Neoadjuvant chemoradiotherapy or chemotherapy alone for oesophageal cancer: population-based cohort study.

BACKGROUND: Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown whether one provides a survival advantage over the other, particularly with respect to histological subtype. This study aimed to compare prognosis after nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). METHODS: Data from the National Cancer Database (2006-2015) were used to identify patients with OAC and OSCC. Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases. RESULTS: The study included 11 167 patients with OAC (nCRT 9972, 89.3 per cent; nCT 1195, 10.7 per cent) and 2367 with OSCC (nCRT 2155, 91.0 per cent; nCT 212, 9.0 per cent). In the matched OAC cohort, nCRT provided higher rates of complete pathological response (35.1 versus 21.0 per cent; P < 0.001) and margin-negative resections (90.1 versus 85.9 per cent; P < 0.001). However, patients who had nCRT had similar survival to those who received nCT (hazard ratio (HR) 1.04, 95 per cent c.i. 0.95 to 1.14). Five-year survival rates for patients who had nCRT and nCT were 36 and 37 per cent respectively (P = 0.123). For OSCC, nCRT had higher rates of complete pathological response (50.9 versus 30.4 per cent; P < 0.001) and margin-negative resections (92.8 versus 82.4 per cent; P < 0.001). A statistically significant overall survival benefit was evident for nCRT (HR 0.78, 0.62 to 0.97). Five-year survival rates for patients who had nCRT and nCT were 45.0 and 38.0 per cent respectively (P = 0.026). CONCLUSION: Despite pathological benefits, including primary tumour response to nCRT, there was no prognostic benefit of nCRT compared with nCT for OAC suggesting that these two modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.

Comparison of multimodal analgesia with thoracic epidural after transthoracic oesophagectomy.

BACKGROUND: Thoracic epidural analgesia (TEA) has been regarded as the standard of care after oesophagectomy for pain control, but has several side-effects. Multimodal (intrathecal diamorphine, paravertebral and rectus sheath catheters) analgesia (MA) may facilitate postoperative mobilization by reducing hypotensive episodes and the need for vasopressors, but uncertainty exists about whether it provides comparable analgesia. This study aimed to determine whether MA provides comparable analgesia to TEA following transthoracic oesophagectomy. METHODS: Consecutive patients undergoing oesophagectomy for cancer between January 2015 and December 2018 were grouped according to postoperative analgesia regimen. Propensity score matching (PSM) was used to account for treatment selection bias. Pain scores at rest and on movement, graded from 0 to 10, were used. The incidence of hypotensive episodes and the requirement for vasopressors were evaluated. RESULTS: The study included 293 patients; 142 (48.5 per cent) received TEA and 151 (51.5 per cent) MA. After PSM, 100 patients remained in each group. Mean pain scores were significantly higher at rest in the MA group (day 1: 1.5 versus 0.8 in the TEA group, P = 0.017; day 2: 1.7 versus 0.9 respectively, P = 0.014; day 3: 1.2 versus 0.6, P = 0.047). Fewer patients receiving MA had a hypotensive episode (25 per cent versus 45 per cent in the TEA group; P = 0.003) and fewer required vasopressors (36 versus 53 per cent respectively; P = 0.016). There was no significant difference in the overall complication rate (71.0 versus 61.0 per cent; P = 0.136). CONCLUSION: MA is less effective than TEA at controlling pain, but this difference may not be clinically significant. However, fewer patients experienced hypotension or required vasopressor support with MA; this may be beneficial within an enhanced recovery programme.

Prehabilitation, improving postoperative outcomes.

Cardiopulmonary fitness impacts upon post-operative outcomes. Improved fitness may lead to a reduction in postoperative morbidity, mortality, reduced length of stay and improvements in patients quality of life. Prehabilitation can be defined as a group of interventions undertaken prior to a surgical procedure, with the aim of reducing peri-operative risk, improving post-operative recovery and outcomes. This is an evolving field which is generating significant scientific and clinical interest. There is growing evidence demonstrating the effectiveness of this approach. It has been proven that prehabilitation could lead to improvement in cardiopulmonary fitness and reduction of postoperative morbidity. Physical exercise composed of aerobic and strengthening exercise is a mainstay of prehabilitation. Multimodal interventions are preferred nowadays and therefore these programmes are commonly enhanced by nutritional and psychological support. Prehabilitation has its place in elective surgery and should be commenced immediately after diagnosis is made. It can be home-based or within hospitals under supervision. Prehabilitation programmes should be individualised, based on patients diagnosis, age, comorbidities, background physical activity and social circumstances in order to achieve the highest possible effectivity of the programmes. It remains unclear as to what the optimal programme looks like in terms of frequency, length and intensity of exercise. High-intensity interval training has been shown to be highly effective. There is a need to answer many questions and bring more substantial evidence of prehabilitation effectivity before this can become part of a routine clinical care. There are several ongoing large randomised clinical in prehabilitation that can help address this knowledge gap.

Significance of Neoadjuvant Downstaging in Carcinoma of Esophagus and Gastroesophageal Junction.

OBJECTIVE: To determine the impact of downstaging on outcomes in esophageal cancer, the prognostic value of clinical and pathological stage, and the difference in survival in patients with similar pathological stages with and without neoadjuvant treatment. BACKGROUND: There is little data evaluating adenocarcinoma and squamous cell carcinoma (SCC) and difference in outcomes for similar pathological stage with and without neoadjuvant treatment. PATIENTS AND METHODS: Consecutive patients with esophageal cancer from a single center were evaluated. Patients with esophageal adenocarcinoma or SCC treated with transthoracic esophagectomy and two-field lymphadenectomy were included. Comparison of outcomes with those primarily treated with surgery was made. The cTNM and ypTNM 8th edition was used. RESULTS: This study included 992 patients, of whom 417 received surgery alone and 575 received neoadjuvant therapy and surgery. In the neoadjuvant group, 7 (1%) had cTNM stage 2 and 418 (73%) had cTNM stage 3. Downstaging rates were similar between adenocarcinoma and SCC (54% vs. 61%, p = 0.5). Downstaging was associated with longer survival than patients with no change (adenocarcinoma, median: 82 vs. 26 months, p < 0.001; SCC, median: NR vs. 29 months, p < 0.001). On Cox regression analysis, downstaging was associated with significantly longer survival in adenocarcinoma but not in SCC. For SCC and more advanced adenocarcinoma, overall survival was significantly better when comparing like-for-like ypTN to pTN groups. CONCLUSIONS: Pathological stage provides a better estimate of prognosis compared with clinical stage. Downstaged patients may have an improved outcome over those with comparable pathological stage who did not receive neoadjuvant treatment.

Impact of Lymphadenectomy on Survival After Unimodality Transthoracic Esophagectomy for Adenocarcinoma of Esophagus.

BACKGROUND: Debate remains regarding the extent of lymphadenectomy required with esophagectomy. In patients who receive neoadjuvant treatment, this may address lymph node metastases. However, patients with early disease and those with comorbidities may not receive neoadjuvant treatment. The aim of this study is to determine the impact of lymph node yield and location on prognosis in patients undergoing esophagectomy without neoadjuvant treatment. PATIENTS AND METHODS: Data from consecutive patients with potentially curable adenocarcinoma of the esophagus or gastroesophageal junction were reviewed. Patients were treated with transthoracic esophagectomy and two-field lymphadenectomy. Outcomes according to lymph node yield were determined. The prognosis of carrying out less radical lymphadenectomy was calculated according to three groups: exclusion of proximal thoracic nodes (group 1), minimal abdominal lymphadenectomy (group 2), and minimal abdominal and thoracic lymphadenectomy (group 3). RESULTS: 357 patients were included. Median survival was 78 months [confidence interval (CI) 53-103 months]. Absolute lymph node retrieval was not related to survival (p = 0.920). An estimated additional 4 (2-6) cancer-related deaths was projected if group 1 nodes were omitted, 15 (11-19) additional deaths if group 2 nodes were omitted, and 4 (2-6) deaths if group 3 nodes were omitted. Minimal lymphadenectomy (groups 1, 2, and 3) was projected to lead to 19 (15-23) additional cancer-related deaths. CONCLUSIONS: Extensive lymphadenectomy allows accurate staging. In patients who do not receive neoadjuvant treatment, it may confer a survival benefit. The number of lymph nodes retrieved may not be a good surrogate for extent of lymphadenectomy, and correlation with location is required.

Anastomotic Leak Does Not Impact on Long-Term Outcomes in Esophageal Cancer Patients.

BACKGROUND: Esophagectomy is a technically demanding procedure associated with high levels of morbidity. Anastomotic leak (AL) is a common complication with potentially major ramifications for patients. It has also been associated with poorer long-term overall survival (OS) and disease recurrence. OBJECTIVE: The aim of this study was to determine whether AL contributes to poor OS and recurrence-free survival (RFS) for patients with esophageal cancer. METHODS: Consecutive patients undergoing a two-stage, two-field transthoracic esophagectomy from a single high-volume unit between 1997 and 2016 were evaluated. Clinicopathologic characteristics, along with oncological and postoperative outcomes, were stratified by no AL versus non-severe leak (NSL) versus severe esophageal AL (SEAL). SEAL was defined as ALs associated with Clavien-Dindo grade III/IV complications. RESULTS: This study included 1063 patients, of whom 8% (87/1063) developed AL; 45% of those who developed AL were SEALs (39/87). SEAL was associated with a prolonged critical care stay (median 8 vs. 3 vs. 2 days; p < 0.001) and prolonged hospital stay (median 43 vs. 27 vs. 15 days; p < 0.001) compared with NSL or no AL. There were no significant differences in number of lymph nodes harvested and rates of R1 resection between groups. OS and RFS were not affected by either NSL or SEAL, and Cox multivariate regression showed NSL and SEAL were not independently associated with OS and RFS. Sensitivity analysis in patients receiving neoadjuvant therapy followed by esophagectomy demonstrated similar findings. CONCLUSION: These results demonstrate that AL leads to prolonged critical care and in-hospital length of stay; however, contrary to previous reports, our results do not compromise long-term outcomes and are unlikely to have a detrimental oncological impact.

Impact of anastomotic leak on long-term survival in patients undergoing gastrectomy for gastric cancer.

BACKGROUND: The impact of anastomotic leak (AL) on long-term outcomes after gastrectomy for gastric adenocarcinoma is poorly understood. This study determined whether AL contributes to poor overall survival. METHODS: Consecutive patients undergoing gastrectomy in a single high-volume unit between 1997 and 2016 were evaluated. Clinicopathological characteristics, oncological and postoperative outcomes were stratified according to whether patients had no AL, non-severe AL or severe AL. Severe AL was defined as anastomotic leakage associated with Clavien-Dindo Grade III-IV complications. RESULTS: The study included 969 patients, of whom 58 (6·0 per cent) developed AL; 15 of the 58 patients developed severe leakage. Severe AL was associated with prolonged hospital stay (median 50, 30 and 13 days for patients with severe AL, non-severe AL and no AL respectively; P < 0·001) and critical care stay (median 11, 0 and 0 days; P < 0·001). There were no significant differences between groups in number of lymph nodes harvested (median 29, 30 and 28; P = 0·528) and R1 resection rates (7, 5 and 6·5 per cent; P = 0·891). Cox multivariable regression analysis showed that severe AL was independently associated with overall survival (hazard ratio 3·96, 95 per cent c.i. 2·11 to 7·44; P < 0·001) but not recurrence-free survival. In sensitivity analysis, the results for patients who had neoadjuvant therapy then gastrectomy were similar to those for the entire cohort. CONCLUSION: AL prolongs hospital stay and is associated with compromised long-term overall survival.

ANTECEDENTES: El impacto de la fuga anastomótica (anastomotic leak, AL) tras una gastrectomía por adenocarcinoma gástrico sobre los resultados a largo plazo es poco conocido. En este estudio se investigó si la AL contribuye a una peor supervivencia global (overall survival, OS). MÉTODOS: Se analizaron todos los pacientes consecutivos sometidos a una gastrectomía en un centro de alto volumen entre 1997 y 2016. Las características clinicopatológicas, los resultados postoperatorios y los resultados oncológicos se clasificaron en función de la AL: no AL versus NSL (Non-Severe Leak, fuga no grave) versus AL grave (severe AL, SAL). SAL se definió como fugas anastomóticas asociadas con complicaciones Clavien-Dindo grado III / IV. RESULTADOS: Se incluyeron 969 pacientes en el estudio, de los cuales el 6% (58/969) presentó una AL. De los que desarrollaron AL, el 26% desarrolló SAL (15/58). SAL se asoció con una estancia prolongada en el hospital (mediana: 50 versus 30 versus 13 días, P < 0,001) y en cuidados intensivos (mediana: 11 versus 0 versus 0 días, P < 0,001) en comparación con NSL o sin AL. No hubo diferencias significativas en los ganglios linfáticos identificados (mediana: 28 versus 30 versus 29 P = 0,5) ni en las tasas de resección R1 (mediana: 7% versus 5% versus 7%, P = 0,9) entre no AL, NSL y SAL, respectivamente. La regresión multivariable de Cox demostraba que SAL se asociaba independientemente con la OS (cociente de riesgos instantáneos, hazard ratio, HR 3,96, i.c. del 95% 2,11-7,44, P < 0,001) pero no la RFS. El análisis de sensibilidad en pacientes que recibieron tratamiento neoadyuvante y posteriormente gastrectomía fue similar a los que se sometieron únicamente a gastrectomía. CONCLUSIÓN: La AL prolonga la estancia hospitalaria y compromete la supervivencia global a largo plazo.

Delivering esophago-gastric cancer care during the COVID-19 pandemic in the United Kingdom: a surgical perspective.

BACKGROUND: The COVID-19 pandemic continues to have a significant impact on the provision of medical care. Planning to ensure there is capability to treat those that become ill with the virus has led to an almost complete moratorium on elective work. This study evaluates the impact of COVID-19 on cancer, in particular surgical intervention, in patients with esophago-gastric cancer at a high-volume tertiary center. METHODS: All patients undergoing potential management for esophago-gastric cancer from 12 March to 22 May 2020 had their outcomes reviewed. Multi-disciplinary team (MDT) decisions, volume of cases, and outcomes following resection were evaluated. RESULTS: Overall 191 patients were discussed by the MDT, with a 12% fall from the same period in 2019, including a fall in new referrals from 120 to 83 (P = 0.0322). The majority of patients (80%) had no deviation from the pre-COVID-19 pathway. Sixteen patients had reduced staging investigations, 4 had potential changes to their treatment only, and 10 had a deviation from both investigation and potential treatment. Only one patient had palliation rather than potentially curative treatment. Overall 19 patients underwent surgical resection. Eight patients (41%) developed complications with two (11%) graded Clavien-Dindo 3 or greater. Two patients developed COVID-19 within a month of surgery, one spending 4 weeks in critical care due to respiratory complications; both recovered. Twelve patients underwent endoscopic resections with no complications. CONCLUSION: Care must be taken not to compromise cancer treatment and outcomes during the COVID-19 pandemic. Excellent results can be achieved through meticulous logistical planning, good communication, and maintaining high-level clinical care.

Long-term outcomes of clinical and pathological-staged T3 N3 esophageal cancer.

Locally advanced esophageal cancer is associated with poor long-term survival. Pre- and post-treatment stages may differ because of neoadjuvant therapy and inaccuracies in staging. The aim of this study was to determine the outcomes of patients staged with clinical T3 N3 and pathological T3 N3 carcinoma of the esophagus and determine differences between the groups. Consecutive patients from a single unit between 2010 and 2018 were included with either clinical (cT3 N3) or pathological (pT3 N3) esophageal cancer. Outcomes were compared between patients that underwent esophagectomy with or without neoadjuvant treatment and those patients staged cT3 N3 treated non-surgically (NSR). Patients were staged using the TNM 8. This study included 156 patients, 63 patients were staged cT3 N3 initially and had NSR treatment, only three of these had radical treatment. Of the remaining 93 patients who underwent esophagectomy, 34 were initially staged as cT3 N3, 54 were found to be pT3 N3 having been staged earlier initially, and five were unchanged before and after treatment. Median overall survival (OS) for surgical cT3 N3 patients was significantly longer than pT3 N3 and NSR (median: NR vs 19 vs 8 months, P < 0.001). Twenty-seven patients with cT3 N3 had lower staging following treatment, while three had a higher stage. T3 N3 disease carries a poor prognosis. Within this cohort, cT3 N3 disease treated surgically has a high 5-year OS suggesting possible over-staging and stage migration due to neoadjuvant therapy. Those not having surgery, have a dismal prognosis. The impact of neoadjuvant treatment cannot be predicted and, current staging modalities may be inaccurate. Clinical stage should be used with caution when counseling patients regarding management and prognosis.

Impact of trainee involvement in esophagectomy on clinical outcomes: a narrative systematic review of the literature.

Changes in the structure of surgical training have affected trainees' operative experience. Performing an esophagectomy is being increasingly viewed as a complex technical skill attained after completion of the routine training pathway. This systematic review aimed to identify all studies analyzing the impact of trainee involvement in esophagectomy on clinical outcomes. A search of the major reference databases (Cochrane Library, MEDLINE, EMBASE) was performed with no time limits up to the date of the search (November 2017). Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality assessed using the MINORS (Methodological Index for Non-Randomized Studies) criteria. Four studies that included a total of 42 trainees and 16 consultants were identified, which assessed trainee involvement in open esophagogastric resectional surgery. A total of 1109 patients underwent upper gastrointestinal procedures, of whom 904 patients underwent an esophagectomy. Preoperative characteristics, histology, neoadjuvant treatment, and overall length of hospital stay were comparable between groups. One study found higher rates of anastomotic leaks in procedures primarily performed by trainees as compared to consultants (P < 0.01)-this did not affect overall morbidity or survival; however, overall anastomotic leak rates from the published data were 10.4% (trainee) versus 6.3% (trainer) (P = 0.10). A meta-analysis could not be performed due to the heterogeneity of data. The median MINORS score for the included studies was 13 (range 11-15). This study demonstrates that training can be achieved with excellent results in high-volume centers. This has important implications on the consent process and training delivered, as patients wish to be aware of the risks involved with surgery and can be reassured that appropriately supervised trainee involvement will not adversely affect outcomes.

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

BACKGROUND: 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. METHODS: CPET was completed before, immediately after (week 0), and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were compared before and after neoadjuvant chemotherapy, and at the three time intervals. RESULTS: Some 31 patients were recruited. The mean anaerobic threshold was lower following neoadjuvant treatment: 15·3 ml per kg per min before chemotherapy versus 11·8, 12·1 and 12·6 ml per kg per min at week 0, 2 and 4 respectively (P < 0·010). Measurements were also significantly different at each time point (P < 0·010). The same pattern was noted for Vo2 peak between values before chemotherapy (21·7 ml per kg per min) and at weeks 0, 2 and 4 (17·5, 18·6 and 19·3 ml per kg per min respectively) (P < 0·010). The reduction in anaerobic threshold and Vo2 peak did not improve during the time between completion of neoadjuvant chemotherapy and surgery. CONCLUSION: There was a decrease in cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was sustained up to the point of surgery at 4 weeks after chemotherapy.

Multimodal analgesia using intrathecal diamorphine, and paravertebral and rectus sheath catheters are as effective as thoracic epidural for analgesia post-open two-phase esophagectomy within an enhanced recovery program.

Thoracic epidural (TE) analgesia has been the standard of care for transthoracic esophagectomy patients since the 1990s. Multimodal anesthesia using intrathecal diamorphine, local anesthetic infusion catheters (LAC) into the paravertebral space and rectus sheaths and intravenous opioid postoperatively represent an alternative option for postoperative analgesia. While TE can provide excellent pain control, it may inhibit early postoperative recovery by causing hypotension and reducing mobilization. The aim of this study is to determine whether multimodal analgesia with LAC was effective with respect to adequate pain management, and compare its impact on hypotension and mobility. Patients receiving multimodal LAC analgesia were matched using propensity score matching to patients undergoing two-phase trans-thoracic esophagectomy with a TE over a two-year period (from January 2015 to December 2016). Postoperative endpoints that had been evaluated prospectively, including pain scores on movement and at rest, inotrope or vasoconstrictor requirements, and hypotension (systolic BP < 90 mmHg), were compared between cohorts. Out of 14 patients (13 male) that received LAC were matched to a cohort of 14 patients on age, sex, and comorbidity. Mean and maximum pain scores at rest and movement on postoperative days 0 to 3 were equivalent between the groups. In both cohorts, 50% of patients had a pain score of more than 7 on at least one occasion. Fewer patients in the LAC group required vasoconstrictor infusion (LAC: 36% vs. TE: 57%, P = 0.256) to maintain blood pressure or had episodes of hypotension (LAC: 43% vs. TE: 79%, P = 0.05). The LAC group was more able to ambulate on the first postoperative day (LAC: 64% vs. TE: 43%, P = 0.14) but these differences were not statistically significant. Within the epidural cohort, three patients had interruption of epidural due to dislodgement or failure of block compared to no disruption in the multimodal local anesthesia catheters group (P = 0.05). Therefore, multimodal anesthesia using spinal diamorphine with combined paravertebral and rectus sheath local anesthetic catheters appears to provide comparable pain relief post two-phase esophagectomy and may provide more reliable and safe analgesia than the current standard of care.

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.

Clinical outcomes and benefits for staging of surgical lymph node mapping after esophagectomy.

Dissection of lymph nodes (LN) immediately after esophagectomy is utilized by some surgeons to aid determination of LN stations involved in esophageal cancer. Some suggest that this increases LN yield and gives information regarding the pattern of lymphatic spread, others feel that this may compromise a circumferential resection margin (CRM) assessment. The aim of this study is to evaluate the effect of ex vivo dissection on the assessment of the CRM and the pattern of lymph node dissemination in patients with adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) undergoing radical surgery after neoadjuvant chemotherapy and their prognostic impact. Data from consecutive patients with potentially curable adenocarcinoma of the distal esophagus and GEJ who received neoadjuvant treatment followed by surgery were analyzed. Clinical and pathological findings were reviewed and LN burden and location correlated with clinical outcome. Pathology specimens were dissected into individual LN groups 'ex-vivo' by the surgeon. A total of 301 patients were included: 295 had a radical proximal and distal resection margin however in 62(20.6%) CRM could not be assessed. A median of 33(10-77) nodes were recovered. A 117(38.9%) patients were ypN0 while 184(61.1%) were LN positive (ypN1-N3). LN stations close to the tumor were most frequently involved. Twenty-seven (14.7%) patients had only thoracic stations involved, 48(26.1%) only abdominal stations and 109 (59.2%) had both. Median survival for yN0 patients was 171 months compared to 24 months for those LN positive (P< 0.001). Multivariate analyses identified ypT-category, ypN-category, male gender, and nonradical resection (proximal or distal) margin as significant prognostic factors. Surgical dissection of nodes after esophagectomy enables accurate LN assessment, but may compromise CRM assessment in up to 20% of cases. It also provides valuable information regarding the pattern of nodal spread.

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.