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

Objective: Most cases of severe metabolic alkalosis have many causes that may result in renal failure and death. Therefore, these should be treated promptly for successful recovery.Patient: A 61-year-old man was hospitalized due to an acute kidney injury (creatinine level of 4.36 mg/dL) after a 3-month history of anorexia and recurrent vomiting. He had been treated for tuberculosis in the past.Results: Blood gas analysis revealed severe metabolic alkalosis with pH=7.66, HCO3=94 mmol/L, and pCO2=82.0 mmHg. Routine biochemical examination revealed severe hypokalemia (K 2.9 mEq/L) that was associated with prolonged QTc interval (0.52 seconds) on the electrocardiogram. Gastrofiberscopic examination also revealed severe stenosis and ulcerated scarring of the gastric pylorus and severe esophagitis. Intravenous hydration and correction of hypokalemia improved renal function and resolved metabolic alkalosis. An investigation that was repeated after 6 days revealed a creatinine level of 1.58 mg/dL, pH=7.47, HCO3=23.4 mmol/L, K=3.6 mEq/L, and QTc of 0.45 seconds. The patient underwent gastrectomy and adenocarcinoma was observed.Conclusion: We described a resolved case of severe metabolic alkalosis and acute kidney injury in a rural medical setting following conservative management.

Introduction: Cabazitaxel (CBZ) is used worldwide for castration-resistant prostate cancer after docetaxel treatment. In July 2014 the drug was approved in Japan with the same induction dose used for Caucasian patients. In this study, we examined and compared the results of an initial low-dose CBZ treatment in patients admitted to our hospital.Patients and Methods: Between July 2014 and August 2018, sixteen mCRPC patients were enrolled and underwent a low-dose CBZ treatment at our hospital. We compared the results with those of a Japanese metastatic docetaxel- and castration-resistant prostate cancer Phase I study.Results: The median patient age was 77 years (range, 53–84 years). Of the 16 patients, eight (50%) had a lymph node metastasis and 11 (68.8%) had a distant metastasis, 10 of whom had only a bone metastasis. The median dose of CBZ was 30 mg (range, 20–32 mg) and the median number of CBZ cycles was 2.5 (range, 1–18). The PSA level of 9 (56.3%) patients decreased after CBZ treatment, including 4 (25%) who showed a decrease to <50%. The median time interval in which the PSA level decreased was 2 months (range, 1–18 months). The observed adverse events (AE) were neutropenia (31.3%), febrile neutropenia (6.3%), fatigue (43.8%), nausea (18.8%), diarrhea (12.5%), decreased appetite (25%), dysgeusia (6.3%), white blood cell count decrease (43.8%), platelet count decrease (12.3%), and anemia (75%). However, no patient listed an AE as the reason for discontinuing the treatment.Conclusions: Even at a low dose, CBZ could improve the PSA value in patients with CRPC previously treated with docetaxel. Dose reduction and prophylactic administration of sustained G-CSF were also safe treatment options. Further studies involving an introduction period including a modulation of duration and dose are necessary, especially in Japanese patients.

A 76-year-old Japanese man visited a nearby medical clinic complaining of abdominal distention. He had undergone extraperitoneal laparoscopic prostatectomy at our institution 5 months before the onset of abdominal distention. An imaging study revealed a large cystic lesion, and biochemical examination of a sample obtained via cyst puncture led to a diagnosis of lymphocele. As the lymphocele was resistant to puncture, drainage, and sclerotherapy with minomycin, laparoscopic fenestration was performed. Although the patient developed an adhesive ileus postoperatively, the cyst has not recurred. Fenestration surgery is a feasible option for lymphocele refractory to various conservative therapies.

Objectives: Gauze remnants form gauzeomas after surgery, if infection has not occurred. We present a case of gauzeoma diagnosed after surgery.Patient: A 72-year-old man noticed a mass in his lower abdomen. He had undergone surgery for left inguinal hernia 21 years ago. A retroperitoneal mass was found on computed tomography (CT) and magnetic resonance imaging (MRI), and he was then referred to our hospital. A detailed abdominal ultrasonography, CT, and MRI revealed a cystic mass with a bulkhead-like structure near the bladder. These findings indicated the possibility of a malignant cyst; hence, an open surgery was performed to excise the mass. Macroscopically, the specimen was clearly bound, covered with a capsule, and filled with pus and had a gauze inside.Results: Based on the patient history and position of the mass, it was diagnosed as gauzeoma, which had strayed into the retroperitoneal cavity during the surgery for inguinal hernia.Conclusion: The imaging findings of gauzeoma are diverse; hence, it is often difficult to diagnose without surgery. However, gauzeoma can be lethal if the cystic mass is infected; thus, it is important to diagnose it correctly.

Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful.

Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m²) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m²) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life.

Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly.

Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.

Two new thiodiketopiperazines (TDKPs), designated graphiumins I (1) and J (2), were isolated from the culture broth of the marine-derived fungus Graphium sp. OPMF00224 by solvent extraction, silica gel column chromatography, and HPLC. Their absolute structures were elucidated by spectroscopic analyses (1D and 2D NMR data, ROESY correlations, and CD data) and chemical methods. They were found to be structurally rare TDKPs with a phenylalanine-derived indolin substructure. Compounds 1 and 2 inhibited yellow pigment production by methicillin-resistant Staphylococcus aureus (MRSA) with IC50 values of 63.5 and 76.5 microg/ml, respectively, without inhibiting its growth, even at 250 microg/ml.
Chromatography ; Chromatography, High Pressure Liquid ; Fungi* ; Inhibitory Concentration 50 ; Methicillin-Resistant Staphylococcus aureus ; Silica Gel