Acute Cholangitis Caused by Boryong Strain of Orientia tsutsugamushi.

Scrub typhus present with a variety clinical manifestations caused by Orientia tsutsugamushi, it is sometimes accompanied by severe complications. The clinical course of this complication is not well clear. Herein, we first report a case with acute cholangitis and acalculous cholecystitis caused by the Boryong genotype of O. tsutsugamushi. A 82-year-old woman presented with fever and acute abdominal pain on the right upper quadrant. Initially, the patient showed an abnormality of liver enzymes of cholestatic pattern. An acute cholangitis and cholecystitis were suspected on the enhanced computed tomography (CT), and emergent endoscopic retrograde cholangiopancreatography (ERCP) performed. However, neither ERCP nor CT detected common bile duct stones or sludge. The patient's illness progressed despite bile drainage and antibiotic therapy. On the fifth day in hospital, an immunofluorescence IgG assay for O. tsutsugamushi was positive, and the patient newly developed a skin rash and an eschar lesion on the right abdomen. The polymerase chain reaction amplification of Orientia genes from blood and bile was positive, genotype of both samples was identified the Boryong type. The presentation of scrub typhus as an acute cholangitis is not reported till now. In endemic areas, scrub typhus would be considered a rare etiology of acute cholangitis.

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series.

A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS)-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.

[Hemoperitoneum from Spontaneous Rupture of a Metastatic Abdominal Lymph Node in Gallbladder Cancer: A Case Report].

Gallbladder (GB) cancer is asymptomatic in nature, making diagnosis and treatment difficult. The lymph node status is the strongest predictor of long-term survival for patients with GB cancer, and a complete removal of regional lymph nodes is important for patients undergoing radical resection of GB cancer. Unfortunately, lymph node metastases are common in the early stages of GB cancer. However, there have only been a few cases describing the symptoms or complications of metastatic lymph nodes in patients with GB cancer. Although hemoperitoneum caused by metastatic lymph nodes can occur with several cancers, it is very rare. To the best of our knowledge, hemoperitoneum from spontaneous ruptures of metastatic lymph nodes with GB cancer has not yet been reported. Herein, we describe such a case in a patient newly diagnosed with GB cancer.

Reduced Autophagy in 5-Fluorouracil Resistant Colon Cancer Cells.

We investigated the role of autophagy in SNUC5/5-FUR, 5-fluorouracil (5-FU) resistant SNUC5 colon cancer cells. SNUC5/5- FUR cells exhibited low level of autophagy, as determined by light microscopy, confocal microscopy, and flow cytometry following acridine orange staining, and the decreased level of GFP-LC3 puncta. In addition, expression of critical autophagic proteins such as Atg5, Beclin-1 and LC3-II and autophagic flux was diminished in SNUC5/5-FUR cells. Whereas production of reactive oxygen species (ROS) was significantly elevated in SNUC5/5-FUR cells, treatment with the ROS inhibitor N-acetyl cysteine further reduced the level of autophagy. Taken together, these results indicate that decreased autophagy is linked to 5-FU resistance in SNUC5 colon cancer cells.

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells.

Colon cancer can be treated with 5-fluorouracil (5-FU), but 5-FU resistance frequently occurs. We determined whether 5-FU resistance arises as a result of endoplasmic reticulum (ER) stress. 5-FU-resistant SNUC5 colon cancer cells (SNUC5/FUR cells) expressed higher levels of ER stress-related proteins than drug-sensitive SNUC5 cells. SNUC5/FUR cells also exhibited more intense ER staining and higher level of mitochondrial Ca(2+) overload. SNUC5/FUR cells transfected with siRNA against GRP78, ATF6, ERK, or AKT were more sensitive to 5-FU than siControl RNA-transfected cells. These results suggested that 5-FU resistance was associated with ER stress in colon cancer.

Induction of Endoplasmic Reticulum Stress via Reactive Oxygen Species Mediated by Luteolin in Melanoma Cells.

BACKGROUND: This study aimed to investigate whether luteolin, a flavonoid, induces apoptosis in human melanoma cells via endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: To investigate the effects of luteolin in human melanoma cells, the anti-proliferation, apoptosis, ER stress induction and reactive oxygen species (ROS) generation were evaluated using MTT, Hoechst 33342, ER-tracker Blue White DPX and DCF-DA staining assays, respectively. RESULTS: Luteolin inhibited cell proliferation and increased apoptotic body formation. Luteolin induced ER stress, as shown by ER staining and mitochondrial Ca(2+) overloading. Luteolin increased expression of the ER stress-related proteins; protein kinase RNA-like ER kinase, phospho eukaryotic translation initiation factor 2α, activating transcription factor (ATF) 6, CCAAT/enhancer-binding protein-homologous protein (CHOP), and cleaved caspase 12. Furthermore, luteolin increased the level of intracellular ROS, leading to ROS-mediated apoptosis and ER stress. However, N-acetyl cysteine, a ROS scavenger, decreased ROS levels, apoptosis, and ER stress induced by luteolin treatment. In addition, knockdown of CHOP and ATF6 by small-interfering RNA inhibited luteolin-induced cell death. CONCLUSION: Luteolin induces apoptosis by ER stress via increasing ROS levels.

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis.

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.

Erratum.

[This corrects the article on p. 355 in vol. 20, PMID: 25548741.][This corrects the article on p. 368 in vol. 20, PMID: 25548743.].

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

BACKGROUND/AIMS: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. METHODS: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. RESULTS: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥ 5.1 × 10(7) IU/mL and ALT ≥ 5 × ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. CONCLUSIONS: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.

Different mechanism of selection of adefovir-resistant mutant viruses during adefovir monotherapy in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND: Adefovir (ADV) resistance is more frequent in lamivudine (LMV)-resistant chronic hepatitis B (CHB) patients than in nucleos(t)ide analogue-naïve patients. The majority of LMV-resistant mutants harbor the rtM204V/I mutation, while a minor fraction harbor the rtA181V/T mutation. We aimed to elucidate the mechanism of the high rate of ADV resistance in LMV-resistant patients during ADV therapy. METHODS: We performed a clonal analysis of HBV reverse transcriptase in treatment-naïve (n = 3) and LMV-resistant patients before ADV therapy (n = 14). Dynamic changes in the viral population (n = 9) during ADV therapy were also analyzed. RESULTS: Before ADV therapy, rtA181V/T was observed in 30 of 680 clones (4.4%) from 7 patients with LMV resistance under dominant rt204V/I mutation and in one of 150 clones in treatment-naïve patients. The rtA181V/T mutation was more frequently found in clones from LMV-resistant patients than in treatment-naïve patients (p = 0.029). The rtN236T mutation was not observed in any clone. During ADV therapy, most rtM204V/I mutants were replaced by wild type in all 3 patients without the rtA181V/T mutation and in one patient with the rtA181V/T mutation. Subsequently, wild type was replaced by the rtN236T and/or rtA181V/T mutant. In patients with the rtA181V/T mutation (n = 6), the rtA181V/T mutant overtook the rtM204V/I mutant in 3 of 4 patients with ADV resistance. In 2 patients without ADV resistance, most of the viral population was replaced by wild type by the last follow-up. CONCLUSION: The high rate of ADV resistance in patients with LMV-resistance might be attributable to preexisting rtA181V/T mutant virus.

Comparison between Midazolam Used Alone and in Combination with Propofol for Sedation during Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is an uncomfortable procedure that requires adequate sedation for its successful conduction. We investigated the efficacy and safety of the combined use of intravenous midazolam and propofol for sedation during ERCP. METHODS: A retrospective review of patient records from a single tertiary care hospital was performed. Ninety-four patients undergoing ERCP received one of the two medication regimens, which was administered by a nurse under the supervision of a gastroenterologist. Patients in the midazolam (M) group (n=44) received only intravenous midazolam, which was titrated to achieve deep sedation. Patients in the midazolam pulse propofol (MP) group (n=50) initially received an intravenous combination of midazolam and propofol, and then propofol was titrated to achieve deep sedation. RESULTS: The time to the initial sedation was shorter in the MP group than in the M group (1.13 minutes vs. 1.84 minutes, respectively; p<0.001). The recovery time was faster in the MP group than in the M group (p=0.031). There were no significant differences between the two groups with respect to frequency of adverse events, pain experienced by the patient, patient discomfort, degree of amnesia, and gag reflex. Patient cooperation, rated by the endoscopist as excellent, was greater in the MP group than in the M group (p=0.046). CONCLUSIONS: The combined use of intravenous midazolam and propofol for sedation during ERCP is more effective than midazolam alone. There is no difference in the safety of the procedure.

Peripancreatic tuberculous lymphadenopathy masquerading as pancreatic malignancy: a single-center experience.

BACKGROUND AND AIM: Peripancreatic tuberculous lymphadenopathy is very rare and can be misdiagnosed with pancreatic or peripancreatic malignancies. The clinical characteristics and treatment outcome have not been well known. Herein, we investigated the accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), clinical features, and treatment outcomes. METHODS: We retrospectively analyzed 42 patients diagnosed with peripancreatic tuberculosis between December 2004 and January 2011 at the tertiary care hospital in Korea. RESULTS: Median age was 36 years (interquartile range, 30-55), and female was 66.7% (28/42). Nineteen patients (45.2%) had no symptoms, while the others had non-specific various symptoms. Thirteen (31.0%) had a previous history of tuberculosis. Initial impressions of the mass were pancreatic cancer in 14 (33.3%) and tuberculous lymphadenopathy in 13 patients (31.0%). EUS-FNA was performed in all 42 patients, with a diagnostic yield of pathologic examinations in 80.5%, polymerase chain reaction for tuberculosis in 42.9%, culture in 47.4%, and acid-fast bacilli staining in 10.0%. Tuberculosis is confirmed in 28 (66.7%), and probable tuberculosis in 14 (33.3%). All patients received anti-tuberculosis treatment, a 6-months regimen in 12 (28.6%) and a 9-months regimen in 28 (66.7%). Treatment response evaluated in 35 patients (83.3%) by computed tomography criteria showed complete response in 10 patients (28.6%), partial response in 23 (65.7%), stable disease in 1 (2.9%), and progressive disease in 1 (2.9%). CONCLUSIONS: Peripancreatic tuberculous lymphadenopathy is frequently mistaken for pancreatic malignancy. EUS-FNA can be helpful for an accurate diagnosis. Complete resolution of the lesion, however, was not common on following imaging study after treatment.

Endoscopic papillary balloon dilation: revival of the old technique.

Radiologists first described the removal of bile duct stones using balloon dilation in the early 1980s. Recently, there has been renewed interest in endoscopic balloon dilation with a small balloon to avoid the complications of endoscopic sphincterotomy (EST) in young patients undergoing laparoscopic cholecystectomy. However, there is a disparity in using endoscopic balloon papillary dilation (EPBD) between the East and the West, depending on the origin of the studies. In the early 2000s, EST followed by endoscopic balloon dilation with a large balloon was introduced to treat large or difficult biliary stones. Endoscopic balloon dilation with a large balloon has generally been recognized as an effective and safe method, unlike EPBD. However, fatal complications have occurred in patients with endoscopic papillary large balloon dilation (EPLBD). The safety of endoscopic balloon dilation is still a debatable issue. Moreover, guidelines of indications and techniques have not been established in performing endoscopic balloon dilation with a small balloon or a large balloon. In this article, we discuss the issue of conventional and large balloon endoscopic dilation. We also suggest the indications and optimal techniques of EPBD and EPLBD.

Forward-viewing endoscopic ultrasound-guided NOTES interventions: a study on peritoneoscopic potential.

AIM: To evaluate the feasibility of diagnostic and therapeutic transgastric (TG) peritoneoscopic interventions with a forward-viewing endoscopic ultrasound (FV-EUS). METHODS: This prospective endoscopic experimental study used an animal model. Combined TG peritoneoscopic interventions and EUS examination of the intra-abdominal organs were performed using an FV-EUS on 10 animal models (1 porcine and 9 canine). The procedures carried out include EUS evaluation and endoscopic biopsy of intraperitoneal organs, EUS-guided fine needle aspiration (EUS-FNA), EUS-guided radiofrequency ablation (EUS-RFA), and argon plasma coagulation (APC) for hemostatic control. The animals were kept alive for 7 d, and then necropsy was performed to evaluate results and complications. RESULTS: In all 10 animals, TG peritoneoscopy, followed by endoscopic biopsy for the liver, spleen, abdominal wall, and omentum, was performed successfully. APC helped control minor bleeding. Visualization of intra-abdominal solid organs with real-time EUS was accomplished with ease. Intraperitoneal EUS-FNA was successfully performed on the liver, spleen, and kidney. Similarly, a successful outcome was achieved with EUS-RFA of the hepatic parenchyma. No adverse events were recorded during the study. CONCLUSION: Peritoneoscopic natural orifice transluminal endoscopic surgery (NOTES) interventions through FV-EUS were feasible in providing evaluation and performing endoscopic procedures. It promises potential as a platform for future EUS-based NOTES.

Prospective evaluation of a treatment algorithm with enhanced guidewire manipulation protocol for EUS-guided biliary drainage after failed ERCP (with video).

BACKGROUND: EUS-guided biliary drainage (EUS-BD) was introduced as an effective alternative to percutaneous transhepatic biliary drainage after failed ERCP. However, EUS-BD is technically challenging. The intraductal manipulation of the guidewire seems to be the most difficult stage of the procedure. Therefore, technical advances in guidewire manipulation may be required for EUS-BD. OBJECTIVE: To evaluate our treatment algorithm for guidewire manipulation protocol for EUS-BD after failed ERCP. DESIGN: Prospective, observational cohort study. SETTING: A tertiary-care academic center. PATIENTS: Forty-five consecutive patients undergoing EUS-BD failed ERCP. INTERVENTIONS: Enhanced guidewire manipulation protocol (with a plane parallel to the long axis of the bile duct with an EUS needle tip or a new 0.025-inch guidewire in an extrahepatic approach and intrahepatic bile duct puncture of segment 2 and 4F cannula with guidewire probing in the intrahepatic approach) for rendezvous and antegrade therapy, EUS-BD with transluminal stenting for duodenal invasion, and crossover to another technique if each technique failed. MAIN OUTCOME MEASUREMENTS: Technical and functional success rates and adverse event rate of the current treatment algorithm for EUS-BD. RESULTS: The overall technical and functional success rates of EUS-BD in this study were 91% (intention to treat, n = 41/45) and 95% (per protocol, n = 39/41), respectively. Specifically, rendezvous (n = 20) and antegrade therapy (n = 14) were initially feasible in 34 of 45 patients (76%). With our protocol, 25 of 45 patients (56%) were eventually treated with rendezvous and antegrade therapy as a first-line or crossover treatment. EUS-guided biliary drainage with transluminal stenting in patients with duodenal invasion or failed antegrade therapy was feasible in the remaining 20 patients (44%). The overall adverse event rate of EUS-BD was 11%. LIMITATIONS: Single-operator, nonrandomized study. CONCLUSIONS: In this prospective study, our treatment algorithm with an enhanced guidewire manipulation protocol appeared to be technically feasible and effective. Given the favorable success rate and acceptable adverse event rate, this may be considered the standard treatment algorithm for future randomized trials of EUS-BD and percutaneous transhepatic biliary drainage.

Comparison of the clinical characteristics of patients with small bowel and gastric anisakiasis in jeju island.

BACKGROUND/AIMS: Anisakiasis is frequent in Jeju Island because of the people's habit of ingesting raw fish. This study evaluated the clinical characteristics of patients with small bowel anisakiasis and compared them with those of patients with gastric anisakiasis. METHODS: We retrospectively reviewed the medical records of 109 patients diagnosed with anisakiasis between May 2003 and November 2011. RESULTS: Of the 109 patients diagnosed with anisakiasis, those with suspicious anisakiasis (n=38) or possible anisakiasis (n=12) were excluded. The age and gender distributions did not differ between patients with small bowel anisakiasis (n=30; age, 45±13 years) and those with gastric anisakiasis (n=29; age, 46±10 years). The mean duration of hospitalization was 5.4±4.3 days for patients with small bowel anisakiasis and 0.5±1.7 days for patients with gastric anisakiasis. Small bowel anisakiasis was accompanied by leukocytosis (76.7% vs 25.5%, p=0.003) and elevated C-reactive protein levels (3.4±3.2 mg/dL vs 0.5±0.3 mg/dL, p=0.009). Contrast-enhanced abdominopelvic computed tomography showed small bowel wall thickening with dilatation in 93.3% (28/30) of patients and a small amount of ascites in 80.0% (24/30) of patients with small bowel anisakiasis. CONCLUSIONS: Compared with gastric anisakiasis patients, small bowel anisakiasis patients had a longer hospitalization time, higher inflammatory marker levels, and small bowel wall thickening with ascites.

Clinical characteristics of intraductal papillary mucinous neoplasm manifesting as acute pancreatitis or acute recurrent pancreatitis.

BACKGROUND AND AIM: Comparatively little is known about acute pancreatitis or acute recurrent pancreatitis (AP/ARP) with intraductal papillary mucinous neoplasm of the pancreas (IPMN) as the causative lesion although there have been many reports about the malignant potential of IPMN as a premalignant lesion. METHODS: From 2000 to 2008, in a single tertiary referral center, out of 784 patients coded by the International Classification of Disease-10 with IPMN, 489 patients fulfilled our diagnostic criteria of IPMN. After careful exclusion of all known causes of AP/ARP, 34 patients with IPMN as the cause of AP/ARP were enrolled. RESULTS: AP/ARP caused by IPMN occurred in 34 (7%) out of 488 patients with IPMN, and the prevalence rate of AP/ARP was higher in the main-duct/combined type than in the branch-duct type (14% [16/111] vs 5% [18/378], respectively, P = 0.002). The severity of pancreatitis was mild, based on the computed tomography severity index score (median 2, range 0-4). Histologic review of 24 patients with surgical resection revealed four adenomas (17%), 17 borderline malignancies (71%), two carcinomas in situ (8%), and one invasive carcinoma (4%). AP/ARP did not recur in any of the 24 surgically resected patients during the follow-up period (median 52 months, range 38-115 months). CONCLUSIONS: AP/ARP caused by IPMN was of infrequent occurrence. AP/ARP caused by IPMN occurred more frequently in the main-duct/combined type than in the branch-duct type. Most cases were mild in severity and benign in histopathology. AP/ARP can be an initial manifestation of IPMN, though uncommon, which leads to diagnosis.

[Obesity and gallbladder diseases].

Obesity is an important health problem in the world and related to many critical diseases, such as diabetes, cardiovascular disease, and metabolic syndrome. Obesity leads to fat infiltration of multiple organs and infiltrated adipose tissue produces many cytokines resulting in the dysfunction of organs such as the gallbladder. In the biliary diseases, obesity and overweight have been known as a major risk factor for gallstones. According to current studies, obesity, insulin resistance, hyperinsulinemia, and metabolic syndrome are related to various gallbladder diseases including gallbladder stones, cholecystitis, gallbladder polyps, and gallbladder cancers. We reviewed further literature on the obesity and gallbladder diseases, in aspects of epidemiology, mechanism, pathology and prevention.