E R C Hagens

Bio: E R C Hagens is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Esophagectomy & Esophageal cancer. The author has an hindex of 7, co-authored 17 publications receiving 160 citations.

Anastomotic leakage after esophagectomy for esophageal cancer: definitions, diagnostics, and treatment

Abstract: Anastomotic leakage is one of the most severe complications after esophagectomy and is associated with increased postoperative morbidity and mortality. Several projects ranging from small retrospective studies to large collaborations have aimed to identify potential pre- and perioperative risk factors and to improve the diagnostic processes and management. Despite the increase in available literature, many aspects of anastomotic leakage are still debated, without the existence of widely accepted guidelines. The purpose of this review is to provide a cutting edge overview of the recent literature regarding the definition and classification of anastomotic leakage, risk factors, novel diagnostic modalities, and emerging therapeutic options for treatment and prevention of anastomotic leakage following esophagectomy.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study

Abstract: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. NCT03222895 , date of registration: July 19th, 2017.

The extent of lymphadenectomy in esophageal resection for cancer should be standardized

Abstract: The incidence of esophageal cancer increases, with approximately 482,000 patients diagnosed with esophageal cancer each year. Despite the growing incidence of esophageal carcinoma, the extent of the lymphadenectomy is still under discussion. Lymph node status is an important prognostic parameter in esophageal cancer and an independent predictor of survival. Surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy differs worldwide. For squamous cell cancer, Japanese surgeons have standardized the 2- or 3-field lymphadenectomy according to the location of the tumor. For adenocarcinoma, in the Western World accounting for 85% of all esophageal cancers, the type of lymphadenectomy to perform is not clear. Moreover, the use of neoadjuvant therapy may influence the mediastinal lymph nodes and the significance of the lymphadenectomy for survival. These aspects have challenged the traditional policy concerning lymphadenectomy, at least in the Western World. Furthermore, an extensive lymphadenectomy may improve survival but, on the other hand, may cause significant more morbidity. An overview of the literature on the extent of lymphadenectomy for esophageal cancer with respect to the supposed lymph node distribution patterns for squamous cell carcinoma and adenocarcinoma, the different lymph node classification systems, the commonly used surgical techniques and outcomes, and the proposal of observational cohort study to standardize the type of lymphadenectomy according to the type of tumor, location and use of neoadjuvant therapy will be provided.

Distribution of Lymph Node Metastases in Esophageal Carcinoma Patients Undergoing Upfront Surgery: A Systematic Review

Abstract: Metastatic lymphatic mapping in esophageal cancer is important to determine the optimal extent of the radiation field in case of neoadjuvant chemoradiotherapy and lymphadenectomy when esophagectomy is indicated. The objective of this review is to identify the distribution pattern of metastatic lymphatic spread in relation to histology, tumor location, and T-stage in patients with esophageal cancer. Embase and Medline databases were searched by two independent researchers. Studies were included if published before July 2019 and if a transthoracic esophagectomy with a complete 2- or 3-field lymphadenectomy was performed without neoadjuvant therapy. The prevalence of lymph node metastases was described per histologic subtype and primary tumor location. Fourteen studies were included in this review with a total of 8952 patients. We found that both squamous cell carcinoma and adenocarcinoma metastasize to cervical, thoracic, and abdominal lymph node stations, regardless of the primary tumor location. In patients with an upper, middle, and lower thoracic squamous cell carcinoma, the lymph nodes along the right recurrent nerve are often affected (34%, 24% and 10%, respectively). Few studies describe the metastatic pattern of adenocarcinoma. The current literature is heterogeneous in the classification and reporting of lymph node metastases. This complicates evidence-based strategies in neoadjuvant and surgical treatment.

Anastomotic leakage after esophagectomy for esophageal cancer: definitions, diagnostics, and treatment

Abstract: Anastomotic leakage is one of the most severe complications after esophagectomy and is associated with increased postoperative morbidity and mortality. Several projects ranging from small retrospective studies to large collaborations have aimed to identify potential pre- and perioperative risk factors and to improve the diagnostic processes and management. Despite the increase in available literature, many aspects of anastomotic leakage are still debated, without the existence of widely accepted guidelines. The purpose of this review is to provide a cutting edge overview of the recent literature regarding the definition and classification of anastomotic leakage, risk factors, novel diagnostic modalities, and emerging therapeutic options for treatment and prevention of anastomotic leakage following esophagectomy.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study

Abstract: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. NCT03222895 , date of registration: July 19th, 2017.

Clinical Impact of the Location of Lymph Node Metastases After Neoadjuvant Chemotherapy for Middle and Lower Thoracic Esophageal Cancer.

Abstract: In the current cancer staging systems, the location of lymph node (LN) metastases is not considered, although LN status is defined according to the number of LN metastases. This study aimed to investigate the clinical impact of the location of LN metastases in esophageal cancer and to evaluate the relevance of minimizing the extent of lymphadenectomy after neoadjuvant therapy. In 561 patients with esophageal cancer who underwent neoadjuvant chemotherapy, the therapeutic value of each LN dissection was estimated by multiplying the incidence of metastasis by the 5-year survival rate of patients with positive nodes. In addition, we examined whether the value was affected by the response to neoadjuvant therapy. Metastasis to the celiac LN and middle mediastinal LN regions was identified as an independent prognostic factor by multivariate analysis, together with the number of LN metastases; however metastasis to the cervical LN and upper mediastinal LN regions was not identified as an independent prognostic factor. The therapeutic value was high in recurrent nerve LNs, paraesophageal LNs, paracardial LNs, and left gastric LNs. The therapeutic value for each LN dissection did not change according to the response to neoadjuvant therapy, excluding the lower mediastinal LN and perigastric LN stations for which the value was relatively high in patients with a poor response. The present study shows that the location and number of LN metastases have a prognostic impact in patients with esophageal cancer undergoing neoadjuvant chemotherapy. Limited lymphadenectomy according to the response to neoadjuvant therapy cannot be justified.

International variation in surgical practices in units performing oesophagectomy for oesophageal cancer: A unit survey from the Oesophago-Gastric Anastomosis Audit (OGAA)

Abstract: BACKGROUND: Anastomotic leaks are associated with significant risk of morbidity, mortality and treatment costs after oesophagectomy. The aim of this study was to evaluate international variation in unit-level clinical practice and resource availability for the prevention and management of anastomotic leak following oesophagectomy. METHOD: The Oesophago-Gastric Anastomosis Audit (OGAA) is an international research collaboration focussed on improving the care and outcomes of patients undergoing oesophagectomy. Any unit performing oesophagectomy worldwide can register to participate in OGAA studies. An online unit survey was developed and disseminated to lead surgeons at each unit registered to participate in OGAA. High-income country (HIC) and low/middle-income country (LMIC) were defined according to the World Bank whilst unit volume were defined as < 20 versus 20-59 versus ≥60 cases/year in the unit. RESULTS: Responses were received from 141 units, a 77% (141/182) response rate. Median annual oesophagectomy caseload was reported to be 26 (inter-quartile range 12-50). Only 48% (68/141) and 22% (31/141) of units had an Enhanced Recovery After Surgery (ERAS) program and ERAS nurse, respectively. HIC units had significantly higher rates of stapled anastomosis compared to LMIC units (66 vs 31%, p = 0.005). Routine post-operative contrast-swallow anastomotic assessment was performed in 52% (73/141) units. Stent placement and interventional radiology drainage for anastomotic leak management were more commonly available in HICs than LMICs (99 vs 59%, p < 0.001 and 99 vs 83%, p < 0.001). CONCLUSIONS: This international survey highlighted variation in surgical technique and management of anastomotic leak based on case volume and country income level. Further research is needed to understand the impact of this variation on patient outcomes.