Tumor length and location of cancer on biopsy predict for side specific extraprostatic cancer extension

PURPOSE: We studied preoperative variables in a contemporary series of men who underwent nonnerve sparing radical prostatectomy in an effort to establish criteria that would predict side specific extraprostatic extension (EPE) of cancer. MATERIALS AND METHODS: We reviewed the records of 430 patients who underwent radical prostatectomy for localized prostate cancer with no prior therapy between 1996 and 1998, and for whom we had at least sextant biopsy information. We evaluated biopsy data (Gleason score, maximum length of cancer in positive cores, percent of cancer per involved core, proportion of positive biopsy cores, tumor location and number of positive biopsy cores) and correlated these findings with EPE at the neurovascular bundle and posterior lateral (NVB/PL) region. RESULTS: We found that a higher number of positive cores, a higher biopsy Gleason score on a side, a positive core at the basal region, 50% or greater tumor in the core or a maximum tumor length of 7 mm or greater increased the likelihood that EPE was present at the NVB/PL region on the corresponding side of the prostate. On multivariate analysis maximum tumor length 7 mm or greater and positive basal core location were the strongest independent predictors of EPE at the NVB/PL region on a given side (p <0.0001 and 0.002, respectively). CONCLUSIONS: Excluding any patient with 1 positive biopsy core with a maximum tumor length of 7 mm or greater plus a positive basal core of any tumor length and grade can decrease the risk of EPE at the NVB/PL region to approximately 10%.     

Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors

PURPOSE: Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation. MATERIALS AND METHODS: From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor. RESULTS: All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free. CONCLUSION: Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.     

The role of complement receptors in production of antibodies specific for Galalpha1,3Gal

By using alpha-galactosyl transferase knockout (GT-/-) mice, which make natural alphaGal-reactive antibodies, we examined the role of complement receptors in the production of alphaGal-specific antibodies. GT-/- mice were crossed with complement receptor 2 loci knockout mice to generate double knockout (DKO) mice. alphaGal-specific natural antibodies were detectable by enzyme-linked immunosorbent assay in the serum of GT-/- mice by 9 weeks of age. In contrast, only low titers of alphaGal-specific natural antibodies were detectable only in the serum of older DKO mice. Serum titers of alphaGal-reactive antibodies in GT-/- mice increased significantly after immunization with pig cells. In contrast, immunization had little effect on alphaGal-reactive antibody levels in DKO mice. Similarly, pretreatment of GT-/- mice with a blocking antibody to CD21 and CD35 inhibited production of alphaGal-reactive antibodies after immunization. However, DKO mice were able to make alphaGal-specific antibodies after secondary immunization. Thus, Cr2 loci-encoded receptors seem to be directly involved in the production of primary alphaGal-reactive antibodies.     

Balancing severe valgus deformity in total knee arthroplasty using a lateral cruciform retinacular release

We report the technique and results of a cruciform lateral release performed on 35 consecutive knees having > or =15 degrees of valgus with minimum 2-year follow-up. The posterior cruciate ligament (PCL) was preserved in all knees. Preoperative valgus averaged 17 degrees, and range of motion averaged 10 degrees to 107 degrees. Postoperative valgus averaged 4.8 degrees, and average postoperative range of motion was 2 degrees to 110 degrees. The PCL was partially released in 5 knees, and further lateral release of the lateral collateral ligament and popliteus were required in 3 knees. Stable flexion and extension gaps were achieved in all cases, and stability was maintained at follow-up. This lateral cruciform retinacular release provides a simple surgical technique for most valgus deformities of the knee and allows for stable ligamentous balancing.     

Severe Protein-Calorie Malnutrition after Bariatric Procedures

Background: Serious nutritional complications after Roux-en-Y gastric bypass (RYGBP) are infrequent. In a retrospective study of patients operated during a 68-month period, malnutrition was investigated to analyze circumstances associated with nutritional failure. Methods: In 236 consecutive RYGBPs, 11 patients with severe malnutrition were identified (4.7%) with age 45.1 ± 10.6 years (10 females/1 male) and initial BMI 54.6 ± 8.4 kg/m². Results: In these 11 patients, the derangement was diagnosed 17.9 ± 15.8 months after RYGBP, following defined events in 63.6% (gastric stenosis, associated diseases ) or mostly exaggeration of expected symptoms in 36.4% (vomiting without endoscopic abnormalities). BMI then was 31.4 ± 8.6 kg/m² (42.5 ± 9.9% total reduction, or 2.4 ± 2.1% decrease/month), and serum albumin and hemoglobin were 24.0 ± 8.2 g/L and 97.0 ± 23.0 g/L respectively. Edema was present in 45.4% (5/11), hospitalization was required in 54.5% (6/11), and 18.2% (2/11) eventually died. Conclusions: Serious malnutrition was unusual but not exceedingly rare in this series. Exogenous precipitating factors were clearly identified in 63.6% of the patients. Careful clinical and nutritional follow-up is recommended to prevent these uncommon but potentially dangerous complications.     

Improving resident research in physical medicine and rehabilitation: impact of a structured training program

OBJECTIVE: This study describes a research training program that implemented several processes and structures with the aim of increasing the quality and quantity of resident research in physical medicine and rehabilitation. Another aim of the program was to address the Accreditation Council for Graduate Medical Education (ACGME) Practice-Based Learning and Improvement competency. DESIGN: Educational program. RESULTS: Data on resident research activity for 11 years before the implementation of the research program were compared with 4 years of data after implementation. There were statistically significant increases in both the total number of publications (P = 0.03) and the number of empirical, data-based publications after implementation of the program (P = 0.03). CONCLUSIONS: The findings from this study suggest that a structured research training program may have a salutary effect on increasing the quality and quantity of resident research.     

Allergen immunotherapy in the prevention of asthma

PURPOSE OF REVIEW: Asthma is a disease causing significant morbidity and mortality. In the recent past, there has been an explosion of pharmacotherapeutic options attempting to control the disease. Unfortunately, none of the current options offers the promise of prevention or a permanent cure. However, there appear to be exciting, new data emerging to support the hypothesis that the prevention or early treatment of allergic rhinitis, such as with the use of allergen immunotherapy, may help mitigate the severity of bronchial symptoms and even prevent the development of asthma. In this paper, we review recent research published proposing immunotherapy as a means of preventing the development of, or at least ameliorating, allergic asthma. RECENT FINDINGS: There is evidence that the upper and lower airways may be considered a single unit, with the nasal and bronchial mucosa having features in common. Epidemiological, pathophysiological and clinical studies have shown that they can be affected by similar inflammatory triggers, with interconnected mechanisms amplifying the inflammatory cascade. Allergic rhinitis is interrelated to, and is a risk factor for, the development of asthma. An evidence-based review validates the successful use of allergen immunotherapy in treating allergic rhinitis and asthma. There is promising evidence advocating its use in the prevention of clinical asthma. SUMMARY: This article explores current research pertaining to the use of immunomodulation, such as by using allergen immunotherapy, to ameliorate and prevent the development of allergic asthma.     

Absorbable microparticulate cation exchanger for immunotherapeutic delivery

An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy.