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By regarding the Fermat variety over a local field as a rigid analytic variety, we construct a family of affinoids in quotients of the Fermat varieties and compute the reduction of them. As a result, we explicitly compute the middle cohomology of the Fermat variety as a Galois representation. As a byproduct, we give an explicit formula for the ramified components of Jacobi sum Hecke characters in many variables.

Aims Patients who undergo permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) have a worse outcome. The aim of this study was to identify risk factors of worse outcomes in patients with post-TAVR PPM implantation. Methods and results This is a single-centre, retrospective study of consecutive patients who underwent post-TAVR PPM implantation from 11 March 2011 to 9 November 2019. Clinical outcomes were evaluated by landmark analysis with cut-off at 1 year after the PPM implantation. Of the 1389 patients underwent TAVR during the study duration and a total of 110 patients were included in the final analysis. Right ventricular pacing burden (RVPB) ≥ 30% at 1 year was associated with a higher likelihood of heart failure (HF) readmission [adjusted hazard ratio (aHR): 6.333; 95% confidence interval [CI]: 1.417–28.311; P = 0.016] and composite endpoint of overall death and/or HF (aHR: 2.453; 95% CI: 1.040–5.786; P = 0.040). The RVPB ≥30% at 1 year was associated with higher atrial fibrillation burden (24.1 ± 40.6% vs. 1.2 ± 5.3%; P = 0.013) and a decrease in left ventricular ejection fraction (−5.0 ± 9.8% vs. + 1.1 ± 7.9%; P = 0.005). The predicting factors of the RVPB ≥30% at 1 year were the presence of RVPB ≥40% at 1 month and the valve implantation depth measured from non-coronary cusp ≥4.0 mm (aHR: 57.808; 95% CI: 12.489–267.584; P < 0.001 and aHR: 6.817; 95% CI: 1.829–25.402; P = 0.004). Conclusions The RVPB ≥30% at 1 year was associated with worse outcomes. Clinical benefit of minimal RV pacing algorithms and biventricular pacing needs to be investigated.

We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer.ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates.Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS.ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.

Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival.Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/mOverall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%).The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC.

This study aimed to evaluate the effectiveness and safety of gemcitabine (GEM) plus nab-paclitaxel (GnP) in patients aged ≥ 75 years with advanced pancreatic cancer and compare it with monotherapy (GEM or S-1).We retrospectively reviewed the data of consecutive patients with advanced pancreatic cancer aged ≥ 75 years who received either GnP or monotherapy (GEM or S-1) between January 2014 and May 2020. The primary efficacy outcome was overall survival (OS).A total of 96 patients were included in this study; 51 were treated with GnP and 45 with monotherapy (31 with GEM and 14 with S-1). The median OS and progression-free survival were 10.8 and 6.7 months in the GnP group and 10.7 and 4.3 months in the monotherapy group, respectively. The treatment effect on OS was consistently favorable in the GnP group across most subgroups, particularly in patients with locally advanced cancer, modified Glasgow prognostic score of 0 or 1, and neutrophil/lymphocyte ratio lt; 3.1. The disease control rates were 76% and 48% in the GnP and monotherapy groups, respectively, and grade 3 or 4 neutropenia occurred in 23 (45%) and 11 (24%) patients of the GnP and monotherapy groups, respectively.This study demonstrated that GnP was not superior to monotherapy with regard to OS. However, multivariate analysis showed that GnP treatment positively affected the OS and could be considered as a treatment option, even for elderly patients.

Previous studies reported that new-onset persistent left bundle branch block (NOP-LBBB) was related to worse outcomes after transcatheter aortic valve implantation (TAVI). However, these results can be confounded by the presence of permanent pacemaker (PPM) implantation before and after TAVI. Long-term outcomes and the risk stratification of NOP-LBBB not having PPM implantation before and after TAVI have not been fully investigated. This is an international, multicenter, retrospective study of patients who underwent TAVI from July 31, 2007, to May 8, 2020. A total of 2,240 patients were included, and 17.5% of patients developed NOP-LBBB. NOP-LBBB was associated with cardiac mortality (adjusted hazard ratio [aHR] 1.419, 95% confidence interval [CI] 1.014 to 1.985, p = 0.041) and the composite outcomes of cardiac mortality and/or heart failure readmission (aHR 1.313, 95% CI 1.027 to 1.678, p = 0.030). Patients who developed NOP-LBBB with pre-TAVI left ventricular ejection fraction (LVEF)40% were significantly associated with cardiac mortality (aHR 2.049, 95% CI 1.039 to 4.041, p = 0.038), heart failure (aHR 3.990, 95% CI 2.362 to 6.741, p 0.001), and the composite outcome (aHR 2.729, 95% CI 1.703 to 4.374, p 0.001). Although NOP-LBBB with pre-TAVI LVEF40% had a significant decrease in LVEF 6 to 12 months after TAVI (-1.8 ± 9.7% vs +0.6 ± 8.1%, p = 0.003), NOP-LBBB with pre-TAVI LVEF40% had a significant increase in LVEF 6 to 12 months after TAVI (+9.7 ± 13.6% vs +13.0 ± 11.7%, p = 0.157). In conclusion, patients with NOP-LBBB without pre-TAVI and post-TAVI PPM developed significantly worse long-term outcomes, especially in patients with pre-TAVI LVEF40%. Further prospective investigation should be undertaken.

Supplementary methods and results

Purpose:Regulatory T cells (Tregs) expressing CC chemokine receptor 4 (CCR4) can suppress antitumor immune responses and are associated with poor prognoses in several cancers. We assessed the safety and efficacy of combined mogamulizumab (anti-CCR4 antibody) and nivolumab [anti-programmed death-1 (PD-1) antibody] in immunotherapy-naïve patients with advanced/metastatic solid tumors.Patients and Methods:This study (NCT02476123) comprised dose-escalation (3+3 design) and expansion parts. Patients received nivolumab (3.0 mg/kg) every 2 weeks, with mogamulizumab (0.3 or 1.0 mg/kg in dose escalation, 1.0 mg/kg in expansion) once weekly for 4 weeks, then every 2 weeks, until progression or unacceptable toxicity. Primary objective was safety; secondary objectives were antitumor effects, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses were conducted.Results:Ninety-six patients were enrolled (July 2015−November 2016): six patients in the dose-escalation part and 90 in the expansion part. No dose-limiting toxicities were observed in the dose-escalation part. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 29% of patients in the expansion part (no grade 5 TRAEs). The most frequent TRAEs were rash (39%), rash maculopapular (20%), diarrhea (13%), stomatitis (12%), and pruritus (11%). There were four (27%) confirmed tumor responses among 15 patients with hepatocellular carcinoma, and one confirmed and two unconfirmed responses among 15 patients with pancreatic adenocarcinoma. During treatment, populations of effector Tregs (CD4+CD45RA−FoxP3high) decreased and CD8+ T cells in tumor-infiltrating lymphocytes increased.Conclusions:Combining an anti–PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer immunotherapy.

Background The WATCHMAN left atrial appendage (LAA) occlusion device has emerged as an alternative for anticoagulation in patients with non-valvular atrial fibrillation who cannot tolerate oral anticoagulation therapy. Cardiac computed tomography (CTA) is increasingly being utilized to guide WATCHMAN device sizing, however no consensus algorithm exists. We present our experience with a new cardiac CTA LAA ostium area based sizing algorithm. Methods This is a single center, prospective study analyzing consecutive patients who underwent cardiac CTA and WATCHMAN device implantation between March 2017 and October 2019 at University Hospitals Cleveland Medical Center. Patients baseline characteristics, procedural data, and clinical outcomes were collected and analyzed. Results 115 patients were included in our study. The mean age of our population was 76.5 years ±8.3 years. 70.4% of our patients had preserved ejection fraction. The predominant indication for device implantation was gastrointestinal bleeding in 57.4% of patients. The mean CHADSVASC score was 4.68 ± 1.4. The procedure success rate was 99.1% and the mean number of device used per case of 1.15 ± 0.4 devices. Our CTA LAA ostium area based sizing algorithm accurately predicted the final deployed WATCHMAN device size in 95.6% of cases. Conclusion Our study demonstrates that cardiac CTA LAA ostium area based sizing algorithm is highly accurate at predicting WATCHMAN device size and demonstrates excellent clinical outcomes with lower device utilization per case than what is reported in literature.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Background The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually. Methods We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging. Results A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM). Conclusion We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.

Case Presentation A 60-year-old man with a history of COPD, uncontrolled diabetes (hemoglobin A1c, 10.6%), obesity (BMI, 33.4), and a family history of Ehlers-Danlos syndrome came to the ED with several hours of acute-onset severe left mid-axillary pleuritic chest pain without alleviating factors. The pain had no specific triggers, including activities or heavy meals. It was associated with nausea, chills, and diaphoresis; also, it was preceded by a few weeks of subacute flulike symptoms for which he did not seek medical attention. He denied previous similar symptoms, recent trauma, or surgeries.

We calculate characters of Weil representations of unitary groups over finite fields geometrically. As a byproduct, we deduce another proof of Gerardin’s trace formula for the Weil representation. ...

The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan.We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM).We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan.

Permanent pacemaker implantation (PPMI) reduction and optimal management of newly acquired conduction disturbances after transcatheter aortic valve implantation (TAVI) are crucial. We sought to evaluate the relation between transcatheter heart valve (THV) implantation depth and baseline and newly acquired conduction disturbances on PPMI after TAVI. This study included 1,026 consecutive patients with severe symptomatic aortic stenosis (mean age 79.7 ± 8.4 years; 47.4% female) who underwent TAVI with the newer-generation self-expanding THVs Primary outcomes were early and late PPMI defined as the need for PPMI during the index admission and between discharge and 30 days, respectively. Early and late PPMI was required for 115 (11.2%) and 21 patients (2.0%), respectively. Early PPMI rates decreased from 26.7% in 2015 and 2016 to 5.7% in 2021, and so did the mean THV depth from 4.4 ± 2.4 mm to 1.8 ± 1.6 mm. Receiver operator characteristics curve analyses showed THV depth had significant discriminatory value for early and late PPMI with cutoff values of 3.0 and 2.2 mm, respectively. Rates of early and late PPMI were significantly lower for patients with shallower compared with deeper implantations (5.1% vs 22.6% and 0.4% vs 4.1%, p 0.001 for both, respectively). Furthermore, rates of early PPMI were lower with shallower implantations in patients with new left bundle branch block after TAVI (2.4% vs 15.9%; p 0.001) and those with baseline right bundle branch block (7.5% vs 29.6%; p = 0.017). Lower rates of PPMI with shallower THV implantation were consistently observed, including in patients with baseline and newly acquired conduction disturbances. Our findings might help optimize the management of a temporary pacemaker after TAVI.

The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma.

SummaryBackground Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.

This case report describes a patient in their 60s with shortness of breath who tested positive for COVID-19.

337 Background: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor, eribulin. Treatment with E7389-LF plus the programmed cell death 1 inhibitor nivolumab may result in an increased antitumor effect through vascular remodeling. The phase 1b part of the open-label Study 120 assessed dosing and safety of E7389-LF combined with nivolumab in patients (pts) with solid tumors; the phase 2 part assessed efficacy and safety in expansion cohorts, including an esophageal cancer (EGC) cohort. Methods: For the EGC cohort in the phase 2 part of Study 120, pts were required to have unresectable, measurable (by RECIST v1.1) EGC lesion(s) that showed progression during or after first-line chemotherapy with no other systemic chemotherapy. The primary objective of the phase 2 part was to assess objective response rate (ORR), with success defined as Bayesian posterior probability over 85% beyond threshold (20%) for best overall response (ie, 9 responders of planned 32 pts enrolled). Secondary objectives included assessment of safety and progression-free survival (PFS). The recommended phase 2 dosing regimen was previously determined to be E7389-LF 2.1 mg/m2 every 3 weeks (Q3W) plus nivolumab 360 mg Q3W. Tumor assessments were performed by RECIST v1.1 every 6 weeks. All adverse events (AEs) were monitored and recorded. Results: In the EGC cohort, 35 pts were included. Most pts (88.6%) were male, and the median age was 69.0 years (range 47–85). At data cutoff (May 31, 2022), 5 pts (14.3%) were still undergoing treatment. Discontinuations occurred in 30 pts (85.7%)—25 (71.4%) due to disease progression, 4 (11.4%) due to an adverse event, and 1 (2.9%) due to patient preference. ORR with E7389-LF + nivolumab was 22.9% (95% CI 10.4–40.1) and the disease control rate (DCR) was 62.9% (95% CI 44.9–78.5). Median PFS was 2.81 months (95% CI 1.31–4.17) and the 6-month PFS rate was 20.2% (95% CI 8.7–35.0). Median OS was not reached (95% CI 6.54–not estimable), and the 6-month OS rate was 71.4% (95% CI 53.4–83.5). Treatment-related treatment-emergent (TE) AEs of any grade and of grade ≥3 occurred in 94.3% and 80.0% of pts, respectively. The most common treatment-related TEAEs of any grade were neutropenia (65.7%), leukopenia (57.1%), and decreased appetite (45.7%). The most common treatment-related TEAEs of grade ≥3 were neutropenia (54.3%), leukopenia (34.3%), and febrile neutropenia (22.9%). TEAEs led to dose reduction of E7389-LF in 17 pts (48.6%). TEAEs led to withdrawal of either E7389-LF or nivolumab in 5 pts (14.3%): pneumonia (n=2), traumatic hemothorax (n=1), acute kidney injury (n=1), and pneumonitis (n=1). Conclusions: E7389-LF combined with nivolumab showed an ORR of 22.9% in pts with EGC. Despite this modest ORR, the DCR of 62.9% was notable. No new safety signals were observed compared to the known profiles of each monotherapy. Clinical trial information: NCT04078295 .

416 Background: Platinum-based definitive chemoradiotherapy (dCRT) is the standard treatment for patients (pts) with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), invading the aorta, vertebral body, or trachea. However, complete response (CR) rates are low (11–25%), with a median overall survival (OS) of 9–10 months. We previously reported atezolizumab following dCRT indicated promising 42.1% of confirmed CR (cCR) rate and 65.8% of 12-months OS (Bando H, et al., ESMO Congress 2022 ). Methods: We investigated predictive biomarkers for cCR in this multicenter phase II study. PD-L1 tumor proportion score (TPS) was examined with VENTANA PD-L1. Immunological phenotypes of tumor microenvironments were assessed with multiplex immunohistochemistry (mIHC) and multi-color flow cytometry (FCM). Cancer gene aberrations and gene expression were investigated with whole exome and whole transcriptome sequencing (WES/WTS), respectively. Results: In 35 pts with an evaluable PD-L1 TPS, the cCR rates of +CD8+PD-1+ T cells and CD3+CD8-FOXP3+ T cells prior to CRT in tumor tissue were significantly correlated with cCR and non-cCR, respectively (both are P+CD8+ T cells prior to CRT, after CRT, and after atezolizumab were significantly correlated with cCR (P+FOXP3highCD45RA-CD4+ regulatory T cells (Treg cells) after CRT were significantly correlated with non-cCR (P+CD8+ T cells prior to CRT may be a predictive biomarker for cCR of CRT followed by atezolizumab, and that several driver gene abnormalities, cancer intrinsic signatures and tumor-infiltrating Treg cells are associated with treatment resistance. These findings could enable subsequent biomarker-selected clinical trials and lead to the development of novel cancer immunotherapeutic strategies. Clinical trial information: UMIN000034373 .

Venous thromboembolism (VTE) is frequently observed in patients with advanced cancer. The objective of this prospective observational study was to estimate, based on intensive screening, using computed tomography, lower‐extremity ultrasonography, and D‐dimer testing, the prevalence of VTE in patients with advanced cancer. Patients with metastatic or locally advanced cancer without anticoagulant therapy, who were planning to receive chemotherapy during 4 weeks, were eligible. Evaluations of VTE were performed at pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy. Primary endpoint was cumulative incidence of VTE for 24 weeks. Secondary endpoints included incidence of VTE (pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy), VTE according to primary cancer site, symptomatic VTE, pulmonary thromboembolism (PE), and treatment of VTE. We enrolled 860 patients with a median age of 68 years, including 34% female and 71% lung cancer. Cumulative incidence of VTE for 24 weeks was 22.6% (95% confidence interval: 19.8%–25.5%) (194 of 860 patients). Incidence of VTE was 11.3% pretreatment, 16.8% 12 weeks, and 14.1% 24 weeks. Symptomatic VTE was observed in 4.0% and PE in 1.0% of patients. By multivariate analysis, sex, D‐dimer level, and platelet count were independent risk factors of VTE for 24 weeks. This large prospective observational study showed that cumulative incidence of VTE was high in advanced cancer patients, mainly lung cancer. Although most patients showed asymptomatic VTE, intensive screening of VTE may be considered in advanced cancer patients, especially in women with high level of D‐dimer and decreased platelet count (UMIN000015243)., In 860 patients with advanced cancer, cumulative incidence of VTE for 24 weeks was 22.6% (95% confidence interval: 19.8%–25.5%). Incidence of VTE was 11.3% pretreatment, 16.8% 12 weeks, and 14.1% 24 weeks. By multivariate analysis, sex, D‐dimer level, and platelet count were independent risk factors of VTE for 24 weeks.

Let q be a power of a prime number. We construct a variety over a finite field F q and show that its middle cohomology realizes the Heisenberg–Weil representations of a general linear group G L n ( q ) for any integer n ≥ 1 . If n is even, by using an endomorphism of this variety, we can construct a representation of a semidirect group G L n ( q ) ⋊ ( Z / 2 Z ) , which is an extension of the Weil representation of G L n ( q ) . By inflating this by a natural homomorphism S p n ( q ) × O 2 + ( q ) → G L n ( q ) ⋊ ( Z / 2 Z ) , we obtain a representation of S p n ( q ) × O 2 + ( q ) . This representation can be used for the Howe correspondence for ( S p n , O 2 + ) in any characteristic. As application, we show that unipotency is preserved under the correspondence for ( S p n , O 2 + ) .

The standard treatment for patients 75 years of age or younger with cStage 2 or 3 esophageal cancer is preoperative chemotherapy followed by esophagectomy. The optimal treatment for elderly patients, especially those considered vulnerable, remains unclear. This study retrospectively reviewed the data for 42 patients ages 75–80 years with cStage 2 or 3 esophageal cancer who underwent esophagectomy between October 2002 and February 2019. The patients who received preoperative chemotherapy were compared with those who did not. The study also examined short- and long-term outcomes and the impact of preoperative chemotherapy on overall survival (OS) stratified by performance status (PS). Of the 42 patients, 18 underwent esophagectomy without preoperative chemotherapy and 24 underwent esophagectomy after preoperative chemotherapy. A significantly greater proportion of the patients with PS 0 received preoperative chemotherapy than the patients with PS 1 (P =0.007). The multivariate analysis showed preoperative chemotherapy to be an independent negative prognostic factor for OS (hazard ratio [HR], 5.025; 95% confidence interval [CI] 1.136–22.222; P = 0.033). Subgroup analysis showed that preoperative chemotherapy had a significant negative impact on the OS of the patients with PS 1 (P

We define affinoids in the Lubin–Tate curve in even equal characteristic, and compute the reductions of them. Each reduction is isomorphic to a smooth affine curve with Artin–Schreier type equation. We expect that the cohomology of the reductions realizes the local Langlands correspondence and local Jacquet–Langlands correspondence for representations of conductor five.

Most of the coronary vasospasms were found intraprocedurally, and it is very rare to see late‐onset vasospasms that happened a few hours after uncomplicated ablations. The recognition of this rare but potentially life‐threatening complication is important to improve the conventional practice of catheter ablation for patients with drug‐refractory atrial fibrillation.