Overall prognostic impact of C-reactive protein level in patients with metastatic renal cell carcinoma treated with sorafenib.

C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC were treated with sorafenib at our institution. The patients were divided into two cohorts according to the pretreatment CRP level: (i) a normal CRP cohort (≤0.30 mg/dl) and (ii) an elevated CRP cohort (>0.30 mg/dl). Kaplan-Meier overall survival analysis was carried out. The effects of selected variables on survival were assessed by multivariate regression using the Cox proportional hazards model. The normal CRP cohort included 16 patients (40.0%) and the elevated CRP cohort included 24 patients (60.0%). The normal CRP cohort showed significantly longer overall survival than the elevated CRP cohort (median, 52.0 vs. 17.0 months; P=0.0072). On multivariate analysis, normal CRP predicted longer overall survival (hazard ratio, 0.367; 95% confidence interval, 0.147-0.914; P=0.0313). Pretreatment normal CRP predicted better overall survival in patients with metastatic RCC treated with sorafenib and CRP level may be a useful biomarker for predicting overall survival of patients treated with sorafenib.

Stevens-Johnson syndrome induced by sorafenib for metastatic renal cell carcinoma.

Sorafenib is an orally administered active multikinase inhibitor for metastatic renal cell carcinoma that is now considered a standard agent. Skin toxicity, such as hand-foot skin reaction, is one of the frequent adverse effects of sorafenib. On the other hand, sorafenib-induced erythema multiforme is very rare, and Stevens-Johnson syndrome and toxic epidermal necrolysis induced by sorafenib have not been reported. We report the first case of Stevens-Johnson syndrome caused by sorafenib for metastatic renal cell carcinoma.

Erythema multiforme induced by sorafenib for metastatic renal cell carcinoma.

OBJECTIVE: Sorafenib is one of the few standard agents for metastatic renal cell carcinoma. Although sorafenib-induced erythema multiforme is rarely reported, we evaluated the cases of erythema multiforme induced by sorafenib for metastatic renal cell carcinoma. METHODS: From November 2006 to November 2011, 36 eligible patients who had been treated with sorafenib were enrolled in this study. Patients received sorafenib 200 or 400 mg orally, twice daily, at 12 h intervals, on a continuous dosing schedule. All patients who experienced rash or erythema multiforme underwent a skin biopsy, and the histopathological diagnosis was confirmed. RESULTS: Twenty-eight patients (78%) experienced a skin reaction of any toxicity grade. Hand-foot skin reactions occurred in 17 (47%), erythema multiforme in 9 (25%), rash/desquamation in 6 (17%) and alopecia in 9 (25%). Skin biopsy was performed and histopathological diagnosis was confirmed for all nine patients (25%) who experienced erythema multiforme. All nine showed a positive reaction to sorafenib on a subsequent patch test. CONCLUSIONS: Sorafenib-induced erythema multiforme may not be rare in Japanese patients. Patients who once showed erythema multiforme after sorafenib treatment are never to be treated with sorafenib again. Patients treated with sorafenib should be monitored carefully, with a multidisciplinary approach. Consultation with a dermatologist is critical because some cases quickly become severe.

[Myocardial metastasis from renal cell carcinoma treated with sorafenib].

We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.

[Holmium laser enucleation of the prostate (HoLEP) in patients with continuous oral anticoagulation: first reported cases in Japan].

Oral anticoagulation (OA) has been considered as a strict contraindication to transurethral resection of the prostate (TURP). In recent years, some studies have shown that holmium laser enucleation of the prostate (HoLEP) has less blood loss compared to TURP. Thus we have performed HoLEP in patients with benign prostatic hyperplasia (BPH) under continuous OA from September 2009, and herein we report our first nine cases. Patients received HoLEP by a single surgeon at our institution. HoLEP was performed successfully in all patients. The mean times to complete enucleation and morcellation were 48.2 and 5.1 minutes, respectively. The mean tissue weight of enucleation was 37 grams. The mean hemoglobin and sodium loss after HoLEP were 1.7 g/dl and 1.3 mEq/L, respectively, and the catheterization time was 1.6 days. Blood transfusion, clot retention or transurethral resection syndrome were not observed in any cases. HoLEP has excellent hemostatic properties, and is a safe and effective procedure for patients with symptomatic BPH under the condition of continuous OA.

[An effective method to shorten the learning curve of HoLEP].

Holmium laser enucleation of the prostate (HoLEP) is a safe and effective treatment for patients with symptomatic benign prostatic hyperplasia (BPH), but is a difficult operation. To shorten the learning curve, we evaluated the surgical outcome of successive bilateral lobe enucleations with HoLEP. Performed by an inexperienced endourologist and an expert. Between March and July on 2009, we evaluated 20 cases of HoLEP performed by a beginner who underwent successive bilateral lobe enucleations and 20 cases of HoLEP performed by an expert. Enucleation time was shortened when successive bilateral lobe enucleations were performed by the beginner using HoLEP (115 vs 92 minutes, p<0.05). The enucleation time was significantly shorter in the expert group than in the beginner group. However, there were no significant differences in morcellation time, enucleated tissue weight, hemoglobin decrease level, sodium decrease level, catheterization time or significant incontinence time between the two groups. The postoperative evaluations was excellent in both groups. We conclude that HoLEP is a safe and effective operation. However, close supervision by an expert is required. In addition, learning from the easier part of enucleation to elaborate skill sets required to perform HoLEP is prerequisite for success.

[A case of primary pulmonary nocardiosis with multiple pulmonary nodules successfully treated with moxifloxacin].

A 18-year-old man was admitted with fever. His chest radiograph and CT scan showed consolidation shadow in the right middle lobe and multiple nodules in both lungs. He was treated with meropenem and minocycline. After this antibiotic therapy, the consolidation shadow disappeared and the multiple nodules were slightly reduced in their size. Since filamentous bacteria suspicious of Nocardia grew transiently in the initial sputum culture, we started to treat him with oral sulfametoxazole-trimethoprim. However, because agranulocytosis was caused by sulfametoxazole-trimethoprim therapy, we had to change the anti-bacterial therapy to minocycline. Minocycline was not effective, and the nodules enlarged. For accurate diagnosis, we employed video-assisted thoracic surgery (VATS) to investigate the histological and bacterial analyses of the pulmonary nodules. Histological findings of the pulmonary nodule obtained by VATS revealed granuloma with central necrosis associated with neutrophilic micro-abscess. Filamentous gram-positive bacteria in pulmonary nodule tissue was stained positively with both Grocott and Ziehl-Neelsen staining. Taking these findings together, we diagnosed primary pulmonary nocardiosis. Three months after initiating moxifloxacin, the size of the multiple pulmonary nodules was markedly reduced. Our experience with this case suggests that moxifloxacin can be recommended for the treatment of pulmonary nocardiosis.

[Case of shakuyakukanzoto-induced CD4 dominant pneumonitis diagnosed on day eight of the challenge test].

We report a case of drug-induced pneumonia associated with the herbal medine Syakuyakukanzo-to. A 82-year-old man was admitted to our hospital complaining of cough, fever, and dyspnea after administration of shakuyakukanzoto for two weeks. Drug-induced lymphocyte stimulation tests were negative, but bronchoalveolar lavage showed an increase in lymphocytes with an increased CD4/CD8 ratio. Cessation of the drug improved the patient's clinical and X-ray findings and then he was able to be discharged. He was admitted again for a challenge test. His clinical symptoms and X-ray findings became worse 8 days after re-administration, therefore we diagnosed drug-induced pneumonia caused by Shakuyakukanzoto. He has had no recurrence after discontinuance of the drug. To the best of our knowledge, there has been no previous case of drug-induced pneumonia due to Shakuyakukanzo-to reported in the world.