Seth D. Goldstein

Use of Respiratory-Correlated Four-Dimensional Computed Tomography to Determine Acceptable Treatment Margins for Locally Advanced Pancreatic Adenocarcinoma

PURPOSE Respiratory-induced excursions of locally advanced pancreatic adenocarcinoma could affect dose delivery. This study quantified tumor motion and evaluated standard treatment margins. METHODS AND MATERIALS Respiratory-correlated four-dimensional computed tomography images were obtained on 30 patients with locally advanced pancreatic adenocarcinoma; 15 of whom underwent repeat scanning before cone-down treatment. Treatment planning software was used to contour the gross tumor volume (GTV), bilateral kidneys, and biliary stent. Excursions were calculated according to the centroid of the contoured volumes. RESULTS The mean +/- standard deviation GTV excursion in the superoinferior (SI) direction was 0.55 +/- 0.23 cm; an expansion of 1.0 cm adequately accounted for the GTV motion in 97% of locally advanced pancreatic adenocarcinoma patients. Motion GTVs were generated and resulted in a 25% average volume increase compared with the static GTV. Of the 30 patients, 17 had biliary stents. The mean SI stent excursion was 0.84 +/- 0.32 cm, significantly greater than the GTV motion. The xiphoid process moved an average of 0.35 +/- 0.12 cm, significantly less than the GTV. The mean SI motion of the left and right kidneys was 0.65 +/- 0.27 cm and 0.77 +/- 0.30 cm, respectively. At repeat scanning, no significant changes were seen in the mean GTV size (p = .8) or excursion (p = .3). CONCLUSION These data suggest that an asymmetric expansion of 1.0, 0.7, and 0.6 cm along the respective SI, anteroposterior, and medial-lateral directions is recommended if a respiratory-correlated four-dimensional computed tomography scan is not available to evaluate the tumor motion during treatment planning. Surrogates of tumor motion, such as biliary stents or external markers, should be used with caution.

Assessment of Robotic Thymectomy Using the Myasthenia Gravis Foundation of America Guidelines

BACKGROUND Robotic thymectomy is an emerging treatment for myasthenia gravis. However, the Myasthenia Gravis Foundation of America clinical research standards have been infrequently adopted in the surgical literature. METHODS Twenty-six patients underwent robotic thymectomy for myasthenia gravis between 2003 and 2008, performed by a single surgeon using the da Vinci system (Intuitive Surgical; Sunnyvale, CA) through a four-port right-sided approach. RESULTS Mean operative times were 68+/-25 minutes of robotic system activation and 127+/-35 minutes from incision to closure. There were no intraoperative or postoperative mortalities; the most common intraoperative complication was desaturation after single-lung ventilation, for which four procedures were converted to open. On histologic examination, there were five thymomas. The average follow-up after surgery was 26 months. Median preoperative and postoperative Myasthenia Gravis Foundation of America disease classifications were 2 and 0, respectively, reflecting a statistically significant decrease in symptoms (p<0.01). Additionally, the average daily dose of cholinesterase inhibitor decreased by 63% postoperatively. Overall, 82% of patients improved and 18% were unchanged; no worsening disease was observed. CONCLUSIONS Robotic thymectomy is a safe and efficacious treatment option for myasthenia gravis. There were no notable differences in patient demographics compared with previously published reports of open thymectomies. Furthermore, surgical and neurologic outcomes in this series compare favorably with conventional approaches in the literature. Of those with follow-up greater than 6 months, 82% of patients undergoing robotic thymectomy demonstrated significant clinical improvement postoperatively, indicating that this approach in concert with optimized medical management is an effective treatment for myasthenia gravis.

Perioperative strategies and technical modifications to the Nuss repair for pectus excavatum in pediatric patients: A large volume, single institution experience

BACKGROUND The safety and efficacy of minimally invasive pectus excavatum repair have been demonstrated over the last twenty years. However, technical details and perioperative management strategies continue to be debated. The aim of the present study is to review a large single-institution experience with the modified Nuss procedure. METHODS A retrospective review was performed of patients who underwent primary pectus excavatum repair at a single tertiary hospital via a modified Nuss procedure that included: no thoracoscopy, retrosternal dissection achieved via a left-to-right thoracic approach, four-point stabilization of the bar, and no routine epidural analgesia. Data collected included demographics, preoperative symptoms, operative characteristics, hospital charges and postoperative outcomes. RESULTS A total of 336 pediatric patients were identified. No cardiac perforations occurred and the rate of pericarditis was 0.6%. Contemporary rates of bar displacement have fallen to 1.2%. Routine use of chlorhexidine scrub reduced superficial site infections to 0.7%. Two patients (0.6%) with severe recurrence required reoperation. Bars were removed after an average period of 31.7(SD 13.2) months, with satisfactory cosmetic and functional results in 94.9% of cases. CONCLUSIONS We report here a single-institution large volume experience, including modifications to the Nuss procedure that make the technique simpler and safer, improve results, and minimize hospital charges.

A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model

The outcome of patients with metastatic osteosarcoma has not improved since the introduction of chemotherapy in the 1970s. Development of therapies targeting the metastatic cascade is a tremendous unmet medical need. The Wnt signaling pathway has been the focus of intense investigation in osteosarcoma because of its role in normal bone development. Although the role of Wnt signaling in the pathogenesis of osteosarcoma is controversial, there are several reports of dickkopf-1 (DKK-1), a Wnt signaling antagonist, possibly playing a pro-tumorigenic role. In this work we investigated the effect of anti-DKK-1 antibodies on the growth and metastasis of patient-derived osteosarcoma xenografts. We were able to detect human DKK-1 in the blood of tumor-bearing mice and found a correlation between DKK-1 level and tumor proliferation. Treatment with the anti-DKK-1 antibody, BHQ880, slowed the growth of orthotopically implanted patient-derived osteosarcoma xenografts and inhibited metastasis. This effect was correlated with increased nuclear beta-catenin staining and increased expression of the bone differentiation marker osteopontin. These findings suggest that Wnt signaling is anti-tumorigenic in osteosarcoma, and support the targeting of DKK-1 as an anti-metastatic strategy for patients with osteosarcoma.

Age at presentation of common pediatric surgical conditions: Reexamining dogma

PURPOSE The commonly cited ages at presentation of many pediatric conditions have been based largely on single center or outdated epidemiologic evidence. Thus, we sought to examine the ages at presentation of common pediatric surgical conditions using cases from large national databases. METHODS A retrospective analysis was performed on Healthcare Cost and Utilization Project databases from 1988 to 2009. Pediatric discharges were selected using matched ICD9 diagnosis and procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis (HPS), incarcerated inguinal hernia (IH), and Hirschsprung disease (HD). Descriptive statistics were computed. RESULTS A total of 63,750 discharges were identified, comprising 2744 cases of malrotation, 5831 of intussusception, 36,499 of HPS, 8564 of IH, and 10,112 of HD. About 58.2% of malrotation cases presented before age 1. Moreover, 92.8% of HPS presented between 3 and 10weeks. For intussusception, 50.3% and 91.4% presented prior to ages 1 and 4years, respectively. Also, 55.8% of IHD cases presented before their first birthday. For HD, 6.5% of cases presented within the neonatal period and 45.9% prior to age 1year. CONCLUSION Our findings support generally cited presenting ages for HPS and intussusception. However, the ages at presentation for HD, malrotation, and IH differ from commonly cited texts.

Regionalization of Pediatric Surgery: Trends Already Underway

Introduction:This study aims to characterize the delivery of pediatric surgical care based on hospital volume stratified by disease severity, geography, and specialty. Longitudinal regionalization over the 10-year study period is noted and further explored. Methods:The Kids’ Inpatient Database (KID) was queried from 2000 to 2009 for patients <18 years undergoing noncardiac surgery. Hospitals nationwide were grouped into commutable regions and identified as high-volume centers (HVCs) if they had more than 1000 weighted procedures per year. Regions that had at least one HVC and one or more additional lower volume center were included for analysis. Low-risk, high-risk neonatal, and surgical subspecialties were analyzed separately. Results:A total of 385,242 weighted pediatric surgical admissions in 33 geographical regions and 224 hospitals were analyzed. Overall, HVCs comprised 33 (14.7%) hospitals, medium-volume center (MVC) 33 (14.7%), and low-volume center (LVC) 158 (70.5%). The four low-risk procedures analyzed were increasingly regionalized: appendectomy (52% in HVCs in 2000 to 60% in 2009, P < 0.001), fracture reduction (63% to 68%, P < 0.001), cholecystectomy (54% to 63%, P < 0.001), and pyloromyotomy (65% to 85%, P < 0.001). Neonatal surgery showed significant regionalization trends for tracheoesophageal fistula (66% to 87%, P < 0.001) and gastroschisis (76% to 89%, P < 0.001). Conclusions:This is the first large-scale, multi-region analysis to demonstrate that pediatric surgical care has transitioned to HVCs over a recent decade, particularly for low-risk patients. It is important for practitioners and policymakers alike to understand such volume trends in order to ensure hospital capacity while maintaining an optimal quality of care.

A randomized trial of laparoscopic versus open Nissen fundoplication in children under two years of age

AIMS The surgery of gastroesophageal reflux disease (GERD) is common in modern pediatric surgical practice. Any differences in perioperative and long-term clinical outcomes following laparoscopic (LN) or open Nissen (ON) fundoplication have not been comprehensively described in young children. This randomized, prospective study examines outcomes following LN versus ON in children<2 years of age. METHODS Four surgeons at a single institution enrolled patients under 2 years of age that required surgical management of GERD, who were then randomized to LN or ON between 2005 and 2012. A universal surgical dressing was employed for blinding. Analgesia and enteral feeding pathways were standardized. The primary outcome was postoperative length of stay. Perioperative outcomes and long-term follow up were collected as secondary outcomes and used to compare groups. RESULTS Of 39 enrolled patients, 21 were randomized to ON and 18 to LN. Length of postoperative hospital stay, time of advancement to full enteral feeds, and analgesic requirements were not significantly different between treatment cohorts. The LN group experienced longer median operating times (173 vs 91 min, P<0.001) and higher surgical charges (

Initial bladder closure of the cloacal exstrophy complex: Outcome related risk factors and keys to success

4450 vs

A pilot comparison of standardized online surgical curricula for use in low- and middle-income countries.

2722, P=0.002). The incidence of post-discharge complications did not differ significantly between the groups at last follow-up (median 42 months). CONCLUSIONS This randomized trial comparing postoperative outcomes following LN vs ON did not detect statistically significant differences in short- or long-term clinical outcomes between these approaches. LN was associated with longer surgical time and higher operating room costs. The benefits, risks, and costs of laparoscopy should be carefully considered in clinical pediatric surgical practice.

Thymectomy for myasthenia gravis in children: A comparison of open and thoracoscopic approaches

PURPOSE This study examines a large single-institution experience with cloacal exstrophy patients, analyzing patient demographics and surgical strategies predictive of bladder closure outcomes. METHODS One hundred patients with cloacal exstrophy were identified. Complete closure history including demographics, operative history, and outcomes was available on 60 patients. Twenty-six patients with a history of failed initial bladder closure were compared to 34 with a history of successful initial bladder closure. Univariate logistic regression analysis was used to compare the two groups. RESULTS Median follow up time after initial closure was 9years (range: 13months-29years). A 1cm increase in pre-closure diastasis resulted in a 2.64 increase in the odds of initial closure failure (p=0.004). Protective strategies against failure included delaying closure (per month) (OR=0.894, p=0.009), employing pelvic osteotomies (OR=0.095, p<0.001), and applying external fixation (OR=0.024; p=0.001). Among patients who underwent osteotomy (31% of patients in the failed group, 82% in the successful group), a longer delay between osteotomy and closure (OR=0.033; p=0.005) was also protective against failure. CONCLUSION Patients with a large diastasis are more likely to fail initial closure. Delaying initial closure for at least 3months, performing pelvic osteotomy, and using an external fixation device post-operatively are strategies that improve closure success.