Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings.

OBJECTIVE: Post-marketing surveillance (PMS) was performed in Japan to obtain information on the safety and efficacy of crizotinib. METHODS: Target patients included almost all patients with anaplastic lymphoma kinase-positive non-small cell lung cancer who were administered crizotinib. The observation period was 52 weeks. In the present study, we focused on the treatment status and safety of crizotinib therapy and analyzed the real-world data obtained by this PMS (ClinicalTrials.gov: NCT01597258). RESULTS: The safety analysis set included 2028 Japanese patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of adverse drug reactions (ADRs) was 91.6%, and common ADRs (incidence ≥15%) were nausea (32.2%), diarrhea (24.3%), photopsia (18.9%), vomiting (17.5%) and dysgeusia (16.8%). Many patients (623 patients) discontinued treatment of crizotinib because of adverse events within 12 weeks after therapy initiation, which tended to frequently occur in the following cases: (1) elderly, (2) body weight <40 kg, (3) body surface area <1.2 m2 (4) ECOG PS 2-4, (5) higher Brinkman index and (6) history of occupational/environmental exposure such as asbestos/pneumoconiosis. The proportions of patients remaining on crizotinib therapy were 68.2% for 3 months, 55.2% for 6 months and 36.1% for 12 months, with a median duration of 7.9 months. Multivariate analysis with a Cox proportional hazard model identified 10 statistically significant patient background factors influencing the duration of crizotinib therapy. CONCLUSIONS: No new safety concerns were observed in this PMS study. Our results provide useful information regarding the status of crizotinib therapy in the clinical setting.

Impaired activity of daily living is a risk factor for high medical cost in patients of non-variceal upper gastrointestinal bleeding.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is still a common and life-threatening disease, thus it would have a big impact on medical care cost. However, little is known about risk factors for increased medical care cost in NVUGIB patients. AIM: The purpose of the study was to clarify predictor of requiring high medical care cost in NVUGIB patients. Patients who underwent endoscopic hemostasis due to NVUGIB between April 2012 and March 2015 were included in this retrospective study. We analyzed the association between patients' background including activity of daily livings (ADL) and high medical care cost using logistic regression model. Medical care cost was calculated in reference to the "Diagnosis Procedure Combination" which is diagnosis-dominant case-mix system in Japan. The cutoff value of high medical care cost was defined as its first quartile. ADL was assessed according to Katz-6 score. We defined impaired ADL patient who revealed Katz-6 score more than 1. RESULTS: A total of 128 consecutive patients were included in this study. Median medical care cost was 5323 USD (IQR 3661-8172 USD). There were 13 patients (10%) in impaired ADL group. In univariate analysis, age and impaired ADL before admission revealed significant association with high cost. Of these, impaired ADL was an only independent risk factor [odds ratio 15.3 (95% CI 2.49-183)] in multivariate analysis. CONCLUSION: Impairment in ADL before admission was an independent predictor for high medical care cost with NVUGIB patients.

Risk Factor for Vital Signs Fluctuation during Colonoscopy under Conscious Sedation Consisting of Midazolam and Meperidine.

BACKGROUND: Sedatives or analgesics are widely used to relieve a patient's discomfort during colonoscopy (CS). Although cardiopulmonary adverse events are sometimes experienced during the examination, the risk factors for vital signs fluctuation (VSF) have not been fully elucidated. This study thus aimed to identify the risk factors for VSF during the examination, as well as to evaluate the frequency and the degree of VSF. SUMMARY: A total of 755 consecutive subjects who received CS under endoscopist-administrated sedation using midazolam, meperidine, or combination of both were retrospectively analyzed. We assessed the distribution of vital signs during the procedure and frequency of VSF. To identify independent risk factors, we analyzed the association between VSF and subjects' characteristics and procedure information using the multivariate logistic regression model. Consequently, VSF was observed in 17% of all; hypotension and oxygen desaturation was observed in 13 and 5%, respectively. However, we could achieve the purpose of all procedure and, no one required hospitalization or extension of hospital stay. Multivariate analysis revealed that age (OR 1.05 [95% CI 1.04-1.07]), being female (OR 1.78 [95% CI 1.19-2.70]), and use of midazolam (OR 5.06 [95% CI 3.18-8.08]) were independent risk factors for VSF.

The Role of History of Gastro-Duodenal Ulcer in Patients with Upper Gastrointestinal Bleeding.

BACKGROUND: Some scoring systems have been introduced to predict the need for performing urgent endoscopy in patients with upper gastrointestinal bleeding (UGIB). However, in an emergency situation, this intervention is insufficient and cannot easily provide the required treatment. AIM: To identify new risk factors that can predict the need for endoscopic intervention (EI) in UGIB patients. METHODS: This is a retrospective cross-sectional study. Patients with UGIB admitted from April 2011 to August 2014 were included. The proportion of cases requiring EI and clinical factors (age, gender, antiplatelet/anticoagulant therapy, history of gastro-duodenal ulcer (GDU), systolic blood pressure, heart rate, hemoglobin, mean corpuscular volume, blood urea nitrogen-creatinine ratio (BUN/Cr ratio), prothrombin time-international normalized ratio, and Glasgow-Blatchford Score (GBS) were analyzed using logistic regression models. RESULT: Of 378 patients who were included in this study, 180 were found to be with GDU. The proportion of cases requiring EI was significantly higher in those with GDU than in other causes except variceal bleeding (53.5 vs. 37.0%, p < 0.01). Multivariate analysis revealed that a history of GDU was an independent risk factor (OR 1.78, 95% CI 1.06-3.00) in addition to BUN/Cr ratio (OR 1.02, 95% CI 1.00-1.03) and GBS (OR 1.19, 95% CI 1.08-1.33). CONCLUSION: A history of GDU was an independent risk factor for predicting the need for EI in UGIB in addition to BUN/Cr ratio and GBS.

Initial Management of Colonic Diverticular Bleeding: Observational Study.

BACKGROUND/AIMS: Although colonic diverticular bleeding (CDB) often ceases spontaneously, re-bleeding occurs in about 30%. Bleeding diverticulum can be treated directly by endoscopic hemostasis; however, it is difficult to perform colonoscopy in all cases with limited medical resource and certain risks. The aim of this study was to clarify who should undergo colonoscopy as well as appropriate methods of initial management in CDB patients. METHODS: A total of 285 patients who were diagnosed as CDB and underwent colonoscopy from March 2004 to October 2015 were retrospectively analyzed. First, the association between re-bleeding and various factors including patients' background and initial management were analyzed. Second, the examination conditions that influenced bleeding point identification were analyzed. RESULTS: Of 285 patients, 187 were men and 98 were women. Median age was 75 years, and the median observation period was 17.5 months. Re-bleeding was observed in 79 patients (28%). A history of CDB (OR 2.1, p = 0.0090) and chronic kidney disease (CKD; OR 2.3, p = 0.035) were risk factors, and bleeding point identification (OR 0.20, p = 0.0037) was a preventive factor for re-bleeding. Bleeding point identification significantly reduced approximately 80% of re-bleeding. Furthermore, extravasation on CT (OR 3.7, p = 0.031) and urgent colonoscopy (OR 5.3, p < 0.001) were predictors for identification of bleeding point. Compared to bleeding point identification of 11% in all patients who underwent colonoscopy, identification rate in those who had extravasation on CT and underwent urgent colonoscopy was as high as 70%. CONCLUSIONS: Contrast-enhanced CT upon arrival is suggested, and patients with extravasation on CT would be good candidates for urgent colonoscopy, as well as patients who have a history of CDB and CKD.

Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib.

INTRODUCTION: The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib, in a real-world clinical setting. METHODS: Post-marketing surveillance was performed in Japan to obtain information on the safety and efficacy of crizotinib. Target patients included all patients with anaplastic lymphoma kinase-positive NSCLC who received crizotinib during the enrollment period between May 2012 and December 2014. The observation period was 52 weeks. Expert analysis of the ILD incidence was performed by an ILD independent review committee composed of five medical specialists. RESULTS: The safety analysis set included 2028 patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of ILD associated with crizotinib therapy was 5.77%; and 3.45% patients showed grade 3 or greater. Pulmonary edema-like shadows with or without diffuse alveolar damage pattern were observed in crizotinib-associated ILD (incidence: 0.39%), but a causal relationship with the prognosis could not be identified. ILD developed within 4 weeks from initiation of crizotinib administration in 41.9% and within 8 weeks in 69.2% of the patients. Age 55 years or older, Eastern Cooperative Oncology Group performance status 2-4, smoking history, previous or concomitant ILD, and comorbid pleural effusion were statistically determined as significant risk factors for crizotinib-induced ILD. CONCLUSIONS: Crizotinib therapy should be applied to the NSCLC patients with any of above risk factors under a cautious monitoring for ILD occurrence, and clinicians should pay attention to the risks of severe ILD.

A Case of Gastroparesis after Cryoballoon Ablation followed by Medication-Induced Recovery within 6 Months.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and cryoballoon ablation was developed as a new treatment modality for symptomatic AF. Gastroparesis is rarely reported as a transient complication of ablation, and its frequency and risk are not clear. We experienced a rare case of gastroparesis after cryoballoon ablation followed by medication-induced recovery within 6 months.

Validation of treatment algorithm based on the Japan narrow-band imaging expert team classification for sub-centimeter colorectal polyps.

BACKGROUND AND STUDY AIMS: Although cold polypectomy (CP) is widely used for colorectal polyps < 10 mm, appropriateness of indications for CP or endoscopic mucosal resection (EMR) are still unclear. The aim of this study was to validate the endoscopic treatment algorithm based on the Japan NBI Expert Team (JNET) classification. PATIENTS AND METHODS: Consecutive patients with at least one colorectal non-pedunculated polyp < 10 mm between July 2014 and October 2016 were included in this retrospective study. During the period, EMR was performed for JNET ≥ 2B lesions and CP for JNET < 2A. Among a total of 3966 lesions, 3368 lesions with JNET ≤ 2A were resected by CP in compliance with the treatment algorithm but 565 resections for JNET ≤ 2A were not compliant (by EMR), while all 24 JNET > 2B lesions were removed by EMR in compliance with the algorithm. Polypectomy outcomes were compared between the compliant and non-compliant groups. Histological outcomes were analyzed in accordance with JNET classification. RESULTS: Post-polypectomy bleeding rate in the compliant group (0 %) was lower than that in the non-compliant group (0.53 %, P  < 0.01). Proportion of lesions diagnosed as cancer (38 % vs 0.36 %, P  < 0.01) or submucosal cancer (4.2 % vs 0.03 %, P  = 0.012), and the lesion with free resection margin (91 % vs 64 %, P  < 0.01) was higher in the JNET ≥ 2B than JNET ≤ 2A. CONCLUSION: This study indicated our algorithm would be valid: CP is suitable for most polyps < 10 mm as incidence of post-polypectomy bleeding is low, whereas EMR is recommended for JNET ≥ 2B lesions for histological complete removal.