Feasibility and Safety of Laparoscopic D2 Gastrectomy in Combination with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Gastric Cancer at High Risk of Recurrence-The PIPAC-OPC4 Study.

BACKGROUND: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. RESULTS: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. CONCLUSIONS: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.

An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

Tension-free mesh versus suture-alone cruroplasty in antireflux surgery: a randomized, double-blind clinical trial.

BACKGROUND: Antireflux surgery is effective for the treatment of gastro-oesophageal reflux disease (GORD) but recurrence of hiatal hernia remains a challenge. In other types of hernia repair, use of mesh is associated with reduced recurrence rates. The aim of this study was to compare the use of mesh versus sutures alone for the repair of hiatal hernia in laparoscopic antireflux surgery. METHODS: Patients undergoing laparoscopic Nissen fundoplication for GORD between January 2006 and December 2010 were allocated randomly to closure of the diaphragmatic hiatus with crural sutures or non-absorbable polytetrafluoroethylene mesh (CruraSoft®). The primary outcome was recurrence of hiatal hernia, as determined by barium swallow study 12 months after surgery. Secondary outcomes were: intraoperative and postoperative complications, use of antireflux medication, postoperative oesophageal acid exposure, quality of life, dysphagia and duration of hospital stay. RESULTS: Some 77 patients were randomized to the suture technique and 82 patients underwent mesh repair. At 1 year, the hiatal hernia had recurred in six of 64 patients (9 per cent) in the mesh group and two of 64 (3 per cent) in the suture group (P = 0·144). Reflux symptoms, use of proton pump inhibitors and oesophageal acid exposure did not differ between the groups. At 3 years, recurrence rates were 13 and 10 per cent in the mesh and suture groups respectively (P = 0·692). Dysphagia scores decreased in both groups, but more patients had dysphagia for solid food after mesh closure (P = 0·013). Quality-of-life scores were comparable between the groups. CONCLUSION: Tension-free crural repair with non-absorbable mesh does not reduce the incidence of recurrent hiatal hernia compared with use of sutures alone in patients undergoing laparoscopic fundoplication. NCT03730233 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía antirreflujo es efectiva para el tratamiento de la enfermedad por reflujo gastroesofágico (gastro-oesophageal reflux disease, GORD), pero la recidiva de la hernia de hiato sigue siendo un desafío. En otros tipos de reparación herniaria, la utilización de mallas se asocia con tasas reducidas de recidiva. El objetivo de este estudio fue comparar la utilización de una malla con suturas solo para la reparación de la hernia de hiato en cirugía antirreflujo laparoscópica. MÉTODOS: Pacientes sometidos a funduplicatura de Nissen por GORD entre enero 2006 y diciembre 2010 fueron asignados de forma aleatoria a cierre del hiato diafragmático con suturas de la crura o malla PTFE no absorbible (CruraSoft®). El resultado primario fue la recidiva de la hernia hiatal determinada mediante estudio radiológico con papilla de bario a los 12 meses de la cirugía. Los resultados secundarios fueron las complicaciones intra- y postoperatorias, utilización de medicación antirreflujo, exposición postoperatoria del esófago al reflujo ácido, calidad de vida, disfagia y duración de la estancia postoperatoria. RESULTADOS: Un total de 77 pacientes fueron aleatorizados a la técnica con suturas y 82 pacientes fueron sometidos a reparación con malla. Al año, se observó recidiva de la hernia de hiato en 6 de 64 pacientes en el grupo con malla (9%) y 2 de 64 pacientes (3%) en el grupo con suturas (P = 0,144). Los síntomas de reflujo, utilización de inhibidores de la bomba de protones (IBPs) y exposición del esófago al ácido no difirieron entre los grupos. A los 3 años, las tasas de recidiva fueron 13% y 10% para el grupo con malla y para el grupo con sutura, respectivamente (P = 0,692). Las puntuaciones de disfagia se redujeron en ambos grupos, pero más pacientes presentaron disfagia para sólidos tras el cierre con malla (P = 0,013). Las puntuaciones de calidad de vida posteriores fueron similares en ambos grupos. CONCLUSIÓN: En pacientes sometidos a funduplicatura laparoscópica, la reparación de la crura sin tensión con malla no absorbible no reduce la incidencia de recidiva de la hernia de hiato en comparación con el uso de suturas solo.

Relevant issues in tumor regression grading of histopathological response to neoadjuvant treatment in adenocarcinomas of the esophagus and gastroesophageal junction.

Multimodality treatment combining surgery and oncologic treatment has become widely applied in curative treatment of esophageal and gastroesophageal junction adenocarcinoma. There is a need for a standardized tumor regression grade scoring system for clinically relevant effects of neoadjuvant treatment effects. There are numerous tumor regression grading systems in use and there is no international standardization. This review has found nine different international systems currently in use. These systems all differ in detail, which inhibits valid comparisons of results between studies. Tumor regression grading in esophageal and gastroesophageal junction adenocarcinoma needs to be improved and standardized. To achieve this goal, we have invited a significant group of international esophageal and gastroesophageal junction adenocarcinoma pathology experts to perform a structured review in the form of a Delphi process. The aims of the Delphi include specifying the details for the disposal of the surgical specimen and defining the details of, and the reporting from, the agreed histological tumor regression grade system including resected lymph nodes. The second step will be to perform a validation study of the agreed tumor regression grading system to ensure a scientifically robust inter- and intra-observer variability and to incorporate the consented tumor regression grading system in clinical studies to assess its predictive and prognostic role in treatment of esophageal and gastroesophageal junction adenocarcinomas. The ultimate aim of the project is to improve survival in esophageal and gastroesophageal adenocarcinoma by increasing the quality of tumor regression grading, which is a key component in treatment evaluation and future studies of individualized treatment of esophageal cancer.

Improvements in esophageal and gastric cancer care in Sweden-population-based results 2007-2016 from a national quality register.

The Swedish National Register for Esophageal and Gastric cancer was launched in 2006 and contains data with adequate national coverage and of high internal validity on patients diagnosed with these tumors. The aim of this study was to describe the evolution of esophageal and gastric cancer care as reflected in a population-based clinical registry. The study population was 12,242 patients (6,926 with esophageal and gastroesophageal junction (GEJ) cancers and 5,316 with gastric cancers) diagnosed between 2007 and 2016. Treatment strategies, short- and long-term mortality, gender aspects, and centralization were investigated. Neoadjuvant oncological treatment became increasingly prevalent during the study period. Resection rates for both esophageal/GEJ and gastric cancers decreased from 29.4% to 26.0% (P = 0.022) and from 38.8% to 33.3% (P = 0.002), respectively. A marked reduction in the number of hospitals performing esophageal and gastric cancer surgery was noted. In gastric cancer patients, an improvement in 30-day mortality from 4.2% to 1.6% (P = 0.005) was evident. Overall 5-year survival after esophageal resection was 38.9%, being higher among women compared to men (47.5 vs. 36.6%; P < 0.001), whereas no gender difference was seen in gastric cancer. During the recent decade, the analyses based on the Swedish National Register for Esophageal and Gastric cancer database demonstrated significant improvements in several important quality indicators of care for patients with esophagogastric cancers. The Swedish National Register for Esophageal and Gastric cancer offers an instrument not only for the control and endorsement of quality of care but also a unique tool for population-based clinical research.

The role of home visits by a nurse to improve palliation in patients treated with self-expandable metallic stents due to incurable esophageal cancer.

Self-expandable metallic stent (SEMS) is a preferred option to relieve dysphagia and to palliate patients with incurable esophageal or gastro-esophageal junction (GEJ) cancer. Health Related Quality of Life (QoL) represents a clinically relevant outcome measure in research focused on palliation of patients with advanced GI cancer. In this context, home visits by a nurse carry the potential to offer important advantages. Eighty patients with incurable esophageal or GEJ cancer were randomized to either standard follow up or to an intervention containing regular home visits by a nurse. The primary outcome variable QoL was assessed by EORTC QLQ-C30 and OES-18 before insertion of SEMS, and at 2, 7 and 12 weeks thereafter. Secondary outcomes were; need for re-interventions, number of patients receiving palliative oncological therapy and overall survival. Sixty-six males and 13 females, with a median age of 71, were included. Self-reported overall QoL was significantly higher in the intervention group (P = 0.03). The organ specific module OES-18 revealed a significant reduction in dysphagia by the intervention (P = 0.03) as well as fewer eating disabilities (P = 0.04). No differences were observed in secondary outcomes except for overall survival, where the median survival was increased from 114 to 183 days by the active intervention (P = 0.02). Home visits by a nurse seem to play an important palliative role after placement of SEMS in patients with incurable esophageal or GEJ cancer by improving QoL and may carry the potential to increase overall survival.

Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study.

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

Phase II randomized clinical trial of endosonography and PET/CT versus clinical assessment only for follow-up after surgery for upper gastrointestinal cancer (EUFURO study).

BACKGROUND: Upper gastrointestinal malignancies have a poor prognosis. There is no consensus on how patients should be followed after surgery. The authors hypothesized that a structured follow-up programme including endoscopic ultrasonography (EUS) and [18 F]fluorodeoxyglucose (FDG) PET/CT would detect cancer recurrences, leading to more patients being eligible for therapy. METHODS: After surgery with curative intent for adenocarcinomas in the gastro-oesophageal junction, stomach or pancreas, patients were randomized 1 : 1 to standard clinical assessment in the outpatient clinic at 3, 6, 9, 12, 18 and 24 months after operation, or clinical assessment plus imaging including [18 F]FDG PET/CT and EUS. The primary endpoint was number of patients receiving oncological treatment for recurrence. Secondary endpoints were overall and progression-free survival, survival after recurrence detection of isolated locoregional recurrences and risk factors affecting survival. RESULTS: In total, 183 patients were enrolled, including 93 who underwent standard follow-up and 90 who had follow-up plus imaging. A recurrence was detected in 84 patients within 2 years after surgery (42 in each group), including 33 of 42 patients in the imaging group who were asymptomatic. Some 25 of 42 patients in the imaging group and 14 of 42 in the standard group received chemotherapy (P = 0·028). Although survival after detection of recurrence in asymptomatic patients was significantly longer than that for symptomatic patients (P < 0·001), overall survival from date of surgery in the two treatment groups was comparable. CONCLUSION: Follow-up after surgery for upper gastrointestinal cancer with EUS and PET/CT leads to detection of more asymptomatic cancer recurrences and patients referred for treatment without prolonging overall survival. Registration number: NCT02209415 ( http://www.clinicaltrials.gov).

ANTECEDENTES: Las neoplasias del tracto digestivo superior tienen un mal pronóstico. No existe consenso sobre en qué pacientes debe indicarse un seguimiento tras la cirugía. Se estableció la hipótesis de que un programa de seguimiento estructurado en el que se incluía ecoendoscopia (endosonography, EUS) y 18F-FDG-PET/CT detecta recidivas del cáncer logrando que más pacientes sean elegibles para tratamiento. MÉTODOS: Después de cirugía con intención curativa para adenocarcinomas de la unión gastroesofágica, estómago o páncreas, los pacientes fueron aleatorizados 1:1 a evaluación clínica estándar en consultas externas a los 3, 6, 9, 12, 18, y 24 meses postoperatorios o evaluación clínica más pruebas de diagnóstico por la imagen en las que se incluían 18F-FDG-PET/CT y EUS. La variable principal fue el número de pacientes que recibieron tratamiento oncológico para la recidiva. Las variables secundarias fueron la supervivencia global y libre de progresión, supervivencia tras la recidiva, la detección de recidivas locorregionales aisladas (isolated loco-regional recurrences, ILR) y factores de riesgo que afectan a la supervivencia. RESULTADOS: En total se reclutaron 183 pacientes, incluyendo 93 pacientes sometidos a un seguimiento estándar (controles) y 90 pacientes con seguimiento y pruebas de imagen. Se detectó recidiva en 84 pacientes dentro de los primeros dos años tras la cirugía (42 pacientes en cada grupo), incluyendo 33 de 42 pacientes (78%) en el grupo con pruebas de imagen que estaban asintomáticos. Veinticinco de 42 pacientes (60%) del grupo con pruebas de imagen y 14 de 42 pacientes (33%) del grupo control recibieron quimioterapia (P = 0,03). Aunque la supervivencia tras la detección de la recidiva en pacientes asintomáticos fue significativamente más larga en comparación con los pacientes sintomáticos (P < 0,001), la supervivencia global desde la fecha de la cirugía en las dos ramas del tratamiento fue comparable. CONCLUSIÓN: El seguimiento tras la cirugía del cáncer gastrointestinal del tracto superior con EUS y PET-CT permite detectar más recidivas asintomáticas de la enfermedad y derivar a los pacientes para tratamiento sin que ello prolongue la supervivencia global.

Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial).

BACKGROUND: There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS: In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS: Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION: HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.

ANTECEDENTES: Se dispone de poca información sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante. MÉTODOS: En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5-Fluorouracilo 750 mg/m2 /infusión de 24 horas en los días 1-5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ-C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad. RESULTADOS: De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT. CONCLUSIÓN: La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.

Texture analysis of computed tomography data using morphologic and metabolic delineation of esophageal cancer-relation to tumor type and neoadjuvant therapy response.

The prognostic values of image-based tumor texture analysis based on computed tomography (CT) and of limiting the segmented tumor volume to metabolically active regions using fludeoxyglucose-positron emission tomography (FDG-PET) were studied in 25 patients with esophageal adenocarcinoma and 11 patients with squamous cell carcinoma. The aims of this study are to describe their CT-image-based texture characteristics before and after neoadjuvant therapy and to evaluate whether limiting the examined tumor volume to metabolically active regions detected with FDG-PET image data would further improve their value. Textural parameters (homogeneity, energy, entropy, contrast, and correlation) based on gray-level co-occurrence matrices (GLCM) were calculated for 3D volumes of segmented esophageal tumors before and after neoadjuvant chemotherapy or radiochemotherapy. Histopathological data after surgical resection and textural parameters before and after neoadjuvant treatment were compared using the Mann-Whitney U test. Significant differences in the textural parameters were observed between adenocarcinoma and squamous cell carcinoma for homogeneity, energy, inertia, and correlation. The use of contrast media during scanning resulted in significant differences in homogeneity, energy, entropy, and inertia for adenocarcinoma but not squamous cell carcinoma. There was also a significant difference in all textural parameters between pathological T status for ypT0-ypT2 and ypT3-ypT4 adenocarcinomas, but not in squamous cell carcinoma patients. No additional value was found from using PET image data to aid segmentation of CT images.

Long-term weight development after esophagectomy for cancer-comparison between open Ivor-Lewis and minimally invasive surgical approaches.

Esophagectomy is an extensive procedure with severe postoperative effects. It can be assumed that the greater the trauma, the longer the nutritional recovery. This retrospective observational single-center cohort study compared weight development after esophagectomy with open and minimally invasive techniques. Three groups were compared in this study, one representing the first 41 patients who underwent the minimally invasive McKeown esophagectomy (MIMK). The second group included the first 84 consecutive patients operated with the minimally invasive Ivor-Lewis esophagectomy (MIIL). The third group comprised 100 consecutive patients operated with open thoracoabdominal Ivor-Lewis esophagectomy (IL). Virtually all patients submitted to a minimally invasive esophagectomy (MIE) and the majority with an IL had a jejunal catheter inserted during operation for postoperative enteral feeding. All together 225 patients were included in this study. The mean weight loss during the first year was 13.1% (±4.1), 11.2% (±6.1), and 9.6% (±7.5) in the IL, MIIL, and MIMK group, respectively (P = 0.85 and P = 0.95, respectively). The median duration of postoperative enteral nutrition support varied substantially within the groups and was 23.5 days in the IL group (range: 0-2033 days), 54.5 days in those having an MIIL (range: 0-308 days; P ≤ 0.001) and 57.0 days among patients in the MIMK group (range: 0-538 days; P ≤ 0.022). There was no difference in the risk of losing at least 10% of the preoperative weight at 3 or 6 months postoperatively between the groups. However, in patients who suffered severe complications (Clavien-Dindo score ≥ IIIb) after MIIL, there was a nonsignificant trend toward a lower risk of a 10% or greater weight loss, 3 months postoperatively. In conclusion, the greater surgical trauma associated with the traditional open esophagectomy was not followed by more severe weight loss, or other signs of poorer nutritional recovery, when compared to minimal invasive surgical techniques.

Effects of neoadjuvant chemoradiotherapy vs chemotherapy alone on the relief of dysphagia in esophageal cancer patients: secondary endpoint analysis in a randomized trial.

Dysphagia is the most significant symptom in patients with esophageal cancer. There are different therapeutic interventions designed to relieve dysphagia, but few studies have addressed the effects of neoadjuvant therapy. The aim of this study is to compare the effects on dysphagia of neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) and further to study the association between dysphagia response and histological response. Patient reported swallowing function was a secondary endpoint in the NeoRes trial, in which patients were randomized between neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Patients completed dysphagia questionnaires before the start and after neoadjuvant therapy, using the European Organization for Research and Treatment of Cancer (EORTC) esophageal cancer modules QLQ-OES24/OG25. Chirieac tumor regression grade (TRG) was used to assess the histological response. Out of 181 patients were randomized, of whom 87% completed the dysphagia questionnaires before and 73% after neoadjuvant treatment. Patient characteristics were similar between the treatment arms. Among patients reporting dysphagia at baseline, neoadjuvant therapy improved dysphagia in both arms. The mean dysphagia score after neoadjuvant treatment was significantly lower after nCT compared to after nCRT (P = 0.022). The reported dysphagia did not differ between those with a complete histological response (TRG 1) and those without any response at all (TRG 4) (P = 0. 583).

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Single center consecutive series cohort study of minimally invasive versus open resection for cancer in the esophagus or gastroesophageal junction.

Minimally invasive esophagectomy (MIE) has been introduced at many centers worldwide as evidence is accumulating that it reduces the risk of postoperative morbidity and mortality and decreases the length of hospital stay compared to conventional open esophagectomy. The study is a single institution cohort study of 366 consecutive patients treated with curative intent for cancer in the esophagus or gastroesophageal junction, comparing MIE to open surgery. The outcomes studied were peroperative bleeding, operation time, lymph node yield, complications, length of stay and overall survival. The results showed that MIE was associated with reduced peroperative bleeding and operation time. The patients in the MIE group had a statistically significant reduced risk of postoperative complications, 60.2% compared to 78.8% in the open group. In the MIE group 28.4% of the patients had postoperative complications classified according to the Clavien-Dindo classification system as grade IIIb-V compared to 38.2% in the open group, P = 0.046. Median hospital stay was reduced with 10 days comparing MIE to open surgery, P < 0.001. Mean number of resected lymph nodes was 31 in the MIE group and 22 in the open group (P < 0.001), while the R0 resections were 91.5% versus 85% (P = 0.057). Overall long-term survival was higher in the MIE group, a difference that however did not reach statistical significance (adjusted hazard ratio for three-year survival 0.76, 95% CI 0.54-1.08). In conclusion, MIE at a high volume center with a devoted specialist team reduces the risk of peroperative bleeding, operation time, and severe postoperative complications compared to open surgery for esophageal or junctional cancer. The number of resected lymph nodes was increased and the R0 resections were similar between the groups indicating a good oncological quality of the surgery.

Outcomes following the main treatment options in patients with a leaking esophagus: a systematic literature review.

Leakage from the esophagus and gastroesophageal junction can be lethal due to uncontrolled contamination of the mediastinum. The most predominant risk factors for the subsequent clinical outcome are the patients' delay as well as the delay of diagnosis. Two major therapeutic concepts have been advocated: either prompt closure of the leakage by insertion of a self-expandable metal stent (SEMS) or more traditionally, surgical exploration. The objective of this review is to carefully scrutinize the recent literature and assess the outcomes of these two therapeutic alternatives in the management of iatrogenic perforation-spontaneous esophageal rupture as separated from those with anastomotic leak. A systematic web-based search using PubMed and the Cochrane Library was performed, reviewing literature published between January 2005 and December 2015. Eligible studies included all studies that presented data on the outcome of SEMS or surgical exploration in case of esophageal leak (including >3 patients). Only patients older than 15 years of age by the time of admission were included. Articles in other languages but English were excluded. Treatment failure was defined as a need for change in therapeutic strategy due to uncontrolled sepsis and mediastinitis, which usually meant rescue esophagectomy with end esophagostomy, death occurring as a consequence of the leakage or development of an esophagorespiratory fistula and/or other serious life threatening complications. Accordingly, the corresponding success rate is composed of cases where none of the failures above occurred. Regarding SEMS treatment, 201 articles were found, of which 48 were deemed relevant and of these, 17 articles were further analyzed. As for surgical management, 785 articles were retrieved, of which 82 were considered relevant, and 17 were included in the final analysis. It was not possible to specifically extract detailed clinical outcomes in sufficient numbers, when we tried to separately analyze the data in relation to the cause of the leakage: i.e. iatrogenic perforation-spontaneous esophageal rupture and anastomotic leak. As for SEMS treatment, originally 154 reports focused on iatrogenic perforation, 116 focused on spontaneous ruptures, and only four described the outcome following trauma and foreign body management. Only five studies used a prospective protocol to assess treatment efficacy. Regarding a leaking anastomosis, 80 reports contained information about the outcome after treatment of esophagogastrostomies and 35 reported the clinical course after an esophagojejunostomy. An overall success rate of 88% was reported among the 371 SEMS-treated patients, where adequate data were available, with a reported in hospital mortality amounting to 7.5%. Regarding the surgical exploration strategy, the vast majority of patients had an attempt to repair the defect by direct or enforced suturing. This surgical approach also included procedures such as patching with pleura or with a diaphragmatic flap. The overall reported success rate was 83% (305/368) and the in-hospital mortality was 17% (61/368). The current literature suggests that a SEMS-based therapy can be successfully applied as an alternative therapeutic strategy in esophageal perforation rupture.

Long-term functional outcomes after replacement of the esophagus with gastric, colonic, or jejunal conduits: a systematic literature review.

It is generally recognized that in patients with an intact stomach diagnosed with esophageal cancer, gastric tubulization and pull-up shall always be the preferred technique for reconstruction after an esophageal resection. However, in cases with extensive gastroesophageal junction (GEJ) cancer with aboral spread and after previous gastric surgery, alternative methods for reconstruction have to be pursued. Moreover, in benign cases as well as in those with early neoplastic lesions of the esophagus and the GEJ that are associated with long survival, it is basically unclear which conduit should be recommended. The aim of this study is to determine the long-term functional outcomes of different conduits used for esophageal replacement, based on a comprehensive literature review. Eligible were all clinical studies reporting outcomes after esophagectomy, which contained information on at least three years of follow-up after the operation in patients who were older than 18 years of age at the time of the operation. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic web-based search using MEDLINE, the Cochrane Library, and EMBASE databases was performed, reviewing medical literature published between January 2006 and December 2015. The scientific quality of the data was generally low, which allowed us to incorporate only 16 full text articles for the final analyses. After a gastric pull-up, the proportion of patients who suffered from dysphagia varied substantially but seemed to decrease over time with a mild dysphagia remaining during long-term follow-up. When reflux-related symptoms and complications were addressed, roughly two third of patients experienced mild to moderate reflux symptoms a long time after the resection. Following an isoperistaltic colonic graft, the functional long-term outcomes regarding swallowing difficulties were sparsely reported, while three studies reported reflux/regurgitation symptoms in the range of 5% to 16%, one of which reported the symptom severity as being mild. Only one report was available after the use of a long jejunal segment, which contained only six patients, who scored the severity of dysphagia and reflux as mild. Very few if any data were available on a structured assessment of dumping and disturbed bowel functions. Few high-quality data are available on the long-term functional outcomes after esophageal replacement irrespective of the use of a gastric tube, the right or left colon or a long jejunal segment. No firm conclusions regarding the advantages of one graft over the other can presently be drawn.

A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction.

BACKGROUND: Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT. PATIENTS AND METHODS: This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm. RESULTS: The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms. CONCLUSION: The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival. CLINICALTRIALSGOV: NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).

Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro-oesophageal junction based on a national data registry.

BACKGROUND: Randomized trials have shown that neoadjuvant treatment improves survival in the curative treatment of oesophageal and gastro-oesophageal junction cancer. Results from population-based observational studies are, however, sparse and ambiguous. METHODS: This prospective population-based cohort study included all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1 N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006-2014. Patients were stratified into three groups: surgery alone, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. RESULTS: Neoadjuvant treatment was given to 521 patients (51·1 per cent) and 499 (48·9 per cent) received surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative surgical complications compared with surgery alone (adjusted odds ratio 2·01, 95 per cent c.i. 1·24 to 3·25; P = 0·005). Postoperative mortality was significantly increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds ratio 2·37, 1·06 to 5·29; P = 0·035). Survival improved in patients with squamous cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant chemoradiotherapy survival was significantly improved only in the subgroup with the highest performance status and without known co-morbidity. In adenocarcinoma there was a trend towards improved overall survival after neoadjuvant chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit. Stratified analysis including only patients with adenocarcinoma in the highest performance category without known co-morbidity showed a strong trend towards improved survival after neoadjuvant chemotherapy compared with surgery alone (adjusted hazard ratio 0·47, 0·21 to 1·04; P = 0·061). CONCLUSION: For patients with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction, neoadjuvant treatments seemed to increase long-term survival, but also the risk of postoperative morbidity and mortality, compared with surgery alone. Neither neoadjuvant treatment option seemed to improve survival significantly among patients with adenocarcinoma, compared with surgery alone.