Gastrointestinal surgical workload in the DGH and the upper gastrointestinal surgeon. (1/276)

Workload implications of upper gastrointestinal (UGI) subspecialisation within the district general hospital (DGH) have been assessed by prospective data collection over a 12-month period in a DGH with six general surgeons serving a population of 320,000. The single UGI surgeon (UGIS) performed all ten oesophageal resections, ten of 11 gastric resections for malignancy and all eight pancreatic operations. He also performed 91 of the 182 cholecystectomies, 164 of the 250 endoscopic retrograde cholangiopancreatograms (ERCP) and all endoscopic procedures for the palliation of unresected oesophageal tumours. The UGIS was responsible for the management of all patients with severe pancreatitis, yet he also performed 51 colorectal resections over the 12-month period. Successful management of severely ill patients with upper GI disease requires consultant supervision on a day-to-day basis. If such UGI disease is to be managed in the DGH, two surgeons with UGI experience will be required if high quality care and reasonable working conditions are to be achieved. Such UGIS will continue to perform some colorectal surgery.  (+info)

Role of the surgical trainee in upper gastrointestinal resectional surgery. (2/276)

The 'New Deal' set out by the Department of Health in 1991, together with the introduction of specialist 6-year training grades by Calman in 1993, has resulted in a decrease in available training time for surgeons in the UK. There is also an emerging belief that surgical procedures performed by trainees might compromise patient outcome. This study examines the level of trainee experience in a specialist gastrointestinal unit and whether operation by a trainee surgeon adversely affects patient outcome. All patients in the University Department of Surgery, Royal Infirmary, Edinburgh, undergoing oesophagogastric, hepatic or pancreatic resection between January 1994 and December 1996 were entered into the study. The early clinical outcome (in-hospital mortality and morbidity, considered in three groups: anastomotic leak, other technique-related complications and non-technique-related complications) was evaluated with regard to the grade of surgeon (consultant or trainee) performing the operation. Of the 222 patients undergoing major upper gastrointestinal resection during the study period, 100 (45%) were operated on by trainees. Trainees were assisted and closely supervised by consultants in all but six resections. There was no major difference in mortality rate (consultant, 4.1% vs trainee, 5%), incidence of non-technique-related complications (consultant, 6.7% vs trainee, 7.1%), anastomotic leaks (consultant, 10.7% vs trainee, 5%) or technique-related complications (consultant, 18.9% vs trainee, 15%) between the two grades of surgeon. In a specialist unit, the early clinical outcome of patients undergoing major upper gastrointestinal resection by supervised trainees is no worse than in those operated on by consultants. Participation of trainees in such complex procedures enhances surgical training and does not jeopardise patient care.  (+info)

O6-benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair. (3/276)

Early phase evaluation of anticancer drugs has traditionally used toxicity (usually hematological) rather than efficacy end points to establish appropriate dosing schedules. To establish a biochemical efficacy end point for overcoming alkylguanine DNA alkyltransferase (AGT)-mediated tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, we performed a novel dose escalation clinical trial for the AGT-depleting agent O6-benzylguanine (BG). The dose of BG required to deplete AGT to undetectable levels (BMD(T)) in sequential computed tomography-guided tumor tissue biopsies before BG and 18 h after BG was determined. Thirty patients received doses of BG ranging from 10 to 120 mg/m2. In tumor tissue, AGT depletion >86% of baseline was demonstrated at all doses tested. Residual tumor AGT activity, present 18 h after BG doses of 10-80 mg/m2, was eliminated at the 120 mg/m2 dose and is thus the BMD(T) of BG. BG pharmacokinetics are characterized by the rapid, dose-independent clearance of BG from plasma Metabolism of BG to its biologically active metabolite, 8-oxo-benzylguanine (8-oxo-BG), was found. The t(1/2) of 8-oxo-BG is longer than BG. Plasma concentrations of 8-oxo-BG well above 200 ng/ml 18 h after the end of the BG infusion were observed at the highest dose levels tested and appeared to correlate with depletion of AGT activity to undetectable levels in tumor tissue. AGT activity in peripheral blood mononuclear cells at baseline did not correlate with tumor tissue AGT activity. Depletion of AGT activity to undetectable levels in peripheral blood mononuclear cells occurred at lower doses and was not a reliable predictor for tumor tissue depletion. No serious side effects were observed with administration of BG alone or in combination with 13 mg/m2 1,3-bis(2-chloroethyl)-1-nitrosourea. This is the first clinical study in which biochemical analyses from pre- and posttreatment tumor biopsies have been used as an efficacy end point for the clinical development of an anticancer agent. From our tumor tissue biopsy data, we have established that a BG dose of 120 mg/m2 infused over 1 h should be used in Phase II clinical trials.  (+info)

Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion. (4/276)

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.  (+info)

Analyzing health surveys for cancer-related objectives. (5/276)

Large-scale health surveys conducted by government agencies record information on a large number of health-related variables. We review the use of these data for performing analyses that address cancer-related objectives. After describing the conduct of a large-scale health survey (the third National Health and Nutrition Examination Survey [NHANES III]), we discuss some of the issues involved in analyzing data collected in such a survey. In particular, the use of sample weights in the analysis and the importance of accounting for the complex survey design when estimating standard errors are discussed. Six applications are then presented that involve the following: 1) estimating demographic factors associated with snuff use, 2) estimating the association of type of health insurance with the probability of receiving a digital rectal examination, 3) estimating the association of body iron stores with the probability of later developing cancer, 4) estimating the changing rates of mammography screening in the United States between 1987 and 1992, 5) evaluating smoking and alcohol consumption as risk factors for digestive cancer by use of a population-based, case-control study, and 6) evaluating a randomized community-intervention experiment to encourage smoking cessation. These applications use data from the National Health Interview Survey, the NHANES I Epidemiologic Followup Study, the 1986 National Mortality Followback Survey, and the Community Intervention Trial for Smoking Cessation. The availability of public-use data files is discussed for surveys sponsored by the U.S. government that collect health-related information. We demonstrate that statistical methods and computer software are available for analyzing public-use data files of surveys to address different types of cancer-related objectives.  (+info)

High inter- and intrapatient variation in 5-fluorouracil plasma concentrations during a prolonged drug infusion. (6/276)

The purpose of the study was to examine inter- and intrapatient variation in 5-fluorouracil (5-FU) plasma concentrations in adult cancer patients receiving a 3-day drug infusion. Fourteen patients received 1266 mg/m2 N-(phosphonacetyl)-L-aspartate (PALA) infused i.v. over 15 min on day 1, followed immediately by a loading dose of 500 mg/m2 calcium leucovorin over 30 min. Then a prolonged infusion of leucovorin at 500 mg/m2/day and 5-FU at 1750 mg/m2/day was administered as either a constant rate or as a circadian infusion over 72 h. During constant rate infusions, 5-FU concentrations within individuals varied by 1.7-fold, but no uniform time of peak or trough concentration was observed. Transformation of these data by setting the time of peak to 0 h and by expressing concentrations as the percentage of the 24-h mean value revealed a nonrandom distribution of the time from peak to trough with a median time of 12 h (P = 0.027). These transformed data were also successfully fit to a circadian cosinor function (P < 0.001). During multiple constant rate 5-FU infusions, the intrapatient variability was high; the times of peak 5-FU concentration occurred at the same approximate sampling time 43% of the time, and troughs coincided 17% of the time. No difference in clinical toxicity was observed when matched constant rate and circadian infusions of 5-FU were compared. High inter- and intrapatient variability exists in 5-FU plasma concentrations in adult cancer patients during constant rate infusions with no evidence of a consistent circadian rhythm in untransformed data.  (+info)

Fish consumption and cancer risk. (7/276)

BACKGROUND: Although several studies have investigated the relation between fish consumption and the risk of cardiovascular diseases, less attention has been paid to the relation between fish consumption and cancer risk. OBJECTIVE: The relation between frequency of consumption of fish and risk of selected neoplasms was analyzed by using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996. DESIGN: The overall data set included the following incident, histologically confirmed neoplasms: oral cavity and pharynx (n = 181), esophagus (n = 316), stomach (n = 745), colon (n = 828), rectum (n = 498), liver (n = 428), gallbladder (n = 60), pancreas (n = 362), larynx (n = 242), breast (n = 3412), endometrium (n = 750), ovary (n = 971), prostate (n = 127), bladder (n = 431), kidney (n = 190), thyroid (n = 208), Hodgkin disease (n = 80), non-Hodgkin lymphomas (n = 200), and multiple myelomas (n = 120). Control subjects were 7990 patients admitted for acute, nonneoplastic conditions unrelated to long-term modifications of diet. Odds ratios (ORs) were computed for subsequent levels of fish consumption compared with no or occasional consumption (<1 serving/wk) by using multiple logistic regression, including terms for several covariates. RESULTS: There was a consistent pattern of protection against the risk of digestive tract cancers with fish consumption: oral cavity and pharynx, OR = 0.5 for the highest compared with the lowest level of consumption; esophagus, OR = 0.6; stomach, OR = 0.7; colon, OR = 0.6; rectum, OR = 0.5; and pancreas, OR = 0.7. There were inverse trends in risk of larynx (OR = 0.7), endometrial (OR = 0.8), and ovarian (OR = 0.7) cancers and multiple myeloma (OR = 0.5). No pattern of cancer risk in relation to fish consumption was observed for cancers of the liver, gallbladder, breast, bladder, kidney, or thyroid or for lymphomas. CONCLUSION: This study suggests that the consumption of even relatively small amounts of fish is a favorable indicator of the risk of several cancers, especially of the digestive tract.  (+info)

Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and during chemoprevention. (8/276)

BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary tumors in the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (alpha, beta, and gamma). Previously, we found that RARbeta expression was suppressed in lung cancer. In this study, we investigated whether expression of RARbeta is modulated by chemopreventive intervention. METHODS: Using in situ hybridization, we analyzed RARbeta messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or placebo. Since we had previously detected RARbeta expression in 90% of bronchial specimens from nonsmokers, we considered loss of RARbeta mRNA expression in at least one of six biopsy specimens at baseline in this study to be aberrant. RESULTS: RARbeta mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13-cis-RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13-cis-RA treatment, the number of subjects who were RARbeta positive in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals with aberrant RARbeta expression decreased to 62.9% (22 of 35), which represents a statistically significant difference from baseline expression (two-sided P =.01). In the placebo group, no statistically significant difference in RARbeta expression was observed between baseline and 6 months. RARbeta expression was not related to current smoking status or reversal of squamous metaplasia. CONCLUSIONS: These results indicate that RARbeta is an independent marker of response to 13-cis-RA and may serve as an intermediate biomarker in chemoprevention trials of upper aerodigestive tract cancers.  (+info)