Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay

The study objective was to determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy measured by progression-free interval (PFI) in a retrospective series of ovarian cancer patients whose tumor specimens had been tested with the ChemoFx assay. A statistically significant correlation between assay prediction of response and PFI was observed in 256 cases with an exact or partial match between drug(s) assayed and received. In 135 cases with an exact match, the hazard ratio for progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the intermediate compared to the sensitive group. The median PFI for patients treated with drugs assayed as resistant was 9 months, 14 months for those with drugs assayed as intermediately sensitive, and PFI had not been achieved for those with drugs assayed as sensitive. These data indicate that the ChemoFx assay is predictive of PFI in ovarian cancer. As the majority of ovarian cancers display different degrees of response to different chemotherapy agents ex vivo, the incorporation of assay information into treatment selection has the potential to improve clinical outcomes in ovarian cancer patients.     

Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII-related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA-1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.     

The human placental bed: histology, immunohistochemistry and pathology

There has been much interest recently on local intra-uterine materno-fetal interactions particularly in the placental bed where cellular relationships between mother and fetus are at their most intimate. While few histopathologists are expected to interpret formal placental bed biopsy specimens, confrontation with tissue from this site is common following abortion, post-partum haemorrhage or molar gestation. This review gives an account of recent advances in our knowledge of the histology, immunohistochemistry and pathology of the placental bed. It focuses particularly on extravillous trophoblast populations and their relationship to maternal cells and emphasizes the importance of vascular changes.     

Delayed Enhancement of Acetaminophen Hepatotoxicity by General Anesthesia Using Diethyl Ether or Halothane

Delayed Enhancement of Acetaminophen Hepatotoxicity by GeneralAnesthesia Using Diethyl Ether or Halothane. WELLS, P. G., RAMJI,P., AND KU, M. S. W. (1986). Fundam. App. Toxicol 6, 299–306.Acetaminophen (Tylenol) is a widely used analgesic/antipyreticdrug which is enzymatically bioactivated, or toxified, by thecytochromes P-450 to a hepatotoxic reactive intermediary metabolite.Brief general anesthesia with diethyl ether has been shown toinhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation,the latter constituting up to 60% of acetaminophen eliminationvia a nontoxifying pathway. Thus ether potentially could producea temporally differentiated inhibition of bioactivating and"detoxifying" pathways, resulting in an enhancement of acetaminophenhepatotoxicity if the balance favored bioactivation. To evaluatethis possibility, separate groups of male NIH strain mice weretreated with acetaminophen at different times after 5 min ofanesthesia with ether. Ether produced a 40-fold enhancementin acetaminophen hepatotoxicity as determined by plasma glutamic-pyruvictransaminase (GPT) concentrations. This toxicologic enhancementwas observed only if acetaminophen administration was delayed,with a maximal enhancement when acetaminophen was given 6 hrafter ether, and no effect with a delay of 16 hr. Similar studiesin male CD-1 mice were carried out using halothane (Fluothane)as the general anesthetic given either over 5 min or over 1hr. While halothane given over 5 min had no effect, a 1 hr anestheticduration produced a 10-fold increase in acetaminophen hepatotoxicityas determined by peak GPT concentration, with no observed hepatotoxicityin the halothane controls. Toxicologic enhancement occurredonly with delayed administration of acetaminophen; however,the maximal enhancement observed with a 6-hr delay was stillevident with a 12-hr delay. Conversely, inhibition of acetaminophenhepatotoxicity was observed if acetaminophen was given either2 hr or 18 hr after halothane. These observations may have clinicalrelevance, and they indicate potential complications in theinterpretation of results obtained from animals subjected togeneral anesthesia.