Minilaparotomy, Cyfra21-1, and Other Predicting Factors for Suboptimal Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer: A Pilot Study.

BACKGROUND: Currently, there is no reliable method to predict the result of the primary cytoreduction to decide whether to go on primary cytoreductive surgery or receive neoadjuvant chemotherapy. This study aimed to identify candidate predicting factors from clinical data, serum biomarkers, CT/MRI imaging, and minilaparotomy for suboptimal cytoreduction in women with advanced epithelial ovarian cancer. METHODS: Women who were clinically suspicious of advanced-stage epithelial ovarian, fallopian tube, and peritoneal cancer undergoing primary cytoreductive surgery were recruited. Clinical data, abdominopelvic CT/MRI, and serum biomarkers, including CA125, HE4, and Cyfra21-1, were collected preoperatively. At the start of the surgery, a minilaparotomy incision was made, the peritoneal cavity was assessed, and the operating surgeons gave the impression of whether the optimal cytoreductive surgery would be attainable. Subsequently, the incision was extended as necessary, and the standard cytoreductive surgery was attempted. After the procedure completion, the surgical outcome (optimal vs. suboptimal cytoreduction) and other operative outcomes were recorded. The association between the potential predicting factors and the surgical outcome was examined. RESULTS: Fourteen patients were included in this pilot study. Twelve patients were diagnosed with primary ovarian or fallopian tube cancer, while two had ovarian metastasis from colorectal cancer. The optimal cytoreduction was achieved in eight women. After minilaparotomy, the surgeons could predict suboptimal surgery correctly in five out of six cases (OR: 24.12, 95%CI: 2.34-Inf., p<0.01). Moreover, no patient with the finding of rectosigmoid invasion from CT had optimal surgery (OR: 12.96, 95%CI: 1.26-Inf., p=0.03). Lastly, increased serum cyfra21-1(>8 ng/mL) and HE4 (>83 pmol/L) were significantly associated with suboptimal cytoreduction, with OR: 35.00, 95%CI: 1.74-702.99, p=0.02 and OR: 15.00, 95%CI: 1.03-218.30, p=0.05, respectively. CONCLUSION: The finding of rectosigmoid invasion from abdominal CT, increased serum cyfra21-1 and HE4, and the initial minilaparotomy impression were potentially associated with suboptimal cytoreduction.

Prognostic Factors for Advanced Epithelial Ovarian Cancer Following Primary Cytoreductive Surgery or Neoadjuvant Chemotherapy.

AIM: To examine the association between clinicopathological factors and survival in advanced epithelial ovarian, tubal, and primary peritoneal cancers patients who had primary cytoreductive surgery (CRS) and those that received neoadjuvant chemotherapy (NAC). METHODS: Women who had CRS or NAC between 2008-2017 were included. Association between clinical characteristics, pretreatment imaging, serum markers, surgical and pathological factors, and disease recurrence/progression/death was examined in multivariable analysis. RESULTS: Two hundred and three women were recruited in this study (CRS 128 women and NAC 75 women). Median overall survival was 33.7 months for the CRS group and 27.9 months for the NAC group (p=0.04). Median progression-free survival was 14.9 months in the CRS group and 12.1 months in the NAC group (p=0.04). For the CRS group, factors independently associated with increased risk of death included primary peritoneal carcinoma (adjusted hazard ratio [aHR] 6.94), stable disease/progression at treatment completion (aHR 5.97), and initial tumor size of more than 12 cm (aHR 1.87). For the NAC group, stable disease/progression after complete treatment (aHR 6.45) and pre-treatment platelet to lymphocyte ratio of more than 310 (aHR 2.20) were significantly associated with an increased risk of death. CONCLUSIONS: NAC appeared to be a good alternative treatment for stage III/IV tubo-ovarian carcinoma. The worse survival outcome associated with primary peritoneal carcinoma and large initial tumor size in the patients who received CRS suggested that NAC could be an attractive option for those with these characteristics.

Metabolic reprogramming in epithelial ovarian cancer.

Cancer cells usually show adaptations to their metabolism that facilitate their growth, invasiveness, and metastasis. Therefore, reprogramming the energy metabolism is one of the current key foci of cancer research and treatment. Although aerobic glycolysis-the Warburg effect-has been thought to be the dominant energy metabolism in cancer, recent data indicate a different possibility, specifically that oxidative phosphorylation (OXPHOS) is the more likely form of energy metabolism in some cancer cells. Due to the heterogeneity of epithelial ovarian cancer, there are different metabolic preferences among cell types, study types (in vivo/in vitro), and invasiveness. Current knowledge acknowledges glycolysis to be the main energy provider in ovarian cancer growth, invasion, migration, and viability, so specific agents targeting the glycolysis or OXPHOS pathways have been used in previous studies to attenuate tumor progression and increase chemosensitization. However, chemoresistant cell lines exert various metabolic preferences. This review comprehensively summarizes the information from existing reports which could together provide an in-depth understanding and insights for the development of a novel targeted therapy which can be used as an adjunctive treatment to standard chemotherapy to decelerate tumor progression and decrease the epithelial ovarian cancer mortality rate.

iPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer.

Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making.

Methods of pain control during endometrial biopsy: A systematic review and meta-analysis of randomized controlled trials.

AIM: To review effectiveness of methods for reducing pain during endometrial biopsy. METHODS: PubMed, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases were searched for randomized controlled trials that examined effectiveness of pain control methods for endometrial biopsy. Risk of bias was assessed from sequence generation, allocation concealment, blinding, incomplete outcome data and selective outcome reporting. Heterogeneity was examined from forest plot, statistical tests of homogeneity, and I2 statistic. For meta-analysis of pain scores, weighted mean difference with 95% confidence interval (CI) were estimated. RESULTS: Twenty-six studies were included in the review. Marginally significant reduction in the pain score during the procedure in participants with intrauterine lidocaine relative to control was observed (mean difference [MD] -1.31, 95% confidence interval [CI] -2.70 to 0.09, P = 0.07). Subgroup analysis showed that in studies that used low-pressure suction devices, intrauterine lidocaine was associated with statistically significant reduction in pain during the procedure (MD -2.22, 95% CI -3.72 to -0.73, P = 0.004). There was a significantly lower pain score during biopsy in the anesthetic spray group compared to control (MD -0.96, 95% CI -1.53 to -0.39, P = 0.001). Significant heterogeneity on types of intervention and outcome measures among studies that examined paracervical block and nonsteroidal anti-inflammatory drugs (NSAID) was observed. However, paracervical block and NSAID were associated with significant pain reduction compared to placebo in most of the related studies. CONCLUSION: Intrauterine anesthetics, anesthetic cervical spray, paracervical block and oral NSAID provide effective pain control during endometrial biopsy.

Predicting factors for resumption of spontaneous voiding following nerve-sparing radical hysterectomy.

OBJECTIVE: To determine factors affecting voiding recovery on the day of Foley catheter removal (postoperative day 7, POD7) after nerve-sparing radical hysterectomy (NSRH) for early-stage cervical cancer. METHODS: Early-stage cervical cancer patients, who underwent type C1 radical hysterectomy between January 2006 and June 2016 were included. Clinical and pathological data were reviewed. Association between inability to attain adequate voiding function on POD7 and potential predicting factors were evaluated in univariate and multivariate analysis. RESULTS: Of 755 patients, 383 (50.7%) resumed adequate voiding function on POD7 while 372 (49.3%) did not. Tumor size was larger in patients whose voiding function was inadequate (2.5 vs. 2.0 cm, p=0.001). Lengths of resected parametria and adjacent vagina were more extensive in patients with inadequate voiding function (p<0.001). In univariate analysis, factors significantly associated with inability to attain adequate voiding function included tumor size >4 cm (p<0.001), primary surgeon (p<0.001), postoperative urinary tract infection (p<0.01), grossly visible tumor (p<0.01), and not having prior conization (p<0.01). In multivariate analysis, tumor size >4 cm, postoperative urinary tract infection, and primary surgeon were significantly associated with inability to attain adequate voiding function on POD7. CONCLUSION: Extent of disease represented by tumor size, urinary tract infection as well as individual surgeon's technique independently predict resumption of adequate voiding function on POD7 following NSRH.

Effect of conventional diet schedule, early feeding and early feeding plus domperidone on postcesarean diet tolerance: A randomized controlled trial.

AIM: To compare time to regular diet tolerance among conventional schedule, early oral feeding and early oral feeding plus domperidone in postcesarean women and to investigate these protocols on other aspects of postoperative well-being. METHODS: During July 2014 to June 2015, 120 postcesarean women were randomly assigned to three groups. Group A, conventional schedule: women fasted for 18-24 h postoperatively, then sipped water, had a liquid diet, soft diet, and regular diet, consecutively. Group B, early oral feeding: women started sipping water at 3-8 h postoperatively, followed by a soft and then a regular diet. Group C consumed the same as group B, plus domperidone. RESULTS: Median time to regular diet tolerance was 52.3 (50.8-54.7), 28.5 (24.8-31.4), and 29.6 (26.5-44.8) h (P < 0.001) in groups A, B and C, respectively. The two early feeding groups had significantly earlier ambulation and shorter hospitalization compared with the control. There were no differences between the two early feeding groups. The rate of postoperative gastrointestinal symptoms, pain scores and patients' satisfaction scores were similar among the three groups. CONCLUSION: Early oral feeding does not significantly increase postoperative complications; however, is associated with earlier regular diet intake. Apparently, domperidone does not enhance postoperative gastrointestinal function.