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Alfredo Mellano

    Alfredo Mellano

    BackgroundMini-invasive surgery (MIS), ERAS, and preoperative nutritional screening are currently used to reduce complications and the length of hospital stay (LOS); however, inter-variable correlations have seldom been explored. This... more
    BackgroundMini-invasive surgery (MIS), ERAS, and preoperative nutritional screening are currently used to reduce complications and the length of hospital stay (LOS); however, inter-variable correlations have seldom been explored. This research aimed to define inter-variable correlations in a large series of patients with gastrointestinal cancer and their impact on outcomes.MethodsPatients with consecutive cancer who underwent radical gastrointestinal surgery between 2019 and 2020 were analyzed. Age, BMI, comorbidities, ERAS, nutritional screening, and MIS were evaluated to determine their impact on 30-day complications and LOS. Inter-variable correlations were measured, and a latent variable was computed to define the patients' performance status using nutritional screening and comorbidity. Analyses were conducted using structural equation modeling (SEM).ResultsOf the 1,968 eligible patients, 1,648 were analyzed. Univariable analyses documented the benefit of nutritional screeni...
    IntroductionTemporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an... more
    IntroductionTemporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an adjuvant treatment, especially considering patient-reported outcomes and health system costs. The aim of the study is to compare the results of an early versus late closure strategy in patients with indication to adjuvant chemotherapy after resection for rectal cancer.Methods and analysisThis is a prospective multicentre randomised trial, sponsored by Rete Oncologica Piemonte e Valle d’Aosta (Oncology Network of Piedmont and Aosta Valley-Italy). Patients undergone to rectal cancer surgery with temporary ileostomy, aged >18 years, without evidence of anastomotic leak and with indication to adjuvant chemotherapy will be enrolled in 28 Network centres. An early closure strategy (between 30 and 40 days from rectal surgery) will be compared with a late one (...
    Lymphadenectomy is crucial for an optimal oncologic resection of colon and rectal cancers. However, without a direct visualization, an aberrant route of lymph node (LN) diffusion might remain unresected. Indocyanine-green (ICG) lymphatic... more
    Lymphadenectomy is crucial for an optimal oncologic resection of colon and rectal cancers. However, without a direct visualization, an aberrant route of lymph node (LN) diffusion might remain unresected. Indocyanine-green (ICG) lymphatic mapping permits a real-time LNs visualization. We designed the GREENLIGHT trial to explore in 100 patients undergoing robotic colorectal resection the clinical significance of a D3 ICG-guided lymphadenectomy. The primary endpoint was the number of patients in whom ICG changed the extent of lymphadenectomy. We report herein the interim analysis on the first 70 patients. After endoscopic ICG injection 24 h (n = 49) or 72 h (n = 21) ahead, 19, 20, and 31 patients underwent right colectomy, left colectomy, and anterior rectal resection. The extent of lymphadenectomy changed in 35 (50%) patients, mostly (29 (41.4%)) for the identification of LNs (median two) outside the standard draining basin. Identification of such LNs was less frequent in rectal tumor...
    Aim. To evaluate the impact of open or laparoscopic rectal surgery on pulmonary complications in elderly (>75 years old) patients. Methods. Data from consecutive patients who underwent elective laparoscopic or open rectal surgery for... more
    Aim. To evaluate the impact of open or laparoscopic rectal surgery on pulmonary complications in elderly (>75 years old) patients. Methods. Data from consecutive patients who underwent elective laparoscopic or open rectal surgery for cancer were collected prospectively from 3 institutions. Pulmonary complications were defined according to the ACS/NSQUIP definition. Results. A total of 477 patients (laparoscopic group: 242, open group: 235) were included in the analysis. Postoperative pulmonary complications were significantly more common after open surgery (8 out of 242 patients (3.3%) versus 23 out of 235 patients (9.8%); p=0.005). In addition, PPC occurrence was associated with the increasing of postoperative pain (5.04 ± 1.62 versus 5.03 ± 1.58; p=0.001) and the increasing of operative time (270.06 ± 51.49 versus 237.37 ± 65.97; p=0.001). Conclusion. Our results are encouraging to consider laparoscopic surgery a safety and effective way to treat rectal cancer in elderly patien...
    Complete Mesocolic Excision (CME) with central vascular ligation has been reported to potentially improve oncological results in right colectomy [1-4]. However, along with the intracorporeal anastomosis, it represents a challenging step... more
    Complete Mesocolic Excision (CME) with central vascular ligation has been reported to potentially improve oncological results in right colectomy [1-4]. However, along with the intracorporeal anastomosis, it represents a challenging step of the laparoscopic procedure [2,3,5]. The video describes a novel bottom-to-up suprapubic approach for robotic right colectomy with CME and intracorporeal anastomosis using the DaVinci Xi Surgical System. This article is protected by copyright. All rights reserved.
    To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. Young surgeons <40 years old affiliated to the Italian Society of... more
    To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months....
    Colorectal cancer is the third most common cancer worldwide, with 1.2 million patients diagnosed annually. In late-stage colorectal cancer, the most commonly used targeted therapies are the monoclonal antibodies cetuximab and panitumumab,... more
    Colorectal cancer is the third most common cancer worldwide, with 1.2 million patients diagnosed annually. In late-stage colorectal cancer, the most commonly used targeted therapies are the monoclonal antibodies cetuximab and panitumumab, which prevent epidermal growth factor receptor (EGFR) activation. Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy. Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in colorectal cancer and little is known about determinants of sensitivity to this therapy. To examine the effect of somatic genetic changes in colorectal cancer on response to anti-EGFR antibody therapy, here we perform complete exome sequence and copy number analyses of 129 patient-derived tumour grafts and targeted genomic analyses of 55 patient tumours, all of which were KRAS wild-type. We analysed the response of tumours to an...
    Recent studies have identified a stem/serrated/mesenchymal (SSM) molecular subtype of colorectal cancer (CRC) that is associated with poor prognosis. We noted that genes upregulated in this subtype are also prominently expressed by... more
    Recent studies have identified a stem/serrated/mesenchymal (SSM) molecular subtype of colorectal cancer (CRC) that is associated with poor prognosis. We noted that genes upregulated in this subtype are also prominently expressed by stromal cells. This led us to hypothesize that the SSM transcripts could derive from the tumor microenvironment, rather than being intrinsic to cancer cells. To test this hypothesis, we analyzed microarray and RNAseq expression data from patient-derived xenografts (PDXs) of CRC, where human cancer cells are supported by murine stroma. Species-specific expression analysis revealed that mRNA levels of SSM genes are mostly due to stromal expression. Considering only genes exclusively expressed by stromal cells in PDXs, We then built three expression signatures specifically reporting the abundance of cancer-associated fibroblasts (CAFs), leucocytes or endothelial cells. In human CRC samples, all stromal signatures were strongly associated with the SSM subtype...
    Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The... more
    Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival. The medi...
    PurposeThe aim of this systematic review was to compare intracorporeal (IA) versus extracorporeal anastomosis (EA) after laparoscopic right hemicolectomy for cancer.MethodsThe meta-analysis was conducted following all aspects of the... more
    PurposeThe aim of this systematic review was to compare intracorporeal (IA) versus extracorporeal anastomosis (EA) after laparoscopic right hemicolectomy for cancer.MethodsThe meta-analysis was conducted following all aspects of the Cochrane Handbook for systematic reviews and Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Studies published from 2009 to 2012 that compare IA and EA after laparoscopic right hemicolectomy were identified. The included non-randomized studies were assessed for their methodological quality using the revised and modified grading system of the Scottish Intercollegiate Guidelines Network. Intraoperative, early postoperative, and postoperative recovery outcomes were compared using weighted mean differences and odds ratios.ResultsFive non-randomized controlled trials published between 2009 and 2011, comprising 425 patients, were included in this analysis. IA was associated with significant faster bowel movement, faster first flatus, shorter time to solid diet, decreased use of analgesics, and shorter duration of the hospital stay. No differences were observed for nasogastric tube reintroduction rate, operative time, incision length, number of nodes harvested, intraoperative complications, mortality, non-surgical site complications, surgical site complications (anastomotic leakage, anastomotic bleeding, wound infection, ileus), reintervention, and readmission rate.ConclusionsEven when the limitations are taken into account due to the observational nature of the included studies, the results suggest that the IA after laparoscopic right hemicolectomy for cancer results in better postoperative recovery outcomes, such as shorter hospital stay, faster bowel movement recovery, faster first flatus, faster time to solid diet, and lesser analgesic usage.
    The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CT×2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout... more
    The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CT×2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout rate after the 1st-stage hepatectomy due to progression of disease (PD). Routine use of CT×2 has been advocated. A total of 47 patients with multiple, bilateral unresectable liver metastases were selected for a 2-stage hepatectomy procedure (±portal vein occlusion). Of the total, 37 patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy (CT×1) and 25 patients (53.2%) underwent CT×2; PD was significantly more common during CT×2 than during CT×1 (P=.002). Of the 47 patients planned for the 2nd-stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25 (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CT×2 group and 13 in the no-CT×2 group; administration of CT×2 did not significantly affect the PD rate (P=.561). The overall dropout rate was 23.4% (n=11 patients): 16% in the CT×2 group vs. 31.8% in the no-CT×2 group (P=.303). The routine use of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee lower PD and dropout rates.
    ABSTRACTThe breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale... more
    ABSTRACTThe breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. A PDXT-based population trial with the anti-EGFR antibody cetuximab revealed variable sensitivities that were consistent with clinical response biomarkers, mirrored tumor growth changes in matched PDXs, and recapitulated the outcome of EGFR genetic deletion. Adaptive signals upregulated by EGFR blockade were computationally and function...