Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well‐known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin‐induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm ). Then, agmatine (10, 100, 500 μm ) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration‐dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin‐induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L‐NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L‐NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L‐NAME combination attenuated CIS‐induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L‐NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co‐administration ameliorates cisplatin‐induced neuropathy and may be a therapeutic alternative.     

Factors Predicting Iliac Metastasis and Overall Survival in Malignant Melanoma of the Lower Extremities

Background : To analyse the patient-related, disease-related and treatment-related factors in a group of melanoma patients to assess their impact on iliac metastasis and on overall survival.

Methods : Medical records of thirty nine patients with lower extremity malignant melanoma were retrospectively reviewed to confirm all of the clinical data. Age and gender were recorded as patient-related factors. Tumor location, size, histology, ulceration status, and TNM stage, Breslow thickness, Clark level, presence of inguinal LN metastases, and locoregional metastases (local recurrences, in transit metastases and regional LN metastases) were evaluated as disease-related factors. Type of surgery (en block excision of primary tumor, en block excision of primary tumor and inguinal lymph node dissection, en block excision of primary tumor and ilioinguinal lymph node dissection) and postoperative chemotherapy were taken into account as treatment-related factors.

Results : The presence of inguinal lymph node metastases was significantly associated with iliac metastasis (p = 0.015). Tumor size (p = 0.046), tumor TNM stage (p = 0.009), Breslow thickness (p = 0.033), Clark level (p = 0.029), presence of in transit metastases (p = 0.010) and postoperative chemotherapy (p = 0.002) has been related to impaired overall survival rate.

Conclusions : Therapeutic lymph node dissection appears to carry a small but definite therapeutic benefit. Selection of appropriate patients for the more extensive procedure would be ideal, but at present there are no well proven selection criteria. The authors advocate therapeutic dissection when the inguinal lymph nodes are involved.