Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial).

The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), Pounds 1703 vs Pounds 1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (Pounds 2930 vs Pounds 3176). The average cost to individuals for reoperations was higher in the lap group (Pounds 762 vs Pounds 553). Overall costs were slightly higher in the lap group (Pounds 6899 vs Pounds 6631), with mean difference of Pounds 268 (95%CI -689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (Pounds 8259 vs Pounds 5586) and open procedures (Pounds 7820 vs Pounds 5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery.

MRI assessment of the bony pelvis may help predict resectability of rectal cancer.

OBJECTIVE: The outcome after surgical treatment of rectal cancer may be influenced by the technical difficulty of the operation, which is thought to be affected by pelvic size. The aim of this study was to examine the association between bony pelvic dimensions and CRM involvement. PATIENTS AND METHODS: All patients with primary rectal cancer between December 1999 and January 2002 were studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were measured from the MR images on a workstation. Pathology reports were obtained for all patients and the mesorectal specimen was examined. Technical difficulty was assessed by circumferential resection margin (CRM) involvement. RESULTS: Of 126 patients with primary rectal cancer, 88 had staging MRI and rectal excision; there were significant differences between the sexes in all 9 pelvic dimensions (P < 0.05). In females, the interspinous diameter was significantly shorter in patients with CRM involvement compared with patients with a negative CRM. In female patients predicted to have a negative CRM, the anteroposterior diameter of the inlet, the anteroposterior diameter of the midplane and the transverse diameter of the midplane (interspinous distance) were significantly shorter in patients who actually had a positive CRM compared with those in whom the CRM was negative. In male patients, there was no correlation between pelvic dimensions and CRM status. CONCLUSIONS: In certain patients with rectal cancer, CRM positivity may be predicted from pre-operative MRI pelvic measurements. This may influence the choice of adjuvant therapy.

Assessing the relative costs of standard open surgery and laparoscopic surgery in colorectal cancer in a randomised controlled trial in the United Kingdom.

The role of laparoscopic surgery for the treatment of colorectal cancer is being explored in a multi-centre, randomised clinical trial in the UK, the MRC CLASICC Trial (Conventional versus Laparoscopic-assisted Surgery in Colorectal Cancer). An important end-point of the trial is the cost-effectiveness of laparoscopic surgery compared with that of conventional open surgery. The economic evaluation of this trial has been modelled on that in a similar trial being conducted in the USA in colon cancer. The aim of this paper is to discuss the rationale for modelling the UK trial on the US trial, and to describe the adaptations necessary for the UK trial. The parallel design of the economic evaluation in both trials will provide a unique opportunity to compare the cost implications of incorporating laparoscopic surgery in the UK and the USA, and to determine any cross-cultural differences. The UK trial will also provide information about the cost-effectiveness of laparoscopic surgery in rectal cancer.

Prenatal detection of trisomy 21 and 18 from amniotic fluid by quantitative fluorescent polymerase chain reaction.

Prenatal diagnosis of fetal trisomies is usually performed by cytogenetic analysis on amniotic fluid. This requires lengthy laboratory procedures and high costs, and is unsuitable for large scale screening of pregnant women. An alternative method, which is both rapid and inexpensive and suitable for diagnosing trisomies even from single fetal cells, is the fluorescent polymerase chain reaction using polymorphic small tandem repeats (STRs). In this paper we present the preliminary results of a larger study comparing parallel prenatal diagnoses of trisomies 21 and 18 using cytogenetics with quantitative fluorescent polymerase chain reaction using STR markers. The results obtained by the two techniques were concordant in all cases. This is the first study reporting significant numbers of prenatal diagnoses using the quantitative fluorescent polymerase chain reaction. We believe that further studies on greater numbers of samples will determine the absolute reliability of this technique. These results also provide a model for diagnosis of trisomy from single fetal cells isolated from maternal blood.

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma.

BACKGROUND: Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome. METHODS: DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS: There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Antenatal screening for cystic fibrosis.

OBJECTIVE: To assess the practicality of implementing antenatal screening for cystic fibrosis in Yorkshire. DESIGN: Prospective study in which all pregnant women were offered testing for the delta F508 mutation which accounts for about 85% of carriers in Yorkshire. The reproductive partners of those found to be cystic fibrosis carriers were then tested and any carrier referred for genetic counselling. SETTING: Antenatal clinics in two hospitals and eight general practices. POPULATION: Six thousand and seventy-one pregnant women. RESULTS: A total of 3773 women (62%) accepted the screening offer. This was a lower uptake rate than in other published UK studies: Aberdeen (85-91%), Manchester (85%), Edinburgh (76-84%) and Oxford (67%). Nonetheless there were large and statistically significant differences in the uptake rate between centres within the study: 78% and 60% for the two hospitals and 67% for the general practices. One hundred and thirty women (3.4%) were found to be carriers and three carrier couples were identified. The median time interval for the laboratory to produce a result was five days and the cost was pounds 16 on average. CONCLUSIONS: Antenatal screening for cystic fibrosis does not pose any special practical difficulties. It would be feasible to introduce it into routine practice in Yorkshire.

Cost effectiveness of antenatal screening for cystic fibrosis.

OBJECTIVE: To estimate the cost effectiveness of different antenatal screening programmes for cystic fibrosis. SETTING: Antenatal clinics and general practices in the United Kingdom. DESIGN: Four components of the screening process were identified: information giving, DNA testing, genetic counselling, and prenatal diagnosis. The component costs were derived from the literature and from a pilot screening study in Yorkshire. The cost of a given screening programme was then obtained by summing the components according to the specific screening strategy adopted (sequential and couple), the proportion of carriers detected by the DNA test, and the uptake of screening. Baseline assumptions were made about the proportion with missing information on carrier status from previous pregnancies (20%), the proportion changing partners between pregnancies (20%), and the uptake of prenatal diagnosis (100%). Sensitivity analysis was performed by varying these assumptions. MAIN OUTCOME MEASURE: Cost per affected pregnancy detected. RESULTS: Under the baseline assumptions sequential screening costs between pounds 40,000 and pounds 90,000 per affected pregnancy detected, depending on the carrier detection rate and uptake. Couple screening was more expensive, ranging from pounds 46,000 to pounds 104,000. From the sensitivity analysis a 10% change in the assumed proportion with missing information from a previous pregnancy alters the cost by pounds 4000; a 10% change in the proportion with new partners has a similar effect but only for couple screening; and cost will change directly in proportion to the uptake of prenatal diagnosis. CONCLUSIONS: While economic analysis cannot determine screening policy, the paper provides the NHS with the information on cost effectiveness needed to inform decisions on the introduction of a screening service for cystic fibrosis.

Microsatellite instability in colorectal cancer: improved assessment using fluorescent polymerase chain reaction.

BACKGROUND & AIMS: Microsatellite instability was first described in hereditary nonpolyposis colorectal cancers and sporadic colorectal cancers, in which it was associated with a good prognosis. The aim of this study was to assess the advantages of a novel fluorescent assay for detecting microsatellite instability. METHODS: Eleven fluorescently tagged microsatellites and an automated DNA sequencer were used to investigate 54 sporadic colorectal adenocarcinomas. RESULTS: This fluorescent assay combined accurate allele sizing with cross-sectional data display and allowed improved assessment of microsatellite instability. Twenty-two percent of cancers (12 of 54) showed microsatellite instability with at least one marker. For tumors showing microsatellite instability, results were obtained for a minimum of eight markers. Six tumors showed microsatellite instability at high frequency (at least 63% of markers affected), and 42% of the patients who had a tumor showing microsatellite instability had a synchronous and/or metachronous colorectal tumor (vs. 7% of patients whose tumor did not show microsatellite instability). Patients with a microsatellite instability-positive tumor had an improved prognosis (P = 0.03). CONCLUSIONS: The use of this fluorescent assay improved the assessment of microsatellite instability with the automated analysis and cross-sectional data display. The assay identified a subgroup of patients who showed microsatellite instability and who also showed clinical features that differed from the microsatellite instability-negative cases.