A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer.

OBJECTIVE: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m²) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. METHODS: In this phase I trial, a time-to-event Bayesian optimal interval design was used. Docetaxel was given at a starting dose of 60 mg/m² and was increased in 5 mg/m² increments until the MTD was determined or the maximum dose level of 75 mg/m² was reached. The dose-limiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. RESULTS: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m², no DLT was reported. DLTs were observed in one patient who received 70 mg/m² docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m² docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. CONCLUSION: Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m²), can be used safely at intraperitoneal doses of 75 mg/m² in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05410483.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Dosage Optimization of Digoxin in Older Patients with Heart Failure and Chronic Kidney Disease: A Population Pharmacokinetic Analysis.

BACKGROUND: Renal function is an important index for digoxin dose adjustment, especially in patients with chronic kidney disease (CKD). Decreased glomerular filtration rate is common in older patients with cardiovascular disease. OBJECTIVE: The aim of this study was to establish a digoxin population pharmacokinetic model in older patients with heart failure and CKD and to optimize the digoxin dose strategy. METHODS: Older patients with heart failure and CKD aged > 60 years from January 2020 to January 2021 and who had an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 or urine protein production were enrolled in this retrospective study. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using NONMEN software. The precision and stability of the final model were analyzed by graphical and statistical methods. RESULTS: Overall, 269 older patients with heart failure were enrolled. A total of 306 digoxin concentrations were collected, with a median value of 0.98 ng/mL (interquartile range [IQR] 0.62-1.61, range 0.04-4.24). The median age was 68 years (IQR 64-71, range 60-94) and eGFR was 53.6 mL/min/1.73 m2 (IQR 38.1-65.2, range 11.4-89.8). A one-compartment model with first-order elimination was developed to describe the digoxin pharmacokinetics. Typical values for clearance and volume of distribution were 2.67 L/h and 36.9 L, respectively. Dosage simulations were stratified by eGFR and metoprolol. Doses of 62.5 and 125 µg were recommended for older patients with eGFR < 60 mL/min/1.73 m2. CONCLUSIONS: A population pharmacokinetic model of digoxin in older patients with heart failure and CKD was established in this study. A novel digoxin dosage strategy was recommended in this vulnerable population.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Efficacy of neoadjuvant hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer (the NHIPEC trial): study protocol for a randomised controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. METHODS: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events. ETHICS APPROVAL AND DISSEMINATION: This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (approval number: 2020-ky-050). Results will be submitted to peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038173.

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy.

Background: To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C among gynecological cancer patients. Methods: In this Phase I dose-finding trial, Bayesian optimal interval (BOIN) design was used. We sought to explore the MTD with a target dose-limiting toxicity (DLT) rate of 20%, 4 prespecified doses (70 mg/m2, 75 mg/m2, 80 mg/m2 and 85 mg/m2), and 30 patients. Results: Between 2019 and 2020, 30 gynecologic cancer patients were enrolled. No patients received bevacizumab in subsequent treatment. The most common adverse events related to cisplatin were nausea and vomiting (100%), followed by tinnitus (26.7%) and kidney injury (23.3%). Of the seven patients with kidney injury, four had persistent renal impairment, and finally progressed into chronic kidney injury. DLTs were noted only in the dose level 4 group (85 mg/m2) and included acute kidney injury, pulmonary embolism, anemia, and neutropenia. When cisplatin was given at dose level four (85 mg/m2), the isotonic estimate of the DLT rate (22%) was closest to the target DLT rate of 20%. Therefore, 85 mg/m2 was selected as the MTD, with a 51% probability that the toxicity probability was greater than the target DLT rate. Conclusions: For gynecological cancer patients who received HIPEC for peritoneal metastases, the MTD of cisplatin in HIPEC at 43°C was 85 mg/m2. Our findings apply to patients who do not receive bevacizumab (ChiCTR1900021555).

Calculating the dose of cisplatin that is actually utilized in hyperthermic intraperitoneal chemotherapy among ovarian cancer patients.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an important treatment for ovarian cancer. A certain portion of cisplatin exits the body via the perfusate at the end of HIPEC, so full-dose utilization cannot be achieved. Herein, we sought to explore how much cisplatin is actually utilized and its prognostic influence. METHODS: Cisplatin (70 mg/m2) was given at 43 °C for 90 min. The actually utilized dose (AD) of cisplatin was calculated using the following formula: AD (mg) = total dose (TD) (mg)-losing dose (LD) (mg); LD = volume (ml) of the perfusate (VPretained) that was retained in the HIPEC treatment system at the end of HIPEC * concentration of cisplatin in the perfusate (mg/ml). RESULT: Sixty-two ovarian cancer patients were included. The median TD, median LD and median AD were 95 mg, 20.7 mg and 75.8 mg, respectively. The utility rate of cisplatin (AD/TD ratio) was 79.2%. On simple linear regression analysis, the TD and VPretained were found to significantly predict the AD. Based on these two factors, multiple linear regression analysis was conducted, and a significant regression equation was formulated [F (2, 59) = 71.419, P < 0.0001]: predicted AD (mg) = 30.079 + 0.667 TD (mg) - 0.010 VPretained (ml) (adjusted R2 = 0.698). In Cox regression analysis, AD was not noted to be associated with progression free survival or overall survival. CONCLUSION: For ovarian cancer patients who receive cisplatin for HIPEC at 43 °C, the AD of cisplatin can be predicted using a regression equation and it has no prognostic impact.

COVID-Net: a tailored deep convolutional neural network design for detection of COVID-19 cases from chest X-ray images.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to have a devastating effect on the health and well-being of the global population. A critical step in the fight against COVID-19 is effective screening of infected patients, with one of the key screening approaches being radiology examination using chest radiography. It was found in early studies that patients present abnormalities in chest radiography images that are characteristic of those infected with COVID-19. Motivated by this and inspired by the open source efforts of the research community, in this study we introduce COVID-Net, a deep convolutional neural network design tailored for the detection of COVID-19 cases from chest X-ray (CXR) images that is open source and available to the general public. To the best of the authors' knowledge, COVID-Net is one of the first open source network designs for COVID-19 detection from CXR images at the time of initial release. We also introduce COVIDx, an open access benchmark dataset that we generated comprising of 13,975 CXR images across 13,870 patient patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge. Furthermore, we investigate how COVID-Net makes predictions using an explainability method in an attempt to not only gain deeper insights into critical factors associated with COVID cases, which can aid clinicians in improved screening, but also audit COVID-Net in a responsible and transparent manner to validate that it is making decisions based on relevant information from the CXR images. By no means a production-ready solution, the hope is that the open access COVID-Net, along with the description on constructing the open source COVIDx dataset, will be leveraged and build upon by both researchers and citizen data scientists alike to accelerate the development of highly accurate yet practical deep learning solutions for detecting COVID-19 cases and accelerate treatment of those who need it the most.

Comparison of two types of the triple incision technique in the treatment of patients with locally advanced vulvar cancer.

Objective: In 2012, we proposed and described a modified triple incision technique (MTIT) for vulvar cancer patients with locally advanced disease. The MTIT has undergone a series of modifications, and a modified MTIT (M-MTIT) has been developed. The purpose of this study was to introduce the M-MTIT and compare it with the MTIT. Study design: This was a retrospective cohort study. Fifty-seven vulvar cancer patients with clinical stage T2 (≥ 4 cm) or T3 disease were included. Of these patients, 28 underwent the MTIT and 29 underwent the M-MTIT. Data on surgery-related complications and survival outcomes were compared. Results: Patients who were treated with the M-MTIT developed significantly less surgery-related morbidities than patients treated with the MTIT (24.1% vs. 60.7%, P = 0.005). Wound breakdown was the most common complication in our cohort, which occurred less frequently in the M-MTIT group than in the MTIT group (10.3% vs. 35.7%, P = 0.022). Multivariate logistic regression analysis identified the M-MTIT as an independent predictor of a reduced risk of wound breakdown. The incidence of other complications, including lymphedema, wound infection and cellulitis, was lower in the M-MTIT group than in the MTIT group; however, the differences did not reach statistical significance. The median follow-up time of this study was 33 months. Kaplan-Meier survival graphs did not show significant differences in recurrence-free survival or overall survival between the two groups. Conclusions: The M-MTIT correlates with lower morbidity rates than the MTIT and does not compromise oncological safety. The M-MTIT can be considered a safe and feasible option for vulvar cancer patients with locally advanced disease.

Feasibility and safety of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy in patients with advanced stage ovarian cancer: a single-center experience.

OBJECTIVES: For patients with advanced ovarian cancer, neoadjuvant chemotherapy (NACT) can significantly increase the rate of optimal cytoreduction. However, this does not translate into a survival benefit. The aim of this study was to investigate the feasibility and effect of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (NLHIPEC). METHODS: Between March 2016 and February 2018, 14 patients with advanced ovarian cancer who were not candidates for optimal cytoreduction via primary debulking surgery (PDS) received NLHIPEC. Their clinical data were retrospectively analyzed. RESULTS: No patients experienced intraoperative complications during NLHIPEC. Grade 3 adverse events (AEs) were noted in two (14.3%) patients, and all patients received planned NACT without dose delay or dose reduction. Following NACT, CA125 levels <35 U/mL and <20 U/mL were observed in six (42.9%) patients and five (35.7%) patients, respectively. All patients underwent interval debulking surgery (IDS) after the last NACT cycle. After IDS, R0 resection was achieved in 10 (71.4%) patients without intraoperative injury, and one (7.1%) patient developed a grade 3 AE. During a median follow-up time of 16 months, no patients died of disease, and the median progression-free survival (PFS) was not achieved. Progression was noted in six (42.9%) patients (range, 9-21 months). CONCLUSIONS: NLHIPEC appears to be a feasible option for ovarian cancer patients who have a low likelihood of achieving optimal cytoreduction during PDS.

Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis.

BACKGROUND: Cervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis. METHODS: Paraffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed. RESULTS: In normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046). CONCLUSIONS: These data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.

Pretreatment glycemic control status is an independent prognostic factor for cervical cancer patients receiving neoadjuvant chemotherapy for locally advanced disease.

BACKGROUND: To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC). METHODS: A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A1c (HbA1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: In total, 388 patients were included and had a median follow-up time of 39 months (range: 4-67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA1c < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA1c ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA1c ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA1c ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT. CONCLUSIONS: Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC.

Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer.

BACKGROUND: The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. METHOD: Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. RESULTS: In total, 347 patients were included. The median follow-up time was 37 months (range: 4-65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose <100 mg/dl). In multivariate analysis, positive surgical margins, parametrium invasion, node metastasis, hyperglycemia and complete response to NACT independently predicted recurrence and cancer-specific death. To further validate the prognostic value of hyperglycemia, we conducted a subgroup analysis based on patient baseline characteristics and prognostic effect of hyperglycemia remained significant in all subgroups. On multivariable logistic regression analysis, euglycemia before NACT, squamous cell tumor and pre-treatment squamous cell carcinoma antigen levels < 3.5 ng/ml were identified as independent predictors of complete response after NACT. CONCLUSIONS: FBG ≥100 mg/dl is a negative prognostic predictor for cervical cancer patients receiving NACT for BESCC. Patients with hyperglycemia are less likely to achieve complete response after NACT. Our findings underscore the clinical utility of hyperglycemia screening of for cervical cancer patients.

Pretreatment serum lactate dehydrogenase is an independent prognostic factor for patients receiving neoadjuvant chemotherapy for locally advanced cervical cancer.

For locally advanced cervical cancer (LACC), hypoxia is a characteristic property. This study aimed to investigate whether baseline lactic dehydrogenase (LDH) level, which is a marker of hypoxia, had clinical value in determining neoadjuvant chemotherapy (NACT) response and prognosis for LACC patients. The study cohort included 418 patients with a median follow-up of 37.5 months. Cox proportional hazards models were used to assess the prognostic value of baseline LDH levels. Multivariate logistic regression analysis was performed to identify independent predictors of complete response after NACT. Backward stepwise selection with the Akaike information criterion was used to identify factors that could be entered into the multivariate regression model. Compared with patients with LDH levels <252.0 µ/L, patients with LDH levels ≥252.0 µ/L were more likely to have an elevated level of squamous cell carcinoma antigen, lymphatic vascular space involvement, lymph node metastasis, and positive parametrium and achieved lower complete remission rates. Baseline LDH levels ≥252.0 µ/L was an independent prognosticator for recurrence-free survival (adjusted hazard ratio [HR], 3.56; 95% confidence interval [CI] 2.22-5.69; P < 0.0001) and cancer-specific survival (adjusted HR, 3.08; 95% CI, 1.89-5.01; P < 0.0001). The predictive value of baseline LDH value remained significant in the subgroup analysis. LDH level ≥252.0 µ/L was identified as an independent predictor of complete remission after NACT (adjusted odds ratio [OR], 0.29; 95% CI, 0.15-0.58; P < 0.0001). Baseline LDH ≥252.0 µ/L is an independent prognostic predictor for patients receiving neoadjuvant chemotherapy for LACC. It helps distinguish patients with different prognosis and select patients who are more likely to benefit from NACT.

Impact of the care provided by gynecologic oncologists on outcomes of cervical cancer patients treated with radical hysterectomy.

For many malignant diseases, specialized care has been reported to be associated with better outcomes. The purpose of this study is to investigate the influence of gynecologic oncologists on treatment outcomes for cervical cancer patients treated by radical hysterectomy. Records of patients who received radical hysterectomy between January 2005 and June 2010 were reviewed. Perioperative morbidity, recurrence-free survival, and cancer-specific survival were assessed. Cox regression model was used to evaluate gynecologic oncologists as an independent predictor of survival. A total of 839 patients were included. Of these patients, 553 were treated by gynecologic oncologists, while 286 were treated by other subspecialties. With regard to operative outcomes, significant differences in favor of operation by gynecologic oncologists were found in number of patients receiving para-aortic node sampling and dissection (P=0.038), compliance with surgical guidelines (P=0.003), operative time (P<0.0001), estimated blood loss (P<0.0001), transfusion rate (P=0.046), number of removed nodes (P=0.033), and incidences of ureteric injury (P=0.027), cystotomy (P=0.038), and fistula formation (P=0.002). Patients who were operated on by gynecologic oncologists had longer recurrence-free survival (P=0.001; hazard ratio [HR] =0.64; 95% confidence interval [CI] [0.48, 0.84]) and cancer-specific survival (P=0.005; HR=0.64; 95% CI [0.47, 0.87]), and this association remained significant in patients with locally advanced disease. Care by gynecologic oncologists was an independent predictor for improved recurrence-free survival (P<0.0001; HR=0.57; 95% CI [0.42, 0.76]) and cancer-specific survival (P=0.001; HR=0.58; 95% CI [0.42, 0.81]), which was still significant among patients with locally advanced cancer. Given the results, we believe for cervical cancer patients receiving radical hysterectomy, operation by gynecologic oncologists results in significantly improved surgical and survival outcomes. The importance of the subspecialty of a gynecologist for cervical cancer patients should be addressed in clinical practice, especially for those in developing countries.

Decrease in circulating myeloid dendritic cell precursors in patients with intracranial large artery atherosclerosis.

Intracranial large artery atherosclerosis (ILAA) is a major cause of ischemic cerebrovascular disease. The aim of this study was to investigate whether the levels of circulating dendritic cell precursors (DCP) could reflect the severity of intracranial large artery atherosclerosis (ILAA). For this purpose, a series of angiography were taken to determine the severity and extent of coronary artery and intracranial large artery stenosis, and flow cytometry were taken to determine the levels of circulating mDC precursors and pDC precursors in patients with severe intracranial large artery atherosclerosis (ILAA) (n = 101) and mild intracranial large artery atherosclerosis (ILAA) (n = 123) according to the angiography. Circulating mDC precursors were lower in patients with severe intracranial large artery atherosclerosis (ILAA) than in mild intracranial large artery atherosclerosis (ILAA) (P < 0.05), but circulating pDC precursors were not significant differences (P > 0.05). According to these data, circulating mDC precursors could predict the severity of ILAA, which also could be able to reflect the severity of ILAA.

Can radical parametrectomy be omitted in occult cervical cancer after extrafascial hysterectomy?

BACKGROUND: Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP. METHODS: A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed. RESULTS: Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence. CONCLUSIONS: Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection.

BACKGROUND: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. MATERIALS AND METHODS: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. RESULTS: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. CONCLUSIONS: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Knee osteoarthritis prevalence in hospitalized elderly patients: a retrospective study.

This study aimed to determine the prevalence rate of knee osteoarthritis (OA) and the risk factors for OA in hospitalized elderly patients. We conducted this retrospective study in elderly patients (aged 65 years and older) who were hospitalized in the Geriatric Ward of General Hospital of Guangzhou Military Command of the People's Liberation Army between January 2011 and June 2013, including general condition, present history, past history, physical examination, X-ray results, and disease diagnosis. The prevalence, awareness, and treatment rates of knee OA in hospitalized elderly patients were calculated. Risk factors were computed using multiple logistic regression analysis. Of a total of 267 (17.4%) hospitalized elderly patients diagnosed with knee OA, the prevalence rate of OA was 9.95% in males and 37.76% in females. The rate of awareness among those with OA was 51.68%; the rate of treatment was 83.33%; and the rate of control was 77.39%. The medical expenses for both females (1143±315 yuan month-1) and males (1192±357 yuan month-1) in knee OA patients are higher than that of the non-knee OA group (989±274 yuan month-1, 1038±295 yuan month-1). The risk factors for knee OA include gender (OR=2.448), age (OR=1.124), transportation mode (OR= 8.972), exercise (OR=7.374), bowel evacuation position (OR=5.767), family history of knee OA (OR=2.195), and body mass index (OR=2.469). The prevalence of knee OA is unexpectedly high in hospitalized elderly patients, and the rates of awareness and treatment are less than desirable. Prevention and control measures should be taken in patients with concomitant risk factors.

Tumor-associated macrophages correlate with progesterone receptor loss in endometrial endometrioid adenocarcinoma.

AIM: It has been well established that tumor-associated macrophages (TAMs) play a tumor promoting role in endometrial endometrioid adenocarcinoma (EEC). But the association with TAMs and sex hormone receptor expression, and progression of precancerous endometrial lesions in EEC has been little reported. MATERIAL AND METHODS: We used immunohistochemistry to examine the expression of CD68, CD34, vascular endothelial growth factor (VEGF), estrogen receptor (ER) and progesterone receptor (PR) in 95 cases of EEC, as well as 35 cases of endometrial hyperplasia (including 15 atypical hyperplasia, 10 complex hyperplasia and 10 simple hyperplasia). We also correlated TAMs count with various clinicopathological factors, sex hormone receptor, and prognostic value in patients with EEC. RESULTS: We identified that TAMs count increased linearly with disease progression (mean count per case at × 200 magnification: simple hyperplasia, 6.30; complex hyperplasia, 11.20; atypical hyperplasia, 29.40; EEC 55.81, respectively; P < 0.001), that microvascular density (MVD) also increased accordingly (27.50, 30.20, 50.13 and 59.94, respectively; P < 0.001). The expression of progesterone receptor, not of estrogen receptor, significantly decreased with disease progression (P < 0.05). Moreover, histopathologic grades, International Federation of Gynecology and Obstetrics (FIGO) stage (2009), depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, and expression of PR and VEGF were associated with TAMs count (P = 0.0001, P = 0.004, P = 0.0001, P = 0.04, P = 0.0001, P = 0.0001, P = 0.0001, respectively). Progesterone receptor expression was also associated with histopathologic grades, lymphovascular space invasion, VEGF and high TAMs (P = 0.035, P = 0.022, P = 0.014, P = 0.001, respectively). The estimated 5-year survival rate of patients with low TAMs was significantly higher than those with high TAMs (96.4% vs 69.8%, P = 0.002). CONCLUSION: TAMs are potentially related to PR loss and progression of precancerous endometrial lesions in EEC.