Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer.

OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase retrospective cohort study. SETTING: West London Gynaecological Cancer Centre, UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT in predicting surgical outcome. RESULTS: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small-bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. CONCLUSIONS: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning.

Supporting the wider use of laparoscopy in the treatment of ovarian masses.

Patients with ovarian masses which have a moderate risk of malignancy are frequently treated by open laparotomy, despite the Royal College of Obstetricians and Gynaecologists (RCOG) guidance indicating that laparoscopic oophorectomy may be performed in selected cases. The reluctance to perform laparoscopic surgery in these cases is normally due to the perception that survival is affected if the mass is subsequently diagnosed as being malignant, the risk of rupture impacting on FIGO stage and the need for additional staging surgery. However, there is no good evidence to support these views. Preoperative diagnosis of ovarian masses is limited and thus a significant number of patients are subjected to open surgery, where they may have benefitted from the advantages of laparoscopic surgery. We argue that in the absence of a definitive preoperative test, there are advantages to the laparoscopic approach in patients who have a moderate risk of malignancy and further high level evidence should be encouraged in this field.

Training the trainees: an evaluation exercise using the TLH and BSO model.

Our aim was to evaluate surgical training in gynaecological oncology by assessing the time required by a trainee to complete a single laparoscopic gynaecologic-oncological operation. A total of 135 patients with a BMI < 40 kg/m2, diagnosed with endometrial cancer, underwent a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH and BSO). Patients in Group I (n = 78) were operated on by a consultant gynaecological oncology surgeon and in Group II (n = 57) by sub-specialist trainees (SSTs). The mean patient age and BMI was 63.5 years and 29.6 kg/m2, respectively, in Group I and 64.5 years and 29.9 kg/m2, respectively, in Group II. Median operating times for Groups I and II were 58 and 90 min, respectively (p < 0.05). Furthermore, significant improvement was noted when comparing the average operating time between the first and second half of SST training. Even experienced gynaecological trainees take significantly longer to perform a reproducible laparoscopic operation. At the completion of training, an SST demonstrates improvement with respect to operation duration but is still not as fast as the trainer.

Abdominal radical trachelectomy in West London.

OBJECTIVE: Traditionally, the surgical management of invasive cervical carcinoma that has progressed beyond microinvasion has been a radical abdominal hysterectomy. However, this results in the loss of fertility, with significant consequences for the young patient. This report describes abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with stage IA2-IIA cervical cancer who desire a fertility-sparing procedure without decreasing the curative rates. DESIGN: Observational, retrospective study. SETTING: Teaching hospital and regional cancer centre in London, UK. POPULATION: Patients undergoing ART. METHODS: Patients presenting during the period 2000-2009 with cervical cancer stage IA2-IIA were offered a trachelectomy, if they expressed a desire to preserve fertility. The type of trachelectomy (vaginal/abdominal) was chosen based on patient anatomy and neoplastic and magnetic resonance imaging characteristics. Each patient was counselled as to the experimental nature of the procedure. MAIN OUTCOME MEASURES: Survival, recurrence and fertility issues among ART patients. RESULTS: A total of 30 patients underwent ART (open and laparoscopic) between 2001 and 2009. Three patients presented with a recurrence, two of which have died (median follow-up: 24 months). Only three patients required further surgical re-intervention because of operative complications. Ten patients attempted to conceive, resulting in three conceptions (30%) and two live children. CONCLUSIONS: Abdominal radical trachelectomy provides a feasible, cost-effective and safe treatment option for young women who have been diagnosed with early-stage cervical cancer and wish to preserve their fertility.

Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women.

This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost-effective and adds to the weight of evidence for its use in this condition.

Functions of human papillomavirus E6 and E7 oncoproteins.

The identification of certain human papillomaviruses as human tumour viruses has been paralleled by our understanding of how the viral oncoproteins function. The virally encoded E6 and E7 proteins act, in part, to abrogate the activities of the tumour suppressor proteins p53 and pRB. The interaction between these viral proteins and regulators of cell growth offers targets for future therapeutic developments.

Human papillomavirus detection by hybrid capture and its possible clinical use.

AIMS: To determine the sensitivity of the hybrid capture method for human papillomavirus (HPV) detection and potential clinical uses as a screening method for the identification of cervical intraepithelial neoplasia. METHODS: The presence of oncogenic types of HPV was tested for in samples taken from the cervix at colposcopy, and compared with detection by polymerase chain reaction (PCR) in 60 patients. Both sets of results were corrected with the pathology determined by biopsy and smear cytology. RESULTS: Hybrid capture detection showed 86% agreement with PCR. Eighty three percent of CIN 3 lesions, 62% of CIN 2, 59% of CIN 1 and 21% of normal controls were positive for oncogenic HPV types. CONCLUSION: The hybrid capture detection method is reliable, sensitive, and easy to use. The addition of HPV testing to cytological screening would detect a greater proportion of cervical dysplasia with a higher false positive rate.

Conserving fertility in the management of gynaecological cancers.

The quality of cancer treatment is judged by both morbidity and mortality. Patients benefit if morbidity is reduced without compromising mortality. This applies particularly for women who develop gynaecological malignancy during their childbearing years where curative treatment also renders them infertile. This study reviews the increasing role of fertility-sparing surgery in such women. A literature search was undertaken using PubMed, entering the terms endometrial cancer, cervical cancer and ovarian cancer in conjunction with the terms fertility and fertility sparing. Each relevant identified paper was reviewed, references checked and results collated to provide an evidence-based summary of fertility-sparing treatments for gynaecological malignancy. Fertility-sparing surgery is appropriate in many circumstances, and all doctors who advise young women with gynaecological malignancy should be aware of these possibilities. However, data are relatively sparse in many situations, and careful counselling and balanced guidance are essential if patients are to understand the full implications of their choices.

Virtual reality simulation training can improve technical skills during laparoscopic salpingectomy for ectopic pregnancy.

OBJECTIVES: To assess the first commercially available virtual reality (VR) simulator to incorporate procedural modules for training of inexperienced gynaecological surgeons to perform laparoscopic salpingectomy for ectopic pregnancy. DESIGN: Prospective cohort study. SETTING: Departments of surgery and gynaecology in central London teaching hospitals. SAMPLE: Thirty gynaecological surgeons were recruited to the study, and were divided into novice (<10 laparoscopic procedures), intermediate (20-50) and experienced (>100) groups. METHODS: All subjects were orientated to the VR simulator with a basic skills task, followed by performing ten repetitions of the virtual ectopic pregnancy module, in a distributed manner. MAIN OUTCOME MEASURES: Operative performance was assessed by the time taken to perform surgery, blood loss and total instrument path length. RESULTS: There were significant differences between the groups at the second repetition of the ectopic module for time taken (median 551.1 versus 401.2 versus 249.2 seconds, P = 0.001), total blood loss (median 304.2 versus 187.4 versus 123.3 ml, P = 0.031) and total instrument path length (median 17.8 versus 8.3 versus 6.8 m, P = 0.023). The learning curves of the experienced operators plateaued at the second session, although greater numbers of sessions were necessary for intermediate (seven) and novice (nine) surgeons to achieve similar levels of skill. CONCLUSIONS: Gynaecological surgeons with minimal laparoscopic experience can improve their skills during short-phase training on a VR procedural module. In contrast, experienced operators showed nonsignificant improvements. Thus, VR simulation may be useful for the early part of the learning curve for surgeons who wish to learn to perform laparoscopic salpingectomy for ectopic pregnancy.

Human papillomavirus and cervical cancer.

Cervical cancer is the fifth most common cancer worldwide, and is second only to breast cancer as the leading cause of cancer deaths in women. Half a million cases are diagnosed annually with the highest rates in developing countries.

PIP: Several evidences have demonstrated the role of some human papillomaviruses (HPVs) in the etiology of cervical cancer. The most compelling evidence has come from numerous epidemiological studies which have identified HPV DNA sequences in the majority (80-90%) of cervical cancers and cervical carcinoma cell lines. In contrast, histologically normal cervices rarely (5-10%) show evidence of HPV infection, a difference that is further emphasized when age is taken into consideration. However, studies have also shown that HPV infection alone is not sufficient to mediate the development of carcinoma, and that further somatic alterations are required for neoplastic progression. Moreover, extensive in-vitro studies have identified two HPV-encoded proteins, E6 and E7, which have transforming properties. Sequences encoding these two proteins are almost always retained and expressed in both carcinomas and cervical cancer cell lines, strongly supporting a causative role for the viral oncoproteins in cancer. These convincing epidemiological evidence of a role for HPV in cervical cancer, together with the increasing knowledge of the molecular biology of HPV-mediated transformation, increase prospects of novel diagnostic, prophylactic and therapeutic approaches to malignant cervical disease.

Posttransplant skin cancer: a possible role for p53 gene mutation but not for oncogenic human papillomaviruses.

BACKGROUND: Loss of p53 tumor suppressor function is a critical step in the development of diverse malignancies, including skin cancers in nonimmunosuppressed patients where UV-specific p53 gene mutations have been identified. In tumors associated with human papillomavirus (HPV), such as cervical carcinoma, p53 may be inactivated instead by binding to a viral oncoprotein. OBJECTIVE: Our purpose was to examine the hypothesis that HPV may play an analogous role in the development of posttransplant skin cancer. METHODS: p53 Immunoreactivity, suggestive of p53 gene mutation, was examined by immunocytochemistry. Oncogenic HPV DNA was detected by polymerase chain reaction. RESULTS: Comparable p53 immunoreactivity was seen in skin tumors from both transplant and nontransplant patients. HPV DNA was not demonstrated in any tumor specimen. CONCLUSION: Our data do not implicate oncogenic HPV in posttransplant skin cancer. p53 Gene mutation, rather than HPV-induced p53 degradation, may be more significant in the development of these tumors.