Faculty Bibliography

BACKGROUND:Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. PATIENTS AND METHODS/METHODS:We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS:In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). CONCLUSION/CONCLUSIONS:Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

BACKGROUND:Obesity is associated with a higher risk of developing cancer and co-morbidities that are part of the metabolic syndrome. Adipose tissue is recognized as an endocrine organ, as it affects a number of physiological functions, and contains adipose tissue-derived stem cells (ASCs). ASCs can differentiate into cells of multiple lineages, and as such are applicable to tissue engineering and regenerative medicine. Yet the question of whether ASC functionality is affected by the donor's body mass index (BMI) still exists. RESULTS:ASCs were isolated from patients having different BMIs (BMI-ASCs), within the ranges of 18.5-32.8. It was hypothesized that overweight BMI-ASCs would be more compromised in early adipogenic and osteogenic potential, and ability to form colonies in vitro. BMI was inversely correlated with ASC proliferation and colony forming potential as assessed by CyQUANT proliferation assay (fluorescence- based measurement of cellular DNA content), and colony forming assays. BMI was positively correlated with early time point (day 7) but not later time point (day 15) intracytoplasmic lipid accumulation as assessed by Oil-Red-O staining. Alizarin red staining and RT-PCR for alkaline phosphatase demonstrated that elevated BMI resulted in compromised ASC mineralization of extracellular matrix and decreased alkaline phosphatase mRNA expression. CONCLUSIONS:These data demonstrate that elevated BMI resulted in reduced ASC proliferation, and potentially compromised osteogenic capacity in vitro; thus BMI is an important criterion to consider in selecting ASC donors for clinical applications.

BACKGROUND:Free silicone injection for breast augmentation, which became widespread in the 1960s and continues illicitly to this day, has well-known adverse effects. In this retrospective chart review of 14 patients treated for silicone mastitis from 1990 to 2002, we present our experience with the surgical management of patients with silicone mastitis. METHODS:All the patients were women, ranging in age from 49 to 76 years old (mean age = 58.8). Patients presented to us a mean of 29.9 years after their free silicone breast injection. Treatment modalities were analyzed, and, specifically, methods of breast reconstruction involving autologous tissue transfers, implants, or a combination were evaluated. RESULTS:The majority of patients (12 of 14) required mastectomies for extensive silicone-infiltrated tissues. The remaining two patients had focal areas of disease and were successfully treated with excision and local breast parenchyma flaps. Autologous reconstruction was performed with a total of 20 flaps, including 12 free transverse rectus abdominis myocutaneous flaps, 4 free superior gluteal artery perforator (SGAP) flaps, and 4 pedicled latissimus dorsi (LD) flaps. Two patients had bilateral implant-based breast reconstruction. CONCLUSION/CONCLUSIONS:A variety of reconstructive options are available for patients presenting with silicone mastitis. Once an appropriate breast cancer workup has been performed, the surgical goal is to excise as much of the silicone-infiltrated tissues as possible before reconstruction. To our knowledge, this is the first reported series that incorporates the use of SGAP and LD flaps as a means of autologous tissue reconstruction for silicone-infiltrated breasts. LEVEL OF EVIDENCE IV/METHODS:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and have diverse functions during development and organogenesis. BMPs play a major role in skeletal development and bone formation, and disruptions in BMP signaling cause a variety of skeletal and extraskeletal anomalies. Several knockout models have provided insight into the mechanisms responsible for these phenotypes. Proper bone formation requires the differentiation of osteoblasts from mesenchymal stem cell (MSC) precursors, a process mediated in part by BMP signaling. Multiple BMPs, including BMP2, BMP6, BMP7 and BMP9, promote osteoblastic differentiation of MSCs both in vitro and in vivo. BMP9 is one of the most osteogenic BMPs yet is a poorly characterized member of the BMP family. Several studies demonstrate that the mechanisms controlling BMP9-mediated osteogenesis differ from other osteogenic BMPs, but little is known about these specific mechanisms. Several pathways critical to BMP9-mediated osteogenesis are also important in the differentiation of other cell lineages, including adipocytes and chondrocytes. BMP9 has also demonstrated translational promise in spinal fusion and bone fracture repair. This review will summarize our current knowledge of BMP-mediated osteogenesis, with a focus on BMP9, by presenting recently completed work which may help us to further elucidate these pathways.

SUMMARY/CONCLUSIONS:The report herein describes the use of a venocutaneous fistula with angiocatheter attachment and near-infrared spectroscopy device to correct venous congestion of a vertical upper gracilis free flap used for breast reconstruction. This method of mechanical leeching was precisely controlled through monitoring trends in the tissue oxygen saturation levels of the flap, allowing venous congestion to be relieved before it became clinically apparent.

In 1971, Micheal Hogan introduced the Lateral Port Control Pharyngeal Flap (LPCPF) which obtained good results with elimination of VPI. However, there was a high incidence of hyponasality and OSA. We hypothesized that preoperative assessment with videofluoroscopy and nasal endoscopy would enable modification and customization of the LPCPF and result in improvement in the result in both hyponasality and obstructive apnea while still maintaining results in VPI. Thirty consecutive patients underwent customized LPCPF. All patients had preoperative diagnosis of VPI resulting from cleft palate. Patient underwent either videofluoroscopy or nasal endoscopy prior to the planning of surgery. Based on preoperative velar and pharyngeal movement, patients were assigned to wide, medium, or narrow port designs. Patients with significant lateral motion were given wide ports while patients with minimal movement were given narrow ports. There was a 96.66% success rate in the treatment of VPI with one patient with persistent VPI (3.33%). Six patients had mild hyponasality (20 %). Two patients had initial OSA (6.67%), one of which had OSA which lasted longer than six months (3.33%). The modifications of the original flap description have allowed for success in treatment of VPI along with an acceptably low rate of hyponasality and OSA.

BACKGROUND:The classic Whipple operation carries substantial risk of complications. A pylorus-preserving pancreaticoduodenectomy might confer the benefit of decreased perioperative morbidity, but existing data comparing both techniques are inconclusive. METHODS:Using a propensity score model to adjust for potentially confounding differences in patient characteristics, 30-d mortality, operative time, red blood cell transfusion requirements, major complications, and length of hospital stay were compared between both techniques in the American College of Surgeons' National Surgical Quality Improvement Program database. Separate analyses were carried out for underlying malignancy or benign disease, as defined by International Classification of Diseases, Ninth Revision codes. RESULTS:A total of 6988 pancreaticoduodenectomies from 2005 through 2010 were included. In 5424 patients (77.6%) with underlying malignancy, there were no significant differences for 30-d mortality (2.4% versus 2.8%, P = 0.33) and major organ system complications (all P > 0.10). Patients undergoing the classic Whipple operation had a significantly longer operative time (389 versus 366 min, P < 0.01), longer length of hospital stay (13.1 versus 12.0 days, P < 0.01), and higher red blood cell transfusion requirements (1.0 versus 0.8 units, P < 0.01). Results were similar for 1564 patients (22.4%) with underlying benign disease, except for a higher occurrence of postoperative pulmonary (P = 0.02) and renal (P = 0.05) complications in patients undergoing the classic Whipple operation. CONCLUSIONS:Short-term outcomes after classic and pylorus-preserving pancreaticoduodenectomy in this large, multicenter database are excellent, without significant differences in postoperative mortality and most major organ system complications. However, small advantages in resource and blood utilization may be accomplished with the pylorus-preserving technique.

PURPOSE/OBJECTIVE:Peripheral tissue oxygen saturation (Sto2) has shown promise as an early indicator of tissue hypoperfusion and as a risk stratification tool in various forms of shock. The purpose of this study was to determine if Sto2 would predict admission to an intensive (ICU) or progressive care unit in patients with early signs of sepsis. METHODS:In this prospective observational study, a rapid response team measured Sto2 levels in patients screening positive for sepsis. Using a logistic regression model, the value of Sto2 as a predictor for ICU admission within 72 hours of the initial assessment was determined. RESULTS:The 31 (47%) of 66 patients who required ICU admission within 72 hours of evaluation had a significantly lower Sto2 value (median, 78% vs 81%; P = .05). All patients with Sto2 less than 70% required ICU admission. A 1-point increase in Sto2 was associated with a 7% decrease in the odds of requiring ICU admission, and the area under the curve for Sto2 was 0.64 (0.51-0.77, P = .01). CONCLUSIONS:Low Sto2 levels in patients screening positive for sepsis are associated with an increased risk of ICU admission, but their reliability as a predictor is rather low. An Sto2 below 70% might be an interesting cutoff value for further study.

Rectovaginal fistula is a rare but debilitating complication of a variety of pelvic operations. Management remains challenging with high incidence of failure. The majority of patients eventually require surgical intervention. Several surgical procedures have been described including local repair, muscle transposition, or laparotomy. Among the muscles used for rectovaginal fistula repair, the gracilis muscle interposition flap is an excellent option. However, in a small percentage of cases it fails, and alternative techniques should be entertained. We describe the case of a 50-year-old female who underwent stapled hemorrhoidopexy that was complicated by a 30 mm rectovaginal fistula, and required fecal diversion. Four months later, gracilis muscle interposition flap was performed but failed. The right gracilis flap was then re-used successfully as a "walking" flap. At three months the patient underwent closure of the temporary loop ileostomy, and continues to do well with no evidence of rectovaginal fistula recurrence one year later. To our knowledge, this is the first report of the use of a gracilis muscle as a "walking" flap for repair of a rectovaginal fistula, and should be considered as an alternative appropriate treatment for persistent rectovaginal fistulas after failure of initial gracilis muscle interposition flap.