patients to return to productive lives, with an improved postoperative life expectancy, or at least one that is not diminished by the surgery. Because colorectal cancer is a major cause of morbidity and mortality in elderly people, we have examined how the outcomes of surgery in elderly patients differ from those in younger patients. METHODS: We did a systematic review of published and aggregate data provided by investigators. Studies were identified by computerised and manual searches of published and unpublished reports, scanning references, and contacting investigators. Within each study, outcomes for patients aged 65-74 years, 75-84 years, and 85+ years were expressed in relation to those aged less than 65 years. FINDINGS: From 28 independent studies, and a total of 34,194 patients, we found that elderly patients had an increased frequency of comorbid conditions, were more likely to present with later-stage disease and undergo emergency surgery, and less likely to have curative surgery than younger patients. The incidence of postoperative morbidity and mortality increased progressively with advancing age. Overall survival was reduced in elderly patients, but for cancer specific survival age-related differences were much less striking. INTERPRETATION: The relation between age and outcomes from colorectal cancer surgery is complex and may be confounded by differences in stage at presentation, tumour site, pre-existing comorbidities, and type of treatment received. However, selected elderly patients benefit from surgery since a large proportion survive for 2 or more years, irrespective of their age.

Age Factors↗
PubMed1992

The effect of family history of cancer, religion, parity and migrant status on survival in colorectal cancer. The Melbourne Colorectal Cancer Study.

The association between 5-year survival and several risk factors was investigated in 705 histologically confirmed, new cases of colorectal adenocarcinoma as one aspect of a comprehensive population-based study of large bowel cancer incidence, aetiology and survival--the Melbourne Colorectal Cancer Study. 5-year survival was not influenced by the previously determined risk of a family history of colorectal cancer in near-relatives. Similarly, other previously determined risk factors of religion, number of children, age at birth of first child and migrant status did not influence survival.

Adenocarcinoma↗
PubMedDate not supplied

Recent advances in colorectal cancer therapy.

Colorectal cancer is the second most common cause of cancer-related mortality in the United States. The American Cancer Society projects that there will be 107,300 new diagnoses of colorectal cancer in the United States in 2002, and 48,100 deaths will be attributed to colorectal cancer.(1) Although for decades there was only one chemotherapeutic agent with any meaningful activity in colorectal cancer, significant research in the last five years has identified several additional active agents. This review will focus on the recently approved chemotherapeutic combinations including capecitabine, irinotecan and oxaliplatin. We will also discuss preliminary data of molecular targeted therapies and highlight ongoing studies that will likely change the treatment paradigm for colorectal cancer in the future.

Antineoplastic Agents↗