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Infrequent somatic mutations of the p73 gene in various human cancers.

AIMS: It has already been reported that loss of heterozygosity (LOH) on chromosome 1p is frequent in a variety of human cancers. This finding implies the presence of some important tumour suppressor genes in this region. p73, a candidate tumour suppressor gene identified recently in chromosome band 1p36.33, encodes a protein highly homologous to p53. To investigate the role of the p73 gene in human carcinogenesis, we studied genetic alterations of this gene in various human cancers. METHODS: We analysed the entire coding exons as well as their surrounding exon-intron boundaries of the p73 gene in 185 cases of various types of tumours (47 breast cancers, 43 colorectal cancers, 31 gastric cancers, 23 neuroblastomas, 21 lung cancer cell lines, and 20 pancreatic cancer cell lines); they are known as a group of tumours with frequent LOHs in the 1p region. PCR-SSCP analysis was performed and tumours in which aberrant migrating sized bands were observed were subjected to direct sequencing analyses. RESULTS: Of the 185 cases, only one somatic mis-sense mutation of glutamine from arginine at codon 269 in exon 7 was found in one breast cancer. In addition, several polymorphisms were found at codons 137, 336, 349, and 610, as well as in introns 6, 8, and 9. Monoallelic expression was also observed in pancreatic cancer cell lines. CONCLUSIONS: Our results suggest that inactivation of the p73 gene does not play a major role in the tumour types analysed in the present study.

Alleles↗

Relative cancer potencies of selected dioxin-like compounds on a body-burden basis: comparison to current toxic equivalency factors (TEFs).

Recent National Toxicology Program (NTP) cancer bioassay data for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and a mixture of these three compounds offer opportunities to assess the accuracy of current World Health Organization (WHO) 1998 toxic equivalency factors (TEFs) for these compounds under a variety of assumptions. An evaluation of the current TEF values for these compounds using body burden in nanograms per kilogram as the dose metric is presented. Average lifetime body burdens were estimated for all compounds at all dose groups based on measured tissue concentrations at 4 time points during the 2-yr NTP studies. Poly-3 adjusted tumor incidences for hepatocellular adenomas, cholangiocarcinomas, and the two tumors combined were modeled using a quantal multistage model and the Hill model with lifetime average body burden as the dose metric. Benchmark doses for a 10% response (BMD10) for each compound and the mixture were estimated. With TCDD as the reference standard, relative potency (REP) estimates were derived from ratios of the BMD10 estimates for PCB 126, 4-PeCDF, and for the toxic equivalent (TEQ) mixture. On a body-burden basis, PCB 126 and 4-PeCDF were 2- to 3-fold and 10- to 12-fold less potent than predicted based on the WHO TEFs, respectively, while the TEQ mixture was approximately 3- to 5-fold less potent than predicted by the TEFs. The current WHO TEF values, which were derived from data on noncancer endpoints evaluated on an administered dose basis, overpredict the carcinogenic potency of these compounds on a body-burden basis compared to TCDD.

Adenoma, Liver Cell↗

An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer.

BACKGROUND: Oral carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard. METHODS: We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of oral carmofur for curatively resected colon cancer in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, carmofur as adjuvant chemotherapy compared with surgery-alone, 5 years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in carmofur and surgery-alone group. Oral carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95% confidence interval (CI) = 0.68-0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95% CI = 0.65-0.91; P = 0.003). CONCLUSIONS: This individual patient-based meta-analysis demonstrated that oral carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers.

Antineoplastic Agents↗

Percutaneous biliary metal wall stenting in malignant obstructive jaundice.

BACKGROUND: Most patients with advanced stage malignant obstructive jaundice will be suitable for palliation only. Metallic stents are safe, effective and minimally invasive. DESIGN: A review of case notes of patients who had Wallstents inserted percutaneously from January 1996 to December 2000. RESULTS: Eighty-nine patients with a median age of 72 years underwent percutaneous insertion of biliary metal stents. The diagnoses were cholangiocarcinoma (41.5%), pancreatic carcinoma (40.5%), nodal metastases at the porta hepatis (14.6%) and gall bladder cancer (3.4%). Ninety-six per cent of patients improved their hyperbilirubinaemia to normal levels by 1 month. The median post-procedure hospital stay was 16 days. Early overall complications (within 30 days of stenting) occurred in 30% of patients (70% of these were disease related). The 30 day mortality rate was 20% (n = 18). Fifty (70%) patients were readmitted to hospital, most commonly because of carcinomatosis (16) or stent obstruction (12). The symptom-free period ranged from 2 weeks to 13 months. Median survival for all patients was 3.5 months. Survival correlated inversely with serum bilirubin at presentation (r = -0.34, P = 0.001), but not with other liver function tests. DISCUSSION: Metal wall stenting for malignant obstructive jaundice provides good palliation with low, procedure-related morbidity and mortality, but poor overall survival from disease-related morbidity. Survival significantly correlates with pre-stenting serum bilirubin levels. There is a need to identify the subgroup of patients in whom stenting has no beneficial effect.

Aged↗

[Surgical treatment of pancreatic and periampullary carcinoma in a specialized unit: a decade later].

INTRODUCTION: Results of surgical treatment for pancreatic and periampullary carcinoma have improved in recent years owing to several factors, particularly the concentration of these patients in specialised surgical units. MATERIAL AND METHODS: Retrospective-prospective comparative study of results in 2 groups of patients treated over 2 different periods of time and with different surgical policy: group A, which included 80 patients treated from 1982 to 1992 in a general surgery unit, and group B, which comprised 151 patients treated from 1998 to 2003 in a specialised hepato-biliary-pancreatic surgery unit. RESULTS: Surgical treatment in patients of groups A and B, respectively, was: resection in 20% and 53.6% and by-pass in 62.5% and 36.4%. Postoperative morbidity after resection was similar (75% vs 74.1%) but higher after by-pass in group B (41.8% vs 34%). Postoperative mortality after surgical resection and by-pass was 25% and 14.1%, respectively, for group A and 3.7% and 16.3%, respectively, for group B. Mean survival for all patients was 7.0 +/- 7.1 months for group A and 14.1 +/- 15.3 months for group B. Mean survival for patients with surgical resection was 11.8 +/- 9.8 months and 18.7 +/- 15.8 months for groups A and B, respectively. CONCLUSIONS: Pancreatic and periampullary carcinoma should be surgically treated in specialised pancreatic surgery units in order to offer the best outcome to patients.

Adult↗

[Preliminary epidemiological study of carriers of Clostridium difficile].

171 samples have been taken from stools of sick persons in three departments of university and hospital centres of Algiers (C.H.U.A.): the department of maternity (C.H.U Parnet), the department of breast diseases (CPMC), the department of women's surgery (CPMC), 13 samples of C. difficile have been isolated with a frequency of 7.6 per 100 of cases. The rate of conveyance seems more important in adults in hospitals and often concerns sick persons enduring digestive cancer (10.25 per 100) or newborn with a frequency of 8.73 per 100.

Adult↗

[Colon and rectum signet-ring cell carcinoma in the National Institute of Neoplastic Diseases].

OBJECTIVE: Primary signet ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine. The purpose of this study was define the incidence, natural history and relation with hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: We reviewed the medical records and pathology of 28 patients with primary signet ring cell carcinoma of the colon and rectum seen at the Instituto de Enfermedades Neoplasicas (INEN), between 1991 and 2002. RESULTS: In the present study the incidence was 5.09% of large bowel adenocarcinoma. Most patients present with late stage disease (Dukes stage C and D). In most cases the signet ring cells diffusely infiltrated through all layers of the intestinal wall (Borrmann IV). Male to female ratio was of 1 : 1.5, mean age was 55.5 and median age was 57 years (range 11 - 83 years). CONCLUSIONS: Comparison of our data with the literature showed some differences that could be related with biological characteristics of our people and different applied inclusion criteria. We couldn't define the relation between HNPCC and primary signet ring cell carcinoma of the colon and rectum.

Academies and Institutes↗

Improved tolerance with two radiation fractions per day for treatment of abdominal and pelvic malignancies.

When major volumes of the abdomen are the tolerable dose is frequently limited by the tolerance of the small intestine and other gastrointestinal tissues. In an attempt to increase the tolerable dose, a twice-daily, 5 day/week fractionation scheme was used. One hundred and thirty-nine patients were started on treatment for abdominal and pelvic malignancies, of whom 124 received the planned dose, usually in the prescribed time. Fifty-five hundred to 6000 rad in about 8 weeks was administered to large volumes of the pelvis and abdomen, frequently with "boost" radiation to 7500 rad to limited volumes. Ninety percent of the patients were able to complete treatment without interruption. In 90% of all cases there were no late radiation-related complications. The acute reactions and late complications have been comparable to those incurred when total doses 20-30% less are administered with one fraction per day. The survival rates of these patients indicates a probable improvement in therapeutic ratio. The physical techniques, areas treated, and time-dose sequence are described. A detailed analysis by primary organ, patient characteristics, performance status, types of complications, cause of death, and survival characteristics is presented.

Abdominal Neoplasms↗

Phase II study of 3-deazauridine in advanced colorectal adenocarcinoma.

A phase II study of 3-deazauridine (DAUR) showed poor activity in previously treated patients with advanced colorectal adenocarcinoma. There were no responses among 15 patients treated on a dose schedule of 1200 mg/m2/day for 5 days repeated at 3-week intervals. Toxicity included mild nausea and vomiting, occasional mucositis, diarrhea, and dizziness. A minimal degree of myelosuppression was observed.

3-Deazauridine↗

[Neoplasms of the large intestine in elderly patients].

The aim of the study was to compare 2 groups of patients with colorectal cancer treated between 1985-1995. The analysed group consisted of 228 patients aged over 70. Reference group consisted of 330 younger ones. The stage of colorectal cancer (Dukes classification) was similar in both groups. Complications of the colorectal cancer often occurred in the elderly patients (21.9% vs. 10%, respectively). The incidence of associated diseases was also higher (70.6% vs. 59.1%). Operability was similar in both groups (93% vs. 98.8%) but resectability was lower in the elderly group (67.4% vs. 80.1%, respectively). Postoperative complications were observed in the similar percent of cases except those aged over 70 (17.5% vs. 4.9%), especially after emergency operations (31.6% vs. 4.7%, respectively).

Adult↗

Efficacy of ultrasonic mass survey for abdominal cancer.

From August 1983 through March 1995, 204,099 people received ultrasonic mass survey of the abdomen for the first time. Among these examinees, 631 (0.31%) malignant neoplasm cases, such as 201 hepatocellular carcinoma (HCC), 81 gallbladder (GB) cancer, 57 pancreatic cancer, and 169 renal cell carcinoma (RCC), were detected. Three hundred seventy six out of 590 cases (64%), excluding chronic leukemia cases and metastatic liver cancer cases, were surgically resected. The resection rate of HCC, GB cancer, pancreatic cancer, and RCC were 25%, 88%, 49%, and 99%, respectively. The cumulative survival rate of the 376 resected cases was 79.5% at 10 years. The cumulative survival rates of resected cases of HCC, GB cancer, pancreatic cancer and cumulative survival rates of resected cases of HCC, GB cancer, pancreatic cancer and RCC were 34% at ten years, 83% at 10 years, 49% at 7 years, and 99% at 10 years, respectively. Ultrasonic mass survey is dramatically useful for early detection of various kinds of abdominal cancers, especially RCC and GB cancer. From now on, many earlier abdominal cancers will be found by establishing and promoting ultrasonic mass survey systems.

Abdominal Neoplasms↗