Prognostic role of early 18-FDG PET/CT during neoadjuvant chemotherapy for resectable adenocarcinoma of the esophagus and esophagogastric junction.

We prospectively investigated whether metabolic response assessed by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) early in the course of neoadjuvant chemotherapy is predictive of survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. PET/CT was performed before and in the third week after the initiation of the first cycle of neoadjuvant chemotherapy, which consisted of epirubicin, cisplatin, and 5-fluorouracil or capecitabine. The metabolic response was defined as a relative decrease in the peak standardized uptake value (SUL) of the tumor by ≥35% or total lesion glycolysis (TLG) by ≥66%. The associations of metabolic response with overall survival (OS) and disease-free survival (DFS) were investigated using Kaplan-Meier curves and multivariable Cox regression analysis. Among 126 recruited patients, the early metabolic response was assessed in 107 patients (90 of them underwent surgical resection). The five-year OS and DFS rates of all patients were 28% and 27%, respectively. No difference was found in OS (p=0.10 for SUL, p=0.08 for TLG) or DFS (p=0.50 for SUL, p=0.20 for TLG) between metabolic responders and non-responders. Post hoc analysis of the patients with a follow-up PET/CT within 16 days showed that metabolic response reflected by SUL predicted OS (p=0.03). We concluded that metabolic response assessed by PET/CT after the first cycle of neoadjuvant chemotherapy does not predict survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. However, proper timing of the follow-up PET/CT may affect the prognostic ability of the early metabolic response.

Serum adiponectin relates to shortened overall survival in men with squamous cell esophageal cancer treated with preoperative concurrent chemoradiotherapy: a pilot study.

BACKGROUND: The convergence of nutritional, genetic, and inflammatory factors plays a significant role in the pathophysiology of squamous cell esophageal cancer (SCEC). The parameters of inflammation, indices of nutritional status, and adipocyte-derived hormones such as leptin, adiponectin, and resistin have been shown to be prognostic factors in some gastrointestinal and pancreatic cancers. MATERIAL/METHODS: Forty-two patients with SCEC were subjected to a multimodal regimen of concurrent neoadjuvant chemoradiotherapy (CRT) followed by surgery. We retrospectively analyzed the impact of pretreatment values of serum leptin, adiponectin, resistin, soluble leptin receptor, C-reactive protein, TNF alpha, leukocytes, and indices of nutritional status (BMI, plasma total protein, albumin, cholesterol, and triacylglycerols) on overall survival (OS). RESULTS: Univariate analysis revealed significant a negative correlation between OS and serum adiponectin (p=0.027), and a positive relationship was found between serum albumin (p=0.002), cholesterol (p=0.049) level, and OS. In multivariate analysis, only the trend (p=0.086) for negative serum adiponectin association with the OS was observed. CONCLUSIONS: In men with SCEC treated by neoadjuvant concurrent CRT and esophagectomy, high pretreatment level of serum adiponectin was associated with shorter OS while the serum albumin and cholesterol were associated with longer OS.

Anastomotic leak and stricture after hand-sewn versus linear-stapled intrathoracic oesophagogastric anastomosis: single-centre analysis of 415 oesophagectomies.

OBJECTIVES: There seems to be a decreased anastomotic leak rate and a late stricture formation after linear-stapled (LS) cervical oesophagogastric anastomosis compared with hand-sewn (HS) technique. The aim of our study was to compare the surgical outcomes of intrathoracic side-to-side LS and end-to-end HS anastomosis after transthoracic oesophagectomy. METHODS: We conducted a retrospective review of all patients undergoing Ivor Lewis oesophagectomy with LS or HS anastomosis for neoplasia at our institution from 2005 to 2012. Anastomotic leak was radiologically and clinically graded as minor or major. End-points included overall and major leak rate, morbidity, mortality, length of hospital stay and endoscopically identified late anastomotic stricture. A propensity score-matched analysis was done to compensate for the differences in baseline characteristics between HS and LS groups. Multivariable analyses of the associations of anastomotic technique and other preoperative and pathological variables with anastomotic leak and stricture were performed. RESULTS: There were 415 patients, 134 with HS and 281 with LS anastomoses. Anastomotic leak occurred in 56 patients (13.5%), significantly more after HS than LS technique (20.9 vs 10.0%; P = 0.002). Major leak rate was not significantly different (9.0 vs 5.7%; P = 0.216, respectively). Overall morbidity (54.7%), in-hospital mortality (3.9%) and length of hospital stay (median 12 days) were not affected by the anastomotic technique. A follow-up endoscopic evaluation was available in 248 patients (59.8%). An anastomotic stricture was detected in 24 patients (9.7%), significantly more after HS than LS technique (20.3 vs 6.3%; P = 0.002). The propensity score-matched analysis of 105 patient pairs confirmed a significantly decreased overall leak rate (11.4 vs 22.9%; P = 0.045) and stricture formation (7.5 vs 18.2%; P = 0.041) in LS technique compared with HS technique. The multivariable analyses found obesity and HS anastomotic technique associated with an increased overall leak rate, chronic hepatopathy and diabetes associated with major leak and HS technique, female sex and the absence of arterial hypertension associated with increased stricture formation. CONCLUSIONS: Our non-randomized study showed that side-to-side LS technique is the preferred method of intrathoracic oesophagogastric anastomosis due to a decreased overall anastomotic leak rate and anastomotic stricture formation compared with HS technique.

Cultivation of circulating tumor cells in esophageal cancer.

The presence of circulating tumor cells (CTCs) in patients with metastatic carcinoma is generally associated with poor clinical outcome. There have been many investigations showing a possible use of CTCs as minimally invasive predictive and prognostic biomarker in cancer medicine. In this report a size-based method (MetaCell®) for quick and easy enrichment and cultivation of CTCs is presented to enable possible CTCs use in esophageal cancer (EC) management. In total, 43 patients with diagnosed EC, 20 with adenocarcinoma (AdenoCa) and 23 with squamous cell carcinoma (SCC), were enrolled into the adaptive prospective-like study .All the patients were candidates for surgery. The CTCs were detected in 27 patients (62.8%), with a higher rate in adenocarcinoma (75%) than SCC (52%). Finally, there were 26 patients with resectable tumors exhibiting CTCs-positivity in 69.2% and 17 patients with non-resectable tumors with 41.7% CTCs-positivity. Interestingly, in the patients undergoing neoadjuvant therapy, the CTCs were detected at time of surgery in 55.5% (10/18). The overall size-based filtration approach enabled to isolate viable CTCs and evaluate to their cytomorphological features by means of vital fluorescent staining. The CTCs were cultured in vitro for further downstream applications including immunohistochemical analysis. This is the first report of the successful culturing of esophageal cancer CTCs. The detection of CTCs presence could help in the future to guide timing of surgical treatment in EC patients.

TP53 gene mutations are rare in nondysplastic Barrett's esophagus.

In search of potential prognostic markers, we analyzed a large series of tissues of Barrett's esophagus and samples of adenocarcinomas arising in the terrain of Barrett's esophagus for TP53 gene mutations by direct sequencing of exons 5 to 9 of the TP53 gene. While 9 of 21 adenocarcinomas tested (42.9%) contained a TP53 mutation, none of 24 samples from Barrett's esophagus were mutated. This observation suggests that TP53 gene mutation may be a relatively late event in the progression from nondysplastic Barrett's esophagus to adenocarcinoma of esophagus. Therefore, TP53 gene mutations alone are not likely to represent a widely useful prognostic marker of the risk of progression to malignancy, at least not in Barrett's esophagus without dysplasia.