Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Introduction: Since the commercial availability of buprenorphine extended-release transdermal patches (BTDP) from the early 2010’s, the therapeutic indications for opioids have widely expanded to include chronic benign diseases. We report a case of a home health care patient with acute opioid withdrawal symptoms due to self-interruption of BTDP. Case: An 84-year-old man using home health care services due to worsening of lumbar spinal canal stenosis had been receiving analgesia with a BTDP, a mixed opioid agonist/antagonist analgesic, for the preceding five months. Since the patient's spouse thought that his pain and symptoms were gradually improving, she secretly replaced the BTDP with an NSAID patch without informing the patient. About 50 hours later, the patient experienced a variety of symptoms, including frequent urination with incontinence every five minutes, watery diarrhea, sweating, decreased blood pressure, discomfort in the feet, and insomnia. Evaluation of the Clinical Opiate Withdrawal Score (COWS) by the home health care physician indicated a score of 12, corresponding to mild withdrawal symptoms. About 12 hours after symptom onset, the severe abnormalities were barely noticeable and completely disappeared after two days. Conclusion: Few previous case reports have described withdrawal symptoms due to rapid discontinuation of BTDP. In addition to the medical considerations, we report the social issues associated with onset of the condition in a home environment. Opioid use for non-cancer pain requires medication management from a different perspective than that for cancer pain.

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. Methods: This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

OBJECTIVE: In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but “seromucinous carcinoma” was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients. METHODS: Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013. RESULTS: Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049). CONCLUSION: Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.
Carcinoma, Endometrioid ; Disease-Free Survival ; Endometrial Neoplasms* ; Endometrium ; Estrogens ; Female ; Genes, Homeobox ; Humans ; Keratins ; Prognosis* ; Receptors, Progesterone ; World Health Organization

OBJECTIVE: Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined. METHODS: The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro. RESULTS: High expression of autophagy-related protein, LC3A, was detected in 78 cases (78%) in all CCC cases. The patients with high LC3A expression showed significantly lower response rate to primary chemotherapy (17% vs. 100%, p<0.010), and had worse progression-free survival (PFS) and overall survival (OS) compared with those with LC3A low expression. Furthermore, multivariate analyses revealed that high expression of LC3A was identified as independent worse prognostic factors for PFS and OS. Inhibition of autophagy protein LC3A using hydroxychloroquine (HCQ) increased sensitivity to cisplatin in CCC cells in vitro. CONCLUSION: High expression of LC3A proteins was associated with lower response to platinum therapy, leading to worse prognoses in CCC. Although further studies are needed to confirm the results, inhibition of autophagy by HCQ was associated with platinum sensitivity. Autophagy protein LC3A could be a promising target for treatment for CCC.
Adenocarcinoma, Clear Cell ; Autophagy* ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Hydroxychloroquine ; In Vitro Techniques ; Multivariate Analysis ; Ovarian Neoplasms ; Platinum ; Prognosis

　　[Purpose] We introduced subcutaneous suture with a synthetic absorption thread and examined its efficacy on surgical site infection after pancreaticduodenectomy (PD). [Method] In hour hospitals, PD was performed in a total of 69 cases from March 2006 through March 2014. They was divided into two groups-one consisting of 31 cases in which the skin wounds with staplers (non-subcutaneous suture group), and the other consisting of 38 cases in which surgical wounds were closed with subcutaneous sutures (subcutaneous suture group), and the incidence of surgical site infection (SSI) were compared between the two groups. [Result] Incidence of surface SSI occurred in eight cases (21.0%) in the non- subcutaneous suture group and three cases (9.7%) in the subcutaneous suture group (p＝0.17). The incidence of SSI was decreased in the subcutaneous suture group than in the non-subcutaneous suture group, but no statistically significant difference was observed between the two groups. However, taking into account the advantages such as the reduction of patient’s medical expenses, and the burden of ward duties, further examination with an additional number of patients was thought to be necessary.

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Adaptor Proteins, Signal Transducing/deficiency/metabolism ; Adenosine Triphosphatases/deficiency/metabolism ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; *DNA Mismatch Repair ; DNA Repair Enzymes/deficiency/*metabolism ; DNA-Binding Proteins/deficiency/*metabolism ; Endometrial Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; MutS Homolog 2 Protein/deficiency/metabolism ; Neoplasm Proteins/deficiency/metabolism ; Nuclear Proteins/deficiency/metabolism ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*metabolism

Objective: The aim of this study was to assess the economic burden of disability of school-aged children and to evaluate the association between disabilities and household socioeconomic status, as well as the economic burden of disability and household socioeconomic status in Vietnam.
Materials and Methods: Nationally representative data for 9,882 children aged 6 to 17 years from the Vietnam Household Living Standard Survey 2006 were used. Disabilities were measured in six basic functional domains, including vision, hearing, remembering or concentrating, mobility, self-care, and communication. We evaluated the association between area, household income, educational attainment, or occupation of household head, and each difficulty. The ratio of health-care expenditure to per capita household income was compared by presence of a disability as well as household socioeconomic status.
Results: The prevalence of difficulty was 1.9% for vision and 2.3% for at least one of the other five domains. Difficulty in vision was more prevalent in the richer households (p=0.001), whereas difficulty in the other five domains was more prevalent in the poorer households (p=0.002). The ratio of health-care expenditure to per capita household income was greater than 0.05 in 4.6% of children. The adjusted odds ratio of children with difficulty in vision having a health-care expenditure share greater than 0.05 compared with children without difficulty was 4.78 (95% CI: 2.95, 7.73; p<0.001), and that for difficulty in the other five domains was 3.13 (95% CI: 2.04, 4.80; p<0.001). Among children with difficulty in at least one of the five domains other than vision, the proportion of children with a health-care expenditure share greater than 0.05 was higher among children from the poorer households (p=0.033).
Conclusions: Children with a disability spent more on health care relative to their income than those without. Visual disability was more prevalent among children from the richer households, whereas other disabilities were more prevalent among children from the poorer households.