Summary Gastric and oesophageal cancers are among the leading causes of cancer-related death worldwide. By contrast with the decreasing prevalence of gastric cancer, incidence and prevalence of ...oesophagogastric junction adenocarcinoma (OGJA) are rising rapidly in developed countries. We provide an update about treatment strategies for resectable OGJA. Here we review findings from the latest randomised trials and meta-analyses, and propose guidelines regarding endoscopic, surgical, and perioperative treatments. Through a team approach, members from all diagnostic and therapeutic disciplines, such as gastroenterologists, surgeons, oncologists, radiologists, and radiotherapists, can effectively administer a range of treatment modalities.
To investigate whether the number of lymph nodes metastasis (LNMs) and the ratio between metastatic and examined lymph nodes (LNs) are better prognostic factors when compared with traditional staging ...systems in patients with esophageal carcinoma.
The accuracy of the 6th UICC/TNM classification is suboptimal, especially when not taking into account neoadjuvant therapy and lymphadenectomy extent.
For 536 patients who underwent curative en bloc esophagectomy, in whom 51.5% (n = 276) received neoadjuvant chemoradiation, LNMs were classified according to the 6th UICC/TNM classification and systems based on the number (< or =4 and >4) or the ratio (< or =0.2 and >0.2) of LNMs. Survival of the respective stages, predictors of survival, and influence of both chemoradiation and number of examined LNs were studied.
After a median follow-up of 50 months, the 5-year survival rates were 47% for the entire population, significantly poorer for patients with >4 LNMs (8% vs. 53%, P < 0.001) or a ratio of LNMs >0.2 (22% vs. 54%, P < 0.001). After adjustment for confounding variables, a number of LNMs >4 and a ratio of LNMs >0.2 were the only predictors of poor prognosis. The prognostic role of both the number and the ratio of LNMs was maintained whether patients received neoadjuvant chemoradiation or not. Moreover, LN ratio is shown to be more accurate for inadequately staged patients (<15 examined LNs), whereas the number of LNMs is pertinent for adequately staged patients (> or =15 examined LNs).
Staging systems for esophageal cancer that use the number (< or =4 or >4) and the ratio (< or =0.2 or >0.2) of LNMs have greater prognostic importance than the current staging systems because of the good stratification of the groups and their clinical utility, taking into account neoadjuvant therapy and lymphadenectomy extent.
Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to ...50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma.
The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A.
Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery.
NCT00937456 (ClinicalTrials.gov).
The hypoxia inducible factor (HIF) signaling pathway is known as the main renal carcinogenetic pathway. MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear renal cell carcinomas ...(cRCC) with correlation to two major prognostic factors: tumor-node-metastasis stage and nuclear Fürhman grade. We questioned whether there is a direct link between the HIF pathway and MUC1 overexpression in renal tumors. Interestingly, we observed concomitant increase of HIF-1alpha and MUC1 in metastatic cRCC group versus nonmetastatic cRCC group. Using different renal cell models and small interfering RNA assays targeting either HIF-1alpha or YC-1, a HIF-1 pharmacologic inhibitor, we showed induction of MUC1 expression under hypoxia by a HIF-dependent mechanism. Chromatin immunoprecipitation assay showed a direct binding of HIF-1alpha at the MUC1 promoter. In addition, combined site-directed mutagenesis and gel shift assay allowed the identification of two functional putative hypoxia responsive elements at -1488/-1485 and at -1510/-1507 in the promoter. Using a rat kidney model of ischemia/reperfusion, we confirmed in vivo that clamping renal pedicle for 1 hour followed by 2 hours of reperfusion induced increased MUC1 expression. Furthermore, MUC1 knockdown induced significant reduction of invasive and migration properties of renal cancer cells under hypoxia. Altogether, these results show that MUC1 is directly regulated by HIF-1alpha and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC.
Background The mechanisms of esophageal reflux leading to esophageal adenocarcinoma (EA) remain poorly understood. This study appraises critically an operatively induced chronic reflux rat model. ...Methods We randomized 108 Sprague-Dawley rats into 2 experimental groups; one was performing esophagoduodenal (ED) anastomosis with or without gastrectomy to induce duodeno-esophageal reflux (DER group; n = 63), and the other involved duodeno-gastro-esophageal reflux (DGER group; n = 45). Control groups included (i) Roux-en-Y esophagojejunal anastomosis, (ii) laparotomy alone, (iii) subtotal gastrectomy to induce duodenogastric reflux (DGR group), and (iv) the same procedure as in the DGER group plus proton pump inhibition (PPI group). The esophagus underwent histologic and molecular analyses. Results The prevalence of Barrett's esophagus (BE), dysplasia, and EA in the experimental groups was 41%, 7%, and 11%, respectively. Histologic and molecular analyses in groups DER, DGER, and DGR suggested that BE occurred through de novo intestinal metaplasia and proximal migration of duodenal cells. No distant metastases were identified. The molecular characteristics of both BE and EA were similar to humans. BE was more common, and dysplasia and EA less frequent in the DER group when compared with the DGER group (44% vs 24% P = .038 and 7% vs 25% P = .012, respectively). Compared with the DGER group, carcinogenic sequence occurred less frequently in the PPI-treated group ( P = .019). Conclusion Despite pathophysiologic differences with humans, the rat model of esophagoduodenostomy reproduces accurately histologic and molecular lesions in the carcinogenetic sequence of BE and allowed us to identify novel, tumor-associated proteins that may be potential biomarkers and new therapeutic targets in EA.
To compare the outcomes of a strategy of surveillance versus surgical resection in patients with esophageal cancer (EC) experiencing complete clinical response (cCR) after chemoradiation (CRT).
In ...EC, it remains unclear whether a strategy of surveillance or esophagectomy is appropriate after cCR to CRT.
From 1995 to 2009, 222 operable patients had a cCR based on the results of a computed tomographic scan, endoscopy with biopsies and, when performed, a positron emission tomographic scan. Through an intention-to-treat case-control study, 59 patients treated with CRT and surveillance (group Surv) were matched 1:2 with 118 patients treated by CRT followed by surgery (group Surg), according to age, gender, tumor location and stage, histology, American Society of Anesthesiologists score, and nutritional status.
The 2 groups were comparable according to the matched variables (P > 0.276). In group Surg, the postoperative mortality rate was 4.2% with evidence of residual tumor in 34.6% of specimens. In group Surv, 2 salvage esophagectomies were performed. Despite the higher dose of radiotherapy received in group Surv (50 vs 45 Gys, P = 0.003), median survival was lower (31 vs 83 months, P = 0.001), with disease recurrence that was more frequent (50.8% vs 32.7%, P = 0.021), occurred earlier (7.8 vs 19.0 months, P = 0.002) and more often locoregional (46.7% vs 16.2%, P = 0.007) in nature. Surgical resection was independently associated with less recurrence odds ratio = 0.4, 95% confidence interval (CI): 0.2-0.8, P = 0.006 and better survival (hazard ratio = 0.5, 95% CI: 0.3-0.8, P = 0.006).
Survival of EC patients with a cCR after CRT is better after surgery compared to simply surveillance. In patients of low operative risk and operable disease, surgery should be considered to improve control of locoregional disease and to overcome the inherent limitations of clinical response assessment.
To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection.
Conflicting data have emerged from ...randomized studies regarding the impact of NCRT on AL.
Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n=593) were compared with those treated by primary surgery (n=1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics.
Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P=0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P=0.110) and 33.4% versus 32.1% (P=0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P=0.291), whereas chylothorax (2.5% vs 1.2%; P=0.020), cardiovascular complications (8.6% vs 0.1%; P=0.037), and thromboembolic events (8.6% vs 6.0%; P=0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P=0.228), with more chylothorax (2.5% vs 0.7%; P=0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P=0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT.
Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).
Background
Percutaneous endoscopic gastrostomy is not widely used in malnourished esophageal cancer (EC) patients because of concerns about its feasibility in frequently obstructive tumors, ...suitability of the stomach as an esophageal substitute, and potential for metastatic inoculation. A percutaneous radiological gastrostomy (PRG) could be an optimal alternative.
Methods
Experience with PRG among 1,205 consecutive patients presenting with EC from 2002 to 2011 in our department was retrospectively reviewed. PRG was mostly utilized for malnourished patients for whom neoadjuvant chemoradiation was scheduled. The rates of both successful placement and major related complications (Dindo-Clavien ≥III) were analyzed. A matched cohort analysis was constructed in patients who underwent esophagectomy with gastroplasty (
n
= 688) to evaluate the impact of PRG placement on the suitability of the gastric conduit and on postoperative course. For 78 resected patients with PRG (PRG group), 156 randomly selected controls without PRG (no PRG group) were matched 2:1 for gender, age, ASA grade, clinical TNM stage, and neoadjuvant treatment delivery.
Results
PRG placement was planned in 269 (22.3 %) patients mainly with locally advanced EC (63.8 %). PRG placement was feasible in 259 (96.3 %) patients. Sixty-day PRG-related mortality and major morbidity rates were 0 and 3.8 % respectively. For resected patients, the PRG and no PRG groups were comparable regarding perioperative characteristics, except for malnutrition, which was more frequent in the PRG group (
P
< 0.001). At the time of operation, PRG takedown and site closure were uncomplicated and the use of the stomach was possible in all 78 patients. Despite a higher malnutrition rate at presentation in the PRG group, rates of overall morbidity, and morbidity related to esophageal surgery, were similar between the two groups (
P
> 0.258).
Conclusion
PRG is feasible, safe, and useful in nonselected patients with EC and does not compromise the suitability of the stomach as an esophageal substitute in patients deemed to be resectable.
Abstract Background The objectives of this study were to compare peri-operative and long-term outcomes from oesophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary ...(PEC) and among ECRF patients and (ii) radiotherapy-induced (RIEC) versus non-radiotherapy–induced EC (NRIEC). Methods Data were collected from 30 European centres from 2000 to 2010. Two thousand four hundred eighty nine EC patients surgically treated were included in the PEC group and 136 in the ECRF group, NRIEC group (n = 61) and RIEC group (n = 75). Propensity score matching analyses were used to compensate for differences in baseline characteristics. Results Compared to the PEC group, the ECRF group was characterised by less use of neoadjuvant chemoradiotherapy (0% versus 29.5%; P < 0.001), less pathological stage III/IV (31.6% versus 39.2%, P = 0.036), greater incidence of R1/2 margins (21.3% versus 10.9%; P < 0.001), increased in-hospital mortality (14.0% versus 7.1%; P = 0.003) and overall morbidity (68.4% versus 56.4%, P = 0.006). After matching, 5-year overall (28.8% versus 50.5%; hazard ratio HR = 1.53, 95% confidence interval CI: 1.15–2.04; P = 0.003) and event-free (32.2% versus 42.5%; HR = 1.56, 95% CI: 1.18–2.05; P = 0.002) survivals were significantly reduced in the ECRF group. There were no significant differences in incidence or pattern of tumour recurrence. Comparing RIEC and NRIEC groups, there were no significant differences in short- or long-term outcomes before and after matching. Conclusions ECRF is associated with poorer long-term survival related to a reduced utilisation of neoadjuvant chemoradiotherapy and an increased incidence of tumour margin involvement at surgery. Outcomes appear to be dictated by the limitations related to previous radiotherapy administration more than the radiotherapy-induced carcinogenesis.
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