M Navidi

The presence of lymphovascular and perineural infiltration after neoadjuvant therapy and oesophagectomy identifies patients at high risk for recurrence

Background:In patients treated for oesophageal cancer the importance of lymphovascular and perineural invasion (PNI) after neoadjuvant therapy has yet to be established. The aim of this study was to assess the incidence and prognostic significance of these factors in a consecutive series of patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) who underwent neoadjuvant therapy followed by oesophagectomy.Methods:Clinical and pathology results from patients with potentially curable adenocarcinoma, or squamous cell carcinoma of the oesophagus or GOJ were reviewed. Patients were treated with neoadjuvant chemotherapy or chemoradiation followed by transthoracic oesophagectomy and two-field lymphadenectomy. The presence of venous invasion (VI), lymph vessel invasion (LI) and perineural invasion (PNI) were correlated with clinical outcomes.Results:A total of 396 patients underwent oesophagectomy after neoadjuvant therapy for oesophageal cancer. Venous invasion was identified in 150 (38%) of patients, LI in 203 (51%) patients and PNI in 204 (52%) patients. In all, 123 (31%) patients had no evidence of either VI, LI or PNI. A total of 96 (24%) had a combination of two factors and 94 (24%) had all three factors. The presence of VI, LI and PNI was significantly related to tumour stage (P=0.001). Median overall survival was 170.8 months when all three factors were absent, 44.0 months when one factor was present, 27.1 months when two factors were present and 16.0 months when all were present. Multivariate analyses revealed VI, LI and PNI or a combination of these factors were independent predictors of prognosis.Conclusions:In oesophageal cancer patients treated with neoadjuvant therapy followed by oesophagectomy the presence of VI, LI and PNI has an important prognostic impact and may identify patients at high risk of recurrence who would benefit from adjuvant therapies.

The impact of neoadjuvant chemotherapy on cardiopulmonary physical fitness in gastro-oesophageal adenocarcinoma

Introduction Operable oesophagogastric adenocarcinoma management in the UK includes three cycles of neoadjuvant chemotherapy (NAC) followed by resection. Determination of oxygen uptake at the anaerobic threshold (AT) with cardiopulmonary exercise testing (CPET) is used to objectively measure cardiorespiratory reserve. Oxygen uptake at AT predicts perioperative risk, with low values associated with increased morbidity. Previous studies indicate NAC may have a detrimental impact on cardiorespiratory reserve. Methods CPET was completed by 30 patients before and after a standardised NAC protocol. The ventilatory AT was determined using the V-slope method, and the peak oxygen uptake and ventilatory equivalents for carbon dioxide measured. Median AT before and after chemotherapy was compared using a paired Students t-test. Results Median oxygen uptake at AT pre- and post-NAC was 13.9±3.1 ml/kg/min and 11.5±2.0 ml/kg/min, respectively. The mean decrease was 2.4 ml/kg/min (95% confidence interval [CI] 1.3-3.85; p<0.001). Median peak oxygen delivery also decreased by 2.17 ml/kg/min (95% CI 1.02-3.84; p=0.001) after NAC. Ventilatory equivalents were unchanged. Conclusions This reduction in AT objectively quantifies a decrease in cardiorespiratory reserve after NAC. Patients with lower cardiorespiratory reserve have increased postoperative morbidity and mortality. Preventing this decrease in cardiorespiratory reserve during chemotherapy, or optimising the timing of surgical resection after recovery of AT, may allow perioperative risk-reduction.

Impact of Extent of Lymphadenectomy on Survival, Post Neoadjuvant Chemotherapy and Transthoracic Esophagectomy

Objective: The aim of this study was to evaluate the influence of lymph node yield and the location of nodes on prognosis in patients with distal esophageal or gastroesophageal junction adenocarcinoma who have received neoadjuvant chemotherapy followed by transthoracic esophagectomy. Background: Debate continues regarding the extent of lymphadenectomy required when carrying out an esophagectomy. Lymph node yield has been used as a surrogate for extent of lymphadenectomy. Node location must, however, be reviewed to determine the true extent of lymphadenectomy. Methods: Data from consecutive patients with potentially curable adenocarcinoma of the lower esophagus or gastroesophageal junction were reviewed. Patients were treated with neoadjuvant chemotherapy, transthoracic esophagectomy, and 2-field lymphadenectomy. Outcomes according to lymph node yield were determined. Projected prognosis of carrying out less radical lymphadenectomies was calculated according to 3 groups: group 1—exclusion of proximal thoracic nodes, group 2—a minimal abdominal lymphadenectomy, and group 3—a minimal abdominal and thoracic lymphadenectomy. Results: Three hundred five patients were included. Median cancer-related survival was 37.7 months (confidence interval 29–46 mo). Absolute lymph node retrieval was not related to survival (P = 0.520). An estimated additional 4 (2–6) cancer-related deaths were projected if group 1 nodes were omitted, 2 (1–4) additional deaths if group 2 nodes were omitted, and 9 (6–12) extra deaths if group 3 nodes were omitted. A minimal lymphadenectomy (groups 1, 2, and 3) was projected to lead to a 23% reduction in survival in patients with N1 or N2. Conclusions: The present study demonstrates high lymph node yields are possible after transthoracic esophagectomy with en bloc 2-field lymphadenectomy in patients post neoadjuvant chemotherapy. This allows excellent postoperative staging. Furthermore, the extent of lymphadenectomy must be correlated with node location, which may have important implications in patients who have a less extensive lymphadenectomy.

Trainee Involvement in Ivor Lewis Esophagectomy Does Not Negatively Impact Outcomes

Objective: The aim of the present study was to determine whether trainee involvement in esophageal cancer resection is associated with adverse patient outcomes. Background: Operative experience for surgical trainees is under threat. A number of factors have been implicated in this leading to fewer hours for training. Esophagogastric cancer training is particularly vulnerable due to the publication of individual surgeon results and a perception that dual consultant operating improves patient outcomes. Resectional surgery is increasingly viewed as a subspeciality to be developed after completion of the normal training pathway. Methods: Data from a prospectively maintained database of consecutive patients undergoing trans-thoracic esophagectomy for potentially curable carcinoma of the esophagus or gastroesophageal junction were reviewed. Patients were divided into 4 cohorts, according to whether a consultant or trainee was the primary surgeon in either the abdominal or thoracic phase. Outcomes including operative time, lymph node yield, blood loss, complications graded by Accordion score, and mortality were recorded. Results: A total of 323 patients underwent esophagectomy during 4 years. The overall in-hospital mortality rate was 1.5%. At least 1 phase of the surgery was performed by a trainee in 75% of cases. There was no significant difference in baseline demographics of age, stage, neoadjuvant treatment, and histology between cohorts. There was no significant difference in blood loss (P = 0.8), lymph node yield (P = 0.26), length of stay (P = 0.24), mortality, and complication rate according to Accordion scores (P = 0.21) between cohorts. Chest operating time was a median 25 minutes shorter when performed by a consultant (P < 0.001). Conclusions: These findings demonstrate that patient outcomes are not compromised by supervised trainee involvement in transthoracic esophagectomy. Training is an essential role of all surgical units and training data should be more widely reported especially in areas of high-risk surgery.

Pre-operative variables including fitness associated with complications after oesophagectomy

Oesophagectomy is a technically‐demanding operation associated with a high level of morbidity. We analysed the association of pre‐operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02–1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre‐operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37–0.80), p = 0.002 and 0.89 (0.82–0.96), p = 0.004, respectively. Survival was associated with the ratio of expected‐to‐observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03–0.91), p = 0.039 and 0.96 (0.90–1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17–1.63), p < 0.0001.

Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer

Neoadjuvant chemotherapy may have a detrimental impact on cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic threshold by cardiopulmonary exercise testing (CPET) provides an objective measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict perioperative risk. A low anaerobic threshold is associated with increased morbidity after oesophagogastrectomy. The aim of this study was to establish whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether there is recovery of fitness before surgery for oesophageal and gastric adenocarcinoma.

PTH-141 Pattern of single lymph node metastasis in carcinoma of the oesophagus

Introduction The presence of lymphatic dissemination in oesophageal cancer affects prognosis. The relevance of location of an involved solitary lymph node is unclear. The concept of sentinel node guided lymphadenectomy to reduce surgical stress of a transthoracic operation has some advocates. However, the site of solitary lymph node metastasis, is unpredictable. Similarly, metastases to anatomically distant lymph nodes, known as skip lesions, could develop in the early phase of lymphatic invasion. The aim of this study was to examine the pattern of a single named lymph node metastasis in patients with oesophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC) who underwent resection with curative intent. No study to date has investigated this concept. Method Results of consecutive patients from a prospectively maintained database were analysed. All patients with potentially curable AC or SCC who underwent a radical two-field, two-stage, transthoracic oesophagectomy were included. Ex-vivo surgical dissection of the specimen was carried out post-operatively by the surgeon, with harvested lymph node stations labelled. This permitted accurate ‘lymph node mapping’. All harvested lymph nodes were examined by a consultant histopathologist. Results Between 1995 and 2014 a total of 120 patients with one positive lymph node who had undergone a radical two-field, two-stage oesophagectomy were identified. A median age of 65 (45–80) was observed. Seventy three ACs and 47 SCCs were noted. Twenty three middle oesophageal (19.2%), 54 lower oesophageal (45%) and 43 (35.8%) junctional tumours were resected. There was no difference between patterns of solitary lymphatic metastases between AC and SCC. The pattern and number of solitary lymph node metastasis is as follows: paracardial 34 (28.3%); paraoesophageal 31 (25.8%); left gastric 28 (23.3%); subcarinal/bronchial 10 (8.3%) and truncal/coeliac/splenic 9 (7.5%). Tumour location and corresponding single node metastasis are summarised in Table 1.Abstract PTH-141 Table 1 Location of tumour Single positive node location Frequency (n) Percent (%) Middle oesophageal N = 23 Abdomen 8 34.8 Chest 15 65.2 Lower oesophageal N = 54 Abdomen 36 66.7 Chest 18 33.3 Junctional N = 43 Abdomen 27 62.8 Chest 16 37.2 Median survival for patients with AD and SCC were similar at 45 months and 52 months respectively (p = 0.84). Conclusion This study provides further support to the concept that metastasis to anatomically distant lymph nodes (skip metastasis), could develop even in the early phase of lymphatic invasion in oesophageal carcinoma. This unpredictability necessitates a radical resection. This can only be achieved with an extended transthoracic operation to allow a complete two-field lymphadenectomy in order to provide locoregional clearance and a potentially curative resection. Disclosure of interest None Declared.

Pattern of single lymph node metastasis in carcinoma of the oesophagus

Introduction The presence of lymphatic dissemination in oesophageal cancer affects prognosis. The relevance of location of an involved solitary lymph node is unclear. The concept of sentinel node guided lymphadenectomy to reduce surgical stress of a transthoracic operation has some advocates. However, the site of solitary lymph node metastasis, is unpredictable. Similarly, metastases to anatomically distant lymph nodes, known as skip lesions, could develop in the early phase of lymphatic invasion. The aim of this study was to examine the pattern of a single named lymph node metastasis in patients with oesophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC) who underwent resection with curative intent. No study to date has investigated this concept. Method Results of consecutive patients from a prospectively maintained database were analysed. All patients with potentially curable AC or SCC who underwent a radical two-field, two-stage, transthoracic oesophagectomy were included. Ex-vivo surgical dissection of the specimen was carried out post-operatively by the surgeon, with harvested lymph node stations labelled. This permitted accurate ‘lymph node mapping’. All harvested lymph nodes were examined by a consultant histopathologist. Results Between 1995 and 2014 a total of 120 patients with one positive lymph node who had undergone a radical two-field, two-stage oesophagectomy were identified. A median age of 65 (45–80) was observed. Seventy three ACs and 47 SCCs were noted. Twenty three middle oesophageal (19.2%), 54 lower oesophageal (45%) and 43 (35.8%) junctional tumours were resected. There was no difference between patterns of solitary lymphatic metastases between AC and SCC. The pattern and number of solitary lymph node metastasis is as follows: paracardial 34 (28.3%); paraoesophageal 31 (25.8%); left gastric 28 (23.3%); subcarinal/bronchial 10 (8.3%) and truncal/coeliac/splenic 9 (7.5%). Tumour location and corresponding single node metastasis are summarised in Table 1.Abstract PTH-141 Table 1 Location of tumour Single positive node location Frequency (n) Percent (%) Middle oesophageal N = 23 Abdomen 8 34.8 Chest 15 65.2 Lower oesophageal N = 54 Abdomen 36 66.7 Chest 18 33.3 Junctional N = 43 Abdomen 27 62.8 Chest 16 37.2 Median survival for patients with AD and SCC were similar at 45 months and 52 months respectively (p = 0.84). Conclusion This study provides further support to the concept that metastasis to anatomically distant lymph nodes (skip metastasis), could develop even in the early phase of lymphatic invasion in oesophageal carcinoma. This unpredictability necessitates a radical resection. This can only be achieved with an extended transthoracic operation to allow a complete two-field lymphadenectomy in order to provide locoregional clearance and a potentially curative resection. Disclosure of interest None Declared.

PTH-141 Pattern of single lymph node metastasis in carcinoma of the oesophagus: Abstract PTH-141 Table 1

Introduction The presence of lymphatic dissemination in oesophageal cancer affects prognosis. The relevance of location of an involved solitary lymph node is unclear. The concept of sentinel node guided lymphadenectomy to reduce surgical stress of a transthoracic operation has some advocates. However, the site of solitary lymph node metastasis, is unpredictable. Similarly, metastases to anatomically distant lymph nodes, known as skip lesions, could develop in the early phase of lymphatic invasion. The aim of this study was to examine the pattern of a single named lymph node metastasis in patients with oesophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC) who underwent resection with curative intent. No study to date has investigated this concept. Method Results of consecutive patients from a prospectively maintained database were analysed. All patients with potentially curable AC or SCC who underwent a radical two-field, two-stage, transthoracic oesophagectomy were included. Ex-vivo surgical dissection of the specimen was carried out post-operatively by the surgeon, with harvested lymph node stations labelled. This permitted accurate ‘lymph node mapping’. All harvested lymph nodes were examined by a consultant histopathologist. Results Between 1995 and 2014 a total of 120 patients with one positive lymph node who had undergone a radical two-field, two-stage oesophagectomy were identified. A median age of 65 (45–80) was observed. Seventy three ACs and 47 SCCs were noted. Twenty three middle oesophageal (19.2%), 54 lower oesophageal (45%) and 43 (35.8%) junctional tumours were resected. There was no difference between patterns of solitary lymphatic metastases between AC and SCC. The pattern and number of solitary lymph node metastasis is as follows: paracardial 34 (28.3%); paraoesophageal 31 (25.8%); left gastric 28 (23.3%); subcarinal/bronchial 10 (8.3%) and truncal/coeliac/splenic 9 (7.5%). Tumour location and corresponding single node metastasis are summarised in Table 1.Abstract PTH-141 Table 1 Location of tumour Single positive node location Frequency (n) Percent (%) Middle oesophageal N = 23 Abdomen 8 34.8 Chest 15 65.2 Lower oesophageal N = 54 Abdomen 36 66.7 Chest 18 33.3 Junctional N = 43 Abdomen 27 62.8 Chest 16 37.2 Median survival for patients with AD and SCC were similar at 45 months and 52 months respectively (p = 0.84). Conclusion This study provides further support to the concept that metastasis to anatomically distant lymph nodes (skip metastasis), could develop even in the early phase of lymphatic invasion in oesophageal carcinoma. This unpredictability necessitates a radical resection. This can only be achieved with an extended transthoracic operation to allow a complete two-field lymphadenectomy in order to provide locoregional clearance and a potentially curative resection. Disclosure of interest None Declared.

PTH-158 The presence of perineural, blood and lymphvessel invasion after neoadjuvant therapy and oesophagectomy identifies high risk patients for recurrence

Introduction In patients with oesophageal cancer, little attention has been paid to the relevance of tumour invasion in blood (AI) and lymphatic vessels (LVI) as well as perineural invasion (PNI) after neoadjuvant therapy. Therefore, the aim of the present study was to assess the incidence and prognostic significance of these factors in a consecutive series of patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) who underwent neoadjuvant therapy followed by oesophagectomy. Method From a prospectively collected database, a consecutive series of patients was analysed. All patients with potentially curable adeno- or squamous cell carcinoma of the oesophagus or GOJ were treated with neoadjuvant chemotherapy or chemoradiation therapy followed by transthoracic oesophagectomy and two-field lymphadenectomy. The presence of AI, LVI and PNI was prospectively collected. Results Between January 2000 and September 2013, a consecutive series of 396 patients underwent a potentially curative oesophagectomy after neoadjuvant therapy for adeno- or squamous cell carcinoma. AI was seen in 150 (38%) of patients, LVI was seen in 203 (51%) of patients and PNI was seen in 204 (52%) of patients. 123 (31%) had no AI, LVI or PNI whatsoever. 96 (24%) had a combination of two out of three factors and 94 (24%) had presence of AI, LVI and PNI. The presence of AI, LVI and PNI was significantly (P = 0.001) related with ypT- and ypN-stage. Median overall survival was 170.8 months (95% CI: 68.9–272.8) if AI, LVI and PNI were all absent, 44.0 months (95% CI: 20.9–67.2) when one factor was present, 27.1 months (95% CI: 22.8–31.4) when two factors were present and 16.0 months (95% CI: 9.4–22.6) when AI, LVI and PNI were all present. On multivariate analyses the presence of AI, LVI and PNI or a combination of these factors were independent predictors. Conclusion These findings suggest the importance of the presence of AI, LVI and PNI after neoadjuvant therapy followed by oesophagectomy. The presence of AI, LVI and PNI should be incorporated in the standardised pathology report. It provides additional information for identyfying patients at high risk who may be candidates for adjuvant therapies. Disclosure of interest None Declared.