The Prognostic Impact of Minimally Invasive Esophagectomy on Survival after Esophagectomy following a Delayed Interval after Chemoradiotherapy; A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT prior to esophagectomy was associated with poorer long-term survival. METHODS: This was an international multi-center cohort study involving seventeen tertiary centers, including patients who received CRT followed by surgery between 2010-2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approach. RESULTS: 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and two years after CRT. Significant differences were observed in ASA grade, radiation dose, clinical T stage, and histological subtype. There were no significant differences between the groups in age, sex, BMI, pathological T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI 1.14 to 2.5) and propensity matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE, in 40-50Gy dose groups (HR=1.9; 95% CI 1.2 to 3.0), and in patients having surgery within six months of CRT (HR=1.6; 95% CI 1.1 to 2.2). CONCLUSION: MIE was associated with an improved overall survival compared to OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer: A Systematic Review and Individual Patient Data Meta-analysis.

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

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer: a modified Delphi consensus process.

BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value.

QOLEC2: a randomized controlled trial on nutritional and respiratory counseling after esophagectomy for cancer.

BACKGROUND: Esophagectomy for cancer strongly impairs quality of life. The aim of this trial was to evaluate the effect of the nutritional and respiratory counseling on postoperative quality of life. METHODS: At hospital discharge, patients were randomized into four groups receiving respectively: nutritional and respiratory counseling, nutritional counseling alone, respiratory counseling alone, or standard care. The main endpoint was the impairment in quality of life in the first month after surgery. Linear mixed effect models were estimated to assess mean score differences (MDs) in quality of life scores. RESULTS: Patients receiving nutritional counseling reported less appetite loss (MD - 17.7, 95% CI - 32.2 to -3.3) than those not receiving nutritional counseling at 1 month after surgery. Dyspnea was similar between patients receiving vs. those not receiving respiratory counseling (MD - 3.1, 95% CI - 10.8 to 4.6). Global quality of life was clinically similar between patients receiving vs. those not receiving nutritional counseling over time (MD 0.9, 95% CI - 5.5 to 7.3), as well as in patients receiving vs. those not receiving respiratory counseling over time (MD 0.7, 95% CI - 5.9 to 7.2). CONCLUSIONS: Intensive postoperative care does not affect global quality of life even if nutritional counseling reduced appetite loss.

MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach.

Gastroesophageal adenocarcinoma (GEA) patients with the microsatellite instability (MSI) subtype emerged as optimal candidates for immunotherapy. To date, immunohistochemistry (IHC) is the gold standard for MSI assessment in formalin-fixed paraffin-embedded (FFPE) specimens. However, IHC, although useful for diagnostic typing, cannot be used to analyze cell-free DNA (cfDNA) in liquid biopsy, a tool that could overcome tumor heterogeneity and enable longitudinal monitoring. In order to find an alternative diagnostic method to IHC, we analyzed 86 retrospective GEAs FFPE samples with multiplex PCR. Moreover, to verify the feasibility of MSI detection in liquid biopsy, cfDNA samples of five patients that resulted in having MSI in a prospective cohort of 35 patients were evaluated by multiplex PCR, real-time PCR and droplet digital PCR (ddPCR). Analysis of FFPE showed 100% concordance between multiplex PCR and IHC (Cohen's Kappa agreement = 1). On the contrary, only ddPCR was able to detect MSI in cfDNAs of T3/T4 GEA patients. In conclusion, data highlight the molecular analysis as an optimal alternative to IHC for the diagnostic typing and suggest that the ddPCR assay can be considered as the most reliable and promising molecular approach to detect MSI in the cfDNA of GEA patients.

Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients.

DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett's esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring.

Cholecystectomy during esophagectomy is safe but unnecessary.

Background: Prophylactic cholecystectomy has been proposed as a concomitant procedure during upper gastrointestinal surgery. This study evaluates the safety and the need of concurrent cholecystectomy during esophagectomy for cancer.Methods: All consecutive esophagectomies for esophageal cancer at the Center for Esophageal Diseases in Padova (Italy) between 1992 and 2011 were included. The safety of concurrent cholecystectomy was evaluated by surgical outcomes (length of stay, postoperative mortality and perioperative complications). The need for concurrent cholecystectomy was evaluated by occurrence of biliary duct stones and of cholelithiasis/cholecystitis after esophagectomy.Results: Cholecystectomy was performed during 67 out of 1087 esophagectomies (6.2%). Cirrhosis or chronic liver disease was associated with receiving cholecystectomy during esophagectomy (OR: 1.99, 95%C.I. 1.10-3.56). Patients receiving and those not receiving cholecystectomy showed similar length of stay (median 14 days, p = .87), postoperative mortality (3.0% vs. 2.5%, p = .68), intraoperative complication (4.5% vs. 7.1%, p = .62), early complications (52.2% vs. 44.6%, p = .25) and late complications (20.9% vs. 24.8%, p = .56). Cholelithiasis/cholecystitis after esophagectomy occurred in 61 (6.1%) patients, with only four requiring cholecystectomy during follow-up. The biliary stone occurrence was nil. Only pathologic stage III-IV (OR: 2.17, 95%C.I. 1.19-3.96) was associated with cholelithiasis/cholecystitis after esophagectomy.Conclusion: Routine prophylactic cholecystectomy during esophagectomy could be safe but unnecessary.

Esophageal Cancer Clinical Presentation: Trends in the Last 3 Decades in a Large Italian Series.

OBJECTIVE: The aim of this study was to investigate trends in patients' characteristics and comorbidities in esophageal cancer (EC) patients. BACKGROUND: Identifying changing pattern is essential to understand and predict further changes and to plan surgical procedures and resource allocation. METHODS: Trends in patients' characteristics and comorbidities were evaluated in 4440 EC patients at the Center for Esophageal Diseases in Padova, Italy, during 1980 to 2011. Joinpoint regression analysis was performed to evaluate trends and to estimate annual percentage changes (APCs). RESULTS: During the study period, there has been a statistically significant increment of the rate of esophageal adenocarcinoma (APC 3.70). The rates of elderly and of asymptomatic patients increased over time (APCs 0.98 and 6.24), whereas the rates of malnutrition, alcoholic drinking, and gastric ulcer decreased (APCs -1.50, -1.72, and -5.20). Reflux rate increased until 1997 and decreased thereafter (APCs 6.96 and -4.48), whereas the rate of Barrett esophagus increased until 1992 (APC 35.84) and then leveled. The rates of patients with previous neoplasms increased over time (APCs 3.22 and 4.86). There have been significant changes in systemic comorbidities, with an increase of hypertension and cardiac disease (APCs 7.56 and 1.86) and a decrease of advanced liver disease and pulmonary disease (APCs -2.67 and -1.74). CONCLUSION: The current EC patient has more often an esophageal adenocarcinoma and is more frequently elderly, asymptomatic, a survivor of previous neoplasms, and a patient with hypertension and cardiac disease than 30 years ago. On the contrary, malnutrition, alcoholic drinking, gastric ulcer, pulmonary disease, and advanced liver disease decreased.

Long-term quality of life after esophagectomy with gastric pull-up.

BACKGROUND AND OBJECTIVES: Data on long-term health-related quality of life (HRQL) after esophagectomy for cancer show contradictory results. The aim was to analyze long-term HRQL at 3 or more years after esophagectomy. METHODS: Survivors were identified among patients who had undergone esophagectomy during 2007-2013 using the local clinic database. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and OG25 questionnaires. Specific aspects were selected a priori and compared with published scores from European healthy subjects (mean difference, MD). RESULTS: Sixty-five long-term survivors (median follow-up 4 years) were identified. All functional scales and most symptom scales were clinically similar between EC long-term survivors and European healthy subjects. Survivors reported more problems concerning eating (MD 13.1, 95% C.I. 10.6-15.6) and reflux (MD 19.7, 95% C.I. 15.9-23.5). HQRL variation from discharge to long term was available in 27 participants who reported improvements in role functioning (MD 40.1, 95%C.I. 24.3-56.0) and dysphagia (MD -41.9, 95% C.I. -51.7 to 32.0). CONCLUSIONS: Long-term HRQL after esophagectomy is similar between EC survivors and European healthy subjects, despite persisting reflux and eating problems. Further research may focus on improvements of postoperative alimentary habits.

Time to diagnosis in esophageal cancer: a cohort study.

BACKGROUND: The association between shorter time to diagnosis and favorable outcome is still unproven in esophageal cancer. This study aims to evaluate the effect of time to diagnosis on patient prognosis. MATERIAL AND METHODS: Retrospective cohort study of all 3613 symptomatic patients referred for esophageal cancer to our center from 1980 to 2011. Time to diagnosis was calculated as the number of days from first symptom onset to the diagnosis of esophageal cancer. The main outcome measures were: resectability and severe malnutrition at diagnosis; postoperative morbidity, mortality and survival. RESULTS: Longer time to diagnosis was significantly associated with severe malnutrition at diagnosis (odds ratio (OR): 1.003, 95% confidence interval (C.I.).: 1.001-1.006) but not with resectability (OR: 0.997, 95% C.I.: 0.994-1.001). Longer time to diagnosis was not associated with postoperative morbidity (OR: 1.000, 95% C.I.: 0.998-1.003), postoperative mortality (OR: 1.002, 95% C.I.: 0.998-1.006), five-year overall survival (hazard ratio (HR): 0.999, 95% C.I.: 0.997-1.001) or five-year disease free survival (HR: 0.999, 95% C.I.: 0.998-1.001). CONCLUSION: Longer time to diagnosis did not affect resectability, postoperative morbidity or survival. Further campaigns to raise awareness of cancer among population and primary health care providers may have limited effect on clinical outcome.

Potential curability and perception of received information in esophageal cancer patients.

PURPOSE: This study aimed to evaluate patients' perceived receipt of information according to the possibility of cure in esophageal cancer. METHODS: One hundred and twelve consecutive patients presenting at the multidisciplinary visit at the Veneto Institute of Oncology for esophageal cancer between 2014 and 2016 were included in the study. The Italian version of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires C30 (core questionnaire), OG25 (esophago-gastric cancer module), and INFO25 (information module) were used. RESULTS: Candidates for palliative treatment were less informed about the disease (adjusted mean difference - 11.5, 95% CI - 23.0 to - 0.02) and less satisfied with information provided (adjusted mean difference - 18.3, 95% CI - 31.9 to - 4.7) than candidates for curative treatment. In addition, candidates for palliative treatment wanted to receive more information than candidates for curative treatment (adjusted mean difference 26.1, 95% CI 0.5 to 51.6). Better quality of life was associated with satisfaction of received information (ß = 0.77, p < 0.0001) and of receiving information about things that the patient can do to help himself (ß = 0.26, p = 0.04). More anxiety was associated to receiving more information about disease (ß = 0.46, p = 0.02) but less information about things that the patient can do to help himself (ß = - 0.38, p = 0.02). CONCLUSIONS: Candidates for palliative treatment were less satisfied with information about the disease and wanted to receive more information. Additionally, some aspects of quality of life were found to be associated with perceived receipt of information. Appropriate training in communication of prognostic information may improve clinical management of incurable cancer patients.

Esophageal adenocarcinoma microenvironment: Peritumoral adipose tissue effects associated with chemoresistance.

Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot-specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy in esophageal adenocarcinoma (EAC). We analyzed: (i) the peritumoral adipose tissue of rats following the induction of esophageal carcinogenesis; (ii) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; (iii) adipose-derived stem cells (ADSC) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. In peritumoral adipose tissue of rats, CD34, CD31 and vascular endothelial growth factor (VEGF) expression increased progressively during EAC development. In patients with EAC, expression of CD34, CD45, CD90 and nucleostemin (NSTM) was higher in peritumoral than in distal adipose tissue and decreased in the presence of neoadjuvant therapy. Moreover, expression of NSTM, octamer-binding transcription factor 4 (OCT-4) and VEGF was higher in peritumoral (but not in distal) adipose tissue of chemoresistant patients. In ADSC, treatment with peritumoral adipose tissue CM increased the adipogenic potential and the expression of CD34, CD90, NSTM and OCT-4. These effects were similar to those induced by cancer-derived CM, but were not observed in ADSC treated with distal adipose tissue CM and were partially reduced by a leptin antagonist. Last, ADSC treated with peritumoral CM of chemoresistant patients displayed increased expression of NSTM, OCT-4, leptin, leptin receptor, alpha-smooth muscle actin (α-SMA), CD34 and VEGF. These results suggest that peritumoral adipose tissue may promote, by paracrine signaling, the expression of depot-specific factors associated with therapeutic resistance.

Immunonutrition before esophagectomy: Impact on immune surveillance mechanisms.

Preoperative oral immunonutrition was demonstrated to improve immune response and to decrease the infection rate in patients with cancer. This study aimed to assess how immunonutrition could influence the immune cell response in the mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective cohort of consecutive patients undergoing esophagectomy for esophageal adenocarcinoma was enrolled. A subgroup of them was given preoperative oral immunonutrition with Oral Impact® and was compared to those who received no preoperative supplementation. Mucosal samples from healthy esophagus were obtained at esophagectomy. Histology, immunohistochemistry, gene expression analysis, and cytofluorimetry were performed. Markers of activation of antigen-presenting cells (CD80, CD86, and HLA-I), innate immunity (TLR4 and MyD88), and cytotoxic lymphocyte infiltration and activation (CD8, CD38, CD69, and CD107) were measured. In all, 50 patients received preoperative Oral Impact® and 129 patients received no nutritional support. CD80, CD86, MyD88, and CD69 messenger RNA expression was significantly increased in patients receiving immunonutrition compared to controls. In the subgroup of patients with stages I-II cancer, the rate of epithelial cells expressing CD80 and HLA-ABC was significantly higher in those receiving immunonutrition compared to controls as well as CD8+ CD28+ cell rate. Immunonutrition administration before surgery was significantly associated to increased degranulating CD8 and natural killer cells (CD107+) infiltrating the healthy esophageal mucosa. All the comparisons were adjusted for cancer stage and preoperative therapy. In conclusion, in healthy esophageal mucosa of patients undergoing esophagectomy, a 5-day course of immunonutrition enhances expression of antigen-presenting cells activity and increased CD8+ T cell activation and degranulating activity. Further studies are warranted to understand the clinical implication in terms of cancer recurrence.

Nodal skip metastasis in thoracic esophageal squamous cell carcinoma: a cohort study.

BACKGROUND: Nodal skip metastasis is a prognostic factor in some sites of malignancies, but its role in esophageal cancer is still unclear. The present study aimed to investigate occurrence and effect of nodal skip metastases in thoracic esophageal squamous cell carcinoma. METHODS: All 578 patients undergoing esophagectomy for thoracic esophageal squamous cell carcinoma at the Center for Esophageal Diseases located in Padova between January 1992 and December 2010 were retrospectively evaluated. Selection criteria were R0 resection, pathological M0 stage and pathological lymph node involvement. Patients receiving neoadjuvant therapy were excluded. RESULTS: The selection identified 88 patients with lymph node involvement confirmed by pathological evaluation. Sixteen patients (18.2%) had nodal skip metastasis. Adjusting for the number of lymph node metastases, patient with nodal skip metastasis had similar 5-year overall survival (14% vs. 13%, p = 0.93) and 5-year disease free survival (14% vs. 9%, p = 0.48) compared to patients with both peritumoral and distant lymph node metastases. The risk difference of nodal skip metastasis was: -24.1% (95% C.I. -43.1% to -5.2%) in patients with more than one lymph node metastasis compared to those with one lymph node metastasis; -2.3% (95% C.I. -29.8% to 25.2%) in middle thoracic esophagus and -23.0% (95% C.I. -47.8% to 1.8%) in lower thoracic esophagus compared to upper thoracic esophagus; 18.1% (95% C.I. 3.2% to 33.0%) in clinical N0 stage vs. clinical N+ stage. CONCLUSIONS: Nodal skip metastasis is a common pattern of metastatic lymph involvement in thoracic esophageal squamous cell carcinoma. However, neither overall survival nor disease free survival are associated with nodal skip metastasis occurrence.

Health related quality of life after oesophagectomy: elderly patients refer similar eating and swallowing difficulties than younger patients.

BACKGROUND: Oesophagectomy for cancer could be safe and worthwhile in selected older patients, but less is known about the effect of oesophagectomy on perceived quality of life of such delicate class of cancer patients. The aim of this study was to evaluate the impact of oesophagectomy for cancer in elderly patients in term of health-related quality of life. METHODS: We retrospectively evaluated all consecutive patients who underwent oesophagectomy for cancer at the Surgical Oncology Unit of the Veneto Institute of Oncology between November 2009 and March 2014. Quality of life was evaluated using EORTC C-30 and OES-18 questionnaires at admission, at discharge and 3 months after surgery. Adjusted multivariable linear mixed effect models were estimated to assess mean score differences (MDs) of selected aspects in older (≥70 years) and younger (<70 years) patients. RESULTS: Among 109 participating patients, 23 (21.1 %) were at least 70 years old and 86 (78.9 %) were younger than 70 years. Global quality of life was clinically similar between older and younger patients over time (MD 4.4). Older patients reported clinically and statistically significantly worse swallowing saliva (MD 17.4, 95 % C.I. 3.6 to 31.2), choking when swallowing (MD 13.8, 95 % C.I. 5.8 to 21.8) and eating difficulties (MD 20.1 95 % C.I. 7.4 to 32.8) than younger patients only at admission. CONCLUSIONS: Early health-related quality of life perception after surgery resulted comparable in older and younger patients. This result may also be due to some predisposition of the elderly to adapt to the new status.

Esophageal cancer management: preoperative CA19.9 and CEA serum levels may identify occult advanced adenocarcinoma.

BACKGROUND: Esophagectomy is contraindicated in case of advanced cancer (i.e., carcinomatosis, distant metastasis, and invasion of other organs). In some cases, preoperative imaging may fail to identify advanced neoplasm and esophagectomy is inappropriately planned. The aim of the study was to identify preoperative biomarkers of occult advanced disease that force surgeons to abort the planned esophagectomy. METHODS: From 2008 to 2014, 244 consecutive patients were taken to the operative room to have esophagectomy for cancer in our department. All of them had blood test at admission and their preoperative biomarker data were retrieved. Their medical history was collected and the intraoperative findings and outcome were recorded. Non parametric tests, multiple regression analysis, and ROC curves analysis were performed. RESULTS: In our study group, 14 (5.7 %) patients, scheduled for esophagectomy, were discovered to have occult advanced disease at laparotomy/laparoscopy or at thoracotomy. Six of them had peritoneal carcinomatosis, three had advanced tumor invading other organs, three had small liver metastasis, and two pleural carcinomatosis. In all these cases, esophagectomy was aborted and a feeding jejunostomy was placed. In patients with unresectable esophageal cancer, CA19.9 and CEA serum levels were significantly higher than patients who could have esophagectomy (p < 0.001 and p = 0.003, respectively). CA19.9 and CEA resulted to be accurate biomarkers of occult advanced disease (AUC = 85 %, p < 0.001 and AUC = 73 %, p = 0.002, respectively). CONCLUSIONS: Preoperative CEA and CA19.9 serum levels should be taken in consideration when evaluating patients candidate to esophagectomy for esophageal cancer to prevent inappropriate laparotomy or thoracotomy. If any doubt arises minimally invasive exploration is warranted.

Oesophageal cancer: assessment of tumour response to chemoradiotherapy with tridimensional CT.

PURPOSE: To investigate whether changes in tumour volume were predictive of histopathological response to neoadjuvant therapy for oesophageal cancer. MATERIALS AND METHODS: Thirty-five consecutive patients with locally advanced oesophageal cancer were treated with chemoradiotherapy and surgery in responders from July 2007 to July 2009. Tumour volume (TV) was calculated using innovative tumour volume estimation software which analysed computed tomography (CT) data. Tumour diameter and area were also evaluated. Variations in tumour measurements following neoadjuvant treatment were compared with the histopathological data. RESULTS: Median baseline tumour diameter, area and volume were 3.51 cm (range 1.67-6.61), 7.51 cm(2) (range 1.79-21.0) and 33.80 cm(3) (range 3.36-101.6), respectively. Differences in TV between the pre- and post-treatment values were significantly correlated with the pathological stage (τ = 0.357, p = 0.004) and the tumour regression grade index (τ = 0.368, p = 0.005). According to the receiver operating characteristic analysis, TV measurements following treatment had moderate predictive values for the pathological T stage (area under the curve, AUC = 0.742, sensitivity = 55.56 %, specificity = 92.86 %, p = 0.005).Comparison of pathological and radiological volume showed a good precision (Pearson rho 0.77). CONCLUSIONS: Changes in TV calculated on CT scans have a limited role in predicting pathological response to neoadjuvant treatment in oesophageal cancer patients. New imaging techniques based on metabolic imaging may provide better results.

Minimally invasive surgery for esophageal cancer: a review on sentinel node concept.

BACKGROUND: Lymphoadenectomy is a cornerstone of esophageal cancer treatment, and sentinel node (SN) biopsy (SNB) might provide surgeons with an extra tool to limit unnecessarily extended lymphadenectomy and to implement a minimally invasive approach. The aim of our study was to review all the available literature on the use of SNB in esophageal surgery for malignancy. METHODS: The review was conducted according to the PRISMA guidelines. A systematic search was performed in PubMed, EMBASE, and the Cochrane database to identify all original articles on the role of SNB in esophageal cancer. Data on methodologies, tumor stage and localization, and results were summarized and used to address relevant clinical questions related to the application of the SNB technique in esophageal cancer. RESULTS: Twelve studies were included, with a total of 492 patients. Different methods for SN identification were used (radionuclide, blue dye, computed tomography [CT] lymphography). The pooled values estimated using the random-effects model were, respectively: technetium-99 m overall detection rate (DR) 0.970 (95 % CI 0.814-0.996), accuracy (ACC) 0.902 (95 % CI 0.736-0.968); blue-dye DR 0.971 (95 % CI 0.890-0.993), ACC 0.790 (95 % CI 0.681-0.870); and CT lymphoscintigraphy DR 0.970 (95 % CI 0.814-0.996), ACC 0.902 (95 % CI 0.736-0.968). CONCLUSION: Based on these results, the concept of SN in esophageal cancer is technically feasible with an acceptable DR and ACC, and it might be applicable in the event of early-stage adenocarcinoma of the gastroesophageal junction in patients with a high surgical risk or in a patient where an endoscopic resection is taken into consideration. Further studies focused on a single tumor type and localizations are needed in order to predict the correct utilization of this concept in minimally invasive treatment of esophageal cancer.