[Show abstract][Hide abstract] ABSTRACT: Aims:
The aims of this study were to compare short- and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.
Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short- and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.
No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short- or long-term outcomes.
The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
Full-text · Article · Mar 2016 · European journal of cancer (Oxford, England: 1990)
[Show abstract][Hide abstract] ABSTRACT: Purpose
Patient and technical factors influencing the postoperative infectious complications (ICs) after elective colorectal resections are satisfactorily described. However, the underlying disease-related factors have not been extensively evaluated. This study aimed to measure the effect of malignancy on postoperative surgical site and extra surgical site infections after elective colorectal resection.
This study is a bicentric retrospective matched pair study of prospectively gathered data. Between 2004 and 2013, 1104 consecutive patients underwent colorectal resection in two centers. Patients undergoing elective resection with supraperitoneal anastomosis for benign diseases (excluding inflammatory bowel disease) (group B, n = 305) were matched to randomly selected patients with malignancy (group M, n = 305). The matching variables were age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, type of resection, and surgical approach. We compared the 30-day IC rates between patients with benign diseases (group B) and malignancy (group M). Multivariate logistic regression analysis was performed to identify the risk factors for ICs.
Group M had a higher overall rate of IC (25.6 vs 16.1 %, P = 0.004) as well as a higher risk of extra surgical site infections (P = 0.007) and anastomotic leakage (P = 0.039). The independent risk factors for ICs were malignancy (odds ratio (OR) = 2.02; P = 0.002), age ≥70 years (OR = 1.73, P = 0.018), tobacco history (OR = 1.87; P = 0.030), and obesity (OR = 1.68; P = 0.039).
Malignancy, age, tobacco history, and obesity increase the risk of ICs after colorectal resection. Improvement of the modifiable risk factors, increased compliance with an enhanced recovery after surgery (ERAS) program in the overall population, and optimization of immune function in patients with malignancy should be considered.
No preview · Article · Feb 2016 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Objective:
This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy.
A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients.
Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC.
We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.
[Show abstract][Hide abstract] ABSTRACT: Background
The prognosis and chemoresistance of signet-ring cell (SRC) gastric adenocarcinoma have been reported and debated, and the utility of perioperative chemotherapy for such a tumor has been questioned
. This study was performed to assess the impact of the SRC type on survival following resection of gastric adenocarcinoma, and to assess whether the prognostic factors (including perioperative chemotherapy) for non-SRC adenocarcinoma differed from those for SRC adenocarcinoma.
1799 cases of adenocarcinoma that were consecutively treated from 1997 to 2010 in 19 French centers by subtotal or total gastrectomy were included in a retrospective study. A D2 lymphadenectomy was performed for antropyloric tumors, and a modified D2 for upper tumors. SRC adenocarcinoma was diagnosed based on the presence of isolated carcinoma cells containing mucin.
A total gastrectomy was performed in 979 (54.4 %) patients. SRC adenocarcinoma was diagnosed in 899 (50 %) patients. Patients with an SRC tumor were more frequently female, younger, and malnourished, had lower ASA scores, and had larger tumors than non-SRC patients. Median survival in patients with non-SRC carcinoma was 51 months, as compared to 26 months in patients with SRC carcinoma (p < 0.001). At multivariate analysis, SRC type remained an independent adverse prognostic factor (HR = 1.182). Factors that were prognostic in the SRC subgroup but not in the non-SRC subgroup were age >60 years, linitis, and involvement of adjacent organs. In contrast to non-SRC tumors, pre- and postoperative chemotherapy did not significantly impact on survival following resection of SRC adenocarcinoma.
In comparison to non-SRC adenocarcinoma, the SRC type has a worse prognosis, different prognostic factors, and is only poorly sensitive to perioperative chemotherapy. Non-SRC and SRC adenocarcinomas should be considered different entities in future therapeutic trials.
[Show abstract][Hide abstract] ABSTRACT: Objective:
This study was designed to investigate the impact of laparoscopic gastric mobilization (LGM) on 30-day postoperative mortality (POM) after surgery for esophageal cancer (EC).
Meta-analyses of nonrandomized studies have failed to demonstrate any significant benefit of hybrid minimally invasive esophagectomy on POM, potentially due to small population samples. Moreover, none of the published randomized trials have been designed to answer this question.
All consecutive patients who underwent EC resection between 2010 and 2012 in France were included in this nationwide study (n = 3009). Data were extracted from the French National Health Service Database with internal and external quality controls. Patients treated with LGM (LGM group, n = 663) were compared with those treated with open approach (open group, n = 2346). Propensity score matching and multivariable analyses were used to compensate for the differences in baseline characteristics.
The 30-day POM rate was 5.2%, significantly lower after LGM, compared with open surgery (3.3% vs 5.7%, P = 0.005), as well as in-hospital (5.6% vs 8.1%, P = 0.028), and 90-day POM (6.9% vs 10.0%, P = 0.016). After propensity score matching, 30-day POM rates were 3.3% versus 5.9%, respectively (P = 0.029). By multivariable analysis, age ≥60 years, malnutrition and cardiovascular comorbidity were independently associated with higher POM, whereas LGM was associated with a decrease in POM (OR 0.60, 95% CI 0.37-0.98, P = 0.041).
This all-inclusive nationwide study strongly suggests that POM is significantly reduced after LGM for EC. This is high valuable evidence that helps decision making regarding the optimal approach for EC surgery.
No preview · Article · Nov 2015 · Annals of Surgery
[Show abstract][Hide abstract] ABSTRACT: Objectives: The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). Background: The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown. Methods: Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. Results: In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively). Conclusions: Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.
No preview · Article · Nov 2015 · Annals of Surgery
[Show abstract][Hide abstract] ABSTRACT: Background:
Patterns of disease recurrence in patients with oesophageal cancer following treatment with neoadjuvant chemoradiotherapy and surgery (nCRTS) or surgery alone are poorly reported. An understanding of patterns of disease recurrence is important for subsequent treatment planning.
An analysis was undertaken of patterns of disease recurrence from a phase III multicentre randomized trial (FFCD9901) comparing nCRTS with surgery alone in patients with stage I and II oesophageal cancer.
Some 170 patients undergoing surgical resection were included in the study. R0 resection rates were similar in the two groups: 94 per cent following nCRTS versus 92 per cent after surgery alone (P = 0·749). After a median follow-up of 94·2 months, recurrent disease was found in 39·4 per cent of the overall cohort (31 per cent after nCRTS versus 47 per cent following surgery alone; P = 0·030). Locoregional recurrence was diagnosed in 41 patients (17 versus 30 per cent respectively; P = 0·047) and distant metastatic recurrence in 47 (23 versus 31 per cent respectively; P = 0·244). Metastatic recurrence was more frequent in patients with adenocarcinoma than in those with squamous cell cancer (40 versus 23·1 per cent respectively; P = 0·032). ypT0 N0 category was associated with prolonged time to mixed locoregional and metastatic recurrence (P = 0·009), and time to locoregional (P = 0·044) and metastatic (P = 0·055) recurrence. In multivariable analysis, node-positive disease predicted both locoregional (P = 0·001) and metastatic (P < 0·001) recurrence.
Locoregional disease control following nCRTS indicated a local field effect not related solely to completeness of resection. pN+ disease was strongly predictive of time to locoregional and metastatic disease recurrence.
No preview · Article · Oct 2015 · British Journal of Surgery
[Show abstract][Hide abstract] ABSTRACT: Prophylactic drainage of the abdominal cavity after gastro-intestinal surgery is widely used. The rationale is that intra-abdominal drainage enhances early detection of complications (gastro-intestinal leakage, hemorrhage, bile leak), prevents collection of fluid or pus, reduces morbidity and mortality, and decreases the duration of hospital stay. However, dogmatic attitudes favoring systematic drain placement should be questioned. The aim of this review was to evaluate the evidence supporting systematic use of prophylactic abdominal drainage following gastrectomy, pancreatectomy, liver resection, and rectal resection. Based on this review of the literature: (i) there was no evidence in favor of intra-peritoneal drainage following total or sub-total gastrectomy with respect to morbidity-mortality, nor was it helpful in the diagnosis or management of leakage, however the level of evidence is low, (ii) following pancreatic resection, data are conflicting but, overall, suggest that the absence of drainage is prejudicial, and support the notion that short-term drainage is better than long-term drainage, (iii) after liver resection without hepatico-intestinal anastomosis, high level evidence supports that there is no need for abdominal drainage, and (iv) following rectal resection, data are insufficient to establish recommendations. However, results from the French multicenter randomized controlled trial GRECCAR5 (NCT01269567) should provide new evidence this coming year. Accumulating data support that systematic drainage of the abdominal cavity in digestive surgery is a non-beneficial and obsolete practice, except following pancreatectomy where the consensus appears to indicate the usefulness of short-term drainage. While the level of evidence is high for liver resections, new randomized controlled trials are awaited regarding gastric, pancreatic and rectal surgery.
Preview · Article · Oct 2015 · Journal of Visceral Surgery
[Show abstract][Hide abstract] ABSTRACT: Objective: The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence. Background: The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results. Methods: A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000-2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence. Results: From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04-1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15-1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05-2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20-2.71; P = 0.014) recurrences. Conclusions: This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.
No preview · Article · Oct 2015 · Annals of Surgery
[Show abstract][Hide abstract] ABSTRACT: The serrated neoplasia pathway accounts for 20 to 30% of colorectal cancers (CRC), which are characterised by extensive methylation (CpG Island Methylation Phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps (42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA), 8 traditional serrated adenoma (TSA)) and 112 conventional adenomas was analysed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA, and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognised among HP and require particular attention. This article is protected by copyright. All rights reserved.
No preview · Article · Oct 2015 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Introduction: EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe. Methods: Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included. Results: United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%. Conclusion: This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.