Critical care interventions are expensive and have a narrow safety margin. It is essential to develop structured and validated approaches to study the delivery of this resource. In this study, the critical care service model performed favorably both in terms of quality and cost.
Aims: Traditionally, advanced stage ovarian carcinoma is treated by debulking surgery followed by chemotherapy. However, in some circumstances preoperative chemotherapy may be given before optimal surgical debulking. This study aims to describe the morphological features found in ovarian carcinoma after chemotherapy because these have not been detailed previously. Methods: Histological sections were examined from 18 cases of ovarian carcinoma that had been treated by preoperative chemotherapy. The morphology was compared with any pre-chemotherapy biopsies that had been performed. Tumours were classified as showing morphological features suggesting a good response to chemotherapy (n = 14) or as showing little or no response (n = 4). Serum CA125 values before and after chemotherapy were compared. In all cases, the mitotic activity index (MAI), volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour cells were calculated. Results: The preoperative biopsies were all typical ovarian serous or endometrioid adenocarcinomas. Morphological features present in the group responding to chemotherapy included the presence of small groups or single tumour cells in a densely fibrotic stroma. Tumour cells were characterised by both nuclear and cytoplasmic alteration, making accurate tumour typing and grading impossible. Nuclear features included the presence of bizarre enlargement with hyperchromatism, irregularity of outline, and chromatin clumping or smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or foam cell change. There were pronounced stromal changes of fibrosis, inflammation, collections of foamy histiocytes, cholesterol cleft formation, haemosiderin deposition, fat necrosis, and dystrophic calcification, including the presence of many free psammoma bodies. There was no correlation between morphological response and biochemical response, as determined by serum CA125 values. In all nine cases in which pre-chemotherapy and post-chemotherapy biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093). Conclusions: Because preoperative chemotherapy is being used increasingly in the management of ovarian cancer, pathologists should be aware of the resultant morphological effects. Accurate tumour typing and grading is impossible. In some cases, it may be difficult to confirm the presence of residual tumour, making it imperative that pre-chemotherapy tissue biopsies are obtained. Definite confirmation of residual tumour may require the examination of multiple histological sections from areas showing pronounced stromal changes, sometimes with multiple levels and immunohistochemistry. In the absence of definite residual tumour, the report should state that the features are consistent with the prior presence of tumour.
The septin family of genes has been implicated in a variety of cellular processes including cytokinesis, membrane transport and fusion, exocytosis, and apoptosis. One member of the septin family maps to chromosome 17q25.3, a region commonly deleted in sporadic ovarian and breast tumours, and has also been identified as a fusion partner of MLL in acute myeloid leukaemias. The present study demonstrates that the pattern of expression of multiple splice variants of this septin gene is altered in ovarian tumours and cell lines. In particular, expression of the zeta transcript is detectable in the majority of tumours and cell lines, but not in a range of non-malignant adult and fetal tissues. Zeta expression is accompanied by loss of the ubiquitous beta transcript. Somatic mutations of the gene were not detected in ovarian tumours, but it was demonstrated that beta expression in tumour cell lines can be reactivated by 5-azacytidine treatment, suggesting a role for methylation in the control of expression of this gene.
AimsCA19.9 is a monosialoganglioside secreted by mucinous tumours of the gastrointestinal tract, including the pancreas and biliary tree. Limited studies have shown that this tumour marker may also be elevated in primary ovarian mucinous neoplasms, but no study has assessed whether serum CA19.9 levels can be used to predict if a primary ovarian mucinous tumour is benign, borderline or malignant. The aim of this study was to correlate the serum CA19.9 level with the histological features in a large series of primary ovarian mucinous neoplasms.Methods144 cases of primary ovarian mucinous neoplasm (79 benign, 45 borderline and 20 malignant) were identified in which a preoperative serum CA19.9 level had been performed. The association between the serum levels and the histological subtype and a variety of other parameters was investigated. In a subset of cases, immunohistochemical staining for CA19.9 was performed on tumour blocks.ResultsSerum CA19.9 levels were elevated in 27%, 38% and 40% of mucinous cystadenomas, borderline mucinous tumours and mucinous carcinomas, respectively. Markedly elevated levels of serum CA19.9 were observed in each group, with the highest serum CA19.9 measurements being noted in borderline mucinous tumours. There was no relationship between the serum CA19.9 level and whether the tumours were benign, borderline or malignant (Kruskal–Wallis test p value=0.32). A weak but statistically significant correlation was found between tumour maximum dimension and CA19.9 level (Spearman's rank correlation coefficient=0.17, p=0.04). In those cases in which CA19.9 immunohistochemistry was performed, all tumours showed positive staining for CA19.9, with 60% of these cases being associated with an elevated serum CA19.9 level.ConclusionPreoperative CA19.9 levels cannot be used to predict whether a suspected ovarian mucinous tumour is benign, borderline or malignant. Markedly elevated serum levels (>1000 U/ml) may be found in benign mucinous neoplasms as well as in borderline and malignant tumours.
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