Major Intraoperative Complications During Minimally Invasive Esophagectomy.

BACKGROUND: Studies have shown minimally invasive esophagectomy (MIE) to be a feasible surgical technique in treating esophageal carcinoma. Postoperative complications have been extensively reviewed, but literature focusing on intraoperative complications is limited. The main objective of this study was to report major intraoperative complications and 90-day mortality during MIE for cancer. METHODS: Data were collected retrospectively from 10 European esophageal surgery centers. All intention-to-treat, minimally invasive laparoscopic/thoracoscopic esophagectomies with gastric conduit reconstruction for esophageal and GE junction cancers operated on between 2003 and 2019 were reviewed. Major intraoperative complications were defined as loss of conduit, erroneous transection of vascular structures, significant injury to other organs including bowel, heart, liver or lung, splenectomy, or other major complications including intubation injuries, arrhythmia, pulmonary embolism, and myocardial infarction. RESULTS: Amongst 2862 MIE cases we identified 98 patients with 101 intraoperative complications. Vascular injuries were the most prevalent, 41 during laparoscopy and 19 during thoracoscopy, with injuries to 18 different vessels. There were 24 splenic vascular or capsular injuries, 11 requiring splenectomies. Four losses of conduit due to gastroepiploic artery injury and six bowel injuries were reported. Eight tracheobronchial lesions needed repair, and 11 patients had significant lung parenchyma injuries. There were 2 on-table deaths. Ninety-day mortality was 9.2%. CONCLUSIONS: This study offers an overview of the range of different intraoperative complications during minimally invasive esophagectomy. Mortality, especially from intrathoracic vascular injuries, appears significant.

Survival after Ivor Lewis versus McKeown esophagectomy for cancer: propensity score matched analysis.

It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Clinical variation in the organization of clinical pathways in esophagogastric cancer, a mixed method multiple case study.

BACKGROUND: Among esophagogastric cancer patients, the probability of having undergone treatment with curative intent has been shown to vary, depending on the hospital of diagnosis. However, little is known about the factors that contribute to this variation. In this study, we sought to understand the organization of clinical pathways and their association with variation in practice. METHODS: A mixed-method study using quantitative and qualitative data was conducted. Quantitative data were obtained from the Netherlands Cancer Registry (e.g., outpatient clinic consultations and diagnostic procedures). For qualitative data, thematic content analysis was performed using semi-structured interviews (n = 30), observations of outpatient clinic consultations (n = 26), and multidisciplinary team meetings (MDTM, n = 16) in eight hospitals, to assess clinicians' perspectives regarding the clinical pathways. RESULTS: Quantitative analyses showed that patients more often underwent surgical consultation prior to the MDTM in hospitals associated with a high probability of receiving treatment with curative intent, but more often consulted with a geriatrician in hospitals associated with a low probability of such treatment. The organization of clinical pathways was analyzed quantitatively at three levels: regional, local, and patient levels. At a regional level, hospitals differed in terms of the number of patients discussed during the MDTM. At the local level, the revision of radiological images and restaging after neoadjuvant treatment varied. At the patient level, some hospitals routinely conduct fitness tests, whereas others estimated the patient's physical fitness during an outpatient clinic consultation. Few clinicians performed a standard geriatric consultation in older patients to assess their mental fitness and frailty. CONCLUSION: Surgical consultation prior to MDTM was more often conducted in hospitals associated with a high probability of receiving treatment with curative intent, whereas a geriatrician was consulted more often in hospitals associated with a low probability of receiving such treatment.

Supervised exercise after oesophageal cancer surgery: the PERFECT multicentre randomized clinical trial.

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).

The eHealth self-management application 'Oncokompas' that supports cancer survivors to improve health-related quality of life and reduce symptoms: which groups benefit most?

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.

Age-related differences in morbidity and mortality after surgery for primary clinical T4 and locally recurrent rectal cancer.

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 and ≥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.

Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer.

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 < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98-2.11). CONCLUSION: LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis-free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

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.

Improved Outcomes for Responders After Treatment with Induction Chemotherapy and Chemo(re)irradiation for Locally Recurrent Rectal Cancer.

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.