The impact of age on long-term survival following gastrectomy for gastric cancer.

INTRODUCTION: Gastrectomy remains the primary curative treatment modality for patients with gastric cancer. Concerns exist about offering surgery with a high associated morbidity and mortality to elderly patients. The study aimed to evaluate the long-term survival of patients with gastric cancer who underwent gastrectomy comparing patients aged <70 years with patients aged ≥70 years. METHODS: Consecutive patients who underwent gastrectomy for adenocarcinoma with curative intent between January 2000 and December 2017 at a single centre were included. Patients were stratified by age with a cut-off of 70 years used to create two cohorts. Log rank test was used to compare overall survival and Cox multivariable regression used to identify predictors of long-term survival. RESULTS: During the study period, 959 patients underwent gastrectomy, 520 of whom (54%) were aged ≥70 years. Those aged <70 years had significantly lower American Society of Anesthesiologists grades (p<0.001) and were more likely to receive neoadjuvant chemotherapy (39% vs 21%; p<0.001). Overall complication rate (p=0.001) and 30-day postoperative mortality (p=0.007) were lower in those aged <70 years. Long-term survival (median 54 vs 73 months; p<0.001) was also favourable in the younger cohort. Following adjustment for confounding variables, age ≥70 years remained a predictor of poorer long-term survival following gastrectomy (hazard ratio 1.35, 95% confidence interval 1.09, 1.67; p=0.006). CONCLUSIONS: Low postoperative mortality and good long-term survival were demonstrated for both age groups following gastrectomy. Age ≥70 years was, however, associated with poorer outcomes. This should be regarded as important factor when counselling patients regarding treatment options.

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.

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.

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.

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.

Trainee performance in radical gastrectomy and its effect on outcomes.

BACKGROUND: This study aimed to determine whether trainee involvement in D2 gastrectomies was associated with adverse outcomes. METHODS: Data from a prospectively created database of consecutive patients undergoing open D2 total (TG) or subtotal (STG) gastrectomy with curative intent between January 2009 and January 2014 were reviewed. Short- and long-term clinical outcomes were compared in patients operated on by consultants and those treated by trainees under consultant supervision. RESULTS: A total of 272 D2 open gastrectomies were performed, 123 (45·2 per cent) by trainees. There was no significant difference between consultants and trainees in median duration of surgery (TG: 240 (range 102-505) versus 240 (170-375) min respectively, P = 0·452; STG: 225 (150-580) versus 212 (125-380) min, P = 0·192), number of resected nodes (TG: 30 (13-101) versus 30 (11-102), P = 0·681; STG: 26 (5-103) versus 25 (1-63), P = 0·171), length of hospital stay (TG: 15 (7-78) versus 15 (8-65) days, P = 0·981; STG: 10 (6-197) versus 14 (7-85) days, P = 0·242), overall morbidity (TG: 44 versus 49 per cent, P = 0·314; STG: 34 versus 25 per cent, P = 0·113) or mortality (TG: 4 versus 2 per cent; P = 0·293). No difference in predicted 5-year overall survival was noted between the two cohorts (TG: 68 per cent for consultants versus 77 per cent for trainees, P = 0·254; STG: 70 versus 75 per cent respectively, P = 0·512). The trainee cohort had lower median blood loss for both TG (360 (range 90-1200) ml versus 600 (70-2350) ml for consultants; P = 0·042) and STG (235 (50-1000) versus 360 (50-3000) ml respectively; P = 0·053). CONCLUSION: Clinical outcomes were not compromised by supervised trainee involvement in D2 open gastrectomy.

ANTECEDENTES: El hecho de que en operaciones complejas la experiencia quirúrgica sea limitada puede influir en los resultados. Esto puede ser especialmente relevante cuando estas operaciones son realizadas por cirujanos en formación bajo supervisión. El objetivo de este estudio fue determinar si la participación del cirujano en formación en las gastrectomías D2 se asociaba con resultados adversos. MÉTODOS: Se revisó la información recogida en una base de datos prospectiva de pacientes consecutivos sometidos a gastrectomía D2 abierta total (total gastrectomy, TG) o subtotal (subtotal gastrectomy, STG) con intención curativa desde enero de 2009 a enero de 2014. Los pacientes se dividieron en dos grupos, uno de pacientes operados por un cirujano consultor y otro, de pacientes operados por un cirujano en periodo formación bajo la supervisión de un cirujano consultor. Se compararon los resultados clínicos a corto y largo plazo incluyendo la supervivencia global esperada a los cinco años. RESULTADOS: Se realizaron un total de 272 gastrectomías D2 abiertas (45% por cirujanos en periodo de formación). Las características demográficas de los pacientes fueron similares en los grupos de los cirujanos en formación y cirujanos consultores. En la TG y STG, no se apreciaron diferencias significativas entre ambas cohortes en el tiempo operatorio (P = 0,45)y (P = 0,19), número de ganglios linfáticos extirpados (P = 0,68) y (P = 0,17), duración de la estancia hospitalaria (P = 0,98) y (P = 0,24), morbilidad global (P = 0,31) y (P = 0,11), mortalidad (P = 0,29) y supervivencia global esperada a los 5 años (P = 0,25) y (P = 0,51). La pérdida sanguínea en ambas TG y STG fue menor en la cohorte de cirujanos en formación (P < 0,05). CONCLUSIÓN: La práctica de una gastrectomía D2 abierta por cirujanos en periodo de formación supervisados por consultores no comprometían los resultados clínicos.

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.

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 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.

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.

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.

Prognostic impact of extracapsular lymph node involvement after neoadjuvant therapy and oesophagectomy.

BACKGROUND: The significance of extracapsular lymph node involvement (LNI) is unclear in patients with oesophageal cancer who have undergone neoadjuvant treatment followed by oesophagectomy. The aim of this study was to assess the incidence and prognostic significance of extracapsular LNI in a large multicentre series of consecutive patients with oesophageal cancer treated by neoadjuvant chemotherapy or chemoradiotherapy and surgery. METHODS: Data from a consecutive series of patients treated at two European centres were analysed. All patients with squamous cell carcinoma or adenocarcinoma of the oesophagus or gastro-oesophageal junction, who received neoadjuvant chemotherapy or chemoradiation followed by transthoracic oesophagectomy and two-field lymphadenectomy with curative intent, were included. RESULTS: Between January 2000 and September 2013, 704 patients underwent oesophagectomy after neoadjuvant therapy. A median of 28 (range 5-77) nodes per patient was recovered. Some 347 patients (49·3 per cent) had no LNI (ypN0). Of the remaining 357 patients (50·7 per cent) with LNI (ypN1-3), extracapsular LNI was found in 190 (53·2 per cent). Five-year overall survival rates were 62·7 per cent for patients with N0 disease, 44·9 per cent for patients without extracapsular spread and 14·0 per cent where extracapsular LNI was identified (P < 0·001). Multivariable analyses demonstrated the presence of extracapsular LNI as an independent prognostic factor. CONCLUSION: The presence of extracapsular LNI after neoadjuvant therapy carries a poor prognosis.

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 Student's 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.

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.

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model.

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% C (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNa diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absorption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Mineral distribution in rat skeletons after exposure to a microgravity model.

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days show non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These findings are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.