Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study.

BACKGROUND: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

Effect of radical trachelectomy on ovarian reserve: A single-institute prospective study.

AIM: Reduced responses to controlled ovarian stimulation (COS) after radical trachelectomy (RT) have been previously reported. We aimed to assess the effect of RT on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels before and after the procedure in this prospective study. METHODS: We included 12 patients who underwent RT between September 2019 and December 2021 in this study. Serum AMH levels were measured preoperatively, 1 month postoperatively, and 6 months postoperatively. Differences in the AMH levels were assessed using a paired t-test. RESULTS: The median age of the patients was 30.6 years, and the median follow-up time was 30.1 months. AMH levels at 1 and 6 months postoperatively did not show a consistent trend. At 1 month postoperatively, the average AMH level decreased insignificantly but returned to preoperative levels at 6 months. The differences in AMH levels before and after RT were insignificant. CONCLUSION: Our findings indicate that RT did not affect ovarian reserve as measured by AMH levels. However, the relationship between unchanged ovarian reserve and reduced response to COS remains unclear. Further research with larger sample sizes and additional measures of ovarian function is needed to corroborate these results and investigate the long-term effects of RT on ovarian reserve. Understanding these mechanisms will help guide surgical practices and provide patients with valuable information about their reproductive outcomes after RT.

An update of oncologic and obstetric outcomes of radical trachelectomy for early-stage cervical cancer: The need for further minimally invasive treatment.

AIMS: To investigate the oncologic and obstetric outcomes of radical trachelectomy (RT) in patients with early-stage cervical cancer and to evaluate the potential role of fertility-preserving treatments in improving pregnancy outcomes while oncologic status is stable. METHODS: In this single-institution study, we analyzed the oncologic and obstetric outcomes of 67 patients with early-stage cervical cancer who underwent RT at Nagoya University Hospital. RESULTS: The cancer recurrence rate (6.0%) and the mortality rate (1.5%) were comparable with those of previous studies. Of the 46 patients who attempted to conceive after RT, 19 (41.3%) became pregnant, and 16 gave birth. Of these 37.5% delivered at term, and delivery at less than 28 weeks of gestation occurred in 31.3% of pregnancies. CONCLUSIONS: RT is a viable treatment option for selected patients with early-stage cervical cancer. However, the use of less invasive techniques, such as conization/simple trachelectomy and pelvic lymph node dissection, may improve pregnancy outcomes while oncologic status is stable.

Spatial distribution of tumor-resident macrophages as predictive biomarkers in endometrial cancer.

BACKGROUND: To investigate the role of CD47 expression and its relationship with tumor-resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. METHODS: A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). RESULTS: The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H-score and the density of CD68-positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68-positive macrophages at the tumor margin but a low density of CD163-positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). CONCLUSIONS: The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model.

BACKGROUND: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. METHODS: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. RESULTS: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. CONCLUSIONS: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.

Mean platelet volume as a potential biomarker for survival outcomes in ovarian clear cell carcinoma.

OBJECTIVE: This study aimed to explore the prognostic value of mean platelet volume (MPV) in patients with ovarian clear cell carcinoma (OCCC) and evaluate the predictive performance of a random forest model incorporating MPV and other key clinicopathological factors. METHODS: A total of 204 patients with OCCC treated between January 2004 and December 2019 were retrospectively analyzed. Clinicopathological characteristics and preoperative laboratory data were collected, and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards models. An optimal MPV cutoff was determined by receiver operating characteristic (ROC) curve analysis. A random forest model was then constructed using the identified independent prognostic factors, and its predictive performance was evaluated. RESULTS: The ROC analysis identified 9.3 fL as the MPV cutoff value for predicting 2-year survival. The MPV-low group had lower 5-year overall survival and progression-free survival rates than the MPV-high group (p = 0.003 and p = 0.034, respectively). High MPV emerged as an independent prognostic factor (p = 0.006). The random forest model, incorporating the FIGO stage, residual tumors, peritoneal cytology, and MPV, demonstrated robust predictive performance (area under the curve: 0.905). CONCLUSION: MPV is a promising prognostic indicator in OCCC. Lower MPV correlated with worse survival rates, advocating its potential utility in refining patient management strategies. The commendable predictive performance of the random forest model, integrating MPV and other significant prognostic factors, suggests a pathway toward enhanced survival prediction, thereby warranting further research.

Niraparib as a therapeutic agent for the treatment of ovarian cancer meningeal dissemination with BRCA1 mutation.

This study analyzed a 63-year-old woman with hereditary BRCA1 mutation. She underwent interval debulking surgery after neoadjuvant chemotherapy for high-grade serous ovarian carcinoma (HGSOC). After 2 years of postoperative chemotherapy, she developed headache and dizziness, and a suspected metastatic cerebellar mass in left ovary was detected. Pathological analysis of the mass revealed HGSOC, which was removed surgically. Eight months and another 6 months after the surgery, local recurrence was noted; hence, she underwent CyberKnife treatment. After 3 months, cervical spinal cord metastasis was found, evidenced by left shoulder pain. Moreover, meningeal dissemination was present around the cauda equina. Chemotherapy treatment, including bevacizumab, was ineffective and increased lesions were observed. After CyberKnife treatment for the cervical spinal cord metastasis, niraparib was initiated for the meningeal dissemination. The cerebellar lesions and meningeal dissemination improved within 8 months of niraparib treatment. Although meningeal dissemination is challenging to treat, niraparib may be useful in BRCA-mutated HGSOC.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis.

OBJECTIVE: In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients' survival. METHODS: Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts. RESULTS: During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234-1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330-2.669), P = 0.905}. CONCLUSIONS: Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. METHODS: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch's t-test was used for comparisons between two independent groups. RESULTS: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). CONCLUSIONS: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.

The current situation of health services for hydatidiform mole in Cambodia.

AIM: Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. METHODS: A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. RESULTS: A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n = 29), provincial hospitals (n = 42), district hospitals (n = 20), health centers (n = 6), and others (n = 29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. CONCLUSIONS: The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? ~Propensity score matched analysis~.

OBJECTIVE: The impact of 'standard full-staged radical surgery (SRS)' on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. METHODS: Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65 years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. RESULTS: The median follow-up duration of all surviving patients was 55.9 months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P = 0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271-2.165), P = 0.615]. CONCLUSIONS: After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

Evaluation of a routine second curettage for hydatidiform mole: a cohort study.

OBJECTIVE: The aim of this study was to evaluate routine second curettage for hydatidiform mole (HM) by comparing the characteristics and outcomes of developing gestational trophoblastic neoplasia (GTN). STUDY DESIGN: This was a cohort study including 173 patients diagnosed with HM between January 2002 and August 2019 who were followed up at Nagoya University Hospital, Japan. After an evacuation, 105 and 68 patients were managed with the routine method (routine group) and elective method (elective group) for a second curettage, respectively. The routine second curettage was performed around 7 days after the first evacuation. Patients in the elective group underwent a second curettage if there was ultrasonographic evidence of molar remnants in the uterine cavity. Socio-clinical factors were retrospectively compared between the routine and elective groups, and between patients showing regression and those who developed GTN. RESULTS: The incidence of GTN was 15.2% in the routine group and 20.6% in the elective group, and the difference was not significant (P = 0.364). The median GTN risk score was significantly higher in the routine group than in the elective group (P = 0.033). Presence of a complete HM, gestational age, and a pre-treatment human chorionic gonadotropin level of ≥ 200,000 mIU/mL were independent risk factors for GTN in molar patients. CONCLUSION: The incidence of GTN was unchanged but the risk score of GTN was higher in the routine group than in the elective group. Routine second curettage may not be necessary, but further study will be needed to confirm this.

The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia.

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN). METHODS: Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated. RESULTS: The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies. CONCLUSION: The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.

The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer.

BACKGROUND: The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. METHODS: Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. RESULTS: Median follow-up was 64.8 (range 4.8-143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan-Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). CONCLUSIONS: Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age.

BACKGROUND: Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. METHODS: The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31-40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. RESULTS: A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1-270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p < 0.001); stage I disease (85.9% vs. 70.4%, p < 0.001); mucinous type (69.2% vs. 35.6%, p < 0.001); conservative surgery (83.8% vs. 41.6%, p < 0.001); no adjuvant chemotherapy (67.2% vs. 44.7%, p < 0.001); and CA125 ≤ 35 U/mL (39.4% vs. 28.8%, p < 0.05). There was a significant difference in the overall survival (p = 0.0051) and the disease-free survival (p = 0.0039) between the two groups. Multivariate analysis revealed that the independent prognostic factors for the overall survival were age, stage, histology, and ascitic fluid cytology. CONCLUSION: In epithelial ovarian neoplasms, younger patients had a survival advantage over older patients.

Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background.

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

Oncologic and reproductive outcomes of cystectomy as a fertility-sparing treatment for early-stage epithelial ovarian cancer.

BACKGROUND: Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking. METHODS: After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed. RESULTS: The median age was 29 years (range 26-38 years). The median follow-up time was 103.6 months (range 42.2-218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients. CONCLUSIONS: Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes?

BACKGROUND: In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy. METHODS: A retrospective cohort study was conducted during 2001-2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes. RESULTS: In the 68-month median follow-up period (range 6-178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320-1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187-2.322); P = 0.558]. Moreover, Kaplan-Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141). CONCLUSIONS: Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence.

Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma.

BACKGROUND: Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. MATERIALS AND METHODS: The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III-IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. RESULTS: The median age of patients with PmOC and MmOC was 55 (18-81) and 51 years (30-82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303-3.654), P = 0.0036]. CONCLUSION: The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study.

AIM: Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. METHODS: Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. RESULTS: A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. CONCLUSION: Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.