Role of ErbB4 in Breast Cancer

Members of the ErbB subfamily of receptor tyrosine kinases are important regulators of normal mammary gland physiology, and aberrations in their signaling have been associated with breast tumorigenesis. Therapeutics targeting epidermal growth factor receptor (EGFR = ErbB1) or ErbB2 in breast cancer have been approved for clinical use. In contrast, relatively little is known about the biological significance of ErbB4 signaling in breast cancer. This review focuses on recent advances in our understanding about the role of ErbB4 in breast carcinogenesis, as well as in the potential clinical relevance of ErbB4 in breast cancer prognostics and therapy.     

Long-term follow-up of patients with necrotizing enterocolitis

Background/Purpose: Despite the rise in the incidence of necrotizing enterocolitis (NEC), there is a paucity of data regarding long-term patient outcome. The authors examined functional outcome of infants with NEC (n = 103) treated at our institution between 1991 and 1995. Methods: The authors reviewed the medical records of infants who were treated both operatively and nonoperatively, n = 103. Variables examined included gestational age, birth weight, Bell stage (I through III), operations performed, and mortality rate. Telephone interviews assessed school enrollment, developmental delay, bowel function, and nutritional status. Results: Children treated operatively had a lower gestational age than those in the nonoperative group. Likewise, birth weight in the operative group was significantly lower. Sixty-three percent of patients had stage III, and the remainder had stage II disease. The telephone response rate was 61%. Mean age at follow-up was 7.5 [plusmn] 2.5 years. All children ate by mouth. Nearly all children were toilet trained. All children were less than the 50th percentile for height and weight, and the majority (83%) were enrolled in school full time. Conclusion: Infants with stage II and III NEC who are treated operatively or nonoperatively have a favorable long-term outcome. J Pediatr Surg 37:1048-1050.     

Risk factors for splenectomy in children with blunt splenic trauma

Background/Purpose: Nonoperative management and splenic preservation have become standards of care for management of pediatric blunt splenic trauma. However, review of the Pennsylvania Trauma Outcome Study (PTOS) registry found that 15% of children with blunt splenic injury still underwent splenectomy. The authors sought to determine the factors that predisposed to splenectomy in this population. Methods: Between 1993 and 1997, 754 children, ages 0 to 16 years, who sustained blunt splenic trauma were entered in the PTOS database. These patients were stratified into groups according to the mode of management: nonoperative, splenorrhaphy, or splenectomy. Logistic regression was performed to determine factors associated with splenectomy. Results: Overall, 15.1% of patients underwent splenectomy, 7.4% underwent splenorrhaphy, and 77.5% were treated nonoperatively. Spleen injury grade, nonspleen abdominal injuries, Glasgow Coma Scale 3 to 8, and age 15 to 16 years were significant determinants of splenectomy by multivariate analysis. Children treated at pediatric trauma centers (PTC) underwent significantly fewer splenectomies. Conclusions: Injury grade, but not hemodynamic instability, was a significant independent determinant of splenectomy in children with blunt splenic trauma. Children treated at PTC are less likely to undergo splenectomy. Ongoing analysis of the management of blunt pediatric splenic injury and reduction of unnecessary splenectomies are needed to optimize care for injured children.     

Ten-year echocardiographic and clinical follow-up of aortic Carpentier-Edwards pericardial and supraannular prosthesis: a case-match study

BACKGROUND: There are little comparative data on Carpentier-Edwards supraannular and pericardial second-generation bioprostheses. The aim of this work was to compare their hemodynamic and clinical outcomes in patients with aortic stenosis. METHODS: We conducted a retrospective study including 150 patients operated on for aortic stenosis between 1989 and 1993. Patients undergoing aortic valve replacement with either a Carpentier-Edwards supraannular or pericardial prosthesis were matched for sex (49% male), age (72 +/- 8 years), body surface area, valve size, associated procedures, and left ventricular ejection fraction. RESULTS: Mean follow-up was 6.5 +/- 3.3 years, giving a total follow-up of 983 patient-years. Thirty-day mortality and 10-year actuarial survival were, respectively, 8% and 51% in the supraannular group and 6.7% and 43.4% in the pericardial group. At 10 years, freedom from thromboembolism, structural failure, and all valve-related events were, respectively, 88.7%, 88.9%, and 68.7% in the supraannular group and 85%, 100%, and 82.2% in the pericardial group. There were four (5.3%) structural failures, and four (5.3%) reoperations for degeneration (n = 3) and endocarditis (n = 1) in the supraannular group. Freedom from structural dysfunction or reoperation was 87.3% in the supraannular group and 100% (p < 0.05) in the pericardial group. Echocardiographic review of 62 of 76 survivors (81.5%) demonstrated a trend toward a better hemodynamic profile of pericardial valves at the end of follow-up. CONCLUSIONS: Ten years after aortic valve replacement for aortic stenosis, Carpentier-Edwards pericardial prostheses give comparable and probably better results than Carpentier-Edwards supraannular prostheses.     

Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro

BACKGROUND: The authors examined the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels, adenosine A1 receptor, and alpha and beta adrenoceptors in desflurane-induced preconditioning in human myocardium, in vitro. METHODS: The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34 degrees C; stimulation frequency, 1 Hz). Before a 30-min anoxic period, 3, 6, and 9% desflurane was administered during 15 min. Desflurane, 6%, was also administered in the presence of 10 microm glibenclamide, a K(ATP) channels antagonist; 10 microm HMR 1098, a sarcolemmal K(ATP) channel antagonist; 800 microm 5-hydroxy-decanoate (5-HD), a mitochondrial K(ATP) channel antagonist; 1 microm phentolamine, an alpha-adrenoceptor antagonist; 1 microm propranolol, a beta-adrenoceptor antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine (DPX), the adenosine A1 receptor antagonist. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). RESULTS: Desflurane at 3% (95 +/- 13% of baseline), 6% (86 +/- 6% of baseline), and 9% (82 +/- 6% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (50 +/- 11% of baseline). Glibenclamide (60 +/- 12% of baseline), 5-HD (57 +/- 21% of baseline), DPX (63 +/- 19% of baseline), phentolamine (56 +/- 20% of baseline), and propranolol (63 +/- 13% of baseline) abolished desflurane-induced preconditioning. In contrast, HMR 1098 (85 +/- 12% of baseline) did not modify desflurane-induced preconditioning. CONCLUSIONS: In vitro, desflurane preconditions human myocardium against simulated ischemia through activation of mitochondrial K(ATP) channels, adenosine A1 receptor, and alpha and beta adrenoceptors.     

A comparison between fibula and iliac crest in mandibular reconstruction

Nowadays the vascularized free fibula flap and the free iliac crest flap are the methods most frequently used to reconstruct the mandible. This is also the case in our clinic. A retrospective nonrandomized study was performed to compare both flaps. The vascularized fibula free flap and the iliac crest free flap were compared in terms of logistics, flap failure, revisionary surgery, donor site morbidity, and recipient site morbidity. No significant differences in flap failure and revision surgery were found between the fibula group and the iliac crest group. Recipient site and donor site complications (major and minor) were significantly less in the fibula group compared to the iliac crest group. In mandibular reconstruction, the free vascularized fibula flap appears to be superior to the free vascularized iliac crest flap in terms of both recipient site and donor site morbidity.     

Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer

OBJECTIVE: To prospectively evaluate the use of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in the initial staging of squamous cell head and neck carcinoma. SUMMARY BACKGROUND DATA: The status of cervical lymph nodes is an important prognostic factor and determinant of management approach in squamous cell head and neck cancer. METHODS: FDG-PET findings were compared with those of computed tomography (CT) before removal of the primary tumor and/or neck dissection. Histopathologic analysis was used as the gold standard for assessment of the sensitivity and specificity of these modalities. RESULTS: FDG-PET correctly identified the primary tumor in 35 of 40 patients in whom the site of the primary was known clinically and still present (sensitivity 88%). None of four unknown primaries were detected. Tumors not detected by FDG-PET were generally superficial, with depths of less than 4 mm. CT correctly identified 18 of the 35 primary tumors (sensitivity 51%). Eleven of 17 CT false-negative tumors were detected by FDG-PET. The sensitivity and specificity for the presence of metastatic neck disease on FDG-PET were 82% and 100%, respectively; those for CT were 81% and 81%, respectively. FDG-PET was true positive for metastatic neck disease in two of the three CT false-negative patients. CONCLUSIONS: FDG-PET shows promise in the initial staging of head and neck cancer and provides additional accuracy to a conventional staging process using CT.     

Effect of reverse shoulder design philosophy on muscle moment arms

This study analyzes the muscle moment arms of three different reverse shoulder design philosophies using a previously published method. Digital bone models of the shoulder were imported into a 3D modeling software and markers placed for the origin and insertion of relevant muscles. The anatomic model was used as a baseline for moment arm calculations. Subsequently, three different reverse shoulder designs were virtually implanted and moment arms were analyzed in abduction and external rotation. The results indicate that the lateral offset between the joint center and the axis of the humerus specific to one reverse shoulder design increased the external rotation moment arms of the posterior deltoid relative to the other reverse shoulder designs. The other muscles analyzed demonstrated differences in the moment arms, but none of the differences reached statistical significance. This study demonstrated how the combination of variables making up different reverse shoulder designs can affect the moment arms of the muscles in different and statistically significant ways. The role of humeral offset in reverse shoulder design has not been previously reported and could have an impact on external rotation and stability achieved post‐operatively. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:605–613, 2015.     

A new bioabsorbable sleeve for lung staple-line reinforcement (FOREseal™): report of a three-center phase II clinical trial

Objective: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. Methods: This prospective open trial included 66 patients (mean age of 56 ± 17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal™, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH₂O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. Results: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9 ± 2.3 days and 6 ± 5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1 ± 6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. Conclusions: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.