Jong-chan Lee

High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor.

AbstractThere is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery.For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data.Eight miRNAs (miRNA-27b, -122, -142–5p, -196a, -223, -590–5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732–153.789; P = 0.015).MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.

Initial Metastatic Site as a Prognostic Factor in Patients With Stage IV Pancreatic Ductal Adenocarcinoma.

Abstract Few studies have evaluated the presence of hepatic or peritoneal metastasis as a prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to elucidate the prognostic value of the initial metastatic, extrahepatic, or hepatic site in patients with metastatic PDAC. Between January 2007 and December 2013, the medical records of 343 patients with metastatic PDAC treated at Seoul National University Bundang Hospital were retrospectively reviewed. Patients were classified as having extrahepatic metastasis alone (EH), hepatic metastasis alone (LV), and both hepatic and extrahepatic metastasis (BOTH). The median age was 67 years; 207 patients were men. Patients were classified as having EH (111 patients), LV (106), and BOTH (126). Totally, 212 patients underwent chemotherapy with a FOLFIRINOX (23 patients) or gemcitabine-based regimen (189). On multivariate analysis, an ECOG score ≥2 (hazard ratio [HR]: 3.2, 95% confidence interval [CI]: 2.2–4.5), albumin < 35 g/L (HR: 1.6, 95% CI: 1.1–2.3), C-reactive protein > 10 mg/L (HR: 2.3, 95% CI: 1.6–3.2), neutrophil-lymphocyte ratio > 5 (HR: 1.4, 95% CI: 1.0–2.0), no chemotherapy (HR: 2.0, 95% CI: 1.0–4.1), and metastatic site (LV, HR: 2.1, 95% CI: 1.4–3.1; BOTH, HR: 2.2, 95% CI: 1.6–3.2) were significantly associated with shorter overall survival (OS). Considering the initial metastatic site, the median OS of patients with EH, LV, and BOTH were 7.5 (95% CI: 6.3–8.8), 4.8 (95% CI: 4.1–5.5), and 2.4 (95% CI: 1.9–2.9) months, respectively. The initial metastatic site is significantly and independently associated with OS in patients with metastatic PDAC, serving as an effective prognostic factor.

Comparison of severity predictive rules for hospitalised nursing home-acquired pneumonia in Korea: a retrospective observational study

Background: Nursing home-acquired pneumonia (NHAP) is the leading cause of death among long-term care residents. Aims: To compare current scoring indices (NHAP model score, Pneumonia Severity Index (PSI), CURB-65 (confusion, urea nitrogen, respiratory rate, blood pressure, age >65 years) and SOAR (systolic blood pressure, oxygenation, age, respiratory rate)) in predicting mortality and admission to the intensive care unit (ICU) in patients with NHAP. Methods: This retrospective observational study was conducted between July 2008 and June 2011 using data from the Korean Nursing Home Networks. Two hundred and eight nursing home residents were hospitalised with pneumonia in one general hospital. The primary outcome measure was 30-day all-cause mortality. Secondary outcome measures were intensive respiratory or vasopressor support (IRVS), and severe pneumonia (ICU admission or IRVS). Results: PSI class V showed the highest Youden index (0.45), specificity (66.7%), positive predictive value (PPV, 40.0%), negative predictive value (NPV, 91.5%), and area under the curve (AUC, 0.73) for 30-day mortality. For severe pneumonia, PSI class V showed the highest Youden index (0.40), specificity (72.8%), PPV (62.2%), NPV (77.1%), and AUC (0.70). Similarly, PSI class V showed the highest Youden index (0.35), specificity (68.3%), PPV (51.1%), NPV (80.5%), and AUC (0.69) for IRVS. Conclusions: The PSI has superior discriminatory power in predicting all three clinical outcomes (30-day mortality, severe pneumonia, and IVRS) compared with the NHAP model score, CURB-65 and SOAR.

Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer.

Background: The adjunctive role of magnetic resonance imaging of the liver before pancreatic ductal adenocarcinoma has been unclear. We evaluated whether the combination of hepatic magnetic resonance imaging with multidetector computed tomography using a pancreatic protocol (pCT) could help surgeons select appropriate candidates and decrease the risk of early recurrence. Methods: We retrospectively enrolled 167 patients in whom complete resection was achieved without grossly visible residual tumor; 102 patients underwent pCT alone (CT group) and 65 underwent both hepatic magnetic resonance imaging and pCT (magnetic resonance imaging group). Results: By adding hepatic magnetic resonance imaging during preoperative evaluation, hepatic metastases were newly discovered in 3 of 58 patients (5%) without hepatic lesions on pCT and 17 of 53 patients (32%) with indeterminate hepatic lesions on pCT. Patients with borderline resectability, a tumor size >3 cm, or preoperative carbohydrate antigen 19–9 level >1,000 U/mL had a greater rate of hepatic metastasis on subsequent hepatic magnetic resonance imaging. Among 167 patients in whom R0/R1 resection was achieved, the median overall survival was 18.2 vs 24.7 months (P = .020) and the disease‐free survival was 8.5 vs 10.0 months (P = .016) in the CT and magnetic resonance imaging groups, respectively (median follow‐up, 18.3 months). Recurrence developed in 82 (80%) and 43 (66%) patients in the CT and magnetic resonance imaging groups, respectively. The cumulative hepatic recurrence rate was greater in the CT group than in the magnetic resonance imaging group (P < .001). Conclusion: Preoperative hepatic magnetic resonance imaging should be considered in patients with potentially resectable pancreatic ductal adenocarcinoma, especially those with high tumor burden.

Comparison of Endoscopic Ultrasonography, Computed Tomography, and Magnetic Resonance Imaging for Pancreas Cystic Lesions.

AbstractConsensus regarding which modality is optimal for the measurement of pancreas cystic lesions (PCLs) was not achieved although cyst size is important for clinical decisions. This study aimed to evaluate the properties of endoscopic ultrasonography (EUS) compared with computed tomography (CT) and magnetic resonance imaging (MRI) in measuring the size of PCL.A total of 34 patients who underwent all 3 imaging modalities within 3 months before surgery were evaluated retrospectively. The size measured by each modality was compared with the pathologic size as a reference standard using Bland–Altman analysis and intraclass correlation coefficients (ICCs).The mean size difference was 1.76 mm (ICC 0.86), 7.35 mm (ICC 0.95), and 8.65 mm (ICC 0.93) in EUS, CT, and MRI. EUS had the widest range of 95% limits of agreement (LOA) (−17.54 to +21.07), compared with CT (−6.21 to +20.91), and MRI (−6.82 to +24.12). The size by EUS tended to be read smaller in tail portion, while those by CT and MRI did not. When the size was more than 4 cm, the size on EUS was estimated to be smaller than on pathology (r = 0.492; P = 0.003).Although 3 modalities showed very good reliability for the size measurement on PCL compared with corresponding pathologic size, EUS had the lowest level of agreement, while CT showed the highest level among the 3 modalities. Therefore, the size estimated by EUS has to be interpreted with caution, especially when it is located in tail and relevantly large.

Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern

Abstract Several reports showed that interleukin-6 (IL-6) or -8 (IL-8) might be useful inflammatory biomarkers for pancreatic ductal adenocarcinoma (PDAC), although these clinical impact is still open to debate. The aim of this study was to elucidate whether serum levels of IL-6 and IL-8 at diagnosis could predict the tumor progression pattern of PDAC, especially in extensive hepatic metastasis. According to the tumor burden of hepatic metastasis at the last follow-up, tumor progression pattern was defined as follows: no or limited (unilobar involvement and 5 or less in the within liver, limited group) and extensive hepatic metastasis (bilobar or more than 5, progressed group). Fifty-three PDAC patients with initially no or limited hepatic metastasis were enrolled retrospectively. Around 42 (79.2%) were included in the limited and 11 (20.8%) in the progressed group. The median serum level of IL-6 in the progressed group was elevated significantly compared with the limited group. However, the median serum level of IL-8 was not. Furthermore, multivariate analysis revealed that the elevated serum level of IL-6 was an independent risk factor for progression to extensive hepatic metastasis (odds ratio 1.928, 95% confidence interval 1.131–3.365, P = 0.019), but IL-8 was not. However, higher IL-6 did not predict shorter survival. High serum IL-6 can be an independent risk factor for progression to extensive hepatic metastasis in PDAC patients.

Comparisons of Gut Microbiota Among Healthy Control, Patients With Conventional Adenoma, Sessile Serrated Adenoma, and Colorectal Cancer

Background Studies on gut microbiota regarding colorectal carcinogenesis, including sessile serrated adenoma (SSA), have been scarce. The aim of this study is to investigate the role of mucosa-associated gut microbiota in the colorectal carcinogenesis. Methods We collected biopsy samples of normal rectal mucosa during colonoscopy from healthy control and patients with conventional adenoma, SSA, and colorectal cancer (CRC), respectively (n = 6). Pyrosequencing for 16S rRNA gene of bacteria was performed to compare gut microbiota. Results The most abundant phylum in total samples was Proteobacteria (55.6%), followed by Firmicutes (27.4%) and Bacteroidetes (11.6%). There was no significant difference in relative abundance of the phylum level among the four groups. Fusobacterium nucleatum, known to be frequently detected during colorectal carcinogenesis, was found in only one sample of patient with SSA. The rarefaction curves showed that the diversity of mucosal communities of patients with CRC is the lowest among the four groups and the diversity of mucosal communities of patients with SSA is higher than that of healthy control. Among the four groups, Shannon’s and Simpson’s index for diversity was the lowest and the highest in the patients with CRC, respectively; it did not reach statistical significance. The proportion of genus Pseudomonas was very high in the samples of patients with stage II–IV CRC compared with those with stage I CRC (59.3% vs. 0.3%, P = 0.064). Conclusions Our study suggests no significant role of mucosa-associated gut microbiota in the colorectal carcinogenesis. Further study for many samples or using fecal material could be helpful.

Effects of Age on Esophageal Motility: Use of High-resolution Esophageal Impedance Manometry

Background/Aims Disturbances of esophageal motility have been reported to be more frequent the aged population. However, the physiology of disturbances in esophageal motility during aging is unclear. The aim of this study was to evaluate the effects of age on esophageal motility using high-resolution esophageal impedance manometry (HRIM). Methods Esophageal motor function of 268 subjects were measured using HRIM in 3 age groups, < 40 years (Group A, n = 32), 40–65 years (Group B, n = 185), and > 65 years (Group C, n = 62). Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures, integrated relaxation pressure, distal contractile integral, contractile front velocity, distal latency, and pressures and duration of contraction on 4 positions along the esophagus, and complete bolus transit were measured. Results Basal UES pressure was lower in Group C (P < 0.001) but there was no significant difference in the LES pressure among groups. Contractile duration on position 3 (10 cm from proximal LES high pressure zone) was longer in Group C (P = 0.001), and the contractile amplitude on position 4 (5 cm from proximal LES high pressure zone) was lower in Group C (P = 0.005). Distal contractile integral was lower in Group C (P = 0.037). Contractile front velocity (P = 0.015) and the onset velocity (P = 0.040) was lower in Group C. There was no significant difference in impedance values. Conclusions The decrease of UES pressure, distal esophageal motility, and peristaltic velocity might be related with esophageal symptoms in the aged population.

Risk Factors for Gallstone Formation in Resected Gastric Cancer Patients

AbstractPrevious studies reported increased incidence of gallstone formation after gastrectomy. However, there were few reports about factors other than surgical technique. The purpose of this study is to investigate the spectrum of risk factors of gallstone formation after gastrectomy.From June 2003 to December 2008, 1480 patients who underwent gastrectomy due to gastric cancer but had no gallstones before surgery were identified. Electronic medical records were retrospectively reviewed. Gallstones were assessed by computerized tomography or ultrasound performed as surveillance for recurrence.There were 987 men (66.7%) and the median age was 59.0 years. The median follow-up period was 47.0 months. According to the surgical technique, 754 (50.9%), 459 (31.1%), and 267 (18.0%) underwent subtotal gastrectomy with Billroth I (STG B-I) and Billroth II (STG B-II) anastomosis, and total gastrectomy (TG). Within the follow-up period, gallstone formation occurred in 106 of 1480 patients (7.2%), the only 9 patients (0.6%) experienced symptomatic cholecystitis. By multivariate Cox regression analysis, age (HR 1.02, 95% CI 1.00–1.04), male (1.65, 1.02–2.67), diabetes mellitus (2.15, 1.43–3.24), ≥4% decrease of body mass index after surgery (1.66, 1.02–2.70), STG B-II (1.63, 1.03–2.57), and TG (2.35, 1.43–3.24) compared with STG B-I were associated with gallstone formation. Common bile duct stone formation occurred in 20 of 1480 patients (1.4%) and was only associated with gallstones.After gastrectomy, there were considerable numbers of patients with newly developed gallstones; however, prophylactic cholecystectomy should not be routinely recommended. Gastrectomy (STG B-II or TG), old age, male sex, diabetes mellitus, and decreased body mass index were associated with gallstones.

Characteristics of Venous Thromboembolism in Pancreatic Adenocarcinoma in East Asian Ethnics: A Large Population-Based Observational Study.

AbstractPancreatic cancer (PC) is known to be frequently associated with venous thromboembolism (VTE). Although treatment and prophylaxis strategies for VTE in PC patients were updated recently, these were mainly based on data from Western populations and were not verified in East Asian ethnic populations.We investigated the clinical characteristics of VTE in East Asian PC patients. We reviewed electronic medical records (EMR) of 1334 patients diagnosed with pancreatic adenocarcinoma from 2005 to 2010 at single tertiary hospital in Korea. All the patients with newly diagnosed VTE were classified by anatomical site and manifestation of symptoms. The primary outcomes of interest were 2-year cumulative incidence of VTE events. Cox proportional hazards models were used to analyze associations between risk factors and clinical outcomes.A total of 1115 patients were eligible for enrollment. The 2-year cumulative VTE incidence was 9.2%. Major risk factors associated with VTE event were advanced cancer stage, major surgery, and poor performance status. Risk factors associated with mortality after PC diagnosis included advanced cancer stage, poor performance score, leukocytosis, and lower albumin level. The overall VTE did not affected mortality. However in subgroup analysis, symptomatic VTE and deep vein thrombosis/pulmonary thromboembolism (DVT/PTE) showed worse prognosis than incidental or intra-abdominal VTE.The overall incidence of VTE events in Korean PC patients was lower than previous studies. Advanced cancer stage was the most important factor for VTE event and mortality. Unlike Western population group, VTE event did not affect overall prognosis after PC diagnosis. However, symptomatic VTE and DVT/PTE showed higher mortality after VTE event.