Aizawa Hospital
  • Honjō, Japan
Recent publications
Background Ischemic bowel injuries are generally caused by arteriosclerosis, thromboembolism, or vasculitis. Ischemic enteritis is less common than ischemic colitis because of the rich collateral arteries of the small intestine. In the present case, smooth muscle degeneration of the mesenteric to the submucosal veins caused ischemic enteritis and small bowel obstruction. Case presentation An 85-year-old woman with recurrent enteritis eventually developed small bowel obstruction. We performed laparoscopic partial resection of the small intestine. The pathological findings revealed smooth muscle degeneration of the mesenteric veins that caused ischemic enteritis. Venous changes were detected not only in the injured region, but also in a part of the normal region of the resected specimen. She continued to experience some minor symptoms postoperatively; however, these symptoms subsided in a short period with medicine discontinuation. Conclusion This report shows the possibility that a disease causes ischemic enteritis with unique venous pathological changes and may recur postoperatively.
Purpose Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy. Methods The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures. Results ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20–0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL. Conclusion Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions.
Background Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC. Materials and methods A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m², oxaliplatin 85 mg/m², levofolinate 200 mg/m², and fluorouracil 2400 mg/m²) plus bevacizumab biweekly were enrolled. The primary endpoint was the objective response rate (ORR). Plasma samples were collected at pre-treatment, 8 weeks after treatment, and progression in participants included in the biomarker study. The levels of circulating tumour DNA (ctDNA) and specific KRAS and NRAS variants were evaluated using real-time PCR assays. Results There were 62 patients (median age: 62.5 years, 92% performance status 0, 27% right side) who were assessable for efficacy and 51 for biomarker analysis. ORR was 75.8% (95% confidence interval 65.1% to 86.5%). The median progression-free survival was 12.1 months, and the median overall survival (OS) was 30.2 months. In 78% of patients, RAS mutations disappeared in the ctDNA at 8 weeks after treatment; these patients tended to have better outcomes than those with RAS mutations. Interestingly, RAS mutations remained undetectable during progression in 62% of patients. Survival analysis indicated that the median OS from progression was significantly longer in patients with RAS mutation clearance than in those with RAS mutation in the ctDNA at disease progression (15.1 versus 7.3 months, hazard ratio: 0.21, P = 0.0046). Conclusions Our biomarker study demonstrated no RAS mutations in ctDNA at disease progression in 62% of patients with RAS-mutant mCRC. Both OS and post-progression survival were better in patients with clearance of RAS mutations in ctDNA after triplet-based chemotherapy.
Background: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients. Methods: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933). Results: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%). Conclusions: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.
Varicella-zoster virus (VZV) may cause aseptic meningitis in the pediatric age group. We describe a pediatric case of aseptic meningitis with a substantial increase of the paired serum antibody to VZV in which the child did not have skin rash during the course of illness. The patient was a 13-year-old boy without any history of exposure to VZV who was admitted with headache, vomiting, and low-grade fever. He had received one dose of varicella vaccine derived from the Oka/Biken strain (vOka) at the age of one year. Cerebrospinal fluid (CSF) analysis on admission revealed an elevated white blood cell count at 609/mm3 with 99.6% mononuclear cells. As his symptoms resolved after lumbar puncture alone, he was discharged on the seventh day of hospitalization without receiving any specific medication. Serum VZV-IgG titer was found to be substantially elevated after two weeks. VZV infection and reactivations associated with vaccination, as well as past infections, should be included in the differential diagnoses of pediatric aseptic meningitis, even in the absence of skin rash in the entire course. Polymerase chain reaction (PCR) testing for VZV DNA in CSF should be performed in all cases, if available.
A 7-year-6-month-old female was diagnosed with a pelvic malignant peripheral nerve sheath tumor and lymph node metastases. Tumorectomy was performed after four cycles of chemotherapy. A 33-mm cystic lesion was observed around the left iliac muscle after three cycles of postoperative chemotherapy, and proton beam therapy (PBT) was recommended. She was referred for absorbable spacer (AS) placement. The left ovarian appendage (OA) was resected due to the direct tumor infiltration. The right OA was fixed to the uterosacral ligament. The AS was fixed to the lateral pelvis. The PBT (70.3 Gy relative biological effectiveness) was performed successfully with the AS, and she also had the reproducing possibility due to prevention of severe irradiation damage of the right OA. AS eliminated the surgical removal of spacers and enabled us high-dose PBT for residual tumor without severe irradiation damage including infertility.
PURPOSE The phase III ACHIEVE trial conducted in Japan was one of six prospective studies included in the International Duration Evaluation of Adjuvant Therapy collaboration, which explored whether 3 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) therapy would be noninferior to 6 months of treatment in patients with curatively resected stage III colon cancer. We report the final analyses of survival and long-term safety. PATIENTS AND METHODS Eligible patients were randomly assigned (1:1) to either 3 or 6 months of adjuvant chemotherapy (modified [m]FOLFOX6 or CAPOX, as selected by the treating physician). Random assignment was stratified according to number of involved lymph nodes, center, regimen, primary site, and age. The primary end point was disease-free survival, assessed in the modified intention-to-treat population. Overall survival (OS) was a secondary end point. RESULTS The modified intention-to-treat population comprised 1,291 patients: 641 in the 6-month treatment group and 650 in the 3-month treatment group. Median follow-up for this analysis was 74.7 months. Five-year OS rates were comparable: 87.0% in the 3-month treatment group and 86.4% in the 6-month treatment group (hazard ratio, 0.91; 95% CI, 0.69 to 1.20; P = .51). Subgroup analysis of OS did not reveal a significant interaction between baseline characteristics and treatment duration. Peripheral sensory neuropathy lasting longer than 5 years was more common in the 6- compared with 3-month treatment group (16% v 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% v 11%, respectively). CONCLUSION In Asian patients, shortening adjuvant therapy duration from 6 to 3 months did not compromise efficacy and reduced the rate of long-lasting peripheral sensory neuropathy. In this setting, 3 months of CAPOX therapy is an appropriate adjuvant treatment option.
Background: Safety of combination chemotherapy using platinum and fluorouracil has not been evaluated adequately for advanced gastric cancer (AGC) in elderly patients. Patients and methods: We initiated a phase II study to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) as first-line therapy for patients with AGC aged ≥70 years. Planned assessment of toxicity was made upon recruitment of the first 20 patients. Results: In five out of 20 patients, unacceptable toxicity was observed, including three patients who were unable to complete the initial two courses due to adverse events. Among the other 15 patients, dose reduction due to toxicity were needed in 10 and treatment delay for adverse events also occurred in 12 patients during the first two courses. Conclusion: Early analyses of safety suggest that the CapeOX regimen was not tolerated without dose reduction for elderly patients with AGC in this study.
Background/aim: The usefulness of angiogenesis inhibitors as second-line treatment after the progression of anti-epidermal growth factor receptor antibody drug-containing regimens for RAS wild-type metastatic colorectal cancer (mCRC) has not been fully investigated. Therefore, we conducted a phase II study to verify the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab (SIRB regimen) as second-line treatment for patients with oxaliplatin and cetuximab-refractory KRAS wild-type mCRC. Patients and methods: Patients with mCRC who had previously received oxaliplatin and cetuximab-containing regimen were eligible for this study. Patients were infused with bevacizumab 7.5 mg/kg and irinotecan 150 mg/m2 intravenously on day 1, whereas S-1 80 mg/m2 was administered orally twice daily until day 15, followed by a 7-day drug holiday period. The primary end point was 6-month progression-free survival (PFS) rate. Results: In total, 17 patients were enrolled in this study. The 6-month PFS rate was 64.7% [95% confidence interval (CI)=41.99-87.43], median PFS was 10.1 months (95%CI=4.11-17.28), and median overall survival was 21.8 months (95%CI=9.79-37.91). The response rate was 23.5% (95%CI=6.81-49.90%). Grade ≥3 adverse events were observed in 10% of patients, and included leukopenia [3 (17.6%)], neutropenia [5 (29.4%)], anorexia [2 (11.8%)], diarrhea [2 (11.8%)], and hypertension [3 (17.6%)]. No treatment-related deaths or febrile neutropenia were observed. Conclusion: The SIRB regimen might be a promising second-line treatment option for patients with oxaliplatin and cetuximab-refractory KRAS wild-type mCRC in terms of efficacy and safety.
This study aims to elucidate the foreign patient‐specific factors associated with emergency department length of stay (EDLOS) in a regional core hospital emergency department (ED) in Japan. This retrospective observational study included non‐Japanese patients who visited the ED in a Japanese regional core hospital between April 1, 2018, and March 31, 2020. The effects on EDLOS were assessed using multivariate linear regression analysis, which included factors such as age, sex, consultation language, interpreter usage, arrival time, day of visit, mode of arrival, underlying disease, triage level, diagnosis of injury/noninjury, diagnostic investigations, consultation with specialists, and treatments or procedures. Of 65,297 ED patients, there were 777 study patients, with a median age of 37 years (interquartile range [IQR], 24.0–50.0). The median EDLOS was 101 min (IQR, 63.0–153.0). Multivariate linear regression analysis indicated that an extended EDLOS was associated with: language apart from Japanese, Chinese, or English (51.7 min; 95% confidence interval [CI], 17.8–85.6), helicopter arrival (115.6 min; 95% CI, 48.8–182.5), blood testing (60.5 min; 95% CI, 34.6–86.4), computed tomography (23.8 min; 95% CI, 3.7–43.9), consultation with specialists (36.2 min; 95% CI, 11.8–60.6), intravenous fluid/medication (29.7 min; 95% CI, 3.3–56.1), and surgical procedure/reduction/fixation in the ED (38.8 min; 95% CI, 14.2–63.4). Consultation in a language other than Japanese, English, or Chinese was associated with a longer EDLOS in a regional core hospital in Japan. Devising ways to accommodate patients who speak various languages could be important. Non‐native‐language medical practice has been shown to have a negative impact on the quality of healthcare. This study illustrated that languages other than Japanese, English, and Chinese for patient care were associated with prolonged emergency department length of stay (EDLOS) in emergency healthcare for foreign patients in a regional core hospital in Japan. Resident or tourist status in Japan and the use of interpreters were not associated with EDLOS.
Backgrounds: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation-related parameters in patients with LA-NSCLC treated with CCRT plus durvalumab. Methods: We recruited 76 LA-NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre-treatment) and 2 months after (post-treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression-free survival (PFS) after durvalumab therapy. Results: The median follow-up time was 17 (range, 3.3-35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non-infectious pneumonitis being the most common reason. Post-treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not-reached vs. 9.6 months. Log-rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post-treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). Conclusions: This study suggests that post-treatment CAR has predictive value for LA-NSCLC patients treated with CCRT plus durvalumab consolidation therapy.
We report a dorsal trans-scaphoid perilunate fracture-dislocation associated with dorsal dislocation of the thumb carpometacarpal joint in a 25-year-old man. This is a rare injury and we discuss a possible mechanism for the injury. Level of Evidence: Level V (Therapeutic)
Endovascular treatment (EVT) is the main treatment for peripheral artery disease (PAD). Despite advances in device development, the restenosis rate remains high in patients with femoropopliteal lesions (FP). This study aimed to evaluate the effectiveness of exercise training in reducing the 1-year in-stent restenosis rate of bare metal nitinol stents for FPs. This prospective, randomized, open-label, multicenter study was conducted from January 2017 to March 2019. We randomized 44 patients who had claudication with de novo stenosis or occlusion of the FP into an intensive exercise group ( n = 22) and non-intensive exercise group ( n = 22). Non-intensive exercise was defined as walking for less than 30 min per session, fewer than three times a week. We assessed exercise tolerance using an activity meter at 1, 3, 6, and 12 months, and physiotherapists ensured maintenance of exercise quality every month. The primary endpoint was instant restenosis defined as a peak systolic velocity ratio > 2.5 on duplex ultrasound imaging. Kaplan–Meier analysis was used to evaluate the data. There were no significant differences in background characteristics between the groups. Six patients dropped out of the study within 1 year. In terms of the primary endpoint, intensive exercise significantly improved the patency rate of bare nitinol stents at 12 months. The 1-year freedom from in-stent restenosis rates were 81.3% in the intensive exercise group and 47.6% in the non-intensive exercise group ( p = 0.043). No cases of stent fracture were observed in the intensive exercise group. Intensive exercise is safe and reduces in-stent restenosis in FP lesions after endovascular therapy for PAD. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (No. UMIN 000025259).
Background: Dural arteriovenous fistulas (dAVFs) are often treated with stereotactic radiosurgery (SRS) to achieve complete obliteration (CO), prevent future hemorrhages, and ameliorate neurological symptoms. Objective: To summarize outcomes after SRS for dAVFs and propose relevant practice recommendations. Methods: Using a PICOS/PRISMA/MOOSE protocol, we included patients with dAVFs treated with SRS and data for at least one of the outcomes of the study. Relevant outcomes were CO, symptom improvement and cure, and post-SRS hemorrhage or permanent neurological deficits (PNDs). Estimated outcome effect sizes were determined using weighted random-effects meta-analyses using DerSimonian and Laird methods. To assess potential relationships between patient and lesion characteristics and clinical outcomes, mixed-effects weighted regression models were used. Results: Across 21 published studies, we identified 705 patients with 721 dAVFs treated with SRS. The CO rate was 68.6% (95% CI 60.7%-76.5%) with symptom improvement and cure rates of 97.2% (95% CI 93.2%-100%) and 78.8% (95% CI 69.3%-88.2%), respectively. Estimated incidences of post-SRS hemorrhage and PNDs were 1.1% (95% CI 0.6%-1.6%) and 1.3% (95% CI 0.8%-1.8%), respectively. Noncavernous sinus (NCS) dAVFs were associated with lower CO (P = .03) and symptom cure rates (P = .001). Higher grade was also associated with lower symptom cure rates (P = .04), whereas previous embolization was associated with higher symptom cure rates (P = .01). Conclusion: SRS for dAVFs results in CO in the majority of patients with excellent symptom improvement rates with minimal toxicity. Patients with NCS and/or higher-grade dAVFs have poorer symptom cure rates. Combined therapy with embolization and SRS is recommended when feasible for clinically aggressive dAVFs or those refractory to embolization to maximize the likelihood of symptom cure.
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19 members
Shoji Yomo
  • Aizawa Comprehensive Cancer Center
Takao Hashimoto
  • Department of Neurology
Masato Nakamura
  • Aizawa comprehensive cancer center
Kayoko Higuchi
  • Surgical pathology
Shigeaki Kobayashi
  • Department of Neurosurgery
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Honjō, Japan