Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea.

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications.

PURPOSE: To evaluate the complications of high-intensity focused ultrasound (HIFU) in patients with hepatic and pancreatic cancer. MATERIALS AND METHODS: From January 2006 to December 2008, 133 sessions of HIFU treatment were performed in 114 consecutive patients with primary hepatic tumor (n = 57), hepatic metastasis (n = 22), and pancreatic cancer (n = 35) under general anesthesia. The extracorporeal, ultrasound-guided Model-JC system (HAIFU, Chongqing, China) was used. Artificial pleural effusion was created to obtain an adequate sonographic window for ablating hepatic dome masses in 53 patients. We reviewed medical records and imaging findings before, during, and after HIFU. RESULTS: All patients had skin redness, edema, and pain in the treatment regions. All hepatic tumor patients had necrosis of the ribs along the main ultrasound beam path that did not require further treatment. Major complications included biliary obstruction, symptomatic pleural effusion, pneumothorax and fistula formation between an abdominal wall abscess and the ablated hepatic tumor. In 35 pancreatic cancer patients, major complications included third-degree burns and fistula formation between the tumor and duodenum. Delayed complications in hepatic tumor patients included a diaphragmatic rupture and rib fractures along the ultrasound pathway. CONCLUSION: The complications of HIFU develop mainly around the targeted lesions or along the ultrasound beam pathway. It is essential to have awareness of the possible complications related to HIFU and its imaging features for to avoiding serious complications.

A case of spontaneous regression of advanced gastric cancer.

An 84 yr-old male with a history of nausea and vomiting for 3 weeks was admitted to our hospital. Esopahgogastroduodenoscopy showed the diffuse infiltrative type of gastric cancer encircling from the cardia to the lower body. On abdominal computerized tomography, the gastric wall was diffusely thickened with overlying mucosal enhancement without lymph node involvement. Histologic examination revealed poorly differentiated adenocarcinoma. So surgical resection was planned. However, patient refused all medical care, and then he was discharged. He lived without any medical support and then he revisited our hospital and showed relieved symptoms on the follow-up exam. On esophagogastroduodenoscopy, the gastric mucosa of the body looked normal without any dysplastic change. Abdominal CT revealed a decreased thickening of the gastric wall of the body. The histology from the endoscopic forceps biopsy showed no evidence of malignancy. The patient is alive without any sign of tumor recurrence after 14 months.

[Remission of ulcerative colitis after appendectomy: a case report].

The inverse correlation of appendectomy and ulcerative colitis is well known, but the effect of appendectomy on the clinical course of ulcerative colitis remains unclear. Although the majority of opinions were negative for the therapeutic advantage of appendectomy in patients with ulcerative colitis, advocates for positive effect of appendectomy have been proposed in a few case reports and a prospective study from Western countries. We herein report a case of ulcerative colitis who experienced clinical remission after appendectomy for acute appendicitis. The patient was 35 year old male and had been managed with immunosuppressant before appendectomy. The very acute change in clinical course and a long period of remission after appendectomy highly suggest the therapeutic effect of appendectomy for ulcerative colitis.

Radiofrequency Ablation of Hepatocellular Carcinoma (≤ 5 cm) with Saline-Perfused Electrodes: Factors Affecting Local Tumor Progression.

Purpose: We aimed to assess local tumor progression (LTP) rate and associated prognostic factors in 92 patients who underwent radiofrequency ablation (RFA) using saline-perfused electrodes to treat hepatocellular carcinoma (HCC) (≤ 5 cm). Materials and Methods: Total 92 patients with 148 HCCs were treated with RFA using salineperfused electrodes, from 2009 to 2015. We retrospectively evaluated technical success, technique efficacy, and LTP rates. Potential prognostic factors for LTP were perivascular tumor, subphrenic tumor, artificial ascites, tumor size (≥ 2 cm), and previous treatment of transarterial chemoembolization. Analysis was performed by lesion, rather than by person. Results: During follow-up period from 1 to 97.4 months, total cumulative LTP rates were 7.9%, 11.4%, and 14.6% at 1, 3, and 5 years, respectively. These values were significantly higher in the perivascular (35.1%; p = 0.009) and subphrenic group (38.9%; p = 0.002) at 5-year. We did not observe any significant difference in LTP according to other prognostic factors (p > 0.05). Conclusion: RFA with saline-perfused electrode is a safe and effective treatment modality for HCC (≤ 5 cm), with lower LTP rates. Nevertheless, perivascular and subphrenic HCCs demonstrated higher LTP rate than other sites. It is imperative to note that perivascular and subphrenic location of HCC are associated with a high risk of local recurrence, despite the use of salineperfused electrodes.

Preliminary experience using high intensity focused ultrasound for treating liver metastasis from colon and stomach cancer.

PURPOSE: To determine the efficacy and safety from our preliminary results of using high intensity focused ultrasound (HIFU) to treat liver metastasis from colon and stomach cancer. MATERIALS AND METHODS: Ten patients with liver metastasis from colon cancer and three from stomach cancer underwent HIFU under general anesthesia. HIFU was performed using an extracorporeal, ultrasound-guided focused system. Complications during the study, extent of coagulative necrosis at two-week follow up, and evidence of tumor on further follow up were analyzed. Patients were divided into four categories: (I) complete ablation with no evidence of recurrence on follow up; (II) apparent complete ablation of target mass with new foci of disease in the target organ or distant malignancy and no local tumor progression; (III) local tumor progression after apparent complete ablation; (IV) partial ablation. RESULTS: Mean follow-up period was 22 weeks in the colon cancer group and 58 weeks in the stomach cancer group. The sum of total lesion size was between 1.8 cm and 21.4 cm (mean: 8.4 cm +/- 6.7 cm) for the colon cancer group and between 1.7 and 16.3 cm (mean: 8.8 cm +/- 7.3 cm) for the stomach cancer group. In the colon cancer group, one patient was categorized as category I, one as category II, three as category III, and the remaining five as category IV. The stomach cancer group showed two patients as category I, and one as category II. CONCLUSION: For treating liver metastasis from colon and stomach cancer HIFU seems safe but its efficacy is questionable. Further research is warranted.

Congenital hemidiaphragmatic agenesis presenting as reversible mesenteroaxial gastric volvulus and diaphragmatic hernia: a case report.

A 70-yr-old woman complained of left sided chest pain and non-bilious vomiting for four days after taking a gastric bloating agent for an upper gastrointestinal study. The chest radiography revealed gastric air-fluid levels and bowel loops in the left thoracic cavity. An emergency thoracotomy was performed. The abdominal organs (stomach, spleen, splenic flexure of the colon) were in the left thorax and the entire left hemidiaphragm was absent. There were no diaphragmatic remnants visible for reconstruction of the left diaphragm. We provided warm saline irrigation and performed a left lower lobe adhesiotomy. Thirteen days after surgery, the chest radiography showed improvement in the herniation but mild haziness remained at the left lower lung field. Here we present the oldest case of congenital diaphragmatic agenesis presenting with transient gastric volvulus and diaphragmatic hernia.

[Change in the serologic markers of hepatitis B after allogenic hematopoietic stem-cell transplantation].

BACKGROUND/AIMS: This study examined the effects of hepatitis B virus (HBV) infection state and immunologic capability in both the recipients and donors of allogenic hematopoietic stem-cell transplantation (allo-HSCT) on changes in HBV serologic markers in recipients. METHODS: A total of 537 patients underwent allo-HSCT for the treatment of leukemia, malignant lymphoma, and solid tumor. HBV serologic markers were examined in both recipients and donors prior to and following the transplantation. The mean follow-up period was 36.6 months (range 3-80 months). RESULTS: Of the 537 patients who underwent allo-HSCT, 45 recipients were positive for HBsAg prior to transplantation. Of these 45 patients, 21 were transplanted from anti-HBs-positive donors and the remaining 24 were transplanted from anti-HBs-negative donors. In the former cases, seroconversion was noted in 4 of the 21 patients (19%). In the latter cases, however, no seroconversion was noted following the transplantation. Thirty patients who were negative for both HBsAg and anti-HBs were transplanted from anti-HBs-positive donors, and 15 out of 30 patients (50%) acquired anti-HBs. Four hundred and seven patients who were positive for anti-HBs were transplanted from anti-HBs-positive or HbsAg-negative donors; 8 of these proved HBsAg-positive following the transplantation. There were no changes in HBV serological markers following transplantation in 41 patients who were transplanted from HbsAg-positive donors. CONCLUSIONS: Due to the adoptive immunity that was transferred from anti-HBs-positive donors, a seroconversion of HBsAg could occur in some HBsAg-positive recipients. HBsAg-positive donors had a lesser effect on the HBV serologic markers of recipients. However, a reactivation of HBV can occur following hematopoietic stem-cell transplantation in the cases of recipients or donors with a history of HBV, infection by an accompanying immune suppression. Therefore, prevention should be instigated.

High intensity focused ultrasound therapy resulted in a complete response in a patient with advanced gastric cancer with liver metastases: a case report.

Different therapeutic strategies have been tried when liver metastasis develops after a gastrectomy for gastric cancer, but the disease still has a poor prognosis. We present a 35-year-old woman who achieved complete radiological remission of liver metastases from advanced gastric cancer after a single therapeutic high intensity focused ultrasound session. Our observations suggest that high intensity focused ultrasound combined with chemotherapy may be an additional treatment option for patients with liver metastases from advanced gastric cancer.

Clinical outcome of Fitz-Hugh-Curtis syndrome mimicking acute biliary disease.

AIM: To analyze the clinical characteristics of patients diagnosed with Fitz-Hugh-Curtis syndrome. METHODS: The clinical courses of patients that visited St. Mary's Hospital with abdominal pain from January 2005 to December 2006 and were diagnosed with Fitz-Hugh-Curtis syndrome were examined. RESULTS: Fitz-Hugh-Curtis syndrome was identified in 22 female patients of childbearing age; their mean age was 31.0+/-8.1 years. Fourteen of these cases presented with pain in the upper right abdomen alone or together with pain in the lower abdomen, and six patients presented with pain only in the lower abdomen. The first impression at the time of visit was acute cholecystitis or cholangitis in 10 patients and acute appendicitis or pelvic inflammatory disease in eight patients. Twenty-one patients were diagnosed by abdominal computer tomography (CT), and the results of abdominal sonography were normal for 10 of these patients. Chlamydia trichomatis was isolated from 18 patients. Two patients underwent laparoscopic adhesiotomy and 20 patients were completely cured by antibiotic treatment. CONCLUSION: For women of childbearing age with acute pain in the upper right abdomen alone or together with pain in the lower abdomen, Fitz-Hugh-Curtis syndrome should be considered during differential diagnosis. Moreover, in cases suspected to be Fitz-Hugh-Curtis syndrome, abdominal CT, rather than abdominal sonography, assists in the diagnosis.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B.

AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for > or = 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by > or = 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy.

OBJECTIVES: The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed. METHOD: Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy. RESULTS: Median decreases from baseline in HBV DNA were 4.65 and 1.96 log(10) copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed. CONCLUSION: Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy.

[The efficacy and safety of telbivudine in korean patients with chronic hepatitis B].

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

[A case of transmesocolic hernia in elderly person without a history of operation].

Internal hernia is defined as the herniation of viscera through an anatomic or pathologic opening within the boundaries of peritoneal cavity. Transmesocolic hernia, a subtype of internal hernia, has a herniated sac through the transverse mesocolon. Transmesocolic hernia has been rarely described in the literature, and most of reported cases were associated with a history of operation or congenital anormaly. A 72-year-old female with chronic intermittent abdominal pain and bloating was admitted. Small bowel series showed multiple jejunal loops confined to the left upper quadrant of abdomen. Abdomen spiral computed tomography (CT) showed a cluster of mildly dilated small bowel loops with mesenteries on the same area. On the three-dimensional reconstruction CT scan, a herniated sac through the transverse mesocolon was identified. She was diagnosed as transmesocolic hernia by using the three-dimensional reconstruction CT and small bowel series, without surgical exploration. The symptoms were managed with conservative measures.

[Portal and superior mesenteric venous thrombosis treated with urokinase infusion via superior mesenteric artery].

Portal and mesenteric venous thrombosis is an uncommon disease, but clinically important, because it accounts for 5% to 15% of acute mesenteric ischemia. The diagnosis is often delayed because the conditions are nonspecific abdominal symptoms. In addition, when this occurs in young individual without any known predisposing factor, the diagnosis may become even more difficult. The treatment of mesenteric venous thrombosis involves anticoagulation therapy alone or in combination with surgery. The addition of thrombolytic therapy to the treatment of portal and mesenteric venous thrombosis may enhance the clearance of thrombus and hasten the clinical improvements. We present a case of mesenteric venous thrombosis treated with catheter-directed infusion of urokinase via the superior mesenteric artery and systemic anticoagulation.

[A case of hepatoid carcinoma of the pancreas].

Hepatoid carcinoma is a primary extrahepatic neoplasm exhibiting features of hepatocellular carcinoma (HCC) in terms of morphology, immunohistochemistry, and behavior. In many cases, tumor cytoplasm is positive for alpha- fetoprotein (alpha-FP) with elevated serum alpha-FP level. Because not all hepatoid carcinomas are associated with alpha- FP overproduction, diagnosis should be made essentially by histological features of the tumor. We present a case of hepatoid carcinoma of the pancreas in a 21-year-old male patient. Abdominal computed tomography and magnetic resonance imaging revealed an inhomogeneously enhanced pancreatic head mass. Serum alpha-FP level was markedly elevated. He underwent pylorus-preserving Whipple's operation. The tumor showed hepatoid and neuroendocrine components simultaneously. The histopathological diagnosis was hepatoid carcinoma associated with neuroendocrine tumor of the pancreas. Seven months after the surgery, the patient is healthy without evidence of recurrence. To date, only 7 cases of hepatoid carcinoma of the pancreas have been reported in the literature, and this is the first case report in Korea.

[Clinical significances of serum soluble fas and soluble fas ligand in chronic hepatitis B].

BACKGROUND/AIMS: Apoptosis via Fas/FasL system is thought to be involved in the development of hepatocyte death in viral hepatitis B. In chronic hepatitis C, sFas/sFasL system was reported to control liver injury induced by Fas/FasL mediated apoptosis. To determine the role of sFas/sFasL system in chronic hepatitis B, we analyzed serum sFas/sFasL in 58 HBV patients and 29 healthy controls. METHODS: HBV patients were categorized into two groups; normal ALT (< or =40 IU/L) and elevated ALT (>40 IU/L). Serum sFas/sFasL levels in HBV patients were measured by ELISA and was compared with those in 29 healthy controls. Serum ALT levels, histological activity, and Fas/FasL expression of liver were compared. RESULTS: Chronic hepatitis B patients with elevated ALT had significantly higher serum sFas levels than those in healthy controls (P<0.01). Serum sFasL levels, however, were significantly lower than those in healthy controls (P<0.01). Patients with moderate to marked degree of inflammation and fibrosis had significantly higher serum sFas levels than those in healthy controls (P<0.05). Serum sFasL levels had no correlation with the hepatic histological activity. Serum sFas/sFasL levels also had no significant correlation with the Fas/FasL expression of liver. CONCLUSIONS: Serum sFas/sFasL levels play a possible role in the pathogenesis of chronic hepatitis B. These results suggest that serum sFas levels might serve as a marker for estimating the degree of hepatic histological activity.

[The detection of antigenic protein of HCV in gastric mucosa].

BACKGROUND/AIMS: As a preliminary study to test the possibility of oral transmission of hepatitis C virus (HCV), many investigations in order to detect the extrahepatic localization of HCV have been performed. In this study, we examined the presence of HCV viral proteins in gastric mucosa. METHODS: Immunohistochemical staining to NS3 protein were done to detect the HCV virus in gastric mucosa. The results were compared with NS5a protein staining to confirm the NS3 protein staining. RESULTS: Total of 164 patient were included. 58 patients with anti-HCV (+) were designated to case group and 70 with anti-HCV (-) to control group. 36 were excluded in this study due to concomitant illness. Anti-HCV (+) group showed 50.0% (29/58) of positivity to NS3 protein staining and anti-HCV (-) group showed 12.6% (9/70) of positivity (p<0.001). Immunohistochemical staining to NS5a protein were done to validate the result of NS3 (+) staining in the anti-HCV (+) group (n=58). NS5a (+) staining were observed in 58.6% (34/58). The results of NS5a staining were consistent with that of NS3 in 70.7%. The reliability coefficients by Chronbach's Alpha for NS3 and NS5a stain test was 0.59. CONCLUSIONS: HCV can exist in gastric mucosal cell as an extrahepatic presence. In the future, this study may provide some fundamental data for the research of possible oral transmission route of HCV.

[Small bowel metastasis from breast cancer: a case report].

Breast cancer is a common malignancy in women and frequently metastasizes to various organs such as liver, lung, brain, bone and so on. But metastasis to gastrointestinal tract is rare. We describe a 73-year-old woman with small intestinal metastasis of breast cancer. She was diagnosed as right breast cancer in stage I, received modified radical mastectomy 6 years ago and had been followed up without any evidence of residual disease. During investigation for lower abdominal pain and weight loss of 9 kg, we found a small bowel mass. The histology of the tissue taken from small bowel mass was adenocarcinoma, poorly differentiated. The immunohistochemical stain of this specimen showed 75% positivity of estrogen receptor and 90% positivity of progesterone receptor. This is a case of small bowel metastasis from breast cancer and we report this case with a review of literatures.

[A case of portal vein thrombosis associated with acute pancreatitis and cholangitis].

Portal vein thrombosis is a rare complication accompanied with acute pancreatitis or cholangitis/cholecystitis. The main pathogenesis of portal vein thrombosis in pancreatitis or cholangitis/cholecystitis are suggested to be venous compression by pseudocyst and an imbalance between the blood coagulation and fibrinolysis. In this case report, we experienced a 63 year old male who developed portal vein thrombosis later in the course of the treatment of acute gallstone pancreatitis with cholangitis/cholecystitis without any symptom or sign. The diagnosis of portal vein thrombosis was given on follow up CT scan and serum protein S activity was decreased to 27% in laboratory study. Immediate anticoagulation therapy with heparin and thrombolytic therapy with urokinase and balloon dilatation were performed. Despite the aggressive treatment, complete reperfusion could not be obtained. With oral warfarin anticoagulation, the patient showed no disease progression and was discharged. We report a case of portal vein thrombosis as a complication of acute pancreatitis and cholangitis/cholecystitis with a review of literatures.