- Pancreatic developmental defect evaluated by celiac artery angiography in a patient with MODY5. [JOURNAL ARTICLE]
- Hum Genome Var 2016.:16022.
The hepatocyte nuclear factor 1β gene (HNF1B) is responsible for maturity-onset diabetes of the young type 5 (MODY5), which is characterized by early-onset diabetes mellitus and urogenital malformations. HNF1B is expressed during visceral endoderm formation. We identified a disruption of the great pancreatic artery in a patient with MODY5 with no pancreatic body or tail. Our finding supports the significance of HNF1B in the development of the pancreas.
- Preoperative defining system for pancreatic head cancer considering surgical resection. [JOURNAL ARTICLE]
- World J Gastroenterol 2016 Jul 14; 22(26):6076-6082.
To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing "resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly". The oncologic correlations with this reporting system were evaluated.Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size ≥ 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 ≥ 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.
- MRI findings of intraductal papillary mucinous neoplasms (IPMNs). [JOURNAL ARTICLE]
- Acta Biomed 2016; 87(3 - S):28-33.
Cystic lesions of the pancreas are relatively frequent imaging findings due to the improvement of imaging technologies. They may be secondary to both benign and malignant disease processes and their prevalence increases with age. In most cases, these lesions are detected incidentally by computed tomography and magnetic resonance imaging (MRI) performed for other reasons. Intraductal papillary mucinous neoplasms (IPMNs) represent 25% of the cystic neoplasms, morphologically classified into "main pancreatic duct IPMN" (MPD-IPMN), "side branches IPMN" (SB-IPMN) and mixed forms. Magnetic Resonance Cholangiopancreatography (MRCP) is a multiparametricity not invasive radiological technique that doesn't use ionizing radiation or organ iodinized contrast agents; it allows an accurate characterization of the lesions (number and size of cystic lesions, internal features of a cyst, ducts dilation, communication with main pancreatic duct) that is important to guide the differential diagnosis and establish a correct follow-up. International guidelines consider IPMN of MPD and mixed forms to be an indication for surgery, while clinical and radiological follow-up is indicated in asymptomatic patients with SB-IPMN, especially when lesions are < 2,5-3 cm in diameter and there are no mural nodules or dilation of MPD.
- Cardiac Assessment of Patients With Type 1 Diabetes Median 10 Years After Successful Simultaneous Pancreas and Kidney Transplantation Compared With Living Donor Kidney Transplantation. [JOURNAL ARTICLE]
- Transplantation 2016 Jun 1.
In recipients with type 1 diabetes, we aimed to determine whether long-term normoglycemia achieved by successful simultaneous pancreas and kidney (SPK) transplantation could beneficially affect progression of coronary artery disease (CAD) when compared with transplantation of a kidney-alone from a living donor (LDK).In 42 kidney transplant recipients with functioning grafts who had received either SPK (n = 25) or LDK (n = 17), we studied angiographic progression of CAD between baseline (pretransplant) and follow-up at 7 years or older. In addition, computed tomography scans for measures of coronary artery calcification and echocardiographic assessment of left ventricular systolic function were addressed at follow-up.During a median follow-up time of 10.1 years (interquartile range [IQR], 9.1-11.5) progression of CAD occurred at similar rates (10 of 21 cases in the SPK and 5 of 14 cases in the LDK group; P = 0.49). Median coronary artery calcification scores were high in both groups (1767 [IQR, 321-4035] for SPK and 1045 [IQR, 807-2643] for LDK patients; P = 0.59). Left ventricular systolic function did not differ between the 2 groups. The SPK and LDK recipients were similar in age (41.2 ± 6.9 years vs 40.5 ± 10.3 years; P = 0.80) and diabetes duration at engraftment but with significant different mean HbA1c levels of 5.5 ± 0.4% for SPK and 8.3 ± 1.5% for LDK patients (P < 0.001) during follow-up.In patients with both type 1 diabetes and end-stage renal disease, SPK recipients had similar progression of CAD long-term compared with LDK recipients. Calcification of coronary arteries is a prominent feature in both groups long-term posttransplant.
- FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience. [JOURNAL ARTICLE]
- Br J Cancer 2016 Jul 28.
FOLFIRINOX has been shown to significantly increase both overall survival (OS) and progression-free survival (PFS) in metastatic pancreas cancer. There is limited data regarding the treatment of locally advanced pancreatic cancer. We present a retrospective study of patients with both locally advanced and metastatic pancreas cancer using FOLFIRINOX as first-line therapy in our centre.This is a retrospective review of patients treated with FOLFIRINOX for pancreatic cancer at Princess Margaret Cancer Centre, between December 2011 and July 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications.One hundred two patients were identified; 66 metastatic and 36 locally advanced. Sixty-eight per cent of patients initiated treatment with a dose reduction. The median (95% CI) OS in the metastatic group was 13.1 (6.3-16.1) months with full dose and 12.9 (10.3-30.1) months with modified dose. The median (95% CI) OS in the locally advanced group was 11.1 (6.1-not reached) months with full dose and 23 (not reached-not reached) months with modified dose. The median (95% CI) PFS in the metastatic group was 6.2 (4.9-15.2) months with full dose and 8.7 (5.7-12.9) months with modified dose. The median (95% CI) PFS in the locally advanced group was 11.1 (3.1-not reached) months with full dose and 10.4 (6.8-not reached) months with modified dose. Grade 3/4 haematologic adverse events were observed in 43% of patients. Grade 3/4 non-haematologic adverse events were observed in 28% of patients. Patient well-being significantly improved from baseline to cycle 4 (P=0.002).Efficacy was achievable with dose-modified FOLFIRINOX in daily setting. The safety of FOLFIRINOX remains a concern with a high rate of grades 3 and 4 neutropaenia despite dose reduction.British Journal of Cancer advance online publication, 28 July 2016; doi:10.1038/bjc.2016.222 www.bjcancer.com.
- Taste Receptors in Upper Airway Immunity. [JOURNAL ARTICLE]
- Adv Otorhinolaryngol 2016.:91-102.
Taste receptors are well known for their role in communicating information from the tongue to the brain about nutritional value or potential toxicity of ingested substances. More recently, it has been shown that taste receptors are expressed in other locations throughout the body, including the airway, gastrointestinal tract, brain and pancreas. The roles of some 'extraoral' taste receptors are largely unknown, but emerging research suggests that bitter and sweet taste receptors in the airway are capable of sensing bacteria and modulating innate immunity. This chapter focuses on the role of bitter and sweet taste receptors in human airway innate immunity and their clinical relevance to rhinosinusitis. The bitter taste receptor T2R38 expressed in sinonasal cilia detects bitter bacterial quorum-sensing molecules and activates a nitric oxide-dependent innate immune response; moreover, there are polymorphisms in T2R38 that underlie susceptibility to chronic rhinosinusitis (CRS). Bitter and sweet receptors in sinonasal solitary chemosensory cells control secretion of antimicrobial peptides in the upper airway and may have a profound impact on airway infections in patients with CRS and diabetes. Future research on taste receptors in the airway has enormous potential to expand our understanding of host-pathogen immune interactions and provide novel therapeutic targets.
- Current Concepts and Diagnosis of IgG4-Related Pancreatitis (Type 1 AIP). [JOURNAL ARTICLE]
- Semin Liver Dis 2016 Aug; 36(3):257-273.
Although now considered to be a member of the systemic entity of immunoglobulin G4- (IgG4-) related disease, IgG4-related pancreatitis is generally referred to as type 1 autoimmune pancreatitis (AIP). Type 1 AIP was established based on a pathological background of lymphoplasmacytic sclerosing pancreatitis, high serum IgG4 concentration, and abundant IgG4-bearing plasma cell infiltration. The characteristic clinical features of type 1 AIP, such as elderly male preponderance, obstructive jaundice, and mass-forming lesions in the pancreas, often mimic those of pancreatic cancer. However, because AIP responds favorably to corticosteroid treatment, careful differentiation from pancreatic cancer is required. An AIP diagnosis is currently based on the 2011 International Consensus Diagnostic Criteria for AIP, which are based on high sensitivity, selectivity, and accuracy. Over the long term, AIP can progress to a chronic condition, with pancreatic stone formation and atrophy resembling that of chronic pancreatitis. Although AIP has been linked to the complication of malignancies, it remains controversial whether an association exists between the disease and tumor formation.
- The Pathology of IgG4-Related Disease in the Bile Duct and Pancreas. [JOURNAL ARTICLE]
- Semin Liver Dis 2016 Aug; 36(3):242-256.
Immunoglobulin G4-related disease (IgG4-RD) in the pancreatobiliary system manifests as sclerosing cholangitis (SC), hepatic inflammatory pseudotumors, and type 1 autoimmune pancreatitis (AIP). The pathology of IgG4-RD involves an inflammatory process and fibrogenic pathway, the combination of which damages the affected organs. Fibroinflammatory injury is characterized by three microscopic findings: a diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, obliterative phlebitis, and storiform fibrosis. Although the diagnosis of IgG4-related pancreatocholangitis is relatively straightforward in surgical specimens, the current clinical requirement is to diagnose patients using biopsy samples, which remains challenging. Histological differential diagnoses include primary SC, follicular cholangitis/pancreatitis, SC with granulocytic epithelial lesions, and type 2 AIP. Although the massive infiltration of IgG4-positive plasma cells is a histological hallmark of IgG4-RD, many other immune cells (e.g., Th2 lymphocytes, regulatory T cells, and M2 macrophages) appear to be strongly involved in orchestral immune reactions.
- Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer. [JOURNAL ARTICLE]
- Cancer Biol Ther 2016 Jul 28.:0.
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme implicated in cancer cell metabolic reprogramming. This is underscored by the detection of functional, somatic IDH1 mutations frequently found in secondary glioblastoma. To our knowledge, there has never been a reported, validated case of an IDH1 mutation in a pancreatic ductal adenocarcinoma (PDA). Herein, we present a case of a patient with metastatic PDA that harbored a potentially actionable, albeit rare, IDH1 mutation. As part of the Know Your Tumor project (Pancreatic Cancer Action Network), a 48-year-old female was diagnosed with metastatic PDA and subsequently started on standard of care chemotherapy, during which her hepatic lesions progressed. Detailed molecular profiling was performed on a biopsy from a liver lesion that demonstrated an IDH1 mutation, R132H. This mutation was confirmed by an independent sequencing reaction from the tumor sample, and by immunohistochemistry using an antibody specific for the IDH1 R132H mutation. The patient subsequently received a mutant IDH1 inhibitor (AG-120, Agios Pharmaceuticals, Cambridge, MA), but with no response. IDH1 mutations are common in certain cancer types, but have not been reported in PDA. We report the first case of an IDH1 mutation in this tumor type, perhaps providing a rare opportunity for a targeted therapy as a treatment option for PDA.
- Long-term Survival After Surgical Treatment of Renal Cell Carcinoma Metastasis Within the Pancreas. [Journal Article]
- Anticancer Res 2016 Aug; 36(8):4273-8.
The role of radical pancreatic surgery for metastatic lesions of renal cell carcinoma (RCC) remains unclear.In this analysis, 19 patients underwent pancreatic resections for metastases of RCC between 2000 and 2014.Pancreatic metastases were diagnosed 10.2±27.1 years after primary diagnosis of RCC. Surgical approaches included pylorus preserving pancreatoduodenectomy (PPPD) (n=10, 55.6%), followed by distal pancreatectomy (n=5, 27.8%) and total pancreatectomy (n=4, 22.2%). The survival after 1, 3 and 5 years was 88.9%, 80% and 71.4%, respectively. Patients after PPPD procedure had a significant worse survival (p=0.030). RCC stage VI tumors seem to be associated with decreased short- and long-term survival rates (p=0.03). Additional metastatic lesions in the further postoperative course had no impact on outcome.The results of our analysis demonstrate promising long-term results with regard to disease-free and overall survival after surgical therapy for pancreatic metastases of renal cell carcinoma.