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Background Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. Methods Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses ('not-NASH,' 'borderline,' and 'NASH') of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. Results Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52-0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. Conclusions A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

Purpose The aim of this retrospective study was to determine the prevalence of early implant failure using a single implant system and to identify the factors contributing to early implant failure. Methods Patients who received implant treatment with a single implant system (Luna®, Shinhung, Seoul, Korea) at Dankook University Dental Hospital from 2015 to 2017 were enrolled. The following data were collected for analysis: sex and age of the patient, seniority of the surgeon, diameter and length of the implant, position in the dental arch, access approach for sinus-floor elevation, and type of guided bone regeneration (GBR) procedure. The effect of each predictor was evaluated using the crude hazard ratio and the adjusted hazard ratio (aHR) in univariate and multivariate Cox regression analyses, respectively. Results This study analyzed 1,031 implants in 409 patients, who comprised 169 females and 240 males with a median age of 54 years (interquartile range [IQR], 47–61 years) and were followed up for a median of 7.2 months (IQR, 5.6–9.9 months) after implant placement. Thirty-five implants were removed prior to final prosthesis delivery, and the cumulative survival rate in the early phase at the implant level was 95.6%. Multivariate regression analysis revealed that seniority of the surgeon (residents: aHR=2.86; 95% confidence interval [CI], 1.37–5.94) and the jaw in which the implant was placed (mandible: aHR=2.31; 95% CI, 1.12–4.76) exerted statistically significant effects on early implant failure after adjusting for sex, age, dimensions of the implant, and type of GBR procedure (preoperative and/or simultaneous) (P, Graphical Abstract

The aim of the present study was to re-visit the gingival dimension using digital scanning in a healthy Korean population. Forty-eight periodontally healthy volunteers (38 males and 10 females, mean age: 24.3 ± 2.2 years) were included. The mucogingival junction was highlighted using 2.5% diluted iodine solution. Then, the facial gingiva and mucosa of both jaws were digitally scanned using an intraoral digital scanner. Using computer software and periodontal probing, the heights and areas of keratinized gingiva (KG) and attached gingiva (AG) were measured. Similar distribution patterns in the gingival heights were noted in the maxilla and mandible. The maxilla showed substantially greater gingival values than the mandible. The heights of the KG and AG were notably smaller on the mandibular first premolar (2.37 mm and 1.07 mm, median value) and second molar (3.28 mm and 1.78 mm) than on the other teeth. The area of the KG was the largest in the canine (63.74 mm2 and 46.85 mm2) and first molar (64.14 mm2 and 58.82 mm2) in each jaw. Mandibular first and second molars, mandibular canine, and maxillary canine showed the highest value of the area under the receiver operation characteristics curve (&gt, 0.7) for differentiating between males and females. The gingival dimensions recorded using intraoral scanner demonstrated similar distribution patterns as in previous studies.

Shin, E.H.; Kang, D.Y., and Lee, J., 2017. Analysis and international comparison of drowning in South Korea. In: Lee, J.L.; Griffiths, T.; Lotan, A.; Suh, K.-S., and Lee, J. (eds.), The 2nd International Water Safety Symposium. Journal of Coastal Research, Special Issue No. 79, pp. 21–25. Coconut Creek (Florida), ISSN 0749-0208. From WHO (World Health Organization), drowning is the third leading cause of accidental death in the world. The number of drowning around the world is collected from the lifesaving organizations through ILS (International Lifesaving Federation) based on the statistics office in the nations. The cause of death is categorized by international and/or national code of disease and most of nations comply with the codes however some of LMICs (Low Middle Income Country) manually count the drowning by accidents reported in the newspapers. After Sewolho ferry wreck in 2014, which brought about 300 drowning in South Korea, more attention has been drawn to water safety but there has ...

Kim, H.M.; Kang, D.Y.; Kim, T., and Lee, J., 2017. Analysis of the awareness change of public CPR training in metropolitan Seoul from 2011 to 2015. In: Lee, J.L.; Griffiths, T.; Lotan, A.; Suh, K.-S., and Lee, J. (eds.), The 2nd International Water Safety Symposium. Journal of Coastal Research, Special Issue No. 79, pp. 30–34. Coconut Creek (Florida), ISSN 0749-0208. Cardiopulmonary Resuscitation (CPR) is the first response for a drowning victim. The quick action of lifeguards and facility operators is crucial to elevate the survival rate. However, there are plenty of beaches and waterfronts without lifeguards; therefore, bystander CPR is equally as important. To increase bystander CPR, public education is essential. This study analyzes the changing perceptions of CPR training and the change in people's confidence in executing CPR after a public CPR education program in metropolitan Seoul from 2011 to 2015. The participants were public school students, teachers, social workers, and public staff w...

Kang, D.Y.; Hong, S., and Lee, J., 2017. An introduction of AELIS (Aquatic Environment Life-saving Integrated System). In: Lee, J.L.; Griffiths, T.; Lotan, A.; Suh, K.-S., and Lee, J. (eds.), The 2nd International Water Safety Symposium. Journal of Coastal Research, Special Issue No. 79, pp. 11–15. Coconut Creek (Florida), ISSN 0749-0208. AELIS (Aquatic Environment Life-saving Integrated System) is designed to monitor the high profiles of drowning and the swimmers approaching the swimming boundary lines in real time in order to prevent accidents in the water environment and maintain high standard of the safety. It also detects the swimmers who attempt to get in the water without lifeguards at night, which has high possibility of drowning. The system automatically recognize the potential danger in the blind spots where lifeguards hardly manage. AELIS proactively reduces the risk of life-threatening accidents and supports fast rescue by paging to the lifeguards and safety officers of the facilities...

We determined the nationwide seroprevalence of hepatitis E virus (HEV) infection in the wild boar population in Korea. Enzyme-linked immunosorbent assay (ELISA) results showed that 42% of the 528 wild boars that were hunted between 2013 and 2014 were anti-HEV antibody positive. Furthermore, all Korean provinces showed an HEV seroprevalence between 9.8% and 51.1%, suggesting that wild boar HEV infection occurs throughout the country. Importantly, infected wild boar could act as a potential reservoir for HEV and could aid transmission to other animals and humans.

A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for visual detection of European (EU) and North American (NA) porcine reproductive and respiratory syndrome viruses (PRRSVs) were established and evaluated with reference PRRSV strains and clinical samples. The assay was performed in two reaction tubes containing each set of primers specific for EU or NA-PRRSV at 58 °C for 40 min, and the results could be visually detected by the naked eye, using hydroxynaphthol blue dye. The detection limit of the assay was 1 or 0.1 TCID 50 /0.1 mL for EU or NA PRRSV, respectively, which was comparable to that of the previously described real-time RT-PCR (qRT-PCR). The detection rate of the assay on 130 field samples was 72.3%, relatively higher than that of qRT-PCR (70.8%), and there was high overall percentage agreement between the two assays. The high specificity, sensitivity, and reliability of the RT-LAMP assay described in this study renders it useful for the rapid and differential diagnosis of EU and NA PRRSVs, even in under-equipped laboratories.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological spectrum characterized by hepatic steatosis without history of significant alcohol use or other known liver disease. The commonly associated factors include obesity, insulin resistance syndrome, and hyperlipidemia. Other associations include jejuno-ileal bypass/gastroplasty surgery for morbid obesity, parenteral nutrition, forms of malnutrition, bacterial contamination of the small bowel, certain inherited metabolic disorders, and a wide range of drugs and environmental toxins [1]. The natural history and histological spectrum of NAFLD range from stable simple steatosis to progressive or advanced disease, such as steatohepatitis, cirrhosis, and even hepatocellular carcinoma [2-13]. A clinicopathological correlation is needed to diagnose NAFLD, as clinical assessment, laboratory tests, and imaging techniques alone provide limited pertinent information. Liver biopsy is the only reliable diagnostic tool to evaluate a patient with suspected NAFLD. Degree of steatosis, liver injury, and fibrosis associated with NAFLD can be identified and differentiated from simple steatosis and nonalcoholic steatohepatitis (NASH), which is the progressive form of NAFLD [14,15]. A NAFLD histopathological grading system was proposed by Brunt et al. in 1999 [16]. They proposed to classify each of steatosis, inflammation, and ballooning degeneration into three grades and fibrosis into four stages. Since then, Kleiner et al. [17] of the NASH Clinical Research Network have proposed a more relevant classification. Other than steatosis, inflammation, and ballooning degeneration, they proposed the classification of fibrosis around the central area into three more detailed grades. Also, they scored each finding and suggested that a score greater than five indicates NASH. However, until now, classifications for NAFLD or NASH have differed depending on the researcher, and no NAFLD histopathological grading system has been standardized, causing confusion for clinicians and pathologists. Furthermore, the histomorphological criteria for NAFLD pathologic features in liver tissue remain subjective. Thus, in this study, we determined the interobserver agreement of NAFLD pathologic features between pathologists and analyzed the causes of the disagreement in order to define the histopathological features in more detail as the basis for a grading system.

In this study, we developed a loop-mediated isothermal amplification (LAMP) with hydroxynaphtol blue dye (HNB) for rapid and direct visual detection of porcine circovirus 2 DNA with high sensitivity and specificity. The LAMP was completed in 40 min at 63 o C, and the results of the LAMP can be con-firmed by naked eye without any detection process. The sensitivity of the LAMP was 10-fold higher than that of the commercial PCR (cPCR) and real time PCR (rPCR) previously reported. In clinical application, the PCV2 detection rate of the LAMP was the same on porcine tissue samples (75.0%, 36/48) between porcine blood samples (75.0%, 39/52). The PCV2 detection rate (75.0%) of LAMP was higher than those of the cPCR and rPCR (67.3%, 35/52) in blood samples. In conclusion, the LAMP developed in the study could be an useful alternative method for the detection of PCV2 in the swine disease diagnostic laboratories. Key words : Porcine circovirus 2 (PCV2), loop-mediated isothermal amplification (LAMP), polymerase chain reaction (PCR), real time-PCR (rPCR)

The clear cell/lipid-rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22-year-old man and a 52-year-old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management.

A eight-month-old blue and yellow macaw ( Ara ararauna ) with psittacine beak and feather disease (PBFD)-suspected signs, such as, abnormal feather, depression and diarrhea, was presented to Animal Disease Intervention Center, Kyungpook National University in 16 April 2014. The partial ORF V1 gene of PBFD virus (PBFDV) was detected by polymerase chain reaction (PCR) from DNA templates extracted from feather, blood and cloacal swab sample of the bird, but no other viral DNAs that often infected in psittacine birds including avian bornavirus and avian polyomavirus were detected from the samples of the bird, indicating this case is due to single infection of PBFDV. Nucleotide sequence anal-ysis of the amplified partial ORF V1 gene was confirmed to have 96.7% and 93.6% homology with that of previously reported PBFDV strain (Genbank no. HM748924 and FJ685980). This report de-scribes the first detection of PBFDV in PBFD-suspected blue and yellow macaw in Korea. Key words : Psittacine beak and feather disease (PBFD), Blue and yellow macaw, Polymerase chain reaction (PCR)

Lee, J.; Park, J.; Kim, I., and Kang, D.Y., 2019. Application of vision-based safety warning system to Haeundae Beach, Korea. In: Lee, J.L.; Yoon, J.-S.; Cho, W.C.; Muin, M., and Lee, J. (eds.), The 3rd International Water Safety Symposium. Journal of Coastal Research, Special Issue No. 91, pp. 216-220. Coconut Creek (Florida), ISSN 0749-0208.Between 2012 and 2017, the number of drowning incidents in South Korean beaches has been on the rise. To prevent drowning accidents, huge number of lifeguards are hired to operate lifesaving activities. This burdens municipal governments in the budget. Nevertheless, because of the limitation in these resources as well as equipment, it is difficult to maintain the effective safety management. Nighttime incidents caused by entering into the water in the absence of lifeguard makes safety management become more critical. In order to resolve the issue of limited numbers of lifeguards and equipment in the aquatic facilities including beaches, it is necessary to develop automated detecting of high profile of drowning and warning systems that support lifeguarding and safety management. Moreover, to provide and maintain safe beach environment in accordance with international standards and prevent injuries and life-threatening incidents, it is essential to develop relevant reliable systems. Among these systems is the application of an intelligent video surveillance technology, the CCTV, for establishing a safe beach environment. The CCTV technology can help in developing a system that detects swimmers and beachgoers approaching dangerous zones and takes proper action. By integrating life-saving technologies that can be applied during both daytime and nighttime, which issue warnings and generate responses when swimmers enter the water at night, it enables to overcome vulnerabilities of other disaster control systems and ensure efficient safety monitoring round the clock.AELIS (Aquatic Environment Life-saving Integrated System) is designed to monitor the high profiles of drowning and the swimmers approaching the swimming boundary lines in real time in order to prevent accidents in the water environment and maintain high standard of the safety. It also detects the swimmers who attempt to get in the water without lifeguards at night, which has high possibility of drowning.

Themodernpeopledoexpresstheirpersonalitiesbyappearanceandactivelyusetheappearanceasthesocialtools,andtheattractiveappearancelargelydoesinfluencethehumanrelationship.Astheappearance'simportanceisbeingmagnified,theattractiveappearanceandfavourableimpressionisanimportantstandardforjobperformanceandsocialposition,andusedasthewaytoreachthesocialgoal.Thisstudydoesinvestigatethedesign'skindandcharacterofthebeardwhichbelongstothemaleexclusivepropertyandcomparethedifferencesoftheimpression'sformationaccordingtothebearddesign.The empirical results confirmed that the male beard design formated the variousimpressionsaccordingtothedesignsandtheirmutualrelationshipexisted.Therefore,thebeardisasymbolofmalenessandanexpressionforthesocialpositionandpersonalcharacter,whereasitpossessestheveryimportantmeaningastheinfluencingfactorontheimpression'schange.First, the pre stimuli were finished through the pre survey for composition ofquestionnaireinordertoevaluatetheimpressionafterselectionofexperimentalmodelsandbeardtypesformeasuringinstruments.Second,sixtythreeuniversitystudentsweresurveyedbyprestimuliandquestionnaireaspreexperiment,andafterwardsthemeasuringinstrumentsandexperimentaldesignwererevised.Third,thestimulicompleted(ninebearddesigns)wereintentionallywelldistributedasquestionnairebysexandagesinSeoulmetropolitan and her environment. and the factorial analysis and the coefficient ofCronbach's forreliabilitytestwerecompletedforquestionnaire‘svalidityusingSPSS/PC+αWindowVer.12.0.Keywords:beardtype,favorability,impression'sformation,perceiver’scharacteristicCorrespondingauthor:AnJongsuk,Tel.+82-41-560-8436, Fax.+82-2-2059-2319E-mail:modean@hoseo.eduThisresearchwassupportedbytheAcademicResearchfundofHoseoUniversityin2012

Purpose The aim of this study is to evaluate the efficacy and the safety of additional 4-week chemotherapy with capecitabine during the resting periods after a 6-week neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer. Methods Radiotherapy was delivered to the whole pelvis at a total dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825 mg/m2 twice daily for 10 weeks. Surgery was performed 2-4 weeks following the completion of chemotherapy. Results Between January 2010 and September 2011, 44 patients were enrolled. Forty-three patients underwent surgery, and 41 patients completed the scheduled treatment. Pathologic complete remission (pCR) was noted in 9 patients (20.9%). T down-staging and N down-staging were observed in 32 patients (74.4%) and 33 patients (76.7%), respectively. Grade 3 to 5 toxicity was noted in 5 patients (11.4%). The pCR rate was similar with the pCR rates obtained after conventional NCRT at our institute and at other institutes. Conclusion This study showed that additional 4-week chemotherapy with capecitabine during the resting periods after 6-week NCRT was safe, but it was no more effective than conventional NCRT.

Purpose As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. Materials and Methods We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. Results Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p

Background/Aims The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. Methods Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. Results Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p

Pathological diagnosis of gastrointestinal stromal tumors (GISTs) is based on histological findings and immunohistochemical demonstration of the KIT protein. KIT-negative GISTs account for ∼5% of cases and cause diagnostic difficulties. In the era of imatinib therapy, a correct diagnosis of GISTs is important for therapeutic reasons regardless of KIT expression. Recently, DOG1 has been introduced as an important diagnostic marker with high sensitivity and specificity. In this study, immunohistochemical staining for DOG1 and protein kinase C-θ (PKC-θ) in whole tissue sections, and mutation analyses for KIT and PDGFRA were performed in 26 KIT-negative GISTs. Tissue microarrays of 112 KIT-positive GISTs were used as controls. Overall, 25 KIT-negative GISTs were located in the stomach, and 1 in the rectum. The histological subtype was spindle in 12, epithelioid in 11, and mixed in 3 cases. The expression of DOG1 and PKC-θ was positive in 24 (92%) and in 25 cases (96%), respectively. All 26 KIT-negative GISTs expressed either DOG1 or PKC-θ, and 23 cases (89%) were positive for both makers. PKC-θ was positive in two cases (8%), which lacked both KIT and DOG1 expressions. Mutation analysis showed PDGFRA exon 18 mutation in 15 cases (58%) and KIT exon 11 mutation in 1 case (4%), whereas the remaining 10 cases (39%) were wild type for both KIT and PDGFRA. The expression of DOG1 and PKC-θ showed no significant difference in KIT-negative and KIT-positive GISTs (P=1.000 and P=0.167, respectively). Our findings suggest that both DOG1 and PKC-θ can be used in the diagnosis of KIT-negative GISTs and they show positive staining even in KIT-negative tumors, which are wild type for KIT and PDGFRA on mutation analysis.

Wilms' tumour-1 (WT-1) encodes a transcription factor originally identified as a tumour suppressor gene, whose mutations are responsible for tumorigenesis of Wilms' tumour. The overexpression of WT-1 has been demonstrated in variable tumours. In this study, WT-1 immunoreactivity was explored in 97 gastrointestinal stromal tumours (GISTs).The expression of WT-1 was compared with other immunohistochemical markers of GIST and the association with clinicopathological features was also evaluated. For comparison, six melanomas and 71 soft tissue tumours were used.All 97 GISTs were positive for WT-1 and the staining intensity was strong in 59 (60.8%), moderate in 28 (28.9%) and weak in 10 cases (10.3%). Cytoplasmic staining with moderate to strong intensity was more frequent in GISTs positive for platelet-derived growth factor receptor-alpha (PDGFRA) (p = 0.04). However, WT-1 immunoreactivity was not related to the clinicopathological variables, including tumour location, histological subtype, risk of progression and recurrence status. Leiomyosarcomas, schwannomas, malignant peripheral nerve sheath tumours (MPNSTs) and melanomas showed cytoplasmic staining, whereas leiomyomas and mesenteric fibromatoses were totally negative for WT-1.Although the biological roles of WT-1 in GIST are still unknown, our findings might provide a rationale for immunotherapy targeting WT-1 and a therapeutic solution to the challenge of imatinib-resistant GISTs.

We report an unusual case of distal cholangiocarcinoma with gastric metastasis mimicking early gastric cancer. A 67-year-old woman presented with a 4-month history of abdominal pain after eating. Computed tomography showed a malignant tumor of the common bile duct located just above the intrapancreatic segment, and endoscopy revealed a 2-cm, flat, elevated lesion with convergence of the surrounding folds, situated at the gastric angle. Based on the endoscopic biopsy results, an adenocarcinoma, thought to be an early gastric cancer, was diagnosed. The patient underwent Whipples's operation. Histopathological findings showed that the adenocarcinomatous tissue was clearly demarcated and infiltrated the gastric mucosa and submucosa, leaving the gastric superficial mucosa intact. Both tumors showed similar pathological features and were positive for cytokeratin (CK)-19 and CK-7. These finding suggest distal cholangiocarcinoma with gastric metastasis.

Sunitinib is a small molecular inhibitor of tyrosine kinases and is used to treat advanced renal cell carcinoma and gastrointestinal stromal tumour after disease progression or intolerance to imatinib therapy. Here, we describe biochemical and pathological response of prostate cancer in a patient with metastatic renal cell carcinoma during sunitinib treatment. A 62-year-old man was referred to our hospital because of a mass in the scalp. He was diagnosed with left renal cell carcinoma with right renal and scalp metastases. In addition, synchronous prostate cancer involving less than one-half of the right lobe was found with a prostate-specific antigen (PSA) value of 23.4 ng/ml. Treatment was begun with sunitinib (50 mg daily, 4 weeks on and 2 weeks off). Regarding the prostate cancer, active monitoring was planned considering the far advanced renal cell carcinoma. Surprisingly, the PSA level was 3.4 ng/ml at week 6 and 0.2 ng/ml at week 12, and it subsequently remained normal. At the time of writing (cycle 6 of sunitinib therapy), the prostate nodule significantly decreased in size. Furthermore, a 12-core re-biopsy revealed pathological evidence of regression with sunitinib treatment, with control of his renal cell carcinoma.

Backgroud and aim: We investigated the incidence of codon 249 mutation of p53 in hepatocelluar carcinoma (HCC) and the relation between cyclooxygenase-2 (COX-2) expression in HCC and survival of the patients. Methods: Forty-one cases of HCC from 1988 to 2007 were retrieved from the files of department of pathology, Chungnam National University Hospital. We performed single strand confirmation polymorphism (SSCP) and direct DNA sequencing for detection of p53 mutation and immunohistochemical staining using monoclonal antibody to COX-2. Results: SSCP and direct DNA sequencing revealed a p53 mutation at exon 7 in one of 41 cases (2.4%). The mutation was observed at codon 249 and consisted of a G–T transversion in the third position of this codon, resulting in an amino acid change from arginine to serine (missense mutation). Positive COX-2 staining (score ≥ 100) was observed in thirty-three of 41 cases (80.5%) and high score (score ≥ 200) in 15 of 41 (36.6%). The high-score group showed a worse survival than the low-score group (score < 200) in Fisher's exact test with confidence level at 90%. Conclusion: This is the first report on the existence of p53 codon 249 mutation of HCC in Korea.

BACKGROUND Low grade endometrial stromal sarcoma (LESS) with dissemination is rare, and its cytomorphology has not been well described. Recently, we experienced a case of LESS with peritoneal dissemination that was confirmed by peritoneal washing cytology and histology. CASE A 51-year-old woman was admitted for evaluation of vaginal bleeding. Uterine ultrasonography revealed a diffisely thickened endomyometrium with a vaguely circumscribed nodular mass-like lesion measuring 7.4 cm in the largest dimension. Under the impression of adenomyosis, an exploratory laparotomy was performed. On examination of the abdominal cavity, multiple tiny, grayish nodular excrescences firmly attached to the peritoneal wall and the serosal surface of the small bowel and uterus were noted. A total hysterectomy with bilateral salpingo-oophorectomy and peritoneal fluid sampling were performed. The peritoneal fluid smear demonstrated several loosely packed clusters of monotonous cells showing round to oval nuclei, rare small nucleoli and scanty cytoplasm. CD10 immunostaining revealed cytoplasmic positivity in these cells, but reactive mesothelial cells showed a negative reaction. Histologic examination of the uterus revealed the typical histologic findings of LESS. CONCLUSION Cytopathologic diagnosis of disseminated LESS is not always easy. Immunocytochemical staining for CD10 can be helpful.

Background and aim: CDX2 is a caudal-type homeobox gene encoding a transcription factor that has an important role in proliferation and differentiation of the intestinal epithelium. Although CDX2-mediated intestinal metaplasia and its association with gastric and esophageal carcinoma have been well described, its function in gallbladder carcinoma remains unclear. Methods: CDX2, MUC2 and MUC5AC expression were examined in carcinoma, intestinal metaplasia and dysplasia of the gallbladder by immunohistochemical staining. Results: CDX2 was not observed in the normal epithelium of the gallbladder but was expressed in 71.4% (20/28) of gallbladder carcinomas including 10 of 18 adenocarcinomas, not otherwise specified, 9 papillary adenocarcinomas and 1 intestinal-type adenocarcinoma. In adenocarcinomas, CDX2 was observed more frequently in well differentiated types than in moderately and poorly differentiated types (P= 0.009). MUC2 and MUC5AC was expressed in 53.6% (15/28) and 71.4% (20/28) of gallbladder carcinomas, respectively. Both CDX2 and MUC2 were observed in 50.0% (14/28) and CDX2 expression was related to MUC2 (P= 0.006) rather than MUC5AC (P= 0.234) in gallbladder carcinomas. CDX2 was also expressed in intestinal metaplasia and dysplasia, which are considered to be premalignant conditions. Conclusions: These results suggest that CDX2 may play an important role in gallbladder carcinogenesis with intestinal differentiation.

The RET/PTC-RAS-BRAF cascade is associated with papillary thyroid carcinoma (PTC).The relationship between PTC and Hashimoto's thyroiditis (HT) is still elusive. To determine whether thyrocytes showing oxyphil cell metaplasia in HT also express RET, RAS, and ERK proteins, which are associated with PTC.We investigated the expression of RET, RAS, and ERK proteins in oxyphil cells in the vicinity of large lymphoid HT infiltrates and in malignant PTC cells. BRAF and N-RAS missense mutations were also examined in oxyphil cells of the HT. We used 47 PTC samples with no HT diagnosis, 28 PTC with HT, 39 HT with no PTC, and 36 HT with PTC. We also studied 75 normal portions of thyroid tissue from PTC specimens. Immunohistochemical analysis and polymerase chain reaction were used to determine activation of the RET/PTC-RAS-BRAF cascade in HT and PTC.In PTC cells, HT oxyphil cells, and normal thyrocytes, the frequency of high RET expression was 23/70 (32.9%), 36/57 (63.2%), and 1/57 (1.8%) (p = 0.000); that of high nuclear localized RAS expression (nuclearRAS) was 65/71 (91.5%), 52/58 (89.7%), and 5/58 (8.6%) (p = 0.000); and that of high ERK expression was 38/70 (54.3%), 34/61 (55.7%), and 0/61 (0.0%) (p = 0.000), respectively. Of 66 HT cases studied for BRAF mutation and 57 HT cases studied for N-RAS mutation, no BRAF exon 15 or N-RAS exon 2 mutations were found in the amplified DNA extracted from oxyphil cells excised by laser capture microdissection.The expression of RET, nuclearRAS, and ERK proteins is greatly enhanced in PTC cells and HT oxyphil cells. Thus, the RET/PTC-RAS-BRAF cascade may be involved in the development of PTC and oxyphil cell metaplasia in HT. Our results show the possibility of a molecular link between oxyphil cell metaplasia in HT and the progression of PTC.

Mesenchymal hamartoma (MH) of the liver is an uncommon benign lesion related to ductal plate malformation. It is usually cystic and mainly composed of myxoid mesenchymal tissue with tortuous or cystic bile ducts. In order to characterize the clinicopathological features of MH, the Korean Gastrointestinal Pathology Study Group collected a total of 17 MH cases diagnosed in 7 hospitals from 1992 to 2002 and compared the clinicopathologic findings of cystic MH with those of solid variant. Among the 17 cases, 7 (41%) were solid. The solid form showed a higher serum level of alpha-fetoprotein (AFP), the smaller bile ducts, and more frequent proliferation of vessels. Serum AFP level was related to the amount of hepatocytes. Two of seven solid cases harbored a larger amount of evenly distributed hepatocytes and proliferation of small duct with focal hepatocyte-bile duct transition. These histologic findings are similar to those of mixed hamartoma. Therefore, the mixed hamartoma and the MH of both solid and cystic types could be the variants of one disease spectrum. And hepatocytes within MH might be rather a genuine tumor component than entrapped into the tumor. In conclusion, MH can show various clinicopathological features and recognition of these features will facilitate accurate diagnosis of MH.

Gastrointestinal stromal tumor is characterized by a gain of function mutation of KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit expression is negative although histological findings of gastrointestinal stromal tumor are most suspicious. The existence of c-kit-negative gastrointestinal stromal tumors points to the need of additional markers for making the diagnosis. In this study, we studied the expression of PKCtheta and correlated their expression with other immunohistochemical profiles of gastrointestinal stromal tumors and evaluated their usability as a diagnostic marker. For this purpose, 220 gastrointestinal stromal tumors were immunohistochemically stained for PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c-kit-positive. PKCtheta was positive in 212 (96%) cases and c-kit was positive in 216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern. Out of 212 PKCtheta-positive GISTs, 208 (98%) cases were c-kit-positive, 174 (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100 protein was positive in 54 cases (26%). Genetic analyses on eight PKCtheta-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCtheta is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity.

Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p = 0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p = 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.

Background Liver cirrhosis is a diffuse hepatic fibrosis and nodule formation. The transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) are very important cytokines in hepatic fibrogenesis. The aim of this study was to examine the relationship between the changes of the serum cytokines and morphological changes following common bile duct ligation in experimental rats. Methods Common bile ducts of fifty male Sprague-Dawley rats were ligated and seven male rats were set aside as controls. Five rats each were sacrificed in 1, 2, 4, 6, 8, and 10 experimental weeks. Light microscopic studies and liver function tests were performed during the above experimental weeks. The levels of serum TGF-β1 and IL-10 were analyzed by ELISA. Also, alpha smooth muscle actin (α-SMA) immunohistochemical stains were performed. Results On the eighth week after common bile duct ligation, most hepatic lobular areas had been replaced by proliferated bile ducts and fibrous tissue (typical biliary cirrhosis). Serum TGF-β1 levels between the control group and the common bile duct ligation group showed statistically significant changes. The α-SMA was stained at proliferated bile ducts. These findings were correlated with each other. Conclusion Thus, this experiment may clarify our understanding of the mechanism in liver fibrogenesis. Also, indicated is a need to explore the therapeutic potential of these cytokines as anti-fibrotic agents.

The clear cell/lipid-rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22-year-old man and a 52-year-old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management.

BACKGROUND/AIMS The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. METHODS We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. RESULTS p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. CONCLUSIONS p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.