Effect of radiation therapy on the potential doubling time of tumours in colorectal cancers.

OBJECTIVE: The aim of the present study was to investigate the effects of standard fractionated radiation therapy on the kinetic parameters of colorectal adenocarcinomas. METHODS: The study of tumour kinetics involved in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed with flow cytometry. This procedure provides a rapid calculation of qualitative parameters such as ploidy and quantitative parameters such as the in vivo S-phase fraction labelling index which indicates the percentage of cells that have entered into the cycle, the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy (group 1) and ten rectal carcinomas were studied following radiation therapy (group 2). In diploid tumours, the labelling index was significantly lower in the post-radiotherapy group than in the pre-radiotherapy group (2.7 +/- 1.1% versus 6.4 +/- 4.2%, respectively; P= 0.01), and the Tpot was significantly longer after radiotherapy (group 2) (22.0 +/- 7.0 days versus 8.6 +/- 6.0 days, P = 0.002). Standard fractionated radiation therapy also appears to result in a longer Tpot in diploid adenocarcinomas of the colon and rectum. This effect was not observed in aneuploid tumours. CONCLUSIONS: The effectiveness of hyperfractionated schedules of radiation therapy for aneuploid rectal tumours with short Tpot warrants further investigation in a larger patient population.

Pudendal neuralgia: CT-guided pudendal nerve block technique.

Chronic anoperineal pain without any apparent etiology may be caused by compression of the pudendal nerve. This presentation illustrates the course of the pudendal nerve and the technique of computed tomography-guided infiltration of the nerve.

Results of pudendal nerve neurolysis-transposition in twelve patients suffering from pudendal neuralgia.

PURPOSE: Pudendal neuralgia caused by nerve compression may be improved by surgical decompression of the pudendal nerve. This study was undertaken to determine if clinical symptoms, electrophysiological investigations, and the efficacy of preoperative pudendal nerve blocks could be used to predict the efficacy of surgery. METHODS: Twelve consecutive patients complaining of anal pain, genital pain, or both, exacerbated in the sitting position and unsuccessfully treated by analgesic drugs before referral were studied. In these 12 patients decompression of the pudendal nerve was performed after unsuccessful CT-guided injection of corticosteroids in the pudendal nerve at the ischial spine or after pain relapse following successful injections. Nineteen nerves were decompressed by surgery, and the compressed area was located between the sacrospinal and sacrotuberal ligaments for 18 nerves. RESULTS: Three months after surgery, four patients were totally relieved, and three were only partially improved. After 21 months of follow-up, three patients were cured, one was slightly improved, and eight remained in pain. In the three patients cured by surgery, pain completely disappeared for at least two weeks after a nerve block repeated twice before surgery, whereas pain relief was observed in only one of the nine other patients (P = 0.018). None of the three patients cured by surgery were being treated for depression, whereas six of the nine remaining patients were receiving antidepressants or were followed by a psychiatrist (P = 0.09). Results of surgery did not depend on other preoperative clinical or electrophysiological data. CONCLUSIONS: This preliminary study suggests that complete disappearance of pain for at least two weeks after a nerve block repeated twice before surgery may be the best criterion to predict success. Based on this criterion, surgery would have been performed in four patients in this study, of whom three would have been cured.

Identification of novel germline hMLH1 mutations including a 22 kb Alu-mediated deletion in patients with familial colorectal cancer.

We analyzed the hMLH1 gene in 17 unrelated families with putative hereditary nonpolyposis colorectal cancer. The complete hMLH1 cDNA was amplified in one step, and after a second amplification, four overlapping segments were directly sequenced. We detected, in five families that did not meet the complete Amsterdam criteria, five alterations, including a double-base change resulting in a missense mutation (Lys-618-Ala), a splicing mutation affecting the intron 4 splice acceptor site, a 2-bp deletion at codon 726, a 7-bp deletion at codon 626, and a deletion of exons 13-16. The latter alteration was shown to result from a 22-kb genomic deletion due to a homologous recombination between Alu repeats located in introns 12 and 16. The detection of five germline hMLH1 mutations in five families that only partially fulfilled the Amsterdam criteria shows that these criteria do not allow the identification of all familial colorectal cancers due to mutations of the mismatch repair genes. The numerous Alu repeats present within the hMLH1 gene and the observation of large genomic deletions suggest that (a) Alu-mediated deletions might frequently be involved in hMLH1 inactivation, and (b) reverse transcription-PCR analysis, which allows the amplification of the entire coding region of the hMLH1 gene in one step, might be the most appropriate method for the detection of hMLH1 alterations.