Assessment of depth of myometrial invasion in endometrial adenocarcinoma

Depth of myometrial invasion in stage I adenocarcinoma of the endometrium is recognized as a prognostic factor for lymph node metastasis and overall survival. To determine if depth of myometrial invasion estimated by gross examination correlated with final histologic depth of invasion, we retrospectively reviewed all cases of surgical stage I endometrial adenocarcinoma treated at our institution between July 1985 and July 1988. Of the 113 evaluable patients, 63 had grade 1 lesions, 37 grade 2 lesions, and 13 grade 3 lesions. The depth of invasion was accurately determined by gross examination in 55 of 63 (87.3%) grade 1 lesions, 24 of 37 (64.9%) grade 2 lesions, and only 4 of 13 (30.8%) grade 3 lesions. Thus, gross examination of fresh tissue to estimate depth of myometrial invasion in endometrial adenocarcinoma is less reliable as the grade of the tumor increases. Alternative methods, such as frozen section, should be considered when evaluating depth of invasion, especially when this affects intraoperative decisions regarding lymph node sampling.     

Health-associated changes in drinking: a period prevalence study of the Atherosclerosis Risk In Communities (ARIC) cohort (1987-1995)

BACKGROUND: Several investigators have suggested that drinking cessation occurs because of poor health which may bias studies on the benefit or risk of alcohol consumption. METHODS: Drinking status, level of alcohol consumption, and two measures of health (perceived health and physician diagnosed chronic disease status) were determined from exams 1 (1987-1989) and 3 (1993-1995) on 12,562 African- and European-American participants, who were aged 45-64 years at exam 1 in the ARIC Study. For those in good health at exam 1, logistic regression analyses were used to model the association between health decline and drinking change at exam 3. RESULTS: Among the total population, drinking cessation was significantly more common among those who reported poor health at exam 3, and nondrinkers were unlikely to begin drinking regardless of exam 3 health. Using different measures of health status resulted in associations whose strength and significance varied with ethnicity and, in some cases, by gender. CONCLUSION: While the current data do not prove that the health decline occurred prior to drinking cessation, our findings support the hypothesis that poor health results in drinking changes which could potentially bias studies of alcohol's benefit and risk even when lifetime abstainers are used as the reference group.     

The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: Outcome and toxicity

Objective: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer.Study design: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins.Results: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved.Conclusion: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.     

Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma

Summary The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP.The antiangiogenic agents alone or in combination did not alter the growth of the tumors. However, their administration along with cyclophosphamide, CDDP, or thiotepa substantially increased the tumor growth delay produced by these cytotoxic therapies in tumors responsive to the drugs — the increase was about 2-fold for TNP-470 and minocycline together. In drug resistant tumors, treatment with the antiangiogenic agents did not reverse drug resistance but did increase the effect of the cytotoxic drugs.Treatment with TNP-470/minocycline also increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline administration increased the efficacy of fractionated radiation therapy, especially when used along with a perflubron emulsion oxygen delivery agent/carbogen.These results indicate that treatment regimens including therapies directed toward the proliferating normal cells within a tumor mass as well as therapies directed toward the malignant cells can produce improved outcomes.     

Long-term impact of previous breast biopsy on breast cancer screening modalities

Approximately 80% of breast biopsies are performed for what proves to be a benign process. The patients who undergo these procedures should continue screening with breast physical examination and mammography. The long-term impact of breast biopsy on these screening modalities has not been well studied. We performed a prospective, follow-up evaluation in 63 patients who underwent needle localization biopsy with benign histology at our institution between 6 and 7 years ago. This evaluation consisted of a directed history, breast physical examination, and follow-up mammogram. Two patients (3%) had undergone mastectomy for an interval breast cancer; 17 others (28%) had undergone subsequent biopsies. No patient had changes on physical examination of the biopsy site. All mammograms were evaluated as normal or as having benign abnormalities. Excisional breast biopsy does not generally produce long-term changes affecting the interpretation of breast physical examination or mammography.     

Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer

PURPOSE: To determine whether local immunosuppression with Cyclosporin A can influence the survival of human fetal retinal pigment epithelium (RPE) xenografts in the rabbit's subretinal space. METHODS: Cultured human fetal RPE cells were transduced with the gene for green fluorescent protein (GFP) using a lentiviral vector. The RPE was transplanted into the subretinal space of rabbits that received intravitreal cyclosporine either by weekly injections (0. 25-0.5 mg) or by slow release (approximately 2 microg/d) from a capsule sutured into the vitreal cavity after prior cryopexy. The transplanted RPE was followed by GFP fluorescence scanning laser ophthalmoscopy and by histology of the transplant site. RESULTS: RPE xenografts in eyes receiving intravitreal cyclosporine survived longer (several months) than they did in control eyes without cyclosporine. Survival was as long with slow release capsules as it was with weekly intravitreal injections at much higher concentrations of cyclosporine. CONCLUSIONS: Local immunosuppression of the eye with cyclosporine prolongs the survival of RPE xenografts in the subretinal space of rabbits, implying that rejection involves activated T lymphocytes. Local immunosuppression with slow release capsules is as effective as weekly injections at much higher concentrations.     

The role of the posterior ciliary body in the biosynthesis of vitreous humour

Recently, several groups have published new information regarding the origins and structure of the vitreous humour, and the inner limiting lamina (ILL) of the retina. This short article provides an overview of this new information. It is proposed that vitreous proteins are derived from several different cell types with the posterior half of the non-pigmented ciliary epithelium being prominent in the expression of several connective tissue macromolecules. In addition, some basement membrane macromolecules are also expressed by the ciliary body and may subsequently be assembled on the surface of the Müller cells to form the ILL. New data suggest that the posterior half of the non-pigmented ciliary epithelium has substantial secretory activity and is likely to play a pivotal role in eye development.     

Lentiviral transduction of green fluorescent protein in retinal epithelium: evidence of rejection

This paper demonstrates lentiviral transduction of the humanized form of the Aequoria victoria gene for green fluorescent protein (GFP) into human fetal retinal pigment epithelium (RPE) in vitro and rabbit RPE in vivo.In vitro GFP expression of cultured human fetal RPE begins within two to three days after 12-16 h of maintained exposure to the virus at titers of 10(8)-10(9) infectious units (IU)/ml. Both stationary and dividing cells are transduced using a lenti viral vector with a cytomegalovirus (CMV) promoter. Expression remains stable for at least three to four months without evidence of toxicity and continues through cell division.In vivo expression is followed non-invasively in rabbit eye using a scanning laser ophthalmoscope (SLO), which can detect single fluorescing retinal cells. In vivo expression begins within a few days after a viral solution is introduced into the subretinal space. A solution of 10(9) IU/ml produces fluorescence within three to four days. Less concentrated solutions lead to slower and less expression. No expression is detectable at concentrations of 10(6) IU/ml. Within one to two weeks after introduction of the viral solution, there is evidence of rejection seen by SLO as a loss of GFP fluorescence and disruption of the RPE. Histology shows damage to the RPE layer and monocytic cell infiltrates in the choroid and subretinal space within the area receiving the viral solution. Strong GFP expression leads to rejection within two weeks. With less expression, rejection is delayed and in some cases undetectable for at least six months. If the GFP gene is not included in the viral vector or if the viral concentration is insufficient to produce detectable GFP expression, rejection is not seen. Using a rhodopsin promoter or injecting the virus intra rather than subretinally produces weak expression and no rejection. Lentivirus can induce expression of a foreign gene in the RPE. Viral induced transduction and GFP expression have no effect on the viability of the RPE in vitro. Continued expression of GFP after cell division implies chromosomal integration of the gene. In vivo expression of GFP in RPE encounters rejection. Rejection may not occur with low GFP expression. The latter occurs with low viral titers, a rhodopsin promoter or intra-retinal injection of viral solution. The results are relevant to gene therapy in retina when gene transduction leads to the expression of foreign proteins.