Contemporary outcomes of left thoraco-abdominal esophagectomy due to cancer in the esophagus or gastroesophageal junction, a multicenter cohort study.

Surgery for cancer of the esophagus or gastro-esophageal junction can be performed with a variety of minimally invasive and open approaches. The left thoracoabdominal esophagectomy (LTE) is an open technique that gives an opportunity to operate in the chest and abdomen with excellent exposure of the gastro-esophageal junction through a single incision, and there is currently no equivalent minimally invasive technique available. The aim of this multi-institutional review was to study a large contemporary international study cohort of patients treated with LTE. An international multicenter cohort study was performed including all patients treated with LTE at six high-volume centers for gastro-esophageal cancer surgery between 2012 and 2022. Patient data were prospectively collected in each participating centers' institutional database. Information about patient, tumor, and treatment details were collected. The study cohort included a total of 793 patients treated with LTE during the study period. The most frequently observed complications were pneumonia in 185/727 (25.5%) patients and atrial fibrillation in 91/727 (12.5%). Anastomotic leak occurred in 35/727 (4.8%) patients; no patient suffered from conduit necrosis. Thirty-day mortality occurred in 15/785 (1.9%) patients and 90-day mortality in 39/785 (5.0%) patients. Factors with statistically significant association with survival were American Society for Anesthesiologists-score, tumor location, tumor stage, and tumor free resection margins. Neoadjuvant therapy was not associated with increased survival compared to surgery alone but neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy showed statistically significant improved survival with hazard ratio 0.60 (95% confidence intervals:0.44-0.80, P = 0.001) in a multivariable adjusted model. This study demonstrates that LTE can be applied in selected patients with results that are comparable to other large studies of open and minimally invasive surgery for esophageal or gastro-esophageal cancer at high-volume centers.

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

ERAS guidelines-driven upper gastrointestinal contrast study after esophagectomy can detect delayed gastric conduit emptying and improve outcomes.

BACKGROUND: Delayed gastric conduit emptying can occur after esophagectomy and has been shown to be associated with increased risk for postoperative complications. Application of a standardized clinical protocol after esophagectomy including an upper gastrointestinal contrast study has the potential to improve postoperative outcomes. METHODS: Prospective cohort including all patients operated with esophagectomy at two high-volume centers for esophageal surgery. The standardized clinical protocol included an upper gastrointestinal contrast study on day 2 or 3 after surgery. All images were compiled and evaluated for the purpose of the study. Clinical data was collected in IRB approved institutional databases at the participating centers. RESULTS: The study included 119 patients treated with esophagectomy of whom 112 (94.1%) completed an upper gastrointestinal contrast study. The results showed that 8 (7.1%) patients had radiological delayed gastric conduit emptying defined as no emptying of contrast through the pylorus. Partial conduit emptying was seen in 34 (30.4%) patients, and 70 (62.5%) patients had complete conduit emptying. Complete or partial emptying was associated with significantly earlier nasogastric tube removal (3 vs. 6 days) and hospital discharge 8 vs. 17 days, P < 0.001). Radiological signs of delayed gastric conduit emptying were shown to be associated with increased risk of postoperative complications. There was, however, no association with severe postoperative complications according to Clavien-Dindo score, pulmonary complications, anastomotic leak or need for intensive care. CONCLUSION: The results of the study demonstrate that postoperative upper gastrointestinal contrast studies can be used to assess the level of emptying of the gastric conduit after esophagectomy. Application of upper gastrointestinal contrast study in the ERAS guidelines-driven standardized clinical pathway after esophagectomy has the potential to improve postoperative outcomes.

Open left thoracoabdominal esophagectomy a viable option in the era of minimally invasive esophagectomy.

Minimally invasive surgical technique has become standard at many institutions in esophageal cancer surgery. In some situations, however other surgical approaches are required. Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky distal esophageal tumors, but there are concerns that this approach is associated with significant morbidity. Prospectively entered esophagectomy databases from three high-volume centers were reviewed for patients undergoing LTE or MIE 2009-2019. Patient demographics, tumor characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 915 patients were included in the study, LTE was applied in 684 (74.8%) patients, and MIE in 231 (25.2%) patients. LTE patients had more locally advanced tumor stage and received more neoadjuvant treatment. Patients treated with MIE had more comorbidities. The results showed no difference in overall postoperative complications (LTE = 61.7%, MIE = 65.7%, P = 0.289), severe complications (Clavien-Dindo ≥IIIa (LTE = 25.9%, MIE 26.8%, P = 0.806)), pneumonia (LTE = 29.0%, MIE = 24.7%, P = 0.211), anastomotic leak (LTE = 7.8%, MIE = 11.3%, P = 0.101), or in-hospital mortality (LTE = 2.6%, MIE = 3.5%, P = 0.511). Median number of resected lymph nodes was 24 for LTE and 25 for MIE (P = 0.491). LTE was used for more advanced tumors in patients that were more likely to have received neoadjuvant treatment compared with MIE, however postoperative morbidity, mortality, and oncologic outcomes were equivalent to that of MIE in this cohort. In conclusion open resection with left thoracoabdominal approach is a valid option in selected patients when performed at high-volume esophagectomy centers.

Health-related quality of life following total minimally invasive, hybrid minimally invasive or open oesophagectomy: a population-based cohort study.

BACKGROUND: Minimally invasive oesophagectomy has been shown to reduce the risk of pulmonary complications compared with open oesophagectomy, but the effects on health-related quality of life (HRQoL) and oesophageal cancer survivorship remain unclear. The aim of this study was to assess the longitudinal effects of minimally invasive compared with open oesophagectomy for cancer on HRQoL. METHODS: All patients who had surgery for oesophageal cancer in Sweden from January 2013 to April 2018 were identified. The exposure was total or hybrid minimally invasive oesophagectomy, compared with open surgery. The study outcome was HRQoL, evaluated by means of the European Organisation for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-OG25 at 1 and 2 years after surgery. Mean differences and 95 per cent confidence intervals were adjusted for confounders. RESULTS: Of the 246 patients recruited, 153 underwent minimally invasive oesophagectomy, of which 75 were hybrid minimally invasive and 78 were total minimally invasive procedures. After adjustment for age, sex, Charlson Co-morbidity Index score, pathological tumour stage and neoadjuvant therapy, there were no clinically and statistically significant differences in overall or disease-specific HRQoL after oesophagectomy between hybrid minimally invasive and total minimally invasive surgical technique versus open surgery. CONCLUSION: In this population-based nationwide Swedish study, longitudinal HRQoL after minimally invasive oesophagectomy was similar to that of the open surgical approach.

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Relevant issues in tumor regression grading of histopathological response to neoadjuvant treatment in adenocarcinomas of the esophagus and gastroesophageal junction.

Multimodality treatment combining surgery and oncologic treatment has become widely applied in curative treatment of esophageal and gastroesophageal junction adenocarcinoma. There is a need for a standardized tumor regression grade scoring system for clinically relevant effects of neoadjuvant treatment effects. There are numerous tumor regression grading systems in use and there is no international standardization. This review has found nine different international systems currently in use. These systems all differ in detail, which inhibits valid comparisons of results between studies. Tumor regression grading in esophageal and gastroesophageal junction adenocarcinoma needs to be improved and standardized. To achieve this goal, we have invited a significant group of international esophageal and gastroesophageal junction adenocarcinoma pathology experts to perform a structured review in the form of a Delphi process. The aims of the Delphi include specifying the details for the disposal of the surgical specimen and defining the details of, and the reporting from, the agreed histological tumor regression grade system including resected lymph nodes. The second step will be to perform a validation study of the agreed tumor regression grading system to ensure a scientifically robust inter- and intra-observer variability and to incorporate the consented tumor regression grading system in clinical studies to assess its predictive and prognostic role in treatment of esophageal and gastroesophageal junction adenocarcinomas. The ultimate aim of the project is to improve survival in esophageal and gastroesophageal adenocarcinoma by increasing the quality of tumor regression grading, which is a key component in treatment evaluation and future studies of individualized treatment of esophageal cancer.

Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study.

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

Cardiorespiratory Comorbidity and Postoperative Complications following Esophagectomy: a European Multicenter Cohort Study.

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial).

BACKGROUND: There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS: In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS: Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION: HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.

ANTECEDENTES: Se dispone de poca información sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante. MÉTODOS: En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5-Fluorouracilo 750 mg/m2 /infusión de 24 horas en los días 1-5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ-C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad. RESULTADOS: De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT. CONCLUSIÓN: La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.

Outcomes of nutritional jejunostomy in the curative treatment of esophageal cancer.

Substantial weight loss and eating problems are common before and after esophagectomy for cancer. The use of jejunostomy might prevent postoperative weight loss, but studies evaluating other outcomes are scarce. This study aims to assess the influence of jejunostomy on postoperative health-related quality of life (HRQOL), complications, reoperation, hospital stay, and survival. This prospective and population-based cohort study included all patients operated on for esophageal or gastroesophageal junction cancer in Sweden in 2001-2005 with follow-up until 31st December 2016. Data regarding patient and tumor characteristics and treatment were prospectively collected. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), whereas Cox regression provided hazard ratios with 95% CI. All risk estimates were adjusted for age, sex, tumor histology, stage, comorbidity, surgical approach, neoadjuvant therapy, and body mass index and weight loss at baseline. Among 397 patients, 181 (46%) received a jejunostomy during surgery. The use of jejunostomy did not influence the HRQOL at 6 months or 3 years after treatment. Jejunostomy users had no statistically significantly increased risk of postoperative complications (OR 1.27; 95% CI 0.86-1.87) or reoperation (OR 1.70; 95% CI 0.88-3.28). Intensive unit care and length of hospital stay was the same independent of the use of jejunostomy. The all-cause mortality was not increased in the jejunostomy group (HR 0.89, 95% CI: 0.74-1.07). This study indicates that jejunostomy does not influence postoperative HRQOL, complications, or survival after esophageal cancer surgery, it can be considered a safe method for early enteral nutrition after esophageal cancer surgery but benefits for the patients need further investigations.

Long-term weight development after esophagectomy for cancer-comparison between open Ivor-Lewis and minimally invasive surgical approaches.

Esophagectomy is an extensive procedure with severe postoperative effects. It can be assumed that the greater the trauma, the longer the nutritional recovery. This retrospective observational single-center cohort study compared weight development after esophagectomy with open and minimally invasive techniques. Three groups were compared in this study, one representing the first 41 patients who underwent the minimally invasive McKeown esophagectomy (MIMK). The second group included the first 84 consecutive patients operated with the minimally invasive Ivor-Lewis esophagectomy (MIIL). The third group comprised 100 consecutive patients operated with open thoracoabdominal Ivor-Lewis esophagectomy (IL). Virtually all patients submitted to a minimally invasive esophagectomy (MIE) and the majority with an IL had a jejunal catheter inserted during operation for postoperative enteral feeding. All together 225 patients were included in this study. The mean weight loss during the first year was 13.1% (±4.1), 11.2% (±6.1), and 9.6% (±7.5) in the IL, MIIL, and MIMK group, respectively (P = 0.85 and P = 0.95, respectively). The median duration of postoperative enteral nutrition support varied substantially within the groups and was 23.5 days in the IL group (range: 0-2033 days), 54.5 days in those having an MIIL (range: 0-308 days; P ≤ 0.001) and 57.0 days among patients in the MIMK group (range: 0-538 days; P ≤ 0.022). There was no difference in the risk of losing at least 10% of the preoperative weight at 3 or 6 months postoperatively between the groups. However, in patients who suffered severe complications (Clavien-Dindo score ≥ IIIb) after MIIL, there was a nonsignificant trend toward a lower risk of a 10% or greater weight loss, 3 months postoperatively. In conclusion, the greater surgical trauma associated with the traditional open esophagectomy was not followed by more severe weight loss, or other signs of poorer nutritional recovery, when compared to minimal invasive surgical techniques.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Single center consecutive series cohort study of minimally invasive versus open resection for cancer in the esophagus or gastroesophageal junction.

Minimally invasive esophagectomy (MIE) has been introduced at many centers worldwide as evidence is accumulating that it reduces the risk of postoperative morbidity and mortality and decreases the length of hospital stay compared to conventional open esophagectomy. The study is a single institution cohort study of 366 consecutive patients treated with curative intent for cancer in the esophagus or gastroesophageal junction, comparing MIE to open surgery. The outcomes studied were peroperative bleeding, operation time, lymph node yield, complications, length of stay and overall survival. The results showed that MIE was associated with reduced peroperative bleeding and operation time. The patients in the MIE group had a statistically significant reduced risk of postoperative complications, 60.2% compared to 78.8% in the open group. In the MIE group 28.4% of the patients had postoperative complications classified according to the Clavien-Dindo classification system as grade IIIb-V compared to 38.2% in the open group, P = 0.046. Median hospital stay was reduced with 10 days comparing MIE to open surgery, P < 0.001. Mean number of resected lymph nodes was 31 in the MIE group and 22 in the open group (P < 0.001), while the R0 resections were 91.5% versus 85% (P = 0.057). Overall long-term survival was higher in the MIE group, a difference that however did not reach statistical significance (adjusted hazard ratio for three-year survival 0.76, 95% CI 0.54-1.08). In conclusion, MIE at a high volume center with a devoted specialist team reduces the risk of peroperative bleeding, operation time, and severe postoperative complications compared to open surgery for esophageal or junctional cancer. The number of resected lymph nodes was increased and the R0 resections were similar between the groups indicating a good oncological quality of the surgery.

A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction.

BACKGROUND: Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT. PATIENTS AND METHODS: This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm. RESULTS: The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms. CONCLUSION: The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival. CLINICALTRIALSGOV: NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).

Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro-oesophageal junction based on a national data registry.

BACKGROUND: Randomized trials have shown that neoadjuvant treatment improves survival in the curative treatment of oesophageal and gastro-oesophageal junction cancer. Results from population-based observational studies are, however, sparse and ambiguous. METHODS: This prospective population-based cohort study included all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1 N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006-2014. Patients were stratified into three groups: surgery alone, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. RESULTS: Neoadjuvant treatment was given to 521 patients (51·1 per cent) and 499 (48·9 per cent) received surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative surgical complications compared with surgery alone (adjusted odds ratio 2·01, 95 per cent c.i. 1·24 to 3·25; P = 0·005). Postoperative mortality was significantly increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds ratio 2·37, 1·06 to 5·29; P = 0·035). Survival improved in patients with squamous cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant chemoradiotherapy survival was significantly improved only in the subgroup with the highest performance status and without known co-morbidity. In adenocarcinoma there was a trend towards improved overall survival after neoadjuvant chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit. Stratified analysis including only patients with adenocarcinoma in the highest performance category without known co-morbidity showed a strong trend towards improved survival after neoadjuvant chemotherapy compared with surgery alone (adjusted hazard ratio 0·47, 0·21 to 1·04; P = 0·061). CONCLUSION: For patients with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction, neoadjuvant treatments seemed to increase long-term survival, but also the risk of postoperative morbidity and mortality, compared with surgery alone. Neither neoadjuvant treatment option seemed to improve survival significantly among patients with adenocarcinoma, compared with surgery alone.

Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers.

BACKGROUND: The long-term survival benefits of neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACR) for oesophageal carcinoma are well established. Both are burdened, however, by toxicity that could contribute to perioperative morbidity and mortality. METHODS: MEDLINE, the Cochrane Library and Embase were searched to capture the incidence of any postoperative complications, cardiac complications, respiratory complications, anastomotic leakage, postoperative 30-day mortality, total postoperative mortality and treatment-related mortality in randomized clinical trials comparing NAC or NACR with surgery alone, or NAC versus NACR. Meta-analyses comparing NAC and NACR were conducted by using adjusted indirect comparison. RESULTS: Twenty-three relevant studies were identified. Comparing NAC or NACR with surgery alone, there was no increase in morbidity or mortality attributable to neoadjuvant therapy. Subgroup analysis of NACR for squamous cell carcinoma (SCC) suggested an increased risk of total postoperative mortality and treatment-related mortality compared with surgery alone: risk ratio 1·95 (95 per cent confidence interval 1·06 to 3·60; P = 0·032) and 1·97 (1·07 to 3·64; P = 0·030) respectively. A combination of direct comparison and adjusted indirect comparison showed no difference between NACR and NAC regarding morbidity or mortality. CONCLUSION: Neither NAC nor NACR for oesophageal carcinoma increases the risk of postoperative morbidity or perioperative mortality compared with surgery alone. There was no clear difference between NAC and NACR. Care should be taken with NACR in oesophageal SCC, where an increased risk of postoperative mortality and treatment-related mortality was apparent.