Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Clinical guidelines for prevention and treatment of CAT in Japan and other countries.

Cancer-associated thrombosis (CAT) is an important prognostic factor for an increasing number of cancer patients. Understanding of CAT among cancer care providers has grown in recent years, and guidelines for the prevention and treatment of CAT have been published in Japan and around the world. In this article, we introduce these major guidelines and discuss differences we identified between the Japanese guidelines and those of other countries, with a focus on problems and issues. Insurance coverage of low-molecular-weight heparin and indications for primary prevention with direct oral anticoagulants in particular require urgent consideration.

Diffuse large B-cell lymphoma with DNA copy number changes in a Japanese black calf.

A 2-month-old Japanese Black calf exhibited mandibular and superficial cervical lymph node swelling. Fine needle aspiration cytology of the superficial cervical lymph node revealed large lymphoblast-like cells with mitoses. Hematological examination revealed remarkable lymphocytosis with atypical lymphocytes. Increased activities of serum total lactate dehydrogenase and thymidine kinase were detected. At necropsy, generalized swelling of lymph nodes was observed. Histopathological analysis revealed diffuse proliferation of medium-sized round centroblastic neoplastic cells that were positive for CD20, CD79α, PAX5, and BLA-36, and negative for CD3, CD5, CD10, and CD34. The calf was diagnosed with centroblastic diffuse large B-cell lymphoma (DLBCL) based on these findings. Analysis of DNA copy number variation revealed an increased copy number for the GIMAP family relative to that in healthy cattle. Moreover, decreases in copy numbers of GBP-1, MIR3141, OR5P1E, and PTPRG relative to those in healthy cattle were also observed. Because DNA copy number variation represent a major contribution to the somatic mutation landscapes in human tumors, these findings suggest that DNA copy number changes might have contributed to the onset of DLBCL in the present case.

A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

BACKGROUND: Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population. METHODS: Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. RESULTS: The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). CONCLUSIONS: All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

A phase 2, open-label study of ibrutinib plus rituximab in Japanese patients with Waldenstrom's macroglobulinemia.

Ibrutinib is a first-in-class Bruton kinase inhibitor against B-cell neoplasms including Waldenström macroglobulinemia (WM). This study evaluated the efficacy and safety of ibrutinib-rituximab in Japanese patients with WM. Patients received ibrutinib 420 mg orally once daily plus weekly rituximab 375 mg/m2 IV (8 infusions total). The primary end point was major response rate (MRR; PR or better) by Independent Review Committee assessment. Secondary endpoints were progression-free survival (PFS), safety, pharmacokinetics, and biomarkers. Primary analysis was conducted in 16 patients [baseline, treatment naïve: 8 (50.0%); relapsed/refractory WM: 8 (50.0%)] who received ibrutinib-rituximab, after all patients completed Week 57 or end of treatment. At primary analysis, MRR was 87.5% [14/16 patients; 95% CI: 61.7, 98.4%; p < 0.0001 (null hypothesis: 32% response rate)]. At final analysis (median study intervention duration: 34.4 months, median follow-up: 35.0 months), MRR was unchanged at 87.5%, but VGPR [6/16 (37.5%)] and PR [8/16 (50.0%)] improved. Prior treatment status did not affect response. At final analysis, median PFS was not reached [36-month PFS rate: 86% (95% CI: 55, 96%)]. No critical safety signals were reported. This study demonstrated a positive benefit/risk profile of ibrutinib-rituximab in Japanese patients with WM, consistent with the iNNOVATE study.

Rikkunshito increases peripheral incretin-hormone levels in humans and rats.

BACKGROUND: It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM: To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS: Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS: In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION: The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

Japanese Encephalitis Outbreak in Young Adults of Bastar District in Chhattisgarh: A Short Observational Study.

Background Instant infections in children due to acute encephalitis syndrome (AES) were reported in a tribal district of Bastar in Chattisgarh, India, between August 2018 and August 2019. Objective The study was conducted to explore the possibility of a viral cause indicating an outbreak. Methods Clinical surveys and serological investigation tests were conducted to identify the viral etiology. The Bastar area in Chhattisgarh reported factors such as paddy fields near homes, a high pig-to-cattle ratio, a significant presence of Culex vishnui mosquitoes, low socioeconomic status, and a lack of health awareness among the tribal people. Result This study, conducted at the Late Baliram Kashyap Memorial Government Medical College in Jagdalpur, Bastar, Chhattisgarh, India, analyzed 128 samples from fever cases out of 213 patients visiting the Japanese encephalitis virus (JEV) testing center. Among these samples, 71 cases exhibited AES, and subsequent JEV IgM ELISA testing identified 18 cases as JEV-positive, signifying recent JEV infections. Notably, the overwhelming majority (94.44%) of JEV-positive patients were under 16 years old, highlighting the heightened vulnerability of children to JEV illness in the Bastar region. Although male patients accounted for 61.11% of the JEV-positive cases compared to 38.88% of female patients, statistical analysis revealed that this gender disparity was not statistically significant (p-value = 0.18). Conclusion The study emphasizes the significance of identifying the etiology and delivering evidence-based care to patients with AES. Improved diagnosis and management of AES may result from a greater comprehension of the advantages and disadvantages associated with the application and administration of common laboratory and diagnostic algorithms.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan.

Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

Sex difference in the association of dietary fiber intake with visceral fat volume in Japanese adults.

PURPOSE: Dietary fiber is a possible nutritional component which aids in the prevention of visceral fat accumulation. We examined the association between dietary fiber intake and visceral fat volume (VFV) by sex, and further analysed the association by major food sources of dietary fiber. METHODS: In this cross-sectional study, we measured VFV in 2779 Japanese (1564 men and 1215 women) aged 40-89 who underwent positron emission tomography/computed tomography for cancer screening between 2004 and 2005. Dietary fiber intake was calculated based on a validated semi-quantitative food frequency questionnaire. The association between dietary fiber intake and VFV was investigated using multivariate linear regression models after adjustment for potential confounders. RESULTS: Total, soluble, and insoluble fiber intakes were inversely associated with VFV in men (Q1: 3740 cm3, Q4: 3517 cm3, Ptrend: 0.0006 for total fiber), but not in women (Q1: 2207 cm3, Q4: 2193 cm3,Ptrend: 0.88 for total fiber). Statistically significant sex difference was observed (Pinteraction = 0.001 for total fiber). Subgroup analyses by major food sources revealed that dietary fiber intakes from beans, vegetables and fruits showed an inverse association with VFV in men, while cereal fiber intake showed a tendency toward a positive association in both sexes (Q1: 3520 cm3, Q4: 3671 cm3, Ptrend: 0.05 in men, Q1: 2147 cm3, Q4: 2227 cm3, Ptrend: 0.10 in women). CONCLUSION: We observed a sex-specific association between dietary fiber intake and VFV in Japanese adults. This study suggests that efforts against visceral fat accumulation should take account of the source of dietary fiber.

Factors affecting nonfunctioning small pancreatic neuroendocrine neoplasms and proposed new treatment strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the WHO 2019 classification. Overall, 1,490 patients met the eligibility criteria, and 1,014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs. G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Outside Europe.

This chapter illustrates that cranial surgery was not limited to Europe. There was however no contribution to improving knowledge outside Europe until medical science departed for the Arab world.

Japanese spotted fever complicated by acute sensorineural hearing loss.

Japanese spotted fever is an emerging rickettsiosis caused by Rickettsia japonica and is characterized by high fever, rash, and eschar formation. Other symptoms are often vague and nonspecific and include headaches, nausea, vomiting, and myalgia. We present a case of a 46-year-old woman with Japanese spotted fever, complicated by transient bilateral sensorineural hearing loss and presenting cutaneous IgM/IgG immune complex vasculitis. The patient was admitted with a history of several days of high fever, generalized skin erythema, and hearing impairment. Laboratory findings revealed thrombocytopenia and elevated liver enzyme and C-reactive protein levels. Pure-tone audiometry revealed bilateral sensorineural hearing loss, and a skin biopsy revealed leukocytoclastic vasculitis with deposition of C3 and IgM on the vessel walls. Under the tentative diagnosis of rickettsiosis, scrub typhus, or Japanese spotted fever, the patient was treated with minocycline, and her symptoms improved within approximately 10 days. A definitive diagnosis was made on the basis of a serological test showing increased antibody levels against Rickettsia japonica. Japanese spotted fever can cause transient sensorineural hearing loss, a rare complication that presents with cutaneous IgM/IgG immune complex vasculitis.

Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study.

BACKGROUND: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R-) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here. METHODS: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R-, D+/R+, and D-/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee. RESULTS: Among 22 participants (12 were D+/R-) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R- participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52. CONCLUSION: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04129398.

Meeting report: the 66th annual meeting of the Japanese Radiation Research Society in Tokyo, Japan, 6-8 November 2023.

The 66th Annual Meeting of the Japanese Radiation Research Society took place in Tokyo, Japan, from 6 to 8 November 2023. The meeting covered a wide range of radiation research topics, including basic mechanisms involved in radiation effects, translational research, and epidemiology. Some sessions were jointly organized with the International Commission on Radiological Protection (ICRP). Here, we report on some plenary and keynote talks presented at the meeting.

A Comparison Between GPT-3.5, GPT-4, and GPT-4V: Can the Large Language Model (ChatGPT) Pass the Japanese Board of Orthopaedic Surgery Examination?

Introduction Recently, large-scale language models, such as ChatGPT (OpenAI, San Francisco, CA), have evolved. These models are designed to think and act like humans and possess a broad range of specialized knowledge. GPT-3.5 was reported to be at a level of passing the United States Medical Licensing Examination. Its capabilities continue to evolve, and in October 2023, GPT-4V became available as a model capable of image recognition. Therefore, it is important to know the current performance of these models because they will be soon incorporated into medical practice. We aimed to evaluate the performance of ChatGPT in the field of orthopedic surgery. Methods We used three years' worth of Japanese Board of Orthopaedic Surgery Examinations (JBOSE) conducted in 2021, 2022, and 2023. Questions and their multiple-choice answers were used in their original Japanese form, as was the official examination rubric. We inputted these questions into three versions of ChatGPT: GPT-3.5, GPT-4, and GPT-4V. For image-based questions, we inputted only textual statements for GPT-3.5 and GPT-4, and both image and textual statements for GPT-4V. As the minimum scoring rate acquired to pass is not officially disclosed, it was calculated using publicly available data. Results The estimated minimum scoring rate acquired to pass was calculated as 50.1% (43.7-53.8%). For GPT-4, even when answering all questions, including the image-based ones, the percentage of correct answers was 59% (55-61%) and GPT-4 was able to achieve the passing line. When excluding image-based questions, the score reached 67% (63-73%). For GPT-3.5, the percentage was limited to 30% (28-32%), and this version could not pass the examination. There was a significant difference in the performance between GPT-4 and GPT-3.5 (p < 0.001). For image-based questions, the percentage of correct answers was 25% in GPT-3.5, 38% in GPT-4, and 38% in GPT-4V. There was no significant difference in the performance for image-based questions between GPT-4 and GPT-4V. Conclusions ChatGPT had enough performance to pass the orthopedic specialist examination. After adding further training data such as images, ChatGPT is expected to be applied to the orthopedics field.

The Impact of Frailty on Surgical Outcome of Patients with Lumbar Spinal Canal Stenosis.

Introduction: Frailty is an important factor in surgical outcomes. The current study aimed to evaluate the effect of preoperative frailty on postoperative outcomes in older patients with lumbar spinal canal stenosis (LSCS). Methods: We retrospectively examined 209 patients aged ≥65 years who underwent surgery for LSCS. Health-related quality-of-life (HRQOL) tools, including the Roland-Morris Disability Questionnaire (RDQ), Zurich Claudication Questionnaire (ZCQ), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), were used in the assessment conducted before surgery and at 6 months and 1 year after surgery. Frailty was categorized based on the 11-item modified frailty index (mFI-11). Patients with mFI-11 of 0, <0.21, and >0.21 were classified under the robust (R), pre-frailty (P), and frailty (F) groups, respectively. Results: According to the mFI-11, 24, 138, and 47 patients were included in the R, P, and F groups, respectively. Regarding preoperative radiographic parameters, there was a remarkable increase in the sagittal vertical axis and a significant decrease in the development of lumbar lordosis with frailty progression. The preoperative scores of RDQ and ZCQ, and lumbar function, walking ability, social life, and psychological disorder domain scores of JOABPEQ differed significantly among these groups. The frequency of revision surgery was not higher in the F group than in the other groups. After adjustment for factors have shown different distributions among the three groups, the frequency of effective surgical cases did not show a clear trend among the three groups in all domains of the JOABPEQ. Conclusions: The preoperative HRQOL scores and the radiographic parameters of patients with LSCS worsened with frailty severity. However, frailty did not affect the rate of revision surgery and surgical efficacy in patients with LSCS. Although this study has limitations, our findings indicated that even LSCS patients with frailty can be considered for surgery if they have an indication for LSCS surgery.

Effect of a variant histology on the oncological outcomes of Japanese patients with upper tract urothelial carcinomas after radical nephroureterectomy: a multicenter retrospective study.

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients. Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses. Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients.

Recovery of the Japanese orthopedic association back pain evaluation questionnaire score and walking ability following lumbar spinal stenosis surgery.

PURPOSE: We investigated the recovery of the Japanese orthopedic association back pain evaluation questionnaire (JOABPEQ) scores and 6 min walk distance (6MWD) in patients after surgery for lumbar spinal stenosis and identified the items among 25 questions of JOABPEQ that showed recovery. METHODS: A total of 227 patients (average age 71.5 years; SD: 7.5; 121 men) were included from a single center. The outcome measures were JOABPEQ, visual analog scale (VAS), and 6MWD and obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Mixed-model repeated measures were used to compare the variables at each time point between the surgery groups. RESULTS: The JOABPEQ, VAS, and 6MWD scores generally improved at 1 month postoperatively compared with those obtained preoperatively, and some parameters further improved at 3 months. However, improvement in the lumbar spine dysfunction item of JOABPEQ was delayed, showing improvement at 3 months postoperatively for decompression surgery (average score: pre, 64.6; 3 months, 78.5) and 6 months postoperatively for fusion surgery (average score: Pre, 64.3; 6 months, 77.1). Responses to the individual JOABPEQ questions generally improved after surgery. No significant changes in lumbar spine dysfunction occurred in the fusion group. CONCLUSION: Our results demonstrated the early postoperative recovery course of JOABPEQ and 6MWD. In the fusion group, significant changes in lumbar spine dysfunction started at 6 months postoperatively. These findings could help medical staff explain postoperative recovery to patients after lumbar spinal stenosis surgery and in their decision making regarding surgery.

Long-term follow-up results from KEYNOTE-041: Phase 1b study of pembrolizumab in Japanese patients with advanced melanoma.

Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.