NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines

The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST.     

Ten-year survival analysis of the PFC total knee arthroplasty-a surgeon’s first 99 replacements

Ninety-seven patients with 99 total knee arthroplasties were operated on by a surgeon in the first 3 years of his surgical career. Complete survival data were available for all 99 knees. The cases were reviewed at a minimum of 10 years after their initial operation, but as 37 patients had died before reaching 10 years, the average follow-up was 8 years 8 months with a maximum of 12 years 4 months. Ninety-one patients had osteoarthritis, five had rheumatoid arthritis, and three had juvenile chronic arthritis. No patients were lost to follow-up. Four required revision. The 10-year survival rate, using revision for all causes as an end-point, was 94.96%. The survival rate for aseptic loosening was 97.04%. The survival rate for loose joints that had not been revised was 94.13%. Three of the four revisions occurred in the first 6 patients operated upon, suggesting there may be a learning curve for surgeons at this stage in their career.     

Evaluation of prognostic factors in medically treated patients of spinal tuberculosis

This study was aimed to determine the prognostic factors in medically treated patients of spinal tuberculosis. In this longitudinal observational study, from July 2010 to December 2011, 70 consecutive patients (40 males and 30 females) spinal tuberculosis were enrolled. Diagnosis of spinal tuberculosis was based on characteristic clinical and neuroimaging features. Diagnosis was histopathologically and/or bacteriologically verified. Patients received antituberculous treatment as per World Health Organization guidelines and were followed for 6 months. Disability was evaluated with modified Barthel index (MBI). Outcome was defined as good (MBI > 12) and poor (MBI ≤ 12). Various clinical and neuroimaging parameters, likely to affect the outcome, were analyzed using univariate and multivariate analysis. After 6 months, 45 patients had a good outcome, while 25 patients had a poor outcome. On univariate analysis, duration of illness >6 months (OR 0.062, CI 0.018–0.212), bladder involvement (OR 0.102, CI 0.033–0.317), spinal deformity (OR 0.050, CI 0.013–0.196), spastic paraparesis (OR 0.572, CI 0.190–1.723), and flexor spasms (OR 0.077, CI 0.021–0.280) were found as important clinical predictors of poor outcome. Involvement of more than 2 vertebrae (OR 0.095, CI 0.028–0.328), complete collapse (OR 0.072, CI 0.022–0.241), cord compression (OR 0.025, CI 0.003–0.204), spinal extension of the abscess (OR 0.044, CI 0.005–0.350), and thick/septate abscess wall (OR 0.062, CI 0.016–0.240) were the neuroimaging parameters associated with poor prognosis. However, on multivariate analysis, duration of illness >6 months (Exp-b 0.086, CI 0.019–0.378), cord compression (Exp-b 0.035, CI 0.003–0348), and spinal extension of the abscess (Exp-b 0.109, CI 0.017–0.91) were significant. Medical management results in clinical improvement in a majority of the patients of spinal tuberculosis. Duration of illness >6 months, cord compression, and spinal extension of abscess are associated with poor outcome.     

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction

Summary— Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H₂O₂. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0***) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24–96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 ± 0.80 (T0***) to 4.57 ± 1.24 (peak), and decreased to 2.96 ± 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.7 ± 7.5 hours. The iron increased significantly from 0.67 ± 0.34 (T0) to 1.15 ± 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 ± 0.28 UI/L at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.4 ± 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.     

Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.     

Single Miniplate Fixation for Mandibular Symphysis and Parasymphysis Fracture as a Viable Alternative to Conventional Plating Based on Champy’s Principles: A Prospective Comparative Clinical Study

To compare long term and short term outcomes of fixing mandibular symphysis and parasymphysis fractures with single mini plate and conventional fixation using two mini plates. Study design: in this prospective clinical comparative study, 30 patients with fracture in study region were randomly divided into two groups. Group A patients received single 2.5 mm titanium miniplate and Group B patients received two 2 mm titanium miniplates as per Champy's lines of osteosynthesis. Patients were followed up at intervals of 1, 12 and 24 weeks. Parameters assessed were: duration of surgery, fracture stabilization, paresthesia, occlusion and wound dehiscence. Statistically significant difference was observed in mean duration of surgery and wound dehiscence (P < 0.05). No significant difference was observed with respect to other parameters. Single 2.5 mm miniplate for mandibular symphysis and parasymphysis fractures is a time saving and cost effective technique with post-operative outcomes similar to conventional 2 plate fixation.