A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery.

Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.

Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury.

Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTß, IL-22R, RANK, LTßR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.

Fish Collagen Peptides Protect against Cisplatin-Induced Cytotoxicity and Oxidative Injury by Inhibiting MAPK Signaling Pathways in Mouse Thymic Epithelial Cells.

Thymic epithelial cells (TECs) account for the most abundant and dominant stromal component of the thymus, where T cells mature. Oxidative- or cytotoxic-stress associated injury in TECs, a significant and common problem in many clinical settings, may cause a compromised thymopoietic capacity of TECs, resulting in clinically significant immune deficiency disorders or impairment in the adaptive immune response in the body. The present study demonstrated that fish collagen peptides (FCP) increase cell viability, reduce intracellular levels of reactive oxygen species (ROS), and impede apoptosis by repressing the expression of Bax and Bad and the release of cytochrome c, and by upregulating the expression of Bcl-2 and Bcl-xL in cisplatin-treated TECs. These inhibitory effects of FCP on TEC damage occur via the suppression of ROS generation and MAPK (p38 MAPK, JNK, and ERK) activity. Taken together, our data suggest that FCP can be used as a promising protective agent against cytotoxic insults- or ROS-mediated TEC injury. Furthermore, our findings provide new insights into a therapeutic approach for the future application of FCP in the prevention and treatment of various types of oxidative- or cytotoxic stress-related cell injury in TECs as well as age-related or acute thymus involution.

Di-(2-ethylhexyl) Phthalate Triggers Proliferation, Migration, Stemness, and Epithelial-Mesenchymal Transition in Human Endometrial and Endometriotic Epithelial Cells via the Transforming Growth Factor-ß/Smad Signaling Pathway.

Di-(2-ethylhexyl) phthalate (DEHP) is a frequently used plasticizer that may be linked to the development of endometriosis, a common gynecological disorder with a profound impact on quality of life. Despite its prevalence, vital access to treatment has often been hampered by a lack of understanding of its pathogenesis as well as reliable disease models. Recently, epithelial-mesenchymal transition (EMT) has been suggested to have a significant role in endometriosis pathophysiology. In this study, we found that DEHP treatment enhanced proliferation, migration, and inflammatory responses, along with EMT and stemness induction in human endometrial and endometriotic cells. The selective transforming growth factor-ß (TGF-ß) receptor type 1/2 inhibitor LY2109761 reversed the DEHP-induced cell proliferation and migration enhancement as well as the increased expression of crucial molecules involved in inflammation, EMT, and stemness, indicating that DEHP-triggered phenomena occur via the TGF-ß/Smad signaling pathway. Our study clearly defines the role of DEHP in the etiology and pathophysiological mechanisms of endometriosis and establishes an efficient disease model for endometriosis using a biomimetic 3D cell culture technique. Altogether, our data provide novel etiological and mechanistic insights into the role of DEHP in endometriosis pathogenesis, opening avenues for developing novel preventive and therapeutic strategies for endometriosis.

A multicentre, randomised, open-label, parallel-group Phase 2b study of belotecan versus topotecan for recurrent ovarian cancer.

BACKGROUND: This Phase 2b study compared the efficacy and toxicity of belotecan and topotecan in recurrent ovarian cancer. METHODS: Patients with platinum-sensitive recurrent or platinum-resistant recurrent ovarian cancer (PRROC) were randomised 1:1 to receive belotecan 0.5 mg/m2 or topotecan 1.5 mg/m2 for five consecutive days every 3 weeks. The primary endpoint was overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 140 (belotecan, n = 71; topotecan, n = 69) and 130 patients (belotecan, n = 66; topotecan, n = 64) were included in the intention-to-treat (ITT) and per-protocol (PP) populations. ORR did not differ significantly between the belotecan and topotecan groups (ITT, 29.6% versus 26.1%; PP, 30.3% versus 25%). Although PFS did not differ between the groups, belotecan was associated with improved OS compared with topotecan in the PP population (39.7 versus 26.6 months; P = 0.034). In particular, belotecan showed longer OS in PRROC and non-high-grade serous carcinoma (non-HGSC; PP, adjusted hazard ratios, 0.499 and 0.187; 95% confidence intervals 0.255-0.977 and 0.039-0.895). Furthermore, there were no differences in toxicities between the two groups. CONCLUSIONS: Belotecan was not inferior to topotecan in terms of overall response for recurrent ovarian cancer. CLINICAL TRIAL REGISTRATION: NCT01630018.

Comparison of long-term survival of total abdominal radical hysterectomy and laparoscopy-assisted radical vaginal hysterectomy in patients with early cervical cancer: Korean multicenter, retrospective analysis.

PURPOSE: The aim of this study was to compare survival outcomes of total abdominal radical hysterectomy (TARH) versus laparoscopy-assisted radical vaginal hysterectomy (LARVH) in stage IA2-IB2 cervical cancer. METHODS: 812 patients who underwent RH between 2008 and 2017 were evaluated in 3 institutions. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier method and compared by log-rank test. The clinical noninferiority of the LARVH to TARH was assessed with a margin of -7.2%. Noninferiority was demonstrated if the low limit of 95% confidence interval (CI) exceeded its predefined margin. RESULTS: 258 patients were treated with TARH and 252 patients with LARVH. TARH and LARVH group had similar 5-year PFS (84.4% vs 86.6%, p = 0.467) and OS rates (85.8% vs 88.0%, p = 0.919). Noninferiority of LARVH to TARH were confirmed with 5-year PFS and OS difference rates of 2.2% (95% CI -2.9-7.3, p = 0.001) and 2.2% (95% CI -2.7-7.1, p = 0.001), respectively. In subgroup of patients with tumors size >2 cm, 5-year PFS (77.6% vs 79.0%, p = 0.682) and OS rates (79.2% vs 81.5%, p = 0.784) did not differ statistically between the two groups. Noninferiority of LARVH to TARH were also confirmed with 5-year PFS and OS difference rates of 1.4% (95% CI -7.0-9.8, p = 0.046) and 2.3% (95% CI -5.8-10.4, p = 0.027), respectively. CONCLUSION: LARVH showed significant noninferiority for PFS and OS versus TARH in early cervical cancer, suggesting the potential oncologic safety of LARVH.

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons.

BACKGROUND: The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC. RESULTS: The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker's staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC. CONCLUSIONS: Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.

Practice Patterns of Hereditary Ovarian Cancer Management in Korea.

OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of the Korean Society of Gynecologic Oncology participated in the inaugural Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail from January to February 2016. The survey was conducted using a self-administered questionnaire. RESULTS: Most physicians (66.7%, 36/54) responded to draw a pedigree of patients with a family history. The rate of genetic test recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54). Physicians tended to select appropriate candidates for the genetic test. Of the respondents, genetic counseling was commonly performed before the genetic test (76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the physician alone (12.8%, 6/47). Participants showed mature response to risk management for the BRCA carriers: at least annual gynecologic surveillance (89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy was considered to recommend in most of respondents (91.5%, 43/47). CONCLUSIONS: Gynecologic oncologic physicians in Korea had high awareness to genetic risk assessment, candidate selection to genetic test, and risk-reducing strategies for the management of hereditary ovarian cancer.

Incidence and treatment outcomes of ovarian carcinosarcoma from the national cancer registry of Korea.

OBJECTIVE: To investigate the incidence and survival outcomes of ovarian carcinosarcoma in Korea between 1999 and 2018. METHODS: Patients diagnosed with ovarian carcinosarcoma between 1999 and 2018 were identified from the Korea Central Cancer Registry (KCCR) and their information was collected. Age-standardized incidence rates (ASRs), annual percent changes (APC), and relative survival rates of ovarian carcinosarcoma were calculated and compared to those of epithelial ovarian cancer. RESULTS: According to the KCCR, 458 cases of ovarian carcinosarcoma were detected, and accounted for 1.5% (458/30,679) of all epithelial ovarian cancers in Korea between 1999 and 2018. The ASR of ovarian carcinosarcoma between 1999 and 2018 was 0.064 per 100,000 women. The incidence rate of ovarian carcinosarcoma increased during the study period, with an ASR of 0.029 per 100,000 in 1999 and 0.073 per 100,000 in 2018. The APC of ovarian carcinosarcoma during 1999-2018 was 5.86 (p<0.001). The median overall survival (OS) of patients with ovarian carcinosarcoma was 39 months, and the 5-year OS rate was 42.5%. Among ovarian carcinosarcomas, patients with localized stages showed better clinical outcomes than those with regional or distant stages (5-year OS, 60.8%, 57.9%, and 32.8%, respectively; p<0.001). In addition, younger (<50 years) patients showed better OS than older (≥50 years) patients (5-year OS, 52.6% vs. 40.2%; p<0.001). CONCLUSION: Our nationwide registry-based study demonstrated that the incidence of ovarian carcinosarcoma increased from 1999 to 2018 in Korea. Patients with advanced-stage disease and older age (≥50 years) had poorer survival outcomes.

Comparison of survival outcome of open, total laparoscopic, and laparoscopy-assisted radical vaginal hysterectomy for stage IB2 cervical cancer patients: A multicenter retrospective study.

The aim of this study was to compare survival outcomes of 3 different radical hysterectomy (RH) types, namely total abdominal radical hysterectomy (TARH), total laparoscopic radical hysterectomy (TLRH), and laparoscopy-assisted radical vaginal hysterectomy (LARVH), in patients with FIGO stage IB2 cervical cancer. We retrospectively identified a cohort of patients who underwent RH for cervical cancer between 2010 and 2017. Patients with stage IB2 cervical cancer were included and were classified into TARH, TLRH, and LARVH treatment groups. Survival outcomes were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to estimate the independent association of RH technique with outcome. 194 patients were included in this study: 79 patients in the TARH group, 55 in the TLRH group, and 60 in the LARVH group. No significant differences were found in clinicopathological characteristics between the 3 RH groups. On comparing survival outcomes with TARH, both TLRH and LARVH showed no significant difference in terms of 5-year overall survival (TARH vs TLRH, P = .121 and TARH vs LARVH, P = .436). Conversely, compared to the TARH group, 5-year progression-free survival (PFS) was significantly worse in the TLRH group (P = .034) but not in the LARVH group (P = .288). Multivariate analysis showed that TLRH surgical approach (hazard ratio, 3.232; 95% confidence interval, 1.238-8.438; P = .017) was an independent prognostic factor for PFS in patients with IB2 cervical cancer. Our study suggests that in patients with FIGO stage IB2 cervical cancer, among the minimally invasive RH approaches, TLRH and LARVH, only TLRH approach was associated with worse PFS when compared with the TARH approach.

Myomectomy with ArtiSential fully articulating laparoscopic instruments: A prospective multicenter study.

BACKGROUND: ArtiSential, a class of innovative laparoscopic instrument, has been developed to overcome the limitations of conventional laparoscopic surgery by enabling free, 360°-unrestricted movement of the wrist joint, as in robotic surgery. OBJECTIVE: The aim of the present study was to describe the initial experiences with these devices in myomectomy and to report the surgical outcomes. METHODS: A total of 77 women undergoing laparoscopic or robotic myomectomy between January 2021 and June 2022 were included in this multicenter prospective study. The ArtiSential instruments used by the surgeons were those chosen according to their respective preferences. The baseline characteristics, surgical outcomes, trocar placement options, and operator survey results were scrutinized. RESULTS: The mean age of the patients was 39.9 ± 6.3, and the mean body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was 22.4 ± 3.4 kg/m2; 46.8% of the patients underwent robotic surgery, while 53.2% underwent laparoscopic surgery. The number of removed myomas was 3.3 ± 3.0, the size of the largest myoma was 7.1 ± 2.3 cm, and the operative time was 130.0 ± 54.0 min. No transfusions or laparotomy conversions were required. Other than one case of ileus, there were no postoperative complications. In most cases, the instruments were inserted through the umbilicus trocar, and the fenestrated forceps, needle holder, and bipolar fenestrated forceps, in that order, were frequently employed. According to a surgeon survey, 29.9% moderately or strongly agreed that the ArtiSential devices utilized were more convenient than conventional laparoscopic instruments, while only 9.7% moderately or strongly agreed that they were more convenient than robotic instruments. CONCLUSIONS: Myomectomy as performed with an ArtiSential instrument seems to be feasible and safe. Further studies are necessary in order to comparatively assess the outcomes and potential benefits of ArtiSential, robotic, and conventional laparoscopic myomectomy.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Transabdominal cardiophrenic lymph node dissection (CPLND) via incised diaphragm replace conventional video-assisted thoracic surgery for cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The objective of this study is to describe the feasibility of the new approach, transabdominal CPLND, via incised diaphragm in patients with ovarian cancer by gynecologic oncologists instead of the conventional video-assisted thoracic surgery. METHODS: From November 2008 to December 2011, 11 women (10 primary and 1 recurrent ovarian cancers) underwent CPLND for the extensive cytoreductive surgeries via incised muscle of the right diaphragm by gynecologic oncologists. All ≥5 mm tumors in CPLN, which were the criterion for suspicious malignancy on preoperative axial computed tomogram, were completely resected by gynecologic oncologists. RESULTS: The median tumor size of the CPLN was 10mm (range, 7-17 mm) and metastasis was identified in 45% (5/11) of ≥5 mm CPLN on preoperative computed tomogram. The median number of harvested CPLND was 3 (range 1-12) and metastatic node was 1 (range, 0-10). There was no significant morbidity related to CPLND and mortality associated with surgery. Ten patients achieved the no gross residual disease and one patient accomplished gross residual-1, indicating residual disease measuring ≤1 cm in maximal diameter. CONCLUSION: Transabdominal CPLND via incised diaphragm is feasible as a part of the cytoreductive surgery without significant morbidities by gynecologic oncologist. This procedure could substitute the conventional video-assisted thoracic surgery.

Preoperative Haematologic Markers for the Differentiation of Endometrial Cancer from Benign Endometrial Lesions in Postmenopausal Patients with Endometrial Masses.

Purpose: The diagnostic value of preoperative hematological changes in endometrial cancer (EC) remains unclear. This study aimed to assess the role of preoperative hematologic parameters in differentiating EC from benign endometrial lesions in postmenopausal women with endometrial masses. Methods: Preoperative laboratory variables were retrospectively reviewed in patients with malignant or benign endometrial lesions, and the significance of intergroup differences was assessed. Receiver operating characteristic curves were used to analyze the optimal cut-off values for each variable. Logistic regression analysis was used to identify the variables predicting the presence of endometrial malignancy. Results: Preoperative laboratory variables of 176 patients (84 EC and 92 benign lesions) with endometrial masses were analyzed. Significant differences were observed between malignant and benign lesions in terms of WBC count, ANC, MCV, MPV, PDW, CA125, NLR, PMR, LMR, and SII (P < 0.05). Multivariate analyses showed that a high WBC count, high ANC, low MCV, low MPV, low PDW, high CA125, high NLR, high PMR, high LMR, and high SII independently predicted the presence of endometrial malignancy. Conclusion: The combination markers, MPV+PDW+NLR, had good discriminatory power for the presence of malignancy (AUC 0.797). Our results suggest that hematologic markers could be useful for the differentiation of malignant and benign endometrial lesions.

Pulmonary cryptococcosis masquerading as lung metastasis in gynecologic cancers: Two case reports.

RATIONALE: Pulmonary cryptococcal infections occur mainly in immunocompromised individuals, such as those with malignancies. Preoperative diagnosis of pulmonary cryptococcosis (PC) can be challenging for both clinicians and radiologists because of nonspecific clinical manifestations and variable radiologic features, as it is easily misdiagnosed as metastatic lung cancer. PATIENT CONCERNS: In case 1, a 76-year-old woman with a history of cervical cancer presented with lung nodules detected on chest computed tomography (CT) 13 months after completing concurrent chemoradiotherapy. In case 2, a 56-year-old woman with a history of ovarian cancer presented with pulmonary nodules on chest CT 19 months after completing chemotherapy. Both patients were clinically asymptomatic, and tumor markers were not elevated. DIAGNOSES: In case 1, chest CT revealed multiple enhanced nodules with lobulated margins in the left lower lobe, and positron emission tomography (PET)-CT showed uptake in the nodule with a standardized uptake value of 3.7. In case 2, chest CT revealed several nodules in the right upper lobe abutting the right major fissure, and PET-CT revealed fluorodeoxyglucose uptake in the nodules. Pathology revealed granulomatous inflammation with cryptococcal infection, and mucicarmine and periodic acid-Schiff staining confirmed cryptococcal infection in both cases. INTERVENTIONS: Presumptive diagnoses of lung metastases were made in both cases and thoracoscopic lobectomy was performed. Postoperatively, the patients received antifungal therapy with fluconazole. OUTCOMES: PC was differentially diagnosed and effectively managed. The patients remained disease-free for both PC and gynecological cancers during subsequent follow-ups. LESSONS: Recognition that PC can mimic lung metastasis is important for managing gynecological cancers. PC should be considered in the differential diagnosis when single or multiple nodules are detected on chest radiography without elevation of tumor markers in patients with gynecological cancer.

Clinical Progression of Colorectal Resection in Gynecologic Cancer Patients: Does the Risk of Anastomotic Leakage Increase after Surgery?

OBJECTIVES: This research aimed to examine the clinicopathological results of colorectal resection in patients with advanced gynecological cancers. METHODS: We retrospectively reviewed the medical records of 104 patients with gynecological cancer who underwent colorectal resection from December 2008 to August 2020 at a single hospital (PNUYH). Using descriptive statistics, variables for risk factors and surgical complications were compared. We eliminated instances with malignancies originating from organs other than the female genitalia, benign gynecological illnesses, primary stoma formation, and any other bowel procedures outside colon resection. RESULTS: The average age of 104 patients was determined to be 62.0 years. The most prevalent gynecological cancer was ovarian cancer (85 patients, 81.7%), and the most frequent procedure was low anterior resection (80 patients, 76.9%). There were postoperative problems in 61 patients (58.7%), while there was anastomotic leaking in just 3 patients (2.9%). Among the risk factors, only preoperative albumin was statistically significant (p=0.019). CONCLUSION: Our findings imply that colorectal resection can be performed safely and effectively on individuals with advanced gynecological cancer.

The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma.

BACKGROUND: B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target. METHODS: A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. RESULTS: B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs. CONCLUSIONS: The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.

Persistent human papillomavirus DNA is associated with local recurrence after radiotherapy of uterine cervical cancer.

Human papillomavirus (HPV) DNA is considered as a hallmark of cervical cancer. We investigated whether persistent HPV DNA at the cervix is associated with local recurrence after radiotherapy in patients with locally advanced cervical cancer. A total of 156 patients with HPV-positive cervical cancer (International Federation of Gynecology and Obstetrics stage IB-IVB) treated with radiotherapy between July 2003 and December 2006 were analyzed. HPV DNA was measured prior to radiotherapy and after completion of radiotherapy. The results of HPV DNA test at postradiotherapy 1, 3, 6 and 12 months were analyzed individually for association with local recurrence-free survival (LRFS). In addition, the result of any last follow-up HPV test within 24 months postradiotherapy was defined as the overall status of HPV at 24 months and was also analyzed for association with LRFS. HPV DNA was cleared in 127 patients (81.4%) and persistent in 29 patients (18.6%) by 24 months. In 18 patients with local recurrences, 14 patients (78%) showed positive HPV tests at 1-3 months. Among the various time points analyzed, a positive HPV test at 3 months was the most accurate predictor of local recurrence. Multivariate analysis indicated that overall status of HPV at 24 months, low HPV viral load and histologic grade as being significantly related to poor LRFS. In HPV-positive cervical carcinoma treated primarily with radiotherapy, persistent HPV DNA within 24 months after treatment indicates a high risk of local recurrence. Diagnostic accuracy of HPV test was highest at 3 months.

Extended cytoreduction of tumor at the porta hepatis by an interdisciplinary team approach in patients with epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to describe the development and experience in resection of tumor at the porta hepatis in patients with ovarian cancer by an interdisciplinary team approach. METHODS: From August 2007 to June 2009, 11 women (2 primary and 9 recurrent ovarian cancers) underwent extended cytoreductive surgery including resection of tumor at the porta hepatis by hepatobiliary surgeons. RESULTS: Tumor resection at the porta hepatis was required in 7.1% of the patients (11/155) during the study period. The median tumor size of the porta hepatis was 2.0cm (range, 0.7-4cm). All visible tumors at the porta hepatis were completely resected with co-operation of hepatobiliary surgeons. Optimal cytoreduction was achieved in all patients. There was no significant morbidity related to tumor resection of the porta hepatis and mortality associated with surgery. Five of 11 patients had recurrent disease at median 8months (range, 1-13) after the surgery with a median follow-up of 8months (range, 3-21months). CONCLUSION: Tumor resection at the porta hepatis is feasible with acceptable morbidities in patients with ovarian cancer by an interdisciplinary team approach with hepatobiliary surgeons. Long term follow up is needed to know the impact on survival.