Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin's Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study.

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis

Association Between ERCC1 rs3212986 and ERCC2/XPD rs1799793 and OS in Patients With Advanced Esophageal Cancer

Esophageal cancer (EC) is a very aggressive tumor, and no reliable prognostic markers exist especially for resectable advanced neoplasia. The principal aim of this study was to investigate the association of germline polymorphisms in nucleotide excision repair (NER) pathway genes with the overall survival (OS) of patients with advanced EC. As a second aim, we also studied the association of NER gene variants with response to cisplatin-based chemotherapy. Among the EC patients referred to our Institution between 2004 and 2012, we selected a cohort of 180 patients diagnosed with a clinical tumor stage ranging from IIB and IVA. Patients were genotyped for four NER variants, two in the ERCC1 (rs11615 and rs3212986) and two in the ERCC2/XPD (rs1799793 and rs13181) genes. Kaplan–Meier analyses and Cox proportional hazards model were used to evaluate the associations of the selected variants with OS; association with response to neoadjuvant therapy was investigated using logistic regression. Results showed that the ERCC1 rs3212986 and the ERCC2/XPD rs1799793 were significantly associated with shorter OS. On the contrary, response association analysis displayed that, while rs11615 and rs3212986 in ERCC1 were associated with response, both ERCC2/XPD variants were not. By creating survival prediction models, we showed that the rs3212986 and the rs1799793 have a better predictability of the tumor stage alone. Furthermore, they were able to improve the power of the clinical model (AUC = 0.660 vs. AUC = 0.548, p = 0.004). In conclusion, our results indicate that the ERCC1 rs3212986 and the ERCC2/XPD rs1799793 could be used as surrogate markers for a better stratification of EC patients with advanced resectable tumor

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

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Physical model tests on a very large floating breakwater

A new concept of floating breakwater (FB) is experimentally and numerically investigated, specifically a very large structure, made in ferrocement, designed to resist to severe wave conditions. Compared to traditional FBs, the new concept of structure has much larger geometrical dimensions (of order 10 times). The mooring system is a critical issue and, in general, a different design is necessary. Two types of spread moorings and a tethered one are analyzed and compared, with the aim of giving precious information to the designer. Results are relative to: (i) the structure efficiency in attenuating the incident waves, that is excellent for waves of period up to 10 s; (ii) the maximum and average loads along the mooring lines and on the anchor (investigated for waves of height up to 6 m). It was found that the mooring has a strong influence on the structure efficiency, and the effects of the different rigidity and compliancy of the analyzed mooring systems are discussed, with reference to snapping events, proposing possible measures to reduce the mooring loads under extreme wave conditions

Il ruolo della linfoadenectomia nella chirurgia del cancro dell’esofago

Objective: The rising incidence of esophageal adenocarcinoma represents a real increase in disease burden, associated with a poor prognosis at 5 year after surgery. Our aim was to study the potential benefit of lymphadenectomy in the surgical treatment for esophageal cancer. Methods: The study population included all patients with cancer of the intrathoracic esophagus and of the gastro-esophageal junction who underwent R0 esophago-gastric resection between 1992 and 2007. Results: 643 patients were included. Median number of nodes removed was 18 (IQR 14-25). There were 110 patients with stage I (17.1%), 199 stage II (31%), 210 stage III (32.6%) and 50 stage IV (7.8%). The overall 5-year survival rate was 27.7%. The lymph node involvement was a significant negative predictor of survival (41.5% for pN0 patients versus 12.7% for pN1 patients, p<0.05) and, among the latter group of patients, the involvement of the celiac nodes determined a worse prognosis (6.5% versus 15%, p<0.05). The optimal threshold predicted by ROC analysis for the survival benefit of a more extended lymphadenectomy was removal of a minimum of 17 nodes. At multivariate analysis, the independent predictors of survival were the presence of nodal metastasis, the number of involved nodes, and patient’s age. Conclusions: The extension of the lymphadenectomy is a key point in the surgical treatment of esophageal cancer. To maximize this survival benefit, a minimum of 17 regional lymph nodes must be removed

Chylothorax complicating esophagectomy for cancer: A plea for early thoracic duct ligation

AbstractObjective: Postoperative chylothorax remains an uncommon but potentially life-threatening complication of esophagectomy for cancer, and the ideal management is still controversial. The aim of the study was to compare the outcomes of patients treated nonoperatively with those of patients promptly undergoing reoperation. Methods: From 1980 to 1998, 1787 esophagectomies for esophageal or cardia cancer were performed, and 19 (1.1%) patients had postoperative chylothorax. We analyzed type of operation, surgical approach, delay of diagnosis of chylothorax, daily chest tube output, type of management, major complications, death, hospital stay, and final outcome. Results: Of the 19 patients with chylothorax, 11 were initially managed nonoperatively (group A): 4 (36%) patients had spontaneous resolution of chylothorax, and the other 7 required reoperation for the persistence of a high-volume output. There were three infectious complications and one postoperative death in this group. No reliable predictive criteria of successful versus unsuccessful nonoperative management could be found. The 8 most recent patients underwent early reoperation (group B). All patients recovered, and no major complications possibly related to chylothorax or hospital deaths were observed. They were discharged after a median of 22 days (range, 12-85 days) compared with a median of 36 days (range, 21-64 days) for patients of group A. Conclusions: Early thoracic duct ligation is the treatment of choice for chylothorax occurring after esophagectomy. Reoperation should be performed immediately after the diagnosis is made to avoid the complications related to nutritional and immunologic depletion caused by prolonged nonoperative treatment. (J Thorac Cardiovasc Surg 2000;119:453-7