Laparoscopic assessment improves case selection for exenterative surgery in recurrent cervical and endometrial cancer.

The objective of this study is to evaluate the role of laparoscopy in the case selection of patients for pelvic exenteration to treat recurrent cervical or endometrial cancer. Pelvic exenteration is a rare surgical procedure performed by specialised multidisciplinary surgical teams. We performed a review of 55 consecutive laparoscopies for patients being evaluated for possible exenterative surgery for recurrent cervical or endometrial cancer at a single centre in the UK with a significant exenterative surgical practice. All patients had no evidence of metastatic disease on imaging prior to the laparoscopy. Despite thorough radiological assessment laparoscopy detected peritoneal, nodal or extrapelvic metastases in 20.8% of cases. 5.6% of the patients who underwent exenterative surgery were found to have unresectable pelvic disease intraoperatively. In these cases, the extent of disease was not determined radiologically or during the initial exploratory laparotomy. In our view, laparoscopic assessment is an essential component of the pre-operative work up of patients with recurrent cervical or endometrial cancer being considered for exenterative surgery.Impact statementWhat is already known on this subject? Pelvic exenteration is potentially curative in cases of recurrent pelvic malignancy. Case selection is essential to determine those patients without metastases and with resectable pelvic disease - this will improve patient outcomes, avoid the unnecessary morbidity of major surgery, as well as the psychological consequences of abandoned procedures. The only two previous studies, published in 1998 (Plante and Roy 1998) and 2002 (Köhler et al. 2002) have shown laparoscopic assessment to be safe and improve case selection.What do the results of this study add? This study provides evidence that in the context of modern imaging modalities, including PET-CT scans, laparoscopic assessment continues to improve case selection for exenterative surgery.What are the implications of these findings for clinical practice and/or further research? This study provides further evidence of the benefit of laparoscopy in the assessment of patients being considered for exenterative surgery for recurrent pelvic cancer. Routine laparoscopy improves case selection and will enhance patient experiences and outcomes.

An Unusual Case of YWHAE-NUTM2A/B Endometrial Stromal Sarcoma With Confinement to the Endometrium and Lack of High-Grade Morphology.

Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion. The initial hysteroscopic biopsy showed a cyclinD1-positive classic LG ESS-like component which merged with a smaller cyclinD1 negative/focally positive fibroblastic component with no HG areas. YWHAE-NUTM2A/B genetic fusion was shown by real-time quantitative polymerase chain reaction and Sanger sequencing. In the subsequent hysterectomy specimen, the tumor was entirely confined to the endometrium and was largely composed of cellular and classic LG ESS-like areas (80%) which were strongly and diffusely positive for cyclinD1 and a focal fibroblastic component (20%) which was largely cyclinD1 negative. Despite the cellular areas showing mild nuclear enlargement, the entire tumor had a very low mitotic and proliferation index and showed strong and diffuse positivity for estrogen and progesterone receptors. The patient remains alive and well with no evidence of disease 14 mo following diagnosis. To our knowledge, this is the first reported case of YWHAE-NUTM2A/B ESS that is confined to the endometrium and which exhibits entirely LG morphology.

Outcome of Appendicectomies at Surgery for Mucinous Ovarian Neoplasms: Report From A UK Center and Review of Literature.

OBJECTIVE: This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT). METHODS: Women with borderline and malignant MOT were identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study. Data were collected from the electronic patient record and case notes. RESULTS: Of 310 women identified with MOT, 203 patients with benign MOT were excluded. Of the remaining 107 patients, 15 patients with previous appendicectomy were also excluded. The study population consisted of 92 patients. There were 57 (62%) patients with borderline MOT and 35 (38%) patients with malignant MOT. In the borderline subgroup, 40/57 (70%) patients had appendicectomy of whom 8 (20%) had macroscopically abnormal appendices. One patient had pseudomyxoma peritonei secondarily involving the appendix and 7 patients had a histologically normal appendix. Normal histology was found in all macroscopically normal appendices. In the malignant subgroup, 29/35 (83%) patients had an appendicectomy. There were 8 (27.5%) macroscopically abnormal appendices with a malignant pathology in 7 (87.5%) patients and 1 patient had a resolving appendicitis. There were 21 macroscopically normal appendices of which, serrated adenoma was found in 1 (4.8%) patient, whereas the remaining 20 (95.2%) patients had normal histology. CONCLUSIONS: In MOT, an abnormal appearing appendix should be excised. If the appendix is grossly normal, our data do not support performing an appendicectomy as part of a surgical staging procedure.

Human Peritoneal Mesothelial Cells Display Phagocytic and Antigen-Presenting Functions to Contribute to Intraperitoneal Immunity.

Mesothelial cells lining the peritoneal cavity are strategically positioned to respond to and counter intraperitoneal infections, cancer cells, and other challenges. We have investigated human peritoneal mesothelial cells (HPMCs) for phagocytic activity, expression of surface Major Histocompatibility Complex (MHC) class II and accessory molecules involved in antigen presentation, and the ability to present recall antigens to T cells. Phagocytosis of dextran, latex beads, and Escherichia coli was observed by flow cytometry, and internalization was visualized using confocal and electron microscopy. Flow cytometry and/or cellular enzyme-linked immunosorbent assay showed constitutive expression of ICAM-1, LFA-3, and B7-1, but not B7-2 or MHC class II. Interferon-gamma induced MHC II and ICAM-1 expression in a dose- and time-dependent manner. Importantly, HPMCs induced autologous CD3 T-lymphocyte proliferation (H incorporation) after pulse with recall antigen. Human peritoneal mesothelial cells equipped with phagocytic and antigen-presenting machinery are anticipated to have an integral role in intraperitoneal immune surveillance.

Exenterative surgery for recurrent gynaecological malignancies.

BACKGROUND: Cancer is a leading cause of death worldwide. Gynaecological cancers (i.e. cancers affecting the ovaries, uterus, cervix, vulva and vagina) are among the most common cancers in women. Unfortunately, given the nature of the disease, cancer can recur or progress in some patients. Although the management of early-stage cancers is relatively straightforward, with lower associated morbidity and mortality, the surgical management of advanced and recurrent cancers (including persistent or progressive cancers) is significantly more complicated, often requiring very extensive procedures. Pelvic exenterative surgery involves removal of some or all of the pelvic organs. Exenterative surgery for persistent or recurrent cancer after initial treatment is difficult and is usually associated with significant perioperative morbidity and mortality. However, it provides women with a chance of cure that otherwise may not be possible. In carefully selected patients, it may also have a place in palliation of symptoms. The biology of recurrent ovarian cancer differs from that of other gynaecological cancers; it is often responsive to chemotherapy and is not included in this review. OBJECTIVES: To evaluate the effectiveness and safety of exenterative surgery versus other treatment modalities for women with recurrent gynaecological cancer, excluding recurrent ovarian cancer (this is covered in a separate review). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of clinical guidelines and review articles and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or non-randomised studies with concurrent comparison groups that included multivariate analyses of exenterative surgery versus medical management in women with recurrent gynaecological malignancies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No studies were found; therefore no data were analysed. MAIN RESULTS: The search strategy identified 1311 unique references, of which seven were retrieved in full, as they appeared to be potentially relevant on the basis of title and abstract. However, all were excluded, as they did not meet the inclusion criteria of the review. AUTHORS' CONCLUSIONS: We found no evidence to inform decisions about exenterative surgery for women with recurrent cervical, endometrial, vaginal or vulvar malignancies. Ideally, a large RCT or, at the very least, well-designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare exenterative surgery versus medical management, including palliative care.

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

OBJECTIVE: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

The use of laparostomy in patients with gynecologic cancer: first report from a UK cancer center.

OBJECTIVE: To report on the use of laparostomy after major gynecologic cancer surgery. METHODS: Operative records and surgical databases of patients who underwent major open abdominal surgery over a 6.5-year period at a tertiary referral center were searched. Patients who had diagnostic procedures, operative laparoscopy, and surgery for vulval cancer were excluded. All patients who had laparostomy were identified; and the diagnosis, indication for laparostomy, method of temporary cover, and complications were recorded. RESULTS: A total of 1592 laparotomies, including 37 emergencies, were performed. Of these, 14 patients (0.88%) had a laparostomy. Seven patients had primary cancer and 7 had recurrent cancer. As more patients had surgery for primary disease, laparostomy was more common in patients who underwent surgery for recurrent cancer. Seven patients had ovarian/fallopian tube/primary peritoneal cancer, 4 patients had uterine cancer, 2 patients had cervical cancer, and one patient had vaginal cancer. Ten laparostomies (71.4%) were performed after an emergency procedure; thus, laparostomy was approximately 100 times more common after emergency than elective major surgery. Massive bowel distension and bowel wall edema were the major indications for laparostomy. The method of temporary closure was variable, and a sterile saline bag was the most commonly used. The laparostomy was closed in all but 2 patients, most often on postoperative day 2 or 3. Two patients (14.3%) died within 30 days of the laparostomy, and 2 others died at postoperative days 40 and 62. Three of these 4 patients had recurrent cancer, and 2 patients had emergency procedures. CONCLUSIONS: The overall incidence of laparostomy associated with laparotomy for gynecological cancer surgery was less than 1:100 cases, was more common after surgery for recurrent cancer, and in particular, was approximately 100 times more common after emergency procedures. The 30-day operative mortality rate was 14.3%.

Dissection of soft-preserved cadavers in the training of gynaecological oncologists: report of the first UK workshop.

OBJECTIVE: To assess the surgical anatomy knowledge of gynaecological oncology (GO) trainees and to evaluate the impact of a cadaveric dissection course on postgraduate surgical training. METHODS: An intensive 3-day cadaveric dissection course with illustrated lectures and supervised dissection, with a multiple-choice questionnaire (MCQ) on surgical anatomy at the beginning and end of the course was organised in the Anatomy Facility of a London Medical School. Each cadaver was embalmed with a mixture of alcohol, phenol and glycerol ("soft-preserved") rather than fixed in formalin, to more closely preserve in vivo conditions of the body. There were ten dissecting delegates, two per cadaver. The delegates dissected the abdomen and pelvis with the emphasis on surgical approaches rather than the classical descriptive anatomy approaches. Delegates also completed a course evaluation. RESULTS: Without negative marking, the mean initial MCQ score was 57%, and final mean score 64%. With negative marking, the mean initial score was 43%, and mean final score 53%. Delegates rated the course highly, would recommend it to other trainees and considered that such a course should be incorporated into subspecialty training. CONCLUSION: The surgical anatomy knowledge of subspecialty trainees was weak but improved as a result of the dissection course. The most positive finding was the course evaluation. Postgraduate surgical training in GO would likely be enhanced by, and arguably requires, cadaveric dissection. "Soft-preserved" rather than formalin-fixed cadavers should be used.

Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation.

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH(2) lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. (1)H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH(2) lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH(2) lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer.

MR imaging features of vaginal malignancies.

Primary vaginal malignancies are rare, accounting for only 1%-2% of all gynecologic malignancies. Squamous cell carcinoma makes up about 85% of primary vaginal malignancies. This tumor characteristically arises from the posterior wall of the upper third of the vagina. The main patterns of disease are an ulcerating or fungating mass or an annular constricting lesion. At magnetic resonance (MR) imaging, squamous cell carcinoma has intermediate signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumors that account for the remaining 15% of primary vaginal malignancies are adenocarcinoma, melanoma, and sarcomas. The signal intensity characteristics on MR images correlate with the histologic subtypes and reflect the MR imaging appearances of these histologic subtypes elsewhere in the body. Secondary malignancy of the vagina is far more frequent than primary vaginal malignancy. Most vaginal metastases occur by means of direct local spread from the cervix, uterus, or rectum. The MR imaging appearances of these metastases reflect the MR imaging appearances of the primary tumor.

Venous thromboembolism at time of diagnosis of ovarian cancer: Survival differs in symptomatic and asymptomatic cases.

OBJECTIVES: To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. MATERIALS AND METHODS: The clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. RESULTS AND CONCLUSIONS: Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n=12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p=0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p=0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?

PURPOSE: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. PATIENTS AND METHODS: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. RESULTS: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients' original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). CONCLUSION: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.

Epithelial ovarian cancer metastasizing to the brain: a late manifestation of the disease with an increasing incidence.

PURPOSE: We present the Royal Marsden Hospital experience of cerebral metastases from primary epithelial ovarian carcinoma (EOC) over the last 20 years and examine the evidence for an increasing incidence of EOC metastasizing to this site. PATIENTS AND METHODS: A total of 3,690 women with EOC were seen at the Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed cerebral metastases. RESULTS: Median age at diagnosis of EOC was 52 years (range, 39 to 67). All patients received at least one line of platinum-based chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four lines. The median treatment interval between each line of chemotherapy was 12, 18, and 4 months. The median interval between diagnosis and CNS relapse was 46 months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to 1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the literature also suggests that the incidence of cerebral metastases from EOC has increased over time. CONCLUSION: CNS metastases in EOC are a rare and late manifestation of the disease, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses. An analysis of our data and the data from the literature suggests that the incidence of metastasis at this site in patients with EOC is increasing.

A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene.

PURPOSE: HER-2/neu oncogene is overexpressed in 10-30% of epithelial ovarian cancers and is associated with a poor prognosis. The E1A gene product of adenovirus type 5 down-regulates HER-2/neu and causes tumor regression in animal models. In the current study, we sought to determine the toxicity and biological activity of E1A-lipid complex in ovarian cancer patients. EXPERIMENTAL DESIGN: A Phase I trial involving intraperitoneal (i.p.) administration of E1A-lipid complex was initiated in ovarian cancer patients to assess biological activity (E1A gene transfer/transcription/translation and HER-2/neu expression) and to determine the maximum tolerated dose. Successive cohorts received E1A-lipid complex at doses of 1.8, 3.6, and 7.2 mg DNA/m(2), given as weekly i.p. infusions for 3 of 4 weeks (each cycle) up to a maximum of six cycles. Peritoneal fluid was sampled at baseline and twice monthly for cellularity, cytology, CA-125, and biological activity RESULTS: Fifteen patients, with a median age of 57 years (range, 43-81) were recruited. Three (1.8 mg DNA/m(2)), 4 (3.6 mg DNA/m(2)), and 8 patients (7.2 mg DNA/m(2)) received i.p. E1A. A total of 91 infusions (range, 1-18) was administered. Abdominal pain was the dose-limiting toxicity, and the maximum-tolerated dose was 3.6 mg DNA/m(2). E1A gene transfer and expression was observed in all of the patients and at all of the dose levels. HER-2/neu down-regulation could be demonstrated in the tumor cells of 2 patients (18%). There was no correlation between dose and biological activity. CONCLUSIONS: I.P. EIA-lipid complex gene therapy is feasible and safe. Future studies, either alone or in combination with chemotherapy, particularly in patients with minimal residual disease, should be evaluated.

Pelvic nerve plexus trauma at radical and simple hysterectomy: a quantitative study of nerve types in the uterine supporting ligaments.

OBJECTIVE: Using neuropeptide and enzyme markers to autonomic nerves, we sought to demonstrate and quantify the nerve types contained within the uterosacral ligaments (USLs) and cardinal ligaments (CLs) that are divided during radical hysterectomy (RH). METHODS: Cross-sectional biopsies were collected from the lateral third of the USL and the CL in 24 women who had an RH for cervical cancer, and from the uterine insertion of these ligaments in 11 women who had a simple hysterectomy for benign disease. We applied indirect immunofluorescence with FITC-conjugated secondary antibodies, using polyclonal primary antibodies to neuropeptide markers that predominate within somatic and autonomic nerves, to show different populations of the following nerve types within the biopsies: neuropeptide Y (NPY) and tyrosine hydroxylase (TH) for sympathetic nerves; vasoactive intestinal polypeptide (VIP) for parasympathetic nerves; substance P (SP) for nociceptive and sensory-motor nerves; and calcitonin gene-related peptide (CGRP) for sensory and sensory-motor nerves. The percentage area of immunoreactivity (PAI), determined by a computer-assisted image analyzer attached to a fluorescent microscope, was used as an objective quantitative measure of nerve density. Confocal microscopy was used to determine the composition and spatial arrangement of nerve fibers in the ligaments. RESULTS: The PAI was greater for all markers tested in both the USL and CL (P <.001) in RH compared with simple hysterectomy biopsies. For RH specimens, the PAI was greater for the sympathetic, sensory, and sensory-motor nerve markers in the USL compared with the CL (P <.01), but the PAI for VIP was similar (P >.05). Conversely, excluding the large trunks and associated ganglia, the free nerve fiber PAI in the CL was greater than that of the USL for all nerve markers (P <.001). The staining of peripheral autonomic ganglia and associated fibers, for NPY and TH, indicates that some sympathetic nerves are preganglionic with their cell bodies within the pelvic plexus. CONCLUSIONS: Significantly more autonomic nerves are transected in the more lateral division of the uterine supporting ligaments during a radical hysterectomy than during a simple hysterectomy. Sympathetic, parasympathetic, sensory, and sensory-motor nerve types are present within the CL and USL. The proportions of each nerve type differ between the two ligaments, and sympathetic nerves in the USL are the single largest nerve type. The uterine supporting ligaments are a major pathway for autonomic nerves to the pelvic organs.

The prevention and management of treatment related morbidity in vulval cancer.

The traditional and the most common management of primary vulval cancer is radical surgery of the vulva and radical groin lymphadenectomy (unilateral or bilateral). Adjuvant radiotherapy is used in poor prognosis cases. Rare vulval cancers, locally advanced cancers and recurrent vulval cancers often are treated with a combination of surgery, radiation therapy and chemotherapy. The treatments, while often curative, are associated with considerable morbidity, which, until recently, has not been well publicized or quantified. Increasingly, younger patients are presenting with extensive and often multi-focal pre-invasive disease and with vulval cancer. Long-term post-treatment physical, sexual and psychological morbidity is of major concern. There is more onus on clinicians to provide less radical but equally curative treatment, while also reducing morbidity. There is also the need to provide treatment and treatment modification based on supporting evidence. For a rare disease such as vulval cancer it is more difficult to generate data and to conduct trials on treatment modifications. Although surgical modifications have been made, the morbidity of radical surgery for vulval cancer is considerable. The prevention and management of treatment-related morbidity will continue to challenge the gynaecological oncology team.