Abstract Background Nutritional status and body composition parameters such as sarcopenia are important risk factors for impaired outcome in patients with esophageal cancer. This study was conducted ...to evaluate the effect of sarcopenia on long-term outcome after esophageal resection following neoadjuvant treatment. Methods Skeletal muscle index (SMI) and body composition parameters were measured in patients receiving neoadjuvant treatment for locally advanced esophageal cancer. Endpoints included relapse-free survival (RFS) and overall survival (OS). Results The study included 130 patients. Sarcopenia was found in 80 patients (61.5%). Patients with squamous-cell cancer (SCC) showed a decreased median SMI of 48 (range 28.4–60.8) cm/m2 compared with that of patients with adenocarcinoma (AC) of 52 (range 34.4–74.2) cm/m2 , P < 0.001. The presence of sarcopenia had a significant impact on patient outcome: HR 1.69 (1.04–2.75), P = 0.036. Median OS was 20.5 (7.36–33.64) versus 52.1 (13.55–90.65) months in sarcopenic and non-sarcopenic patients, respectively. Sarcopenia was identified as an independent risk factor: HR 1.72 (1.049–2.83), P = 0.032. Conclusion Our data provide evidence that sarcopenia impacts long-term outcome after esophageal resection in patients who have undergone neoadjuvant therapy. Assessment of the body composition parameter can be a reasonable part of patient selection and may influence treatment methods.
Background Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the ...clinical impact of lymphangiogenesis (measured by lymphatic microvessel density LMVD) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer. Methods For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed. Results Patients with high LMVD had a significant increased risk to develop LVI ( P = .00123; coefficient of regression CR 0.27) and lymph node metastasis ( P = .00233), independent of the tumor’s histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS ( P < .001; 5-year OS 14% vs 60%) and DFS ( P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions ( P = .008). The amount of ISR correlated significantly with LMVD. Conclusion Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies.
Background Lymph node metastases constitute a strong prognostic factor in esophageal cancer. Nevertheless, the mechanisms and relevance of further spread of tumor cells from these already established ...metastatic sites have not been studied in this disease. The aim of this study was to investigate lymphatic vessel invasion (LVI) of tumor cells and lymphatic microvessel density in lymph node metastases in a large cohort of patients with node-positive esophageal cancer. Methods A total of 120 patients with node-positive esophageal cancer (67 adenocarcinomas, 53 squamous cell carcinomas) and radical esophagectomy were analyzed for LVI and lymphatic microvessel density in primary tumors and lymph node metastases using D2-40 immunostaining. In 18 patients, additional tissue from distant metastases was available. Results LVI was present in 52.1% (62/119) of primary tumors, 52.5% (63/120) of lymph nodes, and 22.2% (4/18) of distant metastases. LVI in primary tumors strongly correlated with LVI in lymph node metastases ( P < .05), regardless of histologic subtype. In univariate analysis, LVI in lymph node metastases was associated with shorter disease-free survival and overall survival in all tumors and in adenocarcinomas, and with shorter disease-free survival in squamous cell carcinomas ( P < .05, log-rank test). Multivariable analysis revealed LVI in lymph node metastases as an independent prognostic factor for disease-free survival in the whole cohort and for disease-free and overall survival in patients with adenocarcinomas ( P < .05, Cox regression). Conclusion LVI in lymph node metastasis is a significant prognostic factor in metastatic esophageal carcinoma and seems to play a relevant role in disease progression.
Background Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene ...is frequently mutated in esophageal cancer. Objective To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer. Patients and Methods The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd, Vienna, Austria). Results Mutations in the TP53 gene were present in 50% of tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53 marker status, compared with 16.7% in those with a mutant TP53 gene. In patients with normal TP53 , neoadjuvant treatment resulted in significant advantages in terms of tumor-associated survival ( P = .0049) and overall survival ( P = .0304) compared with those with mutant TP53 . The median tumor-associated survival was 34.2 months for patients with normal TP53 , compared with 8.9 months for those with mutant TP53 . The latter had a 3-fold higher risk of dying (hazard ratio, 3.01; 95% confidence interval, 1.359-6.86). Conclusions The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response.
Background Diagnostic tools used prior to hepatic surgery have significantly advanced during the last decade. We investigated the value of preoperative staging on detection of additional resectable ...hepatic lesions in metastatic colorectal cancer patients. Methods One hundred ninety-four consecutive resections for colorectal liver metastases between January 2002 and December 2005 were prospectively analyzed. Data on imaging (multidetector computed tomography MDCT and magnetic resonance imaging MRI) were compared to intraoperative findings by intraoperative sonography and bimanual palpation together with histopathological examination. Univariate and multivariate analysis of factors influencing recurrence was performed. Results In 16 (8.2%) resections, additional lesions were detected intraoperatively. In 11 cases (5.7%), these were small (<1 cm) and subcapsular. Detection of additional tumors was associated with shorter median recurrence free survival (5.4 vs. 13.4 months; P < .001) even though all lesions were resected and risk of recurrence was stratified by the Fong score. Patients treated with neoadjuvant chemotherapy did not generally have an increased risk of additional tumors; however, intraoperative detection of new lesions was associated with inferior outcome in this subgroup (median RFS 4.6 vs. 18.3 months in responders, P < .001). Conclusion Preoperative imaging with contrast-enhanced MDCT and MRI is efficient and very seldom leads to changes in intraoperative strategy. Patients exhibiting additional resectable hepatic lesions upon surgery have a high risk for early recurrence and should be monitored closely during follow-up.
Partially uncovered stents provide a better fixation to the esophageal wall than fully covered stents, but indication is limited to palliation because stent removal is compromised by mucosal ...ingrowth. After an unsuccessful attempt to remove a partially uncovered Evolution stent (Cook Medical Inc, Bloomington, IN) we placed a Polyflex stent (Boston Scientific, Natick, MA) inside the first stent, overlapping at the lower part to press the tissue out of the stent mesh. Both stents were easily removed 3 days later. By adopting this procedure to scheduled stent removals, partially uncovered SEMS may be used to prevent the frequently observed migrations of fully-covered stents in the treatment of esophageal perforation or anastomotic leakage.
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