Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

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.

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study.

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

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.

The "Classification Pendulum" of Stage I Colorectal Cancer: A National Level Analysis of the Survival Difference Between T1 and T2 Colorectal Cancer.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer classifies nonmetastatic, node-negative colorectal cancers invading the submucosa (T1) and muscularis propria (T2) as stage I tumors without additional subclassification. OBJECTIVE: The aim of the study was to compare survival of T1N0M0 versus T2N0M0 colorectal cancers and to investigate factors associated with decreased survival. DESIGN: This was an analysis of 2 large population-based data sets. SETTINGS: The study was conducted analyzing data from the Surveillance Epidemiology and End Result program and the National Cancer Database. PATIENTS: Adult patients undergoing major resection without additional therapy for stage I colorectal cancer were included. MAIN OUTCOME MEASURES: Overall and disease-specific survival for T1 versus T2 cancers were measured. Subgroup analyses by tumor location (colon versus rectum) were performed. RESULTS: A total of 30,228 (36.4% T1 and 63.6% T2) and 41,670 (41.1% T1 and 58.9% T2) patients were identified in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5-year overall survival rates were 87.1% and 86.2% for patients with T1 versus 82.7% and 80.7% for patients with T2 (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 10-year overall survival rates were 71.3% and 66.3% for patients with T1 versus 62.2% and 57.2% for patients with T2 tumors (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5- and 10-year disease-specific survival for colorectal cancer in the Surveillance Epidemiology and End Result database was 97.0% (T1) versus 95.2% (T2) and 94.1% (T1) versus 90.3% (T2). Black race (HR = 1.26 and 1.65 for overall survival and disease-specific survival in the Surveillance Epidemiology and End Result database; HR = 1.20 for overall survival in the National Cancer Database) was associated with worse survival. LIMITATIONS: The study was limited by intrinsic biases related to large administrative data sets. CONCLUSIONS: Within stage I colorectal cancer, T2 tumors have decreased overall survival and disease-specific survival as compared with T1 cancers. This survival difference may justify revising the American Joint Committee on Cancer staging system to include the subclassification of stage Ia (T1N0M0) and stage Ib (T2N0M0). See Video Abstract at http://links.lww.com/DCR/B659. LA CLASIFICACIN PNDULO PARA EL CNCER COLORRECTAL EN ESTADIO I UN ANLISIS A NIVEL NACIONAL DE LA DIFERENCIA DE SOBREVIDA ENTRE EL CNCER COLORRECTAL T Y T: ANTECEDENTES:La octava edición del American Joint Committee on Cancer, clasifica los cánceres colorrectales no metastásicos con ganglios negativos, que invaden la submucosa (T1) y la muscularis propia (T2) como tumores en estadio I sin subclasificación adicional.OBJETIVO:El objetivo del estudio fue comparar la sobrevida de los cánceres colorrectales T1N0M0 versus T2N0M0 e investigar los factores asociados con la disminución de la sobrevida.DISEÑO:Análisis de dos grandes conjuntos de datos poblacionales.MARCO:El estudio se realizó analizando datos del Programa de Epidemiología de Vigilancia y Resultados Finales (SEER) y la Base de Datos Nacional del Cáncer.PACIENTES:Pacientes adultos en los cuales se realizó una resección mayor sin terapia adicional por cáncer colorrectal en estadio I.PRINCIPALES VARIABLES ANALIZADAS:Sobrevida global y específica de la enfermedad para los cánceres T1 versus T2. Se realizó un análisis de subgrupos según la ubicación del tumor (colon versus recto).RESULTADOS:Se incluyeron un total de 30.228 (36,4% T1 y 63,6% T2) y 41.670 (41,1% T1 y 58,9% T2) pacientes en las bases de datos SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 5 años fue del 87,1% y el 86,2% para los pacientes con T1 frente al 82,7% y el 80,7% de los pacientes con T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 10 años fue del 71,3% y el 66,3% para los pacientes con T1 frente al 62,2% y el 57,2% de los pacientes con tumores T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida específica de la enfermedad a 5 y 10 años para el cáncer colorrectal en el SEER fue del 97,0% (T1) frente al 95,2% (T2) y del 94,1% (T1) frente al 90,3% (T2), respectivamente. La grupo étnico afroamericano se asoció con una sobrevida menor (Hazard Ratio -HR 1,26 y 1,65 para la sobrevida general y sobrevida específica de la enfermedad-SEER; HR 1,20 para la sobrevida general-Base de de Datos Nacional del Cáncer).LIMITACIONES:Sesgos intrínsecos relacionados con el análisis de grandes conjuntos de datos.CONCLUSIONES:Dentro del cáncer colorrectal en estadio I, los tumores T2 han disminuido la sobrevida general y la sobrevida específica de la enfermedad, en comparación con los cánceres T1. Esta diferencia de sobrevida puede justificar la revisión del sistema de estadificación del American Joint Committee on Cancer para incluir la subclasificación del estadio Ia (T1N0M0) y el estadio Ib (T2N0M0). Consulte Video Resumen en http://links.lww.com/DCR/B659.

IWATE criteria are associated with perioperative outcomes in robotic hepatectomy: a retrospective review of 225 resections.

BACKGROUND: Robotic hepatectomy (RH) is increasingly utilized for minor and major liver resections. The IWATE criteria were developed to classify minimally invasive liver resections by difficulty. The objective of this study was to apply the IWATE criteria in RH and to describe perioperative and oncologic outcomes of RH over the last decade at our institution. METHODS: Perioperative and oncologic outcomes of patients who underwent RH between 2011 and 2019 were retrospectively collected. The difficulty level of each operation was assessed using the IWATE criteria, and outcomes were compared at each level. Univariate linear regression was performed to characterize the relationship between IWATE criteria and perioperative outcomes (OR time, EBL, and LOS), and a multivariable model was also developed to address potential confounding by patient characteristics (age, sex, BMI, prior abdominal surgery, ASA class, and simultaneous non-hepatectomy operation). RESULTS: Two hundred and twenty-five RH were performed. Median IWATE criteria for RH were 6 (IQR 5-9), with low, intermediate, advanced, and expert resections accounting for 23% (n = 51), 34% (n = 77), 32% (n = 72), and 11% (n = 25) of resections, respectively. The majority of resections were parenchymal-sparing approaches, including anatomic segmentectomies and non-anatomic partial resections. 30-day complication rate was 14%, conversion to open surgery occurred in 9 patients (4%), and there were no deaths within 30 days postoperatively. In the univariate linear regression analysis, IWATE criteria were positively associated with OR time, EBL, and LOS. In the multivariable model, IWATE criteria were independently associated with greater OR time, EBL, and LOS. Two-year overall survival for hepatocellular carcinoma and intrahepatic cholangiocarcinoma was 94% and 50%, respectively. CONCLUSION: In conclusion, the IWATE criteria are associated with surgical outcomes after RH. This series highlights the utility of RH for difficult hepatic resections, particularly parenchymal-sparing resections in the posterosuperior sector, extending the indication of minimally invasive hepatectomy in experienced hands and potentially offering select patients an alternative to open hepatectomy or other less definitive liver-directed treatment options.

Practice Patterns and Outcomes of Pediatric Thyroid Surgery: An NSQIP Analysis.

BACKGROUND: Pediatric thyroid cancer rates are rising. The aim of this study was to determine the state of current practice and outcomes for pediatric thyroidectomies using the pediatric National Surgical Quality Improvement Program (NSQIP-P) with specific attention to differences based on surgeon type/specialty. METHODS: All cases of pediatric thyroidectomies and neck dissections within the NSQIP-P database were identified from 2015 to 2017. Patient, disease, and treatment-related factors affecting 30-day outcomes were analyzed using univariate and multivariate analyses. RESULTS: A total of 1300 cases were identified. Mean age at time of surgery was 14.0 (SD 3.5) years. The majority of patients were female (78%) and Caucasian (72%). Pediatric general surgeons performed the largest proportion of cases (42%) followed by pediatric otolaryngologists (33%). Malignancies were present in 29% of cases. The overall rate of complications was 3.0%. On multivariate analysis, non-pediatric surgeons were more likely to operate on Caucasian children, malignant pathology, and perform modified radical neck dissections. Pediatric surgeons were more likely to have longer operative times, have specialized in otolaryngology, and operate on sicker children (ASA>2). There were no differences in length of stay or overall complications rates. CONCLUSIONS: This study shows that pediatric surgeons currently perform the majority of thyroid surgeries in children. While unable to assess surgeon volume, our data show that thyroid surgery is being safely performed at NSQIP-affiliated hospitals by both non-pediatric and pediatric surgeons. Further studies are needed to determine if there are differences in specific procedure-related complications and long-term outcomes between surgeon types.

Comparison of Anal Versus Rectal Staging in the Prognostication of Rectal Squamous Cell Carcinoma: A Population-Based Analysis.

BACKGROUND: Rectal squamous cell carcinoma is a rare malignancy with limited data regarding management and prognosis. It is also unknown whether a rectal squamous cell cancer staging system should be based on size, as for anal squamous cell carcinoma, or depth of invasion, as for rectal adenocarcinoma. OBJECTIVE: The aims of the current study were to determine the optimal management strategy, prognostic factors, and staging system for rectal squamous cell carcinoma. DESIGN: This was a population-based study. SETTINGS: The Surveillance, Epidemiology, and End Results database was used to identify patents diagnosed between 1988 and 2013. PATIENTS: Patients ≥18 years of age undergoing radiation or local excision alone, radiation with local excision, or radiation with radical resection were included. Patients were then staged according to both the American Joint Committee on Cancer classification for rectal adenocarcinoma (American Joint Committee on Cancer-rectum) and anal cancer (American Joint Committee on Cancer-anus). MAIN OUTCOME MEASURES: The main outcome was 5-year, disease-specific survival. RESULTS: In both univariate and multivariate survival analyses, the addition of local excision or radical resection to radiation resulted in similar-to-worse outcomes across all of the stages. Among patients staged according to American Joint Committee on Cancer-rectum (n = 1646), although a significant difference in 5-year survival was observed for stage I as compared with higher stages, no difference was noted between stages II and III (80% vs 61% and 62%). However, in the American Joint Committee on Cancer-anus classification (n = 1327), a significant difference was observed across all of the stages (87% vs 72% vs 59%; p < 0.001). In multivariate analysis, the prognostic discrimination based on HRs provided by the American Joint Committee on Cancer-anus was superior to that of the American Joint Committee on Cancer-rectum. LIMITATIONS: This study was limited by lack of data on chemotherapy and location of positive nodes. CONCLUSIONS: A treatment approach primarily based on radiation should be considered the optimal management strategy for rectal squamous cell carcinoma. Moreover, a staging system based on size (American Joint Committee on Cancer-anus) rather than on depth of invasion (American Joint Committee on Cancer-rectum) appears to be more accurate in predicting its prognosis. See Video Abstract at http://links.lww.com/DCR/A734.

Laparoscopic Splenectomy: Has It Become the Standard Surgical Approach in Pediatric Patients?

BACKGROUND: Splenectomy is often required in the pediatric population as part of the treatment of hematologic disorders and can be performed laparoscopically or open. We evaluated the comparative effectiveness of laparoscopic (LS) and open (OS) splenectomies using the American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) data set. METHODS: The NSQIP-P data set was used to identify children who underwent elective splenectomy between January 2012 and December 2016. Thirty-day outcomes between OS and LS, and LS alone and concurrent LS and cholecystectomy were compared using univariate and multivariate analysis. RESULTS: Most of the splenectomies (91%) were performed laparoscopically. There was no difference in overall complications between OS (n = 60) and LS (n = 613), although OS had a higher risk of perioperative transfusion (OR 3.19, 95% CI 1.52-6.69). LS was associated with a shorter median hospital length of stay (2 versus 4 d, P < 0.001) and similar mean operative times compared to OS (120 versus 133 min, P = 0.559). There was no difference in outcomes of children undergoing LS versus LS and concurrent cholecystectomy (n = 129). CONCLUSIONS: LS has become the standard approach for elective splenectomies in the pediatric population and has minimal morbidity, and when indicated, concurrent cholecystectomies do not increase the risk of complications. LEVELS OF EVIDENCE: III.

The Distal Predilection of Small Bowel Neuroendocrine Tumors.

BACKGROUND: The small bowel (SB) is the most common site of neuroendocrine tumors (NETs) of the GI tract. These are described as being predominantly jejunoileal, but their exact locations within the SB have not been well defined. We sought to determine prospectively the spectrum of SBNET locations. METHODS: Patients undergoing exploration for SBNET primaries had measurement of bowel length, tumor locations, and resection length recorded. Correlations of clinicopathologic factors were performed, and analysis done utilizing Welch's t test, Chi square test, and the Kaplan-Meier method. RESULTS: Measurements were recorded in 123 patients, 107 of whom had complete information. Multifocal tumors (MTs) were found in 69 (56%) and unifocal (UTs) in 54 (44%) patients. Only 1 of 107 patients had a tumor within 100 cm of the ligament of Treitz (LT), whereas 77 of 107 (72%) had tumors within 100 cm of the ileocecal valve (ICV). No MTs were found within 100 cm of LT, whereas 41 of 60 (68%) patients had all (10) or at least one tumor (31) located within 100 cm of the ICV. MTs required a mean resection length of 108 versus 59 cm for UTs (p < 0.01). Seventy-seven percent of UTs (36/47) were within 100 cm of ICV. Tumors occurring only between > 100 cm from the LT and ICV were seen in 29 of 107 (27%) patients. CONCLUSIONS: SBNETs are frequently multifocal and most commonly located within 100 cm of the ICV. SBNETs are less prevalent proximally in the small bowel, which may result from anatomic differences in enterochromaffin cell density, hormonal factors, or environmental exposures in the distal SB.

Individual and combined roles of the master regulators AphA and LuxR in control of the Vibrio harveyi quorum-sensing regulon.

Bacteria use a chemical communication process called quorum sensing to control transitions between individual and group behaviors. In the Vibrio harveyi quorum-sensing circuit, two master transcription factors, AphA and LuxR, coordinate the quorum-sensing response. Here we show that AphA regulates 167 genes, LuxR regulates 625 genes, and they coregulate 77 genes. LuxR strongly controls genes at both low cell density and high cell density, suggesting that it is the major quorum-sensing regulator. In contrast, AphA is absent at high cell density and acts to fine-tune quorum-sensing gene expression at low cell density. We examined two loci as case studies of coregulation by AphA and LuxR. First, AphA and LuxR directly regulate expression of the genes encoding the quorum-regulatory small RNAs Qrr2, Qrr3, and Qrr4, the consequence of which is a specifically timed transition between the individual and the group life-styles. Second, AphA and LuxR repress type III secretion system genes but at different times and to different extents. The consequence of this regulation is that type III secretion is restricted to a peak at mid-cell density. Thus, the asymmetric production of AphA and LuxR coupled with differences in their strengths and timing of target gene regulation generate a precise temporal pattern of gene expression.

Production of an interleukin-10 blocking antibody by genetically engineered macrophages increases cancer cell death in human gastrointestinal tumor slice cultures.

Although it can promote effector T-cell function, the summative effect of interleukin-10 (IL-10) in the tumor microenvironment (TME) appears to be suppressive; therefore, blocking this critical regulatory cytokine has therapeutic potential to enhance antitumor immune function. As macrophages efficiently localize to the TME, we hypothesized that they could be used as a delivery vehicle for drugs designed to block this pathway. To test our hypothesis, we created and evaluated genetically engineered macrophages (GEMs) that produce an IL-10-blocking antibody (αIL-10). Healthy donor human peripheral blood mononuclear cells were differentiated and transduced with a novel lentivirus (LV) encoding BT-063, a humanized αIL-10 antibody. The efficacy of αIL-10 GEMs was assessed in human gastrointestinal tumor slice culture models developed from resected specimens of pancreatic ductal adenocarcinoma primary tumors and colorectal cancer liver metastases. LV transduction led to sustained production of BT-063 by αIL-10 GEMs for at least 21 days. Transduction did not alter GEM phenotype as evaluated by flow cytometry, but αIL-10 GEMs produced measurable quantities of BT-063 in the TME that was associated with an ~5-fold higher rate of tumor cell apoptosis than control.

Glypican-3 targeted positron emission tomography detects sub-centimeter tumors in a xenograft model of hepatocellular carcinoma.

BACKGROUND: Early intrahepatic recurrence is common after surgical resection of hepatocellular carcinoma (HCC) and leads to increased morbidity and mortality. Insensitive and nonspecific diagnostic imaging contributes to EIR and results in missed treatment opportunities. In addition, novel modalities are needed to identify targets amenable for targeted molecular therapy. In this study, we evaluated a zirconium-89 radiolabeled glypican-3 (GPC3) targeting antibody conjugate (89Zr-αGPC3) for use in positron emission tomography (PET) for detection of small, GPC3+ HCC in an orthotopic murine model. Athymic nu/J mice received hepG2, a GPC3+ human HCC cell line, into the hepatic subcapsular space. Tumor-bearing mice were imaged by PET/computerized tomography (CT) 4 days after tail vein injection of 89Zr-αGPC3. Livers were then excised for the tumors to be identified, measured, bisected, and then serially sectioned at 500 µm increments. Sensitivity and specificity of PET/CT for 89Zr-αGPC3-avid tumors were assessed using tumor confirmation on histologic sections as the gold standard. RESULTS: In tumor-bearing mice, 89Zr-αGPC3 avidly accumulated in the tumor within four hours of injection with ongoing accumulation over time. There was minimal off-target deposition and rapid bloodstream clearance. Thirty-eight of 43 animals had an identifiable tumor on histologic analysis. 89Zr-αGPC3 immuno-PET detected all 38 histologically confirmed tumors with a sensitivity of 100%, with the smallest tumor detected measuring 330 µm in diameter. Tumor-to-liver ratios of 89Zr-αGPC3 uptake were high, creating excellent spatial resolution for ease of tumor detection on PET/CT. Two of five tumors that were observed on PET/CT were not identified on histologic analysis, yielding a specificity of 60%. CONCLUSIONS: 89Zr-αGPC3 avidly accumulated in GPC3+ tumors with minimal off-target sequestration. 89Zr-αGPC3 immuno-PET yielded a sensitivity of 100% and detected sub-millimeter tumors. This technology may improve diagnostic sensitivity of small HCC and select GPC3+ tumors for targeted therapy. Human trials are warranted to assess its impact.

Improving pathways to eliminate underrepresentation in the pediatric surgery workforce: A call to action.

Despite progress, diversity and minority representation within the pediatric surgery workforce still does not match the expansive backgrounds of the patients we treat. The problem stems from underrepresentation of minority populations at every step along the pediatric surgery training pathway. Strategies aimed at improving diversity and representation in medical school, general surgery residencies, and ultimately pediatric surgery fellowship are necessary to assemble a more diverse pool of pediatric surgeons. The aim of this paper is to review the current demographic make-up of medical and surgical specialties, highlight the value of diversity, and provide evidence-based strategies for increasing minority representation throughout the pediatric surgery pathway. Future patients will be better served with a more representative pediatric surgery workforce.

The role of feeding advancement strategy on length of stay and hospital costs in newborns with gastroschisis.

BACKGROUND: Infants with gastroschisis require prolonged hospitalization for surgical repair and gradual advancement of feeds. The present study explores the effect of a change in a protocolized enteral feeding regimen with length of hospital stay (LOS) and total costs in newborns with gastroschisis. METHODS: A retrospective review was performed in neonates with uncomplicated gastroschisis at a free-standing pediatric institution from 2012 to 2020. The effect of two different enteral feed advancement protocols on clinical outcomes and hospital costs was analyzed. RESULTS: Seventy-four patients were identified, of which 50 (68%) underwent 10 ml/kg/day feeding advancements, and 24 (32%) underwent 20 ml/kg/day feeding advancements. Compared to neonates who underwent 10 ml/kg/day enteral advancements, neonates receiving 20 ml/kg/day advancements reached goal feeds faster (14 vs 20 days, p<0.001), were younger at goal feeds (26 vs 34 days, p = 0.001), required fewer days of parenteral nutrition (22 vs 29 days, p = 0.001), and had shorter LOS (30 vs 36 days, p = 0.001). On multivariable analysis, total costs decreased by 9.77% in the 20 ml/kg/day advancement cohort (p = 0.071). CONCLUSION: In neonates with uncomplicated gastroschisis who underwent primary repair, a nutritional protocol that incorporated 20 ml/kg/day feeding advancements was safe and resulted in faster attainment of goal feeds and shorter LOS. LEVEL OF EVIDENCE: II/III.

A novel rat model for the study of postoperative pancreatic fistula.

While over the past several decades mortality after pancreatic surgery has decreased to <5%, postoperative morbidity remains remarkably high, ranging from 15% to 65%. The development of a postoperative pancreatic fistula (POPF) is a significant contributor to morbidity in patients undergoing pancreatic surgery. POPF can lead to life-threatening conditions such as intra-abdominal abscess, uncontrolled hemorrhage, sepsis, and death. Rates of POPF have not significantly changed over time, despite the introduction of multiple technical and pharmacologic interventions aimed at their treatment and prevention. Unfortunately, there are few POPF experimental models that have been described in the literature and existing models are unable to reliably reproduce the clinical sequelae of POPF, limiting the development of new methods to prevent and treat POPF. Herein, we describe a new rat experimental model that reliably creates a POPF via transection of the common pancreatic duct.

Bias and discrimination in surgery: Where are we and what can we do about it?

Bias is an inclination or preconceived outlook that favors toward or against an idea, person, or group. It manifests in implicit and explicit ways throughout all aspects and institutions of society. These cognitive shortcuts are often based on stereotypes and can lead to prejudice and discrimination in medicine as they mediate interactions with patients, between providers, and at the institutional level. It is important to understand the drivers and consequences of bias in order to overcome barriers to representation, equity, and inclusion. This paper provides definitions of bias; discusses its manifestations across academic medicine at the institutional and individual levels; and concludes by examining techniques to reduce bias and measure progress. Equity for patients, families, and members of the broader surgical community cannot be achieved without reducing bias and discrimination. We call for action to increase intentional efforts that reduce the influences of bias in healthcare, research, and education, particularly in the field of pediatric surgery.

Presentation, treatment, and prognosis of colorectal adenosquamous carcinoma: A contemporary analysis of the surveillance, epidemiology, and end results database.

INTRODUCTION: Colorectal adenosquamous carcinoma (ASC) represents <0.1% of colorectal cancers. Due to its rarity, there is paucity of data regarding its prognosis and treatment compared to other colorectal cancers. The aim of the study was to evaluate presentation, treatment and prognosis of colorectal ASC in comparison to adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: Adult patients diagnosed with colorectal AC, SCC, and ASC between 2000 and 2017 were identified using Surveillance, Epidemiology, and End Results database. RESULTS: Among the 446,132 patients diagnosed with colorectal cancer, 0.06% had ASC and were more likely to present with higher T stage and distant metastases compared to AC and SCC (p < 0.001). Major surgery was the primary treatment for colonic ASC, while for rectal ASC, chemotherapy and/or radiation were mainly utilized. Localized and distant colonic ASC had an unadjusted 5-year cause-specific survival that was worse than AC, while rectal ASC had the worst survival across all stages. CONCLUSION: Colorectal ASC usually present with advanced stage and have overall worse prognosis. Standardization of treatment strategies may improve survival in colorectal ASC.

A framework for fibrolamellar carcinoma research and clinical trials.

Fibrolamellar carcinoma (FLC), a rare, lethal hepatic cancer, occurs primarily in adolescents and young adults. Unlike hepatocellular carcinoma, FLC has no known association with viral, metabolic or chemical agents that cause cirrhosis. Currently, surgical resection is the only treatment demonstrated to achieve cure, and no standard of care exists for systemic therapy. Progress in FLC research illuminates a transition from an obscure cancer to one for which an interactive community seems poised to uncover fundamental mechanisms and initiate translation towards novel therapies. In this Roadmap, we review advances since the seminal discovery in 2014 that nearly all FLC tumours express a signature oncogene (DNAJB1-PRKACA) encoding a fusion protein (DNAJ-PKAc) in which the J-domain of a heat shock protein 40 (HSP40) co-chaperone replaces an amino-terminal segment of the catalytic subunit of the cyclic AMP-dependent protein kinase (PKA). Important gains include increased understanding of oncogenic pathways driven by DNAJ-PKAc; identification of potential therapeutic targets; development of research models; elucidation of immune mechanisms with potential for the development of immunotherapies; and completion of the first multicentre clinical trials of targeted therapy for FLC. In each of these key areas we propose a Roadmap for future progress.