Carlos Fernández-del castillo

OBJECTIVE: To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND: Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS: Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed...

BACKGROUND: Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. METHODS: The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient...

Pancreatic ductal adenocarcinoma (PDAC) lethality is due to metastatic dissemination. Characterization of rare, heterogeneous circulating tumor cells (CTCs) can provide insight into metastasis and guide development of novel therapies. Using the CTC-iChip to purify CTCs from PDAC patients for RNA-seq characterization, we identify three major correlated gene sets, with stemness genes LIN28B/KLF4, WNT5A, and LGALS3 enriched in each correlated gene set; only LIN28B CTC expression was prognostic. CRISPR knockout of LIN28B-an oncofetal RNA-binding protein exerting diverse effects via negative regulation of let-7 miRNAs and other RNA targets-in cell and animal models confers a less aggressive/metastatic phenotype...

BACKGROUND/AIM: FOLFIRINOX [fluorouracil (5-FU), irinotecan, oxaliplatin] and gemcitabine plus nab-paclitaxel are standard treatments for patients with pancreatic ductal adenocarcinoma (PDAC). Despite efficacy rates of less than 32%, evidence is lacking to guide the use of one drug over the other. Herein, we compared the sensitivity of patient-derived PDAC cell lines to each of these regimens. MATERIALS AND METHODS: Changes in the growth of 19 low-passage patient-derived PDAC cell lines were evaluated in response to treatment with FOLFIRINOX and gemcitabine plus paclitaxel (Gem-Pac)...

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization...

OBJECTIVE: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. BACKGROUND: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity...

BACKGROUND: Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC. METHODS: Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016)...

INTRODUCTION: The inhibition of Hedgehog (Hh) signaling in pancreatic ductal adenocarcinoma (PDAC) reduces desmoplasia and promotes increased vascularity. In contrast to these findings, the Hh ligand Sonic Hedgehog (SHH) is a potent proangiogenic factor in non-tumor models. The aim of this study was to determine the molecular mechanisms by which SHH affects the tumor stroma and angiogenesis. METHODS: Mice bearing three different xenografted human PDAC (n = 5/group) were treated with neutralizing antibodies to SHH...

BACKGROUND: Chronic pancreatitis is a complex multifactorial fibro-inflammatory disease. Consensus guidelines are needed for the histopathological evaluation of non-autoimmune chronic pancreatitis (CP). METHODS: An international working group with experts on the histopathology of CP evaluated 15 statements generated from evidence on seven key clinically relevant questions. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement...

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BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. METHODS: An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP...

BACKGROUND: Diagnosis of depression may be associated with adverse outcomes following surgery. The aim of this study is to investigate whether depression is associated with an increased readmission rate following elective pancreatectomy, which is currently unknown. METHODS: The 2014 Nationwide Readmissions Database was used to evaluate whether diagnosis of depression was associated with 30-day readmission following elective pancreatectomy in adult patients. Univariate and multivariate logistic regression models were adjusted for clustering by facility...

BACKGROUND: The authors hypothesized that in resected pancreatic adenocarcinoma (PDAC), pathologic characteristics, oncologic outcomes, prognostic factors, and the accuracy of the American Joint Committee on Cancer (AJCC) staging system might differ based on tumor location. METHODS: Patients undergoing pancreatectomy for PDAC at two academic institutions from 2000 to 2015 were retrieved. A comparative analysis between head (H-PDAC) and body-tail (BT-PDAC) tumors was performed using uni- and multivariable models...

BACKGROUND: Cancer center accreditation is designed to identify centers that provide high-quality cancer care. This also guides patients and referring physicians towards centers of excellence for specialized care. We sought to examine if cancer center accreditation was associated with improved long-term oncologic outcomes in patients with pancreatic adenocarcinoma. METHODS: Using the SEER-Medicare database, we identified patients who underwent pancreatectomy for pancreatic adenocarcinoma from 1996 to 2013...

INTRODUCTION: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. METHODS: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD...

BACKGROUND: A minimally invasive step-up (MIS) approach has been associated with reduced morbidity compared with open surgical necrosectomy (OSN) for treatment of necrotizing pancreatitis. We sought to determine whether transitioning from an OSN to an MIS-based approach would result in reduced mortality. MIS interventions included percutaneous drainage, endoscopic transgastric necrosectomy, video-assisted retroperitoneal debridement, sinus tract endoscopic necrosectomy, or a combination of techniques, with selective use of OSN...

BACKGROUND: The aim was to evaluate the various operative techniques and outcomes used to manage the pancreatic transection plane (or stump) during a left (distal) pancreatectomy and to develop expert consensus guidelines. METHODS: Evidence-based, clinically relevant questions were discussed and then were circulated among members of the International Study Group of Pancreatic Surgery. After agreement on the questions and statements, voting in a 9-point Likert scale was used to gauge the level of objective support for each...

Selection of elderly patients (aged ≥60 years) for intensive chemotherapy treatment of acute myeloblastic leukaemia (AML) remains challenging. Several cooperative groups such as Acute Leukaemia French Association (ALFA), Haematological Oncology Clinical Studies Group (HOCSG) and MD Anderson Cancer Center (MDACC) have developed predictive models to select those patients who can benefit from intensive chemotherapy. Our purpose is to validate and compare these three models in a cohort of patients treated in real-life setting...

BACKGROUND/OBJECTIVES: We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. METHODS: We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group...

BACKGROUND: There is limited data on the efficacy of adjuvant therapy (AT) in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMN). This single center retrospective cohort study aims to assess the impact of AT on survival in these patients. METHODS: Patients undergoing surgery for invasive IPMN between 1993 and 2018 were included in the study. We compared the clinicopathologic features and evaluated overall survival (OS) using multivariate Cox regression adjusting for adjuvant therapy, age, T and N stage, perineural and lymphovascular invasion...