Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Providers' Perceptions Versus Practices Inform Pediatric Colorectal Enhanced Recovery After Surgery Implementation.

INTRODUCTION: There are many barriers to the implementation of an enhanced recovery after surgery (ERAS) pathway. The aim of this study was to compare surgeon and anesthesia perceptions with current practices prior to the initiation of an ERAS protocol in pediatric colorectal patients and to use that information to inform ERAS implementation. METHODS: This was a mixed method single institution study of barriers to implementation of an ERAS pathway at a free-standing children's hospital. Anesthesiologists and surgeons at a free-standing children's hospital were surveyed regarding current practices of ERAS components. A retrospective chart review was performed of 5- to 18-y-old patients undergoing colorectal procedures between 2013 and 2017, followed by the initiation of an ERAS pathway, and a prospective chart review for 18 mo postimplementation. RESULTS: The response rate was 100% (n = 7) for surgeons and 60% (n = 9) for anesthesiologists. Preoperative nonopioid analgesics and regional anesthesia were rarely used. Intraoperatively, 54.7% of patients had a fluid balance of <10 cc/kg/h and normothermia was achieved in only 38.7%. Mechanical bowel prep was frequently utilized (48%). Median nil per os time was significantly longer than required at 12 h. Postoperatively, 42.9% of surgeons reported that patients could have clears on postoperative day zero, 28.6% on postoperative day one, and 28.6% after flatus. In reality, 53.3% of patients were started on clears after flatus, with a median time of 2 d. Most surgeons (85.7%) expected patients to get out of bed once awake from anesthesia; however, median time that patients were out of bed was postoperative day one. While most surgeons reported frequent use of acetaminophen and/or ketorolac, only 69.3% received any nonopioid analgesic postoperatively, with only 41.3% receiving two or more nonopioid analgesics. Nonopioid analgesia showed the highest rates of improvement from retrospective to prospective: preoperative use of analgesics increased from 5.3% to 41.2% (P < 0.0001), postoperative use of acetaminophen increased by 27.4% (P = 0.5), Toradol by 45.5% (P = 0.11), and gabapentin by 86.7% (P < 0.0001). Postoperative nausea/vomiting prophylaxis with >1 class of antiemetic increased from 8% to 47.1% (P < 0.001). The length of stay was unchanged (5.7 versus 4.4 d, P = 0.14). CONCLUSIONS: For the successful implementation of an ERAS protocol, perceptions versus reality must be assessed to determine current practices and identify barriers to implementation.

Impact of insertion site on complications in central venous access devices.

PURPOSE: There is still debate over the safest route for the placement of long-term central venous access devices. The aim of this study was to review a large, single-institution experience to determine the impact of access location on peri-operative complications. METHODS: The records of patients undergoing subcutaneous port (SQP) and tunneled catheter insertion over a seven-year period were reviewed. Vein cannulated (subclavian (SCV) versus internal jugular (IJ) vein), and 30-day complications were assessed. Surgical complications included pneumothorax, hemothorax, infections, arrhythmia or malpositioning requiring intervention. RESULTS: A total of 1,309 patients were included (618 SQP, 691 tunneled catheters). The location for insertion was SCV (909, 69.4%) and IJ (400, 30.6%). There were 69 complications (5.2%) (41, 4.5% SCV, 28, 7.0% IJV) including: malpositioning/malfunctioning (SCV 13, 1.4% and IJV 14, 3.0%), pneumothorax (SCV 4, 0.4% and IJV 1, 0.3%), hemothorax (SCV 0 and IJV 1, 0.3%), arrhythmia (SCV 1, 0.1%, and IJV 0), and infection within 30 days of placement (SCV 20, 2.2% and IJ 11, 2.8%). The complication rates were not significantly different based on site (p = 0.080). CONCLUSION: There was no significant difference in complication rates when using the subclavian versus the internal jugular vein as the site for long-term central venous access. LEVEL OF EVIDENCE: III, retrospective comparative study.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: To determine the impact of tumor characteristics and treatment approach on (1) local recurrence, (2) scoliosis development, and (3) patient-reported quality of life in children with sarcoma of the chest wall. SUMMARY OF BACKGROUND DATA: Children with chest wall sarcoma require multimodal therapy including chemotherapy, surgery, and/or radiation. Despite aggressive therapy which places them at risk for functional impairment and scoliosis, these patients are also at significant risk for local recurrence. METHODS: A multi-institutional review of 175 children (median age 13 years) with chest wall sarcoma treated at seventeen Pediatric Surgical Oncology Research Collaborative institutions between 2008 and 2017 was performed. Patient-reported quality of life was assessed prospectively using PROMIS surveys. RESULTS: The most common diagnoses were Ewing sarcoma (67%) and osteosarcoma (9%). Surgical resection was performed in 85% and radiation in 55%. A median of 2 ribs were resected (interquartile range = 1-3), and number of ribs resected did not correlate with margin status ( P = 0.36). Local recurrence occurred in 23% and margin status was the only predictive factor(HR 2.24, P = 0.039). With a median follow-up of 5 years, 13% developed scoliosis (median Cobb angle 26) and 5% required corrective spine surgery. Scoliosis was associated with posteriorrib resection (HR 8.43; P= 0.003) and increased number of ribs resected (HR 1.78; P = 0.02). Overall, patient-reported quality of life is not impaired after chest wall tumor resection. CONCLUSIONS: Local recurrence occurs in one-quarter of children with chest wall sarcoma and is independent of tumor type. Scoliosis occurs in 13% of patients, but patient-reported quality of life is excellent.

Impact of Neoadjuvant Chemotherapy on Image-Defined Risk Factors in High-Risk Neuroblastoma.

PURPOSE: Image-defined risk factors (IDRFs) are associated with surgical risks in neuroblastoma. We sought to evaluate the impact of neoadjuvant therapy on IDRFs and associated ability to achieve gross total resection (GTR) of locoregional disease in patients with high-risk neuroblastoma. METHODS: We retrospectively reviewed charts of patients treated on four consecutive high-risk neuroblastoma protocols over a 20-year period at a single institution. The number of IDRFs at diagnosis and just prior to surgery, and the percent decrease of tumor volume from just prior to surgery to the end of induction were determined. RESULTS: Eighty-eight patients were included. There were 438 IDRFs (average 5.0 ± 3.1 per patient) at diagnosis and 198 (average 2.3 ± 1.9 per patient) after neoadjuvant chemotherapy (p < 0.01). A reduction in IDRFs was seen in 81.8% of patients with average decrease of 2.9 ± 2.5 per patient. The average percent reduction in tumor volume was 89.8 ± 18.9% and correlated with the number of IDRFs present after chemotherapy (p < 0.01). Three or fewer IDRFs prior to surgery was associated with the highest odds ratio for > 90% GTR at 9.33 [95% confidence interval 3.14-31.5]. CONCLUSION: Neoadjuvant chemotherapy reduced the number of IDRFs in the majority of patients with high-risk neuroblastoma. The number of IDRFs present after neoadjuvant therapy correlated with the extent of resection.

Thoracoscopy vs thoracotomy for the management of metastatic osteosarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi-institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan-Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow-up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan-Meier analysis showed no significant difference in 5-year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09-4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52-1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64-2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.

Does epidural analgesia really enhance recovery in pediatric surgery patients?

PURPOSE: We sought to determine the benefits of epidural anesthesia (EA) in pediatric surgical patients. METHODS: This study is a single-institution retrospective review of EA for pediatric patients undergoing thoracotomy or laparotomy from 2015 to 2020. Patients with recent or chronic opioid use were excluded. Urgent or emergent cases, patients with hemodynamic instability, or those with surgical complications that significantly impacted their post-operative course were also excluded. The primary objectives were comparison of pain scores and systemic opioid use between those patients with EA and those without EA. RESULTS: Epidural anesthesia was used in 151 (81.6%) laparotomies and 58 (77.3%) thoracotomies. EA use was associated with lower mean systemic opioid administration during the early post-operative period for laparotomy (POD#0-0.33 ± 0.3 oral morphine equivalents per kilogram (OME/Kg) with EA vs 0.93 ± 1.53, p < 0.001, POD#1-1.34 ± 1.79 OME/Kg with EA vs 2.61 ± 2.60, p < 0.001) and thoracotomy (POD#0-0.40 ± 0.37 OME/Kg with EA vs 0.68 ± 0.41, p = 0.008, POD#1-0.89 ± 0.86 OME/Kg with EA vs 2.02 ± 1.92, p < 0.001). There were no differences seen by POD#2. Average pain scores were significantly lower in patients with EA following laparotomy (POD#0-1.22 ± 0.99 with EA vs 1.75 ± 1.33, p = 0.008) and thoracotomy (POD#0-1.71 ± 1.13 with EA vs 2.40 ± 1.52, p = 0.04). CONCLUSIONS: The use of EA in pediatric surgery patients was associated with lower pain scores despite lower systemic opioid requirements in the early post-operative period.

Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma.

BACKGROUND: Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. PROCEDURE: A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification. RESULTS: A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy. CONCLUSIONS: PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real-time pathology assessment of specimen quality.

Renal Tumors in Children and Young Adults Older Than 5 Years of Age.

Renal masses are most common in children between ages 1 to 3 years, with less known about renal tumors in older children and young adults. The aim of this study was to review the presentation, demographics, histology, and outcomes in patients over 5 years of age with renal tumors compared with younger children. 111 renal tumors were diagnosed in patients 5 years of age and older (median, 7 y; range, 5 to 31 y) between 1950 and 2017 at a single institution. Wilms tumor (WT) was the most common histology in 84 patients (75%), followed by renal cell carcinoma in 12 patients (10.7%). Abdominal pain was the most common presenting symptom (46%) followed by hematuria (28.8%), and a palpable abdominal mass (24.3%). For WT, older children more commonly presented with advanced-stage disease (stages 3 and 4) than younger children (57.7% vs. 11.5%; P<0.001). Event-free survival (EFS) and overall survival (OS) for favorable histology WT were not different between younger and older children (OS, P=0.43; EFS, P=0.46). In this cohort, older children more frequently present with variable signs and symptoms, less common histopathologies although WT was still most frequent, and more advanced-stage disease compared with younger cohorts, but without differences in EFS or OS.

A Quality Improvement Intervention to Decrease Postoperative Opioid Prescriptions in Pediatric Oncology Patients.

PURPOSE: This quality improvement initiative aimed to minimize opioid prescribing after oncologic pediatric surgery. METHODS: Retrospective surgical data collected at a pediatric cancer hospital from July 2016 to June 2018 included hospitalization details, oral morphine equivalents prescribed, unplanned visits/calls because of pain, and parental/patient satisfaction with pain control. The quality improvement initiative promoted opioid prescription at discharge on the basis of prior inpatient requirements and education regarding nonopioid analgesia. Upon commencing this project in July 2018, we collected data prospectively. RESULTS: The retrospective and the prospective cohorts included 271 and 99 patients, respectively. Mean (SD) oral morphine equivalents (mg/kg) prescribed upon discharge was significantly reduced in the prospective (0.75±1.34) versus retrospective cohorts (5.48±6.94, P<0.001). The unplanned visits/calls regarding pain were 23 (retrospective, 8.5%) and 2 (prospective, 2.0%). In total, 44 patients (44.4%) received an opioid prescription at discharge in the prospective cohort, significantly fewer than retrospective cohort (251, 92.6%, P<0.001), and used a mean of 34.3 of 159.8 (21.5%) doses dispensed. Length of stay was comparable (P=0.88) between cohorts. Prospective satisfaction rate was 96.2%, leaving 3 patients (3.8%) not satisfied with their pain control regimen. CONCLUSIONS: Dramatic reduction of opioid prescriptions after oncologic surgery can be achieved without detriment to patient satisfaction or readmissions. LEVEL OF EVIDENCE: Level V.

Cytomegalovirus immunoglobulin G titers do not predict reactivation risk in immunocompetent hosts.

Cytomegalovirus (CMV) reactivation occurs in roughly one-third of immunocompetent patients during critical illness, and is associated with worse outcomes. These outcomes have prompted consideration of early antiviral prophylaxis, but two-third of patients would receive unnecessary treatment. Tissue viral load has been associated with risk of reactivation in murine models, and recent work has suggested a relationship between immune responses to CMV and underlying viral load. We, therefore, sought to confirm the hypothesis that serum CMV-specific immunoglobulin G (IgG) correlates with tissue viral load, and might be used to predict the risk of reactivation during critical illness. We confirm that there is a good correlation between tissue viral load and serum CMV-specific IgG after laboratory infection of inbred mice. Further, we show that naturally infected outbred hosts have variable tissue viral DNA loads that do not correlate well with serum IgG. Perhaps as a consequence, CMV-specific IgG was not predictive of reactivation events in immunocompetent humans. When reactivation did occur, those with the lowest IgG levels had longer durations of reactivation, but IgG quartiles were not associated with differing peak DNAemia. Together our data suggest that CMV-specific IgG titers diverge from tissue viral loads in outbred immunocompetent hosts, and their importance for the control of reactivation events remains unclear.

Percutaneous cholecystostomy-tube for high-risk patients with acute cholecystitis: current practice and implications for future research.

BACKGROUND: While cholecystectomy (CCY) is the standard of care for gallstone-related acute cholecystitis, percutaneous cholecystostomy-tube (CCYT-tube) is an alternative option in patients with significant comorbid conditions. We sought to identify immediate and longitudinal hospital outcomes of patients who underwent CCYT-tube placement and determine predictors of CCYT-tube placement and eventual CCY on a national level in the US. METHODS: We identified all adults (age ≥ 18 years) with a primary diagnosis of acute calculous cholecystitis from January to November 2013 in the Nationwide Readmissions Database (NRD). The NRD allows longitudinal follow-up of a patient for one calendar year. Outcomes of patients undergoing CCY and CCYT-tube were compared. Separate univariable and multivariable regression analyses were performed to identify predictors of CCYT-tube placement and failure to undergo subsequent CCY. RESULTS: A total of 181,262 patients had an index hospitalization with acute cholecystitis where 178,095 (98.3%) patients underwent only CCY and 3167 (1.7%) patients were managed with CCYT-tubes. Among patients with CCYT-tube, 1196 (37.8%) underwent eventual CCY in 2013, while 1971 (62.2%) did not. One in five patients with CCYT-tube were readmitted within 30 days of hospital discharge. Multivariable analysis demonstrated that increasing age, male gender, coronary artery disease, cirrhosis, atrial fibrillation, diastolic congestive heart failure, and sepsis were associated with CCYT-tube placement. Longitudinal follow-up revealed that older age (OR 1.16, 95% CI 1.09-1.23), Elixhauser comorbidity score 3-4 (OR 1.94, 95% CI 1.03-3.63), cirrhosis (OR 3.28, 95% CI 1.59-6.79), and diastolic congestive heart failure (OR 2.47, 95% CI 1.33-4.60) were associated with failure to undergo subsequent CCY. CONCLUSION: In this national survey, nearly two in three patients who receive CCYT-tube for acute cholecystitis do not get CCY during longitudinal data capture within the same calendar year. Future research needs to target novel options for drainage of the gallbladder in high-risk patient populations.

Surgery for Abdominal Well-Differentiated Liposarcoma.

OPINION STATEMENT: Retroperitoneal sarcomas are rare tumors of which liposarcoma is the most common histology. Surgical resection remains the mainstay of therapy, particularly for the well-differentiated subtype. They can grow to massive size before causing symptoms or detection. Well-differentiated liposarcoma, while having a negligible metastatic rate, is fraught with a high local recurrence rate, despite a complete surgical resection. Reasons for this are not completely known but may be related to a field defect of the retroperitoneal fat creating a niche for recurrence. These tumors are classically chemo- and radio-resistant. Surgical therapy of recurrences can be challenging, but remains the treatment of choice for well-differentiated liposarcoma. In an attempt to improve on survival and recurrence rates for retroperitoneal liposarcoma, an extended resection approach has been promoted by a few groups. This involves the en bloc resection of contiguous organs that are not macroscopically involved. While this has improved local recurrence rates, benefit for overall survival has not been demonstrated. Interestingly, the improvement in local recurrence rate appeared to be driven by histology and was most improved in the well-differentiated subtype compared to historical data. However, for well-differentiated liposarcomas that are multifocal, this approach may be less useful. The application of this approach still requires further study in terms of balancing increased morbidity of extended resection against the potential for multiple surgeries for recurrence.

Routine staging with endoscopic ultrasound in patients with obstructing esophageal cancer and dysphagia rarely impacts treatment decisions.

BACKGROUND: Endoscopic ultrasound (EUS) has been routinely utilized for the locoregional staging of esophageal cancer. One important aspect of clinical staging has been to stratify patients to treatment with neoadjuvant chemoradiation or primary surgical therapy. We hypothesized that EUS may have a limited impact on clinical decision making in patients with dysphagia and obstructing esophageal masses. METHODS: This retrospective cohort study included all patients with esophageal adenocarcinoma undergoing esophageal EUS between July 2008 and September 2013. Dysplastic Barrett's esophagus without invasive adenocarcinoma or incomplete staging was excluded. Patient demographics, endoscopic tumor characteristics, the presence of dysphagia, sonographic staging, and post-EUS therapy were recorded. Pathologic staging for patients who underwent primary surgical therapy was also recorded. Locally advanced disease was defined as at least T3 or N1, as these patients are typically treated with neoadjuvant therapy. RESULTS: Two hundred sixteen patients underwent EUS for esophageal adenocarcinoma, with 147 (68.1%) patients having symptoms of dysphagia on initial presentation. Patients with dysphagia were significantly more likely to have locally advanced disease on EUS than patients without dysphagia (p < 0.0001). Additionally, 145 (67.1%) patients had a partially or completely obstructing mass on initial endoscopy, of which 136 (93.8%) were locally advanced (p < 0.0001 vs. non-obstructing lesions). CONCLUSIONS: An overwhelming majority of patients presenting with dysphagia and/or the presence of at least partially obstructing esophageal mass at the time of esophageal cancer diagnosis had an EUS that demonstrated at least locally advanced disease. The present study supports the hypothesis that EUS may be of limited benefit for management of esophageal cancer in patients with an obstructing mass and dysphagia.

Laparoscopic redo fundoplication improves disease-specific and global quality of life following failed laparoscopic or open fundoplication.

INTRODUCTION: Laparoscopic fundoplication is associated with failure rates of up to 30% and redo operation rates of 5-8%. Redo fundoplication improves patient symptoms, but its impact on patient quality of life remains unclear. We hypothesized that laparoscopic redo fundoplication improves disease-specific and global quality of life in patients with recurrent symptoms following failed laparoscopic or open fundoplication. METHODS: Data for all patients undergoing a redo fundoplication between August 2009 and June 2014 were collected prospectively. Reflux symptoms and quality of life were assessed using the Gastroesophageal Reflux Symptom Scale (GERSS), the Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL), and the global quality of life Short Form-36 (SF-36) questionnaires obtained at 4 weeks and 16 months post-operatively. RESULTS: Forty-six patients underwent laparoscopic redo fundoplication during the study period for symptomatic hernia (n = 11), GERD (n = 18), or dysphagia (n = 17). GERSS improved from 41 at baseline to 9 at late follow-up (p < 0.001), and GERD-HRQL scores improved from 30 at baseline to 7 at late follow-up (p < 0.001). Median dysphagia scores decreased from 4.5 to 1 (p = 0.035). SF-36 scores demonstrated a significant improvement in general health (p = 0.016) and emotional well-being (p = 0.036) and a trend toward improved physical function (p = 0.068) in the post-operative period, but these improvements were not statistically significant at longer-term follow-up. Overall, 82% of patients reported satisfaction with their operation, and 96% reported that they would have the operation performed again given the benefit of hindsight. CONCLUSIONS: While associated with long operative times and significant complications, laparoscopic redo fundoplication produces a durable improvement in reflux symptoms and disease-specific quality of life. These procedures also improve global quality of life in the short term and are associated with high patient satisfaction.

Timing of Breast Cancer Surgery-How Much Does It Matter?

Timing of surgical resection after breast cancer diagnosis is dependent on a variety of factors. Lengthy delays may lead to progression; however, the impact of modest delays is less clear. The aim of this study was to evaluate the impact of surgical timing on outcomes, including disease-free survival (DFS) and nodal status (NS). The cancer registry from one academic cancer hospital was retrospectively reviewed. Time from initial biopsy to surgical resection was calculated for patients with ductal carcinoma in situ (DCIS) and stage 1 and 2 invasive carcinomas. Early (0-21 days), intermediate (22-42 days), and late (43-63 days) surgery groups were evaluated for differences in NS and DFS for each cancer stage separately. A total of 3,932 patients were identified for analysis. There were no differences in DFS noted for DCIS. For stage 1, early surgery (ES) was associated with worse DFS compared to intermediate surgery (IS) (p = 0.025). There were no significant differences between ES and late surgery (LS) (p = 0.700) or IS and LS (p = 0.065). In stage II cancers, there was a significant difference in DFS in ES compared to IS (p < 0.001) and LS (p = 0.009). There was no significant difference between IS and LS (p = 0.478). Patients were more likely to undergo immediate reconstruction (p < 0.0001 for all stages) in later time-to-surgery groups, while patients in earlier groups were more likely to undergo breast conserving surgery. There was also no significant difference in NS at time of surgery in clinical stage 1 (p = 0.321) or stage 2 disease (p = 0.571). Delays of up to 60 days were not associated with worse outcomes. This study should reassure patients and surgeons that modest delays do not adversely affect breast cancer outcomes. This allows patients time to consider treatment and reconstruction options.

Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts.

Roughly 1/3rd of immune competent patients will reactivate latent cytomegalovirus (CMV) during critical illness. There are no standard methods to detect reactivation, and some investigators have postulated that presence of DNA in BAL fluid is indicative of viral replication. To test this hypothesis, we used a murine model that allows inclusion of matched healthy controls which is not possible in human studies. BALB/c mice infected with Smith-murine CMV or PBS (mock) had BAL evaluated 7, 14, or 21 days after acute infections, during latency, or during bacterial sepsis. Plaque assay, PCR, and rtPCR were performed on BALs and concomitantly obtained lung tissue. BAL cellular compositions, including tetramer evaluation of CMV-specific T cells were evaluated by flow cytometry. CMV DNA were detected in BAL at all time-points during acute infection, becoming undetectable in all mice during latency, then were detected again during bacterial sepsis, peaking 3 weeks after onset. mCMV specific T-cells were most numerous in BAL after acute viral infections, decreasing to low levels during latency, then fluctuating during bacterial sepsis. Specifically, mCMV-specific T-cells contracted at sepsis onset, expanding 2-4 weeks post-sepsis, presumably in response to increased viral loads at that time point. Altogether, our results support the use of BAL PCR for the diagnosis of CMV replication in immune competent hosts. Additionally, we demonstrate dynamic changes in CMV-specific T cells that occur in BAL during CMV infection and during sepsis induced viral reactivation. J. Med. Virol. 88:1408-1416, 2016. © 2016 Wiley Periodicals, Inc.

Pancreaticoduodenectomy outcomes in the pediatric, adolescent, and young adult population.

BACKGROUND: Pancreatic malignancy and chronic pancreatitis are rare in the pediatric, adolescent, and young adult (AYA) population, making pancreas resections an infrequent procedure in this demographic. Only case reports and small case series exist in the literature describing surgical outcomes and complications in this population. The aim of this study was to review the surgical outcomes of pediatric/AYA patients undergoing pancreaticoduodenectomy (PD) at our institution. METHODS: All pediatric/AYA adult patients (≤30 years) undergoing PD over a 15-year period (1998-2013) from a large academic institution were included. We provide adult (>30 years) data from our same institution for observational comparison. Retrospective chart review was performed to identify pertinent preoperative, perioperative, and postoperative data. RESULTS: Twenty-two patients with a median age of 25 years (range, 11-30 years) underwent PD. The most common postoperative histologic diagnoses were chronic pancreatitis (6, 27.3%), solid pseudopapillary neoplasm (5, 22.7%), and adenocarcinoma (4, 18.2%). Complications were 31.8% in the pediatric/AYA cohort and 58.6% in the adult cohort. The most common postoperative complication was intraabdominal abscess, which occurred in three patients (13.6%). Thirty-day mortality was 0% for pediatric/AYA patients. There were no recurrences or disease-related deaths in patients with solid pseudopapillary neoplasm. Pediatric patients with adenocarcinoma had a median survival of 10.2 mo (interquartile range, 9-21), in contrast to adults of 57.8 mo (interquartile range, 11-132). CONCLUSIONS: This is the largest series of PD procedures reported in the pediatric/AYA population. The procedure appears to be safe, with no 30-day mortalities and an acceptable complication rate.