Peripheral neuropathy in osteosclerotic myeloma: Clinical and electrodiagnostic improvement with chemotherapy

A patient with a severe remote-effect polyneuropathy and other paraneoplastic features of osteosclerotic myeloma improved dramatically with melphalan and prednisone treatment. Serial electrodiagnostic studies provided an objective means of following the response to therapy and documented the improvement. We believe this represents the first reported patient with multifocal osteosclerotic myeloma and a myelomatous polyneuropathy responding to melphalan and prednisone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50132/1/880070209_ftp.pd

Retrospective Comparison of Non-Skin-Sparing Mastectomy and Skin-Sparing Mastectomy with Immediate Breast Reconstruction

Background. We compared Skin-sparing mastectomy (SSM) with immediate breast reconstruction and Non-skin-sparing mastectomy (NSSM), various types of incision in SSM. Method. Records of 202 consecutive breast cancer patients were reviewed retrospectively. Also in the SSM, three types of skin incision were used. Type A was a periareolar incision with a lateral extension, type B was a periareolar incision and axillary incision, and type C included straight incisions, a small elliptical incision (base line of nipple) within areolar complex and axillary incision. Results. Seventy-three SSMs and 129 NSSMs were performed. The mean follow-up was 30.0 (SSM) and 41.1 (NSSM) months. Respective values for the two groups were: mean age 47.0 and 57; seven-year cumulative local disease-free survival 92.1% and 95.2%; post operative skin necrosis 4.1% and 3.1%. In the SSM, average areolar diameter in type A & B was 35.4 mm, 43.0 mm in type C and postoperative nipple-areolar plasty was performed 61% in type A & B, 17% in type C, respectively. Conclusion. SSM for early breast cancer is associated with low morbidity and oncological safety that are as good as those of NSSM. Also in SSM, Type C is far superior as regards cost and cosmetic outcomes

A Study of Correlation between Gd-EOB-DTPA-enhanced MRI Using the 3T MRI System and Tc-99m-GSA Hepatic Scintigraphy / Hepatic Function Tests in Prehepatectomy Cases

This study compared results from Gd-EOB-DTPA on two different phases of 3T MRI with those from Tc-99m-GSA hepatic scintigraphy and hepatic function tests. Twenty-four patients with liver tumor were included in this study. All patients underwent Gd-EOB-DTPA-enhanced-MRI and Tc-99m-GSA hepatic scintigraphy. Clearance index (HH15) and receptor index (LHL15) were calculated for the Tc-99m-GSA, while signal intensities (SI) of liver at pre-injection and at 4/20min post-injection, and of spleen at 4 min/20min were measured (SIpre, SI4min, SI20min, SIsp4min, SIsp20min, respectively) for the Gd-EOB-DTPA-MRI. Liver activity at 15min by Tc-99m-GSA scintigraphy or biochemical liver function values were compared with liver spleen contrast at 4min (LSC4min = SI4min/SIsp4min) or 20min post-injection (LSC20min = SI4min/SIsp20min), and the increase in ratio at 4min (IR4min=SI4min/SIsp4min) or 20min (IR20min= SI20min/SIpre). Total bilirubin levels (T-bil), serum albumin levels (Alb), prothrombin activity, and the indocyanine green clearance test (ICG) results were also analyzed. There were statistically significant correlations in all comparisons between Gd-EOB-DTPA and Tc-99m-GSA. The highest coefficient of correlation was obtained in IR4min (LHL15: r = 0.795, P<0.001; HH15: r = -0.782, P<0.001), with IR20min (LHL15: r = 0.690, P<0.01; HH15: r = -0.528, P<0.05), LSC4min (LHL15: r = 0.458, P<0.05; HH15: r = -0.626, P<0.05), and LSC20min (LHL15: r = 0.443, P<0.05, HH15: r = -0.609, P<0.05) also significantly correlated. Correlations in hepatic function data were observed between IR4min and T-bil/Alb, and IR20min and Alb. In 3T-MRI using Gd-EOB-DTPA, the SI of liver at pre- to post-injection (especially at 4 min) significantly correlated with the corresponding Tc-99m-DTPA scintigraphy results, and with some biochemical liver function data

The Incidence of Proximal Extension of Ulcerative Proctitis in Japan and Factors Related to Proximal Extension

The incidence of proximal extension in patients with ulcerative proctitis is reported to be 18%-46%, but recent data on the incidence in Japan is inadequate. The aim of this study was to investigate the incidence of proximal extension of ulcerative proctitis and factors associated with the extension in Japan. This is a retrospective observational study involving a cohort of 53 patients with an initial diagnosis of ulcerative proctitis. Following verification of the diagnoses, demographic and clinical data were compiled. The cumulative incidence of proximal extension was estimated as ‘person-years’ and cumulative probability was calculated by the Kaplan-Meyer method. Univariate and multivariate analyses were performed to identify association factors. During a mean follow-up of 6.8 years, proximal extension was observed in 14 patients (26.4%). The cumulative incidence of proximal extension was 4.22/100 person-years and the cumulative probability at 5 years was 20.1%, consistent with recent reports from Western countries and data obtained in Japan over 2 decades ago. Univariate analysis showed active smoking (P = 0.025) and corticosteroid therapy (P = 0.006) to be risk factors in proximal extension, however multivariate analysis revealed that corticosteroid therapy was the only significant factor (P = 0.005) separating patients with and without proximal extension. No patient underwent colectomy. The incidence of proximal extension in ulcerative proctitis in Japan is comparable to that in Western countries and has not changed significantly over the past two decades. Corticosteroid therapy was identified as the only significant factor in proximal extension

Clinical Outcomes and Prognostic Factors Associated with Survival after Balloon-occluded Retrograde Transvenous Obliteration of Gastric Varices

We evaluated clinical outcomes and prognostic factors associated with survival after balloon-occluded retrograde transvenous obliteration (B-RTO) of gastric varices in patients with portal hypertension. Of 50 patients with gastric varices who underwent B-RTO, 46 (94.0%) patients in whom B-RTO was technically successful were reviewed retrospectively. Gastric and esophageal varices after B-RTO were evaluated by contrast-enhanced computer tomography and endoscopy, respectively. Liver function parameters and Child-Pugh scores were estimated before and at 1 year after B-RTO. The cumulative survival rate was calculated, and univariate and multivariate analyses were used to assess the prognostic factors. No major complications occurred in any of the patients following B-RTO and no recurrence or bleeding of gastric varices was noted. Of the 42 patients who were followed up for the progression of esophageal varices, 13 (31.0%) had worsened varices and of these, 6 (14.3%) showed bleeding. Prothrombin activity had significantly improved at 1 year after B-RTO, although there were no changes in other liver function parameters. The overall cumulative survival rates at 1, 3, and 5 years after B-RTO were 91.6%, 70.9%, and 53.6%, respectively. Multivariate analysis identified the occurrence of advanced hepatocellular carcinoma (HCC) during the observation period as a prognostic factor for survival (hazard ratio = 4.1497, 95% CI = 1.32314-13.0319, P = 0.0148). B-RTO of gastric varices is an effective treatment ensuring lower recurrence and bleeding rates; however, these patients require careful observation for progression of esophageal varices. The management of HCC is crucial for achieving long-term survival after B-RTO

Effects of Interleukin-4-Transduced Tumor Cell Vaccines and Blockade of Programmed Cell Death 1 on the Growth of Established Tumors

Interleukin (IL)-4 exhibits strong antitumor effects and IL-4 gene therapy has been used clinically in the treatment of some types of cancer. In the present study, we evaluated the efficacy of IL-4-transduced tumor cell vaccines in combination with blockade of programmed cell death 1 (PD-1) and investigated the mechanisms underlying the antitumor effects of this therapy. A poorly immunogenic murine colorectal cancer cell line (i.e. MC38) was transduced to overexpress IL-4. In a therapeutic model, MC38-IL4 cells and anti-PD-1 antagonistic antibodies (Ab) were inoculated into parental tumor-bearing mice. Immunohistochemical analyses and tumor-specific lysis were also performed. Additive antitumor effects were observed when mice were treated with IL-4 in combination with an anti-PD-1 Ab. Immunohistochemical analysis of the therapeutic model showed marked infiltration of CD4+ and CD8+ cells into established MC38 tumors of mice treated with anti-PD-1 Ab. Significant tumor-specific cytolysis was detected when the splenocytes of mice treated with both IL-4 and anti-PD-1 Ab were used as effector cells. These results suggest that blockade of the interaction between PD-1 and programmed death ligand 1 (PD-L1) enhances the antitumor immune responses induced by IL-4. Thus, IL-4 gene-transduced tumor cell vaccines in combination with PD-1 blockade may be considered as possible candidates for clinical trials of new cancer vaccines

Открытое контролируемое исследование клинических эффектов препарата Лаеннек® у пациентов с неалкогольным стеатогепатитом или циррозом печени

Objective: to evaluate the efficacy and safety of human placenta hydrolysate (HPH) Laennec® in the treatment of nonalcoholic fatty liver disease (NAFLD) in a clinical trial.Material and methods. The study involved hospitalized NAFLD patients (with non-alcoholic steatohepatitis, cirrhosis) (n=34, mean age 53±14 years). In the therapy group (n=17), patients received Laennec® HPH (4 ml intravenous drip infusion in a solution of 5% glucose 5 times a week for 2 weeks). In the control group (n=17), patients hospitalized in other departments of the clinic did not receive any therapy for NAFLD. The effectiveness of therapy was assessed after 2 and 3 weeks by subjective NAFLD symptoms (fatigue, anorexia, bloating, constipation, nausea, and pain in hypochondrium) and biochemical indicators of liver function: levels of blood serum aspartate aminotrans-ferase (AST), alanine notransferase (ALT), gamma-glutamyltransferase (GGT).Results. At the start of the study, there were no significant differences between the groups in the values of the studied indicators of liver function: blood levels of AST, ALT, GGT, etc. By the end of Week 1, a significant decrease in AST levels was registered in the group receiving Laennec® (–35 U/l; control: –8 U/l; p&lt;0.001), ALT (–45 U/l; control: –10 U/l; p&lt;0.001), and GGT (–23 U/l; control: –8 U/l; p=0.084; trend). At the end of the study (Week 3), the decrease in AST, ALT and GGT levels towards the normal range was even more pronounced for all three biomarkers: AST (–62 U/l; control: –23 U/l; p&lt;0.001), ALT (–78 U/l; control: –20 U/l; p&lt;0.001), GGT (–40 U/l; control: –15 U/l; p=0.005). Subjective NAFLD symptoms significantly improved after 3 weeks. No adverse effects were identified with the use of HPH. Conclusion. Laennec® is an effective and safe treatment for NAFLD.Цель: оценка эффективности и безопасности гидролизата плаценты человека (ГПЧ) Лаеннек® при лечении неалкогольной жировой болезни печени (НАЖБП) в рамках клинического исследования.Материал и методы. В исследовании приняли участие госпитализированные пациенты с НАЖБП (неалкогольный стеатогепатит, цирроз) (n=34, средний возраст 53±14 лет). В группе терапии (n=17) больные получали ГПЧ Лаеннек® (4 мл внутривенная капельная инфузия в растворе 5% глюкозы 5 раз в неделю в течение 2 нед). В контрольной группе (n=17) пациенты, госпитализированные в другие отделения клиники, не получали никакой терапии в связи с НАЖБП. Эффективность лечения оценивали через 2 и 3 нед по субъективным симптомам НАЖБП (утомляемость, анорексия, вздутие живота, запор, тошнота и боль в подреберье) и биохимическим показателям функции печени: уровням аспартатаминотрансферазы (АСТ), аланинаминотрансферазы (АЛТ), гамма-глутамилтрансферазы (ГГТ) в сыворотке крови.Результаты. На момент начала исследования между группами не было достоверных различий в значениях исследованных показателей функции печени: уровни АСТ, АЛТ, ГГТ и др. К концу 1-й недели в группе получавших Лаеннек® зарегистрировано достоверное снижение уровней АСТ (–35 Ед/л; контроль: –8 Ед/л; р&lt;0,001), АЛТ (–45 Ед/л; контроль: –10 Ед/л; р&lt;0,001) и ГГТ (–23 Ед/л; контроль: –8 Ед/л; р=0,084; тренд). На момент окончания исследования (3-я неделя) снижение уровней АСТ, АЛТ и ГГТ в сторону интервала нормы было еще более выраженно для всех трех биомаркеров: АСТ (–62 Ед/л; контроль: –23 Ед/л; р&lt;0,001), АЛТ (–78 Ед/л; контроль: –20 Ед/л; р&lt;0,001), ГГТ (–40 Ед/л; контроль: –15 Ед/л; р=0,005). Субъективная симптоматика НАЖБП достоверно улучшилась через 3 нед. Не было установлено каких-либо нежелательных эффектов при применении ГПЧ.Заключение. Лаеннек® – эффективное и безопасное средство лечения НАЖБП

In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation

Radiofrequency ablation therapy (RFA) is a radical treatment for liver cancers and induces tumor antigen-specific immune responses. In the present study, we examined the antitumor effects of focal OK-432-stimulated dendritic cell (DC) transfer combined with RFA and analyzed the functional mechanisms involved using a murine model. C57BL/6 mice were injected subcutaneously with colon cancer cells (MC38) in their bilateral flanks. After the establishment of tumors, the subcutaneous tumor on one flank was treated using RFA, and then OK-432-stimulated DCs were injected locally. The antitumor effect of the treatment was evaluated by measuring the size of the tumor on the opposite flank, and the immunological responses were assessed using tumor-infiltrating lymphocytes, splenocytes and draining lymph nodes. Tumor growth was strongly inhibited in mice that exhibited efficient DC migration after RFA and OK-432-stimulated DC transfer, as compared to mice treated with RFA alone or treatment involving immature DC transfer. We also demonstrated that the antitumor effect of this treatment depended on both CD8-positive and CD4-positive cells. On the basis of our findings, we believe that combination therapy for metastatic liver cancer consisting of OK-432-stimulated DCs in combination with RFA can proceed to clinical trials, and it is anticipated to be markedly superior to RFA single therapy. © 2013 Springer-Verlag Berlin Heidelberg