BackgroundThe minimally invasive esophagectomy (MIE) is widely being implemented for esophageal cancer in order to reduce morbidity and improve quality of life. Non-randomized studies investigating the mid-term quality of life after MIE show conflicting results at 1-year follow-up. Therefore, the aim of this study is to determine whether MIE has a continuing better mid-term 1-year quality of life than open esophagectomy (OE) indicating both a faster recovery and less procedure-related symptoms.MethodsA one-year follow-up analysis of the quality of life was conducted for patients participating in the randomized trial in which MIE was compared with OE. Late complications as symptomatic stenosis of anastomosis are also reported.ResultsQuality of life at 1 year was better in the MIE group than in the OE group for the physical component summary SF36 [50 (6; 48–53) versus 45 (9; 42–48) p .003]; global health C30 [79 (10; 76–83) versus 67 (21; 60–75) p .004]; and pain OES18 module [6 (9; 2–8) versus 16 (16; 10–22) p .001], respectively. Twenty six patients (44 %) in the MIE and 22 patients (39 %) in the OE group were diagnosed and treated for symptomatic stenosis of the anastomosis.ConclusionsThis first randomized trial shows that MIE is associated with a better mid-term one-year quality of life compared to OE.
IntroductionEsophagectomy for cancer can be performed in a two-stage procedure with an intrathoracic anastomosis: the Ivor Lewis esophagectomy. A growing incidence of distal and gastroesophageal junction adenocarcinomas and increasing use of minimally invasive techniques have prompted interest in this procedure. The aim of this study was to assess short-term results of minimally invasive Ivor Lewis esophagectomy (MIE-IL).MethodsA retrospective cohort study was performed from June 2007 until September 2014, including patients that underwent MIE-IL for distal esophageal and gastroesophageal junction cancer in six different hospitals in the Netherlands and Spain. Data were collected with regard to operative techniques, pathology and postoperative complications.ResultsIn total, 282 patients underwent MIE-IL, of which 90.2 % received neoadjuvant therapy. Anastomotic leakage was observed in 43 patients (15.2 %), of whom 13 patients (4.6 %) had empyema, necessitating thoracotomy for decortication. With an aggressive treatment of complications, the 30-day and in-hospital mortality rate was 2.1 %. An R0-resection was obtained in 92.5 % of the patients. After neoadjuvant therapy, 20.1 % of patients had a complete response.ConclusionsMinimally invasive Ivor Lewis esophagectomy for distal esophageal and gastroesophageal junction adenocarcinomas is an upcoming approach for reducing morbidity caused by laparotomy and thoracotomy. Anastomotic leakage rate is still high possibly due to technical diversity of anastomotic techniques, and a high percentage of patients treated by neoadjuvant chemoradiotherapy. An aggressive approach to complications leads to a low mortality of 2.1 %. Further improvement and standardization in the anastomotic technique are needed in order to perform a safe intrathoracic anastomosis.
Pancreatic cancer has long carried poor prognosis. The development of new therapeutic approaches is particularly urgent. Inactivation of the tumor -suppressor gene p16INK4a / CDKN2 , a specific inhibitor of the cyclin -dependent kinases CDK4 and CDK6, is the most common genetic alteration in human pancreatic cancer, making it an ideal target for gene replacement. Here we transfected tumor cells using a recombinant adenovirus containing the wt -p16 cDNA ( Ad5RSV -p16 ). The overexpression of p16 decreased cell proliferation in all four human pancreatic tumor cell lines ( NP -9, NP -18, NP -29, and NP -31 ). However, G 1 arrest and senescence were observed in only three. In contrast, the fourth ( NP -18 ) showed a significant increase in apoptosis. This differential behavior may be related to the differences found in the expression level of E2F -1. Experiments on subcutaneous pancreatic xenografts demonstrated the effectiveness of p16 in the inhibition of pancreatic tumor growth in vivo. Taken together, our results indicate that approaches involving p16 replacement are promising in pancreatic cancer treatment. Cancer Gene Therapy ( 2001 ) 8, 740 -750
The CYP2B1/cyclophosphamide (CPA) suicide gene therapy approach has been shown to be highly promising in clinical trials for the treatment of pancreatic cancer. However, delivering the therapeutic gene to a sufficient number of tumor cells able to trigger a complete response remains a challenge. Target-specific delivery of adenovirus to fibroblast growth factor receptors (FGFRs) has been obtained in a variety of tumor models and has been shown to highly increase transduction efficiency. In the present paper we have tested the therapeutic outcome of retargeting the adenoviral vector, Ad-CYP2B1, to FGFRs, using an FGF2-Fab conjugate, in pancreatic cancer models. First, we show a heterogeneous subcellular distribution of overexpressed FGFR-1 in pancreatic cancer cells. Higher transduction efficiency was observed in five of the six cell lines studied after FGF2-AdGFPLuc infection. Interestingly, an association between FGFR-1 membrane cell expression and viral entry was found. Moreover, tumors injected with FGF2-AdGFPLuc showed enhanced and persistent transgene expression. Importantly, we demonstrate the relevant enhanced cytotoxic effect of the FGF2-Ad-CYP2B1/CPA system in four of the six cell lines studied. Moreover, retargeting Ad-CYP2B1/CPA to FGFRs resulted in a potent antitumoral effect and in an increased survival rate, in two human pancreatic xenograft models. Thus, our results indicate that redirecting adenoviruses to FGFRs highly increases the potency of the suicide system CYP2B1/CPA. Consequently, it may constitute a promising approach to the treatment of patients with pancreatic tumors, in which a high proportion of FGF receptors precisely localize to the plasma membrane. OVERVIEW SUMMARYBioactivation of the CYP2B1 gene by ifosfamide after local injection of microencapsulated CYP2B1-producing cells has shown promising results in the treatment of inoperable pancreatic carcinoma, suggesting that this system is a potent inducer of cell death. In the present work we aimed to study CYB2B1/cyclophosphamide (CPA) antitumoral activity when delivered by a highly efficient gene transfer system based on retargeting adenoviruses to fibroblast growth factor receptors (FGFRs). We showed that although there was some degree of heterogeneity, pancreatic tumor cells highly expressed FGFRs at the plasma membrane. Moreover, retargeting adenovirus to FGFRs enhanced adenoviral transduction and increased CYP2B1/CPA cytotoxicity. Importantly, intratumoral delivery of the Ad-CYP2B1 through FGFRs in combination with cyclophosphamide resulted in a potent antitumoral effect and a significant increase in the survival rate when assessed in two independent xenograft models, indicating the efficient response of pancreatic tumors to this type of therapy.
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