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Dive into the research topics where Carlos Fernandez-del Castillo is active.

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Featured researches published by Carlos Fernandez-del Castillo.


Pancreatology | 2006

International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas.

Masao Tanaka; Suresh T. Chari; Volkan Adsay; Carlos Fernandez-del Castillo; Massimo Falconi; Michio Shimizu; Koji Yamaguchi; Kenji Yamao; Seiki Matsuno

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.


Nature | 2003

Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis

Sarah P. Thayer; Marina Pasca di Magliano; Patrick W. Heiser; Corinne Nielsen; Drucilla J. Roberts; Gregory Y. Lauwers; Yan Ping Qi; Stephan Gysin; Carlos Fernandez-del Castillo; Vijay Yajnik; Bozena Antoniu; Martin McMahon; Andrew L. Warshaw; Matthias Hebrok

Hedgehog signalling—an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer—may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx–Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis.


Modern Pathology | 2012

Consensus statement on the pathology of IgG4-related disease.

Vikram Deshpande; Yoh Zen; John K. C. Chan; Eunhee E Yi; Yasuharu Sato; Tadashi Yoshino; Günter Klöppel; J. Godfrey Heathcote; Arezou Khosroshahi; Judith A. Ferry; Rob C. Aalberse; Donald B. Bloch; William R. Brugge; Adrian C Bateman; Mollie N. Carruthers; Suresh T. Chari; Wah Cheuk; Lynn D. Cornell; Carlos Fernandez-del Castillo; David G. Forcione; Daniel L. Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Gregory Y. Lauwers; Yasufumi Masaki; Yasuni Nakanuma; Kenji Notohara; Kazuichi Okazaki

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.


Annals of Surgery | 2004

Main-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: Clinical Predictors of Malignancy and Long-term Survival Following Resection

Roberto Salvia; Carlos Fernandez-del Castillo; Claudio Bassi; Sarah P. Thayer; Massimo Falconi; William Mantovani; Paolo Pederzoli; Andrew L. Warshaw

Objective:To describe clinical characteristics and outcomes of a large cohort of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas affecting the main pancreatic duct. Summary Background Data:IPMNs are being diagnosed with increasing frequency. Preoperative determination of malignancy remains problematic, and reported results of long-term survival following resection are conflicting. Methods:The combined databases from the Massachusetts General Hospital and the Pancreatic Unit of the University of Verona were analyzed. To avoid confusing overlap with mucinous cystic neoplasms, only patients with tumors of the main pancreatic duct (with or without side branch involvement) were included. A total of 140 tumors consecutively resected between 1990 and 2002 were classified as either benign (adenoma and borderline tumors) or malignant (carcinoma in situ or invasive cancer) to compare their characteristics and survival. Results:Men and women were equally affected (mean age 65 years). Seven patients (12%) had adenomas, 40 (28%) borderline tumors, 25 (18%) carcinoma in situ, and 58 (42%) invasive carcinoma. The median age of patients with benign IPMN was 6.4 years younger than those with malignant tumors (P = 0.04). The principal symptoms were abdominal pain (65%), weight loss (44%), acute pancreatitis (23%), jaundice (17%), and onset or worsening of diabetes (12%); 27% of patients were asymptomatic. Jaundice and diabetes were significantly associated with malignant tumors. Five- and 10-year cancer-specific survival for patients with noninvasive tumors was 100%, and comparable survival of the 58 patients with invasive carcinoma was 60% and 50%. Conclusions:Cancer is found in 60% of patients with main-duct IPMNs. Patients with malignant tumors are 6 years older than their benign counterparts and have a higher likelihood of presenting with jaundice or new onset diabetes. No patients with benign tumors or carcinoma in situ died of their disease following resection, and those with invasive cancer had a markedly better survival (60% at 5 years) than pancreatic ductal adenocarcinoma. These findings support both the concept of progression of benign IPMNs to invasive cancer and an aggressive policy of resection at diagnosis.


Arthritis & Rheumatism | 2012

Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations

John H. Stone; Arezou Khosroshahi; Vikram Deshpande; John K. C. Chan; J. Godfrey Heathcote; Rob C. Aalberse; Atsushi Azumi; Donald B. Bloch; William R. Brugge; Mollie N. Carruthers; Wah Cheuk; Lynn D. Cornell; Carlos Fernandez-del Castillo; Judith A. Ferry; David G. Forcione; Günter Klöppel; Daniel L. Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Yasufumi Masaki; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant V. Sahani; Yasuharu Sato; Thomas C. Smyrk; James R. Stone

John H. Stone, Arezou Khosroshahi, Vikram Deshpande, John K. C. Chan, J. Godfrey Heathcote, Rob Aalberse, Atsushi Azumi, Donald B. Bloch, William R. Brugge, Mollie N. Carruthers, Wah Cheuk, Lynn Cornell, Carlos Fernandez-Del Castillo, Judith A. Ferry, David Forcione, Gunter Kloppel, Daniel L. Hamilos, Terumi Kamisawa, Satomi Kasashima, Shigeyuki Kawa, Mitsuhiro Kawano, Yasufumi Masaki, Kenji Notohara, Kazuichi Okazaki, Ji Kon Ryu, Takako Saeki, Dushyant Sahani, Yasuharu Sato, Thomas Smyrk, James R. Stone, Masayuki Takahira, Hisanori Umehara, George Webster, Motohisa Yamamoto, Eunhee Yi, Tadashi Yoshino, Giuseppe Zamboni, Yoh Zen, and Suresh Chari


Annals of Surgery | 2008

Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients.

Stefano Crippa; Roberto Salvia; Andrew L. Warshaw; Ismael Domínguez; Claudio Bassi; Massimo Falconi; Sarah P. Thayer; Giuseppe Zamboni; Gregory Y. Lauwers; Mari Mino-Kenudson; Paola Capelli; Paolo Pederzoli; Carlos Fernandez-del Castillo

Objective:Mucinous cystic neoplasms (MCNs) of the pancreas have often been confused with intraductal papillary mucinous neoplasms. We evaluated the clinicopathologic characteristics, prevalence of cancer, and prognosis of a large series of well-characterized MCNs in 2 tertiary centers. Methods:Analysis of 163 patients with resected MCNs, defined by the presence of ovarian stroma and lack of communication with the main pancreatic duct. Results:MCNs were seen mostly in women (95%) and in the distal pancreas (97%); 25% were incidentally discovered. Symptomatic patients typically had mild abdominal pain, but 9% presented with acute pancreatitis. One hundred eighteen patients (72%) had adenoma, 17 (10.5%) borderline tumors, 9 (5.5%) in situ carcinoma, and 19 (12%) invasive carcinoma. Patients with invasive carcinoma were significantly older than those with noninvasive neoplasms (55 vs. 44 years, P = 0.01). Findings associated with malignancy were presence of nodules (P = 0.0001) and diameter ≥60 mm (P = 0.0001). All neoplasms with cancer were either ≥40 mm in size or had nodules. There was no operative mortality and postoperative morbidity was 49%. Median follow-up was 57 months (range, 4–233); only patients with invasive carcinoma had recurrence. The 5-year disease-specific survival for noninvasive MCNs was 100%, and for those with invasive cancer, 57%. Conclusions:This series, the largest with MCNs defined by ovarian stroma, shows a prevalence of cancer of only 17.5%. Patients with invasive carcinoma are older, suggesting progression from adenoma to carcinoma. Although resection should be considered for all cases, in low-risk MCNs (≤4 cm/no nodules), nonradical resections are appropriate.


Journal of Clinical Oncology | 2006

Perioperative CA19-9 Levels Can Predict Stage and Survival in Patients With Resectable Pancreatic Adenocarcinoma

Cristina R. Ferrone; Dianne M. Finkelstein; Sarah P. Thayer; Alona Muzikansky; Carlos Fernandez-del Castillo; Andrew L. Warshaw

PURPOSE Different prognostic factors stratify patients with pancreatic adenocarcinoma. The purpose of this study was to determine whether preoperative CA19-9 levels can predict stage of disease or survival and whether a change in preoperative to postoperative CA19-9 or the postoperative CA19-9 predicts overall survival. PATIENTS AND METHODS Four hundred twenty-four consecutive patients with pancreatic adenocarcinoma underwent resection between January 1, 1985 and January 1, 2004. Of the patients with a bilirubin less than 2 mg/dL, 176 had preoperative CA19-9 values, and 111 had pre- and postoperative CA19-9 values. Survival was measured from the first postoperative CA19-9 level measured (median, 39 days) until death or last follow-up. A multivariate failure time model was fit using clinical, operative, pathologic, and adjuvant treatment characteristics, and a categorization was defined by the values and changes in CA19-9 before and after surgery. RESULTS Of the 176 patients, 128 (73%) had T3 lesions, and 99 (56%) had N1 disease; 138 patients (78%) underwent pancreaticoduodenectomy. Median preoperative CA19-9 levels were lower in N0 patients compared with patients with positive nodes (nine v 164 U/mL, respectively; nonparametric P = .06) and in T1/T2 patients versus T3 patients (41 v 162 U/mL, respectively; P = .03). Median follow-up time (n = 111) was 1.8 years (range, 1 to 12.9 years), with overall actuarial 1-, 3-, and 5-year survival rates of 70%, 36%, and 30%, respectively. Significant predictors of survival on multivariate analysis included a decrease in CA19-9 (P = .0005), negative lymph nodes (P = .001), lower T stage (P = .0008), and postoperative CA19-9 less than 200 U/mL (P = .0007). CONCLUSION In patients with pancreatic adenocarcinoma, preoperative CA19-9 correlates with stage of disease. Both a postoperative decrease in CA19-9 and a postoperative CA19-9 value of less than 200 U/mL are strong independent predictors of survival, even after adjusting for stage. CA19-9 levels should be included in a patients perioperative care and should be considered for prognostic nomograms.


Annals of Surgery | 2005

Serous Cystadenoma of the Pancreas: Tumor Growth Rates and Recommendations for Treatment

Jennifer F. Tseng; Andrew L. Warshaw; Dushyant V. Sahani; Gregory Y. Lauwers; David W. Rattner; Carlos Fernandez-del Castillo

Objective:To define the natural history and optimal management of serous cystadenoma of the pancreas. Summary Background Data:Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. Methods:A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976–2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. Results:Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 ± 3.1 cm, which did not vary by location. Tumors <4 cm were less likely to be symptomatic than were tumors ≥4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors <4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors ≥4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. Conclusions:Large (>4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms.


Annals of Surgery | 2015

Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer.

Cristina R. Ferrone; Giovanni Marchegiani; Theodore S. Hong; David P. Ryan; Vikram Deshpande; Erin McDonnell; Francesco Sabbatino; Daniela Dias Santos; Jill N. Allen; Lawrence S. Blaszkowsky; Jeffrey W. Clark; Jason E. Faris; Lipika Goyal; Eunice L. Kwak; Janet E. Murphy; David T. Ting; Jennifer Y. Wo; Andrew X. Zhu; Andrew L. Warshaw; Keith D. Lillemoe; Carlos Fernandez-del Castillo

PURPOSE On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic pancreatic adenocarcinoma (PDAC), making it a rational choice for locally advanced PDAC (LA). Aims of this study are to evaluate the accuracy of imaging in determining the resectability of PDAC and to determine the surgical and clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX therapy. PATIENTS AND METHODS Clinicopathologic data were retrospectively collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no neoadjuvant therapy between April 2011 and February 2014. Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was reviewed by a blinded senior pancreatic surgeon. RESULTS Of 188 patients undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87 received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in tumor size, yet 19 patients were still classified as LA and 9 as borderline. Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs 400 mL), but significantly lower operative morbidity (36% vs 63%) and no postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%) and perineural invasion (72% vs 95%). Median follow-up was 11 months with a significant increase in overall survival with FOLFIRINOX. CONCLUSIONS After neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional pathologic predictors of survival are improved, and morbidity is decreased in comparison to patients with clearly resectable cancers at the time of presentation.


The New England Journal of Medicine | 1991

Risk Factors for Pancreatic Cellular Injury after Cardiopulmonary Bypass

Carlos Fernandez-del Castillo; Wolfgang Harringer; Andrew L. Warshaw; Gus J. Vlahakes; Greg Koski; Alan M. Zaslavsky; David W. Rattner

BACKGROUND Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it.

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