Radiosensitivity of microscopic tumours of a transplantable mammary adenocarcinoma in mice.

Evidence is presented that microscopic tumours (of a transplantable murine mammary carcinoma, M8013X) grow faster than larger, palpable, tumours. Microscopic tumours are also more radiosensitive than larger tumours. The decrease in radiosensitivity in larger tumours is prevented to a large extent by misonidazole, which has no significant effect on the radiosensitivity of microscopic tumours. The retardation in growth rate which occurs after the fast microscopic growth is probably related to the appearance of hypoxic cells. Both the decrease in growth rate and the progressive development of hypoxia may be caused by the relatively poorer blood flow in larger tumours. Part of the radioresistance in "large" tumours ( approximately 250 mm3) seems to be due to factors other than hypoxia; maybe cell-kinetic factors also play a role. The intrinsic radiosensitivity of tumour cells in microscopic tumours was assessed by means of a modified latency test: the Dq and Do were 2.2 and 2.5 Gy respectively. A number of factors which may influence the reliability of these estimates are discussed.     

Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial.

BACKGROUND AND PURPOSE: The late morbidity of a randomized study was analyzed after a follow up of 2 years. The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters. The correlation with acute toxicity and (pre-existing) bowel complaints was investigated. PATIENTS AND METHODS: 266 T1-4N0M0 prostate cancer patients were randomized for conventional (open fields) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose (66 Gy) and gross target volume-planning target volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self-assessment questionnaire was used to obtain detailed information on morbidity. RESULTS: At 2 years there is only a trend for less rectal toxicity (grade >/=1) in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10 versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A significant relation was found between late rectal toxicity (grade >/=1) and the volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity. The patient self-assessment questionnaire analysis revealed that patients are most bothered by compliance related symptoms like urgency, soiling and fecal loss. In a multivariate analysis, all other variables loose significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation frequency are accounted for. Late anal toxicity is low and related only to acute anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms. The incidence of grade 2 toxicity increases with a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of treatment. CONCLUSIONS: Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal, anal and bladder toxicity compared to conventional radiotherapy. There is a significant relationship between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal (and urological) symptoms at start have a major impact on late toxicity.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

MIB-1 labelling index is an independent prognostic marker in primary breast cancer.

The proliferative activity of a tumour is considered to be an important prognostic factor in primary breast cancer. We have investigated the prognostic value of the MIB-1 labelling index in 341 patients with primary breast cancer and compared the results with the S-phase fraction in 220 patients of the same cohort. All patients were treated in one hospital and had a median follow-up of 128 months. No correlation between MIB-1 labelling and S-phase fraction could be demonstrated. MIB-1 had prognostic value for disease-free survival in the whole group of patients (P < 0.001) and in the node-negative subgroup (P < 0.001). In multivariate analysis, MIB-1 was an independent prognostic factor (P = 0.004) besides axillary lymph node status (P = 0.001). In univariate analysis high S-phase fraction was associated with decreased overall survival (P = 0.04); however, not in multivariate analysis. Moreover, S-phase fraction had a borderline prognostic significance for post-relapse survival in multivariate analysis (P= 0.08). Thus, in conclusion, the growth fraction of a tumour as determined by the MIB-1 labelling index is an important prognostic factor in patients with primary breast cancer.     

Pachymeningitis luetica: a case report

Pachymeningitis luetica is extremely rare in developed countries. We describe a 41-year-old male patient with pachymeningitis luetica, multiple ischaemic infarctions, and severe hydrocephalus. The delay in making the diagnosis contributed to patient's death. Rapid diagnosis is essential on the slightest suspicion of an infection by Treponema pallidum, because timely treatment with antibiotics is effective.     

Being circadian or not: vasopressin release in cultured SCN mirrors behavior in adult voles

We studied vasopressin (AVP) release patterns from organotypic suprachiasmatic nucleus (SCN) cultures obtained from circadian rhythmic and non-rhythmic voles. All eight SCN cultures made from non-rhythmic voles did not produce any circadian pattern in AVP release, while five out of six SCN cultures of rhythmic voles produced significant (circadian) peak values. The total amount of AVP released was 2-fold higher in SCN cultures from rhythmic vole. These data confirm our previously formulated AVP release deficit hypothesis for nonrhythmic voles, and suggest that AVP in the vole SCN plays an important role in mediating output of its circadian clock, regulating circadian organization of locomotor behavior.