Prolonged increase in T-cell receptor (TCR) variant fractions of spleen T lymphocytes in pregnant mice after gamma irradiation.

To investigate the relationship between the radiation-induced increase of T-cell receptor (TCR) defective variant fractions and physiological status such as pregnancy, C57BL/ 6N mice were irradiated with 3 Gy of gamma rays at various days of gestation, just before and just after pregnancy. While the highest level of variant fractions in spleen T lymphocytes appeared at 9 days postirradiation and resolved fairly rapidly for nonpregnant mice, the increased variant fractions for pregnant mice irradiated at 16.5 days of gestation reached a plateau at 14 days postirradiation and remained at high levels until 28 days after irradiation. Therefore, variant fractions 28 days postirradiation were measured to determine the overall effect of radiation on the kinetics of TCR variant fractions during gestation. There was no significant difference in the baseline TCR variant fraction between unirradiated nonpregnant and pregnant mice. TCR variant fractions after irradiation were about twofold higher in pregnant mice (from 10.5 days of gestation until delivery) than those in nonpregnant mice. Both gamma radiation and pregnancy caused a decrease in the proportion of naïve T-cell subsets and an increase in TCR variant fractions of naïve T cells. In addition, the prolonged postirradiation increase in the TCR variant fractions of pregnant mice was associated with an increase in serum progesterone level. Differences between pregnant and nonpregnant mice in the kinetics of postirradiation restoration of T-cell systems may be involved in producing the differences in residual TCR variant fractions of these mice.

The delayed manifestation of T-cell receptor (TCR) variants in X-irradiated mice depends on Trp53 status.

The influence of Trp53 on the radiation-induced elevation of T-cell receptor (TCR) variant fractions was examined in splenic T lymphocytes of Trp53-proficient and -deficient mice. Wild-type Trp53+/+, heterozygous Trp53+/- and null Trp53-/- mice were exposed to 3 Gy of X rays at 8 weeks of age. The fraction of TCR-defective variants was measured at various times after irradiation. Initially, the TCR variant fraction increased rapidly and reached its maximum level at 9 days after irradiation before decreasing gradually. In Trp53+/+ and Trp53+/- mice, the TCR variant fraction fell to normal background levels at 16 and 20 weeks of age, respectively. In contrast, the TCR variant fraction of Trp53-/- mice failed to decrease to background levels during the observation period. Baseline levels were then maintained for approximately 60 weeks in the Trp53+/+ mice and approximately 40 weeks in the Trp53+/- mice. After the long flat period, a significant re-increase in the fraction of TCR variants was found after 72 weeks of age in the irradiated Trp53+/+ mice and after 44 weeks of age in the irradiated Trp53+/- mice. Measurement of the fraction of apoptotic cells in the spleen and thymus 4 h after X irradiation at these ages in Trp53+/+ and Trp53+/- mice demonstrated a reduction in apoptosis in the irradiated mice compared to the nonirradiated mice. This suggests that the delayed increase in TCR variants after irradiation is due to a reduction in Trp53-dependent apoptosis.

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adrenal-preserving laparoscopic surgery in selected patients with bilateral adrenal tumors.

BACKGROUND: There have been few reports of laparoscopic adrenal-sparing surgery for bilateral adrenal tumors. We review our experience with this type of surgery with the aim of evaluating its feasibility and safety. METHODS: Over a 4-year period, we treated 9 patients with bilateral benign adrenal tumors. Seven patients had bilateral pheochromocytomas (MEN 2: 5, VHL: 1, sporadic: 1), and 2 patients had Cushing's syndrome caused by bilateral adrenocortical adenomas. Laparoscopic procedures were performed by a flank approach. The mean diameter of the tumors was 3.7 cm (range, 2.0-8.5 cm). RESULTS: All the tumors were removed laparoscopically. Four patients with hereditary pheochromocytomas underwent bilateral total adrenalectomy because of the large tumor size and multiplicity. The other 5 patients were treated successfully with preservation of adrenocortical function. In 4 of these 5 patients, the adrenal tumors were 3 cm or less in diameter. None of the patients experienced surgical complications. At a mean follow-up of 16 months (range, 4-40 months), none of the 5 patients who were treated by adrenal-sparing surgery required corticosteroid replacement. CONCLUSION: Laparoscopic surgery is feasible for the treatment of bilateral adrenal tumors. Adrenal-preserving laparoscopic surgery may be practicable for the removal of these tumors, if the tumor on either side is 3 cm or less in diameter; however, our follow up is short (mean, 16 months).