Carlo Castoro

Istituto Oncologico Veneto, Padua, Veneto, Italy

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Publications (119)334.36 Total impact

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    ABSTRACT: Our study aimed to identify the best prognostic score for fitness for surgery and postoperative morbidity in elderly patients. A prospectively collected database of a consecutive series of patients with esophageal cancer evaluated for possible esophagectomy at our unit was analyzed. Fitness for surgery and postoperative morbidity were used as measures of outcome. The performances of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) score, the Charlson Comorbidity Index, the age-related Charlson Comorbidity Index (ACCI), the American Society of Anesthesiologists scale and the prognostic nutritional index (PNI) were evaluated in elderly patients. Discrimination was measured with receiver operating characteristics curve analysis; calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. Age did not result a significant predictor for postoperative complications. In elderly patients, ACCI predicted the judgment of the multidisciplinary team about fitness for surgery with the best discrimination (C-index = 0.94). PNI had the best discrimination for postoperative complications (C-index = 0.71) in the elderly group. ACCI best predicted the fitness for surgery in elderly patients. In elderly patients, the most discriminative prognostic score for postoperative complication was PNI, which could be used at admission for surgery to correctly inform patients about their risk and, possibly, to take extra precaution in case of high risk. © 2015 International Society for Diseases of the Esophagus.
    Diseases of the Esophagus 04/2015; DOI:10.1111/dote.12358 · 2.06 Impact Factor
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    ABSTRACT: Several prognostic scores were designed in order to estimate the risk of postoperative adverse events. None of them includes a component directly associated to the nutritional status. The aims of the study were the evaluation of performance of risk-adjusted models for early outcomes after oesophagectomy and to develop a score for severe complication prediction with special consideration regarding nutritional status. A comparison of POSSUM and Charlson score and their derivates, ASA, Lagarde score and nutritional index (PNI) was performed on 167 patients undergoing oesophagectomy for cancer. A logistic regression model was also estimated to obtain a new prognostic score for severe morbidity prediction. Overall morbidity was 35.3% (59 cases), severe complications (grade III-V of Clavien-Dindo classification) occurred in 20 cases. Discrimination was poor for all the scores. Multivariable analysis identified pulse, connective tissue disease, PNI and potassium as independent predictors of severe morbidity. This model showed good discrimination and calibration. Internal validation using standard bootstrapping techniques confirmed the good performance. Nutrition could be an independent risk factor for major complications and a nutritional status coefficient could be included in current prognostic scores to improve risk estimation of major postoperative complications after oesophagectomy for cancer. Copyright © 2015. Published by Elsevier Ltd.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2015; DOI:10.1016/j.ejso.2015.02.014 · 2.89 Impact Factor
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    ABSTRACT: 50 % of esophageal cancers are inoperable at the time of diagnosis, and around 15 % involve the cervical esophagus. The hypopharynx is often involved by these malignancies as well. Palliation of cervical esophageal malignancies through stent insertion is considered limited due to technical challenges, poor patient tolerance and high complication rate. The aim of this study is to review our experience with stent insertion in the cervical segment of the esophagus and to evaluate outcome differences between stent insertions involving or sparing the hypopharynx. We retrospectively reviewed data on 69 consecutive patients that underwent stent insertion for malignant strictures in the cervical esophagus at our Department. Patients were divided according to involvement or sparing of the lower hypopharynx. Dysphagia severity was measured with the Mellow-Pinkas scale before the procedure and on monthly follow-ups. Any complication and its management were recorded. The main outcome parameters were as follows: dysphagia improvement, rate of successful dysphagia palliation (i.e., a reduction of the score to 0 or 1 after stent insertion) and complication rate. Multivariable analysis was carried out to assess the influence of patient- and procedure-related factors on the outcome of the procedure. Stent insertion was achieved in 100 % patients. At 4 weeks, dysphagia score improved from a median of 3-0 (p < 0.001), and a successful palliation was achieved in 76.8 % patients. The 30-day mortality rate was 14.5 %. Successful palliation throughout the follow-up was achieved in 72.9 % of the surviving patients. Complications occurred in 31.9 % patients. Dilation before stent insertion was associated with a less efficient short-term dysphagia palliation (OR 6.77, 95 % CI 1.46-31.29, p = 0.02). Stent insertion is a safe and effective palliative treatment for malignant cervical esophageal strictures. Results are consistent even in patients with hypopharyngeal lesions. Dilation should be avoided before stent insertion.
    European Journal of Surgical Oncology 04/2015; 41(1):S15. DOI:10.1016/j.ejso.2014.10.041 · 2.89 Impact Factor
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    ABSTRACT: Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: In patients with ulcerative colitis (UC) the cumulative risk of colon cancer is lower than the actual rate of dysplasia suggesting an efficient immune surveillance mechanism. Since the co-stimulatory molecule CD80 is overexpressed in dysplastic colonic mucosa of UC patients and T-cell activation entails effective costimulation, we aimed to evaluate the functional implication of CD80 signaling in colonic UC-associated carcinogenesis. In humans, we observed that the percentage of CD80+ and HLA-A+ IEC was increased in the dysplastic colonic mucosa of UC patients. In vitro, IEC activated CD8+ T-cells through a CD80-dependent pathway. Finally, in the AOM/DSS-induced colonic adenocarcinoma model CD80 signaling inhibition significantly increased the frequency and extension of high-grade dysplasia, whereas enhancing CD80 activity with an anti-CTLA4 antibody significantly decreased colonic dysplasia. In conclusion, CD80 signaling between IEC and T-cells represents a key factor controlling the progression from low to high grade dysplasia in inflammatory colonic carcinogenesis.
    Oncotarget 01/2015; · 6.63 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S8. DOI:10.1016/j.ejso.2014.10.022 · 2.89 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S7-S8. DOI:10.1016/j.ejso.2014.10.021 · 2.89 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S9. DOI:10.1016/j.ejso.2014.10.026 · 2.89 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S9. DOI:10.1016/j.ejso.2014.10.025 · 2.89 Impact Factor
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    ABSTRACT: Study objectives: Tumors of hypopharynx and cervical esophagus (HCE) are diagnosed late and long term survival is poor. Resective surgery is demolitive, frequently complicated and the quality of life is poor due to laryngectomy. The target of the study is the analysis of our results in management of HEC cancer. Material and methods: 190 patients (pts) with SCC of HCE were treated at our institution from 1992 to 2010. Selection criteria were: no distant metastases, treatment consisting in primary surgery or first-line platinum-based chemoradiation (CRT). 22% of pts had hypopharynx involvement and 16% had a pure cervical esophageal cancer; the tumor involved both the cervical and upper thoracic esophagus in 54% of pts. Clinical stage was T3-4 in 164 pts (86%), and N+ in 129 pts (68%). 26 pts (14%) underwent primary surgery and 164(86%) were treated with first-line CRT. Pts who underwent first-line surgery had earlier tumors (T1-2 46%, N0 81%) than patients treated with first-line CRT (T3-4 92%, N+ 77%). Main results: The larynx was preserved in 13/26 pts who underwent primary surgery; vocal cord palsy developed in 4/13. Anastomotic morbidity was 27% and medical complications were recorded in 54%. Postoperative mortality was 15.4%. 3-y and 5-y survival after surgery was 23% and 19%, respectively. First-line CRT was suspended due to toxicity in 7% of the pts with 3 toxic deaths. Clinical response was: complete response (CR) in 58 pts (41%) and partial response (PR) in 40 pts (28%). A clinical CR was obtained in all the 9 pts with a T1-2 tumor and in 17/32(53%) N-tumors. Resection surgery was performed in 18/58(31%) pts with a clinical CR (mostly due to recurrence) and in 23/40 (58%) pts with a clinical PR. Postoperative mortality after trimodality treatment was 4% (2/50). The overall 3-year and 5-year survival rate after chemoradiation was 29% and 22%, respectively. The 3-y and 5-y survival rate of pts with a clinical CR was 57% and 41%, respectively, and for pts with a clinical PR it was 39% and 33%, respectively. Conclusion: Pts who underwent primary surgery had worse prognosis than those whom underwent first-line CRT, despite that they had earlier stage tumors. After first-line CRT, surgery for unresponsive or recurrent tumors was required in 50/164 pts (30%) with a 3-y and 5-y survival of 47% and 42% respectively. First-line CRT should be the treatment of choice for cancer of HCE reserving salvage surgery for unresponsive and recurrent tumors.
    European Journal of Surgical Oncology 01/2015; 41(1):S12-S13. DOI:10.1016/j.ejso.2014.10.035 · 2.89 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    PLoS ONE 01/2015; 10(1):e0117070. DOI:10.1371/journal.pone.0117070 · 3.53 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S16. DOI:10.1016/j.ejso.2014.10.043 · 2.89 Impact Factor
  • European Journal of Surgical Oncology 01/2015; 41(1):S7. DOI:10.1016/j.ejso.2014.10.020 · 2.89 Impact Factor
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    ABSTRACT: Esophageal carcinosarcoma (ESC) is a rare malignant lesion of the esophagus with controversial characteristics and prognostic factors. Seventeen consecutive patients with esophageal carcinosarcoma were referred to the Center for Esophageal Diseases located in Padua from January 1, 1980 to December 31, 2011. Clinical characteristics, pathological features, treatment and outcome were retrospectively analyzed in a prospectively collected database. Five patients received palliative treatment and one refused surgery; they died of unresected tumor or progression of disease within 0.6-43.5 months after diagnosis. Eleven patients underwent surgical treatment with complete tumor resection; recurrence rate was 80%, leading to death within 2 years after surgery. Only two resected patients are currently alive and free of disease over 20 years after surgery. Our results did not support the better prognosis concept of esophageal carcinosarcoma and suggested the importance of radical esophagectomy with adequate lymph node dissection. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 12/2014; 34(12):7455-9. · 1.87 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the impact of jejunostomy during esophagectomy for cancer on postoperative health-related quality of life (HRQL). We evaluate all consecutive patients who underwent esophagectomy for cancer at the surgical oncology unit of the Veneto Institute of Oncology (IOV-IRCCS) between January 2008 and March 2014. The primary outcome was HRQL, which was assessed using nine scales of EORTC C30 and OES18 questionnaires. General linear models were estimated to evaluate mean score difference (MD) of each selected scale in patients with and without jejunostomy, adjusting for clinically relevant confounders. The secondary outcomes were morbidity, hospital stay, postoperative weight loss and postoperative albumin impairment. Jejunostomy was performed in 40 on 109 patients (41.3%) who participated in quality of life investigation. A clinically and statistically significantly worse eating at admission (P=0.009) became not clinically significant at 3 months after surgery (MD =9.1). Jejunostomy was associated to clinically and statistically significantly poorer emotional function (EF) at 3 months after surgery (MD =-15.6; P=0.04). Hospital stay was longer in jejunostomy group (median, 20 vs. 17 days, P=0.02). In our series patients who had a jejunostomy during esophagectomy had been selected for their risk for postoperative complication. However, their postoperative outcome was actually similar compared to those without jejunostomy. Nevertheless, jejunostomy was associated to clinically and statistically significantly poorer EF at 3 months after surgery. Therefore, patient candidate to esophagectomy and feeding jejunostomy should receive additional psychological support.
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    ABSTRACT: Chronic gastro-duodenal reflux in the esophagus is a major risk for intestinal metaplasia and Barrett's adenocarcinoma. A role for chronic use of proton pump inhibitor (PPI) in the increased incidence of esophageal adenocarcinoma in Western countries has been previously suggested. The aim of this work was to study the effect of chronic administration of omeprazole (a proton pump inhibitor) per os in a model of reflux induced esophageal carcinogenesis. One week after esophago-gastro-jejunostomy, 115 Sprague-Dawley rats were randomized to receive 10 mg/Kg per day of omeprazole or placebo, 5 days per week. The esophago-gastric specimens were collected 28±2 weeks after randomization and analyzed in a blinded fashion. Mortality and esophageal metaplasia rates did not differ between the two groups (p = 0.99 for mortality, p = 0.36 for intestinal metaplasia and p = 0.66 for multi-layered epithelium). Gastric pancreatic acinar cell metaplasia (PACM) was more frequently observed in PPI-treated rats (p = 0.003). Severe ulcer lesions significantly prevailed in the placebo group (p = 0.03). Locally invasive esophageal epithelial neoplasia were observed in 23/39 PPI-treated versus 14/42 placebo-animals (p = 0.03). In conclusion, chronic omeprazole treatment improved the healing of esophageal ulcerative lesions. Locally invasive neoplastic lesions and PACM prevailed among PPI-treated animals. However, neither an effect on the overall mortality nor on the incidence of pre-neoplastic lesions was observed in this work.
    PLoS ONE 11/2014; 9(11):e112862. DOI:10.1371/journal.pone.0112862 · 3.53 Impact Factor
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    ABSTRACT: Purpose To investigate whether changes in tumour volume were predictive of histopathological response to neoadjuvant therapy for oesophageal cancer. Materials and methods Thirty-five consecutive patients with locally advanced oesophageal cancer were treated with chemoradiotherapy and surgery in responders from July 2007 to July 2009. Tumour volume (TV) was calculated using innovative tumour volume estimation software which analysed computed tomography (CT) data. Tumour diameter and area were also evaluated. Variations in tumour measurements following neoadjuvant treatment were compared with the histopathological data. Results Median baseline tumour diameter, area and volume were 3.51 cm (range 1.67–6.61), 7.51 cm2 (range 1.79–21.0) and 33.80 cm3 (range 3.36–101.6), respectively. Differences in TV between the pre- and post-treatment values were significantly correlated with the pathological stage (τ = 0.357, p = 0.004) and the tumour regression grade index (τ = 0.368, p = 0.005). According to the receiver operating characteristic analysis, TV measurements following treatment had moderate predictive values for the pathological T stage (area under the curve, AUC = 0.742, sensitivity = 55.56 %, specificity = 92.86 %, p = 0.005).Comparison of pathological and radiological volume showed a good precision (Pearson rho 0.77). Conclusions Changes in TV calculated on CT scans have a limited role in predicting pathological response to neoadjuvant treatment in oesophageal cancer patients. New imaging techniques based on metabolic imaging may provide better results.
    La radiologia medica 10/2014; 120(5). DOI:10.1007/s11547-014-0466-0 · 1.37 Impact Factor
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    ABSTRACT: Esophagectomy is contraindicated in case of advanced cancer (i.e., carcinomatosis, distant metastasis, and invasion of other organs). In some cases, preoperative imaging may fail to identify advanced neoplasm and esophagectomy is inappropriately planned. The aim of the study was to identify preoperative biomarkers of occult advanced disease that force surgeons to abort the planned esophagectomy. From 2008 to 2014, 244 consecutive patients were taken to the operative room to have esophagectomy for cancer in our department. All of them had blood test at admission and their preoperative biomarker data were retrieved. Their medical history was collected and the intraoperative findings and outcome were recorded. Non parametric tests, multiple regression analysis, and ROC curves analysis were performed. In our study group, 14 (5.7 %) patients, scheduled for esophagectomy, were discovered to have occult advanced disease at laparotomy/laparoscopy or at thoracotomy. Six of them had peritoneal carcinomatosis, three had advanced tumor invading other organs, three had small liver metastasis, and two pleural carcinomatosis. In all these cases, esophagectomy was aborted and a feeding jejunostomy was placed. In patients with unresectable esophageal cancer, CA19.9 and CEA serum levels were significantly higher than patients who could have esophagectomy (p < 0.001 and p = 0.003, respectively). CA19.9 and CEA resulted to be accurate biomarkers of occult advanced disease (AUC = 85 %, p < 0.001 and AUC = 73 %, p = 0.002, respectively). Preoperative CEA and CA19.9 serum levels should be taken in consideration when evaluating patients candidate to esophagectomy for esophageal cancer to prevent inappropriate laparotomy or thoracotomy. If any doubt arises minimally invasive exploration is warranted.
    Gastroenterology 10/2014; 39(2). DOI:10.1007/s00268-014-2835-1 · 13.93 Impact Factor
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    ABSTRACT: Several studies have demonstrated that obesity is a risk factor for colorectal cancer (CRC), but few data are available regarding its role in multifocal disease and postoperative recurrence. The present study aimed to assess the role of obesity as a risk factor for multifocal disease and postoperative recurrence in patients with CRC.
    Anticancer research 10/2014; 34(10):5735-41. · 1.87 Impact Factor
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    ABSTRACT: AimThis multicentric prospective study aimed to investigate how postoperative complications after surgery for colorectal cancer affect patients’ quality of life and satisfaction with care.Method One hundred and sixteen patients operated on for colorectal cancer were enrolled in this study. Patients answered three questionnaires about generic (EORTC QLQ-C30) and disease specific quality of life (EORTC CR29) and treatment satisfaction (EORTC IN-PATSAT32) at the time of admission, and at one and six months after surgery. Non-parametric tests and linear multiple regression models were used for statistical analysis.ResultsTwelve patients had complications requiring further surgery (anastomotic leakage, abdominal bleeding, abdominal wall sepsis, wound infection). Patients with complications that required surgery reported a worse score of physical function, emotional function and anxiety than patients without such complications one month after surgery. These patients judged their general satisfaction with the quality of care and doctors’ interpersonal skills, technical skills, information provision and availability to be worse than in patients without such complications. The presence of postoperative psychiatric complications and anastomotic leakage were independent predictors of quality of life (β=-0.30, p=0.004 and β=-0.42, p<0.001)Conclusion In patients undergoing surgery for colorectal cancer, complications requiring any kind of surgical management significantly affected patients’ perception of all doctor-related items suggesting an impairment of the entire surgeon-patient relationship. Convincing patients that ‘‘zero risk’’ cannot be achieved in surgical practice is therefore a priority.This article is protected by copyright. All rights reserved.
    Colorectal Disease 08/2014; DOI:10.1111/codi.12752 · 2.02 Impact Factor

Publication Stats

586 Citations
334.36 Total Impact Points

Institutions

  • 2007–2015
    • Istituto Oncologico Veneto
      Padua, Veneto, Italy
  • 1988–2013
    • University of Padova
      • • Department of Surgery, Oncology and Gastroenterology DISCOG
      • • Dipartimento di Scienze Mediche e Chirurgiche
      Padua, Veneto, Italy
  • 2012
    • Venetian Institute of Molecular Medicine
      Padua, Veneto, Italy
  • 1994–2009
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 1989
    • Ospedale Generale Regionale "F. Miulli"
      Acquaviva delle Fonti, Apulia, Italy