Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer.

BACKGROUND: We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial. METHODS: Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m(2) (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations. RESULTS: The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % confidence interval, 0.60-1.28) in the Japanese population and 0.73 (95 % confidence interval, 0.58-0.91) in the Western population. The progression-free survival hazard ratio was 0.50 (95 % confidence interval, 0.35-0.73) in the Japanese population and 0.63 (95 % confidence interval, 0.51-0.79) in the Western population. The objective response rate was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 41.2 % vs 19.4 %; Western population, 26.8 % vs 13.0 %), as was the 6-month survival rate (Japanese population, 94.1 % vs 71.4 %; Western population, 66.0 % vs 49.0 %). CONCLUSIONS: Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. CLINICALTRIALS. GOV IDENTIFIER: NCT01170663.

Imaging modality utilization trends in patients with stage III-IV oropharyngeal squamous cell carcinoma.

The objective of this study is to establish the utilization trends of CT, MRI, and FDG-PET/CT for evaluation of oropharyngeal squamous cell carcinoma (OPSCC) patients. A total of 173 patients with newly diagnosed stage III or IV OPSCC between 2003 and 2009 were included. Frequency of imaging modality use, divided into four time periods (2003-04, 2005-06, 2007-08 and 2009), was evaluated. For initial staging, percentage of PET/CT use was 64.6%, 87.5%, 94.1% and 96.3%, with an increasing trend (p < 0.001). The CT (p = 0.762) and MRI (p = 0.224) use demonstrated no change in trend. For post-treatment imaging, percentage of PET/CT use was 59.5%, 68.6%, 89.7% and 100%, with an increasing trend (p < 0.001). The CT use demonstrated a decreasing trend (p = 0.004) and MRI showed no trend change (p = 0.231). PET/CT is used with an increasing trend for initial staging and has become a central imaging modality for follow up evaluation after treatment, for advanced OPSCC.

Influence of hospital volume on outcomes of laparoscopic gastrectomy for gastric cancer in patients with comorbidity in Japan.

OBJECTIVE: Little information is available on the relationship between hospital volume and the outcomes of laparoscopic gastrectomy for gastric cancer in patients with comorbidity. This study aimed to investigate the influence of hospital volume on patient outcomes of laparoscopic gastrectomy for gastric cancer in patients with comorbidity using a national administrative database. METHODS: A total of 5941 comorbid patients treated with laparoscopic gastrectomy for gastric cancer were referred to 741 hospitals in Japan. We collected patients' data from the administrative database to compare laparoscopy-related complications, in-hospital mortality, length of stay (LOS), and medical costs during hospitalization in relation to hospital volume. Hospital volume was categorized into two groups: low (<40 cases in 3 years; n = 4111) and high (≥ 40 cases; n = 1830). RESULTS: There were no significant differences between the groups in laparoscopy-related complications and in-hospital mortality (p = 0.684 and p = 0.200, respectively). However, significant variations in mean LOS and medical costs were observed between hospital volume categories (26.1 days vs. 20.2 days and 16,163.9 US dollars vs. 14,345.9 US dollars, respectively; p < 0.001). Multiple linear regressions revealed that higher hospital volume was significantly associated with shorter LOS and lower medical costs during hospitalization. The unstandardized coefficient for LOS was -4.62 days (95% confidence interval = -5.63--3.60, p < 0.001), whereas that for medical costs was -1424.1 US dollars (95% confidence interval = -1962.5--885.6, p < 0.001). CONCLUSION: Hospital volume was significantly associated with a decrease of LOS and medical costs of comorbid patients undergoing laparoscopic gastrectomy for gastric cancer.

Endoscopic submucosal dissection for gastric cancer in elderly Japanese patients: an observational study of financial costs of treatment based on a national administrative database.

OBJECTIVE: There is currently little information on the medical economic outcomes of endoscopic submucosal dissection (ESD) for gastric cancer (GC) in elderly patients. This study therefore aimed to investigate the medical economic outcomes of ESD in elderly patients with GC using a national administrative database. METHODS: A total of 27 385 patients treated with ESD for GC were referred to 867 hospitals in Japan from 2009 to 2011. We collected data from the national administrative database and divided them into two groups according to age: elderly patients (≥80 years; n = 5525) and non-elderly patients (<80 years; n = 21 860). We compared ESD-related complications, risk-adjusted length of stay (LOS) and medical costs during hospitalization between elderly and non-elderly patients. RESULTS: There was no significant difference in ESD-related complications between elderly and non-elderly patients (4.3% vs 3.9%, P = 0.152). However, significant differences were observed in mean LOS and medical costs during hospitalization between the two groups (P < 0.001). Multiple linear regression analysis showed that elderly patients experienced a significantly longer LOS and higher medical costs. The unstandardized coefficient for LOS in elderly patients was 2.71 days (95% confidence interval [CI] 2.59-2.84, P < 0.001), while that for medical costs during hospitalization was USD952.1 (95% CI 847.7-1056.5, P < 0.001). CONCLUSIONS: LOS and medical costs during hospitalization were significantly higher in elderly patients undergoing ESD for GC than in non-elderly patients, although there was no difference in the incidence of ESD-related complications.

Multivariate analysis of factors influencing length of hospitalization and medical costs of cholecystectomy for acute cholecystitis in Japan: a national database analysis.

Little information is available on the factors influencing length of stay (LOS) in hospital and medical costs during hospitalization associated with cholecystectomy for acute cholecystitis. We determined the independent factors affecting LOS and medical costs of patients who underwent cholecystectomy for acute cholecystitis based on data from the Diagnosis Procedure Combination (DPC) database. In 2008, a total of 2176 patients with acute cholecystitis were referred for cholecystectomy to 624 hospitals in Japan. We collected patient characteristics and data on treatments for acute cholecystitis using the DPC database and identified independent factors affecting LOS and medical costs during hospitalization using multiple linear regression models. Analysis revealed that early cholecystectomy was significantly associated with a decrease in LOS, whereas longer preoperative antimicrobial therapy was significantly associated with an increase of LOS: the standardized coefficient for early cholecystectomy was -0.372 and that for preoperative antimicrobial therapy was 0.353 (P < 0.001). These procedures were also significant independent factors with regard to medical costs during hospitalization: the standardized coefficient for early cholecystectomy was -0.391 and that for preoperative antimicrobial therapy was 0.335 (P < 0.001). Early cholecystectomy significantly reduces the LOS and medical costs of cholecystectomy for acute cholecystitis, while preoperative antimicrobial therapy increases LOS and medical costs during hospitalization. These results highlight the need for health care implementations such as promotion of early cholecystectomy, appropriate use of antimicrobial drugs, and centralization of patients with cholecystectomy for acute cholecystitis in Japan.

Association between hospital volume and outcomes of elderly and non-elderly patients with acute biliary diseases: a national administrative database analysis.

AIM: This study aimed to investigate the relationship between hospital volume and clinical outcomes of elderly and non-elderly patients with acute biliary diseases using data from a national administrative database. METHODS: Overall, 26720 elderly and 33774 non-elderly patients with acute biliary diseases were referred to 820 hospitals in Japan. Hospital volume was categorized into three groups based on the case numbers during the study period: low-volume, medium-volume and high-volume. We compared the risk-adjusted length of stay (LOS) and in-hospital mortality in relation to hospital volume. These analyses were stratified according to the presence of invasive treatments for acute biliary diseases. RESULTS: Multiple linear regression analyses showed that increased hospital volume was significantly associated with shorter LOS in both elderly and non-elderly patients with and without invasive treatments. Increased hospital volume was significantly associated with decreased relative risk of in-hospital mortality in elderly patients. The odds ratio for high-volume hospitals was 0.672 in elderly patients without invasive treatments (95% confidence interval [CI] 0.533-0.847, P=0.001) and 0.715 in those with invasive treatments (95% C, 0.566-0.904, P=0.005). However, no significant differences for in-hospital mortality were seen in non-elderly patients with and without invasive treatments. CONCLUSION: This study has highlighted that higher volume hospitals significantly reduced LOS and in-hospital mortality for elderly patients with acute biliary diseases, but not non-elderly patients. The current results are of value for elderly healthcare policy decision-making, and highlight the need for further studies into the quality of care for elderly patients.

The care processes for acute cholecystitis according to clinical practice guidelines based on the Japanese administrative database.

Acute cholecystitis is one of the most frequently encountered conditions in daily practice in Japan. However, there is a shortage of detailed data about treatments that have been performed according to the clinical practice guidelines (CPGs) for acute cholecystitis. We therefore examined the management of acute cholecystitis for adherence to the appropriate CPGs using the Japanese administrative database associated with the Diagnosis Procedure Combination (DPC) system. We collected data from 6,070 patients with acute cholecystitis, examining for the application of four recommended treatments (administration of antimicrobial drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) and performance of early and laparoscopic cholecystectomy). The patients were classified according to the procedures documented for each case: no gallbladder drainage (n = 4,333), gallbladder drainage without supportive care (ventilation or hemodiafiltration or the use of vasopressor) (n = 1,591) and gallbladder drainage and supportive care (n = 146). Multiple logistic regression models revealed that patients with gallbladder drainage without supportive care and those with gallbladder drainage and supportive care significantly higher received administration of antimicrobial drugs and NSAIDs, while these patients underwent less early or laparoscopic cholecystectomy than did patients without gallbladder drainage, after adjusting for potential confounding effects of the clinical variables. This study demonstrated that there were various differences with regard to the performance of recommended treatments between the levels of procedures required for acute cholecystitis. In addition, this administrative database was a feasible tool for the evaluation of care processes and will provide useful information contributing to improved quality of medical care.

The influence of diabetes mellitus on short-term outcomes of patients with bleeding peptic ulcers.

PURPOSE: Little information is available on the influence of diabetes mellitus on the short-term clinical outcomes of patients with bleeding peptic ulcers. The aim of this study is to investigate whether diabetes mellitus influences the short-term clinical outcomes of patients with bleeding peptic ulcers using a Japanese national administrative database. MATERIALS AND METHODS: A total of 4863 patients treated by endoscopic hemostasis on admission for bleeding peptic ulcers were referred to 586 participating hospitals in Japan. We collected their data to compare the risk-adjusted length of stay (LOS) and in-hospital mortality of patients with and without diabetes mellitus within 30 days. Patients were divided into two groups: patients with diabetes mellitus (n=434) and patients without diabetes mellitus (n=4429). RESULTS: Mean LOS in patients with diabetes mellitus was significantly longer than those without diabetes mellitus (15.8 days vs. 12.5 days, p<0.001). Also, higher in-hospital mortality within 30 days was observed in patients with diabetes mellitus compared with those without diabetes mellitus (2.7% vs. 1.1%, p=0.004). Multiple linear regression analysis revealed that diabetes mellitus was significantly associated with an increase in risk-adjusted LOS. The standardized coefficient was 0.036 days (p=0.01). Furthermore, the analysis revealed that diabetes mellitus significantly increased the risk of in-hospital mortality within 30 days (odds ratio=2.285, 95% CI=1.161-4.497, p=0.017). CONCLUSION: This study demonstrated that presence of diabetes mellitus significantly influences the short-term clinical outcomes of patients with bleeding peptic ulcers.

Multivariate analysis of factors influencing medical costs of acute pancreatitis hospitalizations based on a national administrative database.

BACKGROUND: Little information is available on the analysis of medical costs of acute pancreatitis hospitalizations. AIM: This study aimed to determine the factors affecting medical costs of patients with acute pancreatitis during hospitalization using a Japanese administrative database. METHODS: A total of 7193 patients with acute pancreatitis were referred to 776 hospitals. We defined "patients with high medical costs" as patients whose medical costs exceeded the 90th percentile in medical costs during hospitalization and identified the independent factors for patients with high medical costs with and without controlling for length of stay. RESULTS: Multiple logistic regression analysis demonstrated that necrosectomy was the most significant factor for medical costs of acute pancreatitis during hospitalization. The odds ratio of necrosectomy was 33.64 (95% confidence interval, 14.14-80.03; p<0.001). Use of an intensive care unit was the most significant factor for medical costs after controlling for LOS. The OR of an ICU was 6.44 (95% CI, 4.72-8.81; p<0.001). CONCLUSION: This study demonstrated that necrosectomy and use of an ICU significantly affected the medical costs of acute pancreatitis hospitalization. These results highlight the need for health care implementations to reduce medical costs whilst maintaining the quality of patient care, and targeting patients with severe acute pancreatitis.

Effect of hospital volume on clinical outcome in patients with acute pancreatitis, based on a national administrative database.

OBJECTIVE: This study aimed to investigate the relationship between hospital volume and clinical outcome in patients with acute pancreatitis, using a Japanese national administrative database. METHODS: A total of 7007 patients with acute pancreatitis were referred to776 hospitals in Japan. Patient data were corrected according to the severity of acute pancreatitis to allow the comparison of risk-adjusted in-hospital mortality and length of stay in relation to hospital volume. Hospital volume was categorized based on the number of cases during the study period into low-volume (<10 cases), medium-volume (10-16 cases), and high-volume hospitals (HVHs, >16 cases). RESULTS: Increased hospital volume was significantly associated with decreased relative risk of in-hospital mortality in both patients with mild and those with severe acute pancreatitis. The odds ratios for HVHs were 0.424 (95% confidence interval [CI], 0.228-0.787; P = 0.007) and 0.338 (95% CI, 0.138-0.826; P = 0.017), respectively. Hospital volume was also significantly associated with shorter length of stay in patients with mild acute pancreatitis. The unstandardized coefficient for HVHs was -0.978 days (95% CI, -1.909 to -0.048; P = 0.039). CONCLUSIONS: This study demonstrated that hospital volume influences the clinical outcome in both patients with mild and those with severe acute pancreatitis.

Prevalence of type 2 diabetes among acute inpatients and its impact on length of hospital stay in Japan.

OBJECTIVE: The goal of this study was to determine the prevalence of type 2 diabetes among acute inpatients and evaluate its impact on the length of hospital stay in Japan. RESEARCH DESIGN AND METHODS: The discharge records of 2,120,170 acute inpatients who were 30 years old or older and discharged between July and December of 2008 were obtained from the Japanese administrative case-mix system, Diagnosis Procedure Combination (DPC), and allocated for analysis. Type 2 diabetes was defined by E11 of the ICD-10 coding system on patient records. Other types of diabetes, including type 1 diabetes and diabetes in pregnancy (defined by ICD-10 codes E10 E12-14 and O24, respectively) were excluded from the analyses. RESULTS: Type 2 diabetes was observed among 11.4% of the records, 9.9% of which were cases of diabetes as a comorbidity. Total length of hospital stay was 33,468,152 days, with diabetes patients occupying 13.9% of the total bed days. Patients with type 2 diabetes as a comorbidity had prolonged lengths of hospital stay compared to patients free from diabetes, and stratification by sex, age, surgical treatment, and disease category did not alter these results. The median length of hospital stay was 9 days among patients without diabetes and 13 days among patients with diabetes. CONCLUSION: Japanese acute health care is experiencing an epidemic of type 2 diabetes, with 1 out of 10 acute inpatients suffering from the disease. Complication of type 2 diabetes is associated with prolonged length of hospital stay.

A descriptive study evaluating the circumstances of medical treatment for acute pancreatitis before publication of the new JPN guidelines based on the Japanese administrative database associated with the Diagnosis Procedure Combination system.

PURPOSE: To examine the circumstances of medical treatment for acute pancreatitis before publication of the new Japanese (JPN) guidelines using the Japanese administrative database associated with the Diagnosis Procedure Combination system. METHODS: We collected data from 7,193 patients with acute pancreatitis in 2008 and examined the recommended medical treatment in the new JPN guidelines [from recommendations B (considered to be recommended treatments) to D (considered to be unacceptable treatments)] according to severity of acute pancreatitis. Patients were divided into two groups: mild cases (n = 6,520) and severe cases (n = 673). RESULTS: Enteral nutrition for severe cases without ileus (recommendation B) was uncommon (13.5%). In contrast, prophylactic antibiotics were administered in a large number (80.4%) of mild cases without acute cholangitis (recommendation D). Furthermore, administration of H(2) receptor antagonists, except for cases of upper gastrointestinal bleeding (recommendation D), were performed in many patients with both mild and severe cases (66.8 vs. 78.6%). CONCLUSIONS: This study demonstrated a discrepancy between actual medical treatment performed and the new JPN guidelines with regard to some of the medical treatments. Future studies are required after publication of the new JPN guidelines to determine how they affect medical treatments.

Profiling of the care processes for laryngeal cancer with the Japanese administrative database.

At present, there is a shortage of detailed data on head and neck cancer treatment in acute care hospitals in Japan. We conducted an analysis of the care process for laryngeal cancer inpatients in Japan using a national administrative database based on the case-mix system known as the Diagnosis Procedure Combination to evaluate the recent clinical situation of a relatively high incidence of head and neck cancers. We obtained discharge data relating to 2790 cases (one case = one hospitalization) involving 2319 laryngeal cancer patients from 346 acute care hospitals that participated in the Japanese national case-mix project between July and December of 2008. The details of their treatment procedures were analyzed according to the Japanese procedure codes managed by the Ministry of Health, Labour, and Welfare of Japan. There were 2156 male and 163 female patients. The median age was 69 years (range: 22-96 years). The most frequent surgical procedure was endoscopic resection which was performed for 781 cases. Chemotherapy was given in 31.6% of cases in the < 60 age group, 28.2% in the 60-79, and 14.1% in the ≥ 80. The most frequently used chemotherapy regimen was a single drug, S-1 (compound of tegafur, gimeracil and oteracil potassium), which was more frequently used in the ≥ 70 age group than in the younger age group. The Diagnosis Procedure Combination database, which collects a large volume of data from all over the country, is useful for analysis of the care process for head and neck cancers in Japan.

Equivalent clinical outcomes of bleeding peptic ulcers in teaching and non-teaching hospitals: evidence for standardization of medical care in Japan.

The clinical outcomes of treatments for several medical conditions are better in teaching hospitals than in non-teaching hospitals. However, there is only limited information for comparisons of the clinical outcomes of bleeding peptic ulcers between teaching and non-teaching hospitals. A total of 4,863 patients treated by endoscopic hemostasis on admission for bleeding peptic ulcers were evaluated in 586 hospitals of the Diagnosis Procedure Combination (DPC) system. We collected their data from the database associated with the DPC system to compare the risk-adjusted length of stay (LOS) and in-hospital mortality within 30 days with respect to the hospital characteristics. The hospitals were categorized into two groups: teaching hospitals that were certified by the Japanese Society of Gastroenterology (3,332 patients in 360 hospitals) and non-teaching hospitals (1,531 patients in 226 hospitals). There was no significant difference with regard to the mean LOS and the crude in-hospital mortality within 30 days between groups (p = 0.181 and 0.174, respectively). Multiple linear regression analyses revealed that the hospital characteristics were not associated with the risk-adjusted LOS. The standardized coefficient for non-teaching hospitals was 0.019 (p = 0.172). Multiple logistic regression analyses further showed no significant difference in the in-hospital mortality within 30 days (non-teaching hospitals, odds ratio = 1.35, 95% confidence interval = 0.786 - 2.319, p = 0.277). In conclusion, both teaching and non-teaching hospitals have equivalent qualities in management of bleeding peptic ulcers. These findings suggest that the standardization of medical treatments for bleeding peptic ulcers has become disseminated in Japan.

Total body irradiation followed by bone marrow transplantation: comparison of once-daily and twice-daily fractionation regimens.

PURPOSE: The purpose of this study was to evaluate the results of two sequential total body irradiation (TBI) regimens, especially focusing on pulmonary complications. MATERIALS AND METHODS: Patients with malignant disease who underwent TBI followed by bone marrow transplantation were retrospectively reviewed. There were 86 patients (51 males, 35 females). Altogether, 36 patients were treated on twice-daily fractions of 2 Gy for 3 days to a total 12 Gy (group A). Another 50 patients were treated on once-daily fractions of 2.4 or 3.0 Gy for 4 or 5 days to a total 12 Gy (group B). RESULTS: The 5-year overall survival rate was 49.2%, and relapse-free survival was 44.3%. There were no significant differences between the two groups regarding overall survival (P = 0.1237) or relapse-free survival (P = 0.1548). Two patients in group A had interstitial pneumonitis of grade 3 or higher severity compared with three patients in group B. There was no significant difference between patients in group A (5-year probability rate was 7.6%) and patients in group B (5-year probability rate was 13.9%) (P = 0.9519). CONCLUSION: We concluded that our once-daily TBI regimen is feasible and had the benefit of reducing the complexity of TBI. We believe that further investigation of the TBI regimen is needed.

White matter changes on magnetic resonance imaging following whole-brain radiotherapy for brain metastases.

PURPOSE: The purpose of this study was to evaluate white matter (WM) abnormalities induced by WBRT. MATERIALS AND METHODS: Twenty-four patients (11 men and 13 women; age range 38-74 years, median 60 years) who survived for more than 1 year after completion of WBRT (radiation dose range 30-40 Gy, median 35 Gy) at our institution between January 2000 and June 2003 were followed up with magnetic resonance (MR) scans for 11-51 months (median 19 months). We evaluated WM changes attributable to WBRT as grade 0-6 and assessed possible contributing factors by statistical analysis. RESULTS: WM changes were found in 20 patients: Eight were assessed as grade 2, three as grade 3, and nine as grade 5. In total, 12 patients developed grade 3 or higher WM changes. Age (<60 vs > or =60 years), sex, radiation dose (< or =35 vs >35 Gy), chemotherapy (with CDDP vs without CDDP), biologically effective dose (< or =120 vs >120 Gy1), and head width (<16.3 vs > or =16.3 cm) were found not to be relevant to the incidence or severity of the WM changes. CONCLUSION: Long-term survivors who have under-gone WBRT may have a higher incidence of WM abnormalities.

Treatment results of stage I oral tongue cancer with definitive radiotherapy.

The medical records of 133 patients with Stage I tongue cancer treated by definitive radiotherapy between 1966 and 2001 were reviewed. Overall survival rate (OS), progression free survival rate (PFS), and survival rate after recurrence were calculated according to the Kaplan-Meier method. We investigated prognostic factors for local control and risk factors of late neck LN metastasis. The 5-year OS was 81.8% and the 5-year PFS was 67.2%. The 5-year OS after local recurrence was 100% by salvage operation, and that after neck LN metastasis was 40.7% despite radical neck dissection. Tumor thickness over 5 mm and treatment without interstitial irradiation were prognostic factors for local control. Tumor diameter over 15 mm and tumor thickness over 5 mm were risk factors of late neck LN metastasis. We should consider prophylactic treatment for neck LN for high risk patients with Stage I tongue cancer in order to improve treatment results further.