Clinical Relevance of the Tumor Location-Modified Laurén Classification System for Gastric Cancer in a Western Population.

BACKGROUND: The Tumor Location-Modified Laurén Classification (MLC) system combines Laurén histologic subtype and anatomic tumor location. It divides gastric tumors into proximal non-diffuse (PND), distal non-diffuse (DND), and diffuse (D) types. The optimum classification of patients with Laurén mixed tumors in this system is not clear due to its grouping with both diffuse and non-diffuse types in previous studies. The clinical relevance of the MLC in a Western population has not been examined. METHODS: A cohort study investigated 404 patients who underwent gastrectomy for gastric adenocarcinoma between 2005 and 2020. The classification of Laurén mixed tumors was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of clinicopathologic characteristics (chi-square). Survival analysis was performed using multivariable Cox regression. RESULTS: The ROC curve analysis demonstrated a slightly higher area under the curve value for predicting survival when Laurén mixed tumors were grouped with intestinal-type rather than diffuse-type tumors (0.58 vs 0.57). Survival, tumor recurrence, and resection margin positivity in mixed tumors also was more similar to intestinal type. Distal non-diffuse tumors had the best 5-year survival (DND 64.7 % vs PND 56.1 % vs diffuse 45.1 %; p = 0.006) and were least likely to have recurrence (DND 27.0 % vs PND 34.3 % vs diffuse 48.3 %; p = 0.001). Multivariable analysis demonstrated that MLC was an independent prognostic factor for survival (PND: hazard ratio [HR], 1.64; 95 % confidence interval [CI], 1.16-2.32 vs diffuse: HR, 2.20; 95 % CI, 1.56-3.09) CONCLUSIONS: The MLC was an independent prognostic marker in this Western cohort of patients with gastric adenocarcinoma. The patients with PND and D tumors had worse survival than those with DND tumors.

Variation in histopathological assessment and association with surgical quality indicators following oesophagectomy.

BACKGROUND: Histopathological outcomes, such as lymph node yield and margin positivity, are used to benchmark and assess surgical centre quality, and are reported annually by the National Oesophago-Gastric Cancer Audit (NOGCA) in England and Wales. The variation in pathological specimen assessment and how this affects these outcomes is not known. METHODS: A survey of practice was circulated to all tertiary oesophagogastric cancer centres across England and Wales. Questions captured demographic data, and information on how specimens were prepared and analysed. National performance data were retrieved from the NOGCA. Survey results were compared for tertiles of lymph node yield, and circumferential and longitudinal margins. RESULTS: Survey responses were received from 32 of 37 units (86 per cent response rate), accounting for 93.1 per cent of the total oesophagectomy volume in England and Wales. Only 5 of 32 units met or exceeded current guidelines on specimen preparation according to the Royal College of Pathologists guidelines. There was wide variation in how centres defined positive (R1) margins, and how margins and lymph nodes were assessed. Centres with the highest nodal yield were more likely to use systematic fat blocking, and to re-examine specimens when the initial load was low. Systematic blocking of lesser curve fat resulted in significantly higher rates of patients with at least 15 lymph nodes examined (91.4 versus 86.5 per cent; P = 0.027). CONCLUSION: Preparation and histopathological assessment of specimens varies significantly across institutions. This challenges the validity of currently used surgical quality metrics for oesophageal and other tumours.

Minimally invasive left-sided esophagectomy (MILO): a novel approach for locally advanced tumors of the gastroesophageal junction.

Recent national audit has shown that levels of minimally invasive esophagectomy for cancer have increased to around 45% in the UK. The hybrid approach is the most common, with a laparoscopic abdominal phase and an open thoracic dissection. A number of centers have now adopted a two-phase Ivor-Lewis minimally invasive esophagectomy using a laparoscopic abdominal phase, followed by a thoracoscopic chest phase with a mini-thoracotomy to extract the specimen. The two-phase nature of the procedure lengthens the operative time and makes returning to the abdominal cavity difficult. The thoracotomy incision can also be painful and may reduce respiratory function post operatively. This report describes a novel single-phase minimally invasive left-sided technique with a mini-laparotomy for specimen extraction. This method offers excellent hiatal exposure, avoids a thoracotomy, and shortens the procedure time. Minimally invasive left-sided esophagectomy is a new useful approach for tumors located at the gastroesophageal junction.

Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin.

BACKGROUND: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. METHODS: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. RESULTS: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4-5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. CONCLUSION: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

ANTECEDENTES: El papel del tratamiento adyuvante en pacientes con adenocarcinoma esofagogástrico tratados con quimioterapia neoadyuvante es polémico. En la práctica del Reino Unido, el estado del margen de resección quirúrgico se utiliza a menudo para identificar a los pacientes que reciben tratamiento adyuvante. El objetivo de este estudio fue evaluar el beneficio en la supervivencia del tratamiento adyuvante en pacientes con márgenes de resección positivos (R1). MÉTODOS: Se combinaron dos bases de datos de instituciones del Reino Unido que recogen información de forma prospectiva para identificar pacientes elegibles. Se utilizaron análisis de regresión de Cox ajustados para comparar la supervivencia global y la supervivencia libre de recidiva según el tratamiento adyuvante. Los patrones de recidiva se evaluaron como resultado secundario. También se realizó un análisis de emparejamiento por puntaje de propensión. RESULTADOS: De 616 pacientes incluidos en la base de datos combinada, se incluyeron en el estudio 242 pacientes con resección R1. De estos pacientes, 112 (46%) recibieron quimiorradioterapia adyuvante, 46 (19%) pacientes fueron tratados con quimioterapia adyuvante y 84 (35%) pacientes no recibieron ningún tratamiento. En el análisis ajustado, la quimiorradioterapia adyuvante mejoró la supervivencia libre de recidiva (cociente de riesgos instantáneos, hazard ratio, HR 0,59, i.c. del 95% 0,38-0,94; P = 0,026) con un beneficio tanto para la recidiva local (HR 0,48, i.c. del 95% 0,24-0,99; P = 0,047) como para la sistémica (HR 0,56, i.c. del 95% 0,33-0,94; P = 0,027). Cuando los pacientes se clasificaron según la respuesta tumoral a la quimioterapia neoadyuvante, los no respondedores (Mandard Grado 4/5) tratados con quimiorradioterapia adyuvante obtuvieron un beneficio en la supervivencia (HR 0,61, i.c. del 95% 0,38-0,97; P = 0,037). En el análisis por emparejamiento por puntaje de propensión, se observó un beneficio en la supervivencia global (HR 0,62, i.c. del 95% 0,39-0,98; P = 0,042) y en la supervivencia libre de recidiva (HR 0,51.i.c. del 95% 0,30-0,87; P = 0,004) con la quimiorradioterapia adyuvante frente a no recibir tratamiento adyuvante. CONCLUSIÓN: El tratamiento adyuvante puede mejorar la supervivencia global y la supervivencia libre de recidiva en pacientes con margen de resección positivo. Este patrón parece más pronunciado con la quimiorradioterapia adyuvante en pacientes que no responden a la quimioterapia.

Clinical significance of pulmonary nodules in decision-making and management of patients diagnosed with esophageal cancer.

In esophageal cancer, metastatic spread to the lungs is detected in 4-9.7% of cases. During staging investigations, 22% of patients have pulmonary nodules detected on cross-sectional imaging. The purpose of this study is to elucidate the clinical importance of these incidentally found pulmonary nodules, in patients with clinically localized esophageal cancer. A retrospective cohort study was conducted from January 2008 to December 2012 in a tertiary esophagogastric referral center. One-hundred and forty-nine patients were included in the study. All patients underwent dedicated staging followed by neoadjuvant chemotherapy and surgery as indicated. Thirty-three (22.1%) patients had pulmonary nodules found in their preoperative staging. Only three (9%) patients proved to develop metastatic pulmonary disease on follow-up. Interestingly, in all three patients, the nodules were negative on initial 18-fluorodeoxyglucose positron emission tomography. Incidentally found pulmonary nodules in newly diagnosed patients with esophageal cancer during staging investigations are rarely metastases. Such nodules, in isolation, should not preclude patients from radical treatment.

Laparoscopic-assisted left thoracoabdominal esophagectomy (LLTA): an innovative approach for locally advanced tumors of the gastroesophageal junction.

PURPOSE: To report a novel approach for locally advanced tumors located at the gastroesophageal junction (GEJ) using a laparoscopic abdominal phase and open left thoracotomy with the patient in a single right lateral decubitus position. BACKGROUND: The standard open left thoracoabdominal approach offers excellent exposure and access to the GEJ and lower esophagus. It also involves a single position for the procedure, shortening the operation time. The disadvantages are a large incision, division of the costochondral junction, and a low-level thoracotomy. The laparoscopic-assisted left thoracoabdominal esophagectomy (LLTA) is performed with the patient in the same right lateral decubitus position, but initially rolled away from the operator at 45° allowing laparoscopic gastric mobilization and lymphadenectomy. The patient is then tilted back to the lateral position for the thoracic phase. An anterolateral left thoracotomy is performed through the higher fifth intercostal space allowing a high intrathoracic anastomosis, just below the aortic arch. No disruption of the costochondral junction is made. METHODS: Consecutive patients selectively treated for locally advanced GEJ tumors with an LLTA approach between 2013 and 2019 were analyzed and compared to national standards (NOGCA). RESULTS: This series of 74 consecutive patients had a mean age of 63 years. The median operation time was 235 minutes. The median inpatient stay was 10 days (NOGCA 9 [11-17]). The tumors were predominantly adenocarcinoma (95%) and located at the GEJ (92%). The majority were locally advanced T3 or T4 tumors. Postoperative morbidity was low, Clavien-Dindo (C-D) 0 in 52.7% patients, C-D1 (1.4%), C-D2 (31.1%), C-D3a (5.4%), C-D4a (9.5%), and C-D5 (1.4%). The median number of total lymph nodes (LN) excised was 28 (NOGCA >15); LN % yield ≥18 was 90% (NOGCA 82.5%). Positive nodes were located at the lesser-curve (40%), paraesophageal (32.4%), and subcarinal regions (2.7%). Positive circumferential resection margins (<1 mm) were present in 28.4% of resected specimens (NOGCA 25.1%). This is reflective of the high proportion T3/T4 tumors selected for this approach. Hospital and 30-day mortality was 1.4% (NOGCA 2.7%). Recurrence after LLTA was 25.7% (local 5.4%, systemic 17.6%, mixed 2.7%) at a median of 311 days (62-1,158). CONCLUSION: This series demonstrates a novel, safe, and reproducible approach for locally advanced cancer of the GEJ. It offers a better exposure of the hiatus than the right-sided approach and avoids division of the costochondral junction and low thoracotomy seen with the open left thoracoabdominal approach.

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.

Background: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.

Health-related quality of life after open transhiatal and transthoracic oesophagectomy for cancer.

BACKGROUND: Transhiatal and transthoracic oesophagectomy in patients with oesophageal cancer have similar survival rates. Whether these approaches differ in health-related quality of life (HRQoL) is uncertain and was examined in this study. METHODS: Patients undergoing transhiatal or transthoracic surgery for lower-third oesophageal or gastro-oesophageal junctional cancer between 2011 and 2015 were selected from an institutional database. HRQoL outcomes were measured at 6 and 12 months after surgery using validated written questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Linear mixed models provided mean score differences (MSDs) with 95 per cent confidence intervals, adjusted for preoperative HRQoL, age, physical status (ASA fitness grade), tumour location, tumour stage, neoadjuvant therapy, adjuvant therapy and postoperative complications. MSD values of 10 or more were regarded as clinically relevant. RESULTS: Some 146 patients underwent transhiatal (86, 58·9 per cent) or transthoracic (60, 41·1 per cent) oesophagectomy. The HRQoL questionnaires were returned by 111 patients at 6 months and 74 at 12 months. At 6 months, transthoracic oesophagectomy was associated with worse role function (MSD -12, 95 per cent c.i. -23 to 0; P = 0·046). At 12 months, patients in the transthoracic group had more nausea and vomiting (MSD 11, 0 to 22; P = 0·045), dyspnoea (MSD 13, 1 to 25; P = 0·029) and constipation (MSD 20, 7 to 33; P = 0·003) than those in the transhiatal group. CONCLUSION: Transhiatal oesophagectomy seems to offer better HRQoL than transthoracic oesophagectomy 6 and 12 months after surgery.

Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma.

BACKGROUND: The aim was to define the pathological response in lymph nodes following neoadjuvant chemotherapy for oesophageal adenocarcinoma and to quantify any associated survival benefit. METHODS: Lymph nodes retrieved at oesophagectomy were examined retrospectively by two pathologists for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive (allocated a lymph node regression score based on the proportion of fibrosis to residual tumour). Lymph node responders (score 1, complete response; 2, less than 10 per cent remaining tumour; 3, 10-50 per cent remaining tumour) and non-responders (score 4, more than 50 per cent viable tumour; 5, no response) were compared in survival analyses using Kaplan-Meier and Cox regression analysis. RESULTS: Among 377 patients, 256 had neoadjuvant chemotherapy. Overall, 68 of 256 patients (26·6 per cent) had a lymph node response and 115 (44·9 per cent) did not. The remaining 73 patients (28·5 per cent) had negative lymph nodes with no evidence of regression. Some patients had a lymph node response in the absence of a response in the primary tumour (27 of 99, 27 per cent). Lymph node responders had a significant survival benefit (P < 0·001), even when stratified by patients with or without a response in the primary tumour. On multivariable analysis, lymph node responders had decreased overall (hazard ratio 0·53, 95 per cent c.i. 0·36 to 0·78) and disease-specific (HR 0·42, 0·27 to 0·66) mortality, and experienced reduced local and systemic recurrence. CONCLUSION: Lymph node regression is a strong prognostic factor and may be more important than response in the primary tumour.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

A national audit of colonic interposition for esophageal replacement.

Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.

Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer.

BACKGROUND: The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic (TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO. METHODS: This was a cohort study based on two prospectively created databases. Short- and long-term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion. RESULTS: Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In-hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in-hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage. CONCLUSION: There was no difference in survival or tumour recurrence for TTO and THO.

Opinion, uptake and current practice of robot-assisted upper gastrointestinal and oesophagogastric surgery in the UK: AUGIS national survey results.

INTRODUCTION: The uptake of upper gastrointestinal (GI) robotic surgery in the United Kingdom (UK), and Europe more widely, is expanding rapidly. This study aims to present a current snapshot of the practice and opinions of the upper GI community with reference to robotic surgery, with an emphasis on tertiary cancer (oesophagogastric) resection centres. METHODS: An electronic survey was circulated to the UK upper GI surgical community via national mailing lists, social media and at an open-invitation conference on robotic upper GI surgery in January 2023. The survey included questions on surgeons' current practice or planned adoption (if any) of robotics at individual and unit level, and their opinions on robotic upper GI surgery in general. Priority ranking and Likert-scale response options were used. RESULTS: In total, 81 respondents from 43 hospitals were included. Thirty-four resectional centres responded, including 30 of 31 (97%) recognised upper GI cancer centres in England. Respondents reported performing robotic surgery in 21 of 34 (61.8%) resectional centres, with a median of 65 procedures per centre performed at the time of the survey (range 0-500, interquartile range 93.75). Every centre without a robotic programme expressed a desire or had active plans to implement one. Respondents ranked surgeon ergonomics as the most important reason for pursuing robotics, followed by improvements in patient outcomes and oncological efficacy. CONCLUSIONS: Robotic upper GI practice is nascent but rapidly growing in the UK with plans for uptake in almost all tertiary centres. There is growing opinion that this is likely to become the predominant surgical approach in future with benefits to both patients and surgeons. This snapshot offers a point of reference to all stakeholders in upper GI surgery.

Association of Upper GI Surgery of Great Britain and Ireland (AUGIS) Delphi consensus recommendations on the adoption of robotic upper GI surgery.

BACKGROUND: The adoption of robotic platforms in upper gastrointestinal (GI) surgery is expanding rapidly. The absence of centralised guidance and governance in adoption of new surgical technologies may lead to an increased risk of patient harm. METHODS: Surgeon stakeholders participated in a Delphi consensus process following a national open-invitation in-person meeting on the adoption of robotic upper GI surgery. Consensus agreement was deemed met if >80% agreement was achieved. RESULTS: Following two rounds of Delphi voting, 25 statements were agreed on covering the training process, governance and good practice for surgeons' adoption in upper GI surgery. One statement failed to achieve consensus. CONCLUSIONS: These recommendations are intended to support surgeons, patients and health systems in the adoption of robotics in upper GI surgery.

Outcomes from chemoradiotherapy for patients with esophageal cancer.

Chemoradiotherapy is a widely used alternative treatment to surgical resection in certain patient groups with early esophageal cancer. The aim of this study was to retrospectively assess toxicity and outcome of patients treated with definitive chemoradiotherapy for early esophageal cancer at one institution. A retrospective analysis of all patients treated with chemoradiotherapy between February 2000 and December 2008 at a single tertiary center was performed with documentation of treatment given, toxicities recorded, and follow-up and outcome data. Sixty-two patients received chemoradiotherapy for esophageal cancer. There were 20 males and 42 female patients with an average age of 68 years. Histology revealed adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All patients were staged with a computerized tomography scan, endoscopic ultrasound and positron emission tomography scan. Selection criteria for chemoradiotherapy were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary tumor, or patient choice. The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 55 Gy in 25 fractions of radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven patients suffered from local recurrence and a stent was required in nine patients. Radiation strictures occurred in 10 patients requiring dilation in four. Five patients required a radiologically inserted feeding gastrostomy. The median overall survival was 21 months. Patients with adenocarcinomas and those with squamous cell carcinoma had a similar median survival. Overall survival was 70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients treated with chemoradiation for localized esophageal cancer suggest a generally well-tolerated treatment with survival rates after chemoradiotherapy comparable with those seen with surgery.

Prevalence and outcome of litigation claims in England after laparoscopic cholecystectomy.

BACKGROUND: Approximately, 50,000 cholecystectomies are performed annually in the United Kingdom resulting in a number of negligence claims referred to the NHS Litigation Authority (NHSLA). The aim of this study was to assess the prevalence and outcomes of claims reported to the NHSLA after laparoscopic cholecystectomy performed in England between 1995 and 2008. METHODS: Data were requested from the NHSLA on all claims related to laparoscopic cholecystectomy which occurred in England between 1995 and 2008. RESULTS: A review of the data provided by the NHSLA data identified over 300 claims in this time period. Of the claims identified, 244 have been completed. Common bile duct injury (41%), bile leak (12%), bowel injury (9%), haemorrhage (9%) and fatality (9%) were the most frequent types of claim. Common bile duct injury resulted in the highest proportion of successful claims (86%) and the largest sums paid to the claimant (average £65,000). DISCUSSION: Common bile duct injury is the most common claim to the NHSLA after laparoscopic cholecystectomy and results in the highest proportion of successful claims and the largest sums paid to the claimant.

Adenovirus-mediated VEGF gene therapy enhances venous thrombus recanalization and resolution.

OBJECTIVE: Rapid thrombus recanalization reduces the incidence of post-thrombotic complications. This study aimed to discover whether adenovirus-mediated transfection of the vascular endothelial growth factor gene (ad.VEGF) enhanced thrombus recanalization and resolution. METHODS AND RESULTS: In rats, thrombi were directly injected with either ad.VEGF (n=40) or ad.GFP (n=37). Thrombi in SCID mice (n=12) were injected with human macrophages transfected with ad.VEGF or ad.GFP. Thrombi were analyzed at 1 to 14 days. GFP was found mainly in the vein wall and adventitia by 3 days, but was predominantly found in cells within the body of thrombus by day 7. VEGF levels peaked at 4 days (376+/-299 pg/mg protein). Ad.VEGF treatment reduced thrombus size by >50% (47.7+/-5.1 mm(2) to 22.0+/-4.0 mm(2), P=0.0003) and increased recanalization by >3-fold (3.9+/-0.69% to 13.6+/-4.1%, P=0.024) compared with controls. Ad.VEGF treatment increased macrophage recruitment into the thrombus by more than 50% (P=0.002). Ad.VEGF-transfected macrophages reduced thrombus size by 30% compared with controls (12.3+/-0.89 mm(2) to 8.7+/-1.4 mm(2), P=0.04) and enhanced vein lumen recanalization (3.39+/-0.34% to 5.07+/-0.57%, P=0.02). CONCLUSIONS: Treatment with ad.VEGF enhanced thrombus recanalization and resolution, probably as a consequence of an increase in macrophage recruitment.

The effect of economic deprivation on oesophageal and gastric cancer in a UK cancer network.

AIMS: The National Health Service (NHS) Cancer Plan aims to eliminate economic inequalities in healthcare provision and cancer outcomes. This study examined the influence of economic status upon the incidence, access to treatment and survival from oesophageal and gastric cancer in a single UK cancer network. METHODOLOGY: A total of 3619 patients diagnosed with either oesophageal or gastric cancer in a London Cancer Network (population = 1.48 million) were identified from the Thames Cancer Registry (1993-2002). Patients were ranked into economic quintiles using the income domain of the Multiple Index of Deprivation. Statistical analysis was performed using a chi(2) test. Survival analysis was performed using a Cox's proportional hazards model. RESULTS: Between 1993-1995 and 2000-2002, the incidence of oesophageal cancer in the most affluent males rose by 51% compared with a 2% rise in the least affluent males. The incidence of gastric cancer in most affluent males between 1993-1995 and 2000-2002 fell by 32% compared with a 7% fall in the least affluent males. These changes were less marked in females. Economic deprivation had no effect on the proportion of patients undergoing either resectional surgery or chemotherapy; the least affluent oesophageal cancer patients with a higher incidence of squamous cell carcinoma received significantly more radiotherapy. Economic deprivation had no effect upon survival for either oesophageal or gastric cancer. CONCLUSIONS: There has been an increase in oesophageal cancer and a decrease in gastric cancer incidence among more affluent males in the last 10 years. Economic status did not appear to influence access to treatment or survival.

Prediction of a positive circumferential resection margin at surgery following neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Background: A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods: Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results: A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion: The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Antecedentes: Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínico­patológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía. Métodos: Se realizó un análisis multivariable de las características clínico­patológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap. Resultados: Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,39­6,01) y un estadio clínico T avanzado (T3­4) (OR 2,93, i.c. del 95% 1,03­9,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,43­8,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,68­0,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09). Conclusión: La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.

The reporting of needlestick injuries sustained in theatre by surgeons: are we under-reporting?

Surgeons frequently sustain needlestick injuries when operating. The aim of this study was to evaluate the incidence and reporting rate of needlestick injuries at one institution. A questionnaire was distributed anonymously to 69 surgeons of all grades and specialties in a district general hospital in the UK. The questionnaire was returned by 42 surgeons (60.9%). There were 840 needlestick injuries over two years, of which 126 caused bleeding. Senior surgeons who spent more hours operating per week had a higher rate of needlestick injuries compared with junior surgeons (29.1 vs 6.59 injuries per surgeon over two years). Of the total number of injuries, 19 (2.26%) were reported to Occupational Health according to the surgeons questioned, but only six reported incidents were found in the Occupational Health records. Junior surgeons were significantly more likely to report needlestick injuries than senior surgeons (9.82% vs 1.10% of injuries reported, P=0.0000045). The main reasons for failure to report needlestick injuries were due to the lack of time and excessive paperwork. Seventy-three percent of surgeons did not routinely use double gloves when operating, mainly because of decreased hand sensation. The rate of needlestick injury reporting by surgeons at this institution is extremely low. Previous studies have shown a higher reporting rate suggesting that, despite awareness of blood-borne infections, surgeons are still not following recommended protocols.