The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian, fallopian tube, and peritoneal cancer.

OBJECTIVE: The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete). METHODS: Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016. RESULTS: Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen ('ultra-radical'), the combined rate of complete and optimal cytoreduction would be only 33.3%. CONCLUSIONS: Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.

Investigating vaginal bleeding in postmenopausal women found to have an endometrial thickness of equal to or greater than 10 mm on ultrasonography.

PURPOSE: This aim of this study is to determine the risk of endometrial cancer in symptomatic postmenopausal women, when endometrial thickness on transvaginal ultrasonography is equal to or greater than 10 mm, and subsequent office-based endometrial sampling histology is negative. METHODS: This is a prospective cross-sectional study, performed in a gynaecological oncology centre in the United Kingdom between February 2008 and July 2012. All postmenopausal women presenting with vaginal bleeding were investigated using transvaginal ultrasonography. Women with endometrial thickness measurements equal to or greater than 10 mm and negative office-based endometrial biopsy underwent hysteroscopy and endometrial biopsies. RESULTS: Over a 52-month period, 4148 women were investigated for postmenopausal vaginal bleeding. 588 (14.2%) women were found to have endometrial thickness measurements of equal to or greater than 10 mm on transvaginal ultrasonography. 170 (28.9%) cases of endometrial cancer were diagnosed in this group: 149 (87.6%) of the cancer cases were diagnosed in the outpatient setting with a Pipelle® endometrial sampler, whilst 21 (12.4%) had a negative Pipelle® sample and were diagnosed with hysteroscopy. The group diagnosed with hysteroscopy had lower BMI (32.7 kg/m2 versus 39.7 kg/m2, p < 0.001) whilst the group diagnosed with Pipelle was more likely to have a history of hypertension and diabetes mellitus (p = 0.019 for both). The sensitivity of Pipelle was 87.65%. CONCLUSION: For women presenting with postmenopausal bleeding and where the endometrial thickness is equal to or greater than 10 mm and Pipelle sampling is negative, hysteroscopic evaluation with directed biopsy is strongly recommended.

Outcome of investigations for postmenopausal vaginal bleeding in women under the age of 50 years.

OBJECTIVE: The objective of this study is to determine the incidence of endometrial cancer in young postmenopausal women presenting with vaginal bleeding. METHODS: Cross-sectional study of postmenopausal women presenting with vaginal bleeding in a gynaecological oncology centre in the United Kingdom. All women underwent transvaginal ultrasound scanning (TVS) as the initial investigation tool to evaluate the endometrium. Endometrial biopsy was performed only in cases where endometrial thickness measured equal to or greater than 5mm. The patients were divided into two groups based on their age: less than 50 years (Group A) and 50 years or older (Group B). RESULTS: Over a 57-month period, 4454 women were investigated for postmenopausal vaginal bleeding. Of these, 259 (5.8%) women were diagnosed with endometrial carcinoma. 260 (5.8%) women were younger than 50 years. Endometrial biopsy was not performed in 130 women in Group A that had an endometrial thickness measurement of less than 5mm on ultrasonography. With a median follow-up period of 3 (1-5) years, we found no cases of endometrial cancer in women under the age of 50 that did not undergo endometrial biopsy at the time of initial evaluation. Overall, no cases of endometrial cancer were diagnosed in postmenopausal women under the age of 50 years. CONCLUSIONS: We found no cases of endometrial cancer amongst 260 women presenting with postmenopausal vaginal bleeding under the age of 50 years. These women could be investigated on a less urgent basis depending on the available resources.

Management of postmenopausal women with vaginal bleeding when the endometrium can not be visualized.

OBJECTIVE: To determine the risk of endometrial cancer when endometrial thickness is not visualized using ultrasonography. DESIGN: Cross-sectional study. SETTING: Gynecological oncology center in the United Kingdom. POPULATION: All postmenopausal women referred with vaginal bleeding. METHODS: All women were investigated using gray-scale transvaginal ultrasonography. Women were arbitrarily stratified into four groups according to the endometrial thickness measurement. Women with endometrial thickness that was not adequately visualized on ultrasonography were included in a separate group. MAIN OUTCOME MEASURES: Endometrial cancer diagnosis. RESULTS: Over a 50-month period, 4454 women were investigated for postmenopausal vaginal bleeding. A total of 259 (6%) of women were diagnosed with endometrial carcinoma. Endometrial thickness measured 5-9.9 mm in 1201 (27%), 10-14.9 mm in 468 (11%), 15-19.9 mm in 209 (5%), and equal to or greater than 20mm in 197 (4%) of women. In 174 (4%) of women, the endometrial thickness was not visualized on transvaginal ultrasonography. For women where the endometrial thickness was not adequately visualized, the final histology included benign endometrium (124), endometrial cancer (26), endometrial polyps (11), endometritis (7), and other pathology (7). The odds of endometrial cancer in women where the endometrial thickness was not visualized were found to be significantly higher than the odds of cancer for women with an endometrial thickness of 5-9.9 mm (OR = 5.23, 95%CI 3.10-8.85, p-value <0.0001). CONCLUSIONS: For women presenting with postmenopausal bleeding and where the endometrial thickness cannot be adequately visualized on ultrasonography, hysteroscopic evaluation is recommended.

A novel approach to postoperative bladder care in women after radical hysterectomy.

PURPOSE: Currently, controversy exists with regard to the duration of bladder drainage and choice of catheter used in women who undergo radical hysterectomy. In this manuscript, we propose a novel approach to improving postoperative bladder care in women who undergo radical hysterectomy. METHODS: This is a retrospective study of women who underwent Type 3 Piver radical hysterectomy in a gynaecological oncology centre in the United Kingdom from January 2009 to September 2011. We report the outcomes of removal of urinary catheter 48-72 h following radical hysterectomy. RESULTS: Over a 32-month period, 30 women underwent radical hysterectomy. 19 (63.3 %) women underwent surgery for treatment of cervical cancer, 5 (16.7 %) women for management of endometrial cancer, 6 (20 %) women for other conditions. One patient underwent partial cystectomy at the time of radical hysterectomy and was not included in the analysis. Of the 29 patients, only five (17.2 %) were found to have urinary residuals greater than 100 ml following the removal of the indwelling catheter on the second postoperative day and required recatheterisation. 82.8 % of the patients had the catheter removed within 48-72 h postoperatively. None of these patients required re-admission with urinary retention. CONCLUSION: Removal of urinary catheter on the second postoperative day following radical hysterectomy is feasible and not associated with increased morbidity. This approach may be particularly useful to complement the introduction of laparoscopic and robotic surgical approaches for surgical management of cervical cancer.

Iatrogenic pneumomediastinum and subcutaneous emphysema as a complication of colonoscopy with cold forceps biopsy.

A 58-year-old woman underwent outpatient colonoscopy with multiple cold forceps biopsy for evaluation of a presumptive diagnosis of ulcerative colitis. Six hours following the procedure, she developed subcutaneous crepitus and presented to the emergency department, where chest X-ray revealed pneumomediastinum and subcutaneous emphysema. Our case discusses this unusual complication of colonoscopy and its diagnosis and management.

Estimating the risk of endometrial cancer in symptomatic postmenopausal women: a novel clinical prediction model based on patients' characteristics.

INTRODUCTION: The aim of this study was to develop a multivariable model to predict the risk of endometrial carcinoma in postmenopausal women with vaginal bleeding using individuals' clinical characteristics. PATIENTS AND METHODS: This prospective study of consecutive postmenopausal women presenting with vaginal bleeding was conducted at a gynecological oncology center in the United Kingdom for a 46-month period. All women underwent transvaginal ultrasound scanning as the initial investigation tool to evaluate the endometrium. Women found to have an endometrial thickness 5 mm or more had endometrial sampling performed. RESULTS: Of a total of 3548 women presenting with vaginal bleeding during the study period, 201 (6%) women had a diagnosis of endometrial carcinoma. An investigator-led best model selection approach used to select the best predictors of cancer in the multiple logistic regression model showed that patient's age (odds ratio [OR], 1.06), body mass index (OR, 1.07), recurrent episodes of bleeding (OR, 3.64), and a history of diabetes (OR, 1.48) increased the risk of endometrial malignancy when corrected for other characteristics. The mentioned clinical variables satisfied the criteria for inclusion in our predictive model called FAD 31 (F for the frequency of bleeding episodes, A for the age of the patient, D for diabetes, and the number 31 represents the BMI cut-off value). The total score for the model varies from 0 to 8. The area under the receiver operating characteristics curve for the developed model was 0.73 (95% confidence interval, 0.70-0.77). DISCUSSION: We have developed a simple model based on patients' clinical characteristics in estimating the risk of endometrial cancer for postmenopausal women presenting with vaginal bleeding. The model shows reasonable discriminatory ability for women with cancer and without, with an area under the receiver operating characteristics curve of 0.73. This will allow clinicians to individualize the diagnostic pathway for women with postmenopausal vaginal bleeding.

How to improve training in bowel surgery for gynecological oncologists-experience from a single center in the United kingdom.

INTRODUCTION: There is now a growing realization of the lack of experience of gynecological oncology trainees in gastrointestinal surgery. Advanced fellowship programs in gastrointestinal surgery have been suggested as a potential solution to this problem. PATIENTS AND METHODS: We present data relating to gastrointestinal procedures performed by the gynecological oncology trainee during a fellowship program over a 3-year period in a single gynecological oncology center in the United Kingdom. RESULTS: Over a 36-month period, 369 cases of invasive ovarian cancer were diagnosed in our institute, of which 278 (75.3%) were stage III/IV disease. Bowel surgery was performed in 86 patients (30.9%) with stage III/IV ovarian cancer. A total of 121 gastrointestinal procedures were performed during the study period, as some patients had more than one procedure. We present the procedures the gynecological oncology fellow performed and assisted during this period. DISCUSSION: To improve competencies in performing bowel surgery among gynecological oncology trainees, we suggest sustained exposure in bowel surgery over the entire duration of the training program.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Cytoplasmic p27 expression is an independent prognostic factor in ovarian cancer.

Dysregulation of the cell cycle is an important prerequisite for cancer development. p27 has an established role in cell cycle control and hence may be disrupted during carcinogenesis. The influence of p27 expression, including its subcellular location, on tumor behavior in ovarian cancer has been controversial. The purpose of this study was to evaluate the expression of p27 in a large population of patients with ovarian cancer and correlate this to clinicopathologic variables including overall survival. Using a tissue microarray of 339 primary ovarian cancers, the expression of p27 was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied. Cytoplasmic p27 showed a progressively negative impact on overall survival (P=0.004). Tumors displaying nuclear p27 also had poorer prognosis (P=0.014). Factors shown to predict prognosis independently of each other were age, stage, and the absence of macroscopic disease after surgery. Cytoplasmic p27 expression, but not nuclear, was independently predictive of prognosis on multivariate analysis (P=0.042). Both subcellular locations of p27 expression were more frequently observed in serous compared with mucinous subtypes. Cytoplasmic p27 independently predicts poorer prognosis in ovarian carcinoma. These results seem counterintuitive, when considering the antiproliferative role of p27, but may reflect a more complex function of p27 within cell cycle regulation. These data support a novel role for p27 within the cytoplasm, possibly through effects on apoptosis, cellular motility, and drug resistance.

Cholecystectomy as Part of Cytoreductive Surgery for Advanced Ovarian Cancer: Perioperative Outcomes.

BACKGROUND/AIM: To assess the perioperative outcomes of cholecystectomy in cytoreductive procedures for epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Prospectively collected perioperative data of patients that underwent cytoreduction for advanced EOC, between 2014 and 2018, were analysed. Patients were divided in two groups on the basis of whether cholecystectomy was performed. RESULTS: A total of 144 patients with stage IIIC/IV EOC were included. Cholecystectomy was performed in 22 (15.3%) patients. Those who underwent cholecystectomy more likely required diaphragmatic peritonectomy, splenectomy, lesser omentectomy, excision of disease from the porta hepatis and liver's capsule (p<0.001). There was no difference in the cytoreductive outcomes (complete or optimal) and the rate of grade 3-5 complications between the two groups (p=0.10 & p=0.06, respectively). No direct complications related to cholecystectomy were observed. CONCLUSION: A significant percentage of patients with advanced EOC require cholecystectomy. Gynecologic oncologists should embrace the opportunity to develop advanced surgical skills including cholecystectomy.

Learning curve for gynecological oncologists in performing upper abdominal surgery.

BACKGROUND: To assess the learning curve for gynecological oncologists in performing upper abdominal surgery for management of patients with advanced epithelial ovarian cancer (EOC). METHODS: Patients undergoing cytoreductive surgery for stage IIIC and IV EOC that required at least one surgical procedure in the upper abdomen were divided in three numerically equal groups: group 1, 2 and 3 that underwent surgery between December 2012 and July 2014, August 2014 to March 2016 and April 2016 to March 2018 respectively. RESULTS: One hundred and twenty-six patients were included. The percentage of patients undergoing primary surgery for group 1, 2 and 3 was 47.6%, 50.0% and 73.8%, respectively (P=0.02). There was significant increase in the percentage of patients undergoing cholecystectomy (P=0.02), resection of disease from porta hepatis (P=0.008), liver capsulectomy (P<0.001), lesser omentectomy (P<0.001) and celiac trunk lymphadenectomy (P<0.001) in the group 3. There was no difference in the percentage of patients undergoing splenectomy, diaphragmatic peritonectomy/resection and gastrectomy. Complete cytoreduction was achieved in 54.8%, 35.7% and 64.3% of patients in group 1, 2 and 3 respectively (P=0.028). There was no significant difference in the occurrence of grade 3-5 complications. Presence of a liver surgeon was required in 9.1%, 5.6% and 0% of cases in group 1, 2 and 3 respectively. CONCLUSIONS: The results reflect the evolution of surgical skills in the upper abdomen through the increase in the percentage of patients undergoing primary surgery, with the surgical team undertaking more complex procedures, less involvement of other specialties and simultaneously achieving higher rates of complete cytoreduction.

The Role of Magnetic Resonance Imaging in the Pre-operative Evaluation of Women Diagnosed With Atypical Endometrial Hyperplasia.

BACKGROUND/AIM: To evaluate the role of MRI in patients with atypical endometrial hyperplasia (AEH) and incorporate MRI findings in predictive models estimating the risk of co-existent endometrial cancer (EC). PATIENTS AND METHODS: Data from 189 women diagnosed with AEH and had MRI scan prior to operation, over nine years, were retrospectively collected. RESULTS: Histology showed EC in 51 (27%) cases. Presence of myometrial invasion on MRI was more commonly detected in patients with EC compared to those with benign pathology (37.3% versus 10.9%, p<0.001). The sensitivity and specificity of MRI in identifying cancer were 37% and 89%, respectively. Age, menopausal status and presence of invasion on MRI were the best predictors for the presence of malignancy. CONCLUSION: Myometrial invasion on MRI is associated with increased risk of EC in women with AEH. Its accuracy in detecting malignancy improves when combined with clinical parameters. This could be of value for conservative-management candidates.

Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus. The purpose of this prospective study was to determine the prevalence and clinical predictors of EoE in patients undergoing elective upper endoscopy. METHODS: We enrolled 400 consecutive adults (median age, 50 years; range, 19-92 years) who underwent routine upper endoscopy from March to September 2007 at a tertiary care military hospital. All patients completed a symptom questionnaire. All endoscopic findings were noted. Eight biopsies were obtained from proximal and distal esophagus and were reviewed by a blinded gastrointestinal pathologist. Patients had EoE if > or =20 eosinophils/high-power field were present. RESULTS: The prevalence of EoE in this cohort was 6.5% (25/385; 95% confidence interval, 4.3%-9.4%). Compared with EoE negative patients, EoE positive patients were more likely to be male (80.0% vs 48.1%, P = .003), younger than 50 years (72.0% vs 48.9%, P = .037), and have asthma (32.0% vs 10.8%, P = .006), a food impaction (32.0% vs 8.9%, P = .002), dysphagia (64.0% vs 38.1%, P = .018), and classic endoscopic findings (rings, furrows, plaques, or strictures) of EoE (all P < .01). Logistic regression identified asthma (odds ratio [OR], 4.48), male gender (OR, 4.23), and esophageal rings (OR, 13.1) as independent predictors of EoE. The presence of classic endoscopic findings of EoE had a sensitivity of 72% (54%-88%), specificity of 89% (87%-90%), and negative predictive value of 98% (95.6%-99.1%). CONCLUSIONS: The prevalence of EoE in an outpatient population undergoing upper endoscopy was 6.5%. The characteristic findings of EoE patients included male gender, history of asthma, and the presence of classic findings of EoE on endoscopy, which is the strongest predictor of this disease process.

Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies?

PURPOSE: Angiogenesis has a vital role in tumor growth and metastasis, and vascular endothelial growth factor (VEGF) represents a potent cytokine in this process. However, the influence of VEGF in ovarian cancer remains controversial. Interest has focused on the use of antiangiogenic drugs in ovarian cancer. This study aims to establish the pattern of expression and effect on prognosis of VEGF in a large population of ovarian cancer patients and to potentially identify a cohort in whom antiangiogenic therapy is appropriate. EXPERIMENTAL DESIGN: Using a tissue microarray of 339 primary ovarian cancers, the expression of VEGF was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied. RESULTS: Tumors expressing high levels of VEGF had significantly poorer survival (P = 0.04). Factors shown to predict prognosis independently of each other were age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. VEGF was independently predictive of prognosis on multivariate analysis (P = 0.02). There was no correlation between VEGF and any clinicopathologic variable. High expression of VEGF was seen in only 7% of the tumors, suggesting that the role of antiangiogenic drugs may be limited to a small subset of patients. CONCLUSION: High VEGF expression occurs in a small proportion of ovarian cancers, and this independently predicts poor prognosis. The small percentage of tumors with high levels of VEGF activity suggests that the role of bevacizumab may potentially be limited to a few patients; these patients could be targeted by molecular profiling.

Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps.

BACKGROUND: Fundic gland polyps (FGP) have been implicated with long-term proton pump inhibitor (PPI) use. AIMS: We attempted to investigate the impact of length and dosage of PPI therapy on the development of FGP. METHODS: A retrospective cohort study of all patients who had gastric polyps removed during elective upper endoscopy between March and September 2007 as part of a prior prospective study protocol was carried out. FGP were determined histologically. Prior to endoscopy, all patients completed a questionnaire regarding PPI use and length of therapy (no PPI use, 1-48 months, >48 months). The dosage of PPI was obtained via a thorough chart review of electronic medical records. RESULTS: Three hundred and eighty-five patients completed upper endoscopy and a questionnaire reporting PPI use (252 [65.4%] patients on PPI). On endoscopy, 55 patients had polyps, with the majority (43/55, 78%) being FGP, resulting in an overall prevalence of 11.1% (43/385). On univariate analysis, FGP were associated with Caucasian race (15 vs. 6%; P=0.009) and chronic PPI therapy (>48 months) (31.9 vs. 7.5%, P<0.001). There was a significant linear-by-linear association between PPI dosage and FGP prevalence (no PPI use, 7.5%; once daily, 10.8%; twice daily 17.4%, P=0.026). On logistic regression, the only independent predictor of FGP was duration of PPI use >48 months (P=0.001, odds ratio [OR] 4.7 [2.0-12.9]). CONCLUSIONS: The only independent predictor of FGP development in our study was duration of PPI therapy greater than 48 months. Increased dosage of therapy did not significantly impact the development of FGP.

Loss of IFN gamma receptor is an independent prognostic factor in ovarian cancer.

PURPOSE: There is evidence that IFN gamma plays an important role in ovarian cancer development. IFN gamma produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFN gamma receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer. EXPERIMENTAL DESIGN: Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFN gamma receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. RESULTS: Tumors expressing high levels of IFN gamma receptor had significantly improved survival (P=0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P=0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFN gamma receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables. CONCLUSIONS: Loss of IFN gamma receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFN gamma in ovarian cancer trials and highlights a subgroup of high expressing IFN gamma receptor tumors which are more likely to be susceptible to such treatments.

The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer.

BACKGROUND: MUC1 and MUC3 are from a large family of glycoproteins with an aberrant expression profile in various malignancies. Much interest has been focused on the role of these proteins in the development and progression of colorectal cancer; however, no previous studies have included the highly confounding variable of vascular invasion in their survival analysis. Using high throughput tissue microarray technology we assessed the prognostic value of MUC1 and MUC3 expression in the largest cohort of colorectal cancer patients to date. We propose that tumours lacking expression of MUC1 and MUC3 will be more likely to metastasise, due to previously observed loss of cell-cell adhesion, and this will therefore lead to more aggressive cancers with poorer prognosis. METHODS: A tissue micro-array was prepared from tumour samples of 462 consecutive patients undergoing resection of a primary colorectal cancer. A comprehensive prospectively recorded data base with mean follow up of 75 months was collected and included common clinicopathological variables and disease specific survival. Immunohistochemical analysis of MUC1 and MUC3 expression was performed using antibodies NCL-MUC1 and 1143/B7 respectively, results were correlated with the variables within the database. RESULTS: Positive expression of MUC1 and MUC3 was seen in 32% and 74% of tumours respectively. On univariate analysis no correlation was seen with either MUC1 or MUC3 and any of the clinicopathological variables including tumour grade and stage, vascular invasion and tumour type. Kaplan-Meier analysis demonstrated a significant reduction in disease specific survival with MUC1 positive tumours (p = 0.038), this was not seen with MUC3 (p = 0.552). On multivariate analysis, using Cox proportional hazards model, MUC1 expression was shown to be an independent marker of prognosis (HR 1.339, 95%CI 1.002-1.790, p = 0.048). CONCLUSION: MUC1 expression in colorectal cancer is an independent marker of poor prognosis, even when vascular invasion is included in the analysis. These results support previous studies suggesting a role for MUC1 in colorectal cancer development possibly through its effects on cell adhesion.

Investigation and management of abnormal peri-menopausal bleeding.

Abnormal peri-menopausal bleeding is a common clinical problem. Decisions to investigate if the menstrual disorders are related to an underlying pathology or represent physiologic changes are often complex especially as no clear guidance is available. The aim of this review is to present a summary of the current available evidence regarding the investigation tools used to evaluate women with abnormal uterine bleeding during menopausal transition and in the post-menopausal period. In this article, we focus mainly on the investigation and exclusion of endometrial carcinoma, as this represents the most common malignancy diagnosed.

Late presentation of metastatic smooth muscle neoplasm of the uterus with low malignant potential.

A 48-year-old woman underwent total abdominal hysterectomy with conservation of the ovaries and tubes. Histology showed a well-circumscribed smooth muscle tumor with foci of degeneration (including infarct-type necrosis) but no coagulative tumor cell necrosis and only mild focal cytological atypia. She presented, 24 years later with shortness of breath and abdominal distension and underwent bilateral salpingo-oophorectomy, appendectomy, omental biopsy and para-aortic lymph node sampling. Histology showed bilateral ovarian smooth muscle tumors with no coagulative tumor cell necrosis or significant cellular atypia. The cells were mitotically active. The tumors in both ovaries were most likely secondary to the previous uterine smooth muscle neoplasm. To our knowledge, this case is the first in the literature to describe a benign cellular leiomyoma that subsequently behaved as a smooth muscle tumor of uncertain malignant potential, which recurred 24 years after the initial diagnosis.