Hyun Joo Jang

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Trends in the eradication rates of Helicobacter pylori infection for eleven years

AIM To evaluate the trends in the eradication rate of Helicobacter pylori (H. pylori) over the past 11 years in a single center. METHODS This retrospective study covered the period from January 2000 to December 2010. We evaluated 5746 patients diagnosed with gastric ulcers (GU), duodenal ulcers (DU), GU + DU, or nonpeptic ulcers associated with an H. pylori infection. We treated them annually with the 2 wk standard first-line triple regimen, proton pump inhibitor (PPI) + amoxicilin + clarithromycin (PAC; PPI, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day). The follow-up test was performed at least 4 wk after the completion of the 2 wk standard H. pylori eradication using the PAC regimen. We also assessed the eradication rates of 1 wk second-line therapy with a quadruple standard regimen (PPI b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.) after the failure of the first-line therapy. Statistical analysis was performed with 95%CI for the differences in the annual eradication rates. RESULTS A total of 5746 patients [2333 males (58.8%), 1636 females (41.2%); mean age of males vs females 51.31 ± 13.1 years vs 52.76 ± 13.6 years, P < 0.05, total mean age 51.9 ± 13.3 years (mean ± SD)] were investigated. Among these patients, 1674 patients were excluded: 35 patients refused treatment; 18 patients ceased H. pylori eradication due to side effects; 1211 patients had inappropriate indications for H. pylori eradication, having undergone stomach cancer operation or chemotherapy; and 410 patients did not undergo the follow-up. We also excluded 103 patients who wanted to stop eradication treatment after only 1 wk due to poor compliance or the side effects mentioned above. Finally, we evaluated the annual eradication success rates in a total of 3969 patients who received 2 wk first-line PAC therapy. The endoscopic and clinical findings in patients who received the 2 wk PAC were as follows: gastric ulcer in 855 (21.5%); duodenal ulcer in 878 (22.1%); gastric and duodenal ulcer in 124 (3.1%), erosive, atrophic gastritis and functional dyspepsia in 2055 (51.8%); and other findings (e.g., MALToma, patients who wanted to receive the therapy even though they had no abnormal endoscopic finding) in 57 (0.5%). The overall eradication rate of the 2 wk standard first-line triple regimen was 86.5%. The annual eradication rates from 2000 to 2010 were 86.7%, 85.4%, 86.5%, 83.3%, 89.9%, 90.5%, 88.4%, 84.5%, 89.1%, 85.8%, and 88.3%, sequentially (P = 0.06). No definite evidence of a significant change in the eradication rate was seen during the past eleven years. The eradication rates of second-line therapy were 88.9%, 82.4%, 85%, 83.9%, 77.3%, 85.7%, 84.4%, 87.3%, 83.3%, 88.9%, and 84% (P = 0.77). The overall eradication rate of 1 wk quadruple second-line therapy was 84.7%. There was no significant difference in the eradication rate according to the H. pylori associated diseases. CONCLUSION This study showed that there was no trend change in the H. pylori eradication rate over the most recent 11 years in our institution.

Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review

The PET Response Criteria in Solid Tumors (PERCIST) is a new method for the quantitative assessment of metabolic changes in solid tumors. The assessments of tumor response between the RECIST and PERCIST have shown considerable difference in several studies. This pooled study was conducted to compare tumor response according to the two criteria in patients with solid tumors. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the RECIST or PERCIST from 2009 and January 2016. There were six articles comparing the RECIST and PERCIST. A total of 268 patients were recruited; 81 with colorectal cancer, 60 with lung cancer, 48 with esophageal cancer, 28 with breast cancer, 14 with basal cell carcinoma, 12 with stomach cancer, 10 with head and neck cancer, and 16 with other rare cancers. The agreement of tumor response between the RECIST and PERCIST was moderate (k = 0.590). Of 268 patients, 101 (37.7%) showed discordance in the tumor responses between two criteria. When adopting the PERCIST, tumor response was upgraded in 85 patients and downgraded in 16. The estimated overall response rates were significantly different between two criteria (35.1% by RECIST vs. 54.1% by PERCIST, P < 0.0001). In conclusion, this pooled analysis demonstrates that the concordance of tumor responses between the RECIST and PERCIST criteria is not excellent. The PERCIST might be more suitable for assessing tumor response than the RECIST criteria.

Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer

Statin has been known not only as their cholesterol-lowering action but also on their pleiotropic effects including anti-inflammatory and anti-oxidant as well as anti-cancer effect. Nrf2 (NF-E2-related factor 2) is a transcription factor to activate cellular antioxidant response to oxidative stress. There are little known whether statins affect activation of Nrf2 and Nrf2 signaling pathway in colon cancer cells. We investigated whether simvastatin stimulates the expression of Nrf2 and nuclear translocation of Nrf2 and which signal pathway is involved in the expression of Nrf2 and antioxidant enzymes. We investigated the effect of simvastatin on the expression of Nrf2 and nuclear translocation of Nrf2 in two human colon cancer cell lines, HT-29 and HCT 116 through cell proliferation assay, Western blotting and immunocytochemical analysis. We evaluated which signal pathway such as ERK or PI3K pathway affect Nrf2 activation and whether simvastatin induces antioxidant enzymes (heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1), γ-glutamate-cysteine ligase catalytic subunit (GCLC)). We demonstrated simvastatin-induced dose-dependent up-regulation of Nrf2 expression and stimulated Nrf2 nuclear translocation in colon cancer cells. We also demonstrated that simvastatin-induced anti-oxidant enzymes (HO-1, NQO1, and GCLC) in HT-29 and HCT 116 cells. PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) suppressed simvastatin-induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells. This study shows that simvastatin induces the activation and nuclear translocation of Nrf2 and the expression of various anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells.

Prevalence of Minimal Change Lesions in Patients with Non-Erosive Reflux Disease: A Case-Control Study

Background/Aims: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). Methods: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). Results: Overall frequency of MC (≥1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72–9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. Conclusions: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

Endoscopic submucosal dissection for early gastric cancer with undifferentiated-type histology: A meta-analysis.

AIM To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with undifferentiated-type histology. METHODS A systematic literature review was conducted using the core databases. Complete resection, curative resection, en bloc resection, recurrence and adverse event rate were extracted and analyzed. A random effect model was applied. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated using a funnel plot, the trim and fill method, Eggers test, and a rank correlation test. RESULTS Fourteen retrospective studies between 2009 and 2014 were identified (972 EGC lesions with undifferentiated-type histology). The total en bloc and complete resection rates were estimated as 92.1% (95%CI: 87.4%-95.2%) and 77.5% (95%CI: 69.3%-84%), respectively. The total curative resection rate was 61.4% (95%CI: 44.5%-75.9%). The overall recurrence rate was 7.6% (95%CI: 3.4%-16%). Limited to histologically diagnosed expanded-criteria lesions, the en bloc and complete resection rates were 91.2% and 85.6%, respectively. The curative resection rate was 79.8%. CONCLUSION In this analysis, ESD is a technically feasible treatment modality for EGC with undifferentiated-type histology. Long-term studies are needed to confirm these therapeutic outcomes.

Familial Mediterranean Fever: The First Adult Case in Korea

Familial Mediterranean fever (FMF) is known to be a genetic disorder that prevalent among populations surrounding the Mediterranean Sea. Since Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been reported in countries not related or close to this area like Japan. In addition it has been generally accepted that the clinical onset of FMF begins before 20 yr of age in most patients. Onset of the disease at an older age may occur but is rare. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. We describe a case of adult-onset FMF confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man, who has no family history of FMF, presented with periodic fever, abdominal pain and vomiting. Though several various tests were thoroughly performed to evaluate the cause of his symptoms, there was no evidence of infectious, autoimmune or neoplastic diseases. Several gene analysis of periodic fever syndrome was finally performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We confirmed the first adult case of FMF through detection of MEFV gene mutations in Korea and describe his clinical characteristics.

Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A Pooled Analysis

Background:We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0. Methods: We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013. Results: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria. Conclusion: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer.

Giant Brunner's Gland Adenoma of the Proximal Jejunum Presenting as Iron Deficiency Anemia and Mimicking Intussusceptions.

Brunners gland adenoma is a rare benign proliferative lesion developing most commonly in the posterior wall of the duodenum. It is usually small in size and asymptomatic. Depending on its size or location, however, the clinical manifestations of this tumor may be variable from nonspecific symptoms to gastrointestinal bleeding or obstruction. Brunners gland adenoma in the proximal jejunum is extremely rare. We report a very rare case of giant Brunners gland adenoma developing in the proximal jejunum which presented as iron deficiency anemia and mimicked intussusceptions on radiologic studies.

Development of Primary Biliary Cirrhosis in a Patient with Crohn's Disease: A Case Report and Review of the Literature

A variety of extraintestinal manifestations has been described in patients with inflammatory bowel disease. Hepatobiliary manifestations in Crohn’s disease (CD) include gallstones, primary sclerosing cholangitis (PSC), pericholangitis, fatty liver, and autoimmune hepatitis (1, 2). Ulcerative colitis (UC) is also associated with many hepatobiliary diseases, with the most common hepatobiliary manifestation being PSC (3). The association of primary biliary cirrhosis (PBC) and UC has sporadically been reported, suggesting a common immunologic basis of the two diseases (4, 5). However, although it seems to be possibile that CD is associated with PBC as a hepatobiliary manifestation, the presentation of PBC in a patient with CD has not been reported except for a case of personal observation (6). We report one case of PBC that developed in a patient with underlying CD.