The incidence of perioperative lymphatic complications after radical hysterectomy and pelvic lymphadenectomy between robotic and laparoscopic approach : a systemic review and meta-analysis.

BACKGROUND: Although many studies have reported perioperative complications after radical hysterectomy and pelvic lymph node dissection using robotic and laparoscopic approaches, the risk of perioperative lymphatic complications has not been well identified. The aim of this meta-analysis is to compare the risks of perioperative lymphatic complications after robotic radical hysterectomy and lymph node dissection (RRHND) with laparoscopic radical hysterectomy and lymph node dissection (LRHND) for early uterine cervical cancer. MATERIALS AND METHODS: The authors searched the PubMed, Cochrane Library, Web of Science, ScienceDirect, and Google Scholar databases for studies published up to July 2022 comparing perioperative lymphatic complications after RRHND and LRHND while treating early uterine cervical cancer. Related articles and bibliographies of relevant studies were also checked. Two reviewers independently performed the data extraction. RESULTS: A total of 19 eligible clinical trials (15 retrospective studies and 4 prospective studies) comprising 3079 patients were included in this analysis. Only 107 patients (3.48%) had perioperative lymphatic complications, of which the most common was lymphedema ( n =57, 1.85%), followed by symptomatic lymphocele ( n =30, 0.97%), and lymphorrhea ( n =15, 0.49%). When all studies were pooled, the odds ratio for the risk of any lymphatic complication after RRHND compared with LRHND was 1.27 (95% CI: 0.86-1.89; P =0.230). In the subgroup analysis, study quality, country of research, and publication year were not associated with perioperative lymphatic complications. CONCLUSIONS: A meta-analysis of the available current literature suggests that RRHND is not superior to LRHND in terms of perioperative lymphatic complications.

Mature Cystic Teratoma Combined With Autoimmune Limbic Encephalitis Mimicking Functional Ovarian Cyst.

Autoimmune limbic encephalitis (ALE) associated with an anti-N-methyl-D-aspartate receptor (NMDAR) is a rare but occasionally fatal condition that could be accompanied by ovarian teratoma. We report a case of a 27-year-old woman with ALE combined with a mature cystic teratoma that looks like a functional cyst in imaging studies. A single port access laparoscopic left oophorectomy was performed. On the 154th postoperative day, symptoms were fully recovered. Teratoma detection and tumor removal are critical for the management of patients diagnosed with or suspected of ALE.

Comparison of General Anesthesia and Combined Spinal and Epidural Anesthesia for Gasless Laparoscopic Surgery in Gynecology.

Background and Objectives: Laparoscopic surgeries in gynecologic field have been performed under general anesthesia (GA) due to the respiratory changes caused by pneumoperitoneum and Trendelenburg position. Therefore, this study aimed to compared general anesthesia and combined spinal and epidural anesthesia (CSEA) for gasless laparoscopic surgery in gynecologic field. Methods: We matched patients with type of surgery who underwent gasless single port access (SPA) laparoscopic surgery under general anesthesia and CSEA. The medical records of 90 patients between March 1, 2018 and June 30, 2020 were reviewed. Gasless laparoscopic surgery was performed in all patients with a SPA using a J-shaped retractor. Results: No significant differences were observed for age, body mass index, parity, and previous abdominal surgery between GA and CSEA groups. During operation under CSEA, six patients (20%) experienced nausea/vomiting. Hypotension (systolic blood pressure < 90 mmHg) was observed in five patients (16.7%). Intravenous analgesics was administrated in four of the patients (13.3%) who suffered from shoulder pain or abdominal discomfort. One patient developed bradycardia. The duration of hospital admission was shorter in the CSEA group than in the GA group (p = 0.014). There was no difference between the groups in terms of surgery type, surgical specific finding, operation time, estimated blood loss, laparotomy conversion rate and use of additional trocar. No major complications such as urologic, bowel, or vessel injuries were found in both groups. Conclusions: CSEA is a safe and feasible technique for application in nonobese patients undergoing gasless laparoscopic surgery in gynecologic field.

Comparative study on gasless laparoscopy using a new device versus conventional laparoscopy for surgical management of postmenopausal patients.

Objective: To compare gasless laparoscopy with conventional laparoscopy for the surgical management of postmenopausal patients. Methods: The medical records of 80 postmenopausal patients who underwent laparoscopic surgeries between February 2016 and February 2020 were reviewed. Forty patients underwent gasless laparoscopy and 40 patients underwent conventional single-port access (SPA) laparoscopy. The two groups were compared in terms of surgical outcomes. Results: : Of 80 patients, 42 underwent adnexal surgeries and 38 underwent uterine surgeries such as total hysterectomy or myomectomy. Between the gasless SPA and conventional SPA laparoscopic groups, no significant differences were observed in terms of age, body mass index, parity or history of previous abdominal surgery. The mean retraction setup time from skin incision was 6.8 ± 1.2 min with gasless laparoscopic surgery. There was no significant difference in mean total operation times for the gasless (71.3 ± 31.4 min) and conventional (82.5 ± 36.4 min) groups. There was also no significant difference between the groups in terms of operation type, laparotomy conversion rate or duration of hospitalisation. There were no major complications in either group. Conclusions: Gasless laparoscopy is a safe and feasible alternative to conventional laparoscopy for postmenopausal women.

The incidence of postoperative symptomatic lymphocele after pelvic lymphadenectomy between abdominal and laparoscopic approach: a systemic review and meta-analysis.

OBJECTIVE: To evaluate the risks of symptomatic lymphocele after pelvic lymphadenectomy between the laparoscopic and abdominal approach in uterine cervical and endometrial cancer. METHODS: We searched Ovid Medline, Ovid EMBASE, and the Cochrane library through April 2020. We selected the comparative studies contained information on symptomatic lymphoceles in postoperative complications. All articles searched were independently reviewed and selected by two researchers. A meta-analysis was performed using the Stata MP version 16.0 software package. RESULTS: A total of 33 eligible clinical trials were ultimately enrolled in this meta-analysis. When all studies were pooled, the odds ratios (OR) of the laparoscopic approach for the risk of symptomatic lymphoceles compared to the abdominal approach was 0.58 [95% confidence interval (CI): 0.42-0.81, p = 0.022, I-squared = 0.0%]. The risk of postoperative symptomatic lymphoceles in the laparoscopic group tended to decrease over time in the cumulative meta-analysis. In the subgroup analysis, there was no evidence for an association between cancer type, quality of the study methodology, hysterectomy type, and postoperative symptomatic lymphoceles. However, in a recently published article, being overweight (body mass index ≥ 25) and studies conducted in oriental area were associated with a lower incidence of postoperative symptomatic lymphoceles. CONCLUSION: Laparoscopic lymphadenectomy was associated with a significantly lower risk of postoperative symptomatic lymphoceles than abdominal lymphadenectomy (PROSPERO registration number: CRD 42,020,187,165).

The prediction of surgical intervention in patients with tubo-ovarian abscess.

The aim of this study was to compare the clinical characteristics of patients with tubo-ovarian abscess (TOA) who responded to medical treatment and those who underwent surgical intervention due to medical treatment failure. Electronic medical records were evaluated retrospectively to identify patients who were diagnosed with TOA. Demographic, clinical, and laboratory data including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were compared between the medical treatment group and the surgical intervention group. Patient age, TOA diameter, WBC count, CRP, and ESR were significantly different between the groups. On multiple regression analysis, significant correlations were identified between age (p = .001), ESR (p = .045), and failure of medical treatment. TOA diameter (p = .065) showed a borderline association with surgical intervention. The risk of needing surgical intervention in TOA patients can be predicted using ESR in addition to age and TOA size as risk factors.IMPACT STATEMENTWhat is already known on this subject? For patients diagnosed with a tubo-ovarian abscess (TOA), the size of TOA and the patient's age are helpful for early identification of patients who are likely to need surgical treatment. Inflammatory markers such as C-reactive protein and white blood cell are also associated with the risk of surgical intervention.What do the results of this study add? Erythrocyte sedimentation rate (ESR) in addition to the size of TOA and the patient's age is a useful marker in determining whether to undergo surgery in patients with TOA.What are the implications of these findings for clinical practice and/or further research? ESR combined with the patient's age and the size of TOA is clinically useful in predicting the need for early surgical intervention in patients with TOA. Large prospective controlled studies are required to establish relationship between inflammatory markers and the risk of surgical intervention.

The incidence of urologic complications requiring urologic procedure in radical hysterectomy and difference between abdominal radical hysterectomy and laparoscopic radical hysterectomy.

OBJECTIVE: To evaluate the incidence of urologic complications requiring a urologic procedure during the perioperative period and compare the differences between abdominal radical hysterectomy (ARH) and laparoscopic radical hysterectomy (LRH). METHODS: We identified all Korean women who underwent radical hysterectomy (RH) between January 2006 and December 2019 using the National Health Insurance Service database. Complications requiring surgical intervention-based urologic procedures between ARH and LRH were investigated. RESULTS: A total of 12,068 patients were classified into the ARH group and 8,837 patients were classified into the LRH group. Urologic complications requiring urologic procedures occurred in 1,546 of 20,905 patients (7.40%) who underwent RH. The most common urologic procedure was double-J insertion (R326, 5.18%), followed by bladder repair (R3550, 0.90%). There was no significant difference in urologic complications requiring urologic procedures between the ARH and LRH groups (odds ratio [OR]=1.027; 95% confidence interval [CI]=0.925-1.141; p=0.612). The incidence of bladder repair (R3550) was significantly higher in patients who underwent LRH (OR=1.620; 95% CI=1.220-2.171; p<0.001). Urologic complications requiring urologic procedures were statistically higher in the LRH group during the first half (OR=1.446; 95% CI=1.240-1.685; p<0.001), but more in the ARH group during the second half (OR=0.696; 95% CI=0.602-0.804; p<0.001) of the study period. CONCLUSION: There was no difference of urologic complications between ARH and LRH with regard to urologic procedures. The incidence of urologic procedures decreases with time in patients who underwent LRH.

Comparison of Survival Outcomes after Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Patients with Cervical Cancer.

OBJECTIVE: A meta-analysis was performed to compare survival outcomes including disease-free survival (DFS) between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in patients with cervical cancer. DATA SOURCES: We searched PubMed, EMBASE, Google scholar, and the Cochrane library for studies published between December 2004 and May 2020. Manual searches of related articles and relevant bibliographies of published studies were also performed. METHODS OF STUDY SELECTION: Two researchers independently extracted the data. Studies with survival outcome information were included. TABULATION, INTEGRATION, AND RESULTS: A total of 36 eligible clinical trials were included in this meta-analysis. When all studies were pooled, the hazard ratio (HR) of LRH for the risk of DFS and overall survival (OS) compared with ARH was 1.24 (95% confidence interval [CI], 1.09-1.41; p = .001; I2 = 37.5%) and 1.27 (95% CI, 1.04-1.56; p = .020; I2 = 45.5%), respectively. In a subgroup analysis, significant harmful effects of DFS in patients with LRH increased in studies using the HR presented by the article (HR, 1.41; 95% CI, 1.21-1.64; p <.001), matched retrospective design (HR, 1.49; 95% CI, 1.19-1.88; p = .001), large-scale studies (HR, 1.34; 95% CI, 1.16-1.55; p <.001), and studies published after the Laparoscopic Approach to Cervical Cancer trial (HR, 1.46; 95% CI, 1.25-1.71; p <.001). However, LRH did not affect DFS (HR, 1.04; 95% CI, 0.59-1.81; p = .898) or OS (HR, 0.57; 95% CI, 0.31-1.05; p = .073) of patients with cervical cancer with cervical masses <2 cm. CONCLUSION: This meta-analysis demonstrated that LRH was associated with higher recurrence rates than ARH. However, LRH showed similar recurrence and OS among patients with cervical masses <2 cm (Centre for Reviews and Dissemination 42020191713).

Gasless single-port access laparoscopy using a J-shaped retractor in patients undergoing adnexal surgery.

OBJECTIVE: The aim of this study was to compare gasless single-port access (SPA) laparoscopy using a J-shaped retractor and conventional SPA laparoscopy in patients undergoing adnexal surgery. Study design The medical records of 80 patients who underwent laparoscopic adnexal surgery between May 2017 and April 2019 were reviewed. Of the 80 patients, 40 patients underwent gasless SPA laparoscopy using a J-shaped retractor and 40 underwent conventional SPA laparoscopy. All surgeries were performed by one laparoscopic surgeon. Surgical outcomes were compared between the two groups. RESULTS: There are no significant differences in age, body mass index, parity, previous abdominal surgery, tumor marker, and tumor diameter between the gasless and conventional groups. The median retraction setup time from skin incision was 7 min (range 5-12 min) in gasless SPA laparoscopic adnexal surgery. The median total operation times were 55.5 min (range 30-155 min) in the gasless group and 55 min (range 30-165 min) in the conventional group without a significant difference. Additionally, there were no differences in operation type, conversion rate of laparotomy, use of an additional trocar, and pathological outcomes between the two groups. No major complications, such as urologic, bowel, and vessel injuries, were found in both groups. CONCLUSIONS: Gasless SPA laparoscopy using a J-shaped retractor appears to offer a better alternative to conventional SPA laparoscopy that avoids the potential negative effects of carbon dioxide gas in selected cases.

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041).

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28-79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1-6). During the median follow-up of 4.9 months (range, 0.2-35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3-13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3-10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

Gasless Laparoscopic Myomectomy Using A J-shaped Retractor and Suture Technique.

OBJECTIVE: This study aimed to compare gasless single-port access (SPA) laparoscopic myomectomy using a J-shaped retractor and conventional SPA laparoscopic myomectomy. STUDY DESIGN: The medical records of 60 patients who underwent laparoscopic myomectomy between January 2016 and August 2019 were reviewed. Thirty patients underwent gasless SPA laparoscopic myomectomy using a J-shaped retractor, and 30 patients underwent conventional SPA laparoscopic myomectomy. The 2 groups were compared in terms of surgical outcomes. In gasless laparoscopic myomectomy, closure of the uterine defect after myomectomy was performed using an extracorporeal suture technique with a Kelly clamp and knot pusher. RESULTS: On comparing gasless SPA and conventional SPA laparoscopic myomectomy, no significant differences were observed in age, body mass index, parity, previous abdominal surgery, and size of the dominant uterine myoma. The median retraction setup time from skin incision was 8 minutes (range, 5 to 15 min) with gasless SPA laparoscopic myomectomy. The median total operation times were 105 minutes (range, 62 to 210 min) with gasless SPA myomectomy and 110 minutes (range, 60 to 270 min) with conventional SPA myomectomy, and there was no significant difference (P=0.251). There was no difference between the groups in terms of estimated blood loss. None of the patients experienced laparotomy conversion in both groups. No major complications, such as urologic, bowel, and vessel injuries, were found in both groups. CONCLUSION: Gasless SPA laparoscopic myomectomy using a J-shaped retractor is a safe and feasible approach, which allows for easy and convenient suturing of a uterine defect after myomectomy.

Comparison of urologic complications between laparoscopic radical hysterectomy and abdominal radical hysterectomy: A nationwide study from the National Health Insurance.

OBJECTIVE: This study aimed to assess the risks of intraoperative and postoperative urologic complications between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH). METHODS: Using the database of the National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA), we identified all Korean women who underwent radical hysterectomy between 2006 and 2018. Intraoperative and postoperative urologic complications were compared between the ARH and LRH groups. RESULTS: A total of 11,399 patients were identified to ARH and 8435 patients to LRH. Urologic complications occurred in 292 of 19,774 patients (1.48%) who underwent radical hysterectomy. LRH was associated with higher complication rates than ARH, although with a borderline significance (OR: 1.23; 90% CI: 1.02-1.51, p = 0.066). There was no difference in intraoperative urologic complications between the ARH and the LRH groups (OR: 1.1 95% CI: 0.86-1.43, p < 0.435). The incidence of postoperative urologic complications was significantly higher in the LRH group (OR: 2.01; 95% CI: 1.18-3.47, p = 0.009). In terms of postoperative urologic complications, the risk of ureterovaginal fistula was not significant between the two groups (OR: 1.53; 95% CI: 0.54-4.24, p = 0.403), whereas the risk of vesicovaginal fistula was significantly higher in the LRH group (OR: 2.24; 95% CI: 1.09-4.58, p = 0.028). There were no significant differences in the overall and urinary tract-specific complications between ARH and LRH in groups under 40 years of age and during the second half (2013-2018), with 2012 as the boundary. CONCLUSION: Among specific urologic complications, the incidence of vesicovaginal fistula was significantly higher in the LRH group than in the ARH group.

Gasless Total Laparoscopic Hysterectomy with New Abdominal-Wall Retraction System.

BACKGROUND AND OBJECTIVES: Gasless laparoscopy is an alternative method to reduce the number of carbon dioxide (CO2)-insufflated, pneumoperitoneum-related problems including shoulder pain, postoperative nausea/vomiting, and decreased cardiopulmonary function. In this study, we investigated the feasibility of gasless total laparoscopic hysterectomy (TLH) with a newly developed abdominal-wall retraction system. METHODS: Abdominal-wall retraction for gasless laparoscopy was performed using the newly developed J-shape retractor and the Thompson surgical retractor. Surgical outcomes between gasless TLH and conventional CO2-based TLH were compared for each of 40 patients for the period from January 2017 to October 2019. RESULTS: Between gasless TLH and conventional CO2-based TLH, no significant differences were observed for age, body mass index, parity, or surgical indications. The mean retraction setup time from skin incision was 7.4 min (range: 4-12 min) with gasless TLH. The mean total operation times were 87.9 min (range: 65-170) with gasless TLH and 90 min (range: 45-180) with conventional TLH, which showed no significant difference. Estimated blood loss and uterus weight also showed no significant intergroup difference. No major complications related to the ureter, bladder, or bowel were encountered. CONCLUSION: Our new abdominal-wall retraction system for gasless TLH allowed for easy setup and a proper operation field in the performance of laparoscopic hysterectomy.

Laparoscopic radical hysterectomy has higher risk of perioperative urologic complication than abdominal radical hysterectomy: a meta-analysis of 38 studies.

OBJECTIVE: A meta-analysis was performed to assess risks of intraoperative and postoperative urologic complications in laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH). METHODS: We searched Pubmed, EMBASE, and Cochrane library for studies published up to December, 2018. Manual searches of related articles and relevant bibliographies of published studies were also performed. Two researchers independently performed data extraction. Inclusion criteria of studies were: (1) had information of perioperative complications, and (2) had at least ten patients per group. RESULTS: A total of 38 eligible clinical trials were collected. Intraoperative and postoperative urologic complications were reported by 34 studies and 35 studies, respectively. When all studies were pooled, odd ratios (OR) of LRH for the risk of intraoperative urologic complications compared to abdominal radical hysterectomy (ARH) was 1.40 [95% confidence interval (CI) 1.05-1.87]. The OR of LRH for postoperative complication risk compared to ARH was 1.35 [95% CI 1.01-1.80]. However, significant adverse effects of intraoperative urologic complications in LRH were not observed among articles published after 2012 (OR 1.12, 95% CI 0.77-1.62) in cumulative meta-analysis or subgroup analysis. The incidence of bladder injury was statistically higher than that of ureter injury (p = 0.001). In subgroup analysis, obesity and laparoscopic type (laparoscopic assisted vaginal radical hysterectomy) were associated with intraoperative urologic complications. CONCLUSION: LRH is associated with significantly higher risk of intraoperative and postoperative urologic complications than abdominal radical hysterectomy.

Robotic Radical Hysterectomy Is Not Superior to Laparoscopic Radical Hysterectomy in Perioperative Urologic Complications: A Meta-Analysis of 23 Studies.

OBJECTIVE: This study aimed to compare the risks of intraoperative and postoperative urologic complications after robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). DATA SOURCES: We searched Pubmed, EMBASE, and the Cochrane Library for studies published up to March 2019. Related articles and relevant bibliographies of published studies were also checked. METHODS OF STUDY SELECTION: Two researchers independently performed data extraction. We selected comparative studies that reported perioperative urologic complications. TABULATION, INTEGRATION, AND RESULTS: Twenty-three eligible clinical trials were included in this analysis. When all studies were pooled, the odds ratio for the risk of any urologic complication after RRH compared with LRH was .91 (95% confidence interval [CI], .64-1.28; p = .585). The odds ratios for intraoperative and postoperative complications after RRH versus LRH were .86 (95% CI, .48-1.55; p = .637) and .94 (95% CI, .64-1.38; p = .767), respectively. In a secondary analysis study quality, study location, and the publication year were not associated with intraoperative or postoperative urologic complications. CONCLUSION: Current evidence suggests that RRH is not superior to LRH in terms of perioperative urologic complications.

Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.

PURPOSE: Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. METHODS: Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. RESULTS: Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. CONCLUSIONS: We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.

Mitochondrial reprogramming via ATP5H loss promotes multimodal cancer therapy resistance.

The host immune system plays a pivotal role in the emergence of tumor cells that are refractory to multiple clinical interventions including immunotherapy, chemotherapy, and radiotherapy. Here, we examined the molecular mechanisms by which the immune system triggers cross-resistance to these interventions. By examining the biological changes in murine and tumor cells subjected to sequential rounds of in vitro or in vivo immune selection via cognate cytotoxic T lymphocytes, we found that multimodality resistance arises through a core metabolic reprogramming pathway instigated by epigenetic loss of the ATP synthase subunit ATP5H, which leads to ROS accumulation and HIF-1α stabilization under normoxia. Furthermore, this pathway confers to tumor cells a stem-like and invasive phenotype. In vivo delivery of antioxidants reverses these phenotypic changes and resensitizes tumor cells to therapy. ATP5H loss in the tumor is strongly linked to failure of therapy, disease progression, and poor survival in patients with cancer. Collectively, our results reveal a mechanism underlying immune-driven multimodality resistance to cancer therapy and demonstrate that rational targeting of mitochondrial metabolic reprogramming in tumor cells may overcome this resistance. We believe these results hold important implications for the clinical management of cancer.

Bcl-2-like Protein 11 (BIM) Expression Is Associated with Favorable Prognosis for Patients with Cervical Cancer.

BACKGROUND/AIM: Bcl-2-like protein 11 (BIM) is a pro-apoptotic member of the Bcl-2 protein family. BIM elicits cell death by binding to pro-survival Bcl-2 proteins. Even though the association of BIM expression with cell death has been investigated, its clinical survival significance in cervical cancer has not. In the current study, the prognostic significance of BIM in cervical cancer was investigated. PATIENTS AND METHODS: The study included normal cervical tissues (n=254), cervical intraepithelial neoplasia (CIN) tissues (n=275), and invasive cervical cancer (n=164). In order to identify BIM expression, immunohistochemistry (IHC) was performed, and IHC scoring by quantitative digital image analysis was determined. Then, the association of BIM with prognostic factors was investigated. RESULTS: BIM expression was higher in cervical cancer than normal cervical tissues (p<0.001). Well and moderate differentiation indicated higher BIM expression than did poor differentiation (p=0.001). Also, BIM expression was high in radiation-sensitive cervical cancer relative to radiation-resistant cancer (p=0.049). High BIM expression showed better 5-year disease-free survival (DFS) and overall survival (OS) rates (p=0.049 and π=0.030, respectively) than did low expression. In a multivariate analysis, BIM was shown to be an independent risk factor for DFS and OS in cervical cancer, with hazard ratios of 0.22 (p=0.006) and 0.46 (p=0.046), respectively. CONCLUSION: BIM is associated with favorable prognostic markers for prediction of DFS and OS in cervical cancer. High BIM expression is a potential prognostic marker as well as a chemotherapeutic target for cervical cancer.

Elevated serum cathepsin B concentration in pregnant women is associated with preeclampsia.

PURPOSE: To compare the circulating levels of cathepsins B and D in preeclamptic and normotensive pregnancies. METHODS: Seventy-two pregnant patients were enrolled in this study. Of the 72 pregnant patients, 25 were preeclamptic and 47 patients were normotensive. Serum levels of soluble cathepsins B and D were measured with an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Cathepsin B levels were significantly higher in preeclamptic women than normotensive pregnant women (125.9 vs. 41.9 ng/mL; p = 0.013). The serum levels of cathepsin D were lower in preeclamptic women, but the differences were not significant (129.3 vs. 200.9 ng/mL; p = 0.077). However, cathepsin B and D levels were not correlated with severity of preeclampsia and small for gestational age. The serum levels of cathepsin D were inversely correlated with uric acid in preeclamptic patients (r = -0.527; p = 0.03). CONCLUSION: The serum levels of cathepsin B levels were increased significantly in preeclamptic women. Correlation with severity of preeclampsia needs further investigation to clarify the role of cathepsin B.