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Advances in genetic sequencing and other diagnostic technologies have enabled the use of precision medicine in clinical cancer care, as well as the development of novel therapies that are targeted to specific molecular drivers of cancer. Developing these new agents and making them accessible to patients requires global clinical studies and regulatory review and approval by different national regulatory agencies. Whereas these global trials present challenges for drug developers who conduct them and regulatory agencies who oversee them, they also raise practical issues about patients with low-frequency cancers who need these therapies. A lack of uniform standards in both regulatory approval for marketing and reimbursement for approved agents across countries may make the newly developed agent either unavailable or inaccessible to patients in certain countries or regions, even if patients from those countries or regions participated in the clinical research that established the safety and efficacy of the agent. In an effort to further understand and address this need, we convened an international workshop in 2017 in North Bethesda, MD. After presentations of the individual regulatory pathways for marketing approval and reimbursement for individual nations, participants discussed expedited pathways and specific challenges for uncommon cancers. As a matter of justice, agents being developed for rare cancers, pediatric cancers, or uncommon molecular subsets of common cancers need a pragmatic, science-based regulatory policy framework to clearly specify the type and quantity of evidence needed to demonstrate efficacy from these trials and evidence to support accessibility.

Background and Aims Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. Methods All consecutive nucleos(t)ide-naive CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. Results Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. Conclusions Delayed AFP response to ETV may serve as an indicator of high HCC risk.

Background/Aims Portal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients. Methods Patients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography. Results Twenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation. Conclusions Warfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.

Background/Aims Gallbladder diseases can give rise to dyspeptic or colonic symptoms in addition to biliary pain. Although most biliary pain shows improvement after cholecystectomy, the fates of dyspeptic or colonic symptoms still remain controversial. This study assessed whether nonspecific gastrointestinal symptoms improved after laparoscopic cholecystectomy (LC) and identified the characteristics of patients who experienced continuing or exacerbated symptoms following surgery. Methods Sixty-five patients who underwent LC for uncomplicated gallbladder stones or gallbladder polyps were enrolled. The patients were surveyed on their dyspeptic or colonic symptoms before surgery and again at 3 and 6 months after surgery. Patients' mental sanity was also assessed using a psychological symptom score with the Symptom Checklist-90-Revised questionnaire. Results Forty-four (67.7%) patients showed one or more dyspeptic or colonic symptoms before surgery. Among these, 31 (47.7%) and 36 (55.4%) patients showed improvement at 3 and 6 months after surgery, respectively. However, 18.5% of patients showed continuing or exacerbated symptoms at 6 months after surgery. These patients did not differ with respect to gallstone or gallbladder polyps, but differed in frequency of gastritis. These patients reported lower postoperative satisfaction. Patients with abdominal symptoms showed higher psychological symptom scores than others. However, poor mental sanity was not related to the symptom exacerbation. Conclusions Elective LC improves dyspeptic or colonic symptoms. Approximately 19% of patients reported continuing or exacerbated symptoms following LC. Detailed history-taking regarding gastritis before surgery can be helpful in predicting patients’ outcome after LC.

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

Takayasu's arteritis (TA) is a nonspecific, chronic and stenotic panarteritis which usually involves the aorta and its major branches. Corticosteroid and immunosuppressants are recommended to manage the acute inflammatory phase, but their long term benefits are uncertain. Blood pressure (BP) control during the chronic phase of TA is essential to preserve renal function, which is associated with the patient's long-term prognosis and survival. Revascularization in organ damaging arterial stenosis with percutaneous angioplasty (PTA)/stenting or bypass surgery have been accepted as established treatment options in chronic complicated phase of TA. We present a case of a 31-year-old female patient with a two-day history of sudden onset oliguria and generalized edema whose acute oliguric renal failure was successfully reversed following PTA and stenting in a solitary functioning kidney with critical renal artery stenosis (RAS) caused by TA.

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.

There is a paucity of studies that compare the differences in published articles submitted from the East and the West in the area of neurogastroenterology and motility (NM). To compare the article topics from the East and the West which have been published, 5 Western (Gastroenterology, Gut, American Journal of Gastroenterology, American Journal of Physiology-Gastrointestinal and Liver Physiology, and Neurogastroenterology and Motility) and 3 Eastern gastrointestinal journals (Journal of Gastroenterology, Journal of Gastroenterology and Hepatology, and Journal of Neurogastroenterology and Motility) were selected based on the impact factor. Published papers were classified into 12 categories and 60 subcategories. The titles and abstracts of review articles, original articles, and meta-analyses from these journals were reviewed for the last 2 years (2013–2014). In case of Journal of Neurogastroenterology and Motility which is published quarterly, this search was performed for 5 years (2010–2014). Of the total 2656 reviewed articles, 842 (260 from the East and 582 from the West) were classified into the category of NM. The most frequently published papers from the Western researchers were categorized as brain-gut interaction, visceral hypersensitivity, and irritable bowel syndrome, whereas those from the Eastern researchers were categorized as gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome. This difference between the East and the West is not just due to the journal itself, but it also depends on the author’s affiliation and their ability to perform high quality research in the area of the NM. These data provide evidence for the research trend and give valuable information to the researchers for determining subjects for the study and for selecting proper journals for publishing their studies.

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

Background/Aims: Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome. Methods: A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85). Results: The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P

Sparganosis is caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissue, but less frequently invades muscle, intestines, spinal cord, and the peritoneopleural cavity. The authors managed a female patient who presented with a recurrent pericardiopleural effusion and peripheral eosinophilia. The anti-sparganum-specific IgG serum level was significantly higher than normal control levels. In this patient, sparganosis was caused by the ingestion of raw frogs in an effort to control her thyroid disease. The recurrent pericardiopleural effusion and peripheral eosinophilia were controlled by 3 consecutive doses of praziquantel (75 mg/kg/day). The patient is doing well 4 years after presentation. Sparganosis should be considered a rare, but possible cause of recurrent pericardial effusion and peripheral eosinophilia. Immunoserologic testing using enzyme linked immunosorbent assays can be helpful in diagnosing human sparganosis, especially in cases without a subcutaneous lump or mass. Praziquantel is an alternative treatment for sparganosis in surgically-unresectable cases.

Purpose: To evaluate the feasibility and usefulness of the transradial approach for intra-arterial chemoembolization therapy in patients with hepatocellular carcinomas. Materials and Methods: Twenty-nine patients with hepatocellular carcinoma who underwent intra-arterial chemoembolization via the radial artery approach were involved in this study. All underwent Allen’s test to check ulnar arterial patency. In all cases, we used the radial approach hepatic artery (RHA) catheter designed by ourselves, evaluating the selection ability of the hepatic artery using an RHA cathter, the number of punctures, the procedure time, and compression time at the puncture site as well as complications occurring during and after the procedure. Results: Except for three in which puncture failure, brachial artery variation or hepatic artery variation occurred, all procedures were successful. The mean number of punctures was 3.5, and the average duration of the whole procedure was one and half hours. This gradually decreased as the number of procedures increased. The average duration at a compression of puncture site was 12 minutes. There were no major complications. Minor complications included minimal intimal dissection of the radial artery (3.8%), reversible vasospasm of the radial artery (7.7%), hematoma at a puncture site (7.7%) and transient neurologic deficit (3.8%). Conclusion: The transradial approach using an RHA catheter for intra-arterial chemoembolization therapy in patients with hepatocellular carcinomas was technically feasible, with acceptable levels of safety. It may be a good alternative to absolute bed rest with a sand bag after the femoral approach.