Differences In Clinical Backgrounds Research Articles

Immunogenicity and Lupus-Like Autoantibody Production Can Be Linked to Each Other along With Type I Interferon Production in Patients with Rheumatoid Arthritis Treated With Infliximab: A Retrospective Study of a Single Center Cohort.

Besides anti-drug antibodies, anti-nuclear antibodies and anti-DNA antibodies are often induced in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. We examined the association between immunogenicity, autoantibody production, and serum cytokine profiles in patients with rheumatoid arthritis treated with infliximab. Japanese patients with rheumatoid arthritis (n = 57) were retrospectively examined. Serum trough levels of infliximab, anti-drug antibody, anti-nuclear antibody, and anti-DNA (Farr), anti-single-stranded DNA and anti-double-stranded DNA antibodies were measured. Interleukin-6, interferon-γ, interferon-α, and B-cell activating factor levels were also measured in the same sera. Then, we validated the association between anti-drug antibody and these serum markers along with clinical response to infliximab. Anti-drug antibodies developed in twenty-one patients (36.8%), whose serum trough levels of infliximab were significantly lower than those in anti-drug antibody-negative patients (0.09 ± 0.03 vs. 2.48 ± 0.326 μg/mL, p < 0.0001). There were no significant differences in clinical backgrounds between the two groups. The anti-drug antibody-positive patients were more likely to develop anti-nuclear antibody titers of ≥ ×160 compared to the negative patients (14 to 57% vs. 17 to 33%). In addition, anti-DNA antibodies (Farr) (from 1.5 ± 0.4 to 35 ± 17 IU/mL, p = 0.0001), especially IgM-anti-double stranded DNA antibody (from 5.1 ± 0.7 to 41 ± 8.9 IU/mL, p < 0.0001), and IgG-anti-single stranded DNA antibody (from 13 ± 1.1 to 35 ± 13, p = 0.0145) were significantly increased in anti-drug antibody-positive but not in negative patients. Moreover, the anti-drug antibody-positive, but not the negative patients, showed significant increased levels of interferon-α (from 248.7 ± 102.3 to 466.8 ± 135.1 pg/mL, p = 0.0353) and B-cell activating factor (from 1073 ± 75.1 to 1387 ± 136.5 pg/mL, p = 0.0208) following infliximab treatment. The development of anti-drug antibody against infliximab and lupus-like autoantibody production in patients with rheumatoid arthritis treated with infliximab can be linked each other along with increased lupus-associated cytokine levels including type I interferons.

Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP.

PROSPECTIVE MULTICENTER SURVEY ON PREDICTIVE FACTORS FOR POSITIVE ORAL FOOD CHALLENGE TESTS IN DIAGNOSIS OF GASTROINTESTINAL FOOD ALLERGY IN NEONATES.

To assess predictors of positive oral food challenge test (OFC) in neonates that are suggestive of gastrointestinal food allergy. A prospective case accumulations study on neonates suspected of having gastrointestinal food allergy was conducted in 126 neonatal intensive care units in Japan between April 2010 and September 2011. Neonates who underwent an OFC for the diagnosis of gastrointestinal food allergy were enrolled. Clinical backgrounds, clinical symptoms, and laboratory findings were compared between neonates with a positive OFC and those with a negative OFC. An analysis was performed in 32 neonates. The OFC results were positive in 9 neonates (28.1%), pseudo-positive in 4, and negative in 19. There were no significant differences in clinical backgrounds between the positive OFC group and the negative OFC group. Vomiting and bloody stool were frequently observed in both groups (approximately 70%), although there were no significant differences in the clinical symptoms between the two groups. Additional diagnostic tests included those for eosinophils in the peripheral blood and stool mucus and allergen-specific lymphocyte stimulation test. There were no significant differences in laboratory findings between the two groups, and many neonates showed pseudo-positive in all of the tests. It was difficult to predict OFC results based on clinical symptoms and additional diagnostic test results. In order to obtain an accurate diagnosis of gastrointestinal food allergy in neonates, OFC should be performed proactively under conditions that enable complete understanding of risks to neonates.

Abstract A61: Association of clinico-pathological features with epidermal growth factor receptor mutant allele frequency in patients with non-small cell lung cancer

Abstract Background: One of the most interesting aspects relating to tumor heterogeneity is the relevance and clinical significance of mutant allele frequency (MAF) within a tumor. However, it remains unknown whether epidermal growth factor receptor (EGFR) MAF is associated with clinico-pathological features in patients. The aim of this study is to assess the clinico-pathological features associated with EGFR MAF in patients with non-small cell lung cancer. Methods: Based on a biobanking system in conjunction with our institution, we assessed EGFR substitution mutation status using the pyrosequencing method. Results: A total of 96 non-small cell lung cancer patients were identified as carrying EGFR substitution mutations using pyrosequencing to analyze histological and surgical specimens. In fifty-seven cases (59.4%) surgical specimens were taken and in 39 cases (40.6%) FFPE specimens were used. The median age of patients was 69 years (range: 37-84 years); stage IA/ IB/ IIA/ IIB/ IIIA/ IIIB/ IV, 32 (33.3%)/ 10 (10.4%)/ 7 (7.3%)/ 3 (3.1%)/ 5 (5.2%)/ 2 (2.1%)/ 37 (38.5%); mutation type L858R/ G719X/ L861Q, 85 (88.5%)/ 9 (9.4%)/ 2 (2.1%); histological type adenocarcinoma/ others, 90 (93.8%)/ 6 (6.2%); and median EGFR MAF was 18% (range: 6%-82%). The EGFR MAF did not differ significantly between 51 early stage (stage I, II) patients (53.1%, median: 19%) and 45 late stage (stage III, IV) patients (46.9%, median: 17%) (p = 0.48), 50 smoker patients (52.1%, median: 19%) and 46 never-smoker patients (47.9%, median: 16.5%) (p = 0.28), 58 non-elderly adults (≤ 70) patients (60.4%, median: 18.5%) and 38 elderly (&amp;gt; 70) patients (39.6%, median: 18%) (p = 0.37), and 47 male patients (49.0%, median: 19%) and 49 female patients (51.0%, median: 16.5%) (p = 0.13). However, the EGFR MAF was significantly elevated in 48 patients with moderately differentiated tumors (50.0%, median: 22%) compared to 30 patients with well differentiated tumors (31.3%, median: 13%) (p = 0.02) and 18 patients with poorly differentiated tumors (18.7%, median: 13%) (p = 0.01). Conclusion: EGFR MAF, measured by pyrosequencing, was not significantly associated with differences in clinical background, but was significantly associated with pathological differentiation in patients with non-small cell lung cancer. Citation Format: Akira Ono, Hirotsugu Kenmotsu, Masakuni Serizawa, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Tateaki Naito, Haruyasu Murakami, Yasuhisa Ohde, Masahiro Endo, Takashi Nakajima, Toshiaki Takahashi. Association of clinico-pathological features with epidermal growth factor receptor mutant allele frequency in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A61.

Abstract CT115: Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients

Abstract Background and purpose: In a phase I trial for advanced hepatocellular carcinoma (HCC), glypican-3(GPC3)-derived peptide vaccination was well-tolerated, and immune responses and antitumor efficacy were noted. The recurrence rates of HCC are still high and immunotherapy, as an adjuvant therapy, is expected. Therefore, we have conducted a phase II study of GPC3 peptide vaccine as an adjuvant therapy for HCC patients. Study design: Forty one patients with initial HCC, who had undergone surgery or radiofrequency ablation (RFA), were analyzed in this phase II, open-label, single-arm trial.Ten vaccinations were performed for one year after curative treatment. The primary endpoints were 1- and 2-year recurrence rates. The secondary endpoints were safety and immune responses. We have evaluated GPC3-specific CTL response in PBMCs by IFN-γ enzyme-linked immunospot (ELISPOT) assay. We have evaluated the expression of GPC3 in the 33 primary tumors and 11 recurrence tumors, that could be obtained, by immunohistochemical analysis, and the phenotype of CTLs in recurrence tumor and vaccine site by flow cytometry. Results: GPC3 peptide vaccine showed no severe adverse events. 1-year and 2-year recurrence rates of the 41 patients treated with the vaccination were 24.4% and 53.7%. In this study, 35 patients had received surgery and 6 patients RFA therapy. We analyzed the case-control study to evaluate the reduction in the risk of post-operative recurrence by vaccination. Thirty three patients with initial HCC who underwent curative resection in the same period were selected as control group. The recurrence rate tended to be lower in 35 patients treated with surgery and the vaccination than in 33 patients with surgery alone (28.6% and 54.3% vs 39.4% and 54.5% at 1 year and 2 year, p = 0.346, 0.983). In the patients with GPC3 positive tumor, the recurrence rate was significantly lower in 25 patients treated with surgery and the vaccination than in 21 patients with surgery alone (24% and 48% vs 52.4% and 61.9% at 1 year and 2 year, p = 0.047, 0.387), and there was no significant difference in clinical background. There were not the correlation between the relapse free survival and the antigen-specific immune response as measured by IFN-γ ELISPOT assay. Two of 11 case appeared to lack GPC3 expression in the recurrence tumor, although GPC3 was expressed in the primary HCC tissue before GPC3 peptide vaccine. In the other case, GPC3 peptide specific CTLs had infiltrated into recurrence tumor, and the expression of PD-1 among CD8 positive T cells, was higher in recurrence tumor and vaccine site than in PBMCs. Conclusions: GPC3 peptide vaccine for patient with GPC3 positive tumor could improve 1-year recurrence rates. This study showed GPC3 expression of the primary tumor could be the biomarker for a larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine. Citation Format: Yu Sawada, Toshiaki Yoshikawa, Kazuya Ofuji, Mayuko Yoshimura, Nobuhiro Tsuchiya, Mari Takahashi, Daisuke Nobuoka, Shoichi Mizuno, Itaru Endo, Tetsuya Nakatsura. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT115. doi:10.1158/1538-7445.AM2015-CT115

Alteration of Delta-like ligand 1 and Notch 1 receptor in various placental disorders with special reference to early onset preeclampsia.

Notch signaling pathway has been shown to be dysregulated in placentas with preeclampsia, but there has been a lack of studies on methylation of Notch family genes in this disorder. We therefore executed methylation-specific polymerase chain reaction and immunostaining for Notch 1 receptor and the activating ligand, Delta-like (DLL) 1, with placental tissues from cases of preeclampsia (early onset, n = 18; late-onset, n = 19) and other placental disorders, including maternal complications such as diabetes mellitus and collagen disease (n = 10), fetal growth restriction (n = 17), fetal anomaly (n = 23), preterm birth (n = 15), miscarriage (n = 25), and hydatidiform moles (n = 9) as well as term births (n = 12). The frequency of DLL1 methylation was higher in early onset preeclamptic placentas (61%) than the other subjects (0%-36%; P ≤ .016). Appreciable samples (36%) of miscarriage also represented DLL1 methylation. None of the samples studied showed Notch 1 methylation. On gestational period-matched analysis, the rate of DLL1 methylation was higher in early onset preeclampsia (83.3%) than preterm birth (13.3%; P < .001), with no significant differences in clinical backgrounds between the two. In this analysis, increase of syncytial knots and accelerated villous maturation were most prominent in DLL1-methylated placentas with early onset preeclampsia. Notch 1 and DLL1 expressions in villous trophoblasts and endothelial cells were significantly lower in early onset preeclamptic placentas as compared with preterm birth controls. In conclusion, altered Notch signaling via methylation of DLL1 is likely involved in possible disease-related mechanisms of early onset preeclampsia. Alternatively, DLL1 methylation in early onset preeclampsia could be a manifestation of a lack of placental maturation, similar to miscarriage.

Effects of supplemental oxygen on urinary 8-hydroxy-2’-deoxyguanosine levels in extremely low birth weight infants

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2’-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.

Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma

To compare the tumor control and safety of stereotactic body radiation therapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) for small, solitary, and hypervascular hepatocellular carcinoma (HCC) with TACE alone. Three hundred and sixty-five HCC patients who had solitary, ≤ 3 cm, and hypervascular nodule were treated with TACE. Among them, 30 patients followed by SBRT (SBRT group) and 38 patients without additional therapy and previous HCC treatment (control group) were enrolled in this retrospective cohort study. Local tumor progression, complication, and disease-free survival were compared between these groups. There was no difference in clinical background between these groups. Complete response to therapy was noted in 29 (96.3%) patients of the SBRT group, and in only one (3.3%) patient of the TACE group (P < 0.001). None of the patients developed acute hematologic toxicity of more than Common Terminology Criteria for Adverse Events Grade 3 during and after the treatment. Furthermore, none of the SBRT group developed radiation-induced liver damage. Disease-free survival of the 12 patients without previous HCC treatments in SBRT group was significantly superior to that in control group (15.7 months vs 4.2 months; P = 0.029). The results indicated that SBRT combined with TACE is a safe and effective modality for locoregional treatment of small solitary primary HCC, and could be potentially a suitable option.

肝動脈化学塞栓療法時の予防的抗生剤投与に関する検討―経口剤と注射剤の比較―

Aim/background: Antibiotic prophylaxis is widely used in transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC). The usefulness of oral antibiotic prophylaxis in TACE has not been established. Material/methods: One hundred forty five HCC, 76 were given oral levofloxacin (LVFX) (PO group) and 69 were administrated with cefotiam (CTM) by intravenous infusion as a historical control (DIV group), were enrolled. We investigated the clinical course and backgrounds of both groups, retrospectively. Results: There are no significant differences in clinical backgrounds, periods of hospitalization and administrating antibiotic drugs between both groups. The cost of antibiotic drugs were significant lower in PO than DIV group (3277.1 vs. 11924.4 yen, P<0.01). Conclusion: Oral LVFX was useful and a low cost medication for preventing infection after TACE.

Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography

In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n = 9) and nonexacerbation (n = 19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P < 0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P < 0.05). Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors.

String-Sign in Left Internal Thoracic Artery Is Associated With Regression in Left Main Trunk Stenosis After Coronary Artery Bypass

The left internal thoracic artery (LITA) is the conduit of choice for coronary artery bypass (CABG) due to favorable long-term patency. Uncommonly, diffuse narrowing like a string without significant stenosis of an anastomosis is observed in the LITA graft (called "string sign"). Isolated left main trunk (LMT) diseases were reported to regress in some cases. However, the relationship between "string sign" and the regression of solitary LMT disease remains unknown.We retrospectively studied 40 consecutive patients with isolated LMT stenosis who underwent CABG using LITA and who underwent angiography before and after operation (31 males, 9 females, mean age, 65.0 years). The patients were divided into 2 groups according to the postoperative angiographic outcomes of the LITA graft: one group included patients with "string sign" (6 patients), the other group consisted of patients with a patent LITA graft (34 patients).There were no significant differences in clinical backgrounds between the two groups. The 2 groups showed similar quantitative % coronary artery stenosis of the LMT before operation (77.5% versus 76.8%) and the observation period was similar in both groups. Coronary angiography after CABG revealed that % stenosis of the LMT in patients with "string sign" was significantly less than that in patients with a patent LITA graft (41.7 ± 26% versus 82.5 ± 11%, P < 0.001). Regression in LMT was significantly more frequently observed in the "string sign group". Furthermore, ostial stenosis was more frequent in patients with "string sign". "String phenomenon" of the LITA graft is one of the signs related to the regression of LMT stenosis, and especially in ostial stenosis of the LMT.

Comparison of Clinical Backgrounds with Anterior Versus Posterior Circulation Infarcts

The aim of this study was to identify the relevant clinical backgrounds for anterior circulation territory infarctions (ACTI) and posterior circulation territory infarctions (PCTI). Data were obtained from April 1995 to May 2005 discharge statistics of the neurologic service in our hospital. The infarctions were divided into anterior circulation territory and posterior circulation territory by computed tomography and magnetic resonance imaging, and we examined clinical backgrounds for small vessel disease, large artery disease, and cardioembolism (CE). A total of 1089 cases were ACTI and 430 were PCTI. Male/female ratio was 1.75 for ACTI and 2.67 for PCTI (P < .05). The mean age was 69.1 years for ACTI and 65.9 years for PCTI (P < .001). Multiple logistic regression analysis showed that significant contributed clinical backgrounds for small vessel disease were age and hyperlipidemia in ACTI. Those for large artery disease were male sex and history of cerebrovascular disease in PCTI. Those for CE were age and atrial fibrillation in ACTI; and diabetes, hypertension, hyperlipidemia, and smoking in PCTI. Those for all cerebral infarctions were age and atrial fibrillation in ACTI; and male sex, diabetes, and hypertension in PCTI. This study showed differences in clinical backgrounds between ACTI and PCTI. Moreover, PCTI were closely related to the conventional vascular risk factors even in CE.

Large Waist Circumference Is a Risk Factor for Reflux Esophagitis in Japanese Males

Background/Aims: The prevalence of reflux esophagitis, which might lead to development of Barrett’s esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. Methods: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. Results: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47–17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94–0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05–4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02–1.15; p = 0.006) were associated with reflux esophagitis. Conclusions: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females.

Safety of transperineal 14‐core systematic prostate biopsy in diabetic men

To examine whether the transrectal ultrasound-guided transperineal 14-core prostate biopsy can be carried out safely in diabetic men and to determine adequate antimicrobial prophylaxis protocol in this setting. The present study included 539 men, 135 with concurrent diabetes mellitus (DM) and 404 without DM, who underwent transperineal extended 14-core biopsy due to elevated prostate-specific antigen > or = 2.5 ng/mL and/or abnormal digital rectal examination. Any complication requiring prolonged hospitalization or rehospitalization during the 4-week post-biopsy period was considered major. All other complications were considered minor. Intensity of antimicrobial prophylaxis was prospectively reduced in a stepwise manner down to single dose of oral levofloxacin. Except for DM, there was no significant difference in clinical background between the diabetic and non-diabetic men. The procedure was completed in all revealing prostate cancer in 42% of the diabetic men and 36% of the non-diabetic men (P = 0.23). Incidence of minor or major complications was not significantly different between the two groups. Minor complications were observed in 15.6% and 16.6% of each group, respectively, with voiding disturbance being the most common. No infectious major complication was observed regardless of the presence of DM. In the diabetic men, there was no statistical difference in incidence of biopsy-related complications according to modality of DM treatment, HbA1c level or antimicrobial prophylaxis protocol. Transperineal 14-core biopsy can be carried out without major infectious complications in diabetic men. Oral levofloxacin 300 mg once before the procedure seems to represent an effective antimicrobial prophylaxis in diabetic men without other risk of infection.

Retrospective analysis of CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) treated with chemotherapy with or without rituximab

8551 Background: CD5+ DLBCL comprises 5–10% of DLBCL, and shows a high incidence of central nervous system (CNS) relapse. It has been included in the 4th WHO classification as an immunohistochemical subgroup. To clarify the prognosis and incidence of CNS relapse of CD5+ DLBCL in the rituximab-era, we conducted a multicenter retrospective study. Methods: We analyzed 313 patients (pts) with CD5+ DLBCL who received chemotherapy with (n=164) or without rituximab (n=149). The current series includes 107 out of 120 pts described in our previous study (Haematologica, 2008). Intravascular large B-cell lymphoma, primary CNS DLBCL, and secondary CD5+ DLBCL were excluded from the study population. Results: 313 pts showed the following clinical features: median age, 67 (range: 15–93); M:F=163:150; elevated serum LDH level, 71%; stage III/IV, 64%; IPI HI/H, 53%. No significant difference in clinical background such as the IPI and its five components, B symptom, male sex, and bone marrow involvement was found between pts who were treated with and without rituximab. Pts treated without rituximab received more dose-intensive chemotherapies (CHOP14, third-generation regimen, and high dose cytarabine-based regimen) than those treated with rituximab (24% vs. 7%, P&lt;0.0001). The CR rate was higher in pts received rituximab than those without (81% vs. 65%; P=0.0014). The median follow-up was 28 months in pts who received rituximab (range: 7–77) and 68 months in those who did not (range: 6–187). Overall survival (OS) was significantly superior for pts with rituximab than for those without (2-yr OS: 68% vs. 54%, P=0.003). Multivariate analysis revealed that the use of rituximab was favorably associated with OS (HR=1.81, 95% CI: 1.26–2.58, P=0.001), but dose-intensive chemotherapies did not affect OS. However, the incidence of CNS relapse was not different between the two groups (2-yr CNS relapse rate: 11.9% vs. 11.4%, P=0.91). 16 of the 20 pts (80%) with CNS relapse in the rituximab group had brain parenchymal disease. Conclusions: Our data show that rituximab improves OS of pts with CD5+ DLBCL, but does not prevent CNS relapse. Future prospective studies to decrease CNS disease for CD5+ DLBCL are warranted. No significant financial relationships to disclose.

Higher incidence and serum levels of minor cardiac biomarker elevation in sirolimus-eluting stent (Cypher) than bare metal stent implantations

Minor cardiac biomarker elevation after percutaneous coronary intervention has long-term prognostic significance. The sirolimus-eluting stent (Cypher) has been reported to require high postinflation pressure for optimal implantation. We examined the incidence of minor cardiac biomarker elevation induced by Cypher implantation. We measured the serum concentration of cardiac troponin-I (cTnI) 24 h after stenting and those of creatine kinase isoenzyme MB and creatine kinase before, immediately after, and 6, 12 and 24 h after implantation in patients who underwent Cypher stent (CS group; n=53) or bare metal stent (BMS group; n=57) implantation. No significant difference in clinical background was observed between the two groups. When a cutoff cTnI value of 0.50 ng/ml was used, the CS group showed a significantly higher incidence of cTnI elevation (35.8%, 19/53) than the BMS group (14.0%, 8/57) (P<0.05). Similarly, the incidence of cTnI > or = 0.03 ng/ml tended to be higher in the CS group (88.7%, 47/53) than in the BMS group (73.7%, 42/57: 0.05<P<0.10). Furthermore, the CS group showed significantly higher cTnI levels than the BMS group (1.32+/-2.38 vs. 0.34+/-0.91 ng/ml. P<0.001). Essentially, similar results were obtained for serum creatine kinase isoenzyme MB and creatine kinase. Among clinical, lesion and procedural characteristics, postinflation pressure for stenting was significantly higher only in the CS group (18.2+/-2.8 atm) than in the BMS group (14.0+/-2.7 atm) (P<0.001). The results demonstrated that CS implantation increases the incidence of minor cardiac biomarker elevation compared with BMS. The difference in postinflation pressure could account for the results.

Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting

Background Minor cardiac marker elevation after percutaneous coronary intervention has long-term prognostic significance. We examined whether nicorandil, a nicotinamide-nitrate ester, reduces the incidence of minor cardiac marker elevation after coronary stenting. Methods Patients ( n = 192) undergoing coronary stenting were randomly assigned to receive nicorandil (nicorandil group, n = 91) or vehicle (control group, n = 101). Nicorandil (2 μg/kg/min, intravenously) was administered immediately after the patients were transferred into the catheterization laboratory and continued for 6 h. We measured the serum concentrations of creatine kinase isoenzyme MB (CK-MB) before, immediately after, and 6, 12, and 24 h after the procedure, and those of cardiac troponin T (cTnT) 24 h after the procedure. Results There was no significant difference in clinical background between the 2 groups. The nicorandil group showed a significantly lower incidence of CK-MB elevation (> 1 × upper limit of control range, 20 IU/l) than the control group (8.8% vs 21.8%, p < 0.05). The levels of serum CK-MB in the nicorandil group were significantly lower than those in the control group (13.4 ± 5.7 vs 16.5 ± 9.7 IU/l, p < 0.01). Similarly, the nicorandil group showed a significantly lower incidence of cTnT elevation [> 1 × (0.1 ng/ml) or > 2 × (0.2 ng/ml)] upper limit of control range than the control group (14.3% vs 26.7%, p < 0.05, or 7.7% vs 17.8%, p < 0.05). Serum cTnT levels were also significantly lower in the nicorandil group than in the control group (0.05 ± 0.10 vs 0.15 ± 0.36 ng/ml, p < 0.05). Conclusions The results demonstrated that nicorandil reduces minor cardiac marker elevation after coronary stenting.

Abnormal Fragile Histidine Triad Expression in Advanced Cervical Cancer and Evaluation of Its Utility as a Prognostic Factor

Objective: The relationship between the abnormal expression of fragile histidine triad (FHIT) and the prognosis in advanced cervical cancer was investigated, focusing on the relation with radiosensitivity. Methods: A retrospective study was performed in 54 patients with stage IIIb cervical squamous cell carcinoma who received radiation therapy as the initial treatment. Formalin-fixed paraffin-embedded tissues were immunohistochemically stained using anti-FHIT antibody. The survival curve for patients with abnormal FHIT expression (low expression) was prepared and the prognosis was compared with that for the normal expression group. The decrease rate of the serum squamous cell carcinoma antigen (SCC) levels (SCC index = SCC level after radiotherapy/SCC level before radiotherapy) was calculated. Results: Abnormal FHIT expression was observed in 25 patients (46%). There were no significant differences in clinical backgrounds between the abnormal and normal FHIT expression groups. The 5-year survival rate was 72% in the abnormal expression group, showing no significant difference from that in the normal expression group (64%). The SCC indices were 0.21 ± 0.14 and 0.29 ± 0.19 in the abnormal and normal expression groups, respectively, showing no significant difference between the two groups. Conclusions: Abnormal FHIT expression was not correlated with radiosensitivity in patients with stage IIIb cervical cancer, showing that abnormal FHIT expression cannot be used as a prognostic factor.

GB virus C/hepatitis G virus infection in Chinese patients with hepatocellular carcinoma

Although hepatitis B and C viruses are closely related to hepatocellular carcinoma (HCC), the association between the newly discovered GB virus C (GBV-C)/hepatitis G virus (HGV) and HCC is not yet known. Sera from 124 patients with HCC in China were tested for GBV-C/HGV RNA by the reverse-transcription polymerase chain reaction with subsequent hybridization using GBV-C/HGV probes located at the 3′-untranslated region of the reported genomes. GBV-C/HGV RNA was detected in 33 (27%) of them, including 18 of the 59 (31%) patients with HBsAg, 12 of the 22 (55%) with both HBsAg and anti-HCV, and three of the 33 (9%) negative for either HBsAg or anti-HCV; it was not detected in any of the 10 with anti-HCV alone. There were no differences in clinical backgrounds between the patients with HBsAg and/or anti-HCV who possessed and who did not possess GBV-C/HGV RNA in serum. These results indicate that, although GBV-C/HGV is highly prevalent in Chinese patients with HCC, the role of GBV-C/HGV in hepatocarcinogenesis would be minimal in the development of non-B, non-C HCC.

Complications of exercise and pharmacologic stress tests: Differences in younger and elderly patients

Background. Age characteristics of patients undergoing various types of stress tests are important because of differences in clinical background and exercise performance between the young and elderly. Adverse effects of pharmacologic agents are known to be more common in the elderly, who are less able to perform vigorous exercise stress testing. We investigated the clinical background, performance characteristics, and complication rate of various stress tests in younger (≤75 years old) and elderly (>75 years old) patient populations. Methods. A total of 3412 patients (2796 younger, 616 elderly) underwent 5 types of stress tests with (1) technetium-99m sestamibi (MIBI) single photon emission computed tomography: symptom-limited exercise (Ex, 1598 younger, 173 elderly), (2) dipyridamole infusion (0.14 mg/kg/min, 4 minutes) without exercise (D, 260 younger, 114 elderly), (3) with exercise (DEx, 339 younger, 112 elderly), (4) adenosine infusion (0.14 mg/kg/min, 5 minutes) without exercise (A, 253 younger, 101 elderly), and (5) with exercise (AEx, 346 younger, 116 elderly). Results. Sixty-seven percent of patients in the younger population were able to achieve 85% of the maximum predicted heart rate, whereas 54% of the elderly reached this level of exercise. No patient had life-threatening complications. In both the younger and elderly groups, chest discomfort, feelings of impending syncope, flushing, and fall in blood pressure occurred less frequently in DEx than D and in AEx than A. Sinus bradycardia occurred less frequently in AEx than A in the younger (1.2% vs 4.3%, P < .05) and elderly groups (0.9% vs 6.9%, P < .05). Atrioventricular block was less frequent in AEx than A in the younger group (3.2% vs 7.9%, P < .05) but not so in the elderly group (13.0% vs 17.8%, not significant). The frequency of ischemic electrocardiographic changes in DEx and AEx was very similar to that of Ex in both the younger and elderly groups, although ischemic electrocardiographic changes in D and A are known to be less frequent. Conclusion. Of the elderly group who were judged to be fit to exercise to 85% of maximum predicted heart rate, nearly half failed to reach this level. In contrast, the younger patients were able to achieve this level in 67% of tests. Supplementation with modest exercise reduced most of the pharmacologically related adverse effects. The elderly group was not protected from atrioventricular block as effectively as the younger group by additional exercise in the adenosine stress test. Ischemic electrocardiographic changes in the pharmacologic stress test were as frequent as in the exercise stress test when modest supplementary exercise was added to the pharmacologic protocol. There were no deaths, myocardial infarction, or other major complications. These observations suggest that exercise and pharmacologic stress tests are safe in the elderly, including those patients more than 75 years old.