Major Gynecologic Cancer Research Articles

2019 ASCO Annual Meeting Highlights for the Advanced Practitioner: Gynecologic Cancers.

Laura Doherty, FNP-BC, AOCNP®, of the Women & Infants Hospital of Rhode Island offers commentary on major gynecologic cancer abstracts featured from the ASCO Annual Meeting by The ASCO Post, including findings in carcinosarcoma of the uterus or ovary, effects of the Affordable Care Act on ovarian cancer diagnosis and treatment, and novel immunotherapy for cervical cancer.

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer.

To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7months. One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and 111 (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE) and 147 (94%) did so systematically; 97 (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. In this survey worldwide, SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Curcumin and endometrial carcinoma: an old spice as a novel agent.

One of the clinically major gynecological cancers is endometrial carcinoma that develops from the lining of the uterus. During the past years, different approaches have been developed to treat endometrial carcinoma, among which natural herbal medicine has recently faired as an effective method. The yellow Indian spice known as curcumin has been extolled for its healing powers and has recently been adopted for investigation by the scientific community as a potent anti-cancerous agent. This review focuses on the effect of curcumin on endometrial cancer (EC) and its role in specific pathways involved in carcinogenesis.

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

BackgroundCervical 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.MethodsParaffin-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.ResultsIn 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).ConclusionsThese 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.

Incidence of cervical, endometrial, and ovarian cancer in Korea during 1999-2015.

ObjectiveTo investigate the incidence and trends of cervical (C53), endometrial (C54.1), and ovarian cancer (C56) among Korean females between 1999 and 2015.MethodsThe incidence of the three major gynecological cancers between 1999 and 2015 was analyzed based on the data from the Korea Central Cancer Registry. The age-standardized rates (ASRs) and the annual percent changes (APCs) for each site were calculated.ResultsThe absolute incidence rates of the three major gynecological cancers increased from 6,394 in 1999 to 8,288 in 2015. ASR for gynecologic cancer decreased from 23.7 per 100,000 in 1999 to 21.1 in 2015. This was mainly due to a definitive decrease in the incidence of cervical cancer, which recorded an APC of −3.7%. The trends of APC for gynecologic cancer were variable, being −1.36% between 1999 and 2006 and −0.11% between 2006 and 2015. A definitive but variable increase was noted for endometrial cancer, and the APC for this cancer was 7.4% between 1999 and 2009 and 3.5% between 2009 and 2015. The incidence of ovarian cancer gradually increased, with an APC of 1.8% between 1999 and 2015.ConclusionOverall, ASRs and APCs for the three major gynecological cancers are decreasing, with a recent reduction in the width of the change. However, there has been a progressive increase in the incidence of endometrial and ovarian cancers.

Identification of Key Candidate Genes and Pathways for Relationship between Ovarian Cancer and Diabetes Mellitus Using Bioinformatical Analysis

Ovarian cancer is one of the three major gynecologic cancers in the world. The aim of this study is to find the relationship between ovarian cancer and diabetes mellitus by using the genetic screening technique. By GEO database query and related online tools of analysis, we analyzed 185 cases of ovarian cancer and 10 control samples from GSE26712, and a total of 379 different genes were identified, including 104 up-regulated genes and 275 down-regulated genes. The up-regulated genes were mainly enriched in biological processes, including cell adhesion, transcription of nucleic acid and biosynthesis, and negative regulation of cell metabolism. The down-regulated genes were enriched in cell proliferation, migration, angiogenesis and macromolecular metabolism. Protein-protein interaction was analyzed by network diagram and module synthesis analysis. The top ten hub genes (CDC20, H2AFX, ENO1, ACTB, ISG15, KAT2B, HNRNPD, YWHAE, GJA1 and CAV1) were identified, which play important roles in critical signaling pathways that regulate the process of oxidation-reduction reaction and carboxylic acid metabolism. CTD analysis showed that the hub genes were involved in 1,128 distinct diseases (bonferroni-corrected P<0.05). Further analysis by drawing the Kaplan-Meier survival curve indicated that CDC20 and ISG15 were statistically significant (P<0.05). In conclusion, glycometabolism was related to ovarian cancer and genes and proteins in glycometabolism could serve as potential targets in ovarian cancer treatment.

Programmed intermittent epidural bolus versus continuous epidural infusion for postoperative analgesia after major abdominal and gynecological cancer surgery: a randomized, triple-blinded clinical trial

BackgroundContinuous epidural infusion (CEI) is the standard application setting for epidural infusion. A new mode, the programmed intermittent epidural bolus (PIEB) technique, showed reduced local anesthetic (LA) consumption and improved analgesia in obstetric analgesia. Goal of this trial was to evaluate the effects of PIEB versus CEI [combined with patient-controlled bolus (PCEA)] on LA consumption and pain scorings in major abdominal cancer surgery.MethodsFollowing ethical approval, patients scheduled for major abdominal cancer surgery under general anesthesia in combination with epidural analgesia were randomized to receive either a PIEB mode of 6 mL/h or a CEI mode set at 6 mL/h of ropivacaine 0.2%, both combined with a PCEA mode set at a 4 mL bolus. LA consumptions and pain scorings were documented until the second postoperative evening.ResultsEighty-four datasets were analyzed (CEI: n = 40, PIEB: n = 44). Regarding the primary endpoint, cumulative LA PCEA bolus volumes until day 2 differed significantly between the groups [PIEB 10 mL (2–28 mL) versus CEI, 28 mL (12–64 mL), median (25th–75th percentiles), p = 0.002]. Overall, LA consumption volumes were significantly lower in the PIEB group versus in the CEI group [PIEB: 329 mL (291–341 mL) vs. CEI: 350 mL (327–381 mL), p = 0.003]. Pain scores were comparable at each time point.ConclusionsThis trial demonstrates reduced needs for PCEA bolus in the PIEB group. There were no clinically relevant benefits regarding morphine consumption, pain scorings, or other secondary outcome parameters.Trial registrationThis study has been registered retrospectively in the ClinicalTrials.gov registry (NCT03378804), date of registration: December, 20th 2017.

Hypoxia is involved in the reduction of HtrA3 in patients with endometrial hyperplasia and cancer

Endometrial cancer (EC) has recently become a major gynecological cancer and endometrial hyperplasia increases the risk for developing EC. Previous studies have reported that human high temperature requirement factor A3 (HtrA3), a member of ATP independent serine proteases family, is involved in endometrial carcinogenesis. However, the underlying mechanism of HtrA3 function is unclear in endometrial hyperplasia and cancer. In this study, we investigated that HtrA3 expression was reduced in endometrial hyperplasia as well as EC. The circulating levels of HtrA3 were also significantly reduced in both atypical hyperplasia and EC. Whether hypoxia is involved in the reduction of HtrA3 in EC was further investigated. Immunohistochemistry (IHC) scores of Glut1 and HtrA3 in type 1 and type 2 EC tissues showed the inverse correlation. And hypoxic condition reduced the expression of HtrA3. Furthermore, silencing HtrA3 promoted EC cell migration. Our study demonstrated the reduced levels of HtrA3 in endometrial hyperplasia including atypical hyperplasia which is a premalignant condition; and as the degree of hypoxia increases in EC, HtrA3 eventually loses its expression. Hypoxia is responsible for the reduction of HtrA3 which in turn promotes EC progression. These findings suggested that HtrA3 is an important adaptor in hypoxic regions that drives endometrial cancer development.

Enhanced recovery after surgery (ERAS®) in gynecologic oncology - Practical considerations for program development.

Enhanced recovery after surgery (ERAS®) in gynecologic oncology - Practical considerations for program development.

Electronic patient-reported outcomes from home in patients recovering from major gynecologic cancer surgery: A prospective study measuring symptoms and health-related quality of life

PurposeWe previously reported on the feasibility of a Web-based system to capture patient-reported outcomes (PROs) in the immediate postoperative period. The purpose of this study was to update the experience of these patients and assess patient and provider satisfaction and feedback regarding the system. MethodsThis is a prospective cohort study of patients scheduled to undergo laparotomy for presumed gynecologic malignancy. Patients completed a Web-based Symptom Tracking and Reporting (STAR) questionnaire preoperatively and weekly during a 6-week postoperative period. Email alerts were sent to study nurses when concerning patient responses were entered. The patient and the nurse assessments of STAR's usefulness were measured via an exit survey. ResultsThe study enrolled 96 eligible patients. Of these, 71 patients (74%) completed at least four of seven total sessions. Of the patients who completed the exit satisfaction survey, 98% found STAR easy to use; 84% found it useful; and 82% would recommend it to other patients. Despite positive feedback from patients, clinical personnel found that the STAR system increased their current workload without enhancing patient care. ConclusionsApplication of an electronic program for PROs in those recovering from major gynecologic cancer surgery is feasible, and acceptable to most patients. While most clinicians did not find STAR clinically helpful, the majority of patients reported a positive experience with the system and would recommend its use. The program helped many patients feel more empowered in their postoperative recovery.

Electronic patient-reported outcomes from home in patients recovering from major gynecologic cancer surgery: A prospective study measuring symptoms and health-related quality of life

Objectives: A pilot study suggested that the use of a web-based system to capture patient-reported outcomes (PROs) is feasible and highly accepted by patients in the acute postoperative period. The objective of this study was to further demonstrate its feasibility, measure patient assessments of its usefulness, and clinician perceptions of its value. Methods: This is a prospective cohort study of patients scheduled for laparotomy for presumed gynecologic malignancy. Patients completed a web-based Symptom Tracking and Reporting (“STAR”) questionnaire preoperatively and weekly during a 6-week postoperative period. The survey consisted of the patient adaptation of the National Cancer Institute’s CTCAE 3.0 and EORTC QLQ-C30 3.0. Email alerts were sent to clinicians when concerning patient responses were entered. The patient and the clinician assessments of STAR’s usefulness were measured via an exit survey. Results: The study enrolled 120 patients. Of these, 69 patients (57.5%) completed at least 4 of 7 total sessions. The CTC generated 84 alerts, which resulted in 28 contacts and 2 ED referrals. One hundred and twelve patient-reported symptoms generated an alert; the most common were poor performance status (15%), nausea (14%), and fatigue (12%). Fifty-one patients (42.5%) completed the exit satisfaction survey; 86% found STAR easy to use and 73% found it useful; 63% reported that STAR improved the ability to remember symptoms at office visits; 57% reported improved discussions with the provider; 43% reported overall improved quality of care; 63% felt more in control of their care by using the STAR system; and 71% would recommend it to other patients and 61% would like to continue use. Most clinicians did not find STAR helpful. Seventy-five percent did not find the self-assessments of pain and quality of life accurate. All clinicians surveyed reported that the STAR system increased their workload. Conclusions: Application of an electronic program for PROs in those recovering from major gynecologic cancer surgery is feasible and acceptable for most patients with a computer and home internet access. Poor performance status, nausea, and fatigue were the most common distressing symptoms reported. The majority of patients reported a positive experience with the system and would recommend its use. The program helped many to feel more empowered in their postoperative recovery. Clinicians reported a less positive experience, possibly associated with the increased work.

Using Bundled Interventions to Reduce Surgical Site Infection After Major Gynecologic Cancer Surgery.

To investigate whether implementing a bundle, defined as a set of evidence-based practices performed collectively, can reduce 30-day surgical site infections. Baseline surgical site infection rates were determined retrospectively for cases of open uterine cancer, ovarian cancer without bowel resection, and ovarian cancer with bowel resection between January 1, 2010, and December 31, 2012, at an academic center. A perioperative bundle was prospectively implemented during the intervention period (August 1, 2013, to September 30, 2014). Prior established elements were: patient education, 4% chlorhexidine gluconate shower before surgery, antibiotic administration, 2% chlorhexidine gluconate and 70% isopropyl alcohol coverage of incisional area, and cefazolin redosing 3-4 hours after incision. New elements initiated were: sterile closing tray and staff glove change for fascia and skin closure, dressing removal at 24-48 hours, dismissal with 4% chlorhexidine gluconate, and follow-up nursing phone call. Surgical site infection rates were examined using control charts, compared between periods using χ or Fisher exact test, and validated against the American College of Surgeons National Surgical Quality Improvement Program decile ranking. The overall 30-day surgical site infection rate was 38 of 635 (6.0%) among all cases in the preintervention period, with 11 superficial (1.7%), two deep (0.3%), and 25 organ or space infections (3.9%). In the intervention period, the overall rate was 2 of 190 (1.1%), with two organ or space infections (1.1%). Overall, the relative risk reduction in surgical site infection was 82.4% (P=.01). The surgical site infection relative risk reduction was 77.6% among ovarian cancer with bowel resection, 79.3% among ovarian cancer without bowel resection, and 100% among uterine cancer. The American College of Surgeons National Surgical Quality Improvement Program decile ranking improved from the 10th decile to first decile; risk-adjusted odds ratio for surgical site infection decreased from 1.6 (95% confidence interval 1.0-2.6) to 0.6 (0.3-1.1). Implementation of an evidence-based surgical site infection reduction bundle was associated with substantial reductions in surgical site infection in high-risk cancer procedures.

Electronic patient-reported outcomes from home in patients recovering from major gynecologic cancer surgery: A prospective study measuring symptoms and health-related quality of life

Electronic patient-reported outcomes from home in patients recovering from major gynecologic cancer surgery: A prospective study measuring symptoms and health-related quality of life

A Comparison of Patient Controlled Epidural Analgesia With Intravenous Patient Controlled Analgesia for Postoperative Pain Management After Major Gynecologic Oncologic Surgeries: A Randomized Controlled Clinical Trial.

Background:Postoperative pain after major open gynecologic surgeries requires appropriate pain management.Objectives:This study aimed at comparing perioperative patient controlled epidural analgesia (PCEA) and patient controlled intravenous analgesia (PCA) after gynecologic oncology surgeries.Patients and Methods:In this clinical trial study, 90 patients with American society of anesthesiologists (ASA) class I or II scheduled for gynecologic oncologic surgeries were randomly allocated to two groups (45 patients each group) to receive: patient-controlled epidural analgesia with bupivacaine and fentanyl (PCEA group), or patient controlled intravenous analgesia (IV PCA group) with fentanyl, pethidine and ondansetron. Postoperative pain was assessed over 48 hours using the visual analog scale (VAS). The frequency of rescue analgesia was recorded. Occurrence of any concomitant events such as nausea, vomiting, ileus, purities, sedation and respiratory complications were recorded postoperatively.Results:There were no statistically significant differences in demographic data including; age, weight, ASA physical status, duration of surgery, intraoperative bleeding, and the amount of blood transfusion (P > 0.05), between the two studied groups. Severity of postoperative pain was not significantly different between the two groups (P > 0.05); however, after first patient mobilization, pain was significantly lower in the epidural group than the IV group (P < 0.001). There was no significant difference between the two groups regarding the incidence of complications such as nausea, vomiting, purities or ileus (P > 0.05). Nevertheless, the incidence and severity of sedation was significantly higher in the IV group (P < 0.001). Respiratory depression was higher in the IV group than the epidural group; this difference, however, was not significant (P = 0.11). In the epidural group, only 10 patients (22.2%) had mild and transient lower extremities parenthesis.Conclusions:Both intravenous and epidural analgesic techniques with combination of analgesics provide proper postoperative pain control after major gynecologic cancer surgeries without any significant complications. Regarding lower sedative and respiratory depressant effects of epidural analgesia, it seems that this method is a safer technique for postoperative pain relief in these patients.

Surgical and systemic management of endometrial cancer: an international survey.

To ascertain the spectrum of clinical management of endometrial carcinoma (EC) the largest international survey was conducted to evaluate and identify differences worldwide. After validation of a 15-item questionnaire regarding surgical and adjuvant treatment of EC in Germany, an English-adapted questionnaire was put online and posted to all the major gynecological cancer Societies worldwide for further distribution commencing in 2010 and continued for 26 months. A total of 618 Institutions around the world participated: Central Europe (CE), Southern Europe (SE), Northern Europe (NE), Asia and USA/Canada/UK. Both a therapeutic and staging value was attributed to systematic pelvic and paraaortic lymph node dissection (LND) in CE (74.6%) and in Asia (67.2%), as opposed to USA/UK where LND was mainly for staging purposes (53.5%; p < 0.001). LND was performed up to the renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1% (p < 0.001) of cases. In advanced disease, centers from Asia were treated most with adjuvant chemotherapy alone (93.6%), as opposed to centers in SE, CE and UK/USA that employed combination chemo-radiotherapy in 90.9% (p < 0.001) of cases. Paclitaxel/carboplatin was mostly used followed by doxorubicin/cisplatin (75 vs. 23.3%; p < 0.001). In total, 94% of all participants supported the concept of treating EC patients within appropriate clinical trials. There is broad range in both the surgical and adjuvant treatment of EC across different countries. Large-scale multicenter prospective trials are warranted to establish consistent, evidence-based guidelines to optimize treatment worldwide.

Role of epithelial to mesenchymal transition proteins in gynecological cancers: pathological and therapeutic perspectives.

Gynecorelogic cancers like ovarian, cervical, and endometrial cancers are among the major threats to modern life, especially to female health. Like some other types of cancers, all of these gynecological cancers have found to be associated with the developmental stage epithelial to mesenchymal transition (EMT). More specifically, the aberrant expression of major EMT markers, such as lower expressions of E-cadherin and alpha-catenin, and overexpressions of N-cadherin, beta-catenin, vimentin, and matrix metalloproteinases, have been reported in ovarian, cervical, and endometrial cancers. The transcription factors, such as Twist, Snail, Slug, and Zeb, which regulate these EMT mediators, are also reported to be overexpressed in gynecological cancers. In addition to the over/lower expression, the promoter methylation of some of these genes has been identified too. In the era of target-specific cancer therapeutics, some promising studies showed that targeting EMT markers might be an interesting and successful tool in future cancer therapy. In this study, we have reviewed the recent development in the research on the association of EMT markers with three major gynecological cancers in the perspectives of carcinogenesis and therapeutics.

Racial Disparities in Uterine Clear Cell Carcinoma: A Multi-Institution Study

The aim of this study was to evaluate the impact of race on the overall survival (OS) and progression-free survival (PFS) of white and African-American patients with uterine clear cell carcinoma (UCCC). A retrospective review was conducted of all primary UCCC cases treated at 1 of 4 major gynecologic cancer centers between 1982 and 2012. Patients and tumor characteristics were retrieved from the cancer databases of the respective institutions and based on a retrospective review of the medical records. Differences in the OS and PFS between African-American and white women were compared using the Kaplan-Meier curves and log-rank test for univariate analysis. Cox regression models for the multivariate analyses were built to evaluate the relative impact of the various prognostic factors. One hundred seventy women with UCCC were included in the study, including 118 white and 52 African-American women. Both groups were comparable with respect to age (P = 0.9), stage at diagnosis (P = 0.34), angiolymphatic invasion (P = 0.3), and depth of myometrial invasion (P = 0.84). In the multivariate analyses for known prognostic factors, OS and PFS were significantly different between white and African-American patients in the early-stage disease (hazard ratio [HR], 5.4; 95% confidence interval [CI], 1.2-23.2; P = 0.023 and HR, 3.5; 95% CI, 1.60-7.77; P = 0.0016, respectively) but not in the advanced-stage disease (HR, 0.83; 95% CI, 0.40-1.67; P = 0.61 and HR, 1.5; 95% CI, 0.84-2.78; P = 0.15, respectively). In the current study, African-American patients have a prognosis worse than that of white patients in early-stage UCCC. We could not prove the same difference in advanced-stage disease.

Inhibitory effect of Panax ginseng C. A. Meyer on gynecological cancer

The root of Panax ginseng C.A. Meyer (PG) has been used worldwide for thousands of years as a traditional medicine. Among its various beneficial pharmacological effects, the anticancer activity of ginseng has been considered as its most important pharmacological function. We investigated the potential effects of PG on cell growth, colony formation, and migration in 3 major gynecological cancer cell lines: ovarian (A2780 and SKOV3), cervical (HeLa and CaSki), and endometrial (Hec1A) cancers. MTT assay was performed to estimate the cell viability and short-term cell growth, and colony formation assay was carried out to examine the long-term cell growth. Cell migration was also investigated using transwell and wound-healing assay. PG was not significantly cytotoxic to the 3 major gynecological cancer cell lines, but it demonstrated significant inhibitory effects on the colony formation of all the cancer cell lines, except HeLa cells. We also found that PG had an inhibitory effect on the early stages of cell migration. In conclusion, PG has an inhibitory effect on colony formation of gynecological cancer cells and inhibits early stages of cellular migration.

The Use of Laparostomy in Patients With Gynecologic Cancer: First Report From a UK Cancer Center

To report on the use of laparostomy after major gynecologic cancer surgery. Operative records and surgical databases of patients who underwent major open abdominal surgery over a 6.5-year period at a tertiary referral center were searched. Patients who had diagnostic procedures, operative laparoscopy, and surgery for vulval cancer were excluded. All patients who had laparostomy were identified; and the diagnosis, indication for laparostomy, method of temporary cover, and complications were recorded. A total of 1592 laparotomies, including 37 emergencies, were performed. Of these, 14 patients (0.88%) had a laparostomy. Seven patients had primary cancer and 7 had recurrent cancer. As more patients had surgery for primary disease, laparostomy was more common in patients who underwent surgery for recurrent cancer. Seven patients had ovarian/fallopian tube/primary peritoneal cancer, 4 patients had uterine cancer, 2 patients had cervical cancer, and one patient had vaginal cancer. Ten laparostomies (71.4%) were performed after an emergency procedure; thus, laparostomy was approximately 100 times more common after emergency than elective major surgery. Massive bowel distension and bowel wall edema were the major indications for laparostomy. The method of temporary closure was variable, and a sterile saline bag was the most commonly used. The laparostomy was closed in all but 2 patients, most often on postoperative day 2 or 3. Two patients (14.3%) died within 30 days of the laparostomy, and 2 others died at postoperative days 40 and 62. Three of these 4 patients had recurrent cancer, and 2 patients had emergency procedures. The overall incidence of laparostomy associated with laparotomy for gynecological cancer surgery was less than 1:100 cases, was more common after surgery for recurrent cancer, and in particular, was approximately 100 times more common after emergency procedures. The 30-day operative mortality rate was 14.3%.

Expression and Humoral Response of A-Kinase Anchor Protein 4 in Cervical Cancer

Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer. In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA). Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades. Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.