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.

Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive esophagectomy results in lower morbidity than open esophagectomy is unclear. METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients 18 to 75 years of age with resectable cancer of the middle or lower third of the esophagus. Patients were randomly assigned to undergo transthoracic open esophagectomy (open procedure) or hybrid minimally invasive esophagectomy (hybrid procedure). Surgical quality assurance was implemented by the credentialing of surgeons, standardization of technique, and monitoring of performance. Hybrid surgery comprised a two-field abdominal-thoracic operation (also called an Ivor-Lewis procedure) with laparoscopic gastric mobilization and open right thoracotomy. The primary end point was intraoperative or postoperative complication of grade II or higher according to the Clavien-Dindo classification (indicating major complication leading to intervention) within 30 days. Analyses were done according to the intention-to-treat principle. RESULTS: From October 2009 through April 2012, we randomly assigned 103 patients to the hybrid-procedure group and 104 to the open-procedure group. A total of 312 serious adverse events were recorded in 110 patients. A total of 37 patients (36%) in the hybrid-procedure group had a major intraoperative or postoperative complication, as compared with 67 (64%) in the open-procedure group (odds ratio, 0.31; 95% confidence interval [CI], 0.18 to 0.55; P<0.001). A total of 18 of 102 patients (18%) in the hybrid-procedure group had a major pulmonary complication, as compared with 31 of 103 (30%) in the open-procedure group. At 3 years, overall survival was 67% (95% CI, 57 to 75) in the hybrid-procedure group, as compared with 55% (95% CI, 45 to 64) in the open-procedure group; disease-free survival was 57% (95% CI, 47 to 66) and 48% (95% CI, 38 to 57), respectively. CONCLUSIONS: We found that hybrid minimally invasive esophagectomy resulted in a lower incidence of intraoperative and postoperative major complications, specifically pulmonary complications, than open esophagectomy, without compromising overall and disease-free survival over a period of 3 years. (Funded by the French National Cancer Institute; ClinicalTrials.gov number, NCT00937456 .).

Associations between the severity of medical and surgical complications and perception of surgeon empathy in esophageal and gastric cancer patients.

OBJECTIVE: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients. METHODS: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses. RESULTS: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications. CONCLUSIONS: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.

Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial: The MIRO Trial.

BACKGROUND: Hybrid minimally invasive esophagectomy (HMIE) has been shown to reduce major postoperative complications compared with open esophagectomy (OE) for esophageal cancer. OBJECTIVES: The aim of this study was to compare short- and long-term health-related quality of life (HRQOL) following HMIE and OE within a randomized controlled trial. METHODS: We performed a multicenter, open-label, randomized controlled trial at 13 study centers between 2009 and 2012. Patients aged 18 to 75 years with resectable cancers of the middle or lower third of the esophagus were randomized to undergo either transthoracic OE or HMIE. Patients were followed-up every 6 months for 3 years postoperatively and global health assessed with EORTC-QLQC30 and esophageal symptoms assessed with EORTC-OES18. RESULTS: The short-term reduction in global HRQOL at 30 days specifically role functioning [-33.33 (HMIE) vs -46.3 (OE); P = 0.0407] and social functioning [-16.88 (HMIE) vs -35.74 (OE); P = 0.0003] was less substantial in the HMIE group. At 2 years, social functioning had improved following HMIE to beyond baseline (+5.37) but remained reduced in the OE group (-8.33) (P = 0.0303). At 2 years, increases in pain were similarly reduced in the HMIE compared with the OE group [+6.94 (HMIE) vs +14.05 (OE); P = 0.018]. Postoperative complications in multivariate analysis were associated with role functioning, pain, and dysphagia. CONCLUSIONS: Esophagectomy has substantial effects upon short-term HRQOL. These effects for some specific parameters are, however, reduced with HMIE, with persistent differences up to 2 years, and maybe mediated by a reduction in postoperative complications.

NORAD01-GRECCAR16 multicenter phase III non-inferiority randomized trial comparing preoperative modified FOLFIRINOX without irradiation to radiochemotherapy for resectable locally advanced rectal cancer (intergroup FRENCH-GRECCAR- PRODIGE trial).

BACKGROUND: Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT. METHODS: This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574. DISCUSSION: The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.

Benchmarking Complications Associated with Esophagectomy.

OBJECTIVE: Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy. SUMMARY OF BACKGROUND DATA: Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects. METHODS: The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period. RESULTS: Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively. CONCLUSION: Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

The role of trait emotional intelligence in quality of life, anxiety and depression symptoms after surgery for esophageal or gastric cancer: A French national database FREGAT.

OBJECTIVE: The main objective was to test the indirect effects of emotional competence (EC) after diagnosis (T1) on the health-related quality of life (HRQoL) after surgery (T2) of esogastric cancer patients via fewer anxiety and depression symptoms (T2). METHODS: Data were collected from 30 French centers via the clinicobiological database French EsoGastric Tumors (FREGAT). Two hundred and twenty-eight participants completed a self-reported questionnaire at T1 and T2, assessing their EC (Profile of Emotional Competence (PEC)), HRQoL (EORTC Quality of Life Questionnaire-Core (QLQ-C30)), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale (HADS)). Regression analyses were used to test the direct effects of intrapersonal and interpersonal EC on their anxiety/depression symptoms and HRQoL at T1 and T2. The PROCESS Macro in SPPS v.22 with bootstrap methods was used to test the indirect effects of intrapersonal and interpersonal EC at T1 on HRQoL at T2 via anxiety and depression symptoms. RESULTS: EC predicted fewer anxiety and depression symptoms of patients at T1 and T2 and better HRQoL at T1. EC at T1 also predicted a better HRQoL at T2 via fewer anxiety and depression symptoms at T2. CONCLUSIONS: Patients who tended to use their EC in daily life could be more effective in regulating the emotional impact of the cancer diagnosis and surgery. This explains why they reported fewer anxiety and depression symptoms, which in turn enabled a better perceived HRQoL after surgery. Therefore, reinforcing the use of patients' EC in daily life following their diagnosis could decrease their emotional distress and, in this way, improve their HRQoL in the preoperative and postoperative stages.

International consensus on a complications list after gastrectomy for cancer.

BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Psychometric validation of the French version of the Supportive Care Needs Survey for Partners and Caregivers of cancer patients.

The objective of this study was to assess the psychometric properties of the French version of the Supportive Care Needs Survey for Partners and Caregivers (SCNS-P&C-F). The SCNS-P&C-F, the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology Quality of Life questionnaire (CarGOQoL) were completed by 327 caregivers at the baseline. The SCNS-P&C-F was completed a second time by 121 participants within 30 days. Four factors were retained with a good explanation of variance (82.65%) and acceptable internal consistencies (α: 0.70 to 0.94): 1) Health Care Service and Information Needs, 2) Emotional and Psychological Needs, 3) Work and Social Security Needs and 4) Communication and Family Support Needs. Overall, convergent and divergent validities were confirmed. The caregiver's gender, age, professional status and level of anxiety and depression, as well as the type of relationship with the patient and cancer, showed an effect on some caregivers' unmet supportive care needs. Lastly, the test-retest reliability was acceptable (> 0.70), except for the communication and family support dimension. The scale is appropriate for clinical and research use (e.g. good reliability and validity).

Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.

OBJECTIVES: The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. BACKGROUND: Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. METHODS: From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. RESULTS: In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. CONCLUSIONS: Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.

Fukuoka-Negative Branch-Duct IPMNs: When to Worry? A Study from the French Surgical Association (AFC).

BACKGROUND: This study analyzed the pathologic findings for patients with Fukuoka-negative branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) who theoretically were eligible for surveillance care with follow-up assessment, but instead underwent resection. METHODS: From January 2005 to December 2012, 820 patients underwent evaluation for IPMN. At initial staging, 319 patients had BD-IPMN, and 89 of these patients presented with Fukuoka-negative criteria. These 89 patients were included in this study. RESULTS: Of the 89 patients, 55 (62%) underwent pancreatectomy. After pathologic examination, the ultimate diagnosis was MT-IPMN for 20 (36%) of these patients (the MT group) and BD-IPMN for 35 (64%) of these patients (the BD group). The remaining 34 patients (38%) underwent enucleation. The patients in the MT group were more likely to be male (P = 0.01) and to have a higher rate of recent (< 1 year) diabetes mellitus diagnosis (P = 0.007) than the patients in the BD group. In the multivariate analysis, diabetes mellitus was independently associated with involvement of the main pancreatic duct (P = 0.05). Malignancy was diagnosed for 14 (16%) of the 89 patients. The rate of invasive IPMN was higher in the MT group than in the BD group (20% vs. 0%, P = 0.02). The 5-year overall survival rate was 100% for the BD group and 84% for the MT group (P = 0.02). For the male patients with diabetes mellitus, the rate of malignancy rose to 67%. CONCLUSIONS: For patients with a diagnosis of Fukuoka-negative BD-IPMN, resection should be considered primarily for male patients with a recent diabetes mellitus diagnosis.

Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

BACKGROUND: Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care. STUDY DESIGN: We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS). RESULTS: The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis. CONCLUSIONS: SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium.

The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers.

BACKGROUND: While the incidence of esophageal and gastric cancers is increasing, the prognosis of these cancers remains bleak. Endoscopy and surgery are the standard treatments for localized tumors, but multimodal treatments, associated chemotherapy, targeted therapies, immunotherapy, radiotherapy, and surgery are needed for the vast majority of patients who present with locally advanced or metastatic disease at diagnosis. Although survival has improved, most patients still present with advanced disease at diagnosis. In addition, most patients exhibit a poor or incomplete response to treatment, experience early recurrence and have an impaired quality of life. Compared with several other cancers, the therapeutic approach is not personalized, and research is much less developed. It is, therefore, urgent to hasten the development of research protocols, and consequently, develop a large, ambitious and innovative tool through which future scientific questions may be answered. This research must be patient-related so that rapid feedback to the bedside is achieved and should aim to identify clinical-, biological- and tumor-related factors that are associated with treatment resistance. Finally, this research should also seek to explain epidemiological and social facets of disease behavior. METHODS: The prospective FREGAT database, established by the French National Cancer Institute, is focused on adult patients with carcinomas of the esophagus and stomach and on whatever might be the tumor stage or therapeutic strategy. The database includes epidemiological, clinical, and tumor characteristics data as well as follow-up, human and social sciences quality of life data, along with a tumor and serum bank. DISCUSSION: This innovative method of research will allow for the banking of millions of data for the development of excellent basic, translational and clinical research programs for esophageal and gastric cancer. This will ultimately improve general knowledge of these diseases, therapeutic strategies and patient survival. This database was initially developed in France on a nationwide basis, but currently, the database is available for worldwide contributions with respect to the input of patient data or the request for data for scientific projects. TRIAL REGISTRATION: The FREGAT database has a dedicated website ( www.fregat-database.org ) and is registered on the Clinicaltrials.gov site, number NCT 02526095 , since August 8, 2015.

Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: implication of the Wnt/ß-catenin pathway.

Secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of ß-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/ß-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis.

Are Thoracotomy and/or Intrathoracic Anastomosis Still Predictors of Postoperative Mortality After Esophageal Cancer Surgery?: A Nationwide Study.

BACKGROUND: Intrathoracic (vs cervical) anastomosis and a thoracotomy (vs absence) have previously been associated with increasing postoperative mortality (POM). Recent improvements in surgical practices and perioperative management may have changed these dogmas. OBJECTIVES: The aim of this study was to evaluate the impact of performing intrathoracic anastomosis and/or thoracotomy on POM after esophageal cancer surgery in recent years. METHODS: All consecutive patients who underwent esophageal cancer surgery with reconstruction between 2010 and 2012 in France were included (n = 3286). Patients with a thoracoscopic approach were excluded (n = 4). We compared 30-day POM between patients having received intrathoracic (vs cervical) anastomosis and between those having received a thoracotomy or not. Multivariate analyses and propensity score matching were used to adjust for confounding factors. RESULTS: Patients had either cervical (n = 548) or intrathoracic (n = 2738) anastomosis. Thirty-day POM was higher after cervical anastomosis (8.8% vs 4.9%, P < 0.001). Having received a thoracotomy (n = 3061) was associated with a decreased risk of 30-day POM (5.3% vs 9.3%, P = 0.011). After adjustment for confounding factors, cervical anastomosis was associated with 30-day POM [odds ratio (OR) 1.71; 95% confidence interval (CI) 1.05-2.77); P = 0.032], whereas performing a thoracotomy was not associated with 30-day POM (OR 0.97; 95% CI 0.51-1.84; P = 0.926). CONCLUSIONS: Nowadays, intrathoracic anastomosis provides a lower 30-day POM rate compared to cervical anastomosis, and performing a thoracotomy is not associated with POM. Systematic anastomosis neck placement or thoracotomy avoidance is not a relevant argument anymore to decrease POM.

Survival Benefit of Neoadjuvant Treatment in Clinical T3N0M0 Esophageal Cancer: Results From a Retrospective Multicenter European Study.

BACKGROUND: Based on current guidelines, clinical T3N0M0 esophageal tumors may or may not receive neoadjuvant treatment, according to their perception as locally advanced (cT3) or early-stage tumors (stage II). The study aim was to assess the impact of neoadjuvant treatment upon survival for cT3N0M0 esophageal cancer patients, with subgroup analyses by histological type (squamous cell carcinoma vs adenocarcinoma) and type of neoadjuvant treatment (chemotherapy vs radiochemotherapy). METHODS: Data from patients operated on for esophageal cancer in 30 European centers were collected. Among the 382 of 2944 patients with clinical T3N0M0 stage at initial diagnosis (13.0%), we compared those treated with primary surgery (S, n = 193) versus with neoadjuvant treatment plus surgery (NS, n = 189). RESULTS: The S and NS groups were similar regarding their demographic and surgical characteristics. In-hospital postoperative morbidity and mortality rates were comparable between groups. Patients were found to be pN+ in 64.2% versus 42.9% in the S and NS groups respectively (P < 0.001), pN2/N3 in 35.2% versus 21.2% (P < 0.001), stage 0 in 0% versus 16.4% (P < 0.001), and R0 in 81.3% versus 89.4% of cases (P = 0.026). Median overall and disease-free survivals were significantly better in the NS group, 38.4 versus 27.9 months (P = 0.007) and 31.6 versus 27.5 months (P = 0.040), respectively, and this difference remained for both histological types. Radiotherapy did not offer a benefit compared with chemotherapy alone (P = 0.687). In multivariable analysis, neoadjuvant treatment was an independent favorable prognostic factor (HR 0.76, 95% CI 0.58-0.99, P = 0.044). CONCLUSION: Neoadjuvant treatment offers a significant survival benefit for clinical T3N0M0 esophageal cancer.

To Drain or Not to Drain Infraperitoneal Anastomosis After Rectal Excision for Cancer: The GRECCAR 5 Randomized Trial.

OBJECTIVE: To assess the effect of pelvic drainage after rectal surgery for cancer. BACKGROUND: Pelvic sepsis is one of the major complications after rectal excision for rectal cancer. Although many studies have confirmed infectiveness of drainage after colectomy, there is still a controversy after rectal surgery. METHODS: This multicenter randomized trial with 2 parallel arms (drain vs no drain) was performed between 2011 and 2014. Primary endpoint was postoperative pelvic sepsis within 30 postoperative days, including anastomotic leakage, pelvic abscess, and peritonitis. Secondary endpoints were overall morbidity and mortality, rate of reoperation, length of hospital stay, and rate of stoma closure at 6 months. RESULTS: A total of 494 patients were randomized, 25 did not meet the criteria and 469 were analyzed: 236 with drain and 233 without. The anastomotic height was 3.5 ±â€Š1.9 cm from the anal verge. The rate of pelvic sepsis was 17.1% (80/469) and was similar between drain and no drain: 16.1% versus 18.0% (P = 0.58). There was no difference of surgical morbidity (18.7% vs 25.3%; P = 0.83), rate of reoperation (16.6% vs 21.0%; P = 0.22), length of hospital stay (12.2 vs 12.2; P = 0.99) and rate of stoma closure (80.1% vs 77.3%; P = 0.53) between groups. Absence of colonic pouch was the only independent factor of pelvic sepsis (odds ratio = 1.757; 95% confidence interval 1.078-2.864; P = 0.024). CONCLUSIONS: This randomized trial suggests that the use of a pelvic drain after rectal excision for rectal cancer did not confer any benefit to the patient.

Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy.

BACKGROUND: The impact of discrepancies between clinical (c) and pathologic (p) stages of esophageal cancer remains a poorly understood issue. This study aimed to compare the prognosis of patient groups treated by primary surgery including clinical N0/pathologic N0 (cN0pN0), clinical N0/pathologic N+ (cN0pN+), clinical N+/pathologic N0 (cN+pN0), and clinical N+/pathologic N+ (cN+pN+). METHODS: Data were collected from 30 European centers during the years 2000 to 2010. Among 2944 recruited patients, 1554 patients receiving primary surgery met the inclusion criteria including 613 cN0pN0, 403 cN0pN+, 220 cN+pN0, and 318 cN+pN+ patients. Analyses with adjustment of the propensity score were used to compensate for differences in baseline characteristics. RESULTS: Clinical T stages 3 and 4 were increased in cN+pN+ (73.0%), cN0pN+ (49.6%), and cN+pN0 (51.8%) compared with cN0pN0 (32.8%). Compared with cN0pN0, cN+pN+ and cN0pN+ showed an increase in the proportion of adenocarcinoma histologic subtype, poor tumor differentiation, pathologic T3 and T4 stages, and R1/2 resection margin. Adjusted 5-year overall survival (hazard ratio [HR] 3.12; 95% confidence interval [CI] 2.57-3.78; P < 0.001) and event-free survival (HR 2.87; 95% CI 2.39-3.45; P < 0.001) were significantly reduced in cN0pN+ compared with cN0pN0. No significant differences in 5-year overall survival or event-free survival between cN0pN+ and cN+pN+ were observed. Regression analysis identified an association of distal tumor location, advanced clinical T stage, and poor tumor differentiation with pN+ disease. CONCLUSIONS: This large multicenter study showed that cN0pN+ has a prognosis similar to that of cN+pN+ and worse than that of cN0pN0. Patients with clinical N0 disease but risk factors for pathologic N+ disease may benefit from neoadjuvant therapy before surgery.

[FREGAT: French clinico-biological database dedicated to esogastric cancers]. / FREGAT : base clinicobiologique nationale française dédiée à la recherche sur les cancers œsogastriques.

Even though esogastric cancers are estimated at 1.5 million new cases worldwide with an expected 2.11 million new cases by 2025, prognosis remains poor and research is unsatisfactory compared to other cancers. There is an urgent need to intensify research via innovative and ambitious programs to improve patient's survival and quality of life. Incidence of esogastric cancers is particularly high in France, and the creation of a national clinicobiological database prospectively collecting epidemiological, human and social, clinical, pathological, biological data, sustained by biobanks of blood and tissues, is a critical point to improve research and care for these cancers considering all determinants of the disease with a more integrated approach. FREGAT clinicobiological database, funded and labeled by the French NCI in 2012, gathers the vast majority of university hospitals and cancer centers in France. This research relies on preexisting networks ensuring its efficacy and quality. Beyond significant increase of inclusions opened since January 2015, the establishment of public multiprivate industrial partnerships and creation of numerous French and European scientific projects, make FREGAT a decisive tool for research on esogastric cancers.