Michael E. Lidsky

Airway interventions in children with Pierre Robin Sequence.

Objective To describe the interventions required for successful airway management in children with Pierre Robin Sequence (PRS). Study Design Case series. Subjects and Methods The records of both a cleft and craniofacial clinic and a pediatric otolaryngology clinic were searched, and all children with PRS were identified. Data concerning feeding interventions, airway interventions, and comorbid conditions were extracted. Results Seventy-four cases of PRS were identified. Thirty eight of the 74 children required airway intervention other than prone positioning. Fourteen of these 38 were managed nonsurgically with nasopharyngeal airway and/or short-term endotracheal intubation, whereas the remaining 24 required surgical intervention. Eighteen of the 24 underwent distraction osteogenesis of the mandible, one underwent tracheostomy, and five underwent tracheostomy followed by eventual distraction. Conclusion In our series, over 50 percent of children with PRS required an airway intervention. These were both nonsurgical and surgical. As otolaryngologists, we must be prepared for the challenges children with PRS may present and the interventions that may be necessary to successfully manage these difficult airways.

Resolving Feeding Difficulties With Early Airway Intervention in Pierre Robin Sequence

Objectives/Hypothesis: To observe rates of gastrostomy tube (g‐tube) placement in Pierre Robin Sequence (PRS) and to determine whether relieving airway obstruction solves feeding difficulties.

Examining Reoperation and Readmission after Hepatic Surgery

BACKGROUND Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy. STUDY DESIGN Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy. RESULTS Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission. CONCLUSIONS In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care.

Laparoscopic Versus Open Hartmann Procedure for the Emergency Treatment of Diverticulitis: A Propensity-matched Analysis

BACKGROUND: A laparoscopic approach has been proposed to reduce the high morbidity and mortality associated with the Hartmann procedure for the emergency treatment of diverticulitis. OBJECTIVE: The objective of our study was to determine whether a laparoscopic Hartmann procedure reduces early morbidity or mortality for patients undergoing an emergency operation for diverticulitis. DESIGN: This is a comparative effectiveness study. A subset of the entire American College of Surgeons National Surgical Quality Improvement Program patient sample matched on propensity for undergoing their procedure with the laparoscopic approach were used to compare postoperative outcomes between laparoscopic and open groups. SETTING: This study uses data from the American College of Surgeons National Surgical Quality Improvement Program Participant User Files from 2005 through 2009. PATIENTS: All patients who underwent an emergency laparoscopic or open partial colectomy with end colostomy for colonic diverticulitis were reviewed. MAIN OUTCOME MEASURES: The main outcome measures were 30-day mortality and morbidity. RESULTS: Included in the analysis were 1186 patients undergoing emergency partial colectomy with end colostomy for diverticulitis. Among the entire cohort, the laparoscopic group had fewer overall complications (26% vs 41.7%, p = 0.008) and shorter mean length of hospitalization (8.9 vs 11.6 days, p = 0.0008). Operative times were not significantly different between groups. When controlling for potential confounders, a laparoscopic approach was not associated with a decrease in morbidity or mortality. In comparison with a propensity-match cohort, the laparoscopic approach did not reduce postoperative morbidity or mortality. LIMITATIONS: This study is limited by its retrospective nature and the absence of pertinent variables such as postoperative pain indices, time for return of bowel function, and rates of readmission. CONCLUSIONS: A laparoscopic approach to the Hartmann procedure for the emergency treatment of complicated diverticulitis does not significantly decrease postoperative morbidity or mortality in comparison with the open technique.

A comparison of tibial artery bypass performed with heparin-bonded expanded polytetrafluoroethylene and great saphenous vein to treat critical limb ischemia

BACKGROUND Expanded polytetrafluoroethylene (ePTFE) bonded with heparin (HePTFE) has been reported to perform equivalent to saphenous vein graft (SVG) for below-knee bypass. This series examines outcomes for tibial artery bypass using HePTFE and SVG over a contemporaneous time period. METHODS A retrospective analysis of prospectively collected data was conducted for 112 tibial bypasses (62 HePTFE, 50 SVG) performed from November 2006 to January 2009. Demographics for age, sex, race, diabetes mellitus, and end-stage renal disease were similar. Indications for revascularization were also similar: disabling claudication, 9%; rest pain, 25%; and tissue loss, 66%. The HePTFE group included more reoperative procedures (45% vs 26%). All HePTFE bypasses were performed using an autologous vein patch at the distal anastomosis. Postoperative graft surveillance by pulse examination, ankle-brachial index, and duplex ultrasound imaging occurred at 1, 3, 6, and 12 months. Follow-up ranged from 1 to 12 months. Kaplan-Meier and Cox regression analysis evaluated results in patients with no missing variables. RESULTS HePTFE and SVG bypasses demonstrated no significant differences in target tibial artery distribution: anterior tibial (15 vs 17), dorsalis pedis (4 vs 5), posterior tibial (22 vs 16), and peroneal (21 vs 12). Graft occlusion occurred in 19 patients (16.9%) during follow-up. Primary patency at 1 year was 75.4% for HePTFE and 86.0% for SVG. There was no significant difference in primary patency due to sex (male, 78%; female, 84%), race (white, 82%; African American, 77%), or diabetes mellitus (no diabetes mellitus, 84%; diabetes mellitus, 76%). End-stage renal disease resulted in decreased patency (57%), with an eightfold reduction (95% confidence interval, 1.8%-39.8%; P = .006). SVG patients had a lower risk of occlusion/death (95% confidence interval, 14.2%-94.5%; P > .05). Sixteen amputations were performed, with no significant difference based on conduit. CONCLUSIONS This experience indicates a trend for single-segment quality saphenous vein to remain the conduit of choice for tibial artery bypass compared with HePTFE. Factors relevant to decreased 1-year patency for the entire cohort were end-stage renal disease and nonhealing ulceration as the indication for revascularization. Although relatively short-term, these results do support HePTFE as a viable alternative conduit for patients with absent or poor quality saphenous vein who need a tibial bypass.

Advanced age is an independent predictor for increased morbidity and mortality after emergent surgery for diverticulitis

BACKGROUND The objectives of our study were to determine the association between age and postoperative outcomes after emergency surgery for diverticulitis and to identify risk factors for postoperative mortality among elderly patients. METHODS All patients from the American College of Surgeons National Surgical Quality Improvement Program 2005-2009 Participant User Files undergoing emergent surgery for diverticulitis were included. Multivariate logistic regression was used to determine the association between age and postoperative morbidity and mortality after adjustment for perioperative variables. A separate regression model was used to determine risk factors for postoperative mortality among elderly patients, with specific postoperative complications being included as potential predictors. RESULTS We included 2,264 patients for analysis, of whom 1,267 (56%) were <65 years old (nonelderly), 648 (28.6%) were 65-79 years old (elderly), and 349 (15.4%) were ≥80 years old (super-elderly). Advanced age was a significant predictor of 30-day postoperative mortality, and to a lesser extent postoperative morbidity. Among those patients ≥65 years old, super-elderly age classification remained a significant predictor of mortality after adjustment for the presence or absence of postoperative complications. Mortality among elderly and super-elderly patients was greatest in the setting of specific complications, such as septic shock, prolonged postoperative mechanical ventilation, and acute renal failure. CONCLUSION Advanced age is an independent risk factor for death after emergency surgery for diverticulitis, with mortality being greatest among elderly patients who experience certain postoperative complications. Prevention of these complications should form the cornerstone of initiatives designed to lower the mortality associated with emergency surgery in elderly patients.

Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.

Background: The response to vemurafenib in V600E BRAF+ve melanoma is short lived due to acquisition of vemurafenib resistance. Results: NRAS expression and increased MAPK activation drive vemurafenib resistance in V600E BRAF+ve melanoma. Conclusion: Resistance to vemurafenib in melanoma is complex and can be mitigated by MAPK and NRAS inhibition. Significance: These findings could lead to improved therapy of V600E BRAF+ve melanoma by targeting MAPKs and NRAS. Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acquisition of resistance to BRAF-targeted therapy in previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem, had higher growth rates and showed differential collateral resistance to cisplatin, melphalan, and temozolomide. The acquisition of vemurafenib resistance was associated with significantly increased NRAS levels in A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells that involves increased activation of all three human MAPKs and the PI3K pathway, as well as increased NRAS expression, which, contrary to previous reports, was not associated with mutations in the NRAS gene. The data highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of optimizing BRAF-targeted therapy in this disease. They also suggest that targeting the MAPKs and/or NRAS may provide a strategy to mitigate such resistance in V600E BRAF+ve melanoma.

Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers

Objective: This study compares outcomes following pancreaticoduodenectomy (PD) for patients treated at local, low-volume centers and those traveling to high-volume centers. Background: Although outcomes for PD are superior at high-volume institutions, not all patients live in proximity to major medical centers. Theoretical advantages for undergoing surgery locally exist. Methods: The 1998 to 2012 National Cancer Data Base was queried for T1–3N0–1M0 pancreatic adenocarcinoma patients who underwent PD. Travel distances to treatment centers were calculated. Overlaying the upper and lower quartiles of travel distance with institutional volume established short travel/low-volume (ST/LV) and long travel/high-volume (LT/HV) cohorts. Overall survival was evaluated. Results: Of 7086 patients, 773 ST/LV patients traveled ⩽6.3 (median 3.2) miles to centers performing ⩽3.3 PDs yearly, and 758 LT/HV patients traveled ≥45 (median 97.3) miles to centers performing ≥16 PDs yearly. LT/HV patients had higher stage disease (P < 0.001), but lower margin positivity (20.5% vs 25.9%, P = 0.01) and improved lymphadenectomy (16 vs 11 nodes, P < 0.01). Moreover, LT/HV patients had shorter hospitalizations (9 vs 12 days, P < 0.01) and lower 30-day mortality (2.0% vs 6.3%, P < 0.01) with similar 30-day readmission rates (10.1% vs 9.8%, P = 0.83). Despite more advanced disease, LT/HV patients had superior unadjusted survival (20.3 vs 15.7 months). After adjustment, travel to a high-volume center remained associated with reduced long-term mortality (hazard ratio 0.75, P < 0.01). Conclusions: Despite an increased travel burden, patients treated at high-volume centers had improved perioperative outcomes, short-term mortality, and overall survival. These data support ongoing efforts to centralize care for patients undergoing PD.

Hepatic Resection for Hepatocellular Carcinoma: Do Contemporary Morbidity and Mortality Rates Demand a Transition to Ablation as First-Line Treatment?

BACKGROUND Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. STUDY DESIGN Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. RESULTS Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001). CONCLUSIONS Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible.

The role of dynamic contrast-enhanced magnetic resonance imaging in the diagnosis and management of patients with vascular malformations.

OBJECTIVE Vascular malformations are uncommon but may confer significant morbidity. Limitations in diagnosis and treatment result from inadequate classification schema and diagnostic algorithms. The crucial distinction is between high-flow and low-flow lesions because this informs prognosis and treatment. This study assessed the utility of dynamic contrast-enhanced magnetic resonance imaging (dceMRI) in distinguishing high-flow from low-flow lesions, a technique that has previously not been widely applied or evaluated in this patient population. METHODS A prospective database of all patients referred to the multidisciplinary vascular malformation team at our institution was reviewed from January 2006 to June 2010. dceMRI was obtained on each patient to determine flow characteristics and lesion extent. Additional studies were used as indicated. Catheter-based arteriography was performed when high-flow lesions were identified with the intention of intervening or to distinguish between high-flow and low-flow lesions when MRI was indeterminate. A triage algorithm was used to stratify patients and formulate therapeutic goals. We analyzed the accuracy of dceMRI in identifying high-flow and low-flow lesions. RESULTS The study included 122 patients (aged <1 to 70 years) comprising 52 males (42.6%) and 70 females (57.4%). Pain (72 patients; 59%) and swelling (88 patients; 72.1%) were the most common presenting symptoms. All patients underwent dceMRI. Of these, 68 had confirmatory imaging (n = 15) or intervention (n = 53). The dceMRI was able to definitively and correctly distinguish high-flow from low-flow lesions in 57 studies, for an accuracy rate of 83.8%. In the remaining 11 studies, dceMRI correctly queried flow status but not definitively, and confirmatory angiography was required. CONCLUSIONS Using a diagnostic tool designed to identify key clinical characteristics, we were able to successfully distinguish between high-flow and low-flow vascular malformations using dceMRI alone in 83.8% of patients, minimizing the need for unnecessary invasive catheter-based procedures.