Ting-Chun Kuo

PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis

PurposeTo correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI.MethodsThis prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model.ResultsADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage.ConclusionThe imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer.

Glycemic Change After Pancreaticoduodenectomy: A Population-Based Study

AbstractThe purpose of this population-based study was to determine the change of glucose metabolism in patients undergoing pancreaticoduodenectomy (PD).We conducted a nationwide cohort study using data from Taiwans National Health Insurance Research Database collected between 2000 and 2010. Our sample included 861 subjects with type 2 diabetes mellitus (DM) and 3914 subjects without DM.Of 861 subjects with type 2 diabetes, 174 patients (20.2%) experienced resolution of their diabetes after PD, including patients with pancreatic ductal adenocarcinoma (PDAC) (20.5%), and non-PDAC (20.1%). Using a multiple logistic regression model, we found that subjects with comorbid chronic pancreatitis (odds ratio, 0.356; 95% CI, 0.167–0.759; P = 0.007) and use of insulin (odds ratio, 0.265; 95% CI, 0.171–0.412; P < 0.001) had significantly lower rates of resolution of diabetes. In the 3914 subjects without diabetes, the only statistically significant comorbidity contributing to pancreatogenic diabetes was chronic pancreatitis (odds ratio, 1.446; 95% CI, 1.146–1.823; P = 0.002).Subjects with comorbid chronic pancreatitis and use of insulin had lower rates of resolution of DM after PD. In subjects without diabetes, chronic pancreatitis contributed significantly to the development of pancreatogenic DM.

Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer

Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation (radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to co-administration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA double-strand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit (DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer.

Utility of the 2006 Sendai and 2012 Fukuoka guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas: A single-center experience with 138 surgically treated patients

AbstractThis study aimed to evaluate the utility of the 2006 Sendai and 2012 Fukuoka guidelines for differentiating malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas from benign IPMN.Between January 2000 and March 2015, a total of 138 patients underwent surgery and had a pathologically confirmed pancreatic IPMN. Clinicopathological parameters were reviewed, and all patients were classified according to both the 2006 Sendai and 2012 Fukuoka guidelines. Univariate and multivariate analyses were used for identifying significant factors associated with malignancy in IPMN.There were 9 high-grade dysplasia (HGD) and 37 invasive cancers (ICs) in the 138 patients. The positive predictive value (PPV) and negative predictive value (NPV) of the Sendai and Fukuoka guidelines for HGD/IC was 35.1%, 43.3%, 100%, and 85.4%, respectively. Of the 36 patients with worrisome features using the Fukuoka guideline, 7 patients had HGD/IC in their IPMNs. According to the multivariate analysis, jaundice, tumors of ≥3 cm, presence of mural nodule on imaging, and aged <65 years were associated with HGD/IC in patients with IPMN.The Sendai guideline had a better NPV, but the Fukuoka guideline had a better PPV. We suggest that patients with worrisome features based on the Fukuoka guideline be aggressively managed.

Change of Both Endocrine and Exocrine Insufficiencies After Acute Pancreatitis in Non-Diabetic Patients: A Nationwide Population-Based Study

AbstractAcute pancreatitis (AP) is the most common pancreatic disease and consists of an acute inflammation of the pancreas. AP can contribute to endocrine and exocrine insufficiencies in survivors as a result of the key role of the pancreas in both glucose metabolism and nutritional digestion. The aim of this population-based study was to determine the endocrine or exocrine insufficiencies in patients after initial AP with biliary or alcohol-associated causes.We conducted a nationwide cohort study using data from Taiwans National Health Insurance Research Database collected between 2001 and 2010. A total of 12,284 patients with AP were identified.Alcohol-associated AP (odds ratio, 1.894; 95% CI, 1.520–2.268; P < 0.001) and ≥2 admissions for AP (odds ratio, 1.937; 95% CI, 1.483–2.391; P < 0.001) were significantly associated with newly diagnosed diabetes mellitus after AP. Further, only alcohol-associated AP (odds ratio, 1.215; 95% CI, 1.133–1.297; P < 0.001) was significantly associated with pancreatic exocrine insufficiency after AP. Additionally, alcohol-associated AP (odds ratio, 1.804; 95% CI, 1.345–2.263; P < 0.001) and ≥2 readmissions for AP (odds ratio, 3.190; 95% CI, 2.317–4.063; P < 0.001) were significantly associated with both exocrine and endocrine insufficiencies after AP.Our data showed that alcohol-associated AP, rather than a biliary cause, contributed to a higher extent to exocrine or endocrine insufficiencies. Furthermore, recurrent AP also led to endocrine insufficiency.

Obstructive jaundice as a complication of a right hepatic artery pseudoaneurysm after laparoscopic cholecystectomy

A hepatic artery pseudoaneurysm is a rare, but a potentially life-threatening complication after laparoscopic cholecystectomy (LC). Obstructive jaundice owing to a hepatic artery pseudoaneurysm after LC has never been reported. We report a patient with a hepatic artery pseudoaneurysm after LC who presented with tarry stools, bloody drainage and obstructive jaundice.

Silencing of MUC20 suppresses the malignant character of pancreatic ductal adenocarcinoma cells through inhibition of the HGF/MET pathway

Mucins are heavily glycosylated proteins that play critical roles in the pathogenesis of tumour malignancies. Pancreatic ductal adenocarcinoma (PDAC) is characterised by the aberrant expression of mucins. However, the role of mucin (MUC) 20 in PDAC remains unclear. PDAC is usually surrounded by a dense fibrotic stroma consisting of an extracellular matrix and pancreatic stellate cells (PSCs). The stroma creates a nutrient-deprived, hypoxic, and acidic microenvironment, and promotes the malignant behaviours of PDAC cells. In this study, immunohistochemical staining demonstrated that high MUC20 expression correlated with poor progression-free survival and high local recurrence rate of PDAC patients (n = 61). The expression of MUC20 was induced by serum deprivation, hypoxia, and acidic pH in PDAC cells. MUC20 knockdown with siRNA decreased cell viability, as well as migration and invasion induced by PSCs in HPAC and HPAF-II cells. In intraperitoneal, subcutaneous, and orthotopic injection models, MUC20 knockdown decreased tumour growth in immunodeficient mice. Phospho-RTK array and western blot analysis indicated that MUC20 knockdown decreased HGF-mediated phosphorylation of MET in PDAC cells. Moreover, HGF-induced malignant phenotypes could be suppressed by MUC20 knockdown. Co-immunoprecipitation revealed the physical association of MUC20 and MET. These findings suggest that MUC20 knockdown suppresses the malignant phenotypes of PDAC cells at least partially through the inhibition of the HGF/MET pathway and that MUC20 could act as a potential therapeutic target.

Preoperative biliary drainage associated with biliary stricture after pancreaticoduodenectomy: a population-based study

The rate of preoperative biliary drainage for pancreaticoduodenectomy has been increasing despite most recent evidence that favors avoiding it. Only a few studies have focused on late surgical complications – biliary stricture after pancreaticoduodenectomy and have produced only inconclusive results. We evaluate the role of preoperative biliary drainage in the formation of biliary stricture after pancreaticoduodenectomy.

Distal Enteral Feeding Helps Blood Sugar Control in Pancreatectomized Patients.

AbstractBackgroundThe change in the route of food passage after pancreaticoduodenectomy (PD) is quite similar to the change after gastric bypass surgery; both procedures bypass the duodenum and directly connect to the distal jejunum. Moreover, both procedures result in resolution of type 2 diabetes mellitus. Therefore, more distal enteral anastomosis after PD may further improve glycemic status.Methods To test the effect of distal enteral feeding on glucose metabolism in patients after PD, we performed a meal test on 20 patients via a nasogastric tube [proximal feeding group (PFG)] on post-operative day 5 and then via an intra-operatively placed jejunostomy feeding tube [distal feeding group (DFG)] on post-operative day. Blood samples were assessed for hormones and glucose.ResultsThe AUC0–120 min levels of GLP-1, C-peptide, and insulin after distal feeding were significantly higher than after proximal feeding. The AUC0–120 min levels of glucose in the DFG were significantly lower than in the PFG.ConclusionsMore distal enteral feeding contributed to better glucose metabolism after PD.