Effect of Donor Age on Graft Function and Pathologic Findings in Living Donor Transplantation.

BACKGROUND: The frequency of renal transplants from elderly living donors has increased because of a shortage of donors. However, the results of renal transplantation using aged kidney grafts have yet to be determined conclusively. METHODS: We evaluated 45 patients who underwent living donor kidney transplantation at our institution. The patients were categorized according to donor age at the time of the transplant: ≥ 60 years (elderly donor group, n = 21) and <60 years (young donor group, n = 24). We reviewed the renal function of the recipients and pathologic findings of the graft including interstitial fibrosis score, tubular atrophy score, tubular atrophy and interstitial fibrosis grades, and arteriosclerosis up to 2 years posttransplantation. RESULTS: Significant differences were observed in the preoperative creatinine clearance of the donor, prevalence of hypertension in the donor, and age of the recipient. Serum creatinine levels in the elderly donor group were significantly higher from 2 months to 1 year posttransplantation, and the estimated glomerular filtration rate was significantly lower from 7 days to 1 year posttransplantation. However, the decline in estimated glomerular filtration rate from 14 days to up to 2 years posttransplantation was similar in the 2 groups. There was no significant difference in the renal biopsy findings between the 2 groups except for arteriosclerosis 1 year posttransplantation. CONCLUSION: Kidney grafts from elderly living donors were not associated with a deterioration in renal function, and their pathologic findings were comparable with those of young donors for up to 2 years posttransplantation.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer.

BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).

Molecular Biomarker Study in a Randomised Phase III Trial of Irinotecan Plus S-1 versus S-1 for Advanced Gastric Cancer (GC0301/TOP-002).

AIMS: Gastric cancer is a common and heterogeneous disease; however, global standard and biomarkers for selecting chemotherapy regimens have not been established. This study was designed retrospectively to identify molecular biomarkers for irinotecan plus S-1 (IRI-S) and S-1 therapy from subset analyses in GC0301/TOP-002, a randomised phase III trial for advanced gastric cancer. MATERIALS AND METHODS: Paraffin-embedded primary tumour specimens were collected from 126 of 326 randomised patients in GC0301/TOP-002. The mRNA was measured for thymidylate synthase, dihydropyrimidine dehydrogenase, topoisomerase I, excision repair cross-complementing gene 1 (ERCC1) and thymidine phosphorylase; categorised into low and high to analyse their association with efficacy end points. RESULTS: There was no significant difference in each mRNA between S-1 and IRI-S groups, whereas there were differences among some clinical characteristics. Multivariate analyses for overall survival showed that mRNA levels were not correlated with prognosis. By comparison, between IRI-S and S-1 arms, low thymidylate synthase, low ERCC1 and high thymidine phosphorylase were associated with better prognosis for IRI-S versus S-1 (hazard ratio = 0.653, 0.702 and 0.709, respectively; P < 0.15 for each interaction). CONCLUSION: Low thymidylate synthase, low ERCC1 and high thymidine phosphorylase are candidates for predictive biomarkers for first-line treatment in advanced gastric cancer by IRI-S. Further study is warranted to confirm these results in other clinical trials and cohort studies.

A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors.

PURPOSE: Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors. METHODS: This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients. RESULTS: Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition. CONCLUSIONS: Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D.

Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia.

Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05).

BACKGROUND: In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC. PATIENTS AND METHODS: Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS). RESULTS: From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group. CONCLUSION: The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

The utility of intra-operative three-dimensional transoesophageal echocardiography for dynamic measurement of stroke volume.

Measurement of left ventricular stroke volume and cardiac output is very important for managing haemodynamically unstable or critically ill patients. The aims of this study were to compare stroke volume measured by three-dimensional transoesophageal echocardiography with stroke volume measured using a pulmonary artery catheter, and to examine the ability of three-dimensional transoesophageal echocardiography to track stroke volume changes induced by haemodynamic interventions. This study included 40 cardiac surgery patients. Haemodynamic variables were measured before and 2 min after haemodynamic interventions, which consisted of phenylephrine 100 µg or ephedrine 5 mg. We used Bland-Altman analysis to assess the agreement between the stroke volume measured by three-dimensional transoesophageal echocardiography and by the pulmonary artery catheter. Polar-plot and 4-quadrant plot analyses were used to assess the trending ability of three-dimensional transoesophageal echocardiography compared with the pulmonary artery catheter. Bias and percentage error were -1.2 ml and 20%, respectively. The concordance rate in the 4-quadrant analysis after phenylephrine and ephedrine administration was 75% and 84%, respectively. In the polar-plot analysis, the angular concordance rate was 66% and 73% after phenylephrine and ephedrine administration, respectively. Three-dimensional transoesophageal echocardiography was clinically acceptable for measuring stroke volume; however, it was not sufficiently reliable for tracking stroke volume changes after haemodynamic interventions.

Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.

BACKGROUND: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease. RESULTS: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%). CONCLUSION: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS. CLINICAL TRIAL NUMBER: JapicCTI-101021.

Preoperative hydroperoxide concentrations are associated with a risk of postoperative complications after cardiac surgery.

This study aimed to assess whether preoperative oxidative stress levels can predict postoperative complications in patients undergoing cardiac surgery. Ninety-five cardiac surgery patients received an assessment of preoperative oxidative stress by measurement of hydroperoxide values in blood via the d-Rom test. Area under the receiver operating characteristic curve and also multivariate logistic regression were used to evaluate the prognostic significance of preoperative hydroperoxide concentrations in predicting the occurrence of major organ morbidity and mortality (MOMM). MOMM included death, deep sternal infection, reoperation, stroke, renal failure requiring haemodialysis and prolonged ventilation (>48 hours). The ability of preoperative hydroperoxide concentrations to predict MOMM was not significantly different from that of the European system for cardiac operative risk evaluation (EuroSCORE) (area under the receiver operating characteristic curve 0.822 versus 0.821 respectively, P=0.983). The optimal threshold value of hydroperoxide concentration to differentiate between patients with and without MOMM was 450 UCarr (sensitivity, 87.0%; specificity, 81.9%). Duration of intensive care unit stay, mechanical ventilation time and hospital stay were significantly longer in patients with preoperative hydroperoxide concentrations ≥450 UCarr (H group) compared to those patients with preoperative hydroperoxide concentrations <450 UCarr (L group). An increase in preoperative hydroperoxide concentrations remained associated with an increased risk of MOMM (odds ratios: 1.01, 95% confidence interval: 1.00 to 1.03) and prolonged intensive care unit stay (odds ratio 1.01, 95% confidence interval: 1.00 to 1.02), after adjusting for age, gender and EuroSCORE. In conclusion, an increased hydroperoxide concentration before cardiac surgery is an independent risk factor for severe postoperative complications.

Usefulness of monitoring cell-mediated immunity for predicting post-kidney transplantation viral infection.

BACKGROUND: Monitoring cell-mediated immunity (CMI) can be used to estimate the risk of viral infections in kidney transplant recipients. The Immuknow (IMK) assay measures CD4(+) T-cell adenosine triphosphate activity, assesses patient CMI status, and assists clinicians in determining the risk of viral infection. METHODS: We retrospectively analyzed 224 IMK values in 39 kidney transplant recipients at our institution from April 2012 to January 2013. We analyzed the relationship between IMK value and viral infection during the early and late post-transplantation periods. Multiple regression analyses were performed, to determine which factors impacted the results of the IMK assay. RESULTS: Eight patients developed viral infections, including BK virus, cytomegalovirus, herpes simplex, and shingles. Five infections occurred in the early post-transplantation period (<50 d) and 3 in the late period (>120 d). The IMK levels in patients who developed an infection in the early period were within normal limits; however, those in the late period were significantly lower than 200 ng/mL (421.0 ± 062.6 for early vs 153.7 ± 72.7 for late; P = .02). Our multiple regression analyses indicated that peripheral white blood cell and neutrophil counts affected IMK values (P = .03 and P = .02, respectively). CONCLUSIONS: The IMK assay is a useful test for identifying patients at risk for post-transplantation viral infections in the late transplant period.

Comparative responsiveness of the Hand 20 and the DASH-JSSH questionnaires to clinical changes after carpal tunnel release.

This study compared the responsiveness of the Hand 20 and the Japanese version of the disabilities of the arm, shoulder and hand (DASH-JSSH) questionnaires in carpal tunnel syndrome. The scores before and 3 months after surgery were used to calculate the standardized response mean and effect size. Of 57 patients enrolled in the study, 13 underwent open carpal tunnel release and 44 had endoscopic carpal tunnel release. The standardized response mean and the effect size of the Hand 20 scale were 0.60 and 0.54, respectively, and those of the disabilities of the arm, shoulder and hand scale were 0.39 and 0.36, respectively. Compared with the Disabilities of the Arm, Shoulder and Hand questionnaire, the Hand 20 questionnaire appears to have better responsiveness for assessing the effect of treatment by carpal tunnel release.

Systemic vascular resistance has an impact on the reliability of the Vigileo-FloTrac system in measuring cardiac output and tracking cardiac output changes.

BACKGROUND: The aim of this study was to examine the ability of the Vigileo-FloTrac system to measure cardiac output (CO) and track changes in CO induced by increased vasomotor tone, under different states of systemic vascular resistance (SVR). METHODS: Forty patients undergoing cardiac surgery were enrolled. Haemodynamic variables including CO measured by the Vigileo-FloTrac system (version 3.02) (APCO), CO measured by a pulmonary artery catheter (ICO), and SVR index (SVRI) were recorded before (T1) and 2 min after (T2) phenylephrine administration (100 µg). Bland and Altman analysis was used to compare ICO and APCO at T1. We used four-quadrant plots and polar plots to compare the trending abilities between ICO and APCO. Patients were divided into three groups according to the SVRI value at T1, with low (<1200 dyn cm(-5) m(2)), normal (1200-2500 dyn cm(-5) m(2)), and high (>2500 dyn cm(-5) m(2)) SVRI states. RESULTS: A total of 155 paired data were collected. The adjusted percentage error was 46.3%, 26.4%, and 61.4%, and the concordance rate between ΔICO and ΔAPCO was 67.5%, 28.8%, and 7.7% in the low, normal, and high SVRI state, respectively. The polar plot analysis showed that the mean angular bias was -22.3°, -46.0°, and -3.51°, and the radial limits of agreement were 70°, 85°, and 87°, in the low, normal, and high SVRI state, respectively. CONCLUSIONS: These results indicate that the reliability of the Vigileo-FloTrac system to measure CO and track changes in CO induced by phenylephrine administration was not clinically acceptable.

Transversus abdominis plane block in combination with general anesthesia provides better intraoperative hemodynamic control and quicker recovery than general anesthesia alone in high-risk abdominal surgery patients.

BACKGROUND: Patients with severe cardiovascular disease are frequently hemodynamically unstable during abdominal surgery. Improving the safety of such patients by stabilizing intraoperative hemodynamics remains a major concern for anesthesiologists. Transversus abdominis plane (TAP) block in combination with general anesthesia may facilitate optimum anesthetic management of these high-risk patients. METHODS: Patients with cardiovascular disease classified as American Society of Anesthesiologists (ASA) physical status 3 were enrolled. The patients were undergoing elective abdominal surgery and were randomized to a group receiving general anesthesia and TAP block (Group T, N.=33) or a group receiving general anesthesia alone (Group G, N.=35). We compared the groups for intraoperative hemodynamic stability, anesthesia emergence time, amounts of anesthetics and opioids given, and frequency of emergency treatment with cardiovascular agents. A preliminary study demonstrated that systolic blood pressure and heart rate were maintained stable within 70-110% of their preanesthesia values throughout surgery in ASA 1 elderly patients without cardiovascular disease. Thus, the hemodynamically stable time was defined as the time when systolic blood pressure and heart rate were 70-110% of their preanesthesia values. The ratio of hemodynamically stable time to total operative time was used as an index of hemodynamic stability. RESULTS: The median (minimum-maximum) percentage of hemodynamically stable time was longer in Group T (91[50-100]%) than Group G (79[40-91]%, P<0.01). The mean sevoflurane concentration, amount of fentanyl given and frequency of vasopressor use were lower in Group T than Group G (P<0.05). Anesthesia emergence time was shorter in Group T (14[4-30] min) than Group G (18[9-52] min, P<0.01). No worsening of cardiovascular complications was observed. CONCLUSION: For abdominal surgery in patients with severe cardiovascular disease, combining TAP block with general anesthesia promotes intraoperative hemodynamic stability and early emergence from anesthesia.

Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage.

BACKGROUND: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. OBJECTIVE: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. METHODS: Thrombocytopenia (platelets < 50 000 µL(-1)) was induced in rabbits by repeated blood withdrawal (100 mL kg(-1) in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. RESULTS: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24 h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25 000 platelets µL(-1)), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. CONCLUSIONS: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

Apparent diffusion coefficient calculated with relatively high b-values correlates with local failure of head and neck squamous cell carcinoma treated with radiotherapy.

BACKGROUND AND PURPOSE: Few studies have investigated the relationship between ADC and clinical outcome in HNSCC. Our hypothesis has that relatively high pretreatment ADC would correlate with local failure of HNSCC treated with radiation therapy. MATERIALS AND METHODS: This includes prospective and validation studies. Seventeen patients treated with radiation therapy for primary HNSCC completed the prospective study. Variables considered to affect local failure including MR imaging-related parameters such as ADC and its change ratio were compared between patients with local failure and controls, and those showing difference or association with local failure were further tested by survival analysis. Furthermore, variables were analyzed in 40 patients enrolled in the validation study. RESULTS: Relatively high ADC calculated with b-values (300, 500, 750, and 1000 s/mm(2)) before treatment, high ADC increase ratio, and treatment method (chemoradiotherapy versus radiation therapy alone) revealed significant difference between patients with local failure and controls or association with local failure. In Cox proportional hazard testing, high ADC before treatment alone showed significant association with local failure (P = .0186). In the validation study, tumor volume before treatment, high ADC before treatment, T stage (T12 versus T34), and treatment method showed significance. Tumor volume before treatment (P = .0217) and high ADC before treatment (P = .0001) revealed significant association with local failure in Cox proportional hazard testing. High ADC before treatment was superior to tumor volume before treatment regarding association with local failure. CONCLUSIONS: These results suggest pretreatment ADC obtained at high b-values as well as tumor volume correlate with local failure of HNSCC treated with radiation therapy.

Proteinase 3-antineutrophil cytoplasmic antibody-(PR3-ANCA) positive necrotizing glomerulonephritis after restarting sulphasalazine treatment.

A 59-year-old woman with ulcerative colitis developed red eyes, pleural effusion, eosinophilia and urinary abnormalities after restarting of sulphasalazine treatment. Light microscopy of a kidney biopsy revealed segmental necrotizing glomerulonephritis without deposition of immunoglobulin or complement. Proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) titer was elevated at 183 ELISA units (EU) in sera (normal range less than 10 EU), myeloperoxidase-ANCA was negative. PR3-ANCA titer was 250 and 1,070 EU in pleural effusions on right and left side, respectively. Although cessation of sulphasalazine treatment resulted in improvements in fever, red eyes, chest pain, titer of C-reactive protein and volume of the pleural effusions, we initiated steroid therapy, because PR3-ANCA titer rose to 320 EU, eosinophil count increased to 1,100 cells/microl, and the pleural effusion remained. One month after steroid therapy, the pleural effusion disappeared, and PR3-ANCA titer normalized 3 months later. This case suggests that sulphasalazine can induce PR3-ANCA-positive necrotizing glomerulonephritis.