Search

Objective. The goal of this article is to systematically review the available evidence on the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) in staging of cervical carcinoma. Methods. A comprehensive computer literature search was performed in MEDLINE and EMBASE databases from January 1985 to May 2002. Two reviewers independently scored methodological quality of included studies and extracted relevant data for data analysis. A bivariate random effect approach was used to summarize estimates of sensitivity and specificity values. Covariates were added to this model to study the influence of sample size, publication year, methodological criteria, and MRI techniques on summary estimates. Results. Fifty-seven articles were included. In 49 articles one imaging modality was evaluated (MRI, 38; CT, 11), and in 8 articles, both. Inclusion criteria were: minimum of 10 patients included, histopathology as reference standard, sufficient data presented to construct 2(X) 2 tables. The exclusion criterion was: data reported elsewhere in more detail. Sensitivity estimates for parametrial invasion were 74% (95% C: 68-79%) for MRI and 55% (95% CI: 44-66%) for CT, and for lymph node involvement, 60% (95% CI 52%-68%) and 43% (95% CI: 37-57%), respectively. MRI and CT had comparable specificities for parametrial invasion and lymph node involvement. For bladder invasion and rectum invasion the sensitivities for MRI were respectively 75% (95% CI: 66-83%) and 71% (95% CI: 53-83%), higher compared with CT. The specificity in evaluating bladder invasion for MRI was significantly higher compared with CT: 91% (95% CI: 83-95%) for MRI and 73% (95% CI: 52-87%) for CT. The specificities for rectum invasion were comparable. Differences in patient sample size, publication year, methodological criteria, and MRI techniques had no effect on the summary estimates. Conclusion. For overall staging of cervical carcinoma, MRI is more accurate than CT. (C) 2003 Elsevier Inc. All rights reserved

5519 Background: Cytoreductive surgery and systemic therapy are essential for newly diagnosed ovarian cancer. We conducted a multicenter phase 3 trial to study whether the addition of intraperitoneal chemotherapy under hyperthermic conditions (HIPEC) to interval cytoreductive surgery would improve outcome among patients receiving neo-adjuvant chemotherapy for stage III epithelial ovarian cancer. Methods: We randomly assigned patients who showed at least stable disease after three cycles of carboplatin (area under the curve 6) and paclitaxel (175 mg/m2) to receive interval cytoreductive surgery with or without HIPEC using cisplatin (100 mg/m2). Randomization was performed per-operatively and eligible patients had no residual mass greater than 2.5 mm. Three additional cycles of carboplatin and paclitaxel were given post-operatively. The primary endpoint was recurrence-free survival. Overall survival, toxicity, and quality-of-life were key secondary endpoints. Results: A total of 245 patients were randomly assigned to one of the two treatment strategies. In an intention-to-treat analysis, interval cytoreductive surgery with HIPEC was associated with longer recurrence-free survival than interval cytoreductive surgery alone (15 vs. 11 months, respectively; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49 to 0.86; P=0.003). At the time of analysis, 49% of patients were alive, with a significant improvement in overall survival favoring HIPEC (48 vs. 34 months; HR, 0.64; 95% CI, 0.45 to 0.91, P=0.01). The number of patients with grade 3-4 adverse events was similar in both treatment arms (28% vs. 24%, p=0.61). Quality-of-life analysis will follow. Conclusions: The addition of HIPEC to interval cytoreductive surgery is well tolerated and improves recurrence free and overall survival in patients with stage III epithelial ovarian cancer. Clinical trial information: NCT00426257.

BACKGROUND The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens. RESULTS Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953. CONCLUSIONS It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted. Cancer 1999;86:652–6. © 1999 American Cancer Society.

Objective This systematic review assessed the effectiveness of hormone therapy (HT) in patients with a granulosa cell tumor (GCT) of the ovary. Methods Medline (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), prospective trial registers and PubMed (as supplied by publisher-subset) were searched up to January 13, 2014. No restrictions were applied. Two reviewers independently screened studies for eligibility and extracted data using a standardized, piloted extraction form. Studies evaluating the response to hormone therapy in patients with a GCT were included. The primary outcome was the objective response rate (ORR) to hormone therapy. Results In total, nineteen studies including 31 patients were eligible. Pooled ORR to hormone therapy was 71.0% (95% Confidence Interval 52–85). In 25.8% a complete response and in 45.2% a partial response was described. Four patients had stable disease. In five patients disease was progressive. Various hormone treatments showed different results, for instance aromatase inhibitors (AI) demonstrated response in nine out of nine therapies (100%) and tamoxifen in none out of three (0%). Median progression free survival (PFS) after the start of hormone therapy was 18months (range 0–60). Conclusions Despite the limited available data, hormone therapy appears to be a good treatment alternative for patients with advanced-stage or recurrent GCT. However, study quality is poor and prospective studies are needed to confirm clinical benefit of hormone therapy in GCTs.

ObjectivePatients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT.MethodsAll consecutive chemotherapy-naive patients in 3 referral hospitals who were treated with chemotherapy for residual or recurrent GCT between 1968 and 2011 were included. Main outcome was the response according to Response Evaluation Criteria in Solid Tumor criteria. A literature search in MEDLINE through PubMed was performed, from inception to August 19, 2013.ResultsTwenty-seven patients with a GCT who received chemotherapy were identified. Eighteen patients were not evaluable because they had either no measurable disease, or no imaging was performed before and after chemotherapy. One of the 9 evaluable patients (11%) had a complete response, and 1 patient (11%) had a partial response, resulting in a response rate of 22% (95% confidence interval, 0%–49%). Seven patients (78%) had stable disease (range, 2–50 months), and none had progressive disease. Fifteen studies that assessed response rates to chemotherapy on measurable disease in a total of 224 patients showed a response rate of 50% (95% confidence interval, 44%–57%). Strict criteria of response, however, were not uniformly applied in the majority of these published series.ConclusionsIn the present study, we present only a moderate beneficial effect of chemotherapy in patients with irresectable GCT with measurable disease. Comparison with previous studies is hampered by a lack of standardized response evaluation in the majority of studies. Given the toxicity of platinum-based chemotherapy, administering this treatment should be a well-considered decision.

ObjectiveThe objective of the study is to determine the risk factors for groin recurrence (GR) in patients with primary vulvar squamous cell carcinoma (SCC) after inguinofemoral lymphadenectomy (IFL) without lymph node metastases and/or adjuvant chemoradiotherapy.MethodsThe study is a multicenter retrospective review of clinical and histopathological data of patients with lymph node–negative vulvar SCC who underwent an IFL. Patients with and without GRs were compared to identify risk factors.ResultsIn 134 patients, 252 groins were eligible for the analyses—16 patients underwent ipsilateral IFL and 118 patients underwent bilateral IFL. Groin recurrences occurred in 4 (1.6%) of the 252 dissected groins. Besides, 1 patient who underwent ipsilateral IFL had a recurrence in the nonoperated contralateral groin; this groin was left out of analysis. The median number of dissected nodes per groin was 9.8 (range, 1–38) in all patients and 6.5 (range, 5–8) in patients with GR. Multivariate analyses showed that GR was related to poor differentiation (P = 0.04), and node count less than 9 (P = 0.04), no association with age, tumor localization, tumor diameter, focality, invasion depth, or stage was found. Nineteen patients with both low node count and poor differentiation had 19% GRs. Survival analyses showed less favorable survival in patients with poor differentiation.ConclusionsThe overall risk of developing GR after negative IFL in patients with vulvar SCC is low (1.6% per groin) but significantly higher in patients with tumors with a poor differentiation and lymph node count less than 9 at IFL. A large well-designed prospective study is needed to evaluate closer surveillance in patients at risk.

Optimal management of advanced vulvar cancer remains one of the most controversial issues within the treatment of gynecologic malignancies. Multimodality therapy that integrates (chemo)radiotherapy with less extensive surgery is well accepted in order to avoid stoma formation; however, the roles for adjuvant therapy after surgical management of both the primary and nodal disease are poorly defined. To avoid exenterative surgery in advanced disease, controversial alternatives including definitive (chemo)radiotherapy and neo-adjuvant chemotherapy have been explored, but are not clearly established. Unfortunately many of these controversies cannot be resolved definitively due to a lack of Level 1 and 2 evidence. Small retrospective series and expert multidisciplinary opinion can guide management in order to obtain the therapeutic advantages of the modalities available and must be tailored to the patient- and tumor-related factors in each situation.

OBJECTIVES: The aim of this study was to investigate the prevalence of human papillomavirus (HPV) after treatment for cervical dysplasia. STUDY DESIGN: The presence of HPV was investigated in cervical scrapes of 91 patients, before and after treatment, using consensus primers in the polymerase chain reaction. RESULTS: Before treatment for cervical dysplasia, 89 of 91 patients (98%) were HPV-positive compared with 28 of 91 patients (31%) after treatment. The HPV type present before treatment was found in the scrapes of only 9 of 89 patients (10%). Detection of HPV after treatment was associated with human immunodeficiency virus infection and incomplete conization. CONCLUSION: The HPV type present before treatment was frequently cleared by treatment for cervical dysplasia

BACKGROUND The biologic rationale for combining cisplatin with locoregional hyperthermia (HT) relates to the potentiating effect of HT on cisplatin cytotoxicity. METHODS Patients with recurrent cervical carcinoma, who had a pelvic recurrence after radiotherapy, were treated with weekly cycles of locoregional HT (using the 70-megahertz, 4 antenna-phased array system for 1 hour and cisplatin, 50 mg/m2 intravenously [i.v.], for a maximum of 12 cycles.) RESULTS Twenty-three patients were entered in this study. A total of 169 cycles were given. Responses were observed in 12 of 23 patients, a response rate of 52% (95% confidence interval, 31-73%). Salvage surgery became possible in 3 of 12 responding patients, whose tumors were previously considered unresectable. The median duration of response was 9.5+ months, the median overall survival was 8+ months, and the 1-year survival was 42%. No correlation was found between treatment outcome and clinical parameters such as age, weight, performance status, and histology. Thermal parameters such as T20, T50, and T90 were higher in responding patients, but were not significantly different from nonresponding patients. Overall toxicity was moderate. Subcutaneous fatty necrosis due to HT occurred in 10% of the cycles, whereas 2 patients developed skin burns. Squamous cell carcinoma antigen proved to be a valuable tool for the evaluation of response and detection of progression. CONCLUSIONS Weekly locoregional HT and cisplatin, 50 mg/m2 i.v., for a maximum of 12 cycles was effective treatment in patients with a previously irradiated recurrent carcinoma of the uterine cervix. Cancer 1997; 79:935-43. © 1997 American Cancer Society.

Background: Concomitant hyperthermia has been shown to improve response rate after cisplatin in recurrent cervical cancer in previously irradiated patients. It is unclear whether similar response rates can be obtained in patients with a recurrence after previous platinum-containing chemoradiation. Objective: This study aimed to evaluate the outcome of cisplatin-based chemotherapy with concurrent hyperthermia in patients with recurrent cervical cancer after radiotherapy and cisplatin. Methods: Patients with recurrent cervical cancer after cisplatin-based chemoradiation or neoadjuvant chemotherapy followed by surgery and radiotherapy who were treated with concurrent platinum-based chemotherapy and hyperthermia were eligible for this retrospective analysis. All patients received six or eight weekly platinum-based chemotherapy cycles in combination with six or eight weekly hyperthermia sessions. The time-to-event variables were estimated using Kaplan-Meier analysis. P-values less than 0.05 were considered significant. Results: All 38 evaluable patients were selected from the hyperthermia database in the Academic Medical Centre (Amsterdam) and the Erasmus Medical Centre (Rotterdam). Mean age at relapse was 45.7 years (range 27-74). Median time to recurrence after first-line treatment was 15 months. A total of 27 patients had a local and/or regional recurrence; 11 had disease beyond the pelvis. All planned courses of cisplatin chemotherapy and hyperthermia were administered in 17/38 patients. Median follow-up was 6.5 months. One patient died during treatment; response rate was 4/37 (14%), with one complete response. Overall survival was 23% at 12 months and 4% at 24 months. The incidence of grade 3-4 haematological complications did not exceed 10%. Conclusion: In this retrospective study, concurrent cisplatin and hyperthermia after first-line cisplatin-containing chemoradiation showed poor response and survival. We do not recommend this treatment for recurrence of locally advanced cervical cancer.

Data on vulvar cancer are subject to a possible selection bias because older patients with vulvar cancer are sometimes not referred to specialized centers. The aim of this study was to compare the variables obtained from the population as a whole with variables obtained from referral and nonreferral hospitals. Population-based data on age, stage, histological type, and treatment modality were registered for 138 patients with vulvar cancer. The characteristics of the patients who were referred to a gynecologic oncology center were compared with those of the patients treated in nonreferral hospitals. The age-adjusted incidence was 2.3 per 100,000 women. Basal cell cancer was less common in the referral center than in the nonreferral centers (3% versus 28%). No difference was found in FIGO stage distribution in the different subgroups. Groin node dissection was omitted in 80% of the patients not referred to a center. Omission of groin node dissection was more common in patients older than 74 years (P = 0.002). Population-based data on vulvar cancer differ significantly from hospital-based data and give better insight into the real characteristics of patients with vulvar cancer.

From January 1982 to December 1991 271 patients underwent radical hysterectomy according to the Okabayashi modification for cervical carcinoma stage IB and IIA. Intraoperative complications occurred in 3.3%. The urinary fistula rate was only 2.2%. The 5-year Disease-free Interval (DFI) was 90%. In a univariate analysis tumor size 3 cm (n = 99), positive pelvic nodes (n = 53), adenocarcinoma (n = 58) and parametrial involvement (n = 36) were all associated with a significantly decreased DFI. Recurrence occurred in 27 patients (10%) of whom 22 died of disease. In adenocarcinoma, DFI was poor when positive pelvic nodes were present. In squamous cell carcinoma however, DFI was not influenced by pelvic node status. In patients with squamous cell carcinoma the locoregional recurrence rate was 3.4% when pelvic nodes were negative, whereas in those with positive nodes it was 5.8%. These data show that the Okabayashi modification of Wertheim’s radical hysterectomy is a safe procedure resulting in very good locoregional tumor control, especially in patients with squamous cell cancer of the cervix.

ObjectiveThis study aimed to compare the negative predictive value (NPV) of clinical examination with or without anesthesia and magnetic resonance imaging (MRI) in identifying patients with cervical carcinoma without parametrial infiltration.MethodsThis retrospective cohort study was conducted at the Academic Medical Center in Amsterdam. The medical files of 203 patients diagnosed with cervical cancer stages IB1-IIA, who underwent surgical treatment between January 1, 2003, and January 31, 2011, were reviewed. We compared clinical International Federation of Gynecology and Obstetrics staging and MRI during the staging procedure. The results were compared with the parametrial status by surgical-pathological investigation, which was considered to be the reference standard.ResultsBased on the surgical-pathological findings, 16.7% of the patients treated surgically had parametrial infiltration. For parametrial infiltration, examination under anesthesia (EUA) had an NPV of 65.3% and MRI of 76.9%, respectively. We found no significant difference between these NPVs.ConclusionsExamination under anesthesia and MRI are equal in identifying cervical cancer patients without parametrial infiltration with a tendency for MRI to perform better than EUA. When outpatient clinical staging is considered inconclusive, pretreatment staging may be limited to MRI. In these cases, EUA seems to have no additional value.

Objective Concurrent presence of endometrial hyperplasia or cancer in patients with granulosa cell tumors (GCTs) is common, with reported incidences of 25.6% to 65.5%. Consequently, bilateral salpingo-oophorectomy and hysterectomy is usually recommended in patients with a GCT, but this remains debatable. Our aim was to evaluate the need for hysterectomy in patients with GCTs by studying the incidence of pathologically confirmed endometrial abnormalities at the time of diagnosis of GCT and during follow-up. Materials/Methods All cases of GCT between 1991 and 2012 were evaluated for endometrial pathology using the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Results A total of 1031 cases of GCT were identified at a mean ± SD age of 55 ± 17 years. The incidence of GCTs in the period 1991–2012 was 0.61 per 100,000 women per year. Concurrent endometrial cancer at the time of diagnosis of GCT was found in 58 patients (5.9%) and endometrial hyperplasia in 251 patients (25.5%), including complex hyperplasia in 89 patients (9.1%) and simple hyperplasia in 162 patients (16.5%). Long-term follow-up of 490 patients (47.5%) without a hysterectomy showed that endometrial abnormalities were found in 10 patients (2.0%) of which 2 had endometrial cancer. Interestingly, 8 (80%) of the 10 patients with endometrial abnormalities had recurrent GCT at the time of diagnosis of endometrial hyperplasia or cancer. Conclusions Our data suggest that after surgical removal of GCT, development of an endometrial abnormality, especially cancer, is very rare. Therefore, hysterectomy is not recommended in patients with a GCT without endometrial abnormalities at the time of diagnosis.

Background. Patients with squamous cell carcinoma of the vulva who present with multiple positive groin lymph nodes have poor survival. Growth of cancer through the capsule of the groin lymph nodes recently has been identified as an important prognostic factor for survival in that patient group. The objective of this study was to determine the influence of several clinicopathologic parameters on the pattern of recurrence and survival. Methods. A review of 71 patients with squamous cell carcinoma of the vulva and positive lymph nodes was performed to assess the independent prognostic value of a number of variables for survival. Variables analyzed included tumor size, stage, number of positive lymph nodes, extracapsular growth of lymph node metastasis, the greatest dimension of tumor in the lymph nodes, the percentage of replacement of the lymph nodes by tumor, clinical lymph node status, and laterality of positive lymph nodes. Results. Using the Mantel-Cox test, extracapsular growth of lymph node metastases (P = 0.00), two or more positive lymph nodes (P = 0.02), and greater than 50% replacement of lymph nodes by tumor (P = 0.03) were predictors of poor survival. No difference was found between the groups with two positive lymph nodes and those with three or more. Extracapsular growth of lymph node metastases was the most significant independent predictor for survival. Distant metastases occurred in 7 of 15 patients (48%) who had a combination of extranodal spread, lymph node replacement greater than 50%, and three or more positive lymph nodes. Conclusion. Extracapsular growth of lymph node metastases in the groin is the most important predictor for poor survival in patients with squamous cell carcinoma of the vulva. Because of the predominant distant failure pattern in a subgroup of patients who have a combination of extranodal spread, multiple positive lymph nodes, and lymph nodes replaced by tumor greater than 50%, a future study of the effectiveness of systemic therapy for vulvar cancer must include these patients. Cancer 1995;75:2885–90.

Background. Hydronephrosis can be a side effect of radical hysterectomy for cervical cancer. The incidence of clinically relevant hydronephrosis has not been studied in a large sample and the benefit of early detection of hydronephrosis is not clear. Objective. To assess the incidence of hydronephrosis, following radical hysterectomy and evaluate the usefulness of routine renal ultrasound (RH). Methods. Retrospective study, January 1998 and December 2008. Cervical cancer patients (FIGO stage IBI-IIA), treated with radical hysterectomy and pelvic lymph node dissection with or without adjuvant radiotherapy, without surgical lesion of the ureter, followed-up 6 months in the Academic Medical Center Amsterdam. Routine renal ultrasound was performed four weeks after RH, and in some on indication before or after the routine ultrasound. We documented which interventions for hydronephrosis were performed and evaluated the profile of patients at risk for hydronephrosis. Results. 281 patients were included: 252 (90%) underwent routine renal ultrasound and 29 (10%) underwent imaging on indication before routine ultrasound. The overall incidence of hydronephrosis was 12%. In symptomatic patients, the incidence was 21% and 9% in asymptomatic women undergoing routine ultrasound. Four patients were invasively treated for hydronephrosis (1% of the total group) after imaging for clinical suspicion of hydronephrosis. Patients with hydronephrosis were significantly more often treated with radiotherapy than patients without (43% versus 25% (p = 0.03). Conclusion. There is no place for routine renal ultrasound following radical hysterectomy. Patients should be instructed about the symptoms that may be related to hydronephrosis, to allow for renal ultrasound on indication. (C) 2011 Elsevier Inc. All rights reserved

This study aims to explain bodily pain using the Sprangers and Schwartz theoretical model (1999) on quality of life (QL) and response shift in its entirety. Response shift refers to the phenomenon that the meaning of a person's self-evaluation changes over time. In this model, response shift mediates effects of changes in health status (catalysts), stable characteristics of the person (antecedents), and coping mechanisms (mechanisms) on QL.Cancer patients (202) were assessed prior to and 3 months following surgery. Measures were for catalysts: type of operation and possibility of tumor resection; for antecedents: age, duration of pain, optimism, and rigidity; for mechanisms: post-traumatic growth, social comparisons, social support, denial, and acceptance; and for QL: bodily pain; for response shift: the pretest-minus-thentest bodily pain score, further referred to as recalibration response shift. Structural equation modeling and sequential regression analyses were used.The final model reached close fit (RMSEA = 0.03; 90% CI = 0.000-0.071; χ2 (18) = 21.13; p = 0.27). Significant effects were found for catalysts on mechanisms, antecedents on mechanisms, mechanisms on response shift, and response shift on bodily pain. Four extra model effects had to be permitted. Using sequential regression analysis, recalibration response shift added 4.4% to the total amount of 29.8% explained variance of bodily pain.Many effects as hypothesized by the model were found. Recalibration response shift had a unique albeit small contribution to the explanation of bodily pain.

BACKGROUND Despite changes in technique, morbidity after surgical treatment for vulvar cancer is considerable and mainly related to the groin dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on the efficacy of primary radiotherapy for the groins in terms of groin recurrences and survival show conflicting results. OBJECTIVES To determine whether the effectiveness and safety of primary radiotherapy to the inguino-femoral lymph nodes is comparable with surgery SEARCH STRATEGY The literature search was carried out using the criteria set by the Cochrane Gynaecological Cancer Group. A MEDLINE and EMBASE search using the Mesh Heading 'vulvar neoplasms' and textword 'vulva' was performed. Publications on the effectiveness of primary radiotherapy treatment of early squamous cell carcinoma of the vulva were selected. SELECTION CRITERIA TYPE OF STUDY Randomized clinical trials, case-control and observational studies of primary radiotherapy of the groin Type of participants: Patients with early squamous cell cancer of the vulva Type of interventions: inguino-femoral lymph node dissection and primary radiotherapy of the inguino-femoral lymph nodes. Type of outcome measurements: incidence of groin recurrences, survival and morbidity DATA COLLECTION AND ANALYSIS Two reviewers independently assessed study quality and extracted results MAIN RESULTS Out of nine reviewed papers only three met the selection criteria. From these studies, (one randomised controlled trial ?RCT? one case-control and one observational study) it became clear from the RCT that the incidence of groin recurrences after primary radiotherapy is higher compared with surgery. survival was also worse in the radiotherapy group. The other two studies showed a higher than expected number of groin recurrences after primary radiotherapy. Morbidity after primary radiotherapy was lower compared with surgery. The conclusion of the RCT was criticized on the grounds of the depth of the radiotherapy administered. The depth of 3 cm used in the RCT, is too shallow to administer an optimal dose to the deeper groin nodes. REVIEWER'S CONCLUSIONS As shown in an RCT, primary radiotherapy to the groin results in less morbidity but also in a higher number of groin recurrences compared with surgery. Although the technique of radiotherapy in the RCT was criticized, other uncontrolled data do not give evidence for a similar or better groin control for radiotherapy when compared to surgery. This means that surgery is still to be considered the cornerstone of therapy for the groin nodes in women with vulvar cancer. Individual patients not fit enough to withstand surgery can be treated with primary radiotherapy.

There is a definite trend toward vulvar conservation and individualized management of patients with early vulvar cancer. This approach initially was used only for patients with T1 disease, but with increasing experience with conservative surgery and the integration of postoperative adjuvant radiation when appropriate, some investigators have broadened the indications to include carefully selected patients with T2 lesions. A recent literature review suggests that the local invasive recurrence rate for T1 disease is 7.2% (12 of 165) after radical local excision compared with 6.3% (23 of 365) after radical vulvectomy (P = 0.85). Surgical margins must be at least 1 cm, and the rest of the vulva must be healthy if an increased local recurrence rate is to be avoided. Local recurrences usually can be treated successfully if diagnosed early, but recurrence in the groin is usually fatal. Inguinal-femoral lymphadenectomy should be done on all patients if the primary tumor is more than 2 cm in diameter and in patients with T1 disease in whom the depth of invasion is greater than 1 mm. Separate groin incisions may be used, but pelvic and groin irradiation should be given if there is at least one large node replaced with tumor or multiple nodes containing micrometastases. Careful patient selection is critical if modified operations are used, or an increased rate of recurrence will follow.

To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant chemotherapy and interval debulking surgery.Four hundred and seventy nine pathology reports from 40 institutions in 11 different countries were checked for the following quality indicators: macroscopic description of all specimens, measuring and weighing of major specimens, description of tumour origin and differentiation.All specimens were macroscopically described in 92.3% of the reports. All major samples were measured and weighed in 59.9% of the reports. A description of the origin of the tumour was missing in 20.5% of reports of the primary debulking group and in 23.4% of the interval debulking group. Assessment of tumour differentiation was missing in 10% of the reports after primary debulking and in 20.8% of the reports after interval debulking. Completeness of reports is positively correlated with accrual volume and adversely with hospital volume or type of hospital (academic versus non-academic). Quality of reports differs significantly by country.This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy.

Introduction: Patients with cervical carcinoma that invade the bladder or rectum (International Federation of Obstetrics and Gynecology stage IVA) have a high risk to develop vesicovaginal and/or rectovaginal fistulae. If we could identify pretreatment factors that predict fistula formation, these patients could be offered less debilitating treatment. Materials and Methods: Data were retrieved from the database of consecutive patients diagnosed with stage IVA cervical cancer from 1992 to 2008. Overall survival and fistula-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to study the association between pretreatment prognostic variables and fistula formation. Results: Thirty patients with stage IVA cervical cancer were diagnosed. Extension to the bladder was present in 27 patients; three patients had only rectal involvement. Twenty-three patients (77%) had curative radiotherapy with or without chemotherapy and/or hyperthermia. Seven patients (23%) received only palliative therapy or no treatment at all. The 5-year overall survival in the curatively treated group was 42%. Five (22%) of these 23 patients developed one or more fistulae: 3 vesicovaginal, 1 rectovaginal, and 1 vesicovaginal and rectovaginal fistulae. The 5-year fistula-free survival of this group was 64%. No significant association was found between the prognostic variables and fistula formation. Conclusions: The risk to develop vesicovaginal and/or rectovaginal fistulae is high after curative radiotherapy with or without chemotherapy and/or hyperthermia in patients with stage IVA cervical cancer. We could not identify further pretreatment factors that might have predicted fistula formation.

Objective. Models that predict survival and recurrence in patients with early-stage cervical cancer are important tools in patient management, We validated 12 existing prognostic models in an independent population of patients with early-stage cervical cancer. Materials and Methods. We searched the literature for prognostic models in patients with surgically treated early-stage cervical cancer. The prognostic performance of these models was assessed in a consecutive group Of Surgically treated patients with early-stage cervical cancer treated in our hospital between 1982 and 2004. The performance of the models was visually assessed with calibration plots, which display the relation between the predicted and observed survival. Results. Twelve published prognostic models met the inclusion criteria. The models categorized the patients into two to four risk groups. Prognostic factors most frequently used in these models were depth of invasion, lymph node metastasis, vascu/vascular space involvement, and tumor size. The models were validated in 563 consecutive patients with early-stage cervical cancer. All of the models underestimated the recurrence-free Survival or disease-specific survival in our patients. Only two models performed reasonably well in our population. The use of more than three prognostic categories in the models was not meaningful. Conclusion. In general, the models underestimated the survival. Only 2 of the 12 prognostic models for patients with early-stage cervical cancer were valid for the prediction of the recurrence-free or disease-specific Survival in our patient Population. (C) 2009 Elsevier Inc. All rights reserved

Background:The frequency of lymph node metastases in stage IA2 cervical cancer is reported to range from 0% to 9.7%. Treatment recommendations vary likewise from a cone biopsy to a Wertheim radical hysterectomy and pelvic lymph node dissection. The objective of this study was to get insight into the true frequency of lymph node metastases and/or parametrial involvement in stage IA2 cervical cancer.Methods:The hospital records of 48 patients with stage IA2 cervical carcinoma who registered from 1994 to 2006 were reviewed, and a literature search was performed.Results:Of 48 registered patients, 14 were confirmed to have stage IA2. No lymph node metastases or parametrial invasion and recurrences were found. The collated literature data showed a risk of lymph node metastases of 4.8% (range, 0%-9.7%). The presence of adenocarcinoma and the absence of lymph vascular space invasion resulted in a low risk on lymph node metastases (0.3% and 1.3%, respectively). Parametrial involvement has not been reported.Conclusions:The risk of the selected patients with stage IA2 cervical cancer on lymph node metastases is low. In patients with stage IA2 squamous cell cancer with lymph vascular space invasion, a standard pelvic lymph node dissection should be recommended. Parametrectomy should be included if the nodes are positive. In the other patients, the treatment can be individualized and does not have to include lymph node dissection or parametrectomy.

Objectives: To validate the results of a previous study with the tissue microarray technology showing that cyclooxygenase 2 (COX-2) overexpression and absent caspase 3 expression are associated with poor disease-specific survival in univariate analysis. Methods: The study group comprised 80 consecutive patients with vulva cancer treated in the period from 1999 to 2003 in a university hospital. A tissue microarray with 3 tumor tissue cores per patient was constructed and stained with antibodies against COX-2, caspase 3, epidermal growth factor receptor, p16(INK4), cyclin D1, and Ki-67. The impact of the expression of these protein markers and selected clinicopathologic variables on disease-specific as well as disease-free survival was measured. Cox proportional hazard model was used for both univariate and multivariate analyses. Results: In multivariate analysis, lymph node metastases and strong COX-2 expression were related to disease-free (hazard ratio [HR], 8.33, 95% confidence interval [CI], 2.97-23.36; P

Objectives: The aim of the current study was, first, to determine whether laterality of lymph node metastases has prognostic significance, independent of the number of lymph node metastases. Second was to determine the prognostic significance of extracapsular spread irrespective of the number of lymph node metastases. Methods: Data on 134 patients with stage III/IVA vulva cancer from 1982 till 2004 and treated with curative intent in either the Academic Medical Centre in Amsterdam or the Mercy Hospital for Women in Melbourne were reviewed. The impact of the number of lymph node metastases, extracapsular spread, and bilateral existence of lymph node metastases on survival was determined. Results: The bilateral presence of lymph node metastases is not a significant predictor for survival if a correction is made for the number of lymph node metastases (hazards ratio, 1.3 1; 95% confidence interval, 0.68-2.51; P = 0.420). If extracapsular spread is put into the model as well, this is the only parameter of prognostic significance in multivariate analysis (hazards ratio, 5.27; 95% confidence interval, 2.60-10.67; P

To determine the discriminative capacity of human papillomavirus (HPV) DNA testing for recurrent and residual cervical dysplasia, 43 patients with abnormal cytology after treatment for cervical dysplasia were tested for the presence of HPV DNA by PCR. An endocervical curettage was performed in all patients for histological examination. Sixteen of the 43 patients showed moderate or severe dysplasia. The HPV test was positive in all 16 patients with recurrent or residual dysplasia and negative in 12 of the 27 patients without dysplasia. The sensitivity and specificity of the HPV test were 100 and 44%, respectively. The likelihood ratio of a positive HPV test was 1.8, whereas a negative HPV test had a likelihood ratio of 0.12. Testing for the presence of HPV has the potential to select patients without recurrent or residual cervical dysplasia who have an abnormal cytological smear. This may have clinical implications, since unnecessary diagnostic conizations may be avoided in patients with abnormal cytology after treatment for cervical dysplasia and a negative HPV test.

The aim of this study is to determine immunohistochemical markers with prognostic significance for disease-specific survival in patients with squamous cell cancer of the vulva. The study material consisted of slides and paraffin blocks of 50 vulvectomy specimens. A tissue microarray was constructed and stained with 16 antibodies. The impact of lymph node metastases, size of tumor, vascular space involvement, and the marker expression on disease-specific survival was calculated. In univariate analysis lymph node metastases, tumor size more than 4 cm, vascular space involvement, strong cyclooxygenase 2 expression, and absent Caspase 3 expression were significantly associated with disease-specific survival. In a multivariate analysis, poor disease-specific survival is independently associated with absent Caspase 3 expression (hazard ratio, 0.2; 95% confidence interval, 0.04-0.97; P = 0.045). Five-year survival was 86% in patients with tumors positive for Caspase 3 (n = 20) and drops to 64% in patients with Caspase 3-negative tumors (n = 30). In this test set, cyclooxygenase 2 and Caspase 3 seem to be immunohistochemical markers with prognostic significance for vulva cancer. The results have to be validated.

Background and Objectives Newly diagnosed cancer patients waiting for initial surgery experience a stressful time. Study objectives were (1) to examine the quality of life (QL) of these patients by comparing QL (a) between the four diagnostic groups included in this study, (b) to the QL of the general population, (2) to determine the factors that contribute most to patients' overall QL. Methods One hundred ninety six patients with lung, periampullary, oesophageal and cervical cancer completed questionnaires on generic QL (SF-36), overall QL, cancer-site specific symptoms (EORTC-modules), anxiety (STAI), health expectations, demographics and comorbidity. Results Between diagnostic groups no significant differences were found on generic QL. As compared to the general population, generic QL was impaired on all aspects except bodily pain. Using stepwise regression analysis, 46% of the variance in overall QL was explained with the SF-36 scales vitality (Beta = 0.43) and mental health (Beta = 0.23) being the most important predictors. Conclusions The QL of these patients is seriously impaired. In this stage, not cancer-site specific aspects but fatigue and emotions colour their lives. It is recommended to keep the waiting period brief. In addition, suggestions are offered by which physicians might help their patients in alleviating the distress. J. Surg. Oncol. 2006;93:571–577. © 2006 Wiley-Liss, Inc.

Purpose To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperative identification of patients with a low likelihood for adjuvant radiotherapy than currently used clinical parameters. Patients and Methods In a cohort study, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, and preoperative serum SCC-ag levels, as determined by enzyme immunoassay, were related to the frequency of postoperative indications for adjuvant radiotherapy in 337 surgically treated, FIGO stage IB/IIA, squamous cell cervical cancer patients. Results In patients with normal preoperative SCC-ag, 16% of IB1 and 29% of IB2/IIA had postoperative indications for adjuvant radiotherapy, in contrast to 57% of IB1 and 74% of IB2/IIA patients with elevated (> 1.9 ng/mL) serum SCC-ag (P < .001). Serum SCC-ag was the only independent predictor for a postoperative indication for radiotherapy (odds ratio, 7.1; P < .001). Furthermore, in IB1 patients that did not have indications for adjuvant radiotherapy, 15% of patients with elevated preoperative serum SCC-ag levels recurred within 2 years, compared with 1.6% of patients with normal serum SCC-ag levels (P = .02). Conclusion In early-stage cervical cancer, determination of serum SCC-ag levels allows more refined preoperative estimation of the likelihood for adjuvant radiotherapy than current clinical parameters, and simultaneously identifies patients at high risk for recurrence when treated with surgery only. The role of preoperative serum SCC-ag in the management of patients with early-stage cervical cancer deserves further investigation.

Quality control of medical performance requires adequate 'state-of-the-art' data and this is currently not uniformly defined for radical hysterectomy. We have used data from a randomised multicentre clinical trial examining the clinical significance of surgical drains following radical hysterectomy (European Organisation for Research and Treatment of Cancer (EORTC)-55962). Although the study was not designed to analyse the quality of the surgical procedure per se, surgical data during and after the operation were carefully noted. A total of 234 patients from 12 European institutes were included in the study. We reported on the clinical and surgical characteristics, the radicality of surgery and short- and long-term complications of radical hysterectomy: median duration of surgery: 240 min; median number of nodes removed: 26; lymph node metastases: 22%; post-operative mortality

Objective. There are no data available on the impact of performance status on outcome in patients with vulvar cancer. It was the objective of this study to determine the impact of performance status on survival in a group of elderly patients. Methods. A retrospective review of records of patients with vulvar cancer aged 80 years or greater and treated in a gynecological referral center was performed. Multiple clinical and pathological variables together with performance status were assessed and the impact on overall survival was determined both by univariate and multivariate analysis. Results. Of 75 patients aged 80 years or older, 57 (76%) had standard treatment. The patients who had standard treatment were characterized by an earlier clinical stage and a better performance status compared with patients who had nonstandard treatment. When preoperatively available parameters of all patients were assessed in relation to survival in the total group, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent prognostic indicator for survival. When all clinical and histopathological variables were assessed in the subgroup who had standard treatment, both ECOG performance status and extracapsular lymph node involvement were independent prognostic variables for overall survival. Age was not a significant prognostic variable. Conclusions. ECOG performance status is the only available pretreatment variable with independent prognostic value for survival in this group of elderly patients with vulvar cancer. These data show the importance of individualizing the treatment of patients with vulvar cancer. Performance status takes a more important place than age in the management process of these patients. (C) 2002 Elsevier Science (USA)

Background. Radiation-induced or -associated sarcoma is a rare event which has been well described in the literature. However, this entity has been infrequently described in association with genital tract malignancies. To our knowledge it has never been described in association with the management of vulvar cancer. Cases. Two different cases of sarcoma developing after primary management for vulvar cancer are presented, the first being a case of angiosarcoma developing in the lower abdominal wall 36 months after initial therapy and the second a case of fibrosarcoma developing on the vulva 7 years after multimodality treatment. Conclusion. Radiation-associated sarcoma after treatment for vulvar carcinoma is a rare event. A multimodality treatment of carcinoma of the vulva should not be withheld because of fear of sarcomagenesis.

Despite changes in technique, morbidity after surgical treatment for vulvar cancer is considerable and mainly related to the groin dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on the efficacy of primary radiotherapy for the groins in terms of groin recurrences and survival show conflicting results.To determine whether the effectiveness and safety of primary radiotherapy to the inguino-femoral lymph nodes is comparable with surgeryThe literature search was carried out using the criteria set by the Cochrane Gynaecological Cancer Group. A MEDLINE and EMBASE search using the Mesh Heading 'vulvar neoplasms' and textword 'vulva' was performed. Publications on the effectiveness of primary radiotherapy treatment of early squamous cell carcinoma of the vulva were selected.Randomized clinical trials, case-control and observational studies of primary radiotherapy of the groin Type of participants: Patients with early squamous cell cancer of the vulva Type of interventions: inguino-femoral lymph node dissection and primary radiotherapy of the inguino-femoral lymph nodes. Type of outcome measurements: incidence of groin recurrences, survival and morbidityTwo reviewers independently assessed study quality and extracted resultsOut of nine reviewed papers only three met the selection criteria. From these studies, (one randomised controlled trial ¿RCT¿ one case-control and one observational study) it became clear from the RCT that the incidence of groin recurrences after primary radiotherapy is higher compared with surgery. survival was also worse in the radiotherapy group. The other two studies showed a higher than expected number of groin recurrences after primary radiotherapy. Morbidity after primary radiotherapy was lower compared with surgery. The conclusion of the RCT was criticized on the grounds of the depth of the radiotherapy administered. The depth of 3 cm used in the RCT, is too shallow to administer an optimal dose to the deeper groin nodes.As shown in an RCT, primary radiotherapy to the groin results in less morbidity but also in a higher number of groin recurrences compared with surgery. Although the technique of radiotherapy in the RCT was criticized, other uncontrolled data do not give evidence for a similar or better groin control for radiotherapy when compared to surgery. This means that surgery is still to be considered the cornerstone of therapy for the groin nodes in women with vulvar cancer. Individual patients not fit enough to withstand surgery can be treated with primary radiotherapy.

The indications for radiotherapy after radical hysterectomy for early stage cervical cancer are changing. In the past only tumor outside the cervix was considered an indication for radiotherapy. Today adjuvant radiotherapy is also considered for an "intermediate-risk" group with tumor confined to the cervix but poor prognostic primary tumor parameters such as large tumor diameter, vascular space invasion, and deep stromal penetration. The aims of this study were to determine the risk of isolated pelvic recurrences in an intermediate-risk group (GOG Study No. 92) and to analyze whether this group will theoretically benefit from adjuvant pelvic radiotherapy. A retrospective analysis was performed on 271 patients with early cervical cancer treated by a radical hysterectomy in a uniform fashion in one institute. Radiotherapy was administered only when tumor was found outside the cervix. Tumor diameter, capillary lymphatic space invasion, and depth of stromal penetration were assessed in all patients. Recurrence pattern, disease-specific survival, and recurrence-free interval were determined in the intermediate-risk group and compared with the remaining patients of the group with tumor confined to the cervix. A significant difference in disease-specific survival (89% versus 97%, P < 0.03) and 5-year recurrence-free interval (86% versus 95%, P < 0.02) was noted in the intermediate-risk group (n = 56) compared with the total group with tumor confined to the cervix. Three patients in the intermediate-risk group died of disease with a pelvic recurrence. Two of these patients had a combined pelvic and distant recurrence. Our retrospective results fail to support a survival benefit of extending indications for adjuvant radiotherapy other than postive nodes, parametrial extension, and positive margins

BACKGROUND. The presence of human papillomavirus (HPV) DNA in relation to cervical cytology was evaluated after treatment of cervical dysplasia. METHODS. Forty patients, 22 with normal and 18 with abnormal cytology (mild or moderate dyskaryosis), with a history of cervical dysplasia were selected. Only patients with HPV DNA positive biopsies obtained before treatment were included. The presence of HPV was assessed in cervical smears at least 1 year after treatment of cervical dysplasia by using a polymerase chain reaction (PCR) with consensus primers (CPI/IIG). HPV typing was done by direct sequence analysis of the CPI/IIG PCR generated amplimers. RESULTS. Smears from 3 of the 22 patients with normal cytology after treatment were positive for HPV DNA (14%). HPV DNA positive smears were found in 13 of the 18 patients with abnormal cytology after treatment (72%) (relative risk : 5.3 ; 95% confidence interval : 1.78-15.75). In 11 of the 16 HPV DNA positive smears (69%), the HPV type was different from that before treatment. In 35 of 40 patients, the HPV type before treatment could not be detected after treatment (88%). CONCLUSIONS. A minority of the patients with normal cytology after treatment of cervical dysplasia had detectable HPV DNA. In contrast, a high prevalence of HPV DNA was found in cervical smears of patients with abnormal cytology after treatment of cervical dysplasia. After treatment, none of the patients with abnormal cytology but HPV DNA negative smears had recurrence of cervical intraepithelial neoplasia. This suggests the value of supplementary HPV DNA testing during follow-up of patients treated for cervical dysplasia.

Carcinoma of the vulva is an uncommon tumor, representing about 4%–5% of gynecological malignancies. About 90% of cases are squamous cell carcinomas, with melanomas, adenocarcinomas, basal cell carcinomas, and sarcomas also occurring. This chapter will limit discussion to squamous cell carcinomas.