Monosomy 13 in metaphase spreads is a predictor of poor long-term outcome after bortezomib plus dexamethasone treatment for relapsed/refractory multiple myeloma

We retrospectively investigated the prognostic impact of high-risk cytogenetic abnormalities (CAs) on the outcome of treatment with bortezomib plus dexamethasone (BD) in 43 relapsed/refractory (Rel/Ref) multiple myeloma patients. Fluorescence in situ hybridization (FISH) analysis identified del(13q) in 25 patients, t(4;14) in 14, t(14;16) in 4, 1q21 abnormality in 12 and del(17p) in 2, while G-banding also detected chromosome 13 monosomy (-13) in metaphase spreads from 7 patients. Eighteen of 25 patients with FISH-detected chromosome 13 abnormalities also exhibited other abnormalities. Median observation period was 510 days, and median overall survival (OS) and progression-free survival (PFS) were 912 days and 162 days, respectively. Detection of del(13q), t(4;14), t(14;16) or 1q21 abnormalities by FISH and co-occurrence of chromosome 13 abnormality with other abnormalities were not associated with poorer outcomes. In contrast, detection of -13 by G-banding in metaphase spreads showed significant association with shorter OS, although the overall response rate and PFS were not inferior to those for patients without -13 detected by G-banding. BD therapy may be a potent weapon for overcoming most classical high-risk CAs, while the detection of -13 in metaphase spreads may serve as a predictor of highly progressive disease, even when treated with BD.     

The effect of celiac plexus block on heart rate variability

Background

Celiac plexus block (CPB) can be used for treating intra-abdominal visceral pain syndromes. The celiac plexus is the largest plexus of the sympathetic nervous system. Several nerve blocks have a marked effect on autonomic nervous activity. Furthermore, stellate ganglion block changes cardiac autonomic nervous activity. Thus, CPB could influence the sympathetic activity of the cardiac plexus. The aim of the present study was to see whether CPB modulated heart rate variability (HRV) in patients with pancreatic cancer.

Methods

Twelve patients received neurolytic CPB using 14 ml absolute alcohol. Data recorded in a palm-sized electrocardiographic unit were analyzed for HRV.

Results

CPB using a neurolytic solution did not induce any significant changes in the low-frequency (LF)/high-frequency (HF) ratio of HRV (LF/HF, P = 0.4642). Furthermore, the procedure did not induce any significant changes in blood pressure (systolic, P = 0.5051; diastolic, P = 0.5180).

Conclusion

CPB did not induce any significant changes in HRV or hemodynamics.     

Retrospective Study Using the Propensity Score to Clarify the Oncologic Feasibility of Thoracoscopic Esophagectomy in Patients with Esophageal Cancer

Background

The present study aimed to clarify the long-term prognostic impact and oncologic feasibility of thoracoscopic esophagectomy (TSE) in patients with esophageal cancer in comparison with open thoracic esophagectomy (OTE).

Methods

Patients with esophageal cancer underwent surgically curative esophagectomy without neoadjuvant therapy from January 1991 to December 2008 and were analyzed retrospectively. Of 257 patients, 91 underwent TSE and 166 had OTE. Relations between the long-term prognosis after surgery, the surgical procedure, and clinicopathologic parameters were analyzed statistically. The propensity scores were calculated for all patients through a multiple logistic regression model that was optimized with Akaike’s Information Criterion. Using Cox’s proportional hazard model with prognostic variables and the propensity scores, we implemented a multivariate analysis for comparing the performance of two surgical methods.

Results

Patient characteristics and the incidence of perioperative morbidity or hospital death were similar for the TSE and OTE groups. Significantly more lymph nodes were dissected in the TSE group than in the OTE group (total p = 0.013; thoracic p = 0.0094; recurrent laryngeal p < 0.0001). The TSE group exhibited a more favorable prognosis after surgery than the OTE group in terms of overall survival (p = 0.011) and disease-specific survival (DSS) (p = 0.0040). Particularly in subgroup analysis of DSS, the TSE group had a favorable prognosis in upper thoracic esophageal cancer (p = 0.0053), invasive cancer (p = 0.046), node-positive cancer (p = 0.020), progressive cancer (p = 0.0052), cancer with lymphatic vessel invasion (p = 0.0019), and cancer without blood vessel invasion (p = 0.0081). In terms of DSS, the TSE group exhibited a more favorable prognosis than the OTE group regardless of the presence or absence of metastasis to lymph nodes around the thoracic (p < 0.0001) or recurrent laryngeal (p < 0.0001) nerves. TSE (p = 0.0430), lymph node metastasis (p = 0.0382), lymphatic invasion (p = 0.0418), and p stage (p = 0.0047) were independent prognostic parameters in the Cox’s proportional hazard model with the propensity scores.

Conclusions

TSE can contribute to prolonged survival after surgery in patients with esophageal cancer by enabling precise thoracic lymph node dissection based on a magnified surgical field. TSE might have maximum oncologic benefit and minimum invasiveness for patients with esophageal cancer.     

Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum

Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum is extremely rare. In this report, we present a case of a 53-year-old man with superior vena cava (SVC) syndrome who developed LCNEC in the middle mediastinum. His chief complaint was facial edema. Chest X-ray revealed an abnormal shadow in the right upper mediastinum. Computed tomography (CT) scan of the chest revealed a 67-mm mass in the middle mediastinum. Tumor invasion caused constriction of the SVC. The patient underwent induction chemoradiotherapy with vinorelbin and cisplatin and concurrent radiation therapy. After induction therapy, the tumor size decreased remarkably and was resected completely. The pathological diagnosis was LCNEC.     

G protein‐coupled receptor 30 contributes to improved remyelination after cuprizone‐induced demyelination

Estrogen exerts neuroprotective and promyelinating actions. The therapeutic effect has been shown in animal models of multiple sclerosis, in which the myelin sheath is specifically destroyed in the central nervous system. However, it remains unproven whether estrogen is directly involved in remyelination via the myelin producing cells, oligodendrocytes, or which estrogen receptors are involved. In this study, we found that the membrane‐associated estrogen receptor, the G protein‐coupled receptor 30 (GPR30), also known as GPER, was expressed in oligodendrocytes in rat spinal cord and corpus callosum. Moreover, GPR30 was expressed throughout oligodendrocyte differentiation and promyelinating stages in primary oligodendrocyte cultures derived from rat spinal cords and brains. To evaluate the role of signaling via GPR30 in promyelination, a specific agonist for GPR30, G1, was administered to a rat model of demyelination induced by cuprizone treatment. Histological examination of the corpus callosum with oligodendrocyte differentiation stage‐specific markers showed that G1 enhanced oligodendrocyte maturation in corpus callosum of cuprizone‐treated animals. It also enhanced oligodendrocyte ensheathment of dorsal root ganglion (DRG) neurons in co‐culture and myelination in cuprizone‐treated animals. This study is the first evidence that GPR30 signaling promotes remyelination by oligodendrocytes after demyelination. GPR30 ligands may provide a novel therapy for the treatment of multiple sclerosis. © 2012 Wiley Periodicals, Inc.