Keith Arthur

An increased frequency of human sperm chromosomal abnormalities after radiotherapy.

13 cancer patients were studied before radiotherapy (RT) and at regular intervals after RT to determine the effect of RT on chromosomal abnormalities in sperm. The men were 19-47 years old and received testicular radiation doses of 0.4-5.0 Gray. Human pronuclear sperm chromosomes were analysed after penetration of zona-pellucida-free hamster eggs. Unfortunately the hamster egg penetration rates were exceedingly low, both before and after RT and this limited the number of sperm chromosome complements which could be analysed. Before RT, the frequency of abnormal sperm chromosome complements was 0% (0/9). After RT, the majority of men were azoospermic for 24 months but complements could be analysed from 4 men. In the first 12 months the frequency of abnormalities was 13% (1/8) and at 24 months it was 13% (7/55). By 36 months after RT, most men had recovered sperm production and the frequency of abnormalities in 8 men was 21% (18/86), which is significantly higher than the rate in control donors (8.5%). For individual men the range was 6-67%, and there was a significant correlation between testicular radiation dose and the frequency of sperm chromosomal abnormalities. The frequencies of both numerical and structural abnormalities were significantly increased after RT. This is the first evidence that radiation may increase the frequency of chromosomal abnormalities in human gametes.

Physical exercise and quality of life in postsurgical colorectal cancer patients

Preliminary evidence indicates that physical exercise may be an effective strategy for optimizing quality of life (QOL) following breast cancer diagnosis but evidence for other cancers is limited. In the present study, we employed a prospective design to examine the relationship between physical exercise and QOL in 53 postsurgical colorectal cancer patients. Participants completed a mailed, self-administered questionnaire at baseline (i.e. about two months postsurgery) that assessed exercise prediagnosis and current QOL. They then monitored and reported their exercise behaviour over a four-month period at which time they completed a second mailed, self-administered questionnaire that reassessed QOL. Analyses of variance and multiple regression analyses indicated that functional QOL was the least possessed but most important dimension underlying overall satisfaction with life. Moreover, correlational analyses indicated that changes in mild exercise from prediagnosis to postsurgery correlated positively wit...

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.

A comparison of chromosomal aberrations induced by in vivo radiotherapy in human sperm and lymphocytes

Chromosomal aberrations in human sperm and lymphocytes were compared before and after in vivo radiation treatment of 13 cancer patients. The times of analyses after radiotherapy (RT) were 1, 3, 12, 24, 36, 48 and 60 months. The median total radiation dose was 30 Gy and the testicular dose varied from 0.4 to 5.0 Gy. Human sperm chromosome complements were analysed after fusion with golden hamster eggs. There were no abnormalities in sperm or lymphocytes before RT. Following RT there was an increase in the frequency of numerical and structural chromosomal abnormalities in both lymphocytes and sperm. For structural abnormalities there were more rejoined lesions (dicentrics, rings) in lymphocytes and more unrejoined lesions (chromosome breaks, fragments) in sperm. After RT there was a dramatic increase in the frequency of chromosomal abnormalities in lymphocytes: at 1 mo. the frequency was 42%, at 3 mo. 25%, at 12 mo. 14%, at 24 mo. 11%, at 36 mo. 9%, at 48 mo. 7% and at 6 mo. 4%. Since the majority of men were azoospermic after RT, there is little data on sperm chromosome complements before the analyses performed at 24 mo. post-RT. At 24 mo. the frequency of abnormalities was 13%, followed by 21% at 36 mo., 12% at 48 mo. and 22% at 60 mo. Thus it appears that the frequency of lymphocyte chromosomal abnormalities had an initial marked increase after RT followed by a gradual decrease with time whereas the frequency of sperm chromosomal abnormalities was elevated when sperm production recovered and remained elevated from 24 to 60 mo. post-RT. This difference in the effect of time makes it very difficult to compare abnormality rates in lymphocytes and sperm and to use analysis of induced damage in somatic cells as surrogates for germ cells since the ratio between sperm and lymphocytes varied from 1:1 (at 24 mo. post-RT) to 5:1 (at 60 mo. post-RT).

Concomitant Radiation, Mitomycin C And 5 Flourouracil Infusion in Gastrointestinal Cancer - A Preliminary Report

For a decade, concomitant radiation and chemotherapy with 5-Fluoro- uracil and Mitomycin C has been used in treating carcinoma of anal canal with favourable results (Nigro1, Cummings2, Byfield3). Similar encouraging results have been reported with esophageal carcinoma (Byfield4, Franklin5, Keane6). To date, this combination therapy has been used chiefly in squamous cell carcinoma. It’s efficacy in adenocarcinoma is not well documented, though felt to be ineffective by some authors. Wassif7 has employed similar combination in patients with advanced stages of rectal carcinoma, and reported local response rate of 79–85%.