CT scan does not predict optimal debulking in stage III-IV epithelial ovarian cancer: a multicentre validation study.

Our aim was to design and validate a model of CT findings that predict suboptimal cytoreduction in primary surgery (PS) for Stage III-IV epithelial ovarian cancer (EOC). We performed a retrospective review of preoperative CT scans of patients undergoing PS for EOC in a cancer centre in London, UK, between November 1995 and October 2003 (n = 91). Radiological features predictive of suboptimal cytoreduction were identified and the model tested in a second cohort undergoing PS in Manchester, June 2005 - March 2007 (n = 35). In the London cohort, liver surface disease and infrarenal para-aortic lymph node involvement predicted suboptimal cytoreduction with 80% accuracy. Accuracy of these predictors dropped to 63% when applied to the Manchester cohort. We concluded that CT prediction of suboptimal cytoreduction is unreliable and may not be reproducible. In the absence of favourable data from larger, prospective trials, it should not be used to guide management.

Hysterectomy.

Hysterectomy is one of the most commonly performed major surgical procedures; approximately 100,000 are performed in the UK each year. Hysterectomy can be total or subtotal. The postulated benefits of subtotal hysterectomy--better pelvic floor and sexual function--have not been confirmed in randomised trials. Traditionally, hysterectomy was performed using either an abdominal or vaginal approach. More recently, laparoscopic techniques have been used. The decision about the technique used is often related to the surgeon's training and expertise, as the indications for each technique overlap. Vaginal hysterectomy is probably the preferred route because it is quicker and cheaper than laparoscopic hysterectomy, with no other clear differences in outcome measures. Laparoscopic hysterectomy has a number of advantages over abdominal hysterectomy: specifically, shorter hospital stay and quicker return to normal activities; complication rates, however, appear to be greater. This also seems to be the case with radical hysterectomy performed for cervical cancer.

Increase in peripheral blood mononuclear cell (PBMC)- and CD56+ cell-mediated killing of endometrial stromal cells by mycobacteria; a possible role in endometriosis immunotherapy?

BACKGROUND: Immunological therapies have shown promising results in the treatment of endometriosis. Mycobacteria are one of the most common immune therapies used in other diseases. We have assessed the effects of mycobacteria in altering the ability of peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells to kill endometrial stromal cells using an in vitro model. This may have implications in the immunotherapy of endometriosis. METHODS: Primary cultures of endometrial stromal cells were grown from female patients and PBMCs were extracted from healthy female volunteers. Effector cells (PBMCs or NK cells) were exposed to varying concentrations of mycobacteria before their ability to kill cultured endometrial cells was tested using a 51Cr-release assay. RESULTS: Treatment of effector cells with the Connaught Substrain Bacillus of Calmette and Guérin (BCG) led to increased killing of target cells by PBMCs and NK cells. The optimal concentration for treatment of effector cells with Connaught BCG was approximately 0.1 multiplicities of infection (m.o.i.). There was a trend towards increased killing after treatment with Pasteur BCG. CD56+ (NK) cells treated with BCG at 0.1 m.o.i. showed increased killing of target cells compared with untreated effector cells. CONCLUSIONS: Endometrial stromal cells are susceptible to killer cells activated by mycobacteria. This in vitro work suggests a possible role for mycobacteria in the immunotherapy of endometriosis.

Anti-proliferative effect of mycobacteria, IFN-gamma and TNF-alpha on primary cultures derived from endometrial stroma: possible relevance to endometriosis?

PROBLEM: To assess the effects of mycobacteria and inflammatory cytokines on proliferation of endometrial stromal cells. An effect on endometrial stromal cell proliferation in vitro may suggest a similar effect on endometriotic cells in vivo. METHOD OF STUDY: Primary cultures of endometrial stromal cells were grown from female volunteers. Proliferation of cells was assessed by cell counting and incorporation of tritiated thymidine after exposure to mycobacteria or inflammatory cytokines. RESULTS: When assessed by cell counting, stromal cell growth was reduced following treatment with Connaught Bacillus of Calmette and Guérin (BCG) and Pasteur BCG: Mycobacterium smegmatis demonstrated a cytotoxic effect. Addition of the cytokines interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha at high concentrations led to a reduction in cell growth by 24 hr in two of three cell lines. A reduction in proliferation was also found when assessed by tritiated thymidine incorporation, which was statistically significant for Connaught BCG and M. smegmatis. CONCLUSIONS: Endometrial stromal cells are susceptible to the anti-proliferative effects of mycobacteria. The BCG and other mycobacteria are known immunomodulators in other disease conditions. Further work is required to assess whether these in vitro effects might translate into a useful therapy for endometriosis.

The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up.

BACKGROUND: This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. METHODS: In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. RESULTS: Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. CONCLUSIONS: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.

The Western Australian experience of the use of en bloc resection of ovarian cancer with concomitant rectosigmoid colectomy.

OBJECTIVES: The aim of this study was to assess the technique of en bloc resection of ovarian cancer with concomitant rectosigmoid colectomy, in relation to perioperative complication rates, and its impact on survival following the procedure. METHODS: A retrospective review was performed of the case notes of 129 consecutive procedures performed between 1989 and 2000 in a regional cancer center. RESULTS. Overall, 48.8% of patients suffered a major or minor complication. Complications relating to bowel anastomosis occurred in 2.4%. Perioperative mortality was 3.1%. Median survival for the group as a whole was 30.6 months. Patients who were optimally debulked had a significantly longer median survival time. CONCLUSION: En bloc resection of ovarian cancer with concomitant rectosigmoid colectomy allows a high rate of optimal debulking with acceptable morbidity, mortality, and survival.

Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer.

OBJECTIVE: To examine the feasibility and safety of a low anterior resection of the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for ovarian cancer. METHODS: This study included 65 consecutive patients with primary ovarian cancer who had debulking surgery from 1996 through 2000. All patients underwent an en bloc resection of ovarian cancer and a rectosigmoid resection followed by an end-to-end anastomosis. Parameters for safety and efficacy were considered as primary statistical endpoints for the aim of this analysis. RESULTS: Postoperative residual tumour was nil, <1 cm, and >1 cm in 14, 34, and 14 patients, respectively. The median postoperative hospital stay was 11 days (range, 6 to 50 days). Intraoperative complications included an injury to the urinary bladder in one patient. Postoperative complications included wound complications (n = 14, 21.5%), septicemia (n = 9, 13.8%), cardiac complications (n = 7, 10.8%), thromboembolic complications (n = 5, 7.7%), ileus (n = 2, 3.1%), anastomotic leak (n = 2, 3.1%), and fistula (n = 1, 1.5%). Reasons for a reoperation during the same admission included repair of an anastomotic leak (n = 1), postoperative hemorrhage (n = 1), and wound debridement (n = 1). Wound complications, septicemia, and anastomotic leak formation were more frequent in patients who had a serum albumin level of < or =30 g/L preoperatively. There was one surgically related mortality in a patient who died from a cerebral vascular accident 2 days postoperatively. CONCLUSIONS: An en bloc resection as part of primary cytoreductive surgery for ovarian cancer is effective and its morbidity is acceptably low.

Neural networks in the diagnosis of malignant ovarian tumours.

OBJECTIVE: To assess the role of neural networks in predicting the likelihood of malignancy in women presenting with ovarian tumours. DESIGN: Retrospective case study. SETTING: University Department of Obstetrics and Gynaecology, St James's Hospital, Leeds. METHODS: Information from 217 cases with histologically proven benign, borderline or malignant tumours was extracted for study. Four variables (age, ultrasound findings with and without colour Doppler imaging and CA125) were entered in the neural network classifier. The neural network results were compared with logistic regression analysis. RESULTS: When used in the neural network the variables of age, CA125 and ultrasound score produced the best result with a sensitivity of 95% and a corresponding specificity of 78% in predicting malignancy. Logistic regression gave a sensitivity or 82% for a specificity of 51%. CONCLUSION: The neural network is a good method of combining diagnostic variables and may be a useful predictor of malignancy in women presenting with ovarian tumours. A comparison of the performance of the neural network with conventional diagnostic methods would be warranted prior to use in clinical practice.

Recurrent pain after hysterectomy and bilateral salpingo-oophorectomy for endometriosis: evaluation of laparoscopic excision of residual endometriosis.

Endometriosis can represent with a variety of symptoms including pelvic pain, dyspareunia and pain with defaecation, up to several years after hysterectomy and bilateral salpingo-oophorectomy. This may occur when all endometriotic tissue is not excised at the time of the initial procedure. Although excision of endometriosis at this time would be preferable, we have found laparoscopic excision of residual endometriosis to be effective in relieving endometriosis associated pain.

Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A.

This study was designed to compare functional effects of phosphorylation of muscle acetyl-CoA carboxylase (ACC) by adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and by AMP-activated protein kinase (AMPK). Muscle ACC (272 kDa) was phosphorylated and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. Functional effects of phosphorylation were determined by measuring ACC activity at different concentrations of each of the substrates and of citrate, an activator of the enzyme. The maximal velocity (Vmax) and the Michaelis constants (Km) for ATP, acetyl-CoA, and bicarbonate were unaffected by phosphorylation by PKA. Phosphorylation by AMPK increased the Km for ATP and acetyl-CoA. Sequential phosphorylation by PKA and AMPK, first without label and second with label, appeared to reduce the extent of label incorporation, regardless of the order. The activation constant (Ka) for citrate activation was increased to the same extent by AMPK phosphorylation, regardless of previous or subsequent phosphorylation by PKA. Thus muscle ACC can be phosphorylated by PKA but with no apparent functional effects on the enzyme. AMPK appears to be the more important regulator of muscle ACC.