Transarterial chemoembolization using drug-eluting bead compared with radiofrequency ablation for treatment of single small hepatocellular carcinoma: a pilot non-randomized trial

Background/Aims@#Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC. @*Methods@#In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications. @*Results@#Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval: 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEBTACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event. @*Conclusions@#Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.

Transarterial chemoembolization using drug-eluting bead compared with radiofrequency ablation for treatment of single small hepatocellular carcinoma: a pilot non-randomized trial

Background/Aims@#Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC. @*Methods@#In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications. @*Results@#Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval: 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEBTACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event. @*Conclusions@#Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.

Nicotinamide adenine dinucleotide phosphate oxidase inhibitor induces apoptosis on EpsteinBarr virus positive B lymphoma cells / 대한해부학회지

Over-expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) isoform enzymes was recently reported in various cancers including Burkitt’s lymphoma (BL). However, the functions of Nox isoform enzymes in BL remain poorly understood. In this study, Nox isoform expression and the effects of a Nox-specific inhibitor were evaluated in Epstein-Barr virus (EBV)-positive Raji BL cells in comparison with EBV-negative Ramos BL cells. To evaluate Nox enzyme expression in Raji and Ramos BL cells, polymerase chain reaction (PCR) and western blot analysis were performed. To verify the intracellular signaling mechanism of the Nox inhibitor-induced apoptosis of Raji cells, WST-1 assay, trypan blue exclusion method, flow cytometry, PCR, western blotting, and bromodeoxyuridine staining were conducted. Experiments using the pan-caspase inhibitor z-VAD, reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), and Bim inhibitor 1 were performed. PCR and western blot results showed that Nox isoform enzymes were highly expressed in EBV-positive BL Raji cells compared with EBV-negative BL Ramos cells. The Nox2 inhibitor induced apoptosis of Raji cells in time- and dosedependent manners. The Nox2 inhibitor also caused up-regulation of Bim and Noxa, down-regulation of Mcl-1, translocation of Bax, release of cytochrome c, and caspase cascade activation, resulting in apoptosis. Furthermore, z-VAD, NAC, and BI-1 effectively blocked the Nox2 inhibitor-induced apoptosis of Raji cells. Taken together, these results provide a novel insight into the mechanism of Nox inhibitor-induced apoptosis and evidence for Nox as a therapeutic target to treat EBV-positive malignancies.

Nicotinamide adenine dinucleotide phosphate oxidase inhibitor induces apoptosis on EpsteinBarr virus positive B lymphoma cells / 대한해부학회지

Over-expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) isoform enzymes was recently reported in various cancers including Burkitt’s lymphoma (BL). However, the functions of Nox isoform enzymes in BL remain poorly understood. In this study, Nox isoform expression and the effects of a Nox-specific inhibitor were evaluated in Epstein-Barr virus (EBV)-positive Raji BL cells in comparison with EBV-negative Ramos BL cells. To evaluate Nox enzyme expression in Raji and Ramos BL cells, polymerase chain reaction (PCR) and western blot analysis were performed. To verify the intracellular signaling mechanism of the Nox inhibitor-induced apoptosis of Raji cells, WST-1 assay, trypan blue exclusion method, flow cytometry, PCR, western blotting, and bromodeoxyuridine staining were conducted. Experiments using the pan-caspase inhibitor z-VAD, reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), and Bim inhibitor 1 were performed. PCR and western blot results showed that Nox isoform enzymes were highly expressed in EBV-positive BL Raji cells compared with EBV-negative BL Ramos cells. The Nox2 inhibitor induced apoptosis of Raji cells in time- and dosedependent manners. The Nox2 inhibitor also caused up-regulation of Bim and Noxa, down-regulation of Mcl-1, translocation of Bax, release of cytochrome c, and caspase cascade activation, resulting in apoptosis. Furthermore, z-VAD, NAC, and BI-1 effectively blocked the Nox2 inhibitor-induced apoptosis of Raji cells. Taken together, these results provide a novel insight into the mechanism of Nox inhibitor-induced apoptosis and evidence for Nox as a therapeutic target to treat EBV-positive malignancies.

The Clinical Usefulness of Simultaneous Placement of Double Endoscopic Nasobiliary Biliary Drainage

BACKGROUND/AIMS: To evaluate the technical feasibility and clinical efficacy of double endoscopic nasobiliary drainage (ENBD) as a new method of draining multiple bile duct obstructions. METHODS: A total of 38 patients who underwent double ENBD between January 2004 and February 2010 at the Asan Medical Center were retrospectively analyzed. We evaluated indications, laboratory results, and the clinical course. RESULTS: Of the 38 patients who underwent double ENBD, 20 (52.6%) had Klatskin tumors, 12 (31.6%) had hepatocellular carcinoma, 3 (7.9%) had strictures at the anastomotic site following liver transplantation, and 3 (7.9%) had acute cholecystitis combined with cholangitis. Double ENBD was performed to relieve multiple biliary obstruction in 21 patients (55.1%), drain contrast agent filled during endoscopic retrograde cholangiopancreatography in 4 (10.5%), obtain cholangiography in 4 (10.5%), drain hemobilia in 3 (7.9%), relieve Mirizzi syndrome with cholangitis in 3 (7.9%), and relieve jaundice in 3 (7.9%). CONCLUSIONS: Double ENBD may be useful in patients with multiple biliary obstructions.

A Case of IgG4-Related Pancreas and Kidney Disease Mimicking a Renal Pelvic Malignancy / 대한내과학회지

IgG4-related sclerosing disease is a disease entity that has recently attracted attention, manifesting as a multiorgan disease characterized by high serum IgG4 levels, extensive IgG4-positive plasma cells and lymphocyte infiltration of the affected organs, with the pancreas (autoimmune pancreatitis) and kidney as representative targets. In cases of renal involvement, parenchymal lesions are predominant, such as renal cortical lesions or diffuse renal enlargement. However, mass-like lesions involving the renal pelvis are very rare, and mass forming or pelvic involvement types should be distinguished from lymphomas, metastatic cancers and other genitourinary malignancies to avoid unnecessary surgery. Herein, we report a case of IgG4-related sclerosing disease involving the kidney as an unusual involvement pattern presenting as a mass-like lesion with pelvic and perirenal involvement.

Factors Affecting Tumor Ablation during High Intensity Focused Ultrasound Treatment

BACKGROUND/AIMS: High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment. METHODS: HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated. RESULTS: Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone. CONCLUSIONS: During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

A comparison of the BISAP score and serum procalcitonin for predicting the severity of acute pancreatitis

BACKGROUND/AIMS: The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactorial scoring system. As more data are needed before clinical application, we compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously. METHODS: Fifty consecutive acute pancreatitis patients were enrolled prospectively. Blood samples were obtained at admission and after 48 hours and imaging studies were performed within 48 hours of admission. The BISAP score was compared with the serum PCT, Ranson's score, and the acute physiology and chronic health examination (APACHE)-II, Glasgow, and Balthazar computed tomography severity index (BCTSI) scores. Acute pancreatitis was graded using the Atlanta criteria. The predictive accuracy of the scoring systems was measured using the area under the receiver-operating curve (AUC). RESULTS: The accuracy of BISAP (> or = 2) at predicting severe acute pancreatitis was 84% and was superior to the serum PCT (> or = 3.29 ng/mL, 76%) which was similar to the APACHE-II score. The best cutoff value of BISAP was 2 (AUC, 0.873; 95% confidence interval, 0.770 to 0.976; p < 0.001). In logistic regression analysis, BISAP had greater statistical significance than serum PCT. CONCLUSIONS: BISAP is more accurate for predicting the severity of acute pancreatitis than the serum PCT, APACHE-II, Glasgow, and BCTSI scores.

Temporary Placement of Fully Covered Self-expandable Metal Stents in Benign Biliary Strictures / 대한소화기학회지

BACKGROUND/AIMS: Benign biliary strictures (BBSs) have been endoscopically managed with plastic stent placement. However, data regarding fully covered self-expandable metal stents (FCSEMSs) in BBS patients remain scarce in Korea. METHODS: Forty-one patients (21 men, 65.9%) with BBSs underwent FCSEMS placement between February 2007 and July 2010 in Asan Medical Center. Efficacy and safety were evaluated retrospectively. Patients were considered to have resolution if they showed evidence of stricture resolution on cholangiography and if an inflated retrieval balloon easily passed through the strictures at FCSEMS removal. RESULTS: The mean FCSEMS placement time was 3.2 (1.9-6.2) months. Patients were followed for a mean of 10.2 (1.0-32.0) months after FCSEMS removal. The BBS resolution rate was confirmed in 38 of 41 (92.7%) patients who underwent FCSEMS removal. After FCSEMS removal, 6 of 38 (15.8%) patients experienced symptomatic recurrent stricture and repeat stenting was performed. When a breakdown by etiology of stricture was performed, 14 of 15 (93.3%) patients with chronic pancreatitis, 17 of 19 (89.5%) with gall stone-related disease, 4 of 4 (100%) with surgical procedures, and 2 of 2 (100%) with BBSs of other etiology had resolution at FCSEMS removal. Complications related to stent therapy occurred in 12 (29%) patients, including post-ERCP pancreatitis (n=4), proximal migration (n=3), distal migration (n=3), and occlusion (n=2). CONCLUSIONS: Temporary FCSEMS placement in BBS patients offers a potential alternative to plastic stenting. However, because of the significant complications and modest resolution rates, the potential benefits and risks should be evaluated in further investigations.

A Case of Mixed Hyperplastic-adenomatous Rectal Polyp with Composition of Invasive Adenocarcinoma

Epithelial colon polyps are largely divided into hyperplastic and adenomatous polyps. Adenomatous polyps are premalignant lesions, whereas hyperplastic polyps are regarded as benign lesions. However, this histological classification has been blurred, as cases of malignant changes in hyperplastic polyposis, mixed hyperplastic adenomatous polyps (MHAPs), and serrated adenomas in the colon have been reported. Rare cases of MHAP have been reported, and are mainly found at the proximal colon with a relatively large size. MHAPs seem to be an intermediate stage of the hyperplastic polyp-adenoma sequence or a collision tumor. Here, we report on a case of a single polyp in the rectum diagnosed with a MHAP combined with an invasive adenocarcinoma.

A Case of Adenosquamous Carcinoma of the Ampulla of Vater / 대한소화기내시경학회지

Primary adenosquamous carcinoma arising from the papilla of Vater is an extremely rare tumor. Here we report a case of adenosquamous carcinoma of the duodenal major papilla. The patient was a 56-year-old man presenting with abdominal discomfort and anorexia. A computed tomography (CT) scan showed dilatation of the common bile duct (CBD) and both intrahepatic ducts with a suspicious mass in the distal CBD. Duodenoscopy revealed a mass with an irregular surface at the papilla. The patient underwent Whipple's operation. He was diagnosed as having adenosquamous carcinoma of the papilla of Vater. Eighteen months after pancreaticoduodenectomy, metastatic lymph nodes were noted in a follow-up CT scan.

Clinical Characteristics of Pancreatic Metastases / 대한소화기학회지

BACKGROUND/AIMS: Histologically confirmed metastatic pancreatic cancers are infrequent. The aim of this study was to analyze clinical, therapeutic and prognostic features of pancreatic metastases. METHODS: We retrospectively evaluated stage of primary malignancies, interval between diagnosis of primary tumors and detection of pancreatic metastases, treatment for metastases to the pancreas, survival rate, and prognostic factors in 31 patients with pancreatic metastases. RESULTS: The mean age at the time of primary cancer diagnosis was 52.4+/-13.2 years. Primary cancers were renal cell carcinoma (n=16), non-small cell lung cancer (n=6), small cell lung cancer (n=3), colorectal carcinoma (n=2), osteosarcoma (n=1), gastric carcinoma (n=1), malignant melanoma (n=1), and thymic carcinoma (n=1). Pancreatic metastases were synchronous in six cases and metachronous in twenty five cases, with median interval time of 40.8 months (range 3-186) between the diagnosis of primary tumor and detection of pancreatic metastases. The median survival after the detection of the metastases was 16 months. In multivariate analysis, non-renal cell carcinoma as primary malignancy and positive symptom related to pancreatic metastases were associated with poor prognosis (hazard ratio [HR], 8.33; 95% CI, 2.1-33; p=0.003, and HR, 4.02; 95% CI, 1.27-12.7; p=0.018). CONCLUSIONS: Metastatic tumors to the pancreas have to be kept in mind when a patient with pancreatic mass has a history of other malignancy, even if treated several years before. In the absence of widely metastatic disease, aggressive diagnostic and therapeutic approach may offer the chance of long-term survival in selected patients.

Biliary Strictures after Liver Transplantation

Biliary strictures are one of the most common complications following liver transplantation, representing an important cause of morbidity and mortality in transplant recipients. The reported incidence of biliary stricture is 5% to 15% following deceased donor liver transplantations and 28% to 32% following living donor liver transplantations. Bile duct strictures following liver transplantation are easily and conveniently classified as anastomotic strictures (AS) or non-anastomotic strictures (NAS). NAS are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and the need for retransplantation. Current endoscopic strategies to correct biliary strictures following liver transplantation include repeated balloon dilatations and the placement of multiple side-by-side plastic stents. Endoscopic balloon dilatation with stent placement is successful in the majority of AS patients. In patients for whom gaining biliary access is technically difficult, a combined endoscopic and percutaneous/surgical approach proves quite useful. Future directions, including novel endoscopic retrograde cholangiopancreatography techniques, advanced endoscopy, and improved stents could allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. The aim of this review is to detail the present status of endoscopy in the diagnosis, treatment, outcome, and future directions of biliary strictures related to orthotopic liver transplantation from the viewpoint of a clinical gastroenterologists.

Involvement of Splenic Hemangioma and Rectal Varices in a Patient with Klippel - Trenaunay Syndrome / 대한소화기학회지

Klippel - Trenaunay syndrome (KTS) is characterized by a cutaneous vascular nevus of the involved extremity, bone and soft tissue hypertrophy of the extremity and venous malformations. We present a case of KTS with splenic hemangiomas and rectal varices. A 29-year-old woman was referred for intermittent hematochezia for several years. She had history with a number of operations for cutaneous and soft tissue hamangiomas since the age of one year old and for increased circumference of her left thigh during the last few months. Abdominal CT revealed multiple hemangiomas in the spleen, fusiform aneurysmal dilatation of the deep veins and soft tissue hemangiomas. There was no evidence of hepatosplenomegaly or liver cirrhosis. Colonoscopy revealed hemangiomatous involvement in the rectum. There were rectal varices without evidence of active bleeding. Upon venography of the left leg, we also found infiltrative dilated superficial veins in the subcutaneous tissue and aneurysmal dilatation of the deep veins. The patient was finally diagnosed with KTS, and treated with oral iron supplementation only, which has been tolerable to date. Intervention or surgery is not required. When gastrointestinal varices or hemangiomatous mucosal changes are detected in a young patient without definite underlying cause, KTS should be considered.

Three Cases of Successful Treatment of Iatrogenic Duodenal Perforation / 대한소화기내시경학회지

Endoscopic retrograde cholangiopancreatography has become a standard procedure for the diagnosis and treatment of pancreatobiliary disease. Like any invasive procedure, it carries a small, but significant rate of serious complications such as duodenal perforation. Primary surgical closure is the treatment of choice for the cases of duodenal perforation. However, there have been some case reports in which endoscopic metal clip closure of an iatrogenic duodenal perforation was successful. We experienced three cases of successful treatment of the iatrogenic duodenal perforation using endoscopic clipping and fibrin glue injections during a duodenoscope insertion.

Small Bowel Obstruction and Capsule Retention by a Small Bowel Ulcer That Was Not Found on Capsule Endoscopy / 대한소화기내시경학회지

Capsule endoscopy (CE) is a valuable modality for directly examining the small bowel in a relatively noninvasive and safe manner. CE is being increasingly used for obscure gastrointestinal bleeding, Crohn's disease, drug induced ulcer and small bowel tumor. Although capsule retention is a relatively infrequent complication, small bowel obstruction and strictures have been considered contraindications to CE. But some authors have reported that capsule endoscopy can be safely used to help identify the etiology and site of small bowel obstruction, and the retention of the capsule indicates the presence of a lesion requiring surgery. We report here on a case of small bowel obstruction and capsule retention by a small bowel ulcer, and the small bowel ulcer was not found when performing capsule endoscopy.

Malignant Transformation of Gastric Gastrointestinal Stromal Tumor in 44 Months Observational Period: A Case Report / 대한소화기내시경학회지

Gastrointestinal stromal tumor is a common type of gastrointestinal mesenchymal tumor. Depending on the patient's age, compliance and health status, and the level of suspicion of malignancy, tumors < or =3 cm in size are typically monitored annually by endoscopic ultrasonography. The examination interval can be extended if no size change is noted on consecutive examinations. We report here on a 44-year-old female who presented with abdominal discomfort and displayed no size change of her gastrointestinal stromal tumor on three consecutive endoscopies over a 44-month interval. The patient was diagnosed with malignant gastrointestinal stromal tumor on the basis of the evident ulceration seen on esophagogastroduodenoscopy and the inhomogenous echo noted on the endoscopic ultrasonography and the pathologic findings by gastric wedge resection.