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Background: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window., Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence)., Results: Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo ( P =0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P =0.03)., Conclusions: JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent., Registration: URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.

Aim: Although hepatectomy is a complex surgical procedure, its incidence among older patients has increased due to global aging. However, few studies have focused on the association between age and failure to rescue (FTR) posthepatectomy. This study aimed to investigate the association between age and FTR and develop a risk model for FTR following hepatectomy., Methods: We analyzed a total of 1371 consecutive patients who underwent primary hepatectomy between July 2003 and September 2022. The patients were divided into three groups according to their age: young-old (<65 years), pre-old (65-74 years), and old group (≥75 years). Additionally, the associations among age, FTR, and risk factors for FTR were investigated. Subsequently, a risk model was developed to predict the FTR., Results: Of the 1371 patients, 373 (27.2%) experienced major complications, and FTR occurred in 15 patients. The older group showed a higher FTR rate (8.4%) than the young-old (1.3%) and pre-old (4.3%) groups (p = 0.03). Multivariate analyses indicated that older age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.00-1.15; p = 0.045) and American Society of Anesthesiologists Physical Status score ≥3 (OR 4.35; 95% CI 1.24-15.2; p = 0.02) were independent predictive factors for FTR. The risk model exhibited an accuracy with an area under the curve of 0.80 (95% CI 0.69-0.92). Calibration plots of the model revealed a concordance index of 0.73., Conclusions: This study identified an association between age, FTR, and risk factors for FTR posthepatectomy. Together, our risk model is a clinically relevant, internally validated, and useful tool for predicting FTR posthepatectomy., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Background/aim: The efficacy of cytotoxic chemo-therapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with single-agent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients., Patients and Methods: We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a "long-term responder" as a patient who achieved a 1-year progression-free survival (PFS)., Results: Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher number of patients with Eastern Cooperative Oncology Group-performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a one-stage dose reduction owing to adverse events, and four patients required a two-stage dose reduction., Conclusion: Nab-PTX administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Treating oral problems with dentist intervention during hospitalisation may improve patients' food intake status., Objectives: This study aimed to clarify whether convalescent rehabilitation ward inpatients in a hospital with hospital dentistry (HHD) had a better diet at discharge than those in a hospital without hospital dentistry (HNHD)., Methods: Retrospective observational study including inpatients with dental involvement in a HHD with dentists and dental hygienists and HNHD with dental hygienist and visiting dental service between 1 March and 31 August 2022. Data included age, sex, body mass index (BMI), Functional Independent Measure (FIM) motor and cognitive, Oral Health Assessment Tool (OHAT) score, Food Intake LEVEL Scale (FILS), whether the FILS ≥8 (indicating that patient eats also a non-texture-modified diet), remained and functional tooth numbers and speech language hearing therapist (SLHT) and dentist interventions. Comparisons between the two hospitals and factors that affected the FILS ≥8 were examined., Results: A total of 333 and 89 inpatients were included in the HHD and HNHD groups, respectively. After propensity score matching, the HHD group had a significantly higher rate of FILS ≥8, functional tooth numbers at discharge, and SLHT and dentist intervention rates. The multivariable logistic regression analysis for propensity score matching participants showed that the significant independent variables for FILS ≥8 were age, BMI, FILS, FIM motor (all at admission) and SLHT and dentist interventions. Odds ratio for dentist intervention was 14.46 (95% CI: 4.36-48.01)., Conclusions: Dentists are necessary to improve patients' food intake status in convalescent rehabilitation wards., (© 2024 John Wiley & Sons Ltd.)

Background/purpose: This study clarifies the short- and long-term outcomes of liver resection with hepatic vein (HV) reconstruction for liver tumors and identifies the risk factors for poor outcome., Methods: We contacted 263 specialized centers in Japan and collected data on this surgical procedure. Patient characteristics, surgical procedures, and outcomes were then analyzed., Results: A total of 187 patients were enrolled from 36 institutions. Grade C post-hepatectomy liver failure (PHLF) and in-hospital mortality were 3.2% and 1.6%, respectively. The median overall survival (OS) and recurrence-free survival (RFS) were 49.9 and 9.8 months, respectively. Surgical outcomes, OS and RFS did not differ among three types of liver tumors, colorectal liver metastasis (CRLM) (n = 127), hepatocellular carcinoma (n = 27), and intrahepatic cholangiocarcinoma (n = 27). Patients with CRLM and seven or more courses of preoperative chemotherapy had significantly worse OS. Compared with HV reconstruction for securing liver remnant (LR) function (n = 148), reconstruction of the only main HV remaining in the LR (n = 39) had significantly worse short-term outcomes, but did not result in increased mortality, and showed equivalent OS and RFS., Conclusions: Liver resection with HV reconstruction can be achieved safely and contributes to a relatively good long-term outcome for patients with advanced liver malignancies., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study)., Methods: This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion., Results: Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion., Conclusions: The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A 76-year-old woman with a 2-year history of Parkinson's disease presented with dropped head, which had developed rapidly after she had been prescribed donepezil hydrochloride (DNP) at 3 ‍mg/day. After one month of medication, the extent of the head drop reached 90°. Examination revealed hypertrophy of the left sternocleidomastoid muscle, but no weakness of the extensor muscles in the cervical region. Surface electromyography demonstrated co-‍contraction of the sternocleidomastoid and splenius capitus muscles during head flexion and extension. DNP was withdrawn, resulting in immediate amelioration of the head drop, and complete resolution was achieved after two months. Although head drop is often seen in patients with Parkinson's disease, few previous reports have documented DNP as a causative factor. If patients with Parkinson's disease develop head drop, it is important to investigate any history of DNP medication.

Axillary artery injuries are rare because of their anatomy but are sometimes fatal because of the difficulty of obtaining vascular integrity. We report a 50-year-old patient with an iatrogenic axillary arterial injury that occurred during the resection of a chest wall tumor. The injury occurred during an incision of the intercostal muscle along the superior margin of the second rib. Following primary hemostasis achieved by forceps and amputation of the pectoralis minor muscle, the injury site was exposed sufficiently and successfully repaired by a vascular surgeon. This successful case provided valuable insight into strategies, primary hemostasis, and subsequent revascularization for an intraoperative vascular injury., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Umeda et al.)

An open penetrating injury of the subclavian artery is an extremely rare catastrophic situation in thoracic surgery. We experienced a 57-year-old case of iatrogenic subclavian artery injury during the resection of a lung tumor. The injury occurred during the dissection of the adhesion between the stapling site of the previous bullectomy and the chest wall. Systolic blood pressure dropped below 50 mmHg immediately after the injury. Following primary hemostasis achieved with suture closure, the site of injury was sufficiently exposed and successfully repaired., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Umeda et al.)

The present study investigated the role of ramucirumab (RAM) in treating liver metastases (LMs) as a second-line or salvage treatment in patients with advanced CRC. Of the 36 patients, 21 (58%) received RAM plus folinic acid, fluorouracil and irinotecan (FOLFIRI) as second-line treatment, whereas 15 (42%) received it in a salvage setting. The median overall survival time was 23 months [95% confidence interval (CI), 12-34 months] for those in the second-line treatment group and 8 months (95% CI, 5-19 months) for those in the salvage treatment group. Of the 36 patients, 14 (39%) underwent surgical resection of LMs during chemotherapy. A total of 6 patients underwent surgical resection for LMs for the first time during second-line RAM plus FOLFIRI (RAM-LM); of the remaining 8 patients, 6 underwent resection of LMs during first-line bevacizumab (BEV)-based chemotherapy (BEV-LM). Immunohistochemical analysis of CD42b showed that the platelet aggregation score (CD42b score), which ranges from 0 (absence of deposition) to 3 (presence of linear deposition), tended to decrease with the increasing duration of treatment with both RAM and BEV. Although there was no significant difference in the mean duration of anti-VEGF antibody treatment between the BEV-LM and RAM-LM groups, the median CD42b score was higher in the RAM-LM group (median CD42b score, 3; range, 0-3) compared with that in the BEV-LM group (median CD42b score, 1; range, 0-3; P=0.01), suggesting that RAM induces a different degree of platelet aggregation in liver sinusoids compared to BEV., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kimura et al.)

Background: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set., Methods: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model., Results: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors., Conclusion: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

T-cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T-cell exhaustion, such as programmed death 1, can reinvigorate tumor-specific T cells and activate antitumor immunity in various types of cancer. In this study, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed antitumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to programmed death 1 blockade. Mechanistically, CD106 inhibited T-cell receptor (TCR) signaling by interacting with the TCR/CD3 complex and reducing its surface expression. Together, these findings provide insights into the immunosuppressive role of CD106 expressed in tumor-specific exhausted CD8+ T cells, identifying it as a potential biomarker and therapeutic target for cancer immunotherapy. Significance: CD106 is specifically expressed in tumor-specific exhausted CD8+ T cells and inhibits the TCR signaling pathway by reducing surface expression of the TCR/CD3 complex to suppress antitumor immunity., (©2024 American Association for Cancer Research.)

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/μl and 307 ‍pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 ‍IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/ Cckar ) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that Cckar mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene Per1 / Per2 in retinal cells was altered in Cckar -/- mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed Per2 transcription, which was altered in a time-dependent manner relative to the Per2 expression. Light irradiation studies in Cckar -/- mice did not exhibit an increase in Period expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. Cckar knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of Period genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of Period gene, which is one of the core clock genes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

Retroperitoneal sarcoma (RPS) is a rare disease. RPS invading the abdominal aorta is exceedingly rare and has a poor prognosis. There have been scattered cases of RPS treated with combined abdominal aortic replacement. However, the average survival time for these cases was only 8 months, with a 2-year survival rate of 21%, indicating a poor prognosis. In this case study, a 44-year-old man presented to our hospital complaining of abdominal pain. Multiple imaging findings suggested a retroperitoneal mass that was diagnosed as a malignant tumor. The patient underwent tumor resection with abdominal aortic replacement due to an RPS tumor invading the abdominal aorta. The histopathological grade was determined to be grade 3, the most malignant grade tumor, according to the Fédération Nationale des Centres de Lutte Contre le Cancer grading system. Postoperative chemotherapy with doxorubicin and ifosfamide was administered for five cycles. The patient has been alive for over 8 years after the operation without any recurrence. This case presents a long-term survival of RPS requiring abdominal aortic replacement., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Inoue et al.)

Background: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear., Objective: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis., Patients and Methods: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020., Results: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03)., Conclusions: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge., (© 2024. The Author(s).)

BRAF -mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF -mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2024.)

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the peribronchiolar space and interstitium in HTLV-1 carriers and in adult T-cell leukemia/lymphoma (ATLL). We herein report an 85-year-old woman carrying HTLV-1 with HABA who presented with a miliary pattern of micronodules in both lungs on high-resolution computed tomography and a lymphocytic infiltrate with non-necrotizing granulomas on pathology. This rare case of HABA should be differentiated from sarcoidosis, hypersensitivity pneumonitis, or miliary tuberculosis.

Background: Although the current trend in pancreatoduodenectomy (PD) has shifted from open surgery to minimally invasive surgery (MIS), evidence on the role of MIS as an element of Enhanced Recovery After Surgery (ERAS) in PD is limited. This study aimed to investigate the effect of robotic surgery using the ERAS protocol on the outcomes of patients undergoing PD., Methods: This retrospective study included 252 patients who underwent open PD (OPD) or robotic PD (RPD) managed using the ERAS protocol between January 2017 and March 2023. Outcomes stratified by the surgical approach were compared. Multivariable analyses were performed to evaluate the effect of ERAS items, including robotic surgery, on outcomes after PD., Results: Of 252 patients, 202 (80.2%) underwent OPD, and 50 (19.2%) underwent RPD. Multivariable analyses demonstrated that perioperative management center support (odds ratio [OR], 2.85; 95% CI, 1.14-7.72; P = .025), robotic surgery (OR, 6.40; 95% CI, 1.94-26.1; P = .002), early solid intake (OR, 2.84; 95% CI, 1.46-5.63; P = .002), and early drain removal (OR, 3.77; 95% CI, 2.04-7.06; P < .001) were significant ERAS items related to early discharge after PD., Conclusion: Our study demonstrated that employing the ERAS protocol for OPD and RPD is feasible and safe. Moreover, our results suggested the role of robotic surgery as an element of the ERAS protocol for PD. A combination of ERAS protocols and MIS may be safe and feasible for accelerating postoperative recovery after PD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sufficient knowledge and surgical management of portal annular pancreas (PAP) are essential for pancreatic surgery. As PAP is a relatively rare pancreatic anomaly, few studies have described surgical techniques for patients with PAP undergoing robotic pancreatoduodenectomy (RPD)., Patients and Methods: An 82-year-old female patient who underwent RPD presented with distal cholangiocarcinoma and type III PAP (the fusion of the uncinate process with the anteportal main pancreatic duct). After the Kocher maneuver and stomach transection, the pancreas was transected into the neck of the anteportal portion. The retroportal portion was dissected, encircled with hanging tape, and compressed. Blood supply from the mesenteric vessels was confirmed using indocyanine green (ICG) fluorescence imaging. Subsequently, the retroportal portion was stapled., Conclusions: This study demonstrates a unique surgical technique for type III PAP using the hanging maneuver with ICG fluorescence imaging. Surgeons should decide on the surgical strategy on the basis of the fusion and ductal anatomy of the pancreas., (© 2023. Society of Surgical Oncology.)

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes., Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities., Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities., Limitations: A retrospective study., Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy., Competing Interests: Dr Yamazaki has received honoraria from Ono pharmaceutical, 10.13039/100002491Bristol-Myers Squibb, MSD, 10.13039/100004336Novartis, and Maruho; has received research grant from Ono pharmaceutical, 10.13039/100002491Bristol-Myers Squibb, 10.13039/100004336Novartis, and 10.13039/100002429Amgen. Dr Ogata has received honoraria from MSD, Novartis, Ono pharmaceutical, and Bristol-Myers Squibb. Dr Nakamura serves on a scientific advisory board and educational steering committee for 10.13039/100004336Novartis, has received honoraria from BMS, Kyowa-Kirin, Maruho, MSD, 10.13039/100004336Novartis, Ono Pharma, and Tanabe-Mitsubishi Pharma, and received institutional grants from Kaken Pharma, Ono, Pola Pharma, and Torii. Dr Namikawa has received honoraria from Ono pharmaceutical, Novartis, Bristol-Myers Squibb, and MSD; serves as an advisory role for Novartis and MSD. Dr Guo serves as consultant or is on advisory boards for MSD, Roche, Pfizer, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, and Oriengene. Dr Flaherty serves on the Board of Directors of Clovis Oncology, Strata Oncology, Vivid Biosciences, and Scorpion Therapeutics;Scientific Advisory Boards of PIC Therapeutics, Apricity, Tvardi, ALX Oncology, xCures, Monopteros, Vibliome, and Soley Therapeutics; consultant to Takeda, Novartis and Transcode Therapeutics. Dr Long serves as a consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, BMS, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics, MSD, Novartis, OncoSec, PHMR Ltd, Pierre-Fabre, Provectus, Qbiotics, Regeneron. Dr Menzies serves as a consultant for BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics. Dr D.B. Johnson has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, has received research funding from BMS and Incyte. Dr Sullivan serves as consultant for Amgen, Asana Biosciences, BMS, Merck, Novartis, Array BioPharma, Compugen, and Replimune; he receives research support from Amgen and Merck. Dr Boland has a sponsored research agreements with Takeda Oncology, Palleon Pharmaceuticals, InterVenn Biosciences, and Olink Proteomics; serves as a consultant for 10.13039/100004334Merck, InterVenn Biosciences, and Ankyra Therapeutics; served as a speaker for Novartis; and served on a scientific advisory board and steering committee for Nektar Therapeutics. Dr Si has received speakers’ honoraria from MSD, Roche, Novartis, Shanghai Junshi Biosciences and Oriengene. Drs Bai, Gerstberger, Park, Umeda and Authors Lawless, Czapla, Jung, R. Johnson, Li have no conflicts of interest to declare., (© 2024 Published by Elsevier Inc. on behalf of the American Academy of Dermatology, Inc.)

Background: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG., Methods: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia., Results: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event., Conclusions: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm)., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO 2 ), F344/DuCrlCrlj rats were exposed to aNTiO 2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m 3 . The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m 3 -exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m 3 -exposed females and were not statistically significant. However, the incidence in the 8 mg/m 3 -exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO 2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m 3 -exposed carcinogenicity groups. The aNTiO 2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.

Introduction: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported., Methods: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29)., Results: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2., Conclusion: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment., (© 2024 S. Karger AG, Basel.)

Introduction: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients., Methods: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients., Results: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI &lt;45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS., Conclusion: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC., (© 2023 S. Karger AG, Basel.)

Purpose: Achieving a secure anastomosis and complete hemostasis is essential for surgically treating type A acute aortic dissection (TAAAD). This study assessed the clinical feasibility of "tailored stand-up collar (TSC)" technique for constructing the distal stump., Methods: We enrolled 68 patients who underwent ascending aortic repair for TAAAD. Patients were categorized according to the technique for distal stump construction: conventional (C) group using only a felt strip (32 cases); post-aortotomy (P) group, with a Hydrofit-felt strip attached after aortotomy (18 cases), and TSC group, where a Hydrofit-felt strip attached during cooling (18 cases). Pre-operative characteristics, procedural profiles, and post-operative outcomes were evaluated., Results: The pre-operative characteristics were identical among the groups. The durations of cardiopulmonary bypass, hemostasis, and surgery were significantly shorter in the P and TSC groups. The duration of open distal in the TSC group (21 min) was significantly shorter than the other two groups. Post-operative additional procedures were not required for the TSC group and their post-operative hospital stay was significantly shorter (47.1% of patients were discharged within 2 weeks)., Conclusion: The TSC technique would be practical because of its high reproducibility in terms of ease of use, shorter anastomotic time, and secure hemostasis.

Purpose: This study aims to evaluate the factors associated with the higher hospitalization cost of lung resection for primary lung cancer to contribute to the reduction of healthcare spending., Methods: A total of 435 consecutive primary lung cancer patients who underwent lung resection by a single surgeon at a single institution were enrolled. Baseline patient characteristics, operative procedures, postoperative complications, and postoperative courses were analyzed in relation to the hospitalization cost. Patients with higher costs (exceeding the third quartile [TQ]) were compared with patients with lower costs (less than TQ)., Results: Median and TQ medical costs for overall cases were 11177 US dollars (USD) and 12292 USD, respectively. Smoking history, history of coronary artery disease, previous thoracotomy, multiple sealant material use, transfusion, tumor factor T3 or higher, squamous cell carcinoma, postoperative complications, and longer postoperative hospital stay (>10 POD) were significant risk factors for increased hospitalization cost in multivariate analysis. The 5-year survival rate was significantly lower in the higher hospitalization cost group., Conclusion: In addition to postoperative complications and prolonged hospitalization, patient background, histological types, and intraoperative factors were also considered as the risk factors for higher medical costs.

Background and Aim: Long-term outcomes after endoscopic submucosal dissection (ESD) for colorectal epithelial neoplasms (CENs) in patients with severe comorbidities have not been clarified; the current study aimed to examine these long-term outcomes and compared them with those in patients with non-severe comorbidities., Methods: We included 231 patients with CENs who underwent ESD between April 2005 and March 2023. Patients with comorbidities were categorized according to the American Society of Anesthesiologists Physical Status (ASA-PS). We conducted a propensity score-matched analysis and compared long-term outcomes of the two groups after ESD for CENs., Results: Of the 156 patients enrolled in the study, 43 and 113 had severe (ASA-PS III) and non-severe (ASA-PS I/II) comorbidities, respectively. The 1:1 propensity score analysis matched 36 patients with severe comorbidities to 36 patients with non-severe comorbidities. After matching, there was no difference in the procedural outcomes of ESD between both groups. Regarding long-term outcomes, the 5-year overall survival rates after matching in the ASA-PS I/II and III groups were 100% and 73.5%, respectively, and patients in the ASA-PS III group exhibited significantly shorter overall survival than those in the ASA-PS I/II group (hazard ratio 7.209; 95% confidence interval 1.592-32.646; P  = 0.010). No colorectal cancer-related deaths were noted in either group., Conclusion: Overall survival after ESD for CENs was shorter in patients with severe comorbidities than in those with non-severe comorbidities. Clinicians should carefully determine whether the benefits of CEN resection with ESD outweigh the procedural risks in patients with severe comorbidities., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers., Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity., Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs., Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed., Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study., Competing Interests: Dr. Alexander Menzies is on advisory boards of BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. Dr. Andrew J.S. Furness has a patent (WO2019008375A1) (co-inventor of methods for identifying responders to cancer treatment), has participated on Data Safety Monitoring Boards or advisory boards of Achilles Therapeutics, GSK, Immunocore and Neogene; and has speaker’s bureau and educational events from BMS, Eisai, Ipsen, Merck, and Pfizer. Dr. Andrew Haydon has received payments for advisory boards from BMS, MSD, Novartis. Dr. Christoffer Gebhardt has received research support by BMS, Novartis, Pierre-Fabre, and Sanofi; is a member of the advisory board of BMS, Immunocore, MSD, Novartis, Pierre-Fabre, Sanofi, SUN Pharma, Sysmex; and has received honoraria by BMS, GSK, Immunocore, MSD, Novartis, Pierre-Fabre, Sanofi, SUN Pharma, Sysmex. He has received travel expenses by BMS, Pierre-Fabre, SUN Pharma. He is a member of the advisory board of BMS, Immunocore, MSD, Novartis, Pierre-Fabre, Sanofi, SUN Pharma, Sysmex; a board member of the DeCOG (ADO), unpaid; he is a board member of the Hiege Foundation, unpaid. He is board member of the Roggenbuck Foundation, unpaid. He is a Co-Founder of Dermagnostix and Dermagnostix R&D. Dr. Douglas Johnson has received grants or contracts from BMS, Incyte; consulting fees from Teiko, Targovax, Mosaic ImmunoEngineering; has participated on a Data Safety Monitoring Board or Advisory Board of BMS, Merck, Novartis, and Pfizer. Dr. Genevieve M. Boland has received grants or contracts from Olink Proteomics, Teiko Bio, InterVenn Biosciences, Palleon Pharaceuticals; consulting fees from Merck, InterVenn Biosciences, Ankyra Therapeutics. She has received visiting professorships, payment from legal review, support as an invited speaker, and has a patent pending (not related to current content). She is on Board of Trustees, Karin Grunebaum Cancer Research Foundation. She has stock of Ankyra Therapeutics. Dr. Georgina Long has received consulting fees from Agenus Inc, Amgen Inc, Array Biopharma, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L, Innovent Biologics USA Inc, Merck Sharp & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals. She has received payment or honoraria for lectures from BMS, Pierre Fabre. Dr. Jun Guo is the member of the advisory board/consultant of MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai Junshi Bioscience, Oriengene. Dr. Keith Flaherty has received grants or contracts from Sanofi, Novartis; consulting fees from Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate Pharmaceuticals, Scorpion Therapeutics, PIC Therapeutics, Apricity, Fog Pharma, Vibliome; participated on a Data Safety Monitoring Board or advisory board of PIC Therapeutics, Apricity, Fog Pharma, Tvardi, xCures, Monopteros, Vibliome, ALX Oncology, OMRx, Soley Therapeutics, Alterome, IntrECate, and Quanta Therapeutics. He is on Board of Directors: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate Pharmaceuticals and Scorpion Therapeutics. He owns stock from Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate Pharmaceuticals Scorpion Therapeutics, PIC Therapeutics, Apricity, Fog Pharma, Tvardi, xCures, Monopteros, ALX, Oncology, OMRx, Soley Therapeutics, Alterome, IntrECate, and Quanta Therapeutics, Transcode Therapeutics. Dr. Kenjiro Namikawa has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ono pharmaceutical, Novartis, BMS, and MSD. He has participated on an Data Safety Monitoring Board or advisory board of Novartis and MSD. Dr. Lu Si has received speakers’ honoraria from MSD, Roche, Novartis, Shanghai Junshi Biosciences and Oriengene. Dr. Mario Mandala (please confirm that I read your handwriting right; section 1 of all support is a bit har to read) has received consulting fees from MSD, BMS, Novartis, Sanofi, Suw Pharma. Dr. Naoya Yamazaki has received grants or contracts from Ono Pharmaceutical CO., LTD., BMS, Novartis Pharma K.K., Amgem Inc; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ono Pharmaceutical CO., LTD., BMS, Novartis Pharma K.K., MSD K.K., Maruho CO., LTD; and participated on a Data Safety Monitoring Board or Advisory Board of Ono Pharmaceutical CO., LTD and Chugai Pharmaceutical CO., LTD. Dr. Paolo A. Ascierto has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Sandoz, Immunocore, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune, Bayer, Erasca. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Travel support by Pfizer, Bio-Al Health, Replimmune. Dr. Paul Lorigan has received consulting fees from Amgen, BMS, MSD, Nektar, Novartis, Pierre Fabre; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, BMS, Merck, MSD, Nektar, NeraCare GmbH, Novartis, Oncology Education, Pierre Fabre, Roche; support for attending meetings and/or travel from BMS, MSD. He works as Chair, EORTC Melanoma Group (unpaid). Dr. Pietro Quaglino has received speaker fee and is advisory board of Novartis, BMS, MSD, Pierrefabre; support for attending meetings and/or travel from Novartis, BMS, MSD, Pierrefabre. Rebecca Johnson has received speaking honoraria from Novartis. Dr. Rebecca Lee is on advisory board of Pierre Fabre. Dr. Ruth Plummer has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and support for attending meetings and/or travel from MSD, BMS. She has participated on a Data Safety Monitoring Board or Advisory Board of GSK. Dr. Ryan Sullivan has received grants or contracts from Merck (to institution); consulting fees from BMS, Novartis, Merck, Pfizer, Replimune, Marengo; participated on a Data Safety Monitoring Board or Advisory Board of Yale University, Duke University. Dr. Yana Najjar has the following disclosure: consulting/advisory board: immunocore, merck, BMS, pfizer, novartis, intervenn bio; speaker's bureau: immunocore; research (to institution): merck, bms, pfizer, replimune. Dr. Yasuhiro Nakamura has received grants or contracts from Torii (to institution), consulting fees from Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol Myers-Squibb, Kyowa Kirin, Maruho, MSD, Novartis, Ono, Leo Pharma Sun Pharma, Tanabe-Mitsubishi Pharma, Torii, Sanofi, Alexion Pharma. Dr. Yoshiyasu Umeda has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Maruho and BMS. The rest of the authors have no declaration of interests., (© 2023 The Author(s).)

A 57-year-old woman, who had been taking azathioprine (AZP) for systemic sclerosis and interstitial pneumonia over 16 years, presented with right hemiparesis and paresthesia. On admission, brain MRI diffusion-weighted imaging (DWI) demonstrated high-signal-intensity lesions in the right frontal lobe. Although the symptoms had disappeared quickly, brain MRI on the 7th day revealed that these lesions had spread to the left cerebellar hemisphere and the right fronto-parietal lobes, appearing as high signal intensity lesions on ADC map. On the basis of the MRI imaging and clinical courses, posterior reversible encephalopathy syndrome (PRES) caused by AZP was suspected, and brain MRI revealed the immediate improvement of the lesions after the AZP discontinuation. There have been a few reports of PRES caused by AZP, all of which occurred within one month after administration. It is noteworthy in considering differential diagnosis that PRES can also occur during long-term administration of AZP.

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown., Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS)., Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months ( p  = 0.24); 15.7 months, 11.6 months, and 10.1 months ( p  = 0.06); and 31.0%, 13.6%, and 37.5% ( p  = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS ( p < 0.05) and OS ( p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths., Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy., (© 2023 The Authors.)

Technique: Minimally invasive congenital biliary dilatation (CBD) surgery is technically demanding. However, few studies have reported surgical approaches of robotic surgery for CBD. This report presents robotic CBD surgery using a scope-switch technique. Our robotic surgery technique for CBD consisted of four steps: step 1, Kocher's maneuver; step 2, dissection of the hepatoduodenal ligament using the scope switch technique; step 3, preparation for the Roux-en-Y loop; and step 4, hepaticojejunostomy., Results: The scope switch technique can provide different surgical approaches for dissecting the bile duct, including anterior approach by the standard position and right approach by the scope switch position. When approaching the ventral and left side of the bile duct, anterior approach with the standard position is suitable. In contrast, the lateral view by the scope switch position is preferable for approaching the bile duct laterally and dorsally. Using this technique, the dilated bile duct can be dissected circumferentially from four directions: anterior, medial, lateral, and posterior. Thereafter, complete resection of the choledochal cyst can be achieved., Conclusions: The scope switch technique in robotic surgery for CBD can be useful for dissecting around the bile duct with different surgical views, leading to the complete resection of the choledochal cyst., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)