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Introduction: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. Methods: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was per -formed based on the aforementioned characteristics. Results: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). Conclusion: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prog-nostically poor characteristics. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Introduction: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer.Materials and methods: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses.Results: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached).Conclusion: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years. (C) 2021 The Authors. Published by Elsevier Ltd.

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).

Aim: Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases. Method: All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis. Results: Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3-year metastasis-free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P

Contains fulltext : 231712.pdf (Publisher’s version ) (Open Access) BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

BACKGROUND: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5?*?5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. FINDINGS: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). INTERPRETATION: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. FUNDING: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Background: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase. Materials and methods: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance. Results: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged

Background: In earlier studies an association between older patients and higher morbidity and mortality after colorectal surgery is shown, especially in the first postoperative year. We conducted this study to investigate if there is improvement in postoperative morbidity and mortality in senior CRC patients over time.Materials and methods: All patients, except those with distant metastasis, who received curative CRC surgery between 2006 and 2017 in the Catharina Hospital (Eindhoven, the Netherlands) were selected retrospectively. Differences in mortality and relative survival between different age groups (= 75 years), period of surgery (2006-2012 and 2013-2017) and type of tumor (colon and rectum) were investigated.Results: In total 2018 patients, of whom 57.4% is male, were selected (n = 1037 colon and n = 981 rectum). 615 (30.5%) patients were >= 75 years old. For electively treated CRC patients aged >= 75 years 30-and 90-day mortality improved from 5.8% to 1.2% (p = 0.004) and 9.1% to 4.6% (p = 0.043) respectively, in favour of the latest time period. Relative one-year survival rates of all electively treated CRC patients were not significantly different between younger and older patients in the latest time period (95.5% vs. 94.3%, p = n.s.)Conclusions: This study shows significant improvement in postoperative morbidity and mortality over time for both age and treatment groups. Relative survival rates improved especially for older patients and no significant differences were seen between both age groups. Senior CRC patients should not be withheld curative treatment based on age or comorbidities alone. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background In most western European countries perioperative chemotherapy is a part of standard curative treatment for gastric cancer. Nevertheless, recurrence rates remain high after multimodality treatment. This study examines patterns of recurrence in patients receiving perioperative chemotherapy with surgery for gastric cancer in a real-world setting. Methods All patients diagnosed with gastric adenocarcinoma between 2010 and 2015 who underwent at least preoperative chemotherapy and a gastrectomy with curative intent (cT1N+/cT2-4a,X; any cN; cM0) in 18 Dutch hospitals were selected from the Netherlands Cancer Registry. Additional data on chemotherapy and recurrence were collected from medical records. Rates, patterns, and timing of recurrence were examined. Multivariable Cox proportional hazard analyses were used to determine prognostic factors for recurrence. Results 408 patients were identified. After a median follow-up of 27.8 months, 36.8% of the gastric cancer patients had a recurrence of which the majority (88.8%) had distant metastasis. The 1-year recurrence-free survival was 71.8%. The risk of recurrence was higher in patients with an ypN+ stage (HR 4.92, 95% CI 3.35-7.24), partial or no tumor regression (HR 2.63, 95% CI 1.22-5.64), 3 instead of >= 6 chemotherapy cycles (HR 3.04, 95% CI 1.99-4.63), R1 resection (HR 1.52, 95% CI 1.02-2.26), and

PURPOSE: This study was designed to assess the impact of age and comorbidity on choice and outcome of definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy plus surgery.METHODS: In this population-based study, all patients with potentially curable EC (cT1N+/cT2-3, TX, any cN, cM0) diagnosed in the South East of the Netherlands between 2004 and 2014 were included. Kaplan-Meier method with log-rank tests and multivariable Cox regression analysis were used to compare overall survival (OS).RESULTS: A total of 702 patients was included. Age ≥ 75 years and multiple comorbidities were associated with a higher probability for dCRT (odds ratio [OR] 8.58; 95% confidence interval [CI] 4.72-15.58; and OR 3.09; 95% CI 1.93-4.93). The strongest associations were found for the combination of hypertension plus diabetes (OR 3.80; 95% CI 1.97-7.32) and the combination of cardiovascular with pulmonary comorbidity (OR 3.18; 95% CI 1.57-6.46). Patients with EC who underwent dCRT had a poorer prognosis than those who underwent nCRT plus surgery, irrespective of age, number, and type of comorbidities. In contrast, for patients with squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, OS was comparable between both groups (hazard ratio [HR] 1.52; 95% CI 0.78-2.97; and HR 0.73; 95% CI 0.13-4.14).CONCLUSIONS: Histological tumor type should be acknowledged in treatment choices for patients with esophageal cancer. Neoadjuvant chemoradiotherapy plus surgery should basically be advised as treatment of choice for operable esophageal adenocarcinoma patients. For patients with esophageal squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, dCRT may be the preferred strategy.

Item does not contain fulltext OBJECTIVE: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL). METHODS: A systematic review was conducted according to the PRISMA guidelines using Ovid MEDLINE, EMBASe, and PubMed databases for studies reporting on outcomes of PPE for symptom relief or QoL. Descriptive statistics were used on pooled patient cohorts. RESULTS: Twenty-three historical cohorts and case series were included, comprising 509 patients. No comparative studies were found. Most malignancies were of colorectal, gynaecological and urological origin. Common indications for PPE were pain, symptomatic fistula, bleeding, malodour, obstruction and pelvic sepsis. The pooled median postoperative morbidity rate was 53.6% (13-100%), the median in-hospital mortality was 6.3% (0-66.7%), and median OS was 14 months (4-40 months). Some symptom relief was reported in a median of 79% (50-100%) of the patients, although the magnitude of effect was poorly measured. Data for QoL measures were inconclusive. Five studies discouraged performing PPE in any patient, while 18 studies concluded that the procedure can be considered in highly selected patients. CONCLUSION: Available evidence on PPE is of low-quality. Morbidity and mortality rates are high with a short median OS interval. While some symptom relief may be afforded by this procedure, evidence for improvement in QoL is limited. A highly selective individualised approach is required to optimise the risk:benefit equation.

Aim Outcomes in elderly patients (>= 75 years) with non-advanced colorectal cancer have improved. It is unclear whether this is also true for elderly patients with clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). We aimed to compare age-related differences in morbidity and mortality after curative treatment for cT4RC and LRRC.Methods All cT4RC and LRRC patients without distant metastasis who underwent curative surgery between 2005 and 2017 in the Catharina Hospital (Eindhoven, The Netherlands) were included. Morbidity and mortality were evaluated based on age (= 75 years) and date of surgery (2005-2011 and 2012-2017).Results Overall, 72 of 474 (15.2%) cT4RC and 53 of 293 (18.1%) LRRC patients were >= 75 years. No significant differences in the incidence of Clavien-Dindo I-IV complications were observed between age groups. However, in elderly cT4RC patients, cerebrovascular accidents occurred more frequently (4.2% vs. 0.5%, P = 0.03). Between 2005-2011 and 2012-2017, 30-day mortality improved from 7.5% to 3.1% and from 10.0% to 0.0% in elderly cT4RC and LRRC patients, respectively. The 1-year mortality during 2012-2017 was worse in elderly than in younger patients (28.1% vs. 6.2%, P = 0.001 for cT4RC and 27.3% vs. 13.8%, P = 0.06 for LRRC). In elderly cT4RC and LRRC patients, 44.4% and 46.2% died due to non-cancer-related causes, while only 27.8% and 23.1% died due to disease recurrence, respectively.Conclusion Although the 30-day mortality in elderly cT4RC and LRRC patients improved after curative treatment, the 1-year mortality in elderly patients continued to be high, which requires more awareness for the elderly after hospitalization.

Purpose The eHealth self-management application ‘Oncokompas’ was developed to support cancer survivors in monitoring health-related quality of life (HRQOL) and symptoms, and obtaining personalized feedback and options for supportive care. The aim of this study was to assess the cost-utility of Oncokompas compared with care as usual (CAU) among cancer survivors. Methods Survivors were randomly allocated to the intervention or control group. Direct (non-)medical, indirect non-medical costs, and HRQOL were measured at 3- and 6-month follow-up, using iMTA Medical Consumption and Productivity Costs and the EuroQol-5D questionnaires. Mean cumulative costs and quality-adjusted life-years (QALYs) were compared between both groups. Results In total, 625 survivors were randomized into intervention (n = 320) or control group (n = 305). Base case analysis showed that incremental costs from a societal perspective were − €163 (95% CI, − 665 to 326), and incremental QALYs were 0.0017 (95% CI, − 0.0121 to 0.0155) in the intervention group compared with those in the control group. The probability that, compared with CAU, Oncokompas is more effective was 60%, less costly 73%, and both more effective and less costly 47%. Sensitivity analyses showed that incremental costs vary between − €40 and €69, and incremental QALYs vary between − 0.0023 and − 0.0057. Conclusion Oncokompas is likely to be equally effective on utilities, and not more expensive than CAU, and will therefore contribute to sustainable cancer survivorship care in a (cost-)effective manner. Implications for Cancer Survivors Oncokompas seems to improve HRQOL and reduces the burden of several tumour-specific symptoms, while costs from a societal perspective are similar to CAU.

Introduction The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. Methods Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. Results Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0–10). Within 3 (IQR 1–4) sessions, users selected 32 (IQR 6–37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). Discussion Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics., Highlights • Main reason for not participating in the RCT was no interest in scientific research. • Main reason for no interest in Oncokompas was wanting to leave the period of being ill behind. • Main reason for not using Oncokompas was no symptom burden. • Many cancer-generic and tumour-specific symptoms were chosen in Oncokompas.

Summary There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine ‘fit-for-discharge’ status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

Geographical variation in cancer care has been observed between and within countries. Variation in treatment may occur at any point along the cancer care continuum attributing to potentially avoidable disparities in patient outcomes such as survival. Other studies have shown a large variation in the proportion of patients undergoing treatment with curative intent for esophageal(EC) and gastric cancer(GC). Due to these studies and thus an increased awareness, we hypothesize that variation has decreased over time. Methods Patients with potentially curable EC (n = 10,115) or GC (n = 3,983) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to examine the differences in the probability of treatment with curative intent between hospitals of diagnosis, comparing 2012-2014 with 2015-2017. We compared relative survival (RS) and relative excess risk of death (RER) between hospitals with different probabilities of treatment with curative intent. Results The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis was 45-95% in 2012-2014 and 54-89% in 2015-2017 for EC, and 52-100% and 45-100% for GC. The adjusted variation declined for EC with Odds Ratios (ORs) ranging from 0.50 to 1.72 between hospitals in the first period to 0.70–1.44 in the second period (p Conclusion Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC, but did not change for GC. A low probability of receiving curative treatment was associated with a worse survival. Further research is needed to elucidate the factors associated with the observed variability.

Background: Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes. Methods: All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS). Results: A pathologic complete response was observed in 22 patients (17%), a “good” response (Mandard 2–3) in 74 patients (56%), and a “poor” response (Mandard 4–5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (p = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (p = 0.004, p = 0.003, and p = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (p = 0.020 and p = 0.028, respectively). Conclusions: Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.

Surgery for esophageal cancer (EC) has been centralized in the Netherlands. However, patients are still diagnosed in referral centers and not all patients are discussed with a resection center. The aim of this study was to examine the impact of the implementation of the regional Upper-GI video multidisciplinary team meeting (MDT) in the Eindhoven region in which all regional patients should be discussed, on the decision-making process, treatment, and survival of patients with EC. Methods All patients diagnosed between 2012 and 2018 with EC, in hospitals currently working together with the Catharina hospital, were selected from the Netherlands Cancer Registry (n = 1119). The regional MDT was implemented in 2 hospitals in May 2014 and the other hospitals gradually joined. The primary outcome of this study was the proportion of patients discussed in any MDT. Secondary outcomes were involvement of a resection center in MDT, treatment and survival. Outcomes were described prior to and after participation in the regional MDT and analyzed by chi-square tests. Kaplan–Meier curves and log-rank tests were used to compare overall survival. Results Since participation in the regional MDT more patients were discussed in any MDT (80%-89%, p Conclusion After implementation of the regional MDT more EC patients were discussed during a MDT and also more often with the involvement of a resection center. This is the first study showing an association of the implementation of a regional MDT with an improved survival. Hypothetically, the implementation of the regional tumor specific video MDT could have had a positive effect on the quality and effectiveness of decision making in patients diagnosed with EC.

Background Thoracic epidural analgesia is the standard postoperative pain management strategy in esophageal cancer surgery. However, paravertebral block analgesia may achieve comparable pain control while inducing less side effects, which may be beneficial for postoperative recovery. This study primarily aims to compare the postoperative quality of recovery between paravertebral catheter versus thoracic epidural analgesia in patients undergoing minimally invasive esophagectomy. Methods This study represents a randomized controlled superiority trial. A total of 192 patients will be randomized in 4 Dutch high-volume centers for esophageal cancer surgery. Patients are eligible for inclusion if they are at least 18 years old, able to provide written informed consent and complete questionnaires in Dutch, scheduled to undergo minimally invasive esophagectomy with two-field lymphadenectomy and an intrathoracic anastomosis, and have no contra-indications to either epidural or paravertebral analgesia. The primary outcome is the quality of postoperative recovery, as measured by the Quality of Recovery-40 (QoR-40) questionnaire on the morning of postoperative day 3. Secondary outcomes include the QoR-40 questionnaire score Area Under the Curve on postoperative days 1–3, the integrated pain and systemic opioid score and patient satisfaction and pain experience according to the International Pain Outcomes (IPO) questionnaire, and cost-effectiveness. Furthermore, the groups will be compared regarding the need for additional rescue medication on postoperative days 0–3, technical failure of the pain treatment, duration of anesthesia, duration of surgery, total postoperative fluid administration day 0–3, postoperative vasopressor and inotrope use, length of urinary catheter use, length of hospital stay, postoperative complications, chronic pain at six months after surgery, and other adverse effects. Discussion In this study, it is hypothesized that paravertebral analgesia achieves comparable pain control while causing less side-effects such as hypotension when compared to epidural analgesia, leading to shorter postoperative length of stay on a monitored ward and superior quality of recovery. If this hypothesis is confirmed, the results of this study can be used to update the relevant guidelines on postoperative pain management for patients undergoing minimally invasive esophagectomy. Trial registration Netherlands Trial Registry, NL8037. Registered 19 September 2019.

Introduction: Surgery for locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) may require total pelvic exenteration with the need for urinary diversion. The aim of this study was to describe outcomes for ileal and colon conduits after surgery for LARC and LRRC.Methods: All consecutive patients from two tertiary referral centers who underwent total pelvic exenteration for LARC or LRRC between 2000 and 2018 with cystectomy and urinary reconstruction using an ileal or colon conduit were retrospectively analyzed. Short- (30 days) complications were described for an ileal and colon conduit.Results: 259 patients with LARC (n = 131) and LRRC (n = 128) were included, of whom 214 patients received an ileal conduit and 45 patients a colon conduit. Anastomotic leakage of the ileo-ileal anastomosis occurred in 9 patients (4%) after performing an ileal conduit. Ileal conduit was associated with a higher rate of postoperative ileus (21% vs 7%, p = 0.024), but a lower proportion of wound infections than a colon conduit (14% vs 31%, p = 0.006). The latter did not remain significant in multivariate analysis. No difference was observed in the rate of uretero-enteric anastomotic leakage, urological complications, mortality rates, major complications (Clavien-Dindo >= 3), or hospital stay between both groups.Conclusion: Performing a colon conduit in patients undergoing total pelvic exenteration for LARC or LRRC avoids the risks of ileo-ileal anastomotic leakage and may reduce the risk of a post-operative ileus. Besides, there are no other differences in outcome for ileal and colon conduits. (C) 2020 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background: Treatment for oesophageal cancer has evolved due to developments including the centralisation of surgery and introduction of neoadjuvant treatment. Therefore, this study evaluated trends in stage distribution, treatment and survival of oesophageal cancer patients in the last 26 years in the Netherlands.Patients and methods: Patients with oesophageal cancer diagnosed in the period 1989-2014 were selected from the Netherlands Cancer Registry. Patients were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in stage distribution, treatment and relative survival rates were evaluated according to histology.Results: Among all 35,760 patients, the percentage of an unknown tumour stage decreased from 34% to 10% during the study period, whereas the percentage of patients with metastatic disease increased from 21% to 34%. Among surgically treated patients 32% underwent a resection in a high-volume hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000-2004 to 43% and 26% in 2010-2014. Five-year relative survival increased from 8% to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to 27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic patients improved from 18 to 22 weeks.Conclusion: In the Netherlands, survival for oesophageal cancer patients improved significantly, especially in the period 2005-2014 which might be the result of better treatment related to the centralisation of surgery and introduction of neoadjuvant chemoradiotherapy. (C) 2018 Elsevier Ltd. All rights reserved.

Background A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. Methods Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. Results Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). Conclusion The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.

Background: The aim of our study was to describe treatment patterns and the impact on overall survival among elderly patients (75 years and older) with potentially curable esophageal cancer. Material and methods: Between 2003 and 2013, 13,244 patients from the nationwide population-based Netherlands Cancer Registry (NCR) were diagnosed with potentially curable esophageal cancer (cT2–3, X, any cN, cM0, X) of which 34% were elderly patients (n = 4501). Results: Surgical treatment with or without neoadjuvant treatment remained stable among elderly patients (around the 16% between 2003 and 2013). However, among younger patients, surgical treatment increased from 60.2 to 67.0%. The use of definitive chemoradiation (dCRT) increased in elderly patients from 1.9 to 19.5% and in younger patients from 5.2 to 17.2%. Due to the increase in dCRT, treatment with curative intent doubled in the elderly from 17 to 37.1%. Multivariable Cox regression revealed that elderly patients with an adenocarcinoma receiving surgery alone or dCRT had a significantly worse overall survival compared to those receiving surgery with neoadjuvant chemo (radio) therapy (nCRT/CT) (HR: 1.7 95% CI 1.4–2.0 and HR: 1.9 95% CI 1.5–2.3). However, among elderly with squamous cell carcinoma overall survival was comparable between dCRT, surgery alone and surgery with nCRT/CT. Conclusions: Survival was comparable among elderly patients with squamous cell carcinoma who underwent surgery with nCRT/CT, surgery alone or received dCRT, while elderly patients with an adenocarcinoma who underwent surgery with nCRT/CT had a better overall survival when compared with surgery alone or dCRT. Therefore, dCRT can be considered as a reasonable alternative for surgery among potentially curable elderly patients with esophageal squamous cell carcinoma. However, in elderly patients with esophageal adenocarcinoma surgery with nCRT/CT is still preferable regarding overall survival.

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard of care for patients with esophageal or junctional cancer, but the long-term impact of nCRT on health-related quality of life (HRQOL) is unknown. The purpose of this study is to compare very long-term HRQOL in long-term survivors of esophageal cancer who received nCRT plus surgery or surgery alone. Patients and methods: Patients were randomly assigned to receive nCRT (carboplatin/paclitaxel with 41.4-Gy radiotherapy) plus surgery or surgery alone. HRQOL was measured using EORTC-QLQ-C30, EORTC-QLQ-OES24 and K-BILD questionnaires after a minimum follow-up of 6 years. To allow for examination over time, EORTC-QLQ-C30 and QLQ-OES24 questionnaire scores were compared with pretreatment and 12 months postoperative questionnaire scores. Physical functioning (QLQ-C30), eating problems (QLQ-OES24) and respiratory problems (K-BILD) were predefined primary end points. Predefined secondary end points were global quality of life and fatigue (both QLQ-C30). Results: After a median follow-up of 105 months, 123/368 included patients (33%) were still alive (70 nCRT plus surgery, 53 surgery alone). No statistically significant or clinically relevant differential effects in HRQOL end points were found between both groups. Compared with 1-year postoperative levels, eating problems, physical functioning, global quality of life and fatigue remained at the same level in both groups. Compared with pretreatment levels, eating problems had improved (Cohen's d-0.37, P=0.011) during long-term follow-up, whereas physical functioning and fatigue were not restored to pretreatment levels in both groups (Cohen's d-0.56 and 0.51, respectively, both P

Background: Substantial variation in the use of (neo) adjuvant treatment in patients with gastric cancer exists. The aim of this study was to identify underlying (organizational and process) factors associated with the use of perioperative therapy. Patients and methods: Patients with resectable gastric cancer who underwent surgery between 2012 and 2014 were selected from the Dutch Upper gastrointestinal Cancer Audit (DUCA). The proportion of perioperatively treated patients was defined per hospital. Five hospitals with the lowest percentage (LP group) and 5 hospitals with the highest percentage (HP group) of perioperative therapy were identified. In the selected hospitals additional information was obtained from patients' medical records using a structured list with predefined variables. Results: In total, 429 patients (231 in LP group, 198 in HP group) from 9 different hospitals were included. Perioperative therapy was given in 16.0% of patients in the LP group compared to 40.4% in the HP group. In the LP group, patients were enrolled in a clinical trial less frequently (10.8% versus 26.8%, P = 3 upper GI specialists prior to treatment decision was positively associated with initiating perioperative therapy (OR 2.08, 95% CI 1.19-3.66). Conclusion: Results of this study confirm considerable hospital variation in the use of perioperative therapy in patients with gastric cancer. Besides known casemix factors, use of perioperative therapy was associated with the level of involvement of multidisciplinary care. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Item does not contain fulltext A nil-by-mouth regime with enteral nutrition via an artificial route is frequently applied following esophagectomy. However, early initiation of oral feeding could potentially improve recovery and has shown to be beneficial in many types of abdominal surgery. Although short-term nutritional safety of oral intake after an esophagectomy has been documented, long-term effects of this feeding regimen are unknown. In this cohort study, data from patients undergoing minimal invasive Ivor-Lewis esophagectomy between 04-2012 and 09-2015 in three centers in Netherlands were collected. Patients in the oral feeding group were retrieved from a previous prospective study and compared with a cohort of patients with early enteral jejunostomy feeding but delayed oral intake. Body mass index (BMI) measurements, complications, and nutritional re-interventions (re- or start of artificial feeding, start of total parenteral nutrition) were gathered over the course of one year after surgery. One year after surgery the median BMI was 22.8 kg/m2 and weight loss was 7.0 kg (9.5%) in 114 patients. Patients in the early oral feeding group lost more weight during the first postoperative month (P = 0.004). However, in the months thereafter this difference was not observed anymore. In the early oral feeding group, 28 patients (56%) required a nutritional re-intervention, compared to 46 patients (72%) in the delayed oral feeding group (P = 0.078). During admission, more re-interventions were performed in the delayed oral feeding group (17 vs. 46 patients P < 0.001). Esophagectomy reduces BMI in the first year after surgery regardless of the feeding regimen. Direct start of oral intake following esophagectomy has no impact on early nutritional re-interventions and long-term weight loss.

Item does not contain fulltext BACKGROUND: The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen. METHODS: DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with ClinicalTrials.gov, number NCT00301457. FINDINGS: Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83.1% (95% CI 80.0-86.3) in the 6-year group and 79.4% (76.1-82.8) in the 3-year group (hazard ratio [HR] 0.79 [95% CI 0.62-1.02]; p=0.066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 [21%] vs 137 [16%]). INTERPRETATION: We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy in all postmenopausal women with hormone receptor-positive breast cancer. FUNDING: AstraZeneca.

Purpose To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Methods and Materials Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. Results Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P =.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P =.036) were both independent predictors of severe complications. Conclusion With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.

Objective Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. Methods and materials Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. Results Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p Conclusions R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Aim The aim this study was to investigate possible differences in outcomes between Ivor-Lewis (IL) versus McKeown esophagectomy (MK) in a population based cohort. Background It is unknown whether IL or MK should be preferred in patients with potentially curable locoregionally oesophageal or gastro-oesophageal junction (GEJ) cancer. Methods Oesophageal and GEJ cancer patients without distant metastases who underwent a transthoracic oesophagectomy between 2015 and 2017 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, and treatment outcomes were analysed and compared between IL and MK after propensity score matching (PSM). Patients were matched based on sex, age, tumour morphology and topography, comorbidities, neoadjuvant treatment, cT and cN stage, ASA-score and hospital volume. Postoperative complications and survival were compared between both groups using Chi-Square and multivariable Cox regression analyses. In the multivariable Cox regression analyses we corrected for infectious complications (wound complications and pneumonia) and anastomotic leakage to investigate its effect on survival. Results Off all 1764 included patients (1201 IL patients and 563 MK patients), 948 patients remained after matching. Significantly more lymph nodes were yielded after IL compared to MK (P=0.02). Surgical radicality did not differ between both groups (P=0.25). The complication rate was significantly lower in the IL group regarding anastomotic leakage (17% vs. 28%, P Conclusion Patients who underwent an IL have better outcomes in terms of anastomotic leakage and recurrent laryngeal nerve palsy rate and overall survival compared to MK. The difference in survival appears not to be related to the differences in infectious complications. Based on these results, IL appears to be the treatment of choice in patients in whom both oncological resections are appropriate.

Aim In oesophageal cancer patients, clinical response to neoadjuvant chemoradiotherapy (nCRT) according to CROSS is assessed after 12 weeks, potentially followed by active surveillance in case of clinically complete response (cCR). Detection of residual tumour by FDG-PET/CT alone is inaccurate, since this cannot be distinguished reliably from post-radiation oesophagitis. We hypothesize that when inflammation diminishes, increasing FDG-uptake over time may be a sensitive parameter to detect local recurrence. We studied the detection of tumour recurrence with PET/CT during systematic follow-up in clinically complete responders beyond 12 weeks after nCRT. Background & Methods Patients from the preSANO- and SANO- trials were included who obtained cCR (no residual tumour on bite-on-bite biopsies and EUS with FNA of suspected lymph nodes) 12 weeks after completion of nCRT, but declined subsequent surgery. Patients were offered active surveillance, including PET/CT every 3 months. Standardised uptake values corrected for lean body mass (SUL) were measured at the primary tumour site. The percentage change in maximum SUL value (SULmax) between the last follow-up scan and the scan 12 weeks after nCRT was calculated. Tumour recurrence was defined as biopsy-proven vital tumour. Results Some 33 patients were eligible for analysis. In 17 of 33 (52%) patients, no biopsy-proven local recurrence was found during a median follow-up of 16 months (range 4.0-25) after CROSS. Some 16 of 33 (48%) patients had tumour recurrence within a median of 6.9 months after CROSS (range 5.3-36). We observed two different patterns of FDG uptake suggesting local recurrence. Three of 16 patients had sudden intense increase in SULmax (mean delta%-SULmax of 216%±42%). In the other 13 of 16 patients with local recurrence, an insidious gradual increase in FDG uptake was seen compared to patients without recurrence: mean delta%-SULmax of 21%±18% versus -10%±22% respectively. Conclusion Increasing FDG-uptake during active surveillance beyond 12 weeks after nCRT was associated with local recurrence and stable FDG-uptake with ongoing local tumour control. Thus, serial PET/CT might be a useful tool to distinguish tumour recurrence from SUL fluctuations in complete responders. To define a cut-off value of delta%-SULmax for local recurrence a larger number of patients is needed.

Background Total minimally-invasive transthoracic esophagectomy (ttMIE) faces increasing application in surgical treatment of esophageal cancer. For esophago-gastric reconstruction, different anastomotic techniques are currently used, but their impact on postoperative anastomotic leakage and morbidity has not been investigated. The aim of this retrospective multicenter analysis was to describe anastomotic techniques used for ttMIE and to analyze the associated morbidity. Patients and Methods Patients were selected from a basic dataset, collected over a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the CD classification and the Comprehensive Complication Index® (CCI). Results Five anastomotic techniques were identified in 966 patients after ttMIE: Intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n=90, purse-string n=337), intrathoracic (n=109) or cervical (n=255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n=175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs. 17.2%, P=0.601), but overall complications (56.7%% vs. 63.7%, P=0.029) and median 90-day CCI (21 (IQR 0-36) vs. 29 (IQR 0-40), P=0.019) favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%) and cervical side-to-side linear-stapled esophago-gastrostomies (11.8%) (P Conclusion Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.

Background Lateral nodal disease in rectal cancer remains a subject of debate and is treated differently in the East and the West. The predictive value of lateral lymph node and MRI-detected extramural vascular invasion (mrEMVI) features on oncological outcomes was assessed in this study. Methods In this retrospective cohort study, data on patients with cT3–4 rectal cancer within 8 cm from the anal verge were considered over a 5-year period (2009–2013). Lateral lymph node size, malignant features and mrEMVI features were evaluated and related to oncological outcomes. Results In total, 192 patients were studied, of whom 30 (15·6 per cent) underwent short-course radiotherapy and 145 (75·5 per cent) received chemoradiotherapy. A lateral lymph node short-axis size of 10 mm or more was associated with a significantly higher 5-year lateral/presacral local recurrence rate of 37 per cent, compared with 7·7 per cent in nodes smaller than 10 mm (P = 0·041). Enlarged nodes did not result in a higher 5-year rate of distant metastasis (23 per cent versus 27·7 per cent in nodes smaller than 10 mm; P = 0·563). However, mrEMVI positivity was related to more metastatic disease (5-year rate 43 versus 26·3 per cent in the mrEMVI-negative group; P = 0·014), but not with increased lateral/presacral recurrence. mrEMVI occurred in 46·6 per cent of patients with nodes smaller than 10 mm, compared with 29 per cent in patients with nodes of 10 mm or larger (P = 0·267). Conclusion Although lateral nodal disease is more a local problem, mrEMVI mainly predicts distant recurrence. The results of this study showed an unacceptably high local recurrence rate in patients with a short axis of 10 mm or more, despite neoadjuvant (chemo)radiotherapy.

Introduction: The aim of this study is to provide insight in accuracy of diagnosing, current treatment and survival in patients with resectable esophageal and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC, MANEC).Methods: All patients with esophageal or gastric (MA)NEC, who underwent surgical resection between 2006 and 2016, were identified from the Dutch national registry for histo-and cytopathology (PALGA). Patients with a neuroendocrine tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes were retrieved from the patient records. Diagnosis by endoscopic biopsy was compared with diagnosis by resection specimen. Kaplan Meier survival analysis was performed.Results: A total of 49 patients were identified in 25 hospitals, including 21 patients with esophageal (MA)NEC and 26 patients with gastric (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27 patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%) esophageal (MA)NEC5 and 12 (46%) gastric (MA)NECs. Survival curves were similar with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%) gastric (MA)NEC5 died within 90 days postoperatively. For esophageal (MA)NEC the median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23 months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively.Conclusion: Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic biopsies. After resection, long-term survival was achieved in respectively 35% and 39% of patients. (C) 2018 Published by Elsevier Ltd.

Background Centralization of surgery has been shown to improve outcomes for oesophageal and pancreatic cancer, and has been implemented for gastric cancer since 2012 in the Netherlands. This study evaluated the impact of centralizing gastric cancer surgery on outcomes for all patients with gastric cancer. Methods Patients diagnosed with non-cardia gastric adenocarcinoma in the intervals 2009–2011 and 2013–2015 were selected from the Netherlands Cancer Registry. Clinicopathological data, treatment characteristics and mortality were assessed for the periods before (2009–2011) and after (2013–2015) centralization. Cox regression analyses were used to assess differences in overall survival between these intervals. Results A total of 7204 patients were included. Resection rates increased slightly from 37·6 per cent before to 39·6 per cent after centralization (P = 0·023). Before centralization, 50·1 per cent of surgically treated patients underwent gastrectomy in hospitals that performed fewer than ten procedures annually, compared with 9·2 per cent after centralization. Patients who had gastrectomy in the second interval were younger and more often underwent total gastrectomy (29·3 per cent before versus 41·2 per cent after centralization). Thirty-day postoperative mortality rates dropped from 6·5 to 4·1 per cent (P = 0·004), and 90-day mortality rates decreased from 10·6 to 7·2 per cent (P = 0·002). Two-year overall survival rates increased from 55·4 to 58·5 per cent among patients who had gastrectomy (P = 0·031) and from 27·1 to 29·6 per cent for all patients (P = 0·003). Improvements remained after adjustment for case mix; however, adjustment for hospital volume attenuated this association for surgically treated patients. Conclusion Centralization of gastric cancer surgery was associated with reduced postoperative mortality and improved survival.

Background Patients with resectable oesophageal cancer are treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery within 3–8 weeks. In practice, surgery is often delayed for various reasons. The aim of this study was to evaluate whether delaying surgery beyond 8 weeks has an effect on postoperative morbidity, long-term survival, and pathologic response in patients treated for oesophageal ADC. Methods Patients who underwent nCRT followed by surgery, for cT1-3, N0-3, M0 ADC between 2001 and 2014 were retrospectively included from a prospectively obtained database. Patients with a time from the end of nCRT to surgery (TTS) ≤8 weeks were compared with patients with a TTS >8 weeks. Results Of 190 patients, 65 had a TTS ≤8 weeks, and 125 had a TTS >8 weeks. Patient characteristics were comparable for both groups, but patients with TTS >8 weeks exhibited higher ASA scores (p = 0.013) and more comorbidities (p = 0.007). Multivariate analysis revealed that TTS did not significantly influence postoperative morbidity, pathologic complete response rates, and five-year survival rates (42% in patients with TTS ≤8 weeks and 37% in patients with TTS >8 weeks). Conclusions Delaying surgery beyond 8 weeks after nCRT did not significantly influence postoperative morbidity, pathologic response, and survival in patients with non-metastatic ADC. Therefore, it appears reasonable to postpone surgery beyond 8 weeks in patients who have not yet recovered from nCRT. However, if the patient is fit for surgery, postponing surgery does not have any additional advantages.

Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival.Methods: We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated.Results: A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p = 0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p Conclusion: The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994–1998 to 25 weeks in 2009–2013. Although this increase could be attributed to stage migration, our population-based study suggests that major changes in treatment strategies and appropriate patient selection might have played a role as well.

Purpose. Repeat sentinel node biopsy (SNB) is an alternative to axillary lymph node dissection (ALND) for axillary staging in recurrent breast cancer. This study was conducted to determine factors associated with technical success of repeat SNB.Methods. A total of 536 patients with locally recurrent nonmetastatic breast cancer underwent lymphatic mapping (LM) and repeat SNB in 29 Dutch hospitals.Results. A total of 179 patients previously underwent breast-conserving surgery (BCS) with SNB, 262 patients BCS with ALND and 61 patients mastectomy, 35 with SNB and 26 with ALND. Another 34 patients underwent breast surgery without axillary interventions. A repeat sentinel node (SN) was identified in 333 patients (62.1 %) and was successfully removed in 235 (53.5 %). The overall repeat SN identification rate was 62.1 %, varying from 35 to 100 % in the participating hospitals. Previous radiotherapy of the breast [odds ratio (OR) 0.16; 95 % confidence interval (CI) 0.03-0.84], subareolar tracer injection (OR 0.34; 95 % CI 0.16-0.73), and a 2-day LM protocol (OR 0.57; 95 % CI 0.33-0.97) after previous BCS were independently associated with failure of SN identification. Injection of a larger amount of tracer (>180 MBq) led to a higher identification rate (OR 4.40; 95 % CI 1.45-13.32).Conclusions. Repeat SNB is a technically feasible procedure for axillary staging in recurrent breast cancer patients. Previous radiotherapy appears to be associated with failure of SN identification. Injection with a larger amount of tracer (>180 MBq) leads to a higher identification rate; subareolar injection and a 2-day LM protocol after previous BCS appear to be less adequate.

Background: For patients who qualify for perioperative chemotherapy and gastrectomy for gastric cancer, the optimal timing of the postoperative chemotherapy (PC) seems equivocal. The aim of this study was to evaluate the influence of timing of PC on overall survival (OS) in patients receiving perioperative chemotherapy. Methods: Patients undergoing perioperative chemotherapy and gastrectomy with curative intent (2010–2014) were extracted from the nationwide population-based Netherlands Cancer Registry. Timing of PC was analyzed as a linear and categorical variable (8 weeks). Risk factors for a late start of PC (≥6 weeks), and the association between timing of PC and OS were assessed by multivariable regression analyses. Results: Among 1066 patients who underwent perioperative chemotherapy and gastrectomy, 463 (43%) patients started PC. PC was administered within 6 weeks in 208 (45%) patients, within 6–8 weeks in 155 (33%) patients, and after 8 weeks in 100 (22%) patients. A total of 419 (91%) and 351 (76%) patients finished all cycles of preoperative and PC, respectively. A late start of PC was associated with a longer hospital stay (+1 hospital day: OR 1.15, 95% CI [1.08–1.23], p < 0.001). Timing of PC was not associated with OS (6–8 weeks vs. 8 weeks vs.

Background Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. Methods All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. Results Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31–7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04–4.65). Conclusion Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery.

SUMMARY Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1–5, where 1 signified ‘not important’ and 5 represented ‘very important.’ Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

Contains fulltext : 193307.pdf (Publisher’s version ) (Closed access) INTRODUCTION: The optimal time between end of neoadjuvant chemoradiotherapy (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the association between this interval and pathologic complete response rate (pCR), morbidity and 30-day/in-hospital mortality. METHODS: Patients with oesophageal cancer treated with nCRT and surgery between 2011 and 2016 were selected from a national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The interval between end of nCRT and surgery was divided into six periods: 0-5 weeks (n = 157;A), 6-7 weeks (n = 878;B), 8-9 weeks (n = 972;C), 10-12 weeks (n = 720;D), 13-14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association between these interval groups and outcomes was investigated using univariable and multivariable analysis with group C (8-9 weeks) as reference. RESULTS: In total, 3102 patients were included. The pCR rate for the groups A to F was 31%, 28%, 26%, 31%, 40% and 37%, respectively. A longer interval was associated with a higher probability of pCR (>/=10 weeks for adenocarcinoma: odds ratio [95% confidence interval]: 1.35 [1.00-1.83], 1.95 [1.24-3.07], 1.64 [0.99-2.71] and >/=13 weeks for squamous cell carcinoma: 2.86 [1.23-6.65], 2.67 [1.29-5.55]. Patients operated >/=10 weeks after nCRT had the same probability for intraoperative/postoperative complications. Patients from groups D and F had a higher 30-day/in-hospital mortality (1.80 [1.08-3.00], 3.19 [1.66-6.14]). CONCLUSION: An interval of >/=10 weeks for adenocarcinoma and >/=13 weeks for squamous cell carcinoma between nCRT and oesophagectomy was associated with a higher probability of having a pCR. Longer intervals were not associated with intraoperative/postoperative complications. The 30-day/in-hospital mortality was higher in patients with extended intervals (10-12 and >/=15 weeks); however, this might have been due to residual confounding.

Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P