Seung Woo Park

Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis

In 2002, the Japan Pancreas Society (JPS) was the first in the world to propose diagnostic criteria for autoimmune pancreatitis (AIP). Since the concept of AIP has changed with the accumulation of AIP cases, the Research Committee of Intractable Pancreatic Diseases (RCIPD) provided by the Ministry of Health, Labour and Welfare of Japan and the JPS issued revised clinical diagnostic criteria of AIP in 2006. The Asan Medical Center of Korea also proposed diagnostic criteria for AIP in 2006. However, there are subtle but clinically challenging differences between the Japanese and Korean criteria. This inconsistency makes it difficult to compare data in studies from different centers and elucidate the characteristics of AIP. To reach a consensus on AIP, the RCIPD and the Korean Society of Pancreatobiliary Diseases established the following Asian criteria for the diagnosis of AIP: I-1. Imaging studies of pancreatic parenchyma show a diffuse/segmental/focally enlarged gland, occasionally with a mass and/or a hypoattenuation rim. I-2. Imaging studies of pancreaticobiliary ducts show diffuse/segmental/focal pancreatic ductal narrowing, often with stenosis of the bile duct. (Both I-1 and I-2 are required for diagnosis). II. Elevated level of serum IgG or IgG4, and detection of autoantibodies. III. Common lymphoplasmacytic infiltration and fibrosis, with abundant IgG4-positive cell infiltration. AIP should be diagnosed when criterion I and one of the other two criteria are satisfied, or when histology shows the presence of lymphoplasmacytic sclerosing pancreatitis in the resected pancreas. A diagnostic trial of steroid therapy can be applied carefully by expert pancreatologists only in patients fulfilling criterion I alone with negative diagnostic work-up results for pancreatobiliary cancer.

Early Surgery Versus Conventional Treatment in Asymptomatic Very Severe Aortic Stenosis

Background— The optimal timing of surgical intervention remains controversial in asymptomatic patients with very severe aortic stenosis. We therefore compared the long-term results of early surgery and a conventional treatment strategy. Methods and Results— From 1996 to 2006, we prospectively included a total of 197 consecutive asymptomatic patients (99 men; age, 63±12 years) with very severe aortic stenosis. Patients were excluded if they had angina, syncope, exertional dyspnea, ejection fraction <0.50, significant mitral valve disease, or age >85 years. Very severe aortic stenosis was defined as a critical stenosis in the aortic valve area ≤0.75 cm2 accompanied by a peak aortic jet velocity ≥4.5 m/s or a mean transaortic pressure gradient ≥50 mm Hg on Doppler echocardiography. The primary end point was defined as the composite of operative mortality and cardiac death during follow-up. Early surgery was performed on 102 patients, and a conventional treatment strategy was used for 95 patients. There were no significant differences between the 2 groups in terms of age, gender, European System for Cardiac Operative Risk Evaluation score, or ejection fraction. During a median follow-up of 1501 days, the operated group had no operative mortalities, no cardiac deaths, and 3 noncardiac deaths; the conventional treatment group had 18 cardiac and 10 noncardiac deaths. The estimated actuarial 6-year cardiac and all-cause mortality rates were 0% and 2±1% in the operated group and 24±5% and 32±6% in the conventional treatment group, respectively (P<0.001), and for 57 propensity score-matched pairs, the risk of all-cause mortality was significantly lower in the operated group than in the conventional treatment group (hazard ratio, 0.135; 95% confidence interval, 0.030 to 0.597; P=0.008). Conclusions— Compared with the conventional treatment strategy, early surgery in patients with very severe aortic stenosis is associated with an improved long-term survival by decreasing cardiac mortality. Early surgery is therefore a therapeutic option to further improve clinical outcomes in asymptomatic patients with very severe aortic stenosis and low operative risk.

The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer

Goals The aims of this study were to determine the clinical use of 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) in the differential diagnosis of patients with suspected pancreatic cancer and in the determination of tumor response after concurrent chemoradiotherapy for pancreatic cancer. Background Despite advances in diagnostic tools for pancreatic cancer, it is difficult to differentiate pancreatic cancer from mass-forming pancreatitis. Even with current imaging modalities, it is also difficult to assess tumor response to therapeutic intervention. Study One hundred two patients with suspected pancreatic cancer were selected for this study. Dynamic computerized tomography (CT) scan and 18FDG-PET were used sequentially to diagnose pancreatic cancer. After diagnostic confirmation their diagnostic yields were compared. We also evaluated the treatment response in 15 patients who underwent chemoradiation therapy with dynamic CT scan and 18FDG-PET and compared their results. Results In 93 out of 102 patients, pancreatic cancer was confirmed. 18FDG-PET showed higher diagnostic accuracy than CT scan (95.1% vs. 76.5%). 18FDG-PET was also superior to CT in the detection of liver metastasis. 18FDG-PET detected treatment response in 5 out of 15 cases after chemoradiation therapy, whereas CT could not detect any treatment response. Comparing responder and nonresponder, 18FDG-PET was able to predict significantly different prognosis (399 vs. 233 d, P<0.05). Conclusions 18FDG-PET is a very useful tool in diagnosing pancreatic cancer. 18FDG-PET may be also used as an adjunct for determining the treatment modality of pancreatic cancer and evaluating tumor response to chemoradiation therapy.

Endoscopic enucleation of upper-GI submucosal tumors by using an insulated-tip electrosurgical knife

BACKGROUND Submucosal tumors often are found incidentally at upper endoscopy. Although the majority of the ones less than 5 cm in size are benign, periodic monitoring for incremental changes in size, which can be stressful and bothersome to patients, is essential. If relatively easy and safe, an endoscopic method of removal would be optimal treatment. Conventional endoscopic enucleation technically is difficult and often leads to serious complications, such as bleeding and perforation. A novel method for endoscopic enucleation of submucosal tumors with an insulated-tip electrosurgical knife is reported. METHODS En bloc enucleation was attempted by using an insulated-tip electrosurgical knife in 15 patients (10 men, 5 women; median age 48 years) with submucosal tumors of the esophagus (5) or stomach (5 cardia/fundus, 4 body, one antrum). EUS was performed to determine the layer of origin and the exact size of the submucosal tumor. RESULTS Tumors arose in the muscularis propria in 11 cases, submucosa in two, and muscularis mucosa in one. Enucleation was relatively easy and successful in 14 cases. In one case, however, piecemeal resection was unavoidable because of fibrotic adhesions with the surrounding tissue; this tumor later was confirmed to be a glomus tumor. Median procedure time was 35 minutes (8-180 minutes) and median size of the submucosal tumors was 2x1.7 cm. The largest lesion, located in the esophagus, measured 6x3 cm. Histopathologic diagnoses included leiomyoma (9), GI stromal tumor (4), stromal tumor of unknown malignant potential (1), and glomus tumor (1). A small perforation occurred in one patient with a 2.5-cm tumor in the anterior wall of proximal gastric body but was managed successfully by endoscopic clip application. Follow-up endoscopy at 2 months in this patient revealed no tumor recurrence and complete healing of the treatment-related ulcer. CONCLUSIONS En bloc endoscopic enucleation of submucosal tumors by using an insulated-tip electrosurgical knife appears to be safer, easier, and less time consuming compared with previously described methods. However, further investigation and comparative studies are required to confirm the safety and efficacy of this method.

Longitudinal 2D strain at rest predicts the presence of left main and three vessel coronary artery disease in patients without regional wall motion abnormality.

AIMS Non-invasive echocardiographic detection of coronary artery disease (CAD), even in left main or three-vessel CAD, usually requires a stress test since regional wall motion abnormalities (RWMA) are not always evident at rest. Strain is a more sensitive parameter of myocardial systolic function and may be abnormal in patients with severe CAD. METHODS AND RESULTS We evaluated whether peak systolic longitudinal strain (PSLS) of left ventricle using 2D speckle tracking method might be useful for screening of severe CAD. One hundred and eight patients who underwent echocardiography and coronary angiography were evaluated. Patients were grouped according to the coronary angiographic findings as follows; high-risk group with left main or three-vessel CAD (n = 38), low-risk group with one- or two-vessel CAD (n = 28), and control group without CAD (n = 30). PSLSs of all left ventricular segments were obtained successfully in 96 (89%) patients. None had RWMA at resting echocardiogram. PSLS was significantly reduced, especially in mid- and basal segments, in the high-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that mid- and basal PSLSs could effectively detect patients with severe CAD (area under ROC curve = 0.83, 95% CI 0.75-0.91). According to ROC curve analysis, -17.9% appears to be a helpful cutoff value for discriminating those with severe CAD (specificity 79% and sensitivity 79%). CONCLUSION PSLS at rest was significantly lower in patients with left main or three-vessel CAD without RWMA, and might be useful for identifying patients with a severe CAD.

Perfusion CT: Noninvasive Surrogate Marker for Stratification of Pancreatic Cancer Response to Concurrent Chemo- and Radiation Therapy

PURPOSE To prospectively determine whether perfusion computed tomography (CT) parameters, such as volume transfer constant (K(trans)) between blood plasma and extracellular extravascular space (EES) and blood volume calculated from dynamic CT data, can be used to predict response of pancreatic cancer to concurrent chemotherapy and radiation therapy (CCRT). MATERIALS AND METHODS This prospective study was institutional review board approved, and written informed consent was obtained. Thirty patients with pancreatic cancer underwent perfusion CT with 64-detector row CT before gemcitabine-based CCRT. Two perfusion parameters (K(trans) and blood volume) measured before treatment were compared between patients who responded to treatment and those who did not, as determined with World Health Organization criteria from first and second posttherapeutic follow-up CT examinations, which were performed at 3- and 6-month follow-up. Statistical analysis was performed with the two-sample t test. A receiver operating characteristic curve was used to determine the best cutoff value of perfusion parameters for differentiation of responders from nonresponders. RESULTS Twenty of 30 patients examined at 3-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (50.8 mL/100 mL/min +/- 30.5 [standard deviation] vs 19.0 mL/100 mL/min +/- 10.8, P = .001). The best cutoff value for differentiating between responders and nonresponders was 31.8 mL/100 mL/min, which yielded 75.0% sensitivity and 90.0% specificity. Ten of 18 patients examined at 6-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (58.6 mL/100 mL/min +/- 43.2 vs 19.8 mL/100 mL/min +/- 10.9, P = .002). Responders also had higher blood volume values, but this difference was not significant. CONCLUSION Tumors with a high pretreatment K(trans) value tended to respond better to CCRT than did tumors with a low pretreatment K(trans) value. Perfusion CT may be used to predict tumor response to CCRT in patients with pancreatic cancer. This might aid in development of a tailored approach to therapy in these patients.

Outcomes of medically treated patients with aortic intramural hematoma

PURPOSE Aortic intramural hematoma has been considered a precursor of aortic dissection, and the same treatment strategy, usually involving surgery, has been applied to both conditions. However, the outcomes of patients with aortic intramural hematoma who are treated medically, including the remodeling process that occurs after an acute event, are not known. SUBJECT AND METHODS A total of 124 patients with acute aortic intramural hematoma (41 in the proximal aorta and 83 in the distal aorta) was enrolled from five institutions in South Korea. Patients received medical treatment without surgery. A follow-up imaging study was performed in 105 patients. RESULTS Pericardial (59% [n = 24] vs. 11% [n = 9], P <0.004) and pleural effusions (63% [n = 26] vs. 45% [n = 37], P = 0.05) were more common in patients with the proximal type than in those with the distal type. In-hospital mortality was somewhat higher with proximal hematomas (7% [n = 3 deaths] vs. 1% [n = 1 death], P = 0.11). A follow-up imaging study in 36 patients with proximal hematomas confirmed resorption of the hematoma in 24 patients (67%) and development of aortic dissection in 9 (25%). Resorption was confirmed in 54 (78%) of the 69 patients with distal hematomas who underwent follow-up imaging; localized aortic dissection developed in 11 (16%) of these patients. The 3-year survival rate was 78% in the proximal type and 87% in the distal type (P = 0.10). CONCLUSION Patients with aortic intramural hematoma had a high rate of resorption with medical treatment regardless of the affected site. Further investigation is necessary to determine the optimal treatment strategy and timing of surgical intervention, especially for patients with proximal hematomas.

[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild-type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53-expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53-expressing cells by inducing temporal growth arrest.

Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis.

Objective: To characterize the role of Oct4 and Nanog, two important homeobox transcription factors of embryonic development, in pancreatic carcinogenesis. Methods: Using a tissue microarray of human pancreatic carcinoma and adjacent noncancerous tissues as well as the N-nitrosobis(2-oxopropyl)amine-induced Syrian golden hamster pancreatic cancer model, we characterized the expression of Oct4 and Nanog. The presence of K-ras mutation with the time course of carcinogenesis in hamster model was also evaluated. Results: Oct4 expression in metaplastic ducts was significantly stronger than in normal acini and pancreatic carcinoma (P < 0.05). Of 24 cases, 19 (79.2%) showed a strong Oct4 expression in metaplastic ducts. In contrast, only 6 (19.4%) of 31 cancer tissues and 3 (16.7%) of 18 noncancer tissues showed a strong Oct4 expression. Nanog also showed similar patterns as Oct4. Restriction fragment length polymorphism-polymerase chain reaction showed the overt K-ras mutation after the expression of Oct4 in the hamster model. Conclusions: The strong expression of Oct4 and Nanog in metaplastic ducts and Oct4 expression preceding Ras mutation suggests that these homeobox transcription factors are associated with the early stage of pancreatic cancer carcinogenesis and may play an important role in that process.

The Clinical Characteristics, Laboratory Parameters, Electrocardiographic, and Echocardiographic Findings of Reverse or Inverted Takotsubo Cardiomyopathy: Comparison With Mid or Apical Variant

Although takotsubo cardiomyopathy (TTC) typically affects the apical and/or midventricular segments, several recent cases have reported a reverse or inverted variant of TTC. The aim of this study was to investigate the clinical characteristics, laboratory parameters, electrocardiographic, and echocardiographic findings in patients presenting as inverted TTC and compare those parameters to those presenting as mid or apical variant.