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.

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 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 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.

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.

Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

Quality assurance of surgery in the randomized ST03 trial of perioperative chemotherapy in carcinoma of the stomach and gastro-oesophageal junction.

BACKGROUND: The UK Medical Research Council ST03 trial compared perioperative epirubicin, cisplatin and capecitabine (ECX) chemotherapy with or without bevacizumab (B) in gastric and oesophagogastric junctional cancer. No difference in survival was noted between the arms of the trial. The present study reviewed the standards and performance of surgery in the context of the protocol-specified surgical criteria. METHODS: Surgical and pathological clinical report forms were reviewed to determine adherence to the surgical protocols, perioperative morbidity and mortality, and final histopathological stage for all patients treated in the study. RESULTS: Of 1063 patients randomized, 895 (84·2 per cent) underwent resection; surgical details were available for 880 (98·3 per cent). Postoperative assessment data were available for 873 patients; complications occurred in 458 (52·5 per cent) overall, of whom 71 (8·1 per cent) developed complications deemed to be life-threatening by the responsible clinician. The most common complications were respiratory (211 patients, 24·2 per cent). The anastomotic leak rate was 118 of 873 (13·5 per cent) overall; among those who underwent oesophagogastrectomy, the rate was higher in the group receiving ECX-B (23·6 per cent versus 9·9 per cent in the ECX group). Pathological assessment data were available for 845 patients. At least 15 nodes were removed in 82·5 per cent of resections and the median lymph node harvest was 24 (i.q.r. 17-34). Twenty-five or more nodes were removed in 49·0 per cent of patients. Histopathologically, the R1 rate was 24·9 per cent (208 of 834 patients). An R1 resection was more common for proximal tumours. CONCLUSION: In the ST03 trial, the performance of surgery met the protocol-stipulated criteria. Registration number: NCT00450203 ( http://www.clinicaltrials.gov).

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.

Influence of national centralization of oesophagogastric cancer on management and clinical outcome from emergency upper gastrointestinal conditions.

BACKGROUND: In England in 2001 oesophagogastric cancer surgery was centralized. The aim of this study was to evaluate whether centralization of oesophagogastric cancer to high-volume centres has had an effect on mortality from different emergency upper gastrointestinal conditions. METHODS: The Hospital Episode Statistics database was used to identify patients admitted to hospitals in England (1997-2012). The influence of oesophagogastric high-volume cancer centre status (20 or more resections per year) on 30- and 90-day mortality from oesophageal perforation, paraoesophageal hernia and perforated peptic ulcer was analysed. RESULTS: Over the study interval, 3707, 12 441 and 56 822 patients with oesophageal perforation, paraoesophageal hernia and perforated peptic ulcer respectively were included. There was a passive centralization to high-volume cancer centres for oesophageal perforation (26·9 per cent increase), paraoesophageal hernia (19·5 per cent increase) and perforated peptic ulcer (23·0 per cent increase). Management of oesophageal perforation in high-volume centres was associated with a reduction in 30-day (HR 0·58, 95 per cent c.i. 0·45 to 0·74) and 90-day (HR 0·62, 0·49 to 0·77) mortality. High-volume cancer centre status did not affect mortality from paraoesophageal hernia or perforated peptic ulcer. Annual emergency admission volume thresholds at which mortality improved were observed for oesophageal perforation (5 patients) and paraoesophageal hernia (11). Following centralization, the proportion of patients managed in high-volume cancer centres that reached this volume threshold was 88·0 per cent for oesophageal perforation, but only 30·3 per cent for paraoesophageal hernia. CONCLUSION: Centralization of low incidence conditions such as oesophageal perforation to high-volume cancer centres provides a greater level of expertise and ultimately reduces mortality.

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.

Systemic inflammatory markers and outcome in patients with locally advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction.

BACKGROUND: Raised levels of systemic inflammatory markers are associated with poor survival in patients with cancer. The aim of this study was to assess the prognostic value of markers of systemic inflammation in patients with adenocarcinoma of the oesophagus or gastro-oesophageal junction. METHODS: Data from a consecutive series of patients undergoing transthoracic oesophagectomy following neoadjuvant therapy at a single centre were analysed. Fibrinogen, albumin, C-reactive protein, leucocyte differential and platelet counts were measured before surgery. The upper quartile (75th percentile) was used as a cut-off for dichotomization. Multivariable regression analysis was performed to identify independent prognostic factors. RESULTS: A series of 199 patients underwent transthoracic oesophagectomy following neoadjuvant therapy. Univariable analysis indicated that reduced median survival was associated with a raised platelet : lymphocyte ratio (158 or above; 25.6 versus 44·4 months for patients with a normal ratio, P = 0·038) and increased fibrinogen levels (4·9 g/l or above; 22·8 versus 59·9 months for those with a normal level, P = 0·005). On multivariable analysis a combination of one or more markers of systemic inflammation was associated with poorer overall survival (hazard ratio 2·12, 95 per cent c.i. 1·20 to 3·74; P = 0·010). CONCLUSION: Preoperative markers of systemic inflammation predict poor outcome in patients undergoing curative treatment for locally advanced oesophageal and gastro-oesophageal adenocarcinoma.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

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.

Cure with ledipasvir/sofosbuvir for chronic hepatitis C virus in an individual with gastric bypass.

WHAT IS KNOWN AND OBJECTIVE: The impact of gastric bypass surgery on the pharmacokinetics of various medications has been reported. Presently, no data exist for the treatment of chronic hepatitis C virus with ledipasvir/sofosbuvir (LDV/SOF) in an individual with a history of gastric bypass. CASE DESCRIPTION: We report the successful cure of an individual who was treated with LDV/SOF who had a history of gastric bypass. The patient tolerated LDV/SOF well while only experiencing a minor headache. WHAT IS NEW AND CONCLUSION: Ledipasvir/sofosbuvir treatment may still be effective in those with a history of gastric bypass surgery.

Management and outcomes of anastomotic leaks after oesophagectomy.

BACKGROUND: Leaks following oesophagectomy include true anastomotic leaks, leaks from the gastrotomy and gastric conduit necrosis. Historically, these complications were associated with high mortality rates. Recent improvements in outcome have been attributed to the wider use of oesophageal stents in patient management. This study examined outcomes of patients who developed a leak in a single high-volume institution that did not use stenting as a primary treatment modality. METHODS: All patients undergoing an oesophagectomy between January 2009 and December 2013 were included. Patients were identified from a prospectively maintained database. RESULTS: A total of 390 oesophagectomies were performed (median age 65 (range 32-81) years). In 96·7 per cent of patients this was a two-stage subtotal oesophagectomy. Overall in-hospital and 90-day mortality rates were both 2·1 per cent (8 patients). Some 31 patients (7·9 per cent) developed a leak (median age 64·5 (range 52-80) years), of whom 27 (87 per cent) were initially managed without surgery, whereas four (13 per cent) required immediate thoracotomy. The median length of stay for patients with a leak was 41·5 (range 15-159) days; none of these patients died. CONCLUSION: Leaks can be managed with excellent outcomes without using oesophageal stents. The results do not support the widespread adoption of endoscopic stenting.

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.

What surgeons tell patients and what patients want to know before major cancer surgery: a qualitative study.

BACKGROUND: The information surgeons impart to patients and information patients want about surgery for cancer is important but rarely examined. This study explored information provided by surgeons and patient preferences for information in consultations in which surgery for oesophageal cancer surgery was discussed. METHODS: Pre-operation consultations in which oesophagectomy was discussed were studied in three United Kingdom hospitals and patients were subsequently interviewed. Consultations and interviews were audio-recorded, transcribed in full and anonymized. Interviews elicited views about the information provided by surgeons and patients' preferences for information. Thematic analysis of consultation-interview pairs was used to investigate similarities and differences in the information provided by surgeons and desired by patients. RESULTS: Fifty two audio-recordings from 31 patients and 7 surgeons were obtained (25 consultations and 27 patient interviews). Six consultations were not recorded because of equipment failure and four patients declined an interview. Surgeons all provided consistent, extensive information on technical operative details and in-hospital surgical risks. Consultations rarely included discussion of the longer-term outcomes of surgery. Whilst patients accepted that information about surgery and risks was necessary, they really wanted details about long-term issues including recovery, impact on quality of life and survival. CONCLUSIONS: This study demonstrated a need for surgeons to provide information of importance to patients concerning the longer term outcomes of surgery. It is proposed that "core information sets" are developed, based on surgeons' and patients' views, to use as a minimum in consultations to initiate discussion and meet information needs prior to cancer surgery.