We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a well-differentiated adenocarcinoma, with negative resection margins (T2N0M0, stage IB). Nine years later, during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type IIIa, and performed bile duct excision, right hepatic lobectomy and Roux-en-Y hepaticojejunostomy. The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis (T1N1M0, stage IIB). Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.

Background/Aims

This study assessed the antibiotic resistance organisms isolated from the blood and bile of acute cholangitis and evaluated risk factors associated with them and their impact on clinical outcomes.

Methods

The identities and antibiotic resistance profiles of bacteria isolated from 433 cases of acute cholangitis from 346 patients were analyzed. Risk factors and the outcomes of patients infected with them were assessed.

Results

Microorganisms were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures. Isolates from bile and blood were identical in 71% of the cases. A total of 20 extended spectrum-β-lactamase (ESBL)-producers and 4 carbapenemase-producing organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase-producers were isolated from bile. Sixty-four (14.8%) cases were infected with any one of these bacteria isolated from blood or bile. Risk factors associated with them in blood were nosocomial infection and prior biliary intervention. In bile, indwelling biliary device was a risk factor associated with them. Antibiotic-resistant bacteria were associated with mortality, independent of other prognostic factors.

Conclusions

ESBL or carbapenemase-producing bacteria were frequently isolated in acute cholangitis patients especially with prior biliary intervention and nosocomial infection. Isolation of antibiotic-resistant bacteria was an independent risk factor of mortality.

Background/Aims

Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.

Methods

Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy.

Results

The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).

Conclusions

ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.

Background/Aims

For proper sedation during endoscopic submucosal dissection (ESD), propofol has been widely used. This study aimed to compare the levels of sedation and tolerance of patients treated with midazolam (M group) and a combination of midazolam and propofol (MP group) during ESD.

Methods

A total of 44 consecutive patients undergoing ESD were randomly assigned to the two groups. In the M group, 2 mg of midazolam was given repeatedly to maintain after a loading dose of 5 mg. The MP group initially received 5 mg of midazolam and 20 mg of propofol. Then, we increased the dosage of propofol by 20 mg gradually.

Results

The average amount of midazolam was 12 mg in the M group. In the M group, 10 patients were given propofol additionally, since they failed to achieve proper sedation. The average amount of propofol was 181 mg in the MP group. Procedure time, vital signs and rates of complications were not significantly different between two groups. Movement of patients and discomfort were lower in the MP group.

Conclusions

During ESD, treatment with propofol and a low dose of midazolam for sedation provides greater satisfaction for endoscopists compared to midazolam alone.

Background/Aims

It is generally believed that cholecystokinin (CCK) stimulates colonic motility, although there are controversial reports. It has also been suggested that postprandial peptide YY (PYY) release is CCK-dependent. Using a totally isolated, vascularly perfused rat colon, we investigated: (1) the roles of CCK and PYY on colonic motility, (2) to determine if CCK modulates PYY release from the colon to influence the motility and (3) to clarify whether the action of CCK and PYY on colonic motility is mediated via the influence of cholinergic input.

Methods

An isolated whole rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers from proximal and distal colon. After a control period, CCK-8 or PYY was administerd intraarterially with or without an anti-PYY serum, loxiglumide or atropine at 12, 60 and 240 pM. Each dose was given for a period of 15-minute and the contractile response was expressed as % changes over basal. PYY concentration in the portal effluent was determined by radioimmunoassay.

Results

Exogenous CCK-8 increased colonic motility which paralleled the increase in PYY release in the portal effluent. Exogenous PYY also significantly increased colonic motility although it was less potent than CCK. The stimulating effect of CCK-8 was significantly inhibited by an anti-PYY serum, and was completely abolished by loxiglumide, and almost completely abolished by atropine.

Conclusions

CCK increases colonic motility via CCK1 receptor and it is mediated partly by PYY. Cholinergic input is required for the increased motility by either PYY or CCK.

The incidence of acute hepatitis in syphilis patient is rare. First of all, our patient presented with hepatitis comorbid with thrombocytosis. To our knowledge, this is only the second report of syphilitic hepatitis with thrombocytosis. The 42-yr-old male complained of flulike symptoms and skin eruptions on his palms and soles. Laboratory findings suggested an acute hepatitis and thrombocytosis. Serologic test results were positive for VDRL. He recovered from his symptoms and elevated liver related enzymes with treatment. Because syphilitic hepatitis can present without any typical signs of accompanying syphilis, syphilis should be considered as a possible cause in acute hepatitis patients.

Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N-acetyltransferase (NAT) 2 acetylation status, and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age- and sex-matched control subjects. NAT2 genotypes were identified using single-nucleotide primer extension reaction methods. Thirty-one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95%CI = 1.57-3.62), heavy drinkers (OR = 1.28, 95%CI = 1.06-1.55), and individuals who eat well-done meat (OR = 1.24, 95%CI = 1.09-1.41). The odds ratios (95% CI) for high intake of kimchi, stews, and soybean paste were 3.27 (2.44-4.37), 1.96 (1.50-2.58), and 1.63 (1.24-2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene-environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews, and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29-4.04) for light smokers and 3.42 (95% CI: 2.06-5.68) for well-done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk.

To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5' -cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K+ and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High K+ (50 mM) produced sustained tonic contraction, and ACh (10 µM) produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high K+-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine (1 µM), inhibitor of voltage-dependent L-type calcium current (VDCCL), almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of VDCCL.

The properties of voltage dependent Ca2+ current (VDCC) were investigated in interstitial cells of Cajal (ICC) distributed in the myenteric layer (ICC-MY) of guinea-pig antrum. In tissue, ICC-MY showed c-Kit positive reactions and produced driving potentials with the amplitude and frequency of about 62 mV and 2 times min-1, respectively, in the presence of 1 µM nifedipine. Single ICC-MY isolated by enzyme treatment also showed c-Kit immunohistochemical reactivity. These cells were also identified by generation of spontaneous inward current under K+ -rich pipette solution. The voltage clamp experiments revealed the amplitude of - 329 pA inward current at irregular frequency. With Cs+-rich pipette solution at Vh=-80 mV, ICC-MY produced voltage-dependent inward currents (VDIC), and nifedipine (1 µM) blocked VDIC. Therefore, we successfully isolated c-Kit positive single ICC from guinea-pig stomach, and found that ICC-MY potently produced dihydropiridine sensitive L-type voltage-dependent Ca2+ currents (VDCCL).

This study was designed to investigate the effects of polyamines on mechanical contraction and voltage-dependent calcium current (VDCC) of guinea-pig gastric smooth muscle. Mechanical contraction and calcium channel current (IBa) were recorded by isometric tension recording and whole-cell patch clamp technique. Spermine, spermidine and putrescine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner. Spermine (2 mM) reduced high K+ (50 mM)-induced contraction to 16±6.4% of the control (n=9), and significantly inhibited IBa in a reversible manner (p<0.05; IC50=0.8 mM). Pre- and post-treatment of tissue with spermine (2-5 mM, n=10) also inhibited acetylcholine (10 µM)-induced phasic contraction to 5±6.4% of the control. Inhibitory effect of spermine on IBa was observed at a wide range of test potentials of current/voltage (I/V) relationship (p<0.05), and steady-state activation of IBa was shifted to the right by spermine (p<0.05). Spermidine and putrescine (1 mM each) also inhibited IBa to 51±5.7% and 81±5.3% of the control, respectively. And putrescine (1 mM) inhibited IBa at whole tested potentials (p<0.05) without significant change of kinetics (p<0.05). Finally, 5 mM putrescine also inhibited high K+-induced contraction to 53±7.1% of the control (n=4). These findings suggest that polyamines inhibit contractions of guinea-pig gastric smooth muscle via inhibition of VDCC.