Antithrombin III for portal vein thrombosis in patients with liver disease: A randomized, double-blind, controlled trial.

AIM: Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT-III). We designed this randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of AT-III for PVT in liver disease patients with those who received no treatment. METHODS: Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross-sectional lumen of the portal vein. Patients with 70% or less serum level of AT-III were included. The study drug was given up to three times in a 5-day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five-grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT-III group and 37 patients to the placebo group. RESULTS: The proportion of patients with complete response or partial response of PVT was significantly higher in the AT-III group (55.6%; 20/36 patients; 95% confidence interval, 38.1-72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2-36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups. CONCLUSION: Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT-III.

Short-Term Safety and Efficacy of Balloon-Occluded Retrograde Transvenous Obliteration Using Ethanolamine Oleate: Results of a Prospective, Multicenter, Single-Arm Trial.

PURPOSE: To evaluate 90-day outcomes after balloon-occluded retrograde transvenous obliteration (BRTO) with ethanolamine oleate (EO) in patients with gastric varices (GVs). MATERIALS AND METHODS: An 8-site prospective single-arm clinical trial was conducted. Patients who had endoscopically confirmed GVs with a gastrorenal shunt were eligible for the study. Overnight BRTO was performed, and efficacy was evaluated by endoscopy and contrast-enhanced computed tomography (CT). RESULTS: Forty-five patients (26 men and 19 women; mean age, 67.8 y) were enrolled. The complete regression rate of GVs based on endoscopic images on day 90 was 79.5% (35 of 44 patients; 95% confidence interval, 64.7%-90.2%). The rate of complete thrombosis of GVs based on contrast-enhanced CT on day 90 was 93.0% (40 of 43 patients; 95% confidence interval, 80.9%-98.5%). One patient experienced 2 events of bleeding from GVs, which was different from the GVs treated with BRTO. Appearance of new esophageal varices (EVs) or worsening of existing EVs occurred in 16 of 45 patients (35.6%). Forty-four of 45 patients (97.8%) experienced adverse events (AEs) related to EO, which included fever in 24 (53.3%), hematuria in 23 (51.1%), hemolysis in 16 (35.6%), back pain in 16 (35.6%), and abdominal pain in 10 (22.2%). One case of moderate to severe ascites (2.3%) was observed on day 90. One case of sepsis was the only serious AE observed in relation to EO. CONCLUSIONS: The present study demonstrates that BRTO with EO for the treatment of GVs is a clinically effective procedure with many mild to moderate AEs.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

11C-Choline positive but 18F-FDG negative pancreatic metastasis from renal cell carcinoma on PET.

Choline is a new PET tracer, which uptake may occur via a choline-specific transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.

Radiotherapy in late elderly (aged 75 or older) patients with paranasal sinus carcinoma: a single institution experience.

The purpose of our study was to assess the feasibility of radiotherapy (RT) for locally advanced paranasal sinus carcinomas in late elderly patients (aged ≥75 years) from a single institution in Japan. From 2000 to 2015, we retrospectively analyzed 14 patients (11 maxillary and 3 ethmoid sinus carcinoma patients) who underwent RT for pathologically confirmed paranasal sinus carcinomas. RT was performed without unexpected cessations. Two patients, however, developed Grade 3 mucositis. The median follow-up duration was 13 months (range 2-54 months). The 1- and 2-year overall survival (OS) rates were 81.8 and 54.5 %, respectively. The local response rate after the initial treatment was 85.7 %. The 1- and 2-year progression-free survival (PFS) rates were 46.2 and 24.8 %, respectively. Univariate analysis of different clinicopathological parameters was conducted to identify associations with OS and PFS. We demonstrated that intensity modulated radiation therapy (IMRT) of >60 Gy with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy led to improved OS and PFS rates, although no statistical significance was observed. Moreover, none of the squamous cell carcinoma (SCC) patients who received 33 fractions of 66 Gy in IMRT died during the median follow-up period of 13 months (range 12-25 months). In conclusion, RT with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy can be considered an effective, well-tolerated, and feasible treatment option for late elderly patients with paranasal sinus carcinomas. In addition, >60 Gy of RT in IMRT led to improved survival outcomes in elderly paranasal sinus carcinoma patients.

Association between ¹8F-FDG uptake and molecular subtype of breast cancer.

PURPOSE: To determine whether (18)F-FDG uptake in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes. METHODS: This retrospective study involved 306 patients with 308 mass-type invasive breast cancers (mean size 2.65 cm, range 1.0-15.0 cm) who underwent (18)F-FDG PET/CT before therapy. The correlations between primary tumour (18)F-FDG uptake on PET/CT, expressed as SUVmax, and clinicopathological findings and molecular subtype, i.e. luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-positive and triple-negative, were analysed. The predictors of these subtypes were investigated. RESULTS: The mean SUVmax of the 308 tumours was 5.33 ± 3.63 (range 1.15-19.01). Among the subtypes of the 308 tumours, 87 (28.2 %) were luminal A, 111 (36.0 %) were luminal B (HER2-negative), 31 (10.1 %) were luminal B (HER2-positive), 26 (8.4 %) were HER2-positive and 53 (17.2 %) were triple-negative, and the corresponding mean SUVmax were 3.41 ± 2.07 (range 1.18-14.30), 5.17 ± 3.52 (range 1.35-19.01), 6.57 ± 3.84 (range 1.42-15.58), 7.55 ± 3.63 (range 2.30-13.60) and 6.97 ± 4.17 (range 1.15-16.06), respectively. A cut-off value of 3.60 yielded 70.1 % sensitivity and 66.1 % specificity with an area under the receiver operating characteristics curve (AUC) of 0.734 for predicting that a tumour was of the luminal A subtype. A cut-off value of 6.75 yielded 65.4 % sensitivity and 75.2 % specificity with an AUC of 0.704 for predicting a HER2-positive subtype. CONCLUSION: SUVmax, a metabolic semiquantitative parameter, shows a significant correlation with the molecular subtype of breast cancer, and is useful for predicting the luminal A or HER2-positive subtype.

Hepatic arterial infusion chemotherapy with fine-powder cisplatin and iodized-oil suspension in patients with intermediate-stage and advanced-stage (Barcelona Clinic Liver Cancer stage-B or stage-C) hepatocellular carcinoma: multicenter phase-II clinical study.

PURPOSE: This single-arm, multicenter, phase-II trial evaluated the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) using fine-powder cisplatin and iodized-oil suspension in patients with intermediate- and advanced-stage [Barcelona Clinic Liver Cancer (BCLC) stage-B and stage-C] hepatocellular carcinomas (HCCs). METHODS: The Institutional Review Board approved this study and patients provided written informed consent. Thirty-five patients (24 men and 11 women, mean 74 ± 6 years [range 60-87 years]) with BCLC stage-B (57 %, 20/35) or stage-C (43 %, 15/35) HCCs who were not candidates for other locoregional treatments were enrolled. HAIC was performed using a suspension of fine-powder cisplatin with a maximum dose of 65 mg/m(2) and iodized oil on demand. The primary endpoint was the response rate evaluated based on Response Evaluation Criteria in Solid Tumor (RECIST) and modified RECIST (mRECIST). Secondary endpoints were overall survival, progression-free survival, and safety. RESULTS: The initial and best overall response rates at 4 weeks and 3 months, respectively, were 14 and 17 % based on RECIST, and 57 and 23 % based on mRECIST. The median overall and progression-free survival times were 18 and 4 months, respectively. The most frequent grade-3 or grade-4 adverse events were elevation of serum alanine (23 %) and aspartate aminotransferase (20 %), and thrombocytopenia (17 %). CONCLUSION: This HAIC provides promising therapeutic effects with acceptable safety to patients with intermediate-stage and advanced-stage HCCs.

Nationwide survey in Japan regarding splenectomy/partial splenic embolization for interferon treatment targeting hepatitis C virus-related chronic liver disease in patients with low platelet count.

AIM: In chronic liver disease associated with hepatitis C virus (HCV), a low platelet count is a major obstacle in carrying out interferon (IFN) treatment. We used a questionnaire to clarify the extent to which splenectomy/partial splenic embolization (PSE) is performed before IFN treatment, as well as the efficacy and complications thereof. METHODS: Two questionnaires were distributed to 413 medical institutes in Japan specializing in the treatment of liver diseases, and responses were obtained from 204 institutes. Furthermore, a more detailed questionnaire was completed by 10 institutes that experienced cases of death. RESULTS: In patients with HCV genotype 1b and a high viral load (HCV1b/High), the sustained viral response (SVR) rate was 28% for the splenectomy group and 22% for the PSE group, with no significant difference between these groups. In patients that were not HCV1b/High, the SVR rate was higher in those that underwent splenectomy (71%) compared to the PSE group (56%; P = 0.025). There were cases of death in seven of 799 splenectomy cases (0.89%) and four of 474 PSE cases (0.84%). Infectious diseases were involved in nine of 11 cases of death, with a peculiar patient background of Child-Pugh B (6/10) and an age of 60 years or greater (7/11). CONCLUSION: The application of splenectomy/PSE before IFN treatment should be avoided in patients with poor residual hepatic function and/or elderly patients. In HCV1b/High patients, splenectomy/PSE should be performed only after selecting those in which IFN treatment should be highly effective.

Phase II trial on neoadjuvant intravenous and trans-uterine arterial chemotherapy for locally advanced bulky cervical adenocarcinoma.

OBJECTIVE: A phase II trial on neoadjuvant trans-uterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy (RH) was conducted for patients with bulky cervical adenocarcinoma (AC). METHODS: Tumors of >4 cm were eligible. The neoadjuvant regimen comprised paclitaxel (60 mg/m(2) intravenously on days 1, 8, and 15) and cisplatin (70 mg/m(2) TUAC followed by transcatheter embolization with gelatin sponge particles on day 2) repeated every 3 weeks for 3 cycles. The primary endpoints were clinical and pathological responses. RESULTS: Twenty-two patients (median age, 51 years; range, 33-75 years) were enrolled. The International Federation of Gynecology and Obstetrics stages were IB2 (9 patients), IIA-IIB (8), IIIB (3), and IVA (2). The adeno/adenosquamous ratio was 16/6. The overall clinical response rate was 95.4% (95% confidence interval [CI], 86.7-100%). RH was completed in 19 patients (86%), including 2 stage IVA patients who underwent anterior or posterior pelvic exenteration. Of the 19 patients, no residual malignant cells were found pathologically in 4; thus, the pathological complete response rate was 18% (4/22). No patients experienced grade 4 thrombocytopenia or febrile neutropenia or required platelet transfusions. The 5-year progression-free survival and overall survival rates in stages IB2-IIB were 70.0% (95%CI, 48.1-92.1%) and 69.5% (95%CI, 47.0-92.0%), respectively. The 2 patients with stage IVA tumors were alive without recurrence for 72 and 84 months after enrollment. CONCLUSIONS: TUAC showed high clinical and pathological response rates. TUAC is promising for stage IB2-IIB and IVA bulky AC.

Prognostic factors for locally advanced cervical cancer treated with neoadjuvant intravenous and transuterine arterial chemotherapy followed by radical hysterectomy.

OBJECTIVE: The aim of this study was to identify prognostic factors associated with neoadjuvant transuterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy. METHODS: The medical histories of patients with stage IB2 to IIB cervical cancer who received neoadjuvant TUAC between 1996 and 2009 at our institution were retrospectively reviewed. RESULTS: Seventy-three patients received TUAC using cisplatin combined with intravenous nedaplatin, irinotecan, paclitaxel, or etoposide administration. Forty-seven patients (64%) had squamous cell carcinoma. The radiological response rate was 96% (95% confidence interval, 91%-100%). Radical hysterectomy was completed for 95% of enrolled patients. Examination of the resected cervical specimens showed that tumor cells were absent in 19 cases and stromal invasion was less than 3 mm in 7 cases. Among these 26 patients, 23 (32%) had pathologically negative pelvic lymph nodes and no recurrence during the follow-up period. The 5-year relapse-free survival and overall survival rates were 69% and 74%, respectively. Among 23 patients with recurrence or progressive disease, the median survival time after recurrence or progression was 12 months. In multivariate analysis, a tumor size of more than 60 mm and pathological positive lymph nodes were negative prognostic factors for overall survival. CONCLUSIONS: Tumor size, pathological response, and lymph node metastases were prognostic factors for cervical cancer. The high pathological response rate associated with TUAC makes it a promising treatment for bulky cervical cancer.

Fertility-sparing management for bulky cervical cancer using neoadjuvant transuterine arterial chemotherapy followed by vaginal trachelectomy.

BACKGROUND: Fertility-sparing management for bulky cervical cancer remains under investigation. We investigated the safety of neoadjuvant transuterine arterial chemotherapy (TUAC) followed by a simple vaginal trachelectomy for patients with tumors larger than 3 cm in diameter who desired uterine preservation. METHODS: First, to assess the safety and efficacy of TUAC, survival and pathological complete response data from 39 patients with a diagnosis of stage IB2 to stage IIB cervical cancer who participated in 2 consecutive trials during 1997-2006 were analyzed. The neoadjuvant chemotherapy regimens were a combination of TUAC using cisplatin with intravenous nedaplatin or irinotecan. Second, to assess the safety of fertility-sparing management with TUAC, medical records of patients matching the following criteria were reviewed during the same period: (1) International Federation of Gynecology and Obstetrics stages IB1 to IIA; (2) maximum diameter of tumor, 3 cm or more; (3) squamous cell carcinoma; (4) no radiological findings of lymph node metastasis; and (5) patient's strong desire for preservation of the uterus and to undergo TUAC. RESULTS: The overall 5-year survival rate of the 39 enrolled patients was 81.0% (95% confidence interval, 64.8%-93.7%). No malignant cells were found in pathologically examined surgical specimens from 14 patients (35.9%), all of whom were alive without recurrence for more than 7 years after treatment. Based on medical records, 7 patients were eligible according to the fertility-sparing criteria, 1 patient with International Federation of Gynecology and Obstetrics stage IB1 cancer, 5 patients with stage IB2, and 1 patient with stage IIA. One patient with stage IB1 cancer and 2 patients with stage IB2 cancer underwent simple vaginal trachelectomy, resection of paracervical tissues, and abdominal lymphadenectomy. Their disease-free intervals were 86, 120, and 65 months, respectively. All 3 patients had regular menses after surgery but no pregnancies, for personal reasons unrelated to fertility. CONCLUSIONS: Powerful neoadjuvant chemotherapy regimens resulted in a pathological complete response. Long-term disease-free interval was achieved after fertility-sparing management for bulky cervical cancer in 3 cases.

[The protocol of dose reduction in liver perfusion computed tomography].

Cerebral perfusion computed tomography (CT) has been widespread, but abdominal perfusion CT has not been very popular because there has been a problem with regard to the limit of irradiation range and respiratory effects. Recently, it became easy to perform perfusion of abdominal organs because the use of multi detector row CT (MDCT) has been extensive. Along with it, the number of hospitals that perform liver perfusion CT has increased. However, patient dose of the liver perfusion CT is very high, making it very important to reduce patient dose. We created the virtual data that reduced the number of irradiation by partly reducing the data obtained on the liver perfusion CT. We compared the analysis results of all data with that of the partly reduced. It is possible to reduce the patient dose by reducing the number of irradiation because there was no significant difference in the analysis results.

The skill qualification system for portal hypertension in Japan.

Objectives: The diverse treatments available for portal hypertension require specialized knowledge of hemodynamics and include endoscopic treatments, interventional radiology (IVR), and surgery. The Japan Society for Portal Hypertension has developed the skill qualification system (SQS) for portal hypertension and began examination in 2014. Here, the status and validity of the judgment of the SQS examination were evaluated. Methods: From 2014 to 2020, 79 applicants were evaluated by the SQS for portal hypertension. Each unedited video submitted as a candidate procedure was evaluated by two judges, and a grade of greater than 70% for the scoring items assessed by the judges was required to pass the examination. Inter-rater agreement of success/failure between the two judges was investigated by the AC1 coefficient. Results: The results of two judges differed for 11 of the 79 videos (13.9%), and five applicants (6.3%) ultimately failed the examination. The percentages of total points received by the applicants with endoscopic treatments, IVR, and surgery were 87.3%, 79.4%, and 80.8%, respectively. There were significant differences in the percentages between endoscopic treatments and IVR (P = 0.0015). The AC1 coefficients were 0.84 for the applicants overall, 0.93 for endoscopic treatments, 0.66 for IVR, and 0.72 for surgery. Similarly, there were significant differences in the AC1 coefficient between endoscopic treatments and IVR (P = 0.021). Conclusions: The SQS for portal hypertension of the Japan Society for Portal Hypertension showed high reliability for video assessments by the judges. This system may contribute to the spread and further development of safe and effective treatments for portal hypertension in Japan.

Balloon-occluded retrograde transvenous obliteration of varices: focusing on the portal hemodynamics and the recent techniques.

PURPOSE: To evaluate the recent topics of Ballloon-occluded retrograde trasnvenous obliteration(B-RTO). METHOD: We overviewed the recent scientific papers regarding B-RTO. RESULT: B-RTO is a treatment method for occluding varices retrogradely using a sclerosing agent under balloon occlusion of a major draining vein. It has been recognized as an effective treatment method for gastric varices. Hepatic function reserve is improved and liver volume is increased after B-RTO. In recent years, various technical options, such as plug-assisted retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration, or foam B-RTO, have also been reported. In performing B-RTO, portal hemodynamics must be thoroughly examined radiologically. Judging the classification of the grade of collateral venous hemodynamics is important to select the appropriate embolization technique of B-RTO and to successfully occlude varices. Finally, the word "portosystemic shunt syndrome" has been proposed and the condition should be considered while selecting a treatment for gastric varices. CONCLUSION: B-RTO is effective for gastrointestinal varices and portosystemic shunts.

Radiological anatomy of spontaneous splenorenal shunts in patients with chronic liver disease.

PURPOSE: We evaluated anatomical variations of spontaneous splenorenal shunt (SSRS) and the prevalence of portosystemic shunts in patients with chronic liver disease by CT. MATERIALS AND METHODS: A total of 451 patients with chronic liver disease underwent contrast-enhanced computed tomography between October 2010 and April 2011. The prevalence of portosystemic shunts including SSRS and gastrorenal shunt, and the frequency of hepatic encephalopathy were examined. The course of the shunt and the point of confluence with the renal vein of the SSRS were analyzed. RESULTS: SSRSs or gastrorenal shunts were found in 11.1 and 5.0% of the patients, respectively. Anatomical variations were classified into three types according to the point of confluence as follows: type 1 = the SSRS joined the inferior phrenic vein (n = 33), type 2 = the SSRS joined the gonadal vein (n = 7), and type 3 = the SSRS joined the left renal vein (n = 14). The course of the SSRS from the splenic hilum was classified as medial (n = 46), posterior (n = 2), or anterolateral (n = 2). CONCLUSIONS: SSRSs were classified into three types depending on the confluence point with the renal vein, and into three types of course. These findings are useful for preoperative information.

Changes in liver perfusion and function before and after percutaneous occlusion of spontaneous portosystemic shunt.

PURPOSE: To evaluate changes in liver perfusion after occlusion of spontaneous portosystemic shunt and to analyze mechanisms of liver profile improvement. MATERIALS AND METHODS: Liver function changes and portal venous and hepatic arterial blood flow were evaluated using perfusion CT before and after shunt occlusion in 23 patients who underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n = 15) or hepatic encephalopathy (n = 8). RESULTS: Portal venous blood flow was significantly higher at 1 week (278.7 ml/min, 92.7-636.7, p = 0.012), 1 month (290.0 ml/min, 110.1-560.1, p < 0.001) and 3 months (299.6 ml/min, 156.7-618.5, p = 0.033) after shunt occlusion than the baseline (220.9 ml/min, 49.5-566.7). Hepatic arterial liver blood flow became lower than the baseline (132.3 ml/min, 47.9-622.3) after shunt occlusion, but a significant decrease was observed only at 1 month later (107.9 ml/min, 45.8-263.6 p = 0.027). Serum albumin concentration became significantly higher than the baseline (3.4 mg/dl, 1.9-4.5) at 1 month (3.8 mg/dl, 2.3-4.3, p = 0.018) and 3 months (3.9 mg/dl, 2.6-4.3, p = 0.024) after shunt occlusion. CONCLUSION: Shunt occlusion increases portal venous blood flow and decreases hepatic arterial blood flow, thereby improving the liver profile.

Pravastatin reduces radiation-induced damage in normal tissues.

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

Prognostic value of pretreatment volume-based quantitative 18F-FDG PET/CT parameters in patients with malignant pleural mesothelioma.

PURPOSE: To investigate the relationships between pretreatment volume-based quantitative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: We retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment 18F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test. RESULTS: The median follow-up was 15 months (range, 1-96 months; median, 17 months). In a univariate analysis of all patients, older age (p<0.05), high EORTC score (p<0.001), non-epithelioid histological subtype (p<0.001), high T stage (p<0.001), positive N/M status (p<0.05, p<0.001), advanced TNM stage (p<0.001), non-surgical treatment (p<0.001), and high SUVmax (p<0.001), MTV (p<0.001), or TLG (p<0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14-2.48; p<0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34-0.95; p<0.05), and high TLG (HR: 1.97, 95% CI: 1.14-3.44; p<0.05) as independent negative predictors. CONCLUSIONS: Pretreatment volume-based quantitative 18F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.

A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia.

BACKGROUND: Acotiamide is widely used to improve symptoms in patients with functional dyspepsia (FD) in multiple large-scale clinical studies, but there are few reports about the drug's mechanism of action. The aim of this study was to assess the effects of acotiamide on gastric accommodation and gastric emptying, gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a placebo-controlled study. METHODS: We conducted a randomized, double-blind placebo-controlled study. Fifty Japanese FD patients were randomly assigned to either placebo (n = 25) or acotiamide 100 mg × 3/day for 2 weeks (n = 25). At baseline and at 2 weeks of treatment, we evaluated the patients' gastric motility using scintigraphy to determine the accommodation and emptying values, gastrointestinal symptom rating scale (GSRS), HR-QOL (SF-8), and anxiety and depression scale (HADS). RESULTS: Four patients failed to complete the medication regimen and were omitted from analysis; data from 24 placebo patients and 22 acotiamide patients were analyzed. Acotiamide significantly increased gastric accommodation compared to the placebo (p = 0.04 vs. p = 0.08; respectively). Acotiamide significantly accelerated gastric emptying (50 % half-emptying time) (p = 0.02 vs. p = 0.59). Acotiamide significantly improved the total GSRS scores compared to placebo (p = 0.0007 vs. p = 0.14). HR-QOL did not differ significantly between the two groups, but acotiamide significantly improved the HADS anxiety score compared to placebo (p = 0.04 vs. p = 0.20). CONCLUSIONS: Our placebo-controlled study demonstrated that acotiamide significantly increased both gastric accommodation and gastric emptying in Japanese FD patients. Acotiamide also improved the patients' dyspeptic symptoms and anxiety score. Clinical Trials Registry no: UMIN000013544.