A Case of Transverse Myelitis Following Treatment with Atezolizumab for Advanced Hepatocellular Carcinoma / 대한소화기학회지

The results of the IMbrave150 study have led to widespread use of the combination therapy of atezolizumab and bevacizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC). Compared to traditional cytotoxic chemotherapy agents, immune checkpoint inhibitors show a spectrum of side effects ranging from mild side effects such as skin rash to potentially severe systemic effects such as myocarditis. We present a case of transverse myelitis diagnosed during the treatment of HCC with atezolizumab and bevacizumab combination therapy.

A case report of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy and sorafenib combination therapy followed by metastasectomy of lung and muscle metastases

Currently, various tyrosine kinase inhibitors and immune checkpoint inhibitors have been suggested in the treatment guidelines for advanced hepatocellular carcinoma (HCC). However, sorafenib was the only systemic drug approved 10 years ago. In 2010, a woman diagnosed with HCC rupture and multiple lung metastases visited our hospital. At the time of visiting our hospital, she had undergone transarterial chemoembolization at another hospital to control bleeding due to HCC rupture. We treated her with hepatic arterial infusion chemotherapy and sorafenib combination therapy to increase the control of intrahepatic tumors in consideration of the modest efficacy of sorafenib. The intrahepatic tumor was almost controlled. Metastasectomy was performed to control lung oligometastasis. Subsequently, additional muscle metastasis was confirmed, and metastasectomy was performed. Although this is a very rare case, it shows that a multidisciplinary approach can improve the prognosis of patients with HCC.

Efficacy of Hepatic Arterial Infusion Chemotherapy and Radiofrequency Ablation against Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization and Vascular Variation: A Case Study / 고신대학교의과대학학술지

Transarterial chemoembolization is often the first-line treatment for multiple hepatocellular carcinomas. However, hepatic arterial infusion chemotherapy is a treatment option for hepatocellular carcinoma refractory to multiple sessions of transarterial chemoembolization. Hepatic arterial infusion chemotherapy requires implantation of an appropriate port into the hepatic artery. However, it may be impossible to implant a port due to hepatic artery variation. We report a case of hepatocellular carcinoma refractory to transarterial chemoembolization and hepatic artery variation treated successfully with hepatic arterial infusion chemotherapy and radiofrequency ablation with complete response after implantation of ports in both liver lobes.

Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study

Background@#The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. @*Methods@#We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. @*Results@#SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. @*Conclusion@#In both treatment groups, SVR was high when treatment was completed.However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.

Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study

Background@#The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. @*Methods@#We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. @*Results@#SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. @*Conclusion@#In both treatment groups, SVR was high when treatment was completed.However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.

Prognostic factors in hepatocellular carcinoma patients with bone metastases

PURPOSE: To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. MATERIALS AND METHODS: A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan–Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. RESULTS: Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). CONCLUSION: Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.

Drug Induced Liver Injury by Prophylactic Administration of Albendazole / 대한소화기학회지

Albendazole is used as a typical antiparasitic agent worldwide. The side effects of albendazole may include nausea, vomiting, abdominal pain, dizziness, headache, alopecia, and increased liver enzymes. Mild elevation of the liver enzyme has been reported in more than 10% of cases, but drug induced liver injury was reported to be very rare. A 30-year-old woman visited the Dong-A University Hospital with anorexia, nausea, jaundice, and elevated liver enzyme. For diagnosis, other acute hepatitis etiologies were excluded, but the prophylactic administration of albendazole was verified. This paper introduces a case of drug-induced liver injury through the prophylactic administration of albendazole. Physicians should be aware of severe liver injury as one of the side effects of albendazole.

Drug Induced Liver Injury by Prophylactic Administration of Albendazole / 대한소화기학회지

Albendazole is used as a typical antiparasitic agent worldwide. The side effects of albendazole may include nausea, vomiting, abdominal pain, dizziness, headache, alopecia, and increased liver enzymes. Mild elevation of the liver enzyme has been reported in more than 10% of cases, but drug induced liver injury was reported to be very rare. A 30-year-old woman visited the Dong-A University Hospital with anorexia, nausea, jaundice, and elevated liver enzyme. For diagnosis, other acute hepatitis etiologies were excluded, but the prophylactic administration of albendazole was verified. This paper introduces a case of drug-induced liver injury through the prophylactic administration of albendazole. Physicians should be aware of severe liver injury as one of the side effects of albendazole.

Concomitant Liver and Brain Abscesses Caused by Parvimonas Micra / 대한소화기학회지

Anaerobic infections have been reported to be responsible for 3–10% of pyogenic liver abscesses in Korea, and reported anaerobes include Fusobacterium, Bacillus fragilis, and Bacteroides melaninogenicus. Parvimonas micra is an anaerobic, Gram-positive, non-spore-forming bacterial species and a constituent of normal flora on skin, vagina, gastrointestinal tract, and oral cavity that can cause opportunistic infections. However, it has only rarely been reported to be a cause of liver abscess; only one such case has been reported in Korea. We experienced a case of concomitant liver and brain abscesses caused by Parvimonas micra in a non-immunodeficient 65-year-old female patient without diabetes or periodontal disease. Parvimonas micra infection was confirmed by blood culture using VITEK® 2 cards and by bacterial 16s ribosomal RNA gene sequencing. We conclude that we should not overlook anaerobes as a cause of liver abscess.

Mushroom Poisoning by Macrolepiota neomastoidea / 대한소화기학회지

There are currently over 5,000-known species of mushrooms worldwide. Only 20–25% of mushrooms have been named, and 3% of these are poisonous. More than 95% of mushroom poisoning cases occur due to difficulties associated with the identification of mushroom species. Most of the fatal mushroom poisoning cases recorded to date have been related to the Amanita species. Until now, a case of fatal poisoning caused by Macrolepiota neomastoidea (M. neomastoidea) has not been reported in Asia. A 57-year-old male patient was admitted to the emergency room with nausea, vomiting, diarrhea, and abdominal pain. He reported ingesting wild mushrooms with his mother and sister about 2 days ago. His mother and sister were treated with only supportive care, but he was admitted to the intensive care unit and underwent liver transplantation due to acute liver failure. We are reporting a case of fatal M. neomastoidea intoxication from wild mushrooms, a rare case of mushroom poisoning.

A Case of Sorafenib-induced DRESS Syndrome in Hepatocelluar Carcinoma / 대한소화기학회지

Sorafenib is currently the only targeted therapy available for advanced stage hepatocellular carcinoma (HCC). Cutaneous adverse events associated with sorafenib treatment include hand-foot skin reaction, but there has been no report of drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS) syndrome. Here, we report a case of 72-year-old man with HCC and alcoholic liver cirrhosis who developed skin eruptions, fever, eosinophilia, and deteriorated hepatic and renal function under sorafenib treatment. He has since successfully recovered with conservative care.

Intraoperative radiofrequency ablation for hepatocellular carcinoma in 112 patients with cirrhosis: a surgeon's view

PURPOSE: This retrospective study was an investigation of overall survival (OS), disease-free survival (DFS) and prognostic factors affecting OS and DFS in cirrhotic patients who received intraoperative radiofrequency ablation (IORFA). METHODS: Between April 2009 and November 2013, 112 patients (94 men, 84%; 18 women, 16%) underwent IORFA for 185 cases of hepatocellular carcinomas (HCC). Repeat IORFA was done in 9 patients during the same period (total of 121 treatments). RESULTS: All patients were followed-up for at least 12 months (mean follow-up, 32 months). Surgical resection combined with IORFA was performed in 20 patients. The technical effectiveness at 1 week was 91.78% (111 of 121). Readmission was 9.1% (11 of 121) and the most common cause was ventral hernia. Procedure-related mortality was 2.7% (3 of 112) and continued fatal biliary leakage was 1.8% (2 of 112). Local recurrence developed in 10 patients (8.9%). Most recurrence was intrahepatic. Cumulative survival was assessed in 33 patients who received IORFA as primary treatment (naive patients) and 79 non-naive patients. The cumulative DFS and OS rate at l and 3 years was 54% and 24%, and 87% and 66%, respectively. Moderate ascites (P = 0.001), tumor located segment I (P = 0.001), portal vein thrombosis (P = 0.001) had poor survival were significant factors by multivariate analysis. CONCLUSION: IORFA alone or in combination with surgical resection extends the spectrum of liver surgery. A fundamental understanding of RFA, additional comorbidities, and postablation complication are necessary to maximize the safety and efficacy of IORFA for treating HCC with cirrhosis.

Solitary Fibrous Tumor of the Pancreas: A Case Report and Review of the Literature / 대한내과학회지

Solitary fibrous tumors (SFTs) are histologically characterized as mesenchymal tumors of probable fibroblastic origin that can arise at pleural and extrapleural sites. SFTs originating in the pancreas are extremely rare. Here, we report a case of pancreatic SFT in a 77-year-old female who presented with jaundice. A malignant neuroendocrine tumor (NET) was suspected based on radiologic findings. However, it is difficult to differentiate SFTs from a NET from radiographs and in this report, we summarize magnetic resonance imaging findings and discuss how to distinguish between SFT and NET using immunohistochemistry. Radical excision is the treatment of choice for SFT; however, in the present case, excision was not possible and close observation showed no changes 10 months after the diagnosis.

A case of focal nodular hyperplasia with growth progression during pregnancy

Focal nodular hyperplasia (FNH) is the second most common benign solid tumor of the liver and is usually found in young females. In FNH, spontaneous bleeding or rupture rarely occurs and malignant transformation is unlikely. The etiology of FNH is unclear, but because of female predominance and young age at onset, it seems that female hormone has an important role for the development of FNH. Although the development and the complications of hepatocellular adenomas have been related to the use of oral contraceptives and pregnancy, the influence of oral contraceptives and pregnancy on the growth and complications of FNH is controversial. Most FNH are stable in size and rarely complicated during pregnancy. We describe here a case of FNH with growth progression during pregnancy in a 27-year-old female. Her course of pregnancy and delivery was uneventful. Two months after delivery, the size of FNH was decreased.

Management of giant hepatic cysts in the laparoscopic era / 대한외과학회지

PURPOSE: We sought to evaluate the feasibility and outcomes of laparoscopic resection of giant hepatic cysts and surgical success, focusing on cyst recurrence. METHODS: From February 2004 to August 2011, 37 consecutive patients with symptomatic hepatic cysts were evaluated and treated at Dong-A University Hospital. Indications were simple cysts (n = 20), multiple cysts (n = 6), polycystic disease (n = 2), and cystadenoma (n = 9). RESULTS: The median patient age was 64 years, with a mean lesion diameter of 11.4 cm. The coincidence between preoperative imaging and final pathologic diagnosis was 54% and half (n = 19) of the cysts were located in segments VII and VIII. Twenty-two patients had American Society of Anesthesiologists (ASA) classification I and II, and nine had ASA classification III. Surgical treatment of hepatic cysts were open liver resection (n = 3), laparoscopic deroofing (n = 24), laparoscopic cyst excision (n = 4), laparoscopic left lateral sectionectomy (n = 2), hand assisted laparoscopic procedure (n = 2), and single port laparoscopic deroofing (n = 2). The mean fellow-up was 21 months, and six patients (16%) experienced radiographic-apparent recurrence. Reoperation due to recurrence was performed in two patients. Among the factors predicting recurrence, multivariate analysis revealed that interventional radiological procedures and pathologic diagnosis were statistically significant. CONCLUSION: Laparoscopic resection of giant hepatic cysts is a simple and effective method to relieve symptoms with minimal surgical trauma. Moreover, the recurrence is dependent on the type of pathology involved, and the sclerotherapy undertaken.

Efficacy and safety of entecavir plus carnitine complex (GODEX(R)) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex(R)) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-gamma secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.

Prognostic factors for gallbladder cancer in the laparoscopy era / 대한외과학회지

PURPOSE: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. METHODS: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). RESULTS: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. CONCLUSION: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.

Review of 100 cases of single port laparoscopic cholecystectomy / 대한외과학회지

PURPOSE: Single port laparoscopic cholecystectomy (SPLC) is a new advanced technique in laparoscopic surgery. Many laparoscopic surgeons seek to gain skill in this new technique. However, little data has been accumulated and published formally yet. This article reports the achievement of 100 cases of SPLC with the hopes it will encourage laparoscopic surgery centers in the early adoption of SPLC. METHODS: A retrospective review of 100 prospectively selected cases of SPLC was carried out. All patients had received elective SPLC by a single surgeon in our center from May 2009 to December 2010. Our review suggests patients' character, perioperative data and postoperative outcomes. RESULTS: Forty-two men and 58 women with an average age of 45.8 years had received SPLC. Their mean body mass index (BMI) was 23.85 kg/m2. The mean operating time took 76.75 minutes. However, operating time was decreased according to the increase of experience of SPLC cases. Twenty-one cases were converted to multi-port surgery. BMI, age, previous low abdominal surgical history did not seem to affect conversion to multi-port surgery. No cases were converted to open surgery. Mean duration of hospital stay was 2.18 days. Six patients had experienced complications from which they had recovered after conservative treatment. CONCLUSION: SPLC is a safe and practicable technique. The operating time is moderate and can be reduced with the surgeon's experience. At first, strict criteria was indicated for SPLC, however, with surgical experience, the criteria and area of SPLC can be broadened. SPLC is occupying a greater domain of conventional laparoscopic cholecystectomy.

Sodium Iodide Symporter and Phosphatase and Tensin Homolog Deleted on Chromosome Ten Expression in Cholangiocarcinoma Analysis with Clinicopathological Parameters

BACKGROUND/AIMS: This study was performed to investigate the correlation of sodium iodide symporter (NIS) expression with the functionality and loss of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression in human cholangiocarcinoma (CCA). METHODS: Immunohistochemistry for the expression of NIS and PTEN was performed in 60 biopsy specimens of CCA. The clinicopathological parameters were retrospectively identified from medical records. The expression pattern of NIS and loss of PTEN expression were analyzed in association with the clinicopathological characteristics, including survival. RESULTS: Normal biliary trees displayed NIS expression, but hepatocytes did not. NIS expression was divided into two patterns: cytoplasmic and membranous. Fifty-nine cases, all except for one case, displayed NIS expression in tumor cells. Twenty-two cases (33.3%) were mixed pattern, and 39 cases (65.05%) were cytoplasmic pattern; the pure membranous pattern was not noted. There was no association between the NIS expression pattern and clinicopathological parameters, including age, sex, differentiation grade, T stage and tumor, node, metastasis stage (p>0.05). The survival rates were similar among various NIS expression patterns. Normal hepatocytes and biliary trees exhibited PTEN expression in the nucleus and cytoplasm. CCA cells displayed nuclear staining. Thirty-six (60.0%) of 60 cases displayed a loss of PTEN expression. The loss of PTEN expression was observed in the advanced T-stage group (p=0.0036), but there was no association between the loss of PTEN expression and other clinicopathological parameters (p>0.05). No association between the loss of PTEN expression and survival was noted. CONCLUSIONS: NIS is expressed in most types of human CCA. The expression pattern suggests a role in cancer development. PTEN loss expression is common in the context of human CCA, especially in the advanced T stage.

Glomus Tumor in Stomach: 3 Cases / 대한내과학회지

Glomus tumors originate in modified vascular smooth muscle cells and are most commonly found in the dermis or subcutis but are rarely observed in the stomach. We report three cases of patients who presented with incidental findings of subepithelial tumors in the stomach. One patient showed a positive cushion sign, and the others showed negative cushion signs. Endoscopic ultrasonography (EUS) demonstrated sharply demarcated hypoechoic tumors with internal hyperechoic spots in the fourth layer of the gastric wall and several hypoechoic halos around the tumors. Contrast-enhanced abdominal computerized tomography (CT) showed homogeneous high enhancement of tumors up to the delayed scan, and one case showed calcification in the tumor. For treatment, laparoscopic wedge resections were performed. Histological and immunochemical analysis of the tumor cells were compatible with glomus tumors. These characteristic findings in EUS and CT seem to be useful for the diagnosis of gastric glomus tumors.