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Purpose Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. Methods From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. Results During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). Conclusion In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.

Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery. A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92). In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19–38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings. Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.

In case of symptomatic varix associated with cerebral arteriovenous malformations (AVM), nidus is usually treated with transarterial embolization (TAE). However, TAE is not always possible due to inaccessible nidus. A man in his 40s presented with numbness and clumsiness in the right hand. Magnetic resonance imaging (MRI) and cerebral angiography revealed a giant varix associated with an AVM nidus in the left parietal lobe. The varix severely compressed the postcentral gyrus with edema. The main feeder was occluded, and tiny collateral vessels fed the nidus. After admission, his symptoms deteriorated rapidly due to the enlarging varix. To extirpate the varix, selective transvenous embolization (TVE) of a small compartment, the varix neck, between the varix and the main cortical drainer with coils was performed. After treatment, the thrombosed varix gradually shrank, and his symptoms improved. The transvenous coil-plugging technique is a potential strategy for symptomatic varix with a varix neck.

A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.

The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores. CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into “high” or “low” CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0–3, favorable group; 4–6 unfavorable group) (0–4, non-catastrophic group; 5–6, catastrophic group). Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1–65.4; P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5–201.0; P

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid–induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid–induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid–induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Trousseau’s syndrome (TS) and tumor thrombosis (TT) are known as cancer-associated thrombosis with poor prognosis. TS is extremely rare in patients with squamous cell carcinoma. In this study, we report an unknown primary squamous cell carcinoma of the head and neck (SCCHN) patient with TS and TT in pulmonary artery definitely diagnosed by autopsy. A 73-year-old man had a past surgical history for unknown primary SCCHN and lung metastases. Three years after the initial surgery, the patient had multiple cerebral infarction, deep venous thrombosis in the legs and mediastinum metastases. Our diagnosis was TS and treatment with chemotherapy and unfractionated molecular heparin started. It could help control the hypercoagulative state and cancer progression, but finally, he died from progressive disease (mediastinum metastases and pulmonary embolism) five years after the initial surgery. An autopsy revealed multiple metastases and thrombosis in the pulmonary artery with squamous cell carcinoma microscopically. Although there is no established treatment for managing TS, intensive therapy such as a combination of chemotherapy and anticoagulant therapy can be effective in improving hypercoagulation therapy. In addition, an autopsy should be considered for patients with thrombosis to distinguish between TS and TT.

OBJECTIVESeveral environmental factors have been reported to correlate with incidence of spontaneous subarachnoid hemorrhage (SAH). However, because of different patient selection and study designs among these studies, meteorological factors that trigger the incidence of SAH in a short hazard period remain unknown. Among meteorological factors, daily temperature changes may disrupt and violate homeostasis and predispose to cerebrovascular circulatory disturbances and strokes. The authors aimed to investigate whether a decline in the temperature from the highest of the previous day to the lowest of the event day (temperature decline from the previous day [TDP]) triggers SAH in the prefecture-wide stroke database.METHODSAll 28 participating institutions with primary or comprehensive stroke centers located throughout Kochi Prefecture, Japan, were included in the study. Data collected between January 2012 and December 2016 were analyzed, and 715 consecutive SAH patients with a defined date of onset were enrolled. Meteorological data in this period were obtained from the Kochi Local Meteorological Observatory. A case-crossover study was performed to investigate association of TDP and other environmental factors with onset of SAH.RESULTSThe increasing TDP in 1°C on the day of the SAH event was associated with an increased incidence of SAH (OR 1.041, 95% CI 1.007–1.077) after adjustment for other environmental factors. According to the stratified analysis, a significant association between TDP and SAH was observed in women, patients < 65 years old, and patients with weekday onset. Among these factors, increasing TDP had a great impact on SAH onset in patients < 65 years old (p = 0.028, Mann-Whitney U-test).CONCLUSIONSTDP, temperature decline from the highest of the previous day to the lowest of the day, was correlated with the incidence of spontaneous SAH, particularly in younger patients < 65 years old.

BACKGROUND Use of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not been elucidated yet. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro. METHODS In this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures. RESULTS Of 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio=6.72, 95% confidence interval [2.05-22.1], P=0.002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation. CONCLUSIONS 5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells.

Background: In general, ISSD may be detected due to clinical symptoms, but some ISSDs are found incidentally during radiological examinations for the assessment of unrelated diseases. This study aims to evaluate the clinical aspects of all ISSDs detected by image inspection. Methods: A total of 94 patients with ISSD were enrolled in this study. The study patients were classified into two groups: a group who improved with conservative treatment (n=25), and a group who did not improve with conservative treatment (n=69). Their clinical symptoms, medical histories, pathologies, and imaging findings were assessed.Results: The incidence of high signal intensity on T2-weighted images in the improvement group was significantly higher compared with the non-improvement group. Conversely, the incidences of bone erosion and expansion were significantly higher in the non-improvement group. Of the 42 cases receiving surgery, 10 cases (23.8%) had asymptomatic ISSD.Conclusion: This study suggests that ISSD with high signal intensity on T2-weighted images and/or without bone erosion and expansion in imaging findings could improve by conservative treatment or watchful waiting. Because some asymptomatic ISSD cases required surgery, proper diagnosis of ISSD regardless of clinical symptoms is important to prevent severe illness.

The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meier method and statistical significance was analyzed using the log-rank test. A total of 29 EOC patients (stage IA, n=14; stage IC1 n=6; stage IC3, n=9) from seven participating institutions belonging to the Tohoku Gynecologic Cancer Unit were enrolled. After a median follow-up duration of 60.6 months (range, 6-135 months), five patients (17.2%) experienced tumor recurrence. The respective five-year relapse-free survival (RFS) and overall survival (OS) rates were 90.9 and 100% for stage IA/IC1, and 43.8 and 87.5% for stage IC3. Significant differences in RFS were observed between stage IA/IC1 and IC3 patients (P=0.026). However, there was no significant difference in OS between patients with 1A/1C1 and those with 1C3 (P=0.712). After FSS, seven pregnancies occurred in five patients, which resulted in the birth of six healthy children. The results of the present study confirmed that FSS may be an acceptable treatment method for stage IA and IC1 EOC, exhibiting a favorable reproductive outcome. However, the safety of FSS for treating stage IC3 EOC is uncertain and warrants further investigation.

Objective Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction. Methods In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients’ clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247–0.987, p < .001) and IDI (0.068, 95% CI: 0.021–0.116, p = .005). Conclusions Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.

The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients’ characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. The median patient age was 44 (20–80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49–51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Background and purpose The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. Methods Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. Results Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. Conclusions Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.

Aim To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012. Methods The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests. Results Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively. Conclusion The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Highlights • Squamous cell carcinoma arising from a mature cystic teratoma of the ovary is rare. • The optimal treatment for this disease is unclear. • We report a successfully treating case of SCC arising from MCT with carboplatin, paclitaxel, and bevacizumab. • Bevacizumab might have been one of the treatment options for patients with advanced-stage of this disease., Ovarian mature cystic teratomas (MCT) are usually benign. However, squamous cell carcinoma (SCC) develops in 0.17–2% of MCT. Because of its low frequency, the optimal treatment for this disease is unclear. We present a case of SCC arising from MCT. Our patient was a 30-year-old nulliparous woman complaining of right lower abdominal pain, who was referred to our hospital for a pelvic solid mass with suspected malignant ovarian tumor. A diagnosis of SCC arising from MCT was suspected based on the elevation in SCC antigen and the imaging. After surgery to remove the tumor, the diagnosis was confirmed based on the pathology. Although the surgery by radical cytoreduction was optimal, the tumor showed early recurrence. Therefore, we administrated combination chemotherapy, consisting of carboplatin, paclitaxel, and bevacizumab, followed by maintenance therapy with bevacizumab. Response to the chemotherapy regimen was complete and the patient was alive with no evidence of recurrence for 45 months after starting the initial surgery. We discuss the clinical characteristics of the malignant transformation of MCT and the treatment of SCC arising from MCT.

The purpose of this study was to investigate whether patients with low preoperative Diffusion-weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) could benefit from mechanical thrombectomy for acute anterior circulation occlusion. This was a retrospective, non-blinded, cohort study. From September 2012 to August 2016, 83 consecutive patients of acute anterior circulation occlusion were treated with thrombectomy using second-generation devices or medical management. The DWI-ASPECTS was scored after the first MRI. Patient characteristics and clinical outcomes were compared between the treatment groups. Significant dependence was defined as a modified Rankin scale score ≥3 at 90 days. As a result, 33 patients underwent mechanical thrombectomy and 50 received medical management. In the mechanical thrombectomy group, the variable of lower DWI-ASPECTS (5, 4–6 vs. 8, 7–8, P < 0.001), especially ≤6, was significantly associated with poor prognosis. However, compared with patients of DWI-ASPECTS ≤ 6 who received medical management, there were significantly fewer patients with poor outcomes in thrombectomy (dependent in 11 of 15 vs. 23 of 23, respectively; P = 0.019). Although patients with lower pretreatment DWI-ASPECTS could benefit less from thrombectomy, their outcomes were still better than medical management. Therefore, mechanical thrombectomy could be considered in some patients with low pretreatment DWI-ASPECTS.

Purpose We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial. Methods PLD was administered intravenously at a dose of 30 mg/m2 on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m2 on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression. The primary endpoint was antitumor efficacy, and the secondary endpoints were adverse events, progression-free survival (PFS), and overall survival (OS). Results The response rate was 32.3% and the disease control rate was 64.5%. Grade 3 and 4 neutropenia, anemia, and a decrease in platelet count were observed in 17 (54.9%), 3 (9.7%), and 1 patient (3.2%), respectively. In terms of grade 3 or higher non-hematologic toxicities, grade 3 nausea occurred in 1 patient (3.2%), vomiting in 3 patients (9.7%), and grade 3 diarrhea and fatigue in 1 patient (3.2%). The median PFS and OS rates were 2 months and not reached, respectively. Of the 11 patients with a treatment-free interval (TFI) of ≥3 months, the response rate was 63.3%, and the median PFS was 7 months. Conclusions The treatment outcomes for the 31 patients enrolled in this study were unsatisfactory. However, sub-analysis suggested that patients with a TFI of ≥3 months had a good response rate and PFS. This suggests that CPT-11/PLD combination therapy may be a chemotherapy option for platinum-resistant recurrent ovarian cancer.

Tumor lysis syndrome (TLS) is an oncological life-threatening complication characterized by hyperuricemia, hyperphosphatemia, and hyperkalemia, which can lead to acute renal failure, cardiac arrhythmias, cardiac arrest and seizures. Although TLS is a rare complication in patients with non-hematological malignancy, the mortality rate of TLS in solid tumors is higher than that in hematological malignancies. Acute renal injury is the most common cause of mortality associated with TLS in solid tumors. We report a case of TLS following chemotherapy for a recurrent uterine serous carcinoma. In this case, we speculated that the cause of death might be a pulmonary tumor embolism caused by TLS., Highlights • Tumor lysis syndrome (TLS) is an oncological life-threatening complication. • The mortality rate of TLS in solid tumors is high, acute renal injury being the most common cause. • We report a case of TLS following chemotherapy for a recurrent uterine serous carcinoma. • We speculated that the cause of death might be a pulmonary tumor embolism caused by TLS. • Clinicians need to assess the risk of TLS before chemotherapy, which should be given to high risk patient appropriately.

Background Globally, cervical cancer is the fourth most common cancer in women. Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer, an extremely rare and treatment-resistant condition. Case presentation A 64-year-old Japanese woman presented with genital bleeding. She was diagnosed as having stage IB1 squamous cell cervical cancer and subsequently treated with radiotherapy. Approximately 2 years after the curative radiotherapy, she developed itching, skin rash, and small nodules on her left femoral and pubic area. Slight 18F-fluorodeoxyglucose uptake was detected at her left femoral skin on positron emission tomography with computed tomography. A histopathological examination was performed on a biopsy sample from an erythematous macule on her left femoral skin and vulva. Consequently, she was diagnosed as having cutaneous lymphangitis carcinomatosa arising from cervical cancer. Paclitaxel (135 mg/m2), cisplatin (50 mg/m2), and bevacizumab (15 mg/kg) combination therapy was administered every 21 days. Both itching and rash improved after three treatment cycles. After the completion of six cycles, skin erythema in the femoral and vulval area disappeared completely. Our patient experienced a 25-month symptom-free interval after the last chemotherapy session. Conclusion Our findings suggest that combination chemotherapy plus bevacizumab is an effective therapeutic option in patients with cutaneous lymphangitis carcinomatosa arising from cervical cancer.

Background: To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. Objective: To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named “Task Calc. Stroke” (TCS), and aimed to investigate the impact of TCS on AIS care. Methods: TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS (“TCS-based CS”), one not using TCS (“phone-based CS”), and one not based on CS (“non-CS”). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. Results: During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min (p = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, p = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. Conclusions: TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.

Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhibition can overcome GSH-mediated resistance to chemotherapeutic agents in uterine serous carcinoma (USC) remains unclear. Thus, the present study investigated the effect of the xCT inhibitor, sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines. The molecular mechanism by which SAS induces ferroptotic cell death in paclitaxel-resistant cells was assessed. The results of the cytotoxicity assay demonstrated that SAS was more cytotoxic in paclitaxel-resistant cells compared with in -sensitive cells; however, paclitaxel cytotoxicity was not enhanced in either of the USC cell lines. Immunoblotting analysis and the cell death assays performed using ferroptosis inhibitors indicated that SAS-mediated cell death was induced through ferroptosis, and not apoptosis, in paclitaxel-resistant cells. Furthermore, ROS production was increased in paclitaxel-resistant but not in -sensitive cells, even at low SAS concentration, and JNK was activated, which is a downstream target in the Ras signaling pathway. Knockdown of JNK reversed the inhibitory effect of SAS on cell proliferation and cell death. The synthetic lethal interaction between ROS accumulation and Ras effector JNK activation may be critical for enhancing the sensitivity to ferroptotic cell death mediated by xCT inhibitor, SAS. Taken together, the results of the present study suggest that xCT inhibition may be an effective treatment for patients with recurrent paclitaxel-resistant USC.

ObjectiveTo identify a proximal anterior circulation occlusion for effectively administering immediate mechanical thrombectomy by developing a novel, simple diagnostic scale to predict the occlusion, to compare its validity with available scales, and to assess its utility.MethodsTo develop a novel clinical scale, we retrospectively analyzed a cohort of 429 patients with acute ischemic stroke from a single center. The novel scale GAI2AA was applied to a prospective cohort of 259 patients from 3 stroke centers for external validation. The utility of the scale as an in-hospital triage was compared for the temporal factors of 158 patients with the occlusion.ResultsIn a scale-developmental phase, those with a proximal anterior circulation occlusion had significantly more frequent signs of hemispheric symptoms, including gaze palsy, aphasia, inattention, arm paresis, and atrial fibrillation. The GAI2AA scale was developed using consolidated hemispheric symptoms and was scored as follows: score = 2, arm paresis score = 1, and atrial fibrillation score = 1. A cutoff value ≥3 was optimal for the correlation between sensitivity (88%) and specificity (81%), with a C statistic of 0.90 (95% confidence interval 0.87–0.93). External validation indicated that discrimination was significantly better than or not different from that of available complex scales. Door-to-puncture time was significantly reduced (91 [82–111] vs 52 [32–75] minutes, p < 0.001).ConclusionThe GAI2AA scale showed high sensitivity and specificity when an optimal cutoff score was used and was useful as an in-hospital triage tool.

Introduction: Although the clinical outcomes of acute ischemic strokes associated with large vessel occlusion have substantially improved by mechanical thrombectomy, the good clinical outcomes were achieved only in 40-50% of the treated patients. In the clinical practice, neuroimaging information is usually interpreted into scalar data, such as ASPECTS or lesion volume. The detection of prognostic factor might lead to the patient selection appropriate for intervention. Hypothesis: We hypothesize that more appropriate information could be directly deduced from high-dimensional neuroimaging data using deep learning algorithm. Methods: All patients with anterior circulation ischemic stroke treated with mechanical thrombectomy at our institution between December 2013 and December 2017 were included. The purpose of each model was designed to predict good clinical outcome, which was determined as modified Rankin Scale 0 to 2 at the 90-day follow-up. The “low-dimensional” model used logistic regressions with DWI-ASPECTS (ASPECTS model) or infarct volume (Lesion volume model), both features were derived from on-arrival diffusion weighted image (DWI). The “high-dimensional” model used 3D convolutional neural network (3D-CNN). The input to the 3D-CNN model was the whole DWI volume data. All models were evaluated and compared for the accuracy with 5-fold cross validation. Results and Conclusions: One hundred sixty-six patients were included for the analysis. The 3D-CNN model showed the highest accuracy 0.70±0.05 (mean±SD), compared with 0.59±0.07 of ASPECTS model and 0.53±0.05 of Lesion volume model, and was signify better than the other two models (p=0.008 with ANOVA). Although this was a preliminary analysis with limited number of patients, it is suggested that deep learning model can retrieve more valuable information from neuroimaging data than conventional low-dimensional neuroimaging factors.

Intravenous nicardipine is generally used to treat hypertension in acute stroke patients but is associated with frequent phlebitis. We aimed to identify the incidence and risk factors of phlebitis in such patients.The incidence and risk factors of phlebitis were investigated in 358 acute stroke patients from July 2014 to June 2015.In total, 138 patients received intravenous nicardipine. Of 45 (12.6%) phlebitis patients in 358 acute stroke patients, 42 (93.3%) were administered nicardipine, which was significantly associated with phlebitis occurrence (P .01). Other candidate risk factors of phlebitis of acute stroke patients in univariate analysis were intracerebral hemorrhage (P .01), nicardipine injection to paralyzed limbs (P = .023), dilution of nicardipine with normal saline (P .01), higher maximum flow rate of nicardipine (7.2 ± 4.1 mg/h versus 1.6 ± 3.1 mg/h; P .01), and higher maximum concentration of nicardipine (271.5 ± 145.0 µg/mL versus 37.6 ± 75.0 µg/mL; P .01). The only statistically significant independent factor following multivariate logistic regression analysis, according to the optimal cutoff values defined from receiver operating characteristic curve analyses, was the maximum concentration of nicardipine greater than 130 µg/mL (OR 57.9; 95% CI 21.5-156; P .01). A gradual decline of pH below 4.3 was observed when the concentration of nicardipine solution increased to greater than or equal to 130 µg/mL in vitro.Nicardipine-related phlebitis is frequently observed in acute stroke patients and is significantly associated with administration of a maximum concentration of nicardipine greater than 130 µg/mL.

Objective We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB–IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy. Methods Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m2) or docetaxel (DTX, 60 mg/m2) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events. Results Twenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%–75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild. Conclusions Taxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB–IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

We appreciate the comments and insights of Grewal and Goldstein on our article.1 As for atrial fibrillation (AF), it has the weakest relation with large vessel occlusion (LVO) (logit [probability of the occlusion] = 3.3 [gaze palsy, aphasia, or inattention [GAI]] + 1.5 [arm paresis] + 1.3 [AF] − 4.4 + e), and the prevalence may vary between the patient groups. In our GAI2AA scale (pronounced “gaia,” who is the Greek goddess of the earth), the addition of AF was intended to reinforce the diagnosis of LVO. If the patients with hemispheric symptoms and arm paresis also have the sign of AF, it not only shows the more probability of an LVO but also with typical cardioembolic origin.