Intraoperative lymph node evaluation using 18F-FDG and a hand-held gamma probe in endometrial cancer surgery--a pilot study.

PURPOSE: The purpose of this pilot study was to assess feasibility, safety, and accuracy of detection of metastatic nodes intraoperatively with a hand-held gamma (PET) probe after administration of 18F-FDG in patients with high risk endometrial cancer (EC). MATERIALS AND METHODS: This is a prospective, cohort study. Twenty-two patients with clinical Stage I or II EC with high-risk histologic subtypes who were candidates for open surgical intervention were screened for the study. After screening, there were seven study patients (mean age: 64; range: 53-77) who were eligible for the study. In the entire cohort, there were 61 nodal stations that were assessed with a gamma counter intraoperatively, in vivo and again after removal of the node. All adverse events were recorded and operating room staff was monitored for radiation exposure. Resected nodes underwent histological assessment as per routine clinical practice. RESULTS: Range of maximal counts per second recorded in vivo and ex vivo were 0-86 and 0-17, respectively. Of all the nodes examined, one node was positive for metastatic disease; however, intraoperatively the lymph node readings were not higher than other lymph node basins assessed in same patient. No adverse events were recorded. The surgeons recorded the maximum average radiation exposure of all healthcare personnel with an average exposure of 0.08 mSV per case (range, 0.06-0.15). CONCLUSION: Use of hand-held gamma probe for intraoperative staging of patients with high risk EC is feasible, safe, and radiation exposure levels for all members of the healthcare team were within radiation safety guidelines. However, its use for detection of lymph node metastases needs further evaluation.

Measuring the biological effect of presurgical metformin treatment in endometrial cancer.

BACKGROUND: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. We tested the hypothesis that short-term presurgical metformin reduces cellular proliferation in atypical endometrial hyperplasia (AEH) and endometrioid EC, and assessed the feasibility of using phosphorylated PI3K-AKT-mTOR proteins as tissue end points. METHODS: Women with AEH or EC received metformin 850 mg twice a day or no drug in the presurgical window between diagnosis and hysterectomy. Before and after the window, tissue samples were obtained; serum markers of insulin resistance (e.g. homeostasis model of assessment of insulin resistance index) were determined; and anthropometrics measured (e.g. BMI). Cell proliferation (Ki-67) and PI3K-AKT-mTOR phosphostatus were assessed by immunohistochemistry and scored blinded to treatment. RESULTS: Twenty-eight metformin-treated and 12 untreated patients, well matched for age and BMI, completed the study. Metformin treatment (median 20 days, range 7-34) was associated with a 17.2% reduction in tumour Ki-67 (95% CI -27.4, -7.0, P=0.002), in a dose-dependent manner. Tumour PI3K-AKT-mTOR protein phosphostatus varied but the effects were not significant after adjusting for changes in controls. CONCLUSIONS: Short-term metformin was associated with reduced Ki-67 expression in EC. Changes in tumour PI3K-AKT-mTOR protein phosphostatus were seen in both groups. Future studies should address the variability attributed to different sampling techniques including devascularisation of the uterus at hysterectomy.

Surgical Stage I high-grade ovarian cancer: is adjuvant chemotherapy warranted?

OBJECTIVE: To review the results of patients with high-grade Stage I ovarian cancer managed without adjuvant treatment. MATERIALS AND METHODS: A retrospective chart review identified patients with newly diagnosed Stage I high-grade ovarian cancer, who underwent comprehensive surgical staging. RESULTS: Thirty-three patients with FIGO surgical Stage I high-grade ovarian cancer were identified. After a median follow-up of 40 months, nine patients (27%) recurred. The median time to recurrence was 19 months. Of the nine patients with recurrences, four (44%) are alive with disease, three (33%) patients have no evidence of disease, and two have died of disease (22%). The two- and five-year overall survival is 100% and 90%, respectively. CONCLUSIONS: It would appear the recurrence rates of Stage I high risk epithelial ovarian cancer completely staged, without adjuvant treatment are comparable to those of treatment arms reported in the literature. A proportion of these patients can be salvaged at recurrence, yielding a high overall survival.

The use of a chaperone in obstetrical and gynaecological practice.

The aim of this study was to assess the use of a chaperone in obstetrical and gynaecological practice in Ireland and to explore patients' opinions. Two questionnaires were designed; one for patients and the other one was sent to 145 gynaecologists in Ireland. One hundred and fifty two women took part in this survey of whom 74 were gynaecological and 78 were obstetric patients. Ninety five (65%) patients felt no need for a chaperone during a vaginal examination (VE) by a male doctor. On the other hand 34 (23%) participating women would request a chaperone if being examined by a female doctor. Among clinicians 116 (80%) responded by returning the questionnaire. Overall 60 (52%) always used a chaperone in public practice, in contrast to 24 (27%) in private practice. The study demonstrated that most patients do not wish to have a chaperone during a VE but a small proportion would still request one regardless of the examiner's gender. Patients should be offered the choice of having a chaperone and their opinion should be respected and documented.

Heparan sulphate synthetic and editing enzymes in ovarian cancer.

Several angiogenic growth factors including fibroblast growth factors 1 and 2 (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We previously showed that all cellular elements in ovarian tumour tissue synthesised HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor) was confined to ovarian tumour endothelium. In this study, we have sought to explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are critical for FGF2 activation. These enzymes were strongly expressed by tumour cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the 3G10 antibody of tissue sections pretreated with heparinases indicated that HS proteoglycans were produced by tumour and endothelial cells. These results indicated that, in contrast to the endothelium, HS produced by tumour cells may be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O-sulphate groups from HS, was abundant in tumour cells but weakly expressed in the endothelium. If this enzyme was responsible for the lack of biologically active HS on the tumour cell surface, we would expect exogenous FGF2 binding to be preserved; we showed previously that this was indeed the case although FGF2 binding was reduced compared to the endothelium and stroma. Thus, the combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes.

The neoadjuvant approach in the treatment of patients with advanced epithelial ovarian carcinoma.

AIMS: Ovarian cancer has a very poor prognosis, with 5-year survival rates of 5-20% for advanced-stage disease. This work was designed to verify whether the neoadjuvant approach had an effect on survival in patients with advanced-stage ovarian cancer. MATERIALS AND METHODS: Patients with stage III or IV disease who received neoadjuvant platinum-based chemotherapy (group 1) were compared with a group of conventionally treated patients (group 2). RESULTS: Most of the patients in group 1 (76%) had partial tumoral responses after chemotherapy. Patients from group 1 (n = 42) had a median survival that was not different from that in patients from group 2 (n = 348). Patients who received platinum-based chemotherapy with taxanes had the same survival of patients who received no taxanes. CONCLUSIONS: Our results showed similar responses and survival rates for patients with stage III or IV ovarian cancer treated with neoadjuvant platinum-based chemotherapy, when compared with patients who underwent primary suboptimal cytoreductive surgery. Our data therefore support the ongoing trials to determine the optimum timing of surgery for ovarian cancer.

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization.

The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis.

Home care patients' responses to point-of-care technology.

Patient response is a critical aspect of successful POC technology implementation. This article presents the results of a pilot POC patient satisfaction study conducted at four home health agencies. Variables impacting patient receptiveness and recommendations for patient education are discussed to help agencies develop individual POC training and education plans.