Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands.

BACKGROUND: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be "complete" in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. METHODS: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery. DISCUSSION: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void. TRIAL REGISTRATION: Dutch Trial Register NTR6624 . Registered 18 August 2017. Medical Ethical Committee approval number: NL62035.078.17 (Medical Ethical Committee Erasmus Medical Centre Rotterdam).

Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. MATERIALS AND METHODS: Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. RESULTS: 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

OBJECTIVE: Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. DESIGN: Retrospective observational study. SETTING: Two teaching hospitals and one university hospital in the south-western part of the Netherlands. POPULATION: Women with advanced stage EOC. METHODS: All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. MAIN OUTCOME MEASURES: The primary outcome measure was OS and the secondary outcome measures were response and PFS. RESULTS: A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. CONCLUSION: PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

What is the recurrence rate of postmenopausal bleeding in women who have a thin endometrium during a first episode of postmenopausal bleeding?

OBJECTIVE: To determine the incidence and significance of recurrent postmenopausal bleeding among women diagnosed with an endometrial thickness < or =4 mm after a first episode of postmenopausal bleeding. METHODS: Consecutive patients not using hormone replacement therapy (HRT) presenting with a first episode of postmenopausal bleeding and an endometrial thickness < or =4 mm at transvaginal ultrasonography (TVU) were managed expectantly. In case of recurrent bleeding, the patient was evaluated according to the hospital's local policy with TVU, office endometrial sampling, hysteroscopy or dilatation and curettage (D&C) or a combination of these tests. We evaluated the incidence of recurrent bleeding, potential risk factors for recurrent bleeding, and the diagnosis made after recurrent bleeding. RESULTS: A total of 607 patients were registered with a first episode of postmenopausal bleeding, of whom 249 had an endometrial thickness < or =4 mm. Follow-up took place with a median of 174 weeks (range: 4-250 weeks). During follow-up, 25 of the 249 patients (10%; 95% CI: 6.6-14%) had recurrent bleeding. Median time until recurrence of bleeding was 49 weeks (range: 9-186 weeks). Two patients with recurrent bleeding turned out to have an endometrial carcinoma (8%; 95% CI: 2.2-25%), and 1 patient had a malignant melanoma. Time since menopause, age, body mass index, hypertension, diabetes and anticoagulants were not predictive for recurrent bleeding. CONCLUSION: The recurrence rate after a first episode of postmenopausal bleeding managed expectantly is low and cannot be predicted by patient characteristics. Patients with recurrent bleeding should be re-evaluated, as they bear a considerable risk of carcinoma.

Preoperative predictors for residual tumor after surgery in patients with ovarian carcinoma.

OBJECTIVES: Suboptimal debulking (>1 cm residual tumor) results in poor survival rates for patients with an advanced stage of ovarian cancer. The purpose of this study was to develop a prediction model, based on simple preoperative parameters, for patients with an advanced stage of ovarian cancer who are at risk of suboptimal cytoreduction despite maximal surgical effort. METHODS: Retrospective analysis of 187 consecutive patients with a suspected clinical diagnosis of advanced-stage ovarian cancer undergoing upfront debulking between January 1998 and December 2003. Preoperative parameters were Karnofsky performance status, ascites and serum concentrations of CA 125, hemoglobin, albumin, LDH and blood platelets. The main outcome parameter was residual tumor >1 cm. Univariate and multivariate logistic regression was employed for testing possible prediction models. A clinically applicable graphic model (nomogram) for this prediction was to be developed. RESULTS: Serum concentrations of CA 125 and blood platelets in the group with residual tumor >1 cm were higher in comparison to the optimally cytoreduced group (p < 0.0001 and <0.01, respectively). Serum albumin and hemoglobin levels were lower in the group with residual tumor (p < 0.0001 and <0.05, respectively). The frequency of preoperative ascites was higher in the group with residual tumor (p < 0.0005). The prediction model, consisting of CA 125 and albumin, for remaining with residual tumor showed an area under the receiver operating characteristics curve of 0.79. A nomogram for probability of residual tumor >1 cm based on serum levels of CA 125 and albumin was established. CONCLUSION: Postoperative residual tumor despite maximal surgical effort can be predicted by preoperative CA 125 and serum albumin levels. With a nomogram based on these two parameters, probability of postoperative residual tumor in each individual patient can be predicted. This proposed nomogram may be valuable in daily routine practice for counseling and to select treatment modality.

Inadequate office endometrial sample requires further evaluation in women with postmenopausal bleeding and abnormal ultrasound results.

OBJECTIVE: To determine whether further histologic assessment can be omitted after office sampling produced a nondiagnostic specimen. METHODS: Data were retrieved from a prospective cohort study of 913 women presenting with postmenopausal bleeding. This study was limited to women with an endometrial thickness either 5 mm or greater or that could not be measured, and in whom an endometrial biopsy performed in the office yielded nondiagnostic results. RESULTS: Endometrial thickness was nonreassuring or unknown in 516 women, of whom 403 (78.1%) underwent office endometrial sampling. In 66 women the amount of tissue obtained was not sufficient for pathologic characterization. Further investigation revealed an endometrial malignancy in 3 of these 66 women and atypical hyperplasia in 1. CONCLUSION: In women with postmenopausal bleeding and a nonreassuring transvaginal ultrasound evaluation, a nondiagnostic office endometrial sample does not rule out endometrial cancer and further endometrial sampling is advisable.

[Extrauterine pregnancy in Netherlands: patient characteristics, treatment, and pregnancy prognosis]. / Extra-uteriene graviditeit in Nederland: patiëntkenmerken, behandeling en zwangerschapsprognose.

OBJECTIVE: To determine the probability of pregnancy after a finished extrauterine pregnancy (EUP) and the length of time in between. DESIGN: Prospective multicentric cohort study. METHOD: Of all patients with an EUP between May 1990 and October 1993, data were collected using a questionnaire from surgeons in five university hospitals and 30 general training and non-training hospitals. During the subsequent 3 years, the patients semi-annually reported on their pregnancy or wish to become pregnant using reply cards. RESULTS: A total of 665 patients with an EUP were reported their mean age was 30.7 years (SD: 4.9). There were 341 patients who during the follow-up desired pregnancy, did not start an IVF procedure and supplied complete follow-up data 207 of them (61%) became pregnant after a median interval of 12 months. Age above 35, previous fertility problems, a Chlamydia antibody titre > or = 1:64 and adnexitis in the anamnesis were correlated with a longer interval until a subsequent pregnancy. The nature of the treatment (laparotomy versus laparoscopy, conservative versus radical and surgical versus pharmaceutical) did not affect the duration of the interval. If the contralateral tube was judged to be abnormal by the operator, pregnancy was still possible, but the occurrence of the pregnancy was delayed. CONCLUSION: The probability of pregnancy after an earlier EUP averages 61%; the interval until the next pregnancy, if any, depends mostly on factors that cannot be influenced at the time of the diagnosis of EUP.

Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

OBJECTIVE: Treatment in advanced stage epithelial ovarian cancer (EOC) is based on primary cytoreductive surgery followed by platinum-based chemotherapy. Successful cytoreduction to minimal residual tumour burden is the most important determinant of prognosis. However, extensive surgical procedures to achieve maximal debulking are inevitably associated with postoperative morbidity and mortality. The objective of this study is to determine predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC. METHODS: All patients in the South Western part of the Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007 were identified from the Rotterdam Cancer Registry database. All peri- and postoperative complications within 30 days after surgery were registered and classified according to the definitions of the National Surgical Quality Improvement Programme (NSQIP). To investigate independent predictors of 30-day morbidity, a Cox proportional hazards model with backward stepwise elimination was utilised. The identified predictors were entered into a nomogram. RESULTS: Two hundred and ninety-three patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. 30-day morbidity was seen in 99 (34%) patients. Postoperative morbidity could be predicted by age (P=0.007; odds ratio [OR] 1.034), WHO performance status (P=0.046; OR 1.757), extent of surgery (P=0.1308; OR=2.101), and operative time (P=0.017; OR 1.007) with an optimism corrected c-statistic of 0.68. CONCLUSION: 30-day morbidity could be predicted by age, WHO performance status, operative time and extent of surgery. The generated nomogram could be valuable for predicting operative risk in the individual patient.

Causes of postoperative mortality after surgery for ovarian cancer.

Residual disease after cytoreductive surgery is an important prognostic factor in patients with advanced stage epithelial ovarian cancer (EOC). Aggressive surgical procedures necessary to achieve maximal cytoreduction are inevitably associated with postoperative morbidity and mortality. To determine causes of postoperative mortality (POM) after surgery for EOC all postoperative deaths in the southwestern part of the Netherlands over a 17-year period were identified and analysed by reviewing medical notes. Between 1989 and 2005, 2434 patients underwent cytoreductive surgery for EOC. Sixty-seven patients (3.1%) died within 30 days after surgery. Postoperative mortality increased with age from 1.5% (26/1765) for the age group 20-69 to 6.6% (32/486) for the age group 70-79 and 9.8% (18/183) for patients aged 80 years or older. Pulmonary failure (18%) and surgical site infection (15%) were the most common causes of death. Only a quarter of deaths resulted from surgical site complications. Our results suggest that causes of postoperative mortality after surgery for EOC are very heterogeneous. Given the impact of general complications, progress in preoperative risk assessment, preoperative preparation and postoperative care seem essential to reduce the occurrence of fatal complications.