Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the field of mass detection of colorectal cancer by Hemoccul test, the results of the Burgundy study confirm the two european studies previously published and encourage to extend this training to the whole country. In oncogenetic field, a recent publication suggest some different clinical criteria that Amsterdam criteria to define a Lynch syndrome. When genetic markers are performed in a population selected according to these type I criteria, HNPCC mutation could be detected in 28% of cases. In colorectal cancer surgery, the debate remains open on the place of coeliosurgery. A recent published series of 135 colon cancers operated by coeliosurgery do not show any recurrence on trocar orifices. A US study has confirmed the prognostic value of the number of lymph nodes analyzed after resection of colorectal cancer. In adjuvant treatment of stage II colon cancer, two contradictory publications have been reported in the Journal of Clinical Oncology. However, the results of the Impact B2 Group are more consistent and support the fact that chemotherapy cannot be recommended as a standard treatment in state II colon cancer. The actualities in the liver metastases focused on the new local destruction technics that are cryosurgery and radiofrequency. Concerning the chemotherapy of metastatic colorectal cancer, important results have been published in second line therapy showing the superiority of Campto compared to best supportive care or 5FU based chemotherapy both in term of overall survival and quality of life. In first line chemotherapy, the superiority of bi-therapies (LV5FU2 and oxaliplatin or LV5FU2 and irinotecan) has been confirmed compared to LV5FU2 alone. A recent publication showed that patients older than 70 years tolerate chemotherapy for colorectal cancer as well as younger patients with the same efficacy. In esophagus carcinoma, the most important study didn't show any efficacy of neoadjuvant chemotherapy by 5FU-cisplatin in operable adenocarcinoma of squamous carcinoma of esophagus. The final results of dutch's study in node dissection for gastric cancer do not find any benefit in overall survival comparing D2 versus D1 dissection with a substantial increase in morbidity and mortality in the D2 arm, specially when splenopancreatectomy was performed. Finally, an important study has confirmed the value of per echoendoscopy biopsies for the diagnosis of positive lymph nodes and pancreatic tumors.
 ...
PMID:[Update on gastroenterology]. 1090 87

Hereditary colorectal cancer syndromes account for about 7% of all colorectal carcinomas. The most frequent form is Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Identification, cloning and sequence analysis of the predisposing genes enables identification of mutation carriers and non-mutation carriers, respectively. These genetic informations can be used in an individually tailored clinical surveillance program and may ultimately result in standard preventive surgical treatment. In classical FAP the surgical standard is performing a restorative proctocolectomy. It is still unclear now, if this procedure should be modified in attenuated forms (colectomy with ileorectostomy). Due to a high rate of synchronous and metachronous carcinomas a subtotal colectomy in the case of first colon cancer seems to be indicated in HNPCC patients. A proctocolectomy or a restorative proctocolectomy should be weighed in case of carcinomas in the lower rectum. These procedures should be performed under the precondition of identification of the pathogenic germline mutation in the patient, only. In addition, a synchronous prophylactic hysterectomy with oophorectomy should be recommended postmenopausal gene carriers. Intensive counseling of the patient should proceed these preventive procedures involving surgeons, gastroenterologists, geneticists, molecular biologists, gynecologists, physicians and psychologists. It is recommended to have patients treated exclusively in specialized centers. Currently, six interdisciplinary centers for cancer surveillance and early diagnosis in hereditary colorectal cancer are being sponsored in Germany by the Deutsche Krebshilfe since 1999. In the future clinical studies have to be conducted to evaluate the efficacy of extended colorectal resections versus efficacy of surveillance and conventional resections according to general oncological principles.
 ...
PMID:[Surgery of hereditary colorectal carcinoma]. 1092 42

Hereditary nonpolyposis colorectal cancer (NHPCC) is the most common form of inherited colon cancer and one of the most frequent autosomal dominant disorders. HNPCC presents an early onset of colorectal cancer (< 50 years), proximal localization of the colonic tumors, and high risk of developing multiple primary colorectal tumors as well as extracolonic tumors. This disease is caused by mutations in at least four DNA mismatch repair genes, (hMSH2, hMLH1, hPMS1 and hPMS2) and estimations indicate that it affects 1:200-1:2,000 people in the Western populations. The identification of the genes responsible for HNPCC has prompted the search for mutations in affected individuals. DNA from an affected member of a family was sent to a Dutch HNPCC Diagnosis Centre. This Centre reported a germinal mutation, which introduces a premature stopcodon and causes the production of a truncated protein. This particular mutation has not been previously registered in the database of mutations related to this disease. After the identification of the mutation in the index patient, we have developed a quick and efficient procedure for detecting mutations in the rest of the family. The methodology is based on the amplification of the exon 13 in the hMSH2 gene using a forward primer that abuts the mutation site and introduces the cutting sequence of the enzyme Haelll++ only in the wild type allele. At present, seventeen members of the family have been diagnosed and nine have been found to be affected. The methodology is simple, specific, sensitive, inexpensive and applicable in low complexity laboratories.
 ...
PMID:[Diagnosis by directed mutagenesis of a mutation at the hMSH2 gene associated with hereditary nonpolyposis colorectal cancer]. 1096 7

The authors report the association of ureteric tumour and colon carcinomas in the context of hereditary predisposition to HNPCC colon cancer (hereditary non polyposis colon cancer). The recall the diagnostic criteria of HNPCC syndrome and emphasize the importance of guiding the clinical interview of patients with upper urinary tract tumours in order to detect a family history and the presence of gastrointestinal tumours.
 ...
PMID:[Urothelial tumor and colonic cancer in the context of a syndrome of hereditary predisposition to HNPCC colonic cancer]. 1121 60

Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described.
 ...
PMID:A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) status, age at diagnosis and cancer risk. 1125 70

MMR gene mutations and MSI are not found in all clinically diagnosed HNPCC families. We evaluated whether MMR genotyping and tumor MSI analysis could identify distinct clinical subgroups among HNPCC families. Twenty-nine clinical HNPCC families were divided into 3 groups: A, families with hMLH1 or hMSH2 gene mutations; B, MMR gene mutations not present but MSI present in at least 50% of tumors tested; C, mutational and MSI analyses negative. We evaluated tumor spectrum, age at onset, risk of cancer in the follow-up and survival for CRC in the 3 groups. Tumors of the target organs in HNPCC (colon and rectum, endometrium, ovary, small bowel, stomach, renal pelvis and ureter) were more frequent in the first 2 groups than in the latter. Colon cancer was more frequently located in the proximal colon and showed an earlier age at onset in families with MMR gene mutation or with MSI than in families with stable tumors. Comparing the occurrence of tumors in the follow-up, in the first 2 groups patients younger than 50 years had a higher RR, which was particularly marked for CRC (RR = 18.6 for group A vs. group C, RR = 16.7 for group B vs. group C). CRC patients in the first 2 groups had a better clinical prognosis. The results of molecular analysis could distinguish, within clinically defined HNPCC families, different subgroups to which specific programs of surveillance could be addressed.
 ...
PMID:Clinical and biologic heterogeneity of hereditary nonpolyposis colorectal cancer. 1149 33

Nonpolyposis Colorectal Cancer (HNPCC) accounts for about 5% of all colorectal cancers and is the most frequent familial form; familial adenomatous polyposis coli accounts for about 1%. Prerequisitive for individually tailored surveillance is the identification of the pathogenic germline mutation. In classical FAP, surgical standard is a restorative proctocolectomy while in HNPCC there is no surgical standard other than standard oncological resection due to missing evidence. In HNPCC, prophylactic colectomy before the onset of the first colorectal cancer is not recommended. Main arguments for the extension of the resection in the case of the first colorectal carcinoma in HNPCC are the rate of metachronous colorectal carcinomas of 40-45% in a 10-year interval and rapid tumor progression. In HNPCC, in the case of first colon cancer a subtotal colectomy seems to be indicated. A proctocolectomy or, if indicated, a restorative proctocolectomy may be considered in the case of carcinomas in the lower rectum. These considerations should be evaluated in a prospective clinical trial. Counselling, molecular diagnosis and surgery in patients with hereditary colorectal cancers should only be performed in interdisciplinary centers.
 ...
PMID:[Hereditary colorectal carcinomas - reflection on preventive surgery]. 1160 Aug 6

To evaluate the malignant potential of synchronous multiple colorectal cancers, we studied clinicopathologically 31 synchronous multiple colorectal cancers resected at our hospital. We also compared the p53 gene mutation rate, replication error (RER) rate, and Ki-67 antigen positivity rate between these cancers and 90 sporadic colorectal cancers. There was no significant difference in lymphoid and venous invasion, hepatic metastasis, or stage of colon cancer between the two types of cancers. The p53 gene mutation rate was lower in synchronous multiple colorectal cancers (p < 0.05). The RER rate and positivity rate for Ki-67 antigen was significantly higher in these cancers (p < 0.05). These results suggest that some synchronous multiple colorectal cancers result from carcinogenesis in which RER genes are involved, as HNPCC does. In the patients with synchronous multiple colorectal cancers, it is clinically important to follow them carefully focusing on multiple metachronous colorectal cancers and multiple organ cancers.
 ...
PMID:[Alternations of p53 gene, microsatellite instability and proliferation associated antigen Ki-67 in the synchronous multiple colorectal cancers]. 1172 53

The main progress in surgical oncology regarding colonic cancer has been made by standardizing the mode of resection: En block resection of the tumor-bearing colon segment together with the draining lymph nodes, including the lymph nodes at the origin of the respective main vessel, is mandatory. Minimal invasive surgery is an option for resection, however, results of ongoing multicenter trials have to clarify the situation. Adjuvant therapy is used for patients in stage III, who are not included in studies. Since quality of surgery has a major influence on prognosis, this factor also needs to be taken into account when judging the impact of adjuvant therapy. New chemotherapeutic agents have been proven to be valid for palliative and probably also for adjuvant treatment. Prophylactic surgery is routine for patients with ulcerative colitis and FAP, the benefit for patients with HNPCC has to be further evaluated. New knowledge on the individual prognosis might optimize treatment; most probably this will be accomplished by detection of minimal residual disease. The impact of the sentinel node concept in colon cancer is unclear. New progress will be possible by an approach adapted to the individual problem together with accumulating and linking experience and knowledge.
 ...
PMID:[Progress in oncological visceral surgery: colon carcinoma]. 1182 72

Recent data have advanced our ability to detect, survey, and manage patients with colonic neoplasia. Current studies and consensus statements increasingly support the role of colonoscopic screening over less invasive testing such as FOBT or FS for appropriately selected individuals. There are many issues, however, that remain unresolved. What is the appropriate surveillance of an individual with a single family member who had colon cancer at an early age? How should family members of suspected HNPCC kindreds be managed? There has yet to be a prospective cohort validation of the Bethesda criteria in directing clinical practice, with the endpoint of mortality reduction. Questions regarding prophylaxis with dietary supplements and medications are exciting areas that are currently under study. As newer technologies become clinically available for molecular diagnostics and screening, and virtual colonoscopy with computed tomography and magnetic resonance disseminates, there will undoubtedly be new questions to be answered regarding their ability to aid in the detection and management of colon cancer.
 ...
PMID:Colon cancer: detection and prevention. 1213 19


<< Previous 1 2 3 4 5 6 Next >>