Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study.

Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

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

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.

A proposal for uniformity in classification of lymph node stations in esophageal cancer.

The 11th edition of the "Japanese Classification of Esophageal Cancer" by the Japan Esophageal Society (JES) and the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) "Cancer Staging Manual" are two separate classification systems both widely used for the clinical and pathological staging of esophageal cancer. Furthermore, the lymph node stations from these classification systems are combined for research purposes in the multinational TIGER study, which investigates the distribution pattern of lymph node metastases. The existing classification systems greatly differ with regard to number, location and anatomical boundaries of locoregional lymph node stations. The differences in these classifications cause significant heterogeneity in studies on lymph node metastases in esophageal cancer. This makes data interpretation difficult and comparison of studies challenging. In this article, we propose a match for these two commonly used classification systems and additionally for the TIGER study classification, in order to be able to compare results of studies and exchange knowledge and to make steps towards one global uniform classification system for all patients with esophageal cancer.

Conditional survival after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

BACKGROUND: Conditional survival accounts for the time already survived after surgery and may be of additional informative value. The aim was to assess conditional survival in patients with oesophageal cancer and to create a nomogram predicting the conditional probability of survival after oesophagectomy. METHODS: This retrospective study included consecutive patients with oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy between January 2004 and 2019. Conditional survival was defined as the probability of surviving y years after already surviving for x years. The formula used for conditional survival (CS) was: CS(x|y)  = S(x + y) /S(x) , where S(x) represents overall survival at x years. Cox proportional hazards models were used to evaluate predictors of overall survival. A nomogram was constructed to predict 5-year survival directly after surgery and given survival for 1, 2, 3 and 4 years after surgery. RESULTS: Some 660 patients were included. Median overall survival was 44·4 (95 per cent c.i. 37·0 to 51·8) months. The probability of achieving 5-year overall survival after resection increased from 45 per cent directly after surgery to 54, 65, 79 and 88 per cent given 1, 2, 3 and 4 years already survived respectively. Cardiac co-morbidity, cN category, ypT category, ypN category, chyle leakage and pulmonary complications were independent predictors of survival. The nomogram predicted 5-year survival using these predictors and number of years already survived. CONCLUSION: The probability of achieving 5-year overall survival after oesophagectomy for cancer increases with each additional year survived. The proposed nomogram predicts survival in patients after oesophagectomy, taking the years already survived into account.

ANTECEDENTES: La supervivencia condicional hace referencia al tiempo ya sobrevivido tras la cirugía y esta información puede tener un valor adicional. El objetivo fue evaluar la supervivencia condicional en pacientes con cáncer de esófago y crear un nomograma para predecir la probabilidad condicional de supervivencia tras una esofaguectomía. MÉTODOS: Estudio retrospectivo incluyó pacientes consecutivos con cáncer de esófago que fueron tratados con quimiorradioterapia neoadyuvante seguida de cirugía, entre enero de 2004 a 2019, en el centro médico de la Universidad de Amsterdam (AMC) de los Países Bajos. La supervivencia condicional se definió como la probabilidad de sobrevivir y años tras haber ya sobrevivido ya durante x años. La formula utilizada fue: CS(x|y) =S(x+y) /S(x) , con S(x) representando la supervivencia global a x años. Se utilizaron modelos de riesgo proporcional de Cox para evaluar los predictores de supervivencia global. Se construyó un nomograma para predecir la supervivencia a los 5 años directamente tras la cirugía y dar la supervivencias a 1-, 2-, 3- y 4 años después de la cirugía. RESULTADOS: Se incluyeron 660 pacientes. La mediana de la supervivencia global fue de 44,4 meses (i.c. del 95% 37,0-51,8). La probabilidad de conseguir una supervivencia global a los 5 años tras la resección aumentó del 45% directamente después de la cirugía al 54%, 65%, 79% y 88% por cada año adicional sobrevivido. La comorbilidad cardiaca, estadio cN, estadio ypT, estadio ypN, quilotórax y complicaciones pulmonares fueron predictores independientes de supervivencia. El nomograma predijo la supervivencia a 5 años utilizando estos predictores y número de años ya sobrevividos. CONCLUSIÓN: La probabilidad de alcanzar una supervivencia global a los 5 años tras una esofaguectomía por cáncer aumenta por cada año adicional sobrevivido. El nomograma propuesto predice la supervivencia en pacientes después de una esofaguectomía, teniendo en cuenta los años ya sobrevividos.

Long-Term Quality of Life After Total Gastrectomy Versus Ivor Lewis Esophagectomy.

BACKGROUND: There is scarce evidence on whether a total gastrectomy or an Ivor Lewis esophagectomy is preferred for gastroesophageal junction (GEJ) cancers regarding effects on morbidity, pathology, survival and health-related quality of life (HR-QoL). The aim of this study was to investigate the difference in long-term HR-QoL in patients undergoing total gastrectomy versus Ivor Lewis esophagectomy in a tertiary referral center. METHODS: Patients with a follow-up of >1 year after a total gastrectomy or an Ivor Lewis esophagectomy for GEJ/cardia carcinoma completed the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. 'Problems with eating,' 'reflux,' and 'nausea and vomiting' were the primary HR-QoL endpoints. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. RESULTS: Thirty patients after gastrectomy and 71 after esophagectomy were included. Mean age was 63 years. Median follow-up was 2 years (range 12-84 months). Patients after gastrectomy reported less 'choking when swallowing' and 'coughing' (ß = - 5.952, 95% CI - 9.437 to - 2.466; ß = - 13.084, 95% CI - 18.525 to - 7.643). More lymph nodes were resected in esophagectomy group (p = 0.008). No difference was found in number of positive lymph nodes, R0 resection or postoperative complications. CONCLUSIONS: After a follow-up of >1 year 'choking when swallowing' and 'coughing' were less common after a total gastrectomy. No differences were found in postoperative complications or radicality of surgery. Based on this study, no general preference can be given to either of the procedures for GEJ cancer. These results support shared decision making when a choice between the two treatment options is possible.

Long-term health-related quality of life after McKeown and Ivor Lewis esophagectomy for esophageal carcinoma.

INTRODUCTION: Both cervical (McKeown) and intrathoracic (Ivor Lewis) anastomosis of transthoracic esophagectomy are surgical procedures that can be performed for distal esophageal or gastro-esophageal junction (GEJ) cancer. The purpose of this study was to investigate the long-term health-related quality of life (HR-QoL) after McKeown and Ivor Lewis esophagectomy in a tertiary referral center. METHODS: Disease-free patients >1 year following a McKeown or an Ivor Lewis esophagectomy with a two-field lymphadenectomy for a distal or GEJ carcinoma visiting the outpatient clinic between 2014 and 2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. HR-QoL was investigated in both groups. RESULTS: A total of 89 patients were included after McKeown and 115 after Ivor Lewis esophagectomy. Median follow-up was 2.4 years (IQR 1.7-3.6). Patients after McKeown esophagectomy reported more problems with 'eating with others' compared to patients after Ivor Lewis esophagectomy (mean scores: 49.9 vs. 38.8). This difference was both clinically relevant and significant after correction for multiple testing (ß = 11.1, 95% CI 3.105-19.127, P = 0.042). Patients in both groups reported a poorer HR-QoL (≥10 points) than the general population with respect to nausea and vomiting, dyspnea, appetite loss, financial difficulties, problems with eating, reflux, eating with others, choked when swallowing, trouble with coughing, and weight loss. CONCLUSION: Long-term HR-QoL of disease-free patients following a McKeown or Ivor Lewis esophagectomy for a distal or GEJ carcinoma is largely comparable. Irrespective of the surgical technique, patients' HR-QoL following esophagectomy is compromised. When given the choice, patients should be informed that after a McKeown esophagectomy more problems while eating with others can occur.

Differences in Esophageal Cancer Surgery in Terms of Surgical Approach and Extent of Lymphadenectomy: Findings of an International Survey.

INTRODUCTION: Esophagectomy and lymphadenectomy are essential parts of the multimodal treatment of esophageal carcinoma with curative intent. Treatment regimens vary globally and are subject to debate. A global survey was designed to gain insight into current practice. METHODS: Fifty-seven international expert upper gastrointestinal surgeons received a personal invitation to participate in the survey, which focused on demographics and experience; extent of lymphadenectomy in adeno and squamous cell carcinoma; use of classification systems; neoadjuvant therapy; surgical approach; and specimen handling. RESULTS: The response rate was 88% (50/57 surgeons), with a mean age of 51.6 years and a median number of 15 years of experience in esophageal surgery. The variety in the extent of lymphadenectomy in proximal, middle and distal squamous cell carcinoma, and Siewert I, II and III adenocarcinoma, was considerable. The number of different combinations of lymph node (LN) stations that were resected in the same tumor was high, while the number of surgeons who removed the exact same combination of LN stations was low. Illustrative is Siewert I adenocarcinoma, in which 27 unique combinations of LN stations were resected, with a maximum of two surgeons performing the exact same dissection. Use of neoadjuvant therapy, surgical approach, and specimen handling also show great variety among participants. CONCLUSION: There is no uniform, worldwide strategy for surgical treatment of esophageal cancer. The extent of lymphadenectomy shows great variation for both histologic types. An international observational study is needed to provide evidence on the distribution pattern of lymph node metastases in esophageal cancer and the necessary extent of lymphadenectomy.

Long-Term Quality of Life Following Transthoracic and Transhiatal Esophagectomy for Esophageal Cancer.

BACKGROUND: The impact of transthoracic (TTE) and transhiatal esophagectomy (THE) on long-term health-related quality of life (HR-QoL) in patients with distal esophageal or gastro-esophageal junction (GEJ) cancer has been studied with variable results. This study investigates long-term HR-QoL in patients having undergone TTE or THE. METHODS: Disease-free patients after TTE or THE for distal esophageal or GEJ cancer with a follow-up > 2 years were included. Patients who visited the outpatient clinic of a tertiary referral center between 2014 and 2018 were asked to complete EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. Uni- and multivariable linear regression analysis of HR-QoL was performed in all patients and in subgroups of minimally invasive esophagectomy and neoadjuvant therapy. RESULTS: A total of 132 patients after TTE and 56 after THE were included. When compared with the general population, all patients reported worse HR-QoL in 'role functioning' and 'social functioning' and in a range of disease- and/or treatment-specific symptoms. The only significant difference between TTE and THE was a better HR-QoL score for "hair loss" following TTE (ß = 29.4,95%CI = -49.108 - -9.671, p = 0.016). Subgroup analysis of minimally invasively operated patients showed better scores in "physical functioning" following TTE (ß = 13.8,95%CI = 2.755-24.933, p = 0.030). No significant differences in HR-QoL were found between TTE and THE after neoadjuvant therapy. CONCLUSION: Long-term HR-QoL is largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ cancer. If there were differences between the surgical groups, they were in favor of TTE. These findings may aid in preoperative counseling of patients with esophageal or GEJ cancer.