Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace.

BACKGROUND: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. METHODS: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and <65 years of age). We performed a logistic regression analysis to determine the relationship between returning to the same workplace and not taking sick leave. RESULTS: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P < 0.001), advanced cancer stage (P = 0.018) and long treatment time (P = 0.032). Interestingly, not taking sick leave was strongly associated with not returning to the same workplace in the multivariable analysis (P < 0.001). CONCLUSIONS: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan.

Hereditary gynecologic tumors and precision cancer medicine.

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.

The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer.

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann-Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 µg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.

The Influence of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life of Gynecologic Cancer Survivors.

OBJECTIVE: The aim of this observational study was to investigate correlations between long-term chemotherapy-induced peripheral neurotoxicity (CIPN) and quality of life (physical well-being, social well-being, emotional well-being, and functional well-being [FWB]) among survivors of gynecologic cancer (GC). METHODS: We aimed to assess the correlation of quality of life and long-term CIPN with the temporal change in recurrence-free GC survival. Questionnaire responses and clinical data of 259 GC survivors were collected and assessed according to treatment received. The χ test was used to determine the significance of correlations. RESULTS: Of 165 evaluable patients treated by chemotherapy, 36 patients (21.8%) developed CIPN of Common Toxicity Criteria for Adverse Events grade 1 or higher during the study. Chemotherapy-induced peripheral neurotoxicity had significantly improved over time in the domain of FWB at 61 months or more after the end of chemotherapy (posttreatment 4) among GC survivors (P = 0.003). Furthermore, CIPN treated by more than 6 courses of the paclitaxel and carboplatin regimen among GC survivors showed significant improvement over time in the emotional well-being domain at 25 to 60 months and 61 months or more after the end of chemotherapy (posttreatments 3 and 4) (P = 0.037 and P = 0.023) and in FWB at posttreatment 4 (P < 0.001). CONCLUSIONS: Emotional and functional domains of CIPN improved over time among GC survivors treated by more than 6 courses of the paclitaxel and carboplatin regimen. Based on these results, further research is required to identify additional preventative or curative approaches.

Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy.

OBJECTIVE: This study aimed to investigate the correlation of sarcopenia findings with prognostic factors in patients with cervical cancer (CC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively collected data on body composition and clinicopathological features from the medical records of 60 patients with CC who underwent CCRT and analyzed correlations between prognosis and changes in body composition as measured by computed tomography (skeletal muscle and iliopsoas muscle [IM]). Statistical analyses were performed using the Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the last follow-up was 33.5 months (range, 1-104 months). The PFS and OS rates were worse for patients with at least 15.0% than for those with less than 15.0% loss of skeletal muscle and IM from baseline (P < 0.001 for both). Furthermore, multivariate analyses showed that at least 15.0% loss of IM was an independent prognostic factor for PFS and OS (P = 0.002 for both). CONCLUSIONS: Sarcopenia (≥15.0% loss of IM from baseline) was revealed to be an important prognostic factor in patients with CC undergoing CCRT.

Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer.

OBJECTIVE: Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer. METHODS: Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The χ test was used to determine the significance of the correlations. RESULTS: The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return to work in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than-6-month interval between treatment and return to work and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034). CONCLUSIONS: Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer.

The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer.

OBJECTIVE: The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physical well-being [PWB], social well-being, emotional well-being [EWB], and functional well-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patients with gynecologic cancer (GC). METHODS: From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The χ test was used to determine the significance of correlations. RESULTS: Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017). CONCLUSIONS: Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

Return to work after cancer treatment of gynecologic cancer in Japan.

BACKGROUND: Gynecologic cancer is one of the most common malignant diseases in working-age women. This study investigated whether several characteristics influence return to work after treatment of gynecologic cancer. METHODS: We investigated the correlations between return to work and several other characteristics in 199 gynecologic cancer survivors. Questionnaires were distributed to patients with cancer (≥1 year after treatment and age of <65 years) who visited Okayama University. Logistic regression analysis and receiver operating characteristic curves were used to determine whether each characteristic influenced return to work (no return to work or job change) in these gynecologic cancer survivors. RESULTS: For all patients, the mean age at the time of diagnosis was 47.0 years, and the average number of years after treatment was 4.5. Forty-four patients (53.7 %) who were non-regular employees continued to be employed at the same workplace. Non-regular employment had a significantly higher area under the curve (AUC) (0.726) than other characteristics in terms of negatively affecting return to work. Additionally, non-regular employment tended to have a higher AUC (0.618) than other characteristics in terms of job changes. CONCLUSIONS: Non-regular employment was the variable most likely to negatively affect return to work and job changes in employed patients who underwent treatment for gynecologic cancer.

Surgical training in extraperitoneal laparoscopic para­aortic lymphadenectomy for the treatment of gynecological cancer using a Thiel­embalmed cadaver.

The extraperitoneal laparoscopic approach (ELPAN) for para-aortic lymphadenectomy provides excellent visibility of the left side of the aorta, thus facilitating surgery in the retroperitoneal space. This technique is highly complex compared with the transperitoneal approach. In particular, advanced techniques are required to develop an appropriate surgical field in the narrow retroperitoneal space; therefore, surgeons need to undergo a significant amount of training to become competent. A variety of tools are available for surgical training but are limited by their ability to reproduce complex anatomy. Thus, cadavers may represent the most suitable tool for learning this unique technique. The present study describes a surgical training protocol for the ELPAN technique using a Thiel-embalmed human cadaver and provides a step-by-step description of the ELPAN technique performed at Okayama University (Okayama, Japan). A 72-year-old Thiel-embalmed female cadaver was used to develop a protocol for surgical training in the ELPAN technique that effectively reproduced the methodology required in clinical practice. A training method for ELPAN surgery was developed and successfully completed using the Thiel-embalmed cadaver that secured the surgical field in the retroperitoneal space and permitted resection of the lymph nodes. The Thiel-embalmed cadaver tissue possessed excellent properties for surgical training, including color tone, flexibility, and the membrane structure of connective and fat tissues. In addition, this method of fixation preserved stiffness and elasticity of the peritoneum, although large vessels were slightly fragile and poorly extensible. Surgical training using a Thiel-embalmed human cadaver represents a valuable option for learning the ELPAN surgical technique. However, this technique may be unsuitable for training in perivenous manipulation. To the best of our knowledge, this is the first report to describe the use of Thiel-embalmed cadavers as a tool for surgeons to undergo training in the ELPAN technique.

Pure abscopal effect in a patient with advanced uterine carcinosarcoma.

The abscopal effect is a rare phenomenon, in which tumor shrinkage in the nonirradiated metastatic region is observed after radiotherapy. Certainly, this response is sometimes reported with the combined use of immune-checkpoint inhibitors, but a pure abscopal effect is extremely rare, especially in endometrial cancer. We present the case of a 79-year-old woman with an advanced endometrial carcinosarcoma. She was treated with surgical reduction of the primary lesion, followed by radiotherapy of the metastatic regional lymph nodes. Distant metastases were detected in radiological imaging test 2 months after the completion of radiotherapy, and we carefully followed up without any treatment considering the patient's tolerability for further procedures. Six months after recurrence, she experienced cytoreduction in the metastatic lesions confirmed through imaging findings, which was believed to be an abscopal effect, and maintained this shrinking state for 15 months. Herein, we describe this pure abscopal effect from the perspective of imaging, pathological and molecular findings, and therapeutic strategies.

DNA mismatch repair deficiency and p53 abnormality are age-related events in mixed endometrial carcinoma with a clear cell component.

Mixed endometrial carcinoma (MEC) is defined as a tumor composed of two or more spatially distinct subtypes, at least one of which is serous or clear cell carcinoma. In this study, the clinicopathological features of 15 MEC cases containing a clear cell component (MEC-C) were investigated. The ages of patients ranged from 32 to 83 years (median, 61 years). The combinations of carcinoma components observed were endometrioid and clear cell in ten patients; endometrioid, clear cell and serous in three; and clear cell and serous in two. Immunohistochemically, nine had DNA mismatch repair (MMR) protein deficiency (MMR-d), nine had loss of ARID1A and three cases had aberrant p53 expression. MMR-d and loss of ARID1A showed a strong correlation. Only one case showed both MMR-d and aberrant p53 expression. The patients with MMR-d were younger than those without MMR-d (median; 58 years vs. 71 years). Loss of ARID1A also showed significant predilection for younger women than ARID1A intact cases. In conclusion, MMR-d was observed in 60 % of MEC-C, showed predilection for young women, and was associated with ARID1A loss. In contrast, non- MMR-d MEC-C occurred in elder women and some tumors may associate with TP53 mutation. These findings suggest that MEC-C develop via two different molecular mechanisms and they are age-related events.

Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis.

Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

Sarcopenia Is Not a Prognostic Factor of Outcome in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy.

BACKGROUND/AIM: The objective of this study was to determine if sarcopenia was a predictor of poor prognosis in patients with cervical cancer (CC) undergoing concurrent chemoradiation therapy (CCRT) or radiation therapy (RT). MATERIALS AND METHODS: A total of 236 patients with CC undergoing CCRT or RT were retrospectively examined. We determined if clinical characteristics and survival were correlated with pretreatment sarcopenia, measured as psoas muscle index (PI) or skeletal muscle index (SMI). RESULTS: Pretreatment PI and SMI were related to parametrial involvement with CC undergoing CCRT or RT (p=0.002, and, p=0.034, respectively). The median progression-free survival (PFS) and overall survival (OS) times in patients undergoing CCRT or RT were 29.0 and 34.5 months, respectively. Neither PI nor SMI were prognostic predictors in patients with CC undergoing CCRT or RT. CONCLUSION: Sarcopenia is not a predictive factor of outcome in patients with CC undergoing CCRT or RT.

Prognostic nutritional index as a predictor of survival in patients with recurrent cervical cancer.

Systemic inflammatory responses (SIRs) can help predict survival in various cancers. The present study investigated the accuracy of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI) in predicting survival for patients with recurrent cervical cancer. A retrospective review of prognoses examined the associations among NLR, PLR, and PNI, and clinical characteristics and survival in 79 patients with recurrent cervical cancer after undergoing concurrent chemoradiation therapy (CCRT) or radical hysterectomies with or without CCRT. The Mann-Whitney U-test was used for statistical analyses. In addition, 12-month, 24-month and overall survival were analyzed by the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. Median survival was 15.0 months over follow-up periods of 2-93 months. At the last follow-up point, 54 had succumbed to disease and 25 were alive with disease. In univariate analysis, NLR, PLR and PNI were significantly associated with 12-month, 24 month and overall survival (12 months: P=0.021, P=0.001 and P<0.001; 24 months: P=0.020, P=0.008 and P<0.001; overall; P=0.032, P=0.032 and P<0.001, respectively). In multivariate analyses, PNI was an independent prognostic factor for 12-month, 24-month and overall survival (P=0.001, P=0.001 and P<0.001, respectively). PNI is a useful predictor of survival of recurrent cervical cancer.

Glasgow prognostic score is a prognosis predictor for patients with endometrial cancer.

OBJECTIVE: This study investigated whether the inflammation-based Glasgow prognostic score (GPS) predicted the prognosis of patients with endometrial cancer (EC) in terms of progression-free survival (PFS) and overall survival (OS). STUDY DESIGN: Pretreatment GPS was examined to determine the correlations with recurrence and survival in 431 patients with EC. Statistical analyses were performed using the Mann-Whitney U test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. RESULTS: Median PFS and OS were 49.7 and 52.7 months, respectively. The follow-up range was 1 to 140 months. Kaplan-Meier analysis revealed that patients with EC cancer and high GPS (GPS 2) had a shorter PFS and OS than those with lower GPS (GPS 0+1) (PFS: P<0.001; OS; P<0.001). On multivariate analysis, GPS (GPS 2) was an independent predictor of both recurrence (P<0.001) and survival (P<0.001) for all cases of EC. CONCLUSION: GPS can be useful as an indicator of poor prognosis in patients with EC.

Oxidative DNA damage induced by metabolites of chloramphenicol, an antibiotic drug.

Chloramphenicol (CAP) was an old antimicrobial agent. However, the use of CAP is limited because of its harmful side effects, such as leukemia. The molecular mechanism through which CAP has been strongly correlated with leukemogenesis is still unclear. To elucidate the mechanism of genotoxicity, we examined DNA damage by CAP and its metabolites, nitroso-CAP (CAP-NO), N-hydroxy-CAP (CAP-NHOH), using isolated DNA. CAP-NHOH have the ability of DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in the presence of Cu(II), which was greatly enhanced by the addition of an endogenous reductant NADH. CAP-NO caused DNA damage in the presence of Cu(II), only when reduced by NADH. NADH can non-enzymatically reduce the nitroso form to hydronitroxide radicals, resulting in enhanced generation of reactive oxygen species followed by DNA damage through the redox cycle. Furthermore, we also studied the site specificity of base lesions in DNA treated with piperidine or formamidopyrimidine-DNA glycosylase, using (32)P-5'-end-labeled DNA fragments obtained from the human tumor suppressor gene. CAP metabolites preferentially caused double base lesion, the G and C of the ACG sequence complementary to codon 273 of the p53 gene, in the presence of NADH and Cu(II). Therefore, we conclude that oxidative double base lesion may play a role in carcinogenicity of CAP.