Ampullary carcinomas have a significantly higher resectability rate and better prognosis than other periampullary carcinomas, although the prognosis is poor with advanced disease. Accurate tumour staging is therefore important in surgical planning. Our objective was to evaluate the usefulness of, and problems associated with, endoscopic ultrasound (EUS) in the pre-operative staging of ampullary tumours. 35 patients with ampullary tumours were pre-operatively examined with EUS. The imaging results were compared with histopathological findings of the resected specimen according to the TNM staging classification. The overall accuracy of tumour (T) staging was 74% (26/35) for all tumours, and 67% (6/9), 71% (10/14) and 83% (10/12) respectively for T1, T2 and T3 tumours. The overall accuracy of nodal (N) staging was 63%. In diagnosing pancreatic invasion, EUS had an accuracy of 86% (30/35), a sensitivity of 83% (10/12), and a specificity of 87% (20/23). In conclusion, EUS provides an accurate method of evaluating the stage of ampullary tumours, especially infiltration into the pancreas. This modality is useful to surgeons in deciding on an appropriate therapeutic approach and in giving a prognosis.
A disruption of immune checkpoints leads to imbalances in immune homeostasis, resulting in immune-related adverse events. Recent case studies have suggested the association between immune checkpoint inhibitors (ICIs) and the disorders of the coagulation-fibrinolysis system, implying that systemic immune activation may impact a balance between clotting and bleeding. However, little is known about the association of coagulation-fibrinolysis system disorder with the efficacy of ICIs. We retrospectively evaluated 83 lung cancer patients who received ICI at Kumamoto University Hospital. The association between clinical outcome and diseases associated with disorders of the coagulation-fibrinolysis system was assessed along with tumor PD-L1 expression. Among 83 NSCLC patients, total 10 patients (12%) developed diseases associated with the disorder of coagulation-fibrinolysis system. We found that disorders of the coagulation-fibrinolysis system occurred in patients with high PD-L1 expression and in the early period of ICI initiation. In addition, high tumor responses (72%) were observed, including two complete responses among these patients. Furthermore, we demonstrate T-cell activation strongly induces production of a primary initiator of coagulation, tissue factor in peripheral PD-L1high monocytes, in vitro. This study suggests a previously unrecognized pivotal role for immune activation in triggering disorders of the coagulation-fibrinolysis system in cancer patients during treatment with ICI.
Background Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. The role of vascular endothelial growth factor (VEGF) in pathogenesis of AE-ILD is conflicting. The influence of bevacizumab (Bev), a monoclonal antibody against VEGF, on lung cancer patients with pre-existing ILD remains unclear. We examined the effect of Bev on reducing AE-ILD risk in non-squamous non-small cell lung cancer (NSCLC) patients receiving chemotherapy. Methods We analysed incidence of AE-ILD and outcomes of 48 patients with advanced non-squamous NSCLC with ILD who received first-line chemotherapy with (Bev group, n = 17) and without (non-Bev group, n = 31) Bev between July 2011 and July 2016. Gray’s test, which was competing risk analysis during the study period, was performed for both groups. Results The most common regimen used for first-line chemotherapy was the combination of carboplatin plus pemetrexed (PEM) in both groups. The incidences of chemotherapy-related AE-ILD 120 days after first-line chemotherapy initiation were significantly lower in the Bev than in the non-Bev groups (0% vs. 22.6%, p = 0.037, Gray’s test). However, there were no differences in development of progressive disease of lung cancer and other events as the competing risk factors of AE-ILD between the two groups. Only patients receiving PEM-containing regimens also showed a significant difference in the incidence of AE-ILD between the two groups ( p = 0.044). The overall-cumulative incidence of AE-ILD during the first-line and subsequent chemotherapy was 29.2% (14 of the 48). The median progression-free survival was significantly longer in the Bev than in the non-Bev groups (8.0 vs. 4.3 months, p = 0.026). Conclusions The addition of Bev to chemotherapy regimens may reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer. Electronic supplementary material The online version of this article (10.1186/s12890-019-0838-2) contains supplementary material, which is available to authorized users.
Background:Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) therapy has been approved for sepsis-associated acute respiratory distress syndrome, but its efficacy for other rapidly progressive interstitial pneumonias (RPIPs) is unclear. The purpose of this study was to examine the efficacy of PMX-DHP therapy for acute respiratory failure in patients with RPIPs, when compared with a historical control receiving conventional treatment without PMX-DHP.Methods:This study comprised 77 patients with RPIPs in our institute between January 2002 and December 2015. The initial 36 patients between January 2002 and March 2007 were treated without PMX-DHP (historical control group), and the following 41 patients between April 2007 and December 2015 were treated with PMX-DHP (PMX-DHP group) once daily for two successive days concurrently with corticosteroids and/or immunosuppressive agents. The 90-day mortality and clinical factors were compared between the groups. Cox proportional hazards models were constructed to analyze 90-day mortality and identify predictors.Results:The 90-day mortality rate was significantly lower in the PMX-DHP group than in the controls (41.5% versus 66.7%, p = 0.019). PMX-DHP therapy was significantly associated with mortality (hazard ratio 0.505; 95% confidence interval, 0.270–0.904; p = 0.032). There were significant differences in the serial changes in the PaO2/FiO2 ratio, SOFA score, and blood neutrophil counts from days 0–5 after PMX-DHP between the survivor and non-survivor groups (p = 0.015, p < 0.001, p = 0.035, respectively). The improved PaO2/FiO2 ratio on day 3 significantly correlated with the change in blood neutrophil counts (rs = −0.431, p = 0.006).Conclusions:PMX-DHP therapy may be effective in RPIPs patients accompanied by acute respiratory failure and is expected to reduce mortality rates.
The conversion from mitosis to meiosis is a phenomenon specific to the cellular progenitors of gametes
BackgroundRapidly progressive interstitial pneumonias (RPIPs) associated with clinically amyopathic dermatomyositis (CADM) are highly resistant to therapy and have a poor prognosis. Multimodal therapies, including direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP), have a protective effect on RPIPs. We evaluated the effects of PMX-DHP on CADM-associated RPIPs.MethodsWe retrospectively enrolled 14 patients with CADM-associated RPIPs and acute respiratory failure treated with PMX-DHP, corticosteroids, and immunosuppressive agents. Clinical manifestations were compared between survivors and non-survivors at 90 days after PMX-DHP.ResultsThe survival rate at 90 days after PMX-DHP was 35.7% (5/14). Before PMX-DHP, the survivor group exhibited a significantly higher PaO2/FiO2 (P/F) ratio and serum surfactant protein-D (SP-D) levels and significantly lower lactate dehydrogenase (LDH) and ferritin levels than the non-survivor group. Platelet counts were significantly decreased after PMX-DHP therapy in both groups, but remained higher in the survivor group than the non-survivor group over the course of treatment. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody positive patients demonstrated a poor 90-day survival rate, lower platelet counts and P/F ratio, and higher LDH levels than anti-MDA-5 antibody negative patients.ConclusionsCADM-associated RPIPs with anti-MDA-5 antibody is associated with a very poor prognosis. A higher P/F ratio and SP-D level, lower LDH and ferritin levels, higher platelet counts, and anti-MDA-5 antibody negativity are important prognostic markers in patients with CADM-associated RPIPs treated with PMX-DHP.
Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0–0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1–3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7–34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4–74.3%], p < 0.01). Conclusions: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.
The aim of the study was to evaluate the usefulness of and problems associated with a new endoscopically guided ultrasound miniprobe, used for pre-operative staging of gastric cancers. 59 cases of gastric cancer were prospectively examined with a 15 MHz ultrasound miniprobe. The results of the ultrasound imaging were compared with the histological findings of the resected specimens. The accuracy of the miniprobe for depth of invasion (T category) was 61% for all tumours, and 72% and 40%, respectively, for T1 and T2 to T4 lesions. If indeterminate cases due to ultrasound attenuation were excluded, the accuracy was improved to 82% for T1 and 57% for T2 to T4 tumours, respectively. The accuracy of the miniprobe for nodal staging (N category) was 69% overall, and 86%, 25% and 14% for stages N0, N1 and N2, respectively. In tumours classified on the basis of endoscopic types, the miniprobe staged early type gastric cancers (T category = 73%, N category = 80%) significantly (p < 0.01) more accurately than advanced ones (T category = 21%, N category = 36%). This study suggests that the miniprobe is indicated for pre-operative TN staging when endoscopy reveals an early gastric cancer.
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