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Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease.

A tumour-positive proximal margin (PPM) after extended gastrectomy for oesophagogastric junction (OGJ) adenocarcinoma is observed in approximately 2–20% of patients. Although a PPM is an unfavourable prognostic factor, the clinical relevance remains unclear as it may reflect poor tumour biology. This narrative review analyses the most relevant literature on PPM after gastrectomy for OGJ cancers. Awareness of the risk factors and possible measures that can be taken to reduce the risk of PPM are important. In patients with a PPM, surgical and non-surgical treatments are available but the effectiveness remains unclear.

Objective: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. Summary Background Data: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. Methods: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. Results: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. Conclusions: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were 3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Purpose Current studies have demonstrated conflicting results regarding surgical care for acute appendicitis during the COVID-19 pandemic. This study aimed to assess trends in diagnosis as well as treatment of acute appendicitis in the Netherlands during the first and second COVID-19 infection wave. Methods All consecutive patients that had an appendectomy for acute appendicitis in nine hospitals from January 2019 to December 2020 were included. The primary outcome was the number of appendectomies for acute appendicitis. Secondary outcomes included time between onset of symptoms and hospital admission, proportion of complex appendicitis, postoperative length of stay and postoperative infectious complications. Outcomes were compared between the pre-COVID group and COVID group. Results A total of 4401 patients were included. The mean weekly rate of appendectomies during the COVID period was 44.0, compared to 40.9 in the pre-COVID period. The proportion of patients with complex appendicitis and mean postoperative length of stay in days were similar in the pre-COVID and COVID group (respectively 35.5% vs 36.8%, p = 0.36 and 2.0 ± 2.2 vs 2.0 ± 2.6, p = 0.93). There were no differences in postoperative infectious complications. A computed tomography scan was used more frequently as a diagnostic tool after the onset of COVID-19 compared to pre-COVID (13.8% vs 9.8%, p Conclusion No differences were observed in number of appendectomies, proportion of complex appendicitis, postoperative length of stay or postoperative infectious complications before and during the COVID-19 pandemic. A CT scan was used more frequently during the COVID-19 pandemic.

OBJECTIVE: To evaluate changes in treatment and outcomes of esophagogastric cancer surgery after introduction of the DUCA. In addition, the presence of risk-averse behavior was assessed. SUMMARY OF BACKGROUND DATA: Clinical auditing is seen as an important quality improvement tool; however, its long-term efficacy remains largely unknown. In addition, critics claim that enhancements result from risk-averse behavior rather than positive effects of auditing. METHODS: DUCA data were used from registration start (1-1-2011) until 31-12-2018. Trends in patient, tumor, hospital and treatment characteristics were univariably assessed. Trends in short-term outcomes were investigated using multilevel multivariable logistic regression. Presence of risk aversion was described by the corrected proportion of patients undergoing surgery, using data from the Netherlands Cancer Registry. To evaluate the impact of centralization on time trends identified, the association between hospital volume and outcomes was investigated. RESULTS: This study included 6172 patients with esophageal and 3,690 with gastric cancer who underwent surgery. Pathological outcomes (lymph node yield, radicality) improved and futile surgery decreased over the years. In-hospital/30-day mortality decreased for esophagectomy (4.2% to 2.5%) and for gastrectomy (7.1% to 4.3%). Reinterventions, (minor) complications and readmissions increased. Risk aversion appeared absent. Between 2011-2018, annual median hospital volumes increased from 38 to 53 for esophagectomy and from 14 to 29 for gastrectomy. Higher hospital volumes were associated with several improved outcomes measures. CONCLUSIONS: During 8 years of auditing, outcomes improved, with no signs of risk-averse behavior. These improvements occurred in parallel with centralization. Feedback on postoperative complications remains the focus of the DUCA.

Contains fulltext : 288475.pdf (Publisher’s version ) (Open Access) Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.

Background Patients with different ethnic and genetic backgrounds may respond differently to anticancer therapies. This study aimed to assess whether patients with oesophageal squamous cell carcinoma (OSCC) treated with neoadjuvant chemoradiotherapy (nCRT) in East Asia had an inferior pathological response compared with patients treated in Northwest Europe. Methods Patients with OSCC who underwent nCRT according to the CROSS regimen (carboplatin and paclitaxel with concurrent 41.4 Gy radiotherapy) followed by oesophagectomy between June 2012 and April 2020 were identified from East Asian and Dutch databases. The primary outcome was pCR, defined as ypT0 N0. Groups were compared using propensity score matching, adjusting for sex, Charlson Co-morbidity Index score, tumour location, cT and cN categories, interval between nCRT and surgery, and number of resected lymph nodes. Results Of 725 patients identified, 133 remained in each group after matching. A pCR was achieved in 37 patients (27.8 per cent) in the Asian database and 58 (43.6 per cent) in the Dutch database (P = 0.010). The rate of ypT1–4 was higher in Asian than Dutch data (66.2 and 49.6 per cent; P = 0.004). The ypN1–3 rate was 44.4 per cent in the Asian and 33.1 per cent in the Dutch data set. Clear margins were achieved in 92.5 per cent of Asian and 95.5 per cent of Dutch patients. Conclusion Regional differences in responses to CROSS nCRT for oesophageal cancer were apparent, the origin of which will need evaluation.

Introduction: Laparoscopic paraesophageal hernia repair is an effective treatment for symptomatic paraesophageal hernias. To reduce recurrence rates, the use of prosthetics for the crural repair has been suggested. Mesh-related complications are rare but known to be disastrous. To address another form of crural repair, polypropylene strips are suggested. This study aimed to assess peri- and postoperative complications of reinforcement of cruroplasty with polypropylene strips. Methods: From 2013 to 2020, patients with a primary or recurrent type 2, 3, or 4 paraesophageal hernia that underwent cruroplasty with polypropylene strips were retrospectively reviewed. Intra- and postoperative complications were graded according to the Clavien-Dindo classification. The incidence of symptomatic recurrent hiatal hernia (CT or endoscopy proven) and hospital stay were assessed. Results: One hundred fifty-eight patients were included. Mean age was 65 years (standard deviation 10.4), and 119 patients were female (75.3%). Almost 50% of surgeries took place between 2018 and 2020. Median follow-up was 7 months (interquartile range 17.5). Mean operation time in the primary hernia group was 159 min (standard deviation 39.0), and length of stay was 4.4 days. In 3/158 patients (2.0%), intraoperative complications occurred. Two patients developed a grade 4 and seven patients a grade 3 postoperative complication. No mortality was recorded. Twelve recurrences (8.2%) were detected in the primary hernia group and one (9.1%) in the recurrent hernia group. Conclusion: There were no mesh-related complications seen and symptomatic recurrence rate was low, but longer follow-up is needed.

Contains fulltext : 291108.pdf (Publisher’s version ) (Open Access) Active surveillance may be a safe and effective treatment in oesophageal cancer patients with a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). In the NOSANO-study we gained insight in patients' motive to opt for either an experimental treatment called active surveillance or for standard immediate surgery. Both qualitative and quantitative analyses methods were used. Forty patients were interviewed about their treatment preference, 3 months after completion of nCRT (T1). Data were recorded, transcribed verbatim and analysed according to the principles of grounded theory. In addition, at T1 and T2 (12 months after completion of nCRT) questionnaires on health-related quality of life, coping, anxiety and decisional regret (only T2) were administered. Interview data analyses resulted in a conceptual model with 'dealing with threat of cancer' as the central theme. Patients preferring active surveillance tend to cope with this threat by confiding in their bodies and good outcomes. Their mind-set is one of 'enjoy life now'. Patients preferring surgery tend to cope by minimizing uncertainty and eliminating the source of cancer. Their mind-set is one of 'don't give up, act now'. Furthermore, questionnaire results showed that patients with a preference for standard surgery had a lower quality of life. Patient preferences are individualized and thus difficult to predict. Our model can help healthcare professionals to determine patient preferences for treatment. Coping style and mind-set seem to be determining factors here.

Optimal surgical treatment for Siewert type II esophagogastric junction adenocarcinoma is debated. The aim of this study was to compare transhiatal extended gastrectomy (TEG) and transthoracic esophagectomy (TTE). Patients with Siewert type II tumors who underwent a resection by TEG or TTE in two centers (Erasmus University Medical Center, Rotterdam, and University of Verona) between 2014 and 2019 were identified. To limit selection bias, patients were matched for baseline characteristics and compared with a multivariable logistic regression model. Some 159 patients treated by TEG (60 patients, 37.7%) or TTE (99 patients, 62.3%) were included. Patients in the TEG group were older, had less tumor invasion of the esophagus, and were more often excluded from neoadjuvant therapy. Post-operative morbidity was comparable (P = 0.88), while 90-day mortality was higher after TEG (90-day mortality 10.0% in TEG group vs. 2.0% in TTE group P = 0.01). R0 resection was achieved in 83.3% of patients after TEG and in 97.9% after TTE (P

Background This study investigated whether a supervised exercise programme improves quality of life (QoL), fatigue and cardiorespiratory fitness in patients in the first year after oesophagectomy. Methods The multicentre PERFECT trial randomly assigned patients to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate- to high-intensity aerobic and resistance exercise programme supervised by a physiotherapist. Primary (global QoL, QoL summary score) and secondary (QoL subscales, fatigue and cardiorespiratory fitness) outcomes were assessed at baseline, 12 and 24 weeks and analysed as between-group differences using either linear mixed effects models or ANCOVA. Results A total of 120 patients (mean(s.d.) age 64(8) years) were included and randomized to EX (61 patients) or UC (59 patients). Patients in the EX group participated in 96 per cent (i.q.r. 92–100 per cent) of the exercise sessions and the relative exercise dose intensity was high (92 per cent). At 12 weeks, beneficial EX effects were found for QoL summary score (3.5, 95 per cent c.i. 0.2 to 6.8) and QoL role functioning (9.4, 95 per cent c.i. 1.3 to 17.5). Global QoL was not statistically significant different between groups (3.0, 95 per cent c.i. –2.2 to 8.2). Physical fatigue was lower in the EX group (–1.2, 95 per cent c.i. –2.6 to 0.1), albeit not significantly. There was statistically significant improvement in cardiorespiratory fitness following EX compared with UC (peak oxygen uptake (1.8 ml/min/kg, 95 per cent c.i. 0.6 to 3.0)). After 24 weeks, all EX effects were attenuated. Conclusions A supervised exercise programme improved cardiorespiratory fitness and aspects of QoL. Trial registration Dutch Trial Register NTR 5045 (www.trialregister.nl/trial/4942).

Contains fulltext : 237885.pdf (Publisher’s version ) (Closed access) BACKGROUND: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. OBJECTIVE: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. INTERVENTION: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. MAIN OUTCOMES AND MEASURES: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. RESULTS: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. TRIAL REGISTRATION: Trialregister.nl Identifier: NL4183 (NTR4333).

Background Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. Methods This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. Results Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. Conclusion A long-term symptom burden is common after oesophageal cancer surgery.

OBJECTIVE: To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy.SUMMARY OF BACKGROUND DATA: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy.METHODS: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070).RESULTS: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P = 0.75] after intention-to-treat analysis and 0.93 (95% CI: 0.56-1.54, P = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection.CONCLUSIONS: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.

Over one-quarter of patients would choose not to undergo standard oesophagectomy again, at least 1 year after they underwent neoadjuvant chemoradiotherapy and standard oesophagectomy. These patients had worse short- and long-term health-related quality of life (HRQoL) than patients who chose standard oesophagectomy. Considering both treatments, 5-year survival and long-term HRQoL were considered most important factors by individual patients.

SUMMARY Background Endoscopic surveillance of adults with esophageal atresia is advocated, but the optimal surveillance strategy remains uncertain. This study aimed to provide recommendations on appropriate starting age and intervals of endoscopic surveillance in adults with esophageal atresia. Methods Participants underwent standardized upper endoscopies with biopsies. Surveillance intervals of 3–5 years were applied, depending on age and histopathological results. Patient’s age and time to development of (pre)malignant lesions were calculated. Results A total of 271 patients with esophageal atresia (55% male; median age at baseline endoscopy 26.7 (range 15.6–68.5) years; colon interposition n = 17) were included. Barrett’s esophagus was found in 19 (7%) patients (median age 32.3 (17.8–56.0) years at diagnosis). Youngest patient with a clinically relevant Barrett’s esophagus was 20.9 years. Follow-up endoscopies were performed in 108 patients (40%; median follow-up time 4.6 years). During surveillance, four patients developed Barrett’s esophagus but no dysplasia or cancer was found. One 45-year-old woman with a colon interposition developed an adenoma with high-grade dysplasia which was radically removed. Two new cases of esophageal carcinoma were diagnosed in patients (55 and 66 years old) who were not under surveillance. One of them had been curatively treated for esophageal carcinoma 13 years ago. Conclusions This study shows that endoscopic screening of patients with esophageal atresia, including those with a colon interposition, can be started at 20 years of age. Up to the age of 40 years a surveillance interval of 10 years appeared to be safe. Endoscopic surveillance may also be warranted for patients after curative esophageal cancer treatment.

Purpose: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. Methods: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). Results: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. Conclusion: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy.

Esophagectomy is considered the cornerstone of the radical treatment of esophageal cancer. In the past decades, minimally invasive techniques including robot-assisted approaches have become popular. The aim of minimally invasive surgery is to reduce the surgical trauma, resulting in faster recovery, reduction in complications, and better quality of life after surgery. Secondly, a more precise dissection may lead to better oncological outcomes. As such, minimally invasive esophagectomy is now seen by many as the standard surgical approach. However, evidence supporting this viewpoint is limited. This narrative review summarizes recent prospectively designed studies on minimally invasive esophagectomy.

Active surveillance for patients with esophageal cancer and a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is being studied. Active surveillance requires accurate clinical response evaluations. 18F-FDG PET/CT might be able to detect local tumor recurrence after nCRT as soon as the esophagus recovers from radiationinduced esophagitis. The aims of this study were to assess the value of serial 18F-FDG PET/CT scans for detecting local recurrence in patients beyond 3 mo after nCRT and to determine when radiation-induced esophagitis has resolved. Methods: This retrospectivemulticenter study included patients who had cCR after nCRT, who initially declined surgery, and who subsequently underwent active surveillance. Clinical response evaluations included 18F-FDG PET/CT, endoscopic biopsies, and endoscopic ultrasound with fine-needle aspiration at regular intervals. SUVmax normalized for lean body mass (SULmax) was measured at the primary tumor site. The percentage change in SULmax (D%SULmax) between the last follow-up scan and the scan at 3 mo after nCRT was calculated. Tumor recurrence was defined as biopsy-proven vital tumor at the initial tumor site. Results: Of 41 eligible patients, 24 patients had recurrent disease at a median of 6.5 mo after nCRT and 17 patients remained cancer free during a median follow-up of 24 mo after nCRT. Five of 24 patients with tumor recurrence had sudden intense SULmax increases of greater than 180%. In 19 of 24 patients with tumor recurrence, SULmax gradually increased (median D%SULmax, 118%), whereas SULmax decreased (median D%SULmax, -12%) in patients with ongoing cCR (P , 0.001, independent-samples t test). In patients with ongoing cCR, SULmax was lowest at 11 mo after nCRT. Conclusion: Serial 18F-FDG PET/CT might be a useful tool for detecting tumor recurrence during active surveillance. In patients with ongoing cCR, the lowest SULmax was reached at 11 mo after nCRT, suggesting that radiation-induced esophagitis had mostly resolved by that time. These findings warrant further evaluation in a larger cohort.

Purpose Patients presenting with acute appendicitis are usually hospitalized for a few days for appendectomy and postoperative recovery. Shortening length of stay may reduce costs and improve patient satisfaction. The purpose of this study was to assess the safety of same-day discharge after appendectomy for acute appendicitis. Methods A systematic review was performed according to PRISMA guidelines. A literature search of EMBASE, Ovid MEDLINE, Web of Science, Cochrane Central, and Google Scholar was conducted from inception to April 14, 2020. Two reviewers independently screened the literature and selected studies that addressed discharge on the same calendar day as the appendectomy. Risk of bias was assessed with the ROBINS-I tool. Main outcomes were hospital readmission, complications, and unplanned hospital visits in the postoperative course. A random effects model was used to pool risk ratios for the main outcomes. Results Of the 1912 articles screened, 17 comparative studies and 8 non-comparative studies met the inclusion criteria. Most only included laparoscopic procedure for uncomplicated appendicitis. Most studies were considered at moderate or serious risk of bias. In meta-analysis, same-day discharge (vs. overnight hospitalization) was not associated with increased rates of readmission, complication, and unplanned hospital visits. Non-comparative studies demonstrated low rates of readmission, complications, and unplanned hospital visits after same-day discharge. Conclusion This study suggests that same-day discharge after laparoscopic appendectomy for uncomplicated appendicitis is safe without an increased risk of readmission, complications, or unplanned hospital visits. Hence, same-day discharge may be further encouraged in selected patients. Trial registration PROSPERO registration no. CRD42018115948

Objective: This study aimed to describe failure to cure in terms of incidence, hospital variation, and as an outcome parameter for salvage esophagectomy. Summary Background Data: Failure to cure is a composite outcome measure that could be used for hospital comparison in esophageal carcinoma care. Methods: All patients registered in the Dutch Upper GI Cancer Audit who underwent potentially curative esophageal carcinoma surgery in 2011 to 2018, were included in this nationwide cohort study. Failure to cure was defined as: 1) no surgical resection due to intraoperative metastasis or locally irresectable tumor, 2) macroscopically or microscopically incomplete resection, or 3) 30- day/in-hospital mortality. Association of baseline characteristics with failure to cure was analyzed using multivariable logistic regression in the total population and in salvage patients. Results: Some 5894 patients from 22 hospitals were included, of whom 630 (10.7%) had failure to cure (hospital variation [5.5%–19.1%]). Higher age, preoperative weight loss, higher ASA-score, higher N-stage, neoadjuvant chemotherapy, or no neoadjuvant therapy (compared with neoadjuvant chemoradiotherapy), open surgery, and resection before 2014 were associated with failure to cure. After case-mix correction, 2 hospitals had statistically significant higher failure to cure percentages, whereas 2 had lower percentages. Of 151 salvage esophagectomy patients, 32.5% had failure to cure. The failure to cure rate after salvage surgery was 27.6% in high-volume hospitals and 47.6% in medium-volume hospitals. Conclusions: The incidence of failure to cure was 10.7%. Given the significant hospital variation in the percentage of failure to cure, improvement is needed. Since salvage procedures are more often successful in high-volume hospitals, further centralization of this procedure is warranted

Background Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. Methods A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. Results 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %–36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02–1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95–4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10–1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75–0.86). Conclusions A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice.

Objective To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. Background Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. Patients and methods Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. Results A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively. Conclusion Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Background Previous studies evaluating the association of lymph node (LN) yield and survival presented conflicting results and many may be influenced by confounding and stage migration. Objective This study aimed to evaluate whether the quality indicator ‘retrieval of at least 15 LNs’ is associated with better long-term survival and more accurate pathological staging in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy and resection. Methods Data of esophageal cancer patients who underwent neoadjuvant chemoradiotherapy and surgery between 2011 and 2016 were retrieved from the Dutch Upper Gastrointestinal Cancer Audit. Patients with Results In 2260 of 3281 patients (67%) ≥ 15 LNs were retrieved. In total, 992 patients with ≥ 15 LNs were matched to 992 patients with p = 0.28). pN+ was scored in 41% of patients with ≥ 15 LNs versus 35% of patients with p = 0.01). Conclusions n this propensity score-matched cohort, 3-year survival was comparable for patients with ≥ 15 LNs, although increasing nodal yield was associated with more accurate staging. In node-negative patients, 3-year survival was higher for patients with ≥ 15 LNs.

The optimal treatment of esophageal cancer is still controversial. Neoadjuvant chemoradiotherapy followed by radical esophagectomy is a standard treatment. Morbidity after esophagectomy however is still considerable and has an impact on patients' quality of life. Given a pathologic complete response rate of approximately 30% in patients after neoadjuvant chemoradiation followed by surgery, active surveillance has been introduced as a new alternative approach. Active surveillance involves regular clinical response evaluations in patients after neoadjuvant therapy to detect residual or recurrent disease. As long as there is no suspicion of disease activity, surgery is withheld. Esophagectomy is reserved for patients presenting with an incomplete response or resectable recurrent disease. Active surveillance after neoadjuvant treatment has been previously applied in other types of malignancy with encouraging results. This paper discusses its role in esophageal cancer., Morbidity after esophagectomy is still considerable and has an impact on patients' quality of life. Given a pathologic complete response rate of approximately 30% in patients after neoadjuvant chemoradiation followed by surgery, active surveillance is currently under investigation as a new alternative approach.

Objective The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Summary of background data After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified. Methods Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses. Results Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma. Conclusions Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.

Objective: The aim was to compare leak rate between hand‐sewn end‐to‐end anastomosis (ETE) and semi‐mechanical anastomosis (SMA) after esophagectomy with gastric tube reconstruction. Background Data: The optimal surgical technique for creation of an anastomosis in the neck after esophagectomy is unclear. Methods: Patients with esophageal cancer undergoing esophagectomy with gastric tube reconstruction and cervical anastomosis were eligible for participation after written informed consent. Patients were randomized in 1:1 ratio. Primary endpoint was anastomotic leak rate defined as external drainage of saliva from the site of the anastomosis or intra‐thoracic manifestation of leak. Secondary endpoints included anastomotic stricture rate at one year follow up, number of endoscopic dilatations, dysphagia‐score, hospital stay, morbidity, and mortality. Patients were blinded for intervention. Results: Between August 2011 and July 2014, 174 patients with esophageal cancer underwent esophagectomy. Ninety‐three patients were randomized to ETE (n = 44) or SMA (n = 49). Anastomotic leak occurred in 9 of 44 patients (20%) in the ETE group and 12 of 49 patients (24%) in the SMA group (absolute difference 4%, 95% CI −13% to +21%; p = .804). There was no significant difference in dysphagia at 1 year postoperatively (ETE 25% vs. SMA 20%; p = .628), in stricture rate (ETE 25% vs. 19% in SMA, p = .46), nor in median hospital stay (17 days in the ETE group, 13 days in the SMA group), morbidity (82% vs. 73%, p = .460) or mortality (0% vs. 4%, p = .175) between the groups.

Esophageal cancer (EC) remains one of the most common and aggressive diseases worldwide. This review discusses some debates in the modern management of the disease. Endoscopic procedures for early cancer (T1a-b) are now embedded in routine care and the challenge will be to more accurately select patients for endoscopic resection with or without adjuvant therapy. Perioperative multimodal therapies are associated with improved survival compared to surgery alone for locally advanced esophageal cancer. However, there is no global consensus on the optimal regimen. Furthermore, histological subtype (adenocarcinomavs. squamous cell cancer) plays a role in the choice for treatment. New studies are underway to resolve some issues. The extent of the lymphadenectomy during esophagectomy remains controversial especially after neoadjuvant chemoradiation. The ideal operation balances between limiting surgical trauma and optimizing survival. Minimally invasive esophagectomy and enhanced recovery pathways are associated with decreased morbidity and faster recovery albeit there is no consensus yet what approach should be used. Finally, immune checkpoint inhibitors present promising preliminary results in the novel treatment of advanced or metastatic EC but their widespread application in clinical practice is still awaited.

A tumour-positive proximal margin (PPM) after extended gastrectomy for oesophagogastric junction (OGJ) adenocarcinoma is observed in approximately 2-20% of patients. Although a PPM is an unfavourable prognostic factor, the clinical relevance remains unclear as it may reflect poor tumour biology. This narrative review analyses the most relevant literature on PPM after gastrectomy for OGJ cancers. Awareness of the risk factors and possible measures that can be taken to reduce the risk of PPM are important. In patients with a PPM, surgical and non-surgical treatments are available but the effectiveness remains unclear.

Background Current perioperative patient care aims to maintain homeostasis by attenuation of the stress response to surgery, as a more vigorous stress response can have detrimental effects on postoperative recovery. This systematic review and meta-analysis aims to assess the effect of perioperative music on the physiological stress response to surgery. Methods The Embase, Medline Ovid, Cochrane Central, Web of Science, and Google Scholar databases were searched from inception date until February 5, 2019, using a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for randomized controlled trials investigating the effect of music before, during, and/or after surgery in adult surgical patients on the stress response to surgery. Meta-analysis was performed using a random effects model and pooled standardized mean differences were calculated with 95% confidence intervals. This study was registered in the PROSPERO database (CRD42018097060). Results The literature search identified 1076 articles. Eighteen studies (1301 patients) were included in the systematic review, of which eight were included in the meta-analysis. Perioperative music attenuated the neuroendocrine cortisol stress response to surgery (pooled standardized mean difference −0.30, [95% confidence interval −0.53 to −0.07], P = 0.01, I2 = 0). Conclusions Perioperative music can attenuate the neuroendocrine stress response to surgery.

Objective:This study compared outcomes of patients with esophageal cancer and clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) undergoing active surveillance or immediate surgery. Background:Since nearly one-third of patients with esophageal cancer show pathologically complete response after nCRT according to CROSS regimen, the oncological benefit of immediate surgery in cCR is topic of debate. Methods:Patients with cCR based on endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration initially declining or accepting immediate surgery after nCRT were identified between 2011 and 2018. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), rate and timing of distant dissemination, and postoperative outcomes. Results:Some 98 patients with cCR were identified: 31 in the active surveillance- and 67 in the immediate surgery group with median followup of survivors of 27.7 and 34.8 months, respectively. Propensity score matching resulted in 2 comparable groups (n = 29 in both groups). Patients undergoing active surveillance or immediate surgery had a 3-year OS of 77% and 55% (HR 0.41; 95% CI 0.14-1.20, P = 0.104), respectively. The 3-year PFS was 60% and 54% (HR 1.08; 95% CI 0.44-2.67, P = 0.871), respectively. Patients undergoing active surveillance or immediate surgery had a comparable distant dissemination rate (both groups 28%), radical resection rate (both groups 100%), and severity of postoperative complications (Clav- ien-Dindo grade ≥ 3: 43% vs 45%, respectively). Conclusion:In this retrospective study, OS and PFS in patients with cCR undergoing active surveillance or immediate surgery were not significantly different. Active surveillance with postponed surgery for recurrent disease was not associated with a higher distant dissemination rate or more severe adverse postoperative outcomes.

Aim Laparoscopic paraesophageal hernia repair is an effective treatment for symptomatic paraesophageal hernias. To reduce recurrence rates, the use of prosthetics for the crural repair has been suggested. Mesh-related complications are rare, but known to be disastrous. To address another form of crural repair, polypropylene strips are suggested. This study aimed to assess peri- and postoperative complications of reinforcement of the cruroplasty with polypropylene strips. Material and Methods From 2013 to 2020, patients with a type II, III or IV primary or recurrent paraesophageal hernia that underwent cruroplasty with polypropylene strips were retrospectively reviewed. Intra- and postoperative complications were graded according to the Clavien-Dindo classification. The incidence of symptomatic recurrent hiatal hernia (CT or endoscopy proven) and hospital stay were assessed. Results One-hundred-and-fifty-eight patients were included. Mean age was 65 years (standard deviation 10.4), 119 patients were female (75.3%). Almost 50% of surgeries took place between 2018 and 2020. Median follow-up was 7 months (interquartile range 17.5). Mean operation time in the primary hernia group was 159 minutes (standard deviation 39.0), and length of stay was 4.4 days. In 3/158 patients (2.0%) intra-operative complications occurred. Two patients developed a grade IV and seven patients a grade III postoperative complication. No mortality was recorded. Twelve recurrences (8.2%) were detected in the primary hernia group, and one (9.1%) in the recurrent hernia group. Conclusions There were no mesh-related complications seen and symptomatic recurrence rate was low, but longer follow up is needed.

Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20 and 50% of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30% of these patients. The aim of this study was to assess the pattern of recurrence in patients with pCR after nCRT and surgery. Methods All patients with pCR after neoadjuvant chemoradiotherapy and surgery included in the phase II and III ChemoRadiotherapy for Oesophageal followed by Surgery Study (CROSS) trials (April 2001—March 2009) and after the CROSS trials (September 2009—October 2017) were identified. The site of recurrence was compared to the applied radiation and surgical fields. Outcomes were median time to recurrence, overall and progression-free survivals. Results A total of 141 patients with a median follow-up of 100 (interquartile range [IQR] 64–134) months were included. Some 29 of 141 patients (21%) developed recurrence. Of these, four (14%) had isolated locoregional recurrence, 15 (52%) distant recurrence only and ten (34%) had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five were within the radiation field, seven outside the radiation field and two at the border. Median (IQR) time to recurrence was 24 (10–62) months. The 5-year overall survival was 74% and recurrence-free survival 70%. Conclusion Despite good overall survival, recurrence still occurred in 21% of patients. Most recurrences were distant, outside the radiation and surgical fields.

To compare complications following totally minimally invasive (TMIE), laparoscopically assisted (hybrid) and open Ivor Lewis esophagectomy in patients with esophageal cancer. Three randomized trials have reported benefits for minimally invasive esophagectomy. Two studies compared TMIE versus open esophagectomy and another compared hybrid versus open Ivor Lewis esophagectomy. Only small retrospective studies compared TMIE with hybrid Ivor Lewis esophagectomy. Methods Data were used from the International Esodata Study Group assessing patients undergoing TMIE, hybrid or open Ivor Lewis esophagectomy. Primary outcome was pneumonia, secondary outcomes included incidence and severity of anastomotic leakage, (major) complications, length of stay, escalation of care and 90-day mortality. Data were analyzed using multivariate multilevel models. Results In total, 4733 patients were included in this study (TMIE:1472, hybrid:1364 and open:1897). Patients undergoing TMIE had lower incidence of pneumonia compared to hybrid (10.9% vs 16.3%, Odds Ratio (OR):0.56, 95%CI: 0.40–0.80) and open esophagectomy (10.9% vs 17.4%, OR:0.60, 95%CI: 0.42–0.84) and had shorter length of stay (median 10 days (IQR 8–16)) compared to hybrid (14 (11–19), p = 0.041) and open esophagectomy (11 (9–16), p = 0.027). Patients undergoing TMIE had higher rate of anastomotic leakage compared to hybrid (15.1% vs 10.7%, OR:1.47, 95%CI: 1.01–2.13) and open esophagectomy (7.3%, OR:1.73, 95%CI: 1.26–2.38). No differences were reported between hybrid and open esophagectomy. Conclusion Compared to hybrid and open Ivor Lewis esophagectomy, TMIE resulted in a lower pneumonia rate, a shorter hospital length of stay but a higher anastomotic leakage rate. The impact of these individual complications on survival and long-term quality of life should be further investigated.

Active surveillance after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal cancer is currently topic of investigation. In a discrete choice experiment, patients’ preferences can be quantified by asking patients to state their preference over hypothetical treatment alternatives. The aim of the present study was to assess patients’ preferences for either active surveillance or standard esophagectomy in patients who underwent neoadjuvant chemoradiotherapy followed by surgery without signs of recurrence. Methods A discrete choice experiment was performed in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by standard esophagectomy at least one year earlier. Patients completed a questionnaire consisting of eighteen choice sets considering active surveillance or standard esophagectomy. Treatment alternatives were characterized by attributes with varying attribute levels hypothesized to influence treatment choice: five-year survival, short-term and long-term health related quality of life (HRQOL), annual number of diagnostics required and the risk that esophagectomy is still necessary later in time. The importance of attributes and willingness to trade-off 5-year survival for other attributes were assessed using panel latent class model. Results A total of 107 patients were consecutively included, of whom 100 (93%) responded between August 2018 and October 2020. Regardless of the attribute levels, 28 patients preferred active surveillance and 28 patients preferred standard esophagectomy. When considering both treatments, five-year survival and long-term HRQOL were considered most important attributes. Patients were willing to trade-off 5.4% five-year overall survival to obtain a better long-term HRQOL. Conclusion At least one year after neoadjuvant chemoradiotherapy and esophagectomy, over a quarter of patients would choose not to undergo standard esophagectomy again, regardless of the attribute levels. Patients were willing to trade-off five-year survival chance in order to achieve an HRQOL which was much better than their own situation. When considering both treatments, five-year survival and long-term HRQOL were the most important determinants in the choice for treatment.

The need for standard surgical resection in esophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) is subject of debate. Possibly, active surveillance (AS) is an option for patients with a clinically complete response (cCR), in whom no vital tumor cells are detected after nCRT. In a large Dutch multicenter randomized trial (SANO trial), standard surgery is compared to AS in patients with a cCR. Within this trial, we performed a side-study on patient treatment preferences. Methods Esophageal cancer patients, who declined participation in the SANO-trial due to a strong treatment preference for either AS or surgery were included. In-depth interviews were held on patient’s motives for their treatment choice. First, personal motives were addressed in an open manner, and later specific topics were addressed: earlier experiences with illness and health care, future health expectations, emotional motives, religious or spiritual believes and values in life. Data was recorded, transcribed verbatim and qualitatively analyzed according to the grounded theory principles. In addition, questionnaires on health literacy, coping, anxiety and decision regret were administered at two time points. Results Forty patients participated: twenty preferred AS and twenty standard surgery. The central principle for all patients is striving for safety while dealing with the threat of cancer. However, patients express different coping strategies in dealing with this threat. Patients preferring AS rely on trusting their bodies and good outcomes, while questioning the need for surgery. Patients preferring surgery try to minimize insecurity by eliminating the source of the cancer, while arguing that chances for undergoing surgery are high anyway. Interestingly, for either treatment option comparable arguments were used, with the most striking one of wishing ‘not to become a patient’. Conclusion Patients’ preferences in the treatment of esophageal cancer are determined by the way they cope with the threat of cancer. Since the arguments given for either AS or standard surgery can be comparable or even similar, the need for healthcare professionals to discuss what truly matters to their patients is of high importance. Subsequently, attuning to the personal needs of esophageal cancer patients will benefit the decision making process on future treatment.

Standard treatment for locally advanced oesophageal cancer is neoadjuvant chemoradiotherapy (nCRT), plus surgery 6-8 weeks later. Time to surgery (TTS) after nCRT seems safe up to 12 weeks, and possibly improves patient condition and pathological response. However, it is unknown whether prolonged TTS is safe in patients with residual disease. The aim of this study was to investigate whether prolonged TTS leads to inferior surgical outcomes and survival in patients with residual disease after nCRT. Methods Patients with pathologically confirmed residual disease 4-6 weeks after nCRT who underwent preoperative PET/CT and surgery were selected from the preSANO-trial and SANO-trial. Patients were stratified by TTS ≤12 weeks versus TTS >12 weeks after completion of nCRT. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), peroperative unresectability, microscopically radical resections (R0), tumour regression grade (TRG), postoperative complications and risk of distant dissemination. Effects of TTS on OS, PFS and distant dissemination were analysed with Cox regression, adjusted for Charlson comorbidity index (CCI) at baseline, as well as WHO performance score and weight loss after nCRT. Results Forty-two patients were included in the TTS >12 weeks and 132 patients in the TTS ≤12 weeks group. Median follow-up was 20.6 months (IQR 16.1-30.3). Adjusted hazard ratios for OS and PFS were 0.50 (95% CI: 0.24-1.02) and 0.47 (95% CI: 0.25-0.91), respectively, in favour of TTS >12 weeks. Patients with TTS >12 weeks had more postoperative complications (89% vs 72%, p = 0.049), but comparable peroperatively unresectable tumours (11.9% vs. 3.8%, p = 0.11), R0-resections (89% vs 87%, p = 0.89), and TRG-scores (p = 0.97) compared to patients with TTS ≤12 weeks. Patients with TTS >12 weeks showed less distant dissemination (HR 0.40, 95% CI: 0.18-0.88). Conclusion Prolonged TTS beyond 12 weeks in patients with clinically proven residual disease after nCRT did not have a negative effect on OS and on PFS, but was correlated with an increase in postoperative complications. The (non-significantly) better survival outcomes for TTS >12 weeks may be explained by the fact that patients had a lower risk of developing distant dissemination, which may reflect improved selection prior to surgery.