Effectiveness of Anti-PD-1 Antibody Monotherapy for the Primary Malignant Melanoma of the Esophagus： A Case Report

Primary malignant melanoma of the esophagus（PMME）is extraordinarily rare with a high degree of malignancy and poor prognosis, and a standard therapy remains to be established. The anti-PD-1 antibody nivolumab is a promising agent for various cancers. To our knowledge, this is the first case report of PMME where a complete response was achieved using nivolumab. We report an 80-year-old woman who was diagnosed with PMME with bone metastasis and lymph node metastases. Although dacarbazine combined chemotherapy was performed and continued for six cycles, the primary tumor progressed and liver metastases appeared. The patient then received nivolumab monotherapy. After three cycles, nivolumab monotherapy for PMME resulted in a complete response as shown by positron emission tomography, computed tomography, and esophagogastroduodenoscopy. In our case, nivolumab exerted a curative effect on PMME, thus suggesting that nivolumab can be effective in the treatment of this rare disease

Association between interstitial lung abnormality and mortality in patients with esophageal cancer

The version of record of this article, first published in Japanese Journal of Radiology, is available online at Publisher’s website: https://doi.org/10.1007/s11604-024-01563-x.Purpose: To investigate the relationship between interstitial lung abnormalities (ILAs) and mortality in patients with esophageal cancer and the cause of mortality. Materials and methods: This retrospective study investigated patients with esophageal cancer from January 2011 to December 2015. ILAs were visually scored on baseline CT using a 3-point scale (0 = non-ILA, 1 = indeterminate for ILA, and 2 = ILA). ILAs were classified into subcategories of non-subpleural, subpleural non-fibrotic, and subpleural fibrotic. Five-year overall survival (OS) was compared between patients with and without ILAs using the multivariable Cox proportional hazards model. Subgroup analyses were performed based on cancer stage and ILA subcategories. The prevalences of treatment complications and death due to esophageal cancer and pneumonia/respiratory failure were analyzed using Fisher’s exact test. Results: A total of 478 patients with esophageal cancer (age, 66.8 years ± 8.6 [standard deviation]; 64 women) were evaluated in this study. Among them, 267 patients showed no ILAs, 125 patients were indeterminate for ILAs, and 86 patients showed ILAs. ILAs were a significant factor for shorter OS (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.10–2.55, P = 0.016) in the multivariable Cox proportional hazards model adjusting for age, sex, smoking history, clinical stage, and histology. On subgroup analysis using patients with clinical stage IVB, the presence of ILAs was a significant factor (HR = 3.78, 95% CI 1.67–8.54, P = 0.001). Subpleural fibrotic ILAs were significantly associated with shorter OS (HR = 2.22, 95% CI 1.25–3.93, P = 0.006). There was no significant difference in treatment complications. Patients with ILAs showed a higher prevalence of death due to pneumonia/respiratory failure than those without ILAs (non-ILA, 2/95 [2%]; ILA, 5/39 [13%]; P = 0.022). The prevalence of death due to esophageal cancer was similar in patients with and without ILA (non-ILA, 82/95 [86%]; ILA 32/39 [82%]; P = 0.596). Conclusion: ILAs were significantly associated with shorter survival in patients with esophageal cancer

Diagnostic approach for patients with unidentified fever according to the classical criteria of fever of unknown origin in the field of autoimmune disorders

ArticleImmunological medicine. 42(4): 176-184 (2019)journal articl

Long-term maintenance of the mucosal healing induced by azacitidine therapy in a patient with intestinal Behçet's-like disease accompanied with myelodysplastic syndrome involving trisomy 8

ArticleImmunological medicine. 42(3): 135-141 (2019)journal articl

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging to visualize the effects of direct electrical brain stimulation in macaque monkeys and human neurosurgery patients. We discovered comparable effective connectivity between caudal auditory cortex and both ventro-lateral prefrontal cortex (VLPFC, including area 44) and parahippocampal cortex in both species. Human-specific differences were clearest in the form of stronger hemispheric lateralization effects. In humans, electrical tractography revealed remarkably rapid evoked potentials in VLPFC following auditory cortex stimulation and speech sounds drove VLPFC, consistent with prior evidence in monkeys of direct auditory cortex projections to homologous vocalization-responsive regions. The results identify a common effective connectivity signature in human and nonhuman primates, which from auditory cortex appears equally direct to VLPFC and indirect to the hippocampus

Large Right Pulmonary Vein Is a Predictor of Atrial Fibrillation Recurrence after Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation

Pulmonary vein isolation（PVI）is an effective treatment for atrial fibrillation（AF）. However, outcomes differ between paroxysmal AF and persistent AF. We analyzed the predictors of recurrence by examining the recurrence group after ablation. Of 372 consecutive patients with AF who underwent PVI between June 2016 and December 2018, we evaluated 250 patients（age, 67±12y, 65％ men）whose left atrium（LA）was constructed using the PENTARAY catheter（BioSense Webster, Los Angeles, CA）, a multipolar electrode catheter with a novel shape and excellent mapping capability. We measured the LA total volume（LATV）, right pulmonary vein＋antrum volume（RPAV）, left PV＋antrum volume（LPAV）, LA central volume（LACV）, and LA bipolar voltage. Of the 250 patients, 78 had persistent AF（recurrence, 20）and 172 had paroxysmal AF（recurrence, 16）. In all patients, LATV, LACV, RPAV, and LPAV were significantly larger in patients with persistent AF than those with paroxysmal AF. The mean LA bipolar voltage in patients with persistent AF was significantly lower than those with paroxysmal AF. In cases of persistent AF, RPAV was significantly larger in the recurrence group than that in the non-recurrence group（15.9±4.8 vs 13.4±5.4ml; P＜0.05）. In cases of paroxysmal AF, there were no differences in any volume between the recurrence and non-recurrence groups. In conclusion, larger right PV is a predictor of AF recurrence after PVI in patients with persistent AF. The right PV is close to the atrial septum and the septopulmonary bundle, and the expansion of RPAV reflects the disruption of these structures, which may be involved in this result

Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway

Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway