Role of oxygen free radicals in patients with acute pancreatitis

AIM:The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis. METHODS:The plasma levels of C-reactive protein(CRP), lipid peroxide(LPO),myeloperoxidase(MPO)and superoxide dismutase(SOD)were measured in 13 patients with acute pancreatitis and 14 healthy volunteers. RESULTS:Among the patients with acute pancreatitis,there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis.However,there was no significant difference in the serum marker of oxidative stress no matter what the etiology was.The LPO level was especially correlated with the concentration of serum CRP and CT severity index. CONCLUSION:The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis.Especially,the concentration of plasma LPO is a meaningful index for determining the severity of the disease.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging.RESULTSThe median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.

Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A casecontrol study in Korea

AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma(ECC) and 83 intrahepatic cholangiocarcinoma(ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.RESULTS:There was an association between cholangiocarcinoma and hepatitis B virus(HBV) infection, diabetes mellitus(DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios(AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM(AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC(AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC(AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM(OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.CONCLUSION: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanismsfor such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTS The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSION m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

Placement of a fully covered self-expandable metal stent in a young patient with chronic pancreatitis

Plastic stent insertion is a treatment option for pancreatic duct stricture with chronic pancreatitis.However, recurrent stricture is a limitation after removing the plastic stent.Self-expandable metal stents have long diameters and patency.A metal stent has become an established management option for pancreatic duct stricture caused by malignancy but its use in benign stricture is still controversial.We introduce a young patient who had chronic pancreatitis and underwent several plastic stent insertions due to recurrent pancreatic duct stricture.His symptoms improved after using a fully covered self-expandable metal covered stent and there was no recurrence found at follow-up at the outpatient department.

FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer treatment.However,studies that compared these two regimens and studies in Asian populations are lacking.AIM To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean population.METHODS Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry.Treatment efficacy,treatment-related adverse events and economic aspects were compared.RESULTS Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at diagnosis.The median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX group.Grade≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group.The drug costs of both regimens were similar.CONCLUSION Treatment efficacy and economic burdens were comparable between the two regimens.But,the details of adverse event were different.Gem+nabPTX regimen might be considered preferentially in certain conditions.

Incidence of coronary artery disease before valvular surgery in isolated severe aortic stenosis

Background Angina pectoris has been recognized as one of the principal symptoms of aortic valve stenosis （AS）,even in patients without significant coronary artery disease （CAD）.However,the incidence of angina pectoris and related CAD in such patients is controversial.There is continuing debate as to whether coronary angiography is necessary before aortic valve replacement （AVR） in patients with severe AS.The purpose of this study was to evaluate the incidence and predictors of CAD in patients with severe AS in a Korean population.Methods Data from all consecutive patients with severe AS undergoing AVR at a major tertiary cardiac and vascular center in Korea were entered in a prospective registry beginning in 1995.Clinical and echocardiographic follow-up data were recorded into the database annually.Significant CAD was defined as one or more major coronary arteries having an estimated narrowing of ≥70％ and left main coronary arteries having an estimated narrowing of ≥50％ on coronary angiography.We excluded patients with multiple valve disease,significant aortic regurgitation,or prior CAD or valve surgery.Results Totally 574 patients with severe AS （mean age,（65.9±9.6） years） were enrolled in this study.Significant CAD was found in 61 patients （10.6％）.Factors associated with increased likelihood of CAD were age,hypertension,diabetes mellitus,chronic renal failure,carotid disease,and aorta calcification.In Logistic regression analysis,the independent predictor of the presence of CAD was age （P=0.011）.The incidence of CAD increased significantly at 69.2 years of age.Having two risk factors for cardiovascular disease was the most useful cutoff to predict whether a patient was going to have significant CAD.Conclusions There was a low incidence of significant CAD in a population of Korean patients with severe AS.Therefore,coronary angiography before AVR will be considered in patients with multiple risk factors for cardiovascular disease or in patients more than 69 years of age without risk factors for cardiovascular disease.