Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Induction chemotherapy followed by surgery for advanced oesophageal cancer.

BACKGROUND: Patients with locoregionally advanced oesophageal tumours or disputable distant metastases are referred for induction chemotherapy with the aim to downstage the tumour before an oesophagectomy is considered. STUDY DESIGN: Patients who underwent induction chemotherapy between January 2005 and December 2012 were identified from an institutional database. Treatment plan was discussed in the multidisciplinary team. Response to chemotherapy was assessed by CT. Survival was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: In total 124 patients received induction chemotherapy mainly for locoregionally advanced disease (n = 80). Surgery was withheld in 35 patients because of progressive disease (n = 16) and persistent unresectability (n = 19). The median overall survival of this group was 13 months (IQR: 8-19). The remaining 89 patients underwent surgery of which 13 still had unresectable tumour or distant metastases. Of the 76 patients that underwent an oesophagectomy, 50 patients had tumour free resection margins (66%) with an estimated 5-year survival of 37%. A positive resection margin (HR 4.148, 95% CI 2.298-7.488, p < 0.0001) was associated with a worse survival in univariable analysis, but only pathological lymph node status with increasing hazard ratio's (6.283-10.283, p = 0.001) remained significant after multivariable analysis. CONCLUSION: Induction chemotherapy downstages the tumour and facilitates a radical oesophagectomy in patients with advanced oesophageal cancer. Pathological lymph node status is an independent prognostic factor for overall survival.

Review article: The management of non-cirrhotic non-malignant portal vein thrombosis and concurrent portal hypertension in adults.

BACKGROUND: Extrahepatic portal vein thrombosis is an important cause of non-cirrhotic portal hypertension. AIM: To provide an update on recent advances in the aetiology and management of acute and chronic non-cirrhotic non-malignant extrahepatic portal vein thrombosis. METHOD: A PubMed search was performed to identify relevant literature using search terms including 'portal vein thrombosis', 'variceal bleeding' and 'portal biliopathy'. RESULTS: Myeloproliferative disease is the most common risk factor in patients with non-cirrhotic non-malignant extrahepatic portal vein thrombosis. Anticoagulation therapy for at least 3 months is indicated in patients with acute extrahepatic portal vein thrombosis. However, in patients with extrahepatic portal vein thrombosis due to a prothrombotic disorder, permanent anticoagulation therapy can be considered. The most important complication of extrahepatic portal vein thrombosis is oesophagogastric variceal bleeding. Endoscopic treatment is the first-line treatment for variceal bleeding. In several of the patients with extrahepatic portal vein thrombosis biliopathy changes on endoscopic retrograde cholangiography (ERCP) have been reported. Dependent on the persistence of the biliary obstruction, treatment can vary from ERCP to hepaticojejunostomy. CONCLUSION: Prothrombotic disorders are the major causes of non-cirrhotic, non-malignant extrahepatic portal vein thrombosis and anticoagulation therapy is warranted in these patients. The prognosis of patients with non-cirrhotic, non-malignant extrahepatic portal vein thrombosis is good, and is not determined by portal hypertension complications but mainly by the underlying cause of thrombosis.