New Strategies for Colorectal Cancer Prevention and Treatment

Colorectal cancer (CRC) is the second most common fatal malignancy in the Western world, with more than 150,000 new cases accounting for 55,000 deaths in the United States every year. Surgical resection is an effective treatment for localized disease, achieving a 5-year survival rate of 90%; but chemotherapy and other novel treatments for metastatic disease remain ineffective. There have been significant efforts to identify risk factors associated with the development of CRC and to explore potential preventive therapies. Both genetic and epigenetic factors contribute to the development of colorectal cancer. Specific genetic changes in proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes have led to a genetic model of CRC. Cooperative genetic aberrations involving APC (adenomatous polyposis coli), beta-catenine, K-ras, and p53 are involved in the multistep adenoma-carcinoma sequence of CRC. Emerging data have implicated cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of colorectal carcinoma. Several reports indicate a close relation between the intake of nonsteroidal antiinflammatory drugs (NSAIDs) and a decreased risk for developing colorectal cancer. Epidemiologic studies indicate a 40% to 50% reduction in mortality due to colorectal cancer in individuals taking NSAIDs (e.g., aspirin). Epigenetic factors including age, diet, angiogenesis, and immune responses also appear to contribute to the development of CRC. Combining knowledge of the genetic and epigenetic events implicated in this disease may allow a broader understanding of the pathogenesis of CRC. These developments may yield benefits in earlier detection and in the design of better antitumor interventions.     

Outcome treatment of pseudoarthrosis of long bones with decortication method depends on osteosynthesis]

Purpose of work was estimation of the results of treatment of pseudoarthrosis of the long bone with the method of decortication, with use of autogenic bone depends on kind of pseudoarthrosis and kind of osteosynthesis. In the years 1995-2005 56 patients were treated because of pseudoarthrosis of long bone in our Clinic. Pseudoarthrosis is classified according to Weber-Cech classification. In the methodology of clinical estimation and subjective estimation of the patient Stewart and Hundley and Anderson classification were used. Union was achieved in 51 cases. Time of bone union achievement was 5 months. The results of treatment are depends on morfology of pseudoartrosis and are independs of kind of osteosynthesis.     

Correlation between thigh pain and radiological findings with a proximally porous-coated stem

Thigh pain has been consistently reported with cementless hip arthroplasty. The correlation between thigh pain and radiological findings and the clinical significance of thigh pain have not been studied in any detail. We carried out a retrospective study to analyse the performance of a proximally porous-coated cementless femoral component. Ninety-eight total hip arthroplasties were followed up clinically and radiologically for an average of 33 months (range: 12 to 64) after operation. The clinical results were good or excellent in 85 cases (87%). Thirteen patients (13%) reported thigh pain at latest follow-up. Subsidence of the stem was recorded in 10 cases, cortical thickening occurred in 14 hips (14%), and 17 hips (17%) presented proximal osteopenia. Proximally, radiolucent lines were observed in 11 cases. Thigh pain correlated with radiolucent lines, femoral thickening, fibrous fixation and stem migration. Bone remodelling was noted to continue even five years after implantation. Our observations demonstrated bone ingrowth in the majority of the cases and a low incidence of thigh pain. The correlation between radiological changes and thigh pain suggests implant micromotion and migration in some hips. Patients with thigh pain, changes in the proximal femur and progressive subsidence need further clinical and radiological follow-up.     

Tattooing Breast Cancers Treated with Neoadjuvant Chemotherapy

Background In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy. Methods In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy. Results Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion. Conclusions On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.     

Lateral popliteal sciatic nerve block: a single injection targeting the tibial branch of the sciatic nerve is as effective as a double-injection technique

BACKGROUND: Evidence indicating that single- and double-injection techniques for inducing a sciatic nerve block via a posterior subgluteal approach yield a similar success rate prompted us to investigate whether the two anesthetic techniques yield a similar success rate via a lateral approach. We also hypothesized that, owing to the peculiar anatomic features of the sciatic nerve at the popliteal level, a single injection via the lateral approach might induce effective anesthesia by targeting the tibial nerve only. METHODS: Ninety-six patients undergoing popliteal sciatic nerve block via a lateral popliteal approach for foot surgery were randomized to receive a single 30-ml injection of ropivacaine 7.5 mg/ml to block the tibial nerve (TN group, n= 32) or the common peroneal nerve (CPN group, n= 32), or two separate 15-ml injections (TN + CPN group, n= 32), after stimulation to evoke motor responses from the target nerves. RESULTS: The mean time to obtain a complete sensory blockade (surgical anesthesia) was shorter in the TN group than in the CPN and TN + CPN groups (14 +/- 7 min vs. 23 +/- 17 and 21 +/- 14 min, respectively; P < 0.05). The success rate was similar in the TN and TN + CPN groups (94%) and, 25 min after the initial injection, was already better in these groups than in the CPN group (94% vs. 75%; P < 0.05). CONCLUSIONS: A lateral popliteal sciatic nerve block obtained with a single 30-ml injection of ropivacaine 7.5 mg/ml after electrostimulation to locate the tibial nerve is as effective as multiple TN + CPN stimulation and injection, and local anesthesia has a significantly shorter onset time.     

Avantage double mobility press--fit cup in total hip arthroplasty]

The Avantage double mobility press-fit cup was devised by Dr. Bousquet in the 70's to bring reasonable response to a problem of recurrent dislocation after total hip arthroplasty. The cup is attached to the femoral head by a bipolar polyethylene liner. The polyethylene liner moves freely inside a shiny--polished metal cup. The angular range of motion before impingement is increased by the mobility of the liner. The double connection (cup-liner, liner-head) reduces the stress on the metal cup and improve the stability of the prosthesis. The solution has proved to be efficient in reducing dislocation risk and maintains at the same time the appropriate range of motion. Between January 2004 and November 2005, 113 hip arthroplasties in 108 women with use of the double mobility cup were performed. The cemented version of the Avantage cup was inserted in 15 patients (mean age--76.9 years). Uncemented, HA coated implant was used in 98 patients (with mean age of 55 years). The mean follow-up was 20.4 months. No one patient was lost to follow-up. No postoperative dislocation was observed during follow-up. There was no unwanted leg lengthening greater than 1 cm. The Avantage cup may be indicated in any primary total hip arthroplasty especially in those with increased risk of postoperative dislocations. This cup enables a correct balance of the hip without a need of the unwanted lengthening of the leg.     

Mechanisms of shock wave induced endothelial cell injury

BACKGROUND AND OBJECTIVES: Medical procedures, for example, laser angioplasty and extracorporeal lithotripsy as well as high-energy trauma expose human tissues to shock waves (SWs) that may cause tissue injury. The mechanisms for this injury, often affecting blood vessel walls, are poorly understood. Here we sought to assess the role of two suggested factors, viz., cavitation or reactive oxygen species (ROS). STUDY DESIGN/MATERIALS AND METHODS: A laser driven flyer-plate model was used to expose human umbilical cord vein endothelial cell (HUVEC) monolayers to SWs or to SWs plus cavitation (SWC). Cell injury was quantified with morphometry, trypan blue staining, and release of (51)Cr from labeled HUVECs. RESULTS: HUVECs, exposed to SWs only, could not be distinguished from controls in morphological appearance or ability to exclude trypan blue. Yet, release of (51)Cr, indicated a significant cell injury (P < 0.05). HUVEC cultures exposed to SWC, exhibited cell detachment and cell membrane damage detectable with trypan blue. Release of (51)Cr was fourfold compared to SW samples (P < 0.01). Signs of cell injury were evident at 15 minutes and did not change over the next 4 hours. No protective effects of ROS scavengers were demonstrated. CONCLUSIONS: Independent of ROS, SWC generated an immediate cell injury, which can explain, for example, vessel wall perturbation described in relation to SW treatments and trauma.     

Medullary Thyroid Cancer: Are Practice Patterns in the United States Discordant From American Thyroid Association Guidelines?

Background  

Surgery is the mainstay of treatment for medullary thyroid cancer (MTC), with long-term patient outcomes associated with adequacy of resection. This study benchmarked national practice patterns against 2009 American Thyroid Association (ATA) guidelines for MTC regarding use of thyroidectomy, lymphadenectomy, radioactive iodine (RAI), and external-beam radiotherapy (EBRT).     

Predictors of Survival in Sinonasal Adenocarcinoma

Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15–0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26–0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis.     

Surgically Managed Gastrointestinal Stromal Tumors: A Comparative and Prognostic Analysis

BACKGROUND: Tyrosine kinase inhibitors have been shown to have marked clinical efficacy in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). We performed a comparative and prognostic analysis of our experience with surgically managed GIST to determine factors associated with adverse oncologic outcomes. METHODS: Oncologic outcomes of 191 patients with primary GIST surgically managed between 1978 and 2004 at a single institution were reviewed. Prognostic factors were analyzed by Cox analysis (hazard ratio [HR] and 95% confidence interval [95% CI]) and included age, sex, disease presentation (asymptomatic vs. symptomatic), tumor site (stomach, small bowel, colorectal), disease extent (localized vs. metastatic) and risk levels (high, intermediate, low, very-low) assigned on the basis of size and number of mitoses according to current National Institutes of Health recommendations. Primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: A total of 186 patients (97%) had c-kit-positive GIST. There were 54% high, 22% intermediate, 18% low, and 8% very low risk GIST originating from the stomach (54%), small bowel (36%), and colon and rectum (10%). Median patient age was 65 (range, 13-91) years, and 108 subjects (57%) were male. Seventy-two percent of patients had symptomatic local disease, and 21% patients had synchronous metastases. Most (95%) underwent R0 resections of their primary tumor. Among 146 patients (76%) with localized disease at presentation undergoing R0 resection, the 5-year DFS was 65%. High-risk GIST (HR 12, 95% CI, 5-32, P < .0001), symptomatic presentation (HR 2.5, 95% CI, 1.1-6, P = .04), and GIST in the small bowel (HR 2.8, 95% CI, 1-5, P = .003) were independently associated with decreased DFS. After a median follow-up of 63 months among survivors, the 5-year DSS was 68%. High-risk disease (HR 14.3, 95% CI, 5-41, P < .0001), symptomatic presentation (HR 3.1, 95% CI, 1.2-7.9, P = .02), and GIST in the small bowel (2.6,3 95% CI, 1-5, P = .006) were independently associated with decreased DSS. CONCLUSIONS: High-risk GIST are associated with increased disease recurrence and decreased survival despite complete surgical resection. These patients should receive adjuvant therapy in the form of tyrosine kinase inhibitors.