Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients. MATERIALS AND METHODS: This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model. RESULTS: Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age > or =55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN. CONCLUSION: We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B

Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.

Long-term Follow-up Results of Tilt Training in Patients with Neurocardiogenic Syncope

BACKGROUND AND OBJECTIVES: Tilt training as a non pharmacological therapy was recently introduced to treat the patients with neurocardiogenic syncope. Tilt training has been known to prevent neurocardiogenic syncope by desensitizing abnormal autonomic reflex. Herein, the early effect of tilt training and the preventive effect on the relapse of syncope were studied during a long-term follow-up period. SUBJECTS AND METHODS: Fifteen patients (11 males) who experienced recurrent syncope, despite drug treatment or were intolerant to drug treatment, among those diagnosed as neurocardiogenic syncope by the head-up tilt test at Samsung Medical Center between March 2000 and May 2003 were recruited. Each patient underwent tilt training after admission and was educated to continue self-tilt training after discharge. Data for recurrences after discharge were obtained via questionnaires on outpatient visits or by telephone interviews. RESULTS: Eleven (73%) of the 15 who underwent tilt training on admission showed therapeutic effects. The mean follow-up period was 21+/-10 months (5-40 months). Only one patient was excluded due to follow-up loss. Ten of the above patients underwent training by themselves for an average of 4 months after discharge, and experience no relapse of syncope during the follow-up period. CONCLUSION: Tilt training maintained its therapeutic effect during long-term follow-up. This could be a new treatment for patients non responsive or intolerant to medical therapy.

Four cases of transient hyperammonemic encephalopathy following continuous infusion of 5-fluorouracil / 대한내과학회지

5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used in the treatment of a variety of solid tumors. Common adverse effects of fluorouracil chemotherapy include diarrhea, mucositis and myelosuppression. However, neurologic toxicities including hyperammonemic encephalopathy are rare and not well recognized. Transient hyperammonemic encephalopathy related to continuous infusion of high-dose 5-FU has rarely been reported. We report four cases of transient hyperammonemic encephalopathy in patients receiving continuous infusion of 5-FU. The mentality of all patients was altered during or just after the infusion of 5-FU. There were no focal neurological signs, laboratory excluding hyperammonemia or radiological abnormalities. After patients received adequate hydration and repeated lactulose enema, the mental status completely recovered within one or two days, and serum ammonium level subsequently returned to normal. In conclusion, we suggest that a transient hyperammonemic encephalopathy should be considered in differential diagnosis of patients receiving continuous 5-FU infusion with altered mentality.

Role of NT-proBNP in Evaluation of Functional Status in Congestive Heart Failure

BACKGROUND AND OBJECTIVE: NT-proBNP, a sensitive and specific marker of congestive heart failure (CHF), is also useful in monitoring the effectiveness of treatment and in predicting prognosis. However, the usefulness of NT-proBNP for measuring the functional capacity as a component of the quality of life (QoL) in patients with CHF remains to be discovered. The Korean Activity Scale/Index (KASI) is a Koreanized tool for measuring the functional capacity in patients with cardiac diseases during daily activities, thus representing the physical domain of the QoL. The purpose of this study was to evaluate the relationship between NT-proBNP and the KASI. SUCJECTS AND METHODS: Between July, 2003 and September, 2003, the NT-proBNP levels were measured in 76 patients with CHF that visited the OPD or who were hospitalized. They were asked to fill out a self-administered questionnaire, from which their KASI scores were obtained. NYHA Fc and Heart Failure scores were also obtained from a history taking and physical examination conducted by the investigator. RESULTS: The level of NT-proBNP increased with increasing NYHA Fc (p<0.001 by Kruskall-Wallis test). The Spearman correlation coefficient between NT-proBNP and the KASI score was -0.730 (p<0.001), which was higher than that between the HF and KASI scores (rho=-0.557, p<0.001). The level of NT-proBNP also had a positive correlation with the HF score (rho=0.706, p<0.001). CONCLUSION: The level of NT-proBNP has a strong negative correlation with the KASI score, reflecting the functional capacity during daily activities. This suggests that NT-proBNP is useful in measuring the functional capacity as an element of the QoL in patients with CHF.

N-Terminal Pro-B-Type Natriuretic Peptide as a Prognostic Marker in Acute Coronary Syndrome

BACKGROUND AND OBJECTIVES: Biochemical markers are useful for the prediction of cardiac events in patients with acute coronary syndrome (ACS). The N-terminal fragment of the BNP prohormone (NT-proBNP), which is synthesized by cardiac ventricles in response to increased wall stress, may be a prognostic marker in ACS. The relation between the NT-pro BNP levels on admission and major adverse cardiovascular events (MACEs) were assessed in a cohort of patients with ACS. SUBJECTS AND METHODS: Between October 2002 and April 2004, blood samples for the determination of NT-proBNP level were obtained on admission from 78 patients with ST-elevation myocardial infarction (STEMI), 32 with non-ST elevation MI(NSTEMI) and 66 with unstable angina (UA). Patients were followed concerning MACEs (death, MI, heart failure, stroke and revascularization) for a median of 7 months in median. RESULTS: 22 patients (13%) had events. The mean NT-proBNP level was significantly lower in the event-free survivors than in those with events (1342+/-1598 versus 6129+/-6522 pg/mL, p<0.0001). The optimal cut-off value of the NT-proBNP level using a receiver-operating-characteristic curve was 1445 pg/mL. The unadjusted risk ratio of patients with an NT-proBNP level greater than the threshold was 7.0 (95% confidence interval, 2.6 to 19.0). In a multivariate Cox regression model, including clinical background factors and other biochemical markers, the NT-proBNP level was the most powerful indicator of MACEs (risk ratio, 8.0 [95% confidence interval, 1.7 to 37.1]). The coronary angiographic Gensini score was also a predictor of prognosis in ACS (risk ratio, 3.8 [95% confidence interval, 1.0 to 14.0]). CONCLUSION: A single measurement of the NT-proBNP level on admission appears to be useful as a prognostic factor in the prediction of MACEs in patients after ACS.