Poorly differentiated neuroendocrine cell carcinoma of the rectum : report of a case and literal review

A 56-year-old man was admitted to our hospital because of anal bleeding. Colonoscopy and barium enema revealed type 4 tumor in the rectum. Biopsy revealed poorly differentiated adenocarcinoma. Low anterior resection with total mesorectal excision and lymph node dissection was performed. In immunohistochemical staining, chromogranin A and synaptophysin were positive at major lesion, and CEA were focal positive. The resected tumor was diagnosed pathologically as neuroendocrine cell carcinoma. The Ki-67 labeling index (LI) was 87.8%, so proliferative activity and potential malignancy was very high. Multiple metastatic tumors appeared in pelvis and lung eight months after operation. Treatment for neuroendocrine cell carcinoma of the rectum was controversial. Surgical resection and adjuvant chemotherapy might be one of the methods for gastrointestinal neruroendocrine cell carcinoma

Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker

Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity

Super-responder to pirfenidone therapy in IPF

Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients

カブ チョクチョウ ガン ノ ジュツゼン ホウシャセン カガク リョウホウ ニヨル アタラシイ チリョウ センリャク

Purpose : To report cases of advanced rectal cancer that showed significant responses after administration of preoperative chemoradiation therapy. Methods : 5-Fluorouracil（5-FU, 300mg//day）was administered by 24-hour continuous intravenous infusion after cancers had been decreased in size by radiation（2Gy）administered for 20 days preoperatively. All patients then underwent low anterior resection with lymph node dissection（two cases had super-low anterior resection）. Results : Clinical stages of all patients were down-staged preoperatively. All of operations resulted in a curative resection of the cancer cells macroscopically. In one, histological examination revealed no residual cancer cells in the resected specimen（CR）. Conclusion : Preoperative chemoradiation therapy was demonstrated as a promising regimen for patients with advanced lower rectal cancer, and should be considered to extend indications for even laparoscopic operations for advanced rectal cancer; a therapy tailor made for advanced rectal cancer

Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases : Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial

Background: The efficacy of nintedanib in progressive fibrosing interstitial lung diseases (ILDs) was demonstrated in the randomised, double-blind, placebo-controlled INBUILD trial. This subgroup analysis evaluated the efficacy and safety of nintedanib in the Japanese population. Methods: Patients with progressive fibrosing ILDs (evaluated by physicians within 24 months of screening) were randomised (1:1) to twice-daily 150-mg nintedanib or placebo; treatment continued until the last patient completed 52 weeks. The primary endpoint was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. Time-to-first acute ILD exacerbation or death and time-to-death up until the last patient had completed the week 52 visit were evaluated. This subgroup analysis included 108 Japanese patients. Results: The adjusted annual rates of FVC decline (mL/year) over 52 weeks for Japanese patients were −148.31 (nintedanib) and −240.36 (placebo), adjusted difference: 92.05 (95% CI: −10.69–194.80) and for non-Japanese patients were −67.41 (nintedanib) and −177.65 (placebo), adjusted difference: 110.24 (95% CI: 64.97–155.52). No heterogeneity in treatment effect between Japanese and non-Japanese subgroups was observed (treatment-by-subgroup interaction, p = 0.75). The risks of “acute exacerbation or death” (hazard ratio, 0.30 [95% CI: 0.10–0.91]) and mortality (hazard ratio, 0.54 [95% CI: 0.14–2.11]) in Japanese patients were numerically lower for nintedanib than placebo. There were no new or unexpected safety findings. Conclusions: In Japanese patients, nintedanib slowed ILD progression, evidenced by a reduction in the annual rate of decline in FVC vs placebo. The efficacy and safety of nintedanib in Japanese patients were consistent with the overall INBUILD population

The Reality of the Mobilization of Koreans During World War II : An analysis based on statistics and written records

In 1965, Japan and South Korea normalized their diplomatic relations and Japan paid South Korea 300 million dollars with no strings attached in accordance with the Agreement Concerning the Settlement of Problems in Regard to Property and Claims and Economic Cooperation. With this payment, both countries confirmed that all post-war claims, including for Koreans who participated in wartime mobilization, had been settled “completely and finally.” Some refer to the wartime of mobilization of people based on the laws of the time as an inhumane form of “slave labor.” This paper sheds light on the reality of the wartime mobilization of Korean workers by analyzing official statistics and written records, showing that there are layers of untruth to descriptions of young men forcibly being taken from peaceful farm villages to work as slaves