Surveillance Endoscopy in Pediatric Esophageal Atresia: Toward an Evidence-Based Algorithm.

BACKGROUND: Individuals with esophageal atresia (EA) have lifelong increased risk for mucosal and structural pathology of the esophagus. The use of surveillance endoscopy to detect clinically meaningful pathology has been underexplored in pediatric EA. We hypothesized that surveillance endoscopy in pediatric EA has high clinical yield, even in the absence of symptoms. STUDY DESIGN: The medical records of all patients with EA who underwent at least 1 surveillance endoscopy between March 2004 and March 2023 at an international EA referral center were retrospectively reviewed. The primary outcomes were endoscopic identification of pathology leading to an escalation in medical, endoscopic, or surgical management. Logistic regression analysis examined predictors of actionable findings. Nelson-Aalen analysis estimated optimal endoscopic surveillance intervals. RESULTS: Five hundred forty-six children with EA underwent 1,473 surveillance endoscopies spanning 3,687 person-years of follow-up time. A total of 770 endoscopies (52.2%) in 394 unique patients (72.2%) had actionable pathology. Esophagitis leading to escalation of therapy was the most frequently encountered finding (484 endoscopies, 32.9%), with most esophagitis attributed to acid reflux. Barrett's esophagus (intestinal metaplasia) was identified in 7 unique patients (1.3%) at a median age of 11.3 years. No dysplastic lesions were identified. Actionable findings leading to surgical intervention were found in 55 children (30 refractory reflux and 25 tracheoesophageal fistulas). Significant predictors of actionable pathology included increasing age, long gap atresia, and hiatal hernia. Symptoms were not predictive of actionable findings, except dysphagia, which was associated with stricture. Nelson-Aalen analysis predicted occurrence of an actionable finding every 5 years. CONCLUSIONS: Surveillance endoscopy uncovers high rates of actionable pathology even in asymptomatic children with EA. Based on the findings of the current study, a pediatric EA surveillance endoscopy algorithm is proposed.

The impact of surgical-oncologic textbook outcome in patients with stage I to III pancreatic ductal adenocarcinoma: A cross-validation study of two national registries.

BACKGROUND: Using national registries, we aimed to evaluate oncologic textbook outcomes in pancreatic ductal adenocarcinoma patients. METHODS: Patients with stage I to III pancreatic ductal adenocarcinoma and surgical resection from 2010 to 2020 in the US and Germany were identified using the National Cancer Database and National Cancer Registries data. The surgical-oncologic textbook outcome was defined as complete oncologic resection with no residual tumor and ≥12 harvested lymph nodes. The composite endpoint was defined as surgical-oncologic textbook outcome and receipt of perioperative systemic and/or radiation therapy. RESULTS: In total, 33,498 patients from the National Cancer Database and 14,589 patients from the National Cancer Registries were included. In the National Cancer Database, 28,931 (86%) patients had complete oncologic resection with no residual tumor, and 11,595 (79%) in the National Cancer Registries. 8,723 (26%) patients in the National Cancer Database and 556 (4%) in the National Cancer Registries had <12 lymph nodes harvested. The National Cancer Database shows 26,135 (78%) underwent perioperative therapy and 8,333 (57%) in the National Cancer Registries. Surgical-oncologic textbook outcome was achieved in 21,198 (63%) patients in the National Cancer Database and in 11,234 (77%) patients from the National Cancer Registries. 16,967 (50%) patients in the National Cancer Database and 7,878 (54%) patients in the National Cancer Registries had composite textbook outcome. Median overall survival in patients with composite textbook outcomes was 32 months in the National Cancer Database and 27 months in the National Cancer Registries (P < .001). In contrast, those with non-textbook outcomes had a median overall survival of 23 months in the National Cancer Database and 20 months in the National Cancer Registries (P < .001). CONCLUSION: Surgical-oncologic textbook outcomes were achieved in > 50% of stage I to III pancreatic ductal adenocarcinoma for both the National Cancer Database and the National Cancer Registries. Failure to achieve textbook outcomes was associated with impaired survival across both registries.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS: This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS: Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION: In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

Sofosbuvir más glecaprevir/pibrentasvir como terapia de rescate postrasplante hepático en pacientes con exposición previa a inhibidores de NS5A. Serie de casos / Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series

Resumen Antecedentes: El tratamiento de la infección crónica por el virus de la hepatitis C (VHC) con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). Objetivo: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). Material y métodos: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. Resultados: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. Conclusión: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.

Abstract Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rates higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. Objective: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. Material and methods: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. Results: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. Conclusion: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.

Facility type is associated with improved perioperative and oncologic outcomes after minimally invasive surgery for pancreatic cancer.

BACKGROUND: This study sought to evaluate outcome differences by facility type in patients who underwent minimally invasive surgery (MIS) for pancreatic ductal adenocarcinoma (PDAC). METHODS: The National Cancer Database was used to identify patients with clinical stage I-III PDAC who underwent MIS from 2010 to 2019 in academic or community facilities. RESULTS: Of 6806 patients who fulfilled inclusion criteria; 1788 (26.3%) were treated at community facilities and 5018 (74.7%) at academic facilities. Patients treated at academic facilities were more likely to receive care at a high-volume facility (62% vs. 32%, p < 0.001), undergo a Whipple (64% vs. 61%, p < 0.001), and be clinical stage II (42% vs. 38%) and III (5.6% vs. 4.9%, p = 0.001). Treatment at academic facilities was predictive of receiving neoadjuvant therapy (OR 2.08, p < 0.001), negative margin resection (OR 0.80, p = 0.004), lower 90-day mortality (OR 0.72, p = 0.02), decreased length of stay (IRR 0.96, p < 0.001), and longer OS (HR 0.88, p = 0.002). CONCLUSION: Patients who underwent MIS for PDAC at academic facilities experienced an association with improved perioperative and oncologic outcomes than those treated in community facilities.

Identification of high-risk features in mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms of the pancreas are uncommon tumors that have the potential of becoming cancer. There is no consensus regarding the high-risk features of these tumors. Our study aimed to identify the preoperative demographic, clinical, or radiologic factors that can predict the presence of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. METHODS: We identified 157 patients who underwent resection and fulfilled the pathologic criteria for mucinous cystic neoplasms of the pancreas in a prospectively maintained database spanning 3 decades (1990-2020). Multivariable logistic regression was used to identify predictors of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. RESULTS: The rate of high-grade dysplasia or invasive carcinoma was 11%. Tumor size ≥4 cm (P < .001), mural nodularity (P = .04), and a serum CA 19-9 level >37 U/mL (P < .001) were associated with high-grade dysplasia or invasive carcinoma. In the multivariable analysis, tumor size ≥4 cm (odds ratio 16.9, 95% confidence interval 2.04-140, P = .009) and a CA 19-9 level >37 U/mL (odds ratio 5.68, 95% confidence interval 1.52-21.3, P = .010) were predictors of high-grade dysplasia or invasive carcinoma. There were no tumors with high-grade dysplasia or invasive carcinoma in patients with tumor size <4 cm in the absence of an elevated CA 19-9 or mural nodularity. CONCLUSION: Tumors with a size ≥4 cm and/or a high CA 19-9 level should be considered for prompt surgical resection. Conversely, tumors <4 cm with no other high-risk features have a negligible risk for high-grade dysplasia or invasive carcinoma and may benefit from nonoperative surveillance. Mural nodularity is an additional suspicious feature. These findings may contribute to future guidelines.

Immunotolerance in liver transplantation: a primer for the clinician.

The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.

Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.