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Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2–3N0–1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m2 of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1–116·8, IQR 70·7–96·6), median overall survival was 48·6 months (95% CI 32·1–65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2–33·7) in the surgery alone group (HR 0·68 [95% CI 0·53–0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2–116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4–26·7) in the surgery alone group (HR 0·48 [95% CI 0·28–0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9–61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0–41·2) in the surgery alone group (HR 0·73 [95% CI 0·55–0·98]; log-rank p=0·038). Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. Dutch Cancer Foundation (KWF Kankerbestrijding).

Background Esophagogastric junction (EGJ) carcinoma has attracted considerable attention because of the marked increase in its incidence globally. However, the optimal extent of esophagogastric resection for this tumor entity remains highly controversial. Methods This was a questionnaire-based national retrospective study undertaken in an attempt to define the optimal extent of lymph node dissection for EGJ cancer. Data from patients with EGJ carcinoma, less than 40 mm in diameter, who underwent R0 resection between January 2001 and December 2010 were reviewed. Results Clinical records of 2807 patients without preoperative therapy were included in the analysis. There are distinct disparities in terms of the nodal dissection rate according to histology and the predominant tumor location. Nodal metastases frequently involved the abdominal nodes, especially those at the right and left cardia, lesser curvature and along the left gastric artery. Nodes along the distal portion of the stomach were much less often metastatic, and their dissection seemed unlikely to be beneficial. Lower mediastinal node dissection might contribute to improving survival for patients with esophagus-predominant EGJ cancer. However, due to low dissection rates for nodes of the middle and upper mediastinum, no conclusive result was obtained regarding the optimal extent of nodal dissection in this region. Conclusions Complete nodal clearance along the distal portion of the stomach offers marginal survival benefits for patients with EGJ cancers less than 4 cm in diameter. The optimal extent of esophageal resection and the benefits of mediastinal node dissection remain issues to be addressed in managing patients with esophagus-predominant EGJ cancers.

Little consensus exists regarding the endoscopic assessment of the esophagogastric junction after antireflux surgery. The purpose of this report is to characterize the gastroesophageal valve appearance unique to each type of antireflux procedure and to introduce an endoscopic lexicon by which to describe this anatomic region. Endoscopic images were obtained from patients who had undergone any one of the following procedures: Nissen, Collis-Nissen, Toupet, and Dor fundoplications and Hill repair. Images were excluded if patients had any symptoms of heartburn, regurgitation, dysphagia, chest pain, or gas bloat or if they were using antisecretory medication. Seven photographs per operation type were evaluated by experienced surgeons and gastroenterologists tasked with describing defining characteristics of each procedure. Ten valve criteria were developed to uniquely identify and quantify the ideal endoscopic appearance of each procedure. Illustrations were created to clearly depict those traits. Using 10 gastroesophageal valve criteria, the key components of a successful functional repair of the esophagogastric junction were defined. These criteria can be employed when evaluating upper gastrointestinal complaints after antireflux surgery and may ultimately serve as a dependable outcome measure.

The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial. In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1–14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40–60 mg twice a day on days 1–14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40–60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints—R0 resection rate and safety—were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete. Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0–75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3–57·5) for the adjuvant-CapOx group, 61·0% (55·3–66·2) for the adjuvant-SOX group, and 60·0% (54·2–65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62–1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61–0·98, p=0·033), compared with adjuvant-CapOx. Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients. The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis. For the Chinese translation of the abstract see Supplementary Materials section.

In resectable gastric and gastroesophageal junction cancer, adding durvalumab to perioperative chemotherapy improved event-free survival and pathological complete response, with no major increase in high-grade adverse events.

Mini-abstract We developed a novel technique for valvuloplastic esophagogastrostomy, named tri double-flap hybrid method (TDF). TDF is shown to be simple and useful for Siewert type II esophagogastric junction carcinoma. Background Research has found valvuloplastic esophagogastrostomy using the conventional hand-sutured double-flap (CDF) technique to be a useful anti-reflux procedure after proximal gastrectomy. However, no study has focused on this reconstruction procedure after laparoscopic transhiatal lower esophagectomy and proximal gastrectomy (LEPG) for esophagogastric junction carcinoma primarily because of its profound difficulty. Thus, we devised a novel technique for valvuloplastic esophagogastrostomy comprising triangular linear-stapled esophagogastrostomy and hand-sutured flap closure, which we term the tri double-flap hybrid (TDF) method. Methods After reviewing our institution’s prospective gastric cancer database, 59 consecutive patients with Siewert type II esophagogastric junction carcinoma who underwent LEPG with valvuloplastic esophagogastrostomy from January 2014 to August 2018 were analyzed. Short- and mid-term surgical outcomes were then compared between the LEPG-TDF and LEPG-CDF groups to evaluate the efficacy of the TDF method. Results The median operative time was 316 min (184–613 min) and blood loss was 22.5 ml (0–180 ml). In comparison between the two groups, the LEPG-TDF group had a significantly shorter operative time (298 vs. 336 min, p  = 0.041) and significantly lower postoperative anastomotic leak/stenosis rates (0 vs. 14.2%, p  = 0.045), compared to the LEPG-CDF group. No patient suffered from severe gastroesophageal reflux symptoms (Visick score ≥ III). Conclusions This study showed that double-flap valvuloplastic esophagogastrostomy is safe and feasible for reconstruction after LEPG for Siewert type II esophagogastric junction carcinoma. Moreover, the TDF method is a simple and useful technique that offers a shorter operative time and lower morbidity compared to the CDF technique.

BackgroundThe surgical approach for patients with Siewert type II AEG remains controversial. Several studies have described a new laparoscopic radical resection approach of Siewert type II AEG through the left diaphragm. However, the technical safety and feasibility of the new surgical approach compared with the transhiatal approach have not yet been tested.Study designWe retrospectively reviewed patients with AEG who underwent TSLG and LTH operations in the Guangdong Provincial Hospital of Chinese Medicine between January 2017 and April 2021. Histologically confirmed AEG and D2 lymphadenectomy with curative R0 patients were included, and patients with Siewert I/III AEG or distant metastasis were excluded. Blood loss, the amount of harvested lymph node, and complications related to surgery were evaluated.ResultsA total of 99 patients with Siewert type II AEG were analyzed, 44 in the TSLG group and 55 in the LTH group. There was no difference in clinicopathological features between the two groups. The more harvested lymph node (23.33 ± 11.41 vs. 32.18 ± 12.85, p < 0.01), lower mediastinal lymph node (1.07 ± 2.08 vs. 3.25 ± 3.31, p < 0.01), and longer proximal margin length (3.08 ± 1.19 vs. 4.47 ± 0.95 cm, p < 0.01) were observed in the TSLG group. The rate of cure (R0 gastrectomy) in the TSLG group was higher than that in the LTH group (100% vs. 89.09%, p = 0.03).ConclusionThe TSLG approach is associated with improved surgical views, simplified lymphatic dissection in the inferior mediastinum, and more reliable margins. TSLG surgery may be an effective addition to LTH surgery, particularly when lower mediastinal lymph node metastases are suspected.

Surgical resection is regarded as the only curative option for resectable oesophageal cancer, but pulmonary complications occurring in more than half of patients after open oesophagectomy are a great concern. We assessed whether minimally invasive oesophagectomy reduces morbidity compared with open oesophagectomy. We did a multicentre, open-label, randomised controlled trial at five study centres in three countries between June 1, 2009, and March 31, 2011. Patients aged 18–75 years with resectable cancer of the oesophagus or gastro-oesophageal junction were randomly assigned via a computer-generated randomisation sequence to receive either open transthoracic or minimally invasive transthoracic oesophagectomy. Randomisation was stratified by centre. Patients, and investigators undertaking interventions, assessing outcomes, and analysing data, were not masked to group assignment. The primary outcome was pulmonary infection within the first 2 weeks after surgery and during the whole stay in hospital. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. We randomly assigned 56 patients to the open oesophagectomy group and 59 to the minimally invasive oesophagectomy group. 16 (29%) patients in the open oesophagectomy group had pulmonary infection in the first 2 weeks compared with five (9%) in the minimally invasive group (relative risk [RR] 0·30, 95% CI 0·12–0·76; p=0·005). 19 (34%) patients in the open oesophagectomy group had pulmonary infection in-hospital compared with seven (12%) in the minimally invasive group (0·35, 0·16–0·78; p=0·005). For in-hospital mortality, one patient in the open oesophagectomy group died from anastomotic leakage and two in the minimally invasive group from aspiration and mediastinitis after anastomotic leakage. These findings provide evidence for the short-term benefits of minimally invasive oesophagectomy for patients with resectable oesophageal cancer. Digestive Surgery Foundation of the Unit of Digestive Surgery of the VU University Medical Centre.

Background The incidence of adenocarcinoma of the esophagogastric junction (AEG) has rapidly increased in recent years. Popular surgical approaches for AEG are proximal gastrectomy (PG) and total gastrectomy (TG), but it is controversial as to which approach is superior. Therefore, we conducted a systematic review and meta-analysis to evaluate the short- and long-term clinical outcomes of PG and TG for AEG. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to 1 June 2021. The Newcastle–Ottawa scale was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. Results In all, 1,734 patients with Siewert II/III AEG in 12 studies were included in the meta-analysis. PG was associated with less number of harvested lymph nodes (WMD =  − 9.00, 95% CI − 12.61 to − 5.39,  P  < 0.00001), smaller tumor size (WMD =  − 1.02, 95% CI − 1.71 to − 0.33, P  = 0.004), shorter hospital length of stay (WMD =  − 3.99, 95% CI − 7.27 to − 0.71, P  = 0.02), and better long-term nutritional status compared with TG. Overall complications, other complications, and overall survival were not significantly different between the two groups. Moreover, subgroup analysis revealed that the occurrence of anastomotic strictures and reflux esophagitis was associated with the use of novel gastrointestinal tract (GI) anastomoses (double-tract reconstruction, jejunal interposition, and semi-embedded valve anastomosis) after PG. Conclusions Based on the available evidence, we recommend that surgeons accept PG combined with multiple novel anastomoses as an optimal surgical approach in patients diagnosed with resectable Siewert type II/III AEG.