Citations

OBJECTIVESTo report the oncology and functional outcomes of transoral laser microsurgery (TLM) for untreated glottic carcinoma.STUDY DESIGNA 2 center prospective case series analysis.SETTINGAcademic, tertiary referral centers.RESULTSSeventy‐six patients underwent TLM. Pathologic T stages were: T1, 45 (59%); T2, 21 (28%); T3, 5 (7%); and T4, 5 (7%). Five (7%) patients had neck dissections. Five (7%) patients received adjuvant radiotherapy. Mean follow‐up was 42 months. Respective T1 and T2 5‐year Kaplan‐Meier estimates were: local control, 90% and 93%; loco‐regional control, 90% and 93%; disease specific survival, 90% and 93%; and overall survival, 94% and 93%. The average hospital stay was 2 days. Two (3%) patients experienced major complications. The overall laryngeal preservation rate was 95% (72 of 76).CONCLUSIONSTLM is a safe and effective treatment in select carcinoma of the glottic larynx. Low morbidity and mortality and short periods of hospitalization make TLM an attractive therapeutic option.SIGNIFICANCETLM is an emerging strategy in the treatment of laryngeal cancer.

Abstract Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).

Abstract The role of genes that influence the risk of developing pancreatic cancer (PC) has not been well studied. The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multifunctional and has been implicated in many diseases, including cancer. To evaluate whether single nucleotide polymorphisms in mitochondrial DNA (mtSNP) are associated with increased risk of PC, we screened Caucasian cases diagnosed or seen at the Mayo Clinic with primary pancreatic adenocarcinoma (n = 955), and healthy clinic-based Caucasian controls (n = 1,102). A total of 24 mtSNPs, including 10 of the most common tagSNPs, 7 non-tagSNPs in the coding region, and 7 common SNPs in the regulatory region were genotyped. For analysis, these samples were grouped into two phases, the “testing” set (474 cases and 615 controls), and the “validation” set (481 cases and 487 controls). In the testing set, one mtSNP (SNP11719) suggested an association in single SNP analysis, with an odds ratio of 1.34 (95% confidence intervals, 1.05-1.72; P = 0.020), but did not remain statistically significant after correction for multiple testing. In the validation set, none of the 24 variants indicated any association with PC. For haplogroup analysis, 10 core SNPs that form common haplogroups in Caucasians (1719, 4580, 7028, 8251, 9055, 10398, 12308, 13368, 13708, and 16391) were evaluated. No significant associations with PC were identified either by analyzing the two sets separately or combined (combined global P = 0.17). Overall, these results do not support a significant involvement of mitochondrial DNA variation in the risk of developing PC. Investigation of other mitochondrial genetic variations (i.e., nuclear-encoded mitochondrial proteins) would be necessary to elucidate any role of mitochondrial DNA variation in PC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1455–9)

OBJECTIVE—Type 1 and type 2 diabetes are characterized by an ∼98 and ∼65% loss of pancreatic β-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility of promoting β-cell replacement and/or regeneration. Islet transplantation has been explored, but it does not provide long-term insulin independence. One possible source of β-cell regeneration is hematopoietic stem cells. In mice, there are conflicting data as to whether hematopoietic stem cells contribute to pancreatic β-cells. We sought to establish whether hematopoietic stem cells (derived from adult donors) transdifferentiate into pancreatic β-cells in adult humans. RESEARCH DESIGN AND METHODS—We addressed this in 31 human pancreata obtained at autopsy from hematopoietic stem cell transplant recipients who had received their transplant from a donor of the opposite sex. RESULTS—Whereas some donor-derived cells were observed in the nonendocrine pancreata, no pancreatic β-cells were identified that were derived from donor hematopoietic stem cells, including two cases with type 2 diabetes. CONCLUSIONS—We conclude that hematopoietic stem cells derived from adult donors contribute minimally to pancreatic β-cells in nondiabetic adult humans. These data do not rule out the possibility that hematopoietic stem cells contribute to pancreatic β-cells in childhood or in individuals with type 1 diabetes.

Compared with adults, infants and children who undergo cardiopulmonary bypass for cardiac surgery present with a myriad of anticoagulation considerations. Inadequate anticoagulation during cardiopulmonary bypass may cause “subclinical” or “overt” thrombosis, while effective anticoagulation decreases excessive bleeding and transfusions. Current strategies for heparinization and its neutralization in pediatric patients undergoing congenital heart repair requiring cardiopulmonary bypass are examined. The coagulation system of the neonate and infant is immature and is further weakened by congenital heart disease. Changes in coagulation and fibrinolytic activity occur during cardiopulmonary bypass as a result of hemodilution and exposure of the blood to the extracorporeal circuit. Adequate anticoagulation is essential to minimize the thrombin generation that will result. The extent of excessive thrombin formation in pediatric patients undergoing cardiopulmonary bypass is better appreciated today than in the past, but no controlled study defines the optimal dose or technique for heparin dosing in these patients. Heparin concentration may even fall to 1.5 U/mL during cardiopulmonary bypass. However, the activated clotting time and heparin concentration correlate poorly. The ideal method to achieve adequate thrombin inhibition is unknown. Additionally, the dangers of excessive protamine are becoming more apparent. Heparin continues to be the most effective agent to achieve anticoagulation and protamine the most effective agent to neutralize it. A technique for heparin and protamine dosing with determination of heparin concentrations, may remove many variables associated with pediatric cardiac surgery that requires cardiopulmonary bypass and may provide clinicians with new therapies to achieve better anticoagulation for patients and consequently better outcomes.

The Cognitive Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r=0.393; p=0.008) and 30 months (r=0.742; p=0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r=0.181; p=0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were graded and compared to similar tissue from 12 cadaveric spec imens. All studies were done by a single pathologist who had no knowledge of the origin of the specimen. The surgical specimens were interpreted as abnormal in all 11 specimens, and all 12 of the control specimens were reported as being without histologic abnormality. Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens. Neither feature was present in any of the control material (P < 0.001). These data suggest that chronic refractory lateral epicondylitis requiring sur gery is a degenerative rather than inflammatory proc ess. This may account for the lack of response to rest and antiinflammatory medication.

This study analyzed forces in the tibiofemoral and pa tellofemoral joints during isokinetic exercise using an analytical biomechanical model. The results show that isokinetic exercise can produce large loads on these joints, especially during extension exercises. The tibio femoral compressive force (4.0 body weight) is approx imately equal to that obtained during walking but it occurs at 55° of knee flexion. Anterior shear forces (resisting force to anterior drawer) exist during exten sion exercise at less than 40° of knee flexion, with a maximum of 0.3 body weight. Posterior shear forces (resisting force to posterior drawer) exist during exten sion exercise at knee joint angles greater than 40° and during the flexion portion of isokinetic exercise. The maximum posterior shear force is 1.7 body weight. The patellofemoral joint can encounter loads as high as 5.1 body weight which are 10 times higher than during straight leg raises. These results suggest that isokinetic exercise should be used cautiously in patients with knee lesions.