T Van Gorp

Lymph node metastasis in stages I and II ovarian cancer: A review

OBJECTIVES The purpose of this review is to determine the incidence of lymph node metastases in clinical stages I and II ovarian cancer. METHODS Relevant articles were identified from MEDLINE and EMBASE, supplemented with citations from reference lists from the primary studies. Eligibility was evaluated by two authors. Included studies were prospective or retrospective cohort studies, which analyzed patients with clinical early stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as a part of a staging laparotomy. RESULTS Fourteen studies were included in the analysis. The mean incidence of lymph node metastases in clinical stages I-II EOC was 14.2% (range 6.1-29.6%), of which 7.1% only in the para-aortic region, 2.9% only in the pelvic region, and 4.3% both in the para-aortic and pelvic region. Grade 1 tumors had a mean incidence of lymph node metastases of 4.0%, grade 2 tumors 16.5.8% and grade 3 tumors 20.0%. According to histological subtype, the highest incidence of lymph node metastases was found in the serous subtype (23.3%), the lowest in the mucinous subtype (2.6%). In unilateral tumors, pelvic lymph node metastases were found in 9.7% on both sides, 8.3% only at the ipsilateral side, and in 3.5% only at the contralateral side. CONCLUSIONS The incidence of lymph node metastases in clinical early stage EOC is considerable. Based on the scarce literature data, omitting a systematic lymphadenectomy can only be considered in grade I mucinous tumors.

Role of diaphragmatic surgery in 69 patients with ovarian carcinoma

Diaphragmatic stripping or coagulation is a technique aiming to optimally cytoreduce ovarian cancer. We investigated the complications, the overall survival, and the relapse rate following this procedure. Records of 69 patients with diaphragmatic involvement who underwent debulking surgery between September 1993 and December 2001 were reviewed. A total of 69 patients underwent diaphragmatic surgery as part of cytoreductive surgery for epithelial ovarian cancer. In 17 cases, the diaphragmatic tumors were stripped from the muscle, in 22 cases coagulated, and in 30 cases stripped and coagulated. Postoperative complications were pleural effusion (41 cases, 3 needed a chest drain, 7 needed a pleural puncture, 1 needed both) and pneumothorax (4 cases, 1 needed a chest drain). In one case of bilateral pleural effusion, the patient developed pneumonia. In one case of pleural effusion on the right side, the patient needed a pleural puncture and developed a partial atelectasis of the middle lobe of the right lung. The median overall survival was 66 months in the stripping group compared with 49 months in the coagulation group. In 56 cases (81%), the patient developed a relapse, and the first site of relapse was the diaphragm in 11 cases (20%). We conclude that diaphragmatic resection is an important part of optimal debulking surgery with an acceptable morbidity.

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma — Analysis of patient data in the prospective OVCAD study

OBJECTIVE Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. METHODS Data of 191 patients with advanced serous (FIGO III-IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. RESULTS The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus >28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08-4.66), P=0.031]. CONCLUSION Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.

Subjective assessment versus ultrasound models to diagnose ovarian cancer: A systematic review and meta-analysis

INTRODUCTION Many national guidelines concerning the management of ovarian cancer currently advocate the risk of malignancy index (RMI) to characterise ovarian pathology. However, other methods, such as subjective assessment, International Ovarian Tumour Analysis (IOTA) simple ultrasound-based rules (simple rules) and IOTA logistic regression model 2 (LR2) seem to be superior to the RMI. Our objective was to compare the diagnostic accuracy of subjective assessment, simple rules, LR2 and RMI for differentiating benign from malignant adnexal masses prior to surgery. MATERIALS AND METHODS MEDLINE, EMBASE and CENTRAL were searched (January 1990-August 2015). Eligibility criteria were prospective diagnostic studies designed to preoperatively predict ovarian cancer in women with an adnexal mass. RESULTS We analysed 47 articles, enrolling 19,674 adnexal tumours; 13,953 (70.9%) benign and 5721 (29.1%) malignant. Subjective assessment by experts performed best with a pooled sensitivity of 0.93 (95% confidence interval [CI] 0.92-0.95) and specificity of 0.89 (95% CI 0.86-0.92). Simple rules (classifying inconclusives as malignant) (sensitivity 0.93 [95% CI 0.91-0.95] and specificity 0.80 [95% CI 0.77-0.82]) and LR2 (sensitivity 0.93 [95% CI 0.89-0.95] and specificity 0.84 [95% CI 0.78-0.89]) outperformed RMI (sensitivity 0.75 [95% CI 0.72-0.79], specificity 0.92 [95% CI 0.88-0.94]). A two-step strategy using simple rules, when inconclusive added by subjective assessment, matched test performance of subjective assessment by expert examiners (sensitivity 0.91 [95% CI 0.89-0.93] and specificity 0.91 [95% CI 0.87-0.94]). CONCLUSIONS A two-step strategy of simple rules with subjective assessment for inconclusive tumours yielded best results and matched test performance of expert ultrasound examiners. The LR2 model can be used as an alternative if an expert is not available.

Diaphragmatic surgery during primary debulking in 89 patients with stage IIIB-IV epithelial ovarian cancer

OBJECTIVES The aim of this study was to describe the role of diaphragmatic surgery in achieving optimal debulking in patients with advanced ovarian cancer and the assessment of the relative post-operative complications. METHODS Retrospective review was performed of medical records of 89 patients with epithelial ovarian cancer who underwent diaphragmatic surgery during their primary debulking surgery between September 1993 and December 2007. Four different approaches were performed: coagulation (group 1), stripping (group 2), combination stripping with coagulation (group 3) and diaphragm full thickness resection (group 4). Cytoreductive outcome, morbidity, overall survival (OS) and disease-free survival (DFS) were analysed. RESULTS Eight (8.9%) patients had FIGO stage IIIB, 64 (72%) stage IIIC and 17 (19.1%) stage IV disease. In 20 patients (22%) the diaphragmatic disease was coagulated, in 31 patients (35%) was only stripped, in 31 patients (35%) a combination of these techniques was applied and in 7 (8%) the disease was resected with the adjacent infiltrated part of the diaphragm muscle and the pleura above it. Debulking to no residual tumor was achieved in 90%, 86%, 86% and 100% for groups 1, 2, 3 and 4 respectively. Median DFS was 15, 15, 17 and overall survival OS for groups 1, 2, and 3 was 40, 42, and 50 months respectively and was not yet reached for group 4. Minor and major complications were comparable among the groups. Pleural effusion was the most frequent associated complication and chest tube placement (17%) or thoracocentesis (12%) was necessary for the relief of respiratory distress. The perioperative mortality rate was 0%. The majority of cases were treated in the last five years of our 15-year experience. CONCLUSIONS Diaphragmatic surgery increases the rates of optimal primary debulking surgery and improves survival with an acceptable and manageable morbidity rate. In patients with thick (>0.3 cm) or large (>4 cm) lesions stripping the diaphragm or full thickness resection of the diaphragmatic muscle is preferred.

Mucinous borderline tumours of the ovary and the appendix: a retrospective study and overview of the literature.

OBJECTIVES Appendectomy is often recommended in patients with mucinous borderline ovarian tumours (mBOTs) based on studies suggesting that metastatic disease from a primary appendiceal tumour can mimic mBOT. The present study assessed the incidence of mucinous neoplasms in the appendix associated with the presence of mBOT. METHODS A retrospective cohort study was performed in two university hospitals in the Netherlands between 1990 and 2011. All patients with mBOT and/or a mucinous appendiceal tumour were included. RESULTS Of 127 patients included, 98 had a primary mBOT and 29 had a primary mucinous appendiceal tumour. In patients with a mBOT, the appendix was either removed at prior surgery (4%), resected as part of the staging procedure showing no pathological abnormalities (13%), described as normal and not resected (58%), or not described and not resected (25%). During a median follow-up period of 5 years (range 2-23), two patients developed a recurrence in which the appendix was not involved. In all patients with a primary mucinous tumour of the appendix, the appendix appeared abnormal at the time of surgery. Eight of these patients (28%) were diagnosed with invasive ovarian metastases. A review of the literature including the cases from this study identified 510 mucinous ovarian tumours with borderline features and 214 associated appendectomies, of which 4 (1.9%) contained a primary appendiceal malignancy. CONCLUSIONS A thorough inspection of the appendix should be performed in patients with a mucinous ovarian tumour with borderline features. An appendectomy should only be performed when the appendix is macroscopically abnormal.

External validation of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.

Background:For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.Methods:A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands.Results:In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi’s model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable.Conclusion:The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.

Are serum HE4 or ROMA scores useful to experienced examiners for improving characterization of adnexal masses after transvaginal ultrasonography

To determine whether serum human‐epididymis protein‐4 (HE4) levels or Risk of Ovarian Malignancy Algorithm (ROMA) scores are useful second‐stage tests for tumors thought to be difficult to characterize as benign or malignant on the basis of ultrasound findings by experienced examiners, and to investigate whether adding information on serum HE4 levels or ROMA scores to ultrasound findings improves diagnostic performance.

Lymph-node metastasis in stage I and II sex cord stromal and malignant germ cell tumours of the ovary: A systematic review

OBJECTIVES The aim of this systematic review is to determine the incidence of lymph-node metastasis in clinical stage I and II sex cord stromal tumours and germ cell tumours of the ovary. METHODS Relevant articles were identified from MEDLINE and EMBASE and supplemented with citations from the reference lists of the primary studies. Eligibility was determined by two authors. Included studies were prospective or retrospective cohort and cross-sectional studies analysing at least ten patients with clinical early-stage non-epithelial ovarian cancer who underwent lymphadenectomy or lymph-node sampling as part of a staging laparotomy. RESULTS For sex cord stromal tumours, five articles including 578 patients were analysed and lymph-node metastasis was not detected in the 86 patients who underwent lymph-node removal. The median number of removed lymph nodes was 13 (range 9-29). For malignant germ cell tumours, three articles were eligible including 2436 patients of whom 946 patients underwent lymph-node resection. The mean number of removed nodes was 10 (range 2-14) with a mean incidence of lymph-node metastasis of 10.9% (range 10.5-11.8%). CONCLUSIONS The incidence of lymph-node metastasis in patients with clinical stage I and II sex cord stromal tumours is low, whereas the incidence in patients with clinical stage I-II germ cell tumours is considerable, although limited data are available.

Estimating risk of malignancy in adnexal masses: external validation of the ADNEX model and comparison with other frequently used ultrasound methods

To validate externally the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model and compare this model with other frequently used models in the differentiation between benign and malignant adnexal masses.