Cardiorespiratory comorbidity and postoperative complications following esophagectomy: a European multicenter cohort study

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk

Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: a direct and adjusted indirect comparison meta-analysis

Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65–0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67–1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45–1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69–1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future

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

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

Pseudoachalasia: a systematic review of the literature

Pseudoachalasia, also known as secondary achalasia, is a clinical condition mimicking idiopathic achalasia but most commonly caused by malignant tumors of gastroesophageal junction (GEJ). Our aim was to systematically review and present all available data on demographics, clinical features, and diagnostic modalities involved in patients with pseudoachalasia. A systematic search of literature published during the period 1978–2019 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (end-of-search date: June 25th, 2019). Two independent reviewers extracted data with regards of study design, interventions, participants, and outcomes. Thirty-five studies met our inclusion criteria and were selected in the present review. Overall, 140 patients with pseudoachalasia were identified, of whom 83 were males. Mean patient age was 60.13 years and the mean weight loss was 13.91 kg. A total of 33 (23.6%) patients were wrongly ‘treated’ at first for achalasia. The most common presenting symptoms were dysphagia, food regurgitation, and weight loss. The median time from symptoms’ onset to hospital admission was 5 months. Most common etiology was gastric cancer (19%). Diagnostic modalities included manometry, barium esophagram, endoscopy, and computed tomography (CT). Pseudoachalasia is a serious medical condition that is difficult to be distinguished from primary achalasia. Clinical feature assessment along with the correct interpretation of diagnostic tests is nowadays essential steps to differentiate pseudoachalasia from idiopathic achalasia. © 2020, The Japan Esophageal Society