Bone turnover biomarkers identify unique prognostic risk groups in men with castration resistant prostate cancer and skeletal metastases: Results from SWOG S0421.

BACKGROUND: Skeletal metastases often occur in men with castration-resistant prostate cancer (CRPC) where bone biomarkers are prognostic for overall survival (OS). In those with highly elevated markers, there is preferential benefit from bone-targeted therapy. In the phase IIIS0421 docetaxel +/- atrasentan trial, clinical covariates and bone biomarkers were analyzed to identify CRPC subsets with differential outcomes. SUBJECTS AND METHODS: Markers of bone resorption [N-telopeptide-NTx; pyridinoline-PYD] and formation [C-terminal collagen propeptide-CICP; bone alkaline phosphatase-BAP] were measured in pre-treatment sera. Bone biomarkers and clinical covariates were included in a Cox model for OS; bone markers were added in a stepwise selection process. Receiver operating characteristic (ROC) curves were constructed for risk factor models +/- bone markers. Significant variables were allowed to compete in a classification and regression tree (CART) analysis. Hazard ratios(HR) were calculated by comparing OS in each of the terminal nodes to a reference group in a Cox model. RESULTS: 750 patients were included. Each bone marker significantly contributed to the risk factor-adjusted OS Cox model, with higher levels associated with worse OS. BAP (HR = 1.15, p = 0.008), CICP (HR = 1.27, p < 0.001), and PYD (HR = 1.21, p = 0.047) in combination were significantly associated with OS. Prognostic accuracy was improved by addition of bone markers to clinical covariates. CART analysis selected CICP, BAP, hemoglobin, and pain score for the final OS model, identifying five prognostic groups. CONCLUSIONS: Elevated serum bone biomarker levels are associated with worse OS in bone-metastatic CRPC. Bone biomarkers can identify unique prognostic subgroups. These results further define the role of bone biomarkers in the design of CRPC trials.

Primary primitive neuroectodermal tumor of the kidney. Case report and review of the literature.

Small cell tumors are a heterogeneous group of neoplasms with similar morphologic features. They include lymphomas, carcinomas with variable degrees of neuroendocrine differentiation, rhabdomyosarcomas, and neuroblastomas. The authors describe a rare case of primitive neuroectodermal tumor (PNET) located in the kidney that was thoroughly studied with modern diagnostic techniques, including expression of protein P 30/32 MIC2 with the antibody 013 with subsequent demonstration of a genetic translocation consistent with t(11;22). The literature on small cell tumors of the kidney, with special emphasis on PNET, is reviewed.

Closure of laparoscopic trocar sites using a spring-loaded needle.

Closure of laparoscopic trocar sites can be difficult, particularly in the obese patient. We have begun using a spring-loaded needle to facilitate closure of these sites. We have found that the device allows for accurate suture placement, the potential of decreased closure time, reduced risk for trocar site dehiscence, and can be used in obtaining hemostasis of abdominal wall vessels.

Uric acid stone and gastric bladder augmentation.

We describe a stone occurring in a bladder augmented with stomach. The stone was composed of uric acid, the expected mineral component in an acid medium.

Multimodal therapy for neoplasms arising from a vesical diverticulum.

Both radical cystectomy and diverticulectomy for the treatment of neoplasms arising in a vesical diverticulum have resulted in poor survival, mainly secondary to early metastatic spread. In this study, nine patients were treated with a multispecialty approach in hopes of eradicating both local and distant disease. All patients underwent a combination of therapeutic modalities with three patients undergoing pre-operative radiotherapy (RT) and diverticulectomy; diverticulectomy and chemotherapy (three patients); diverticulectomy with chemotherapy and pre-operative RT (two patients); and definitive RT with cisplatin (one patient). With a mean follow-up of 4.0 years (median 3.2), four patients are free of disease, two are dead of other causes, one patient has developed an invasive recurrence, one patient is alive with metastatic disease, and one patient is dead of disease. Five patients (55%) developed local recurrences. Disease-specific survival for the group was 89%. Surgical monotherapy has been ineffective in controlling both local and metastatic disease in patients with diverticular tumors. This study suggests a significant benefit from systemic chemotherapy and RT when combined with surgery for these neoplasms.