Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC.

Clinicopathological characteristics of colon cancer diagnosed at primary health care institutions.

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic characteristics of colon cancers detected at the SOK Sokpeynhan Internal Medical Network, a nationwide system of primary health care institutions. METHODS: We analyzed 579 colon cancer patients diagnosed using colonoscopy at the SOK network from January 2011 through December 2012. Cancers from the rectum to the splenic flexure were classified as left colon cancer. Patients over 65 were classified as senior. RESULTS: The mean age (±SD) of subjects was 60.9±10.5 years and 61.1% were men. More than one quarter (28.2%) of patients were asymptomatic. The prevalence of left colon cancer was higher (77.9%) than that for right colon cancer. The most frequent macroscopic and histologic types were depressed (58.9%) and moderately differentiated adenocarcinoma (52.2%), respectively. Asymptomatic subjects displayed protruding or well differentiated adenocarcinoma, while symptomatic patients were more likely to display depressed or moderately differentiated adenocarcinoma (P<0.05). The mean age of the right colon cancer group was higher than that for the left colon cancer group (P<0.05). Among symptomatic patients, the most frequent symptoms were bloody stool for patients with left colon cancer and abdominal discomfort for patients with right colon cancer (P<0.05). The prevalence of depressed cancer was higher in older subjects as compared to younger subjects (P<0.05). The prevalence of right colon cancer tended to increase with age, although this difference did not achieve statistical significance (P>0.05). CONCLUSIONS: Study results indicated an increase of colon cancer amongst younger demographics in recent years. The effectiveness of colonoscopy screening was also evident, as asymptomatic patients demonstrated frequent findings of well differentiated adenocarcinomas. Study results also suggested a need for closer examination of older patients, as right colon cancer tended to increase with age.

The clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener's): a retrospective study of 45 patients in Korea.

OBJECTIVES: The aim of this study was to determine the clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener's) (GPA) in Korean patients. METHODS: The medical records of 45 patients with GPA treated in a single tertiary referral hospital were retrospectively analyzed with respect to clinical manifestations, including histology, ANCA positivity, disease stage, and disease activity. Patients were categorized into granulomatous, vasculitic, or mixed form based on an immunopathologic scoring system of granulomatous-vasculitic activity. RESULTS: Thirty-one patients (68.9 %) showed ANCA positivity (C-ANCA/P-ANCA, 42.2 %/20.0 %, proteinase-3 (PR3) ANCA/myeloperoxidase (MPO) ANCA, 44.1 %/16.1 %), and these patients (female 48.4 %) were found to be associated with a higher frequency of renal involvement (51.6 vs. 7.1 %, p = 0.004), elevated serum creatinine (29.0 vs. 0 %, p = 0.018), and higher mortality (29 vs. 7.1 %, p = 0.041) than ANCA-negative patients. Thirty-three patients (73.3 %, female 60.6 %) had the granulomatous form, whereas 8.9 and 17.8 % had the vasculitic and mixed forms, respectively. Patients with the granulomatous form were diagnosed earlier in their lives (mean age 51.2 vs. 62.3, p = 0.002) and had a lower frequency of renal involvement (21.2 vs. 100 %, p = 0.005) compared with those with the vasculitic form. Initial remission (69.7 vs. 25.0 %) and relapse (60.8 vs. 0 %) rates were higher for the granulomatous than for the vasculitic form. CONCLUSIONS: Taken together, in Korean patients with GPA, the granulomatous form was predominant and associated with a younger age at diagnosis and a lower frequency of renal involvement than the vasculitic form. ANCA positivity was found in 68.9 % and associated with renal involvement and higher mortality.

[Clinicopathologic characteristics of superficial gastric cancer diagnosed at primary health care institutions in 2011].

BACKGROUND/AIMS: Stomach cancer is prevalent in Korea. The purpose of this study was to evaluate the characteristics of superficial gastric cancers detected at SOK Sokpeynhan Internal Medical Network, the nationwide primary health care institutions. METHODS: We prospectively analysed the clinicopathologic and endoscopic characteristics of 218 superficial gastric cancer patients diagnosed using gastric endoscopy at SOK network from January 2011 through December 2011. RESULTS: The mean age was 58.5 years old and male to female ratio was 1.7 : 1. Asymptomatic patients were most common (45.0%). The macroscopic classification revealed that simple types (63.8%) were more common than complex types (36.2%). The most common type was IIc (28.4%) and other types were as follows; IIb (16.1%), IIb+IIc (13.3%), IIa (10.6%), III (9.2%), IIa+IIc (7.3%), IIc+IIa (6.0%), IIc+IIb (5.0%). The most commonly involved sites were the body (53.1%) and greater curvature (32.6%) of the stomach. The size of lesion was less than 1 cm (69.3%) and less than 5 mm (33.5%) in diameter. The most common pathologic type was tubular adenocarcinoma (75.7%). Helicobacter pylori infection rate was 50.2%. Fifty five percent of the cases were diagnosed via endoscopy of National Health Insurance Corporation screenings. CONCLUSIONS: Superficial gastric cancers in 2011 at primary health care SOK network were different from those of previous reports. Type IIc was most common but type IIb was more prevalent and the body and greater curvature of the stomach were the most commonly involved sites. Therefore, careful observation of the proximal gastric mucosa and mucosal color change is needed.

[Clinical, radiological and pathological exploration of focal nodular hyperplasia of liver reported in Korea].

BACKGROUND/AIMS: Focal nodular hyperplasia (FNH) is mandatory to be differentiated from other hepatic tumorous conditions such as hepatocellular carcinoma and adenoma. The purpose of this study was to explore the clinical, radiological and pathological features of FNH cases reported in Korea. METHODS: We have searched the journals from the web site "http://koreamed.org" using keywords "focal nodular hyperplasia" and "liver" - total of 38 cases of FNH, 37 cases from 17 published articles and one case from our experience confirmed histologically, were reviewed and analyzed. RESULTS: Thirty eight cases were diagnosed between gestational age of 36 weeks and 67 years. Seventeen female patients (45%) had no history of taking oral contraceptives. Twenty cases (52.6%) experienced clinical symptoms such as abdominal pain and palpable mass. Computed tomography revealed contrast-enhancement in 34 nodules (85%) and typical central stellate scar in 9 (22.5%) of 40 nodules. Magnetic resonance imaging showed T1 weighted low signal in 18 (60%) and T2 weighted high signal in 22 (73.3%) of 30 nodules. Six (60%) of 10 cases showed hypervascular staining on hepatic angiography. Among 38 cases, 32 (84.2%) cases had single nodule and their mean size was 3.9 cm (0.5-16 cm). Pathologically, fibrous septa, proliferation of bile ductules and arterial wall thickening were seen in most cases. CONCLUSIONS: Of all the FNH cases reported in Korea, there were some differences in clinical aspects of sex ratio, accompanying clinical symptoms, and relationship with oral contraceptives, compared with previous reports. Further prospective studies are needed by means of nation-wide clinical survey and analysis.

[Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor].

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC.

Human cytomegalovirus IE1 protein enhances herpes simplex virus type 1-induced syncytial formation in U373MG cells.

Co-infection of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV) is not uncommon in immunocompromised hosts. Importantly, organ transplant recipients concurrently infected with HSV-1 and HCMV have a worse clinical outcome than recipients infected with a single virus. However, factors regulating the pathologic response in HSV-1, HCMV co-infected tissues are unclear. We investigated the potential biologic role of HCMV gene product immediate early 1 (IE1) protein in HSV-1-induced syncytial formation in U373MG cells. We utilized a co-infection model by infecting HSV-1 to U373MG cells constitutively expressing HCMV IE1 protein, UMG1-2. Syncytial formation was assessed by enumerating nuclei number per syncytium and number of syncytia. HSV-1-induced syncytial formation was enhanced after 24 hr in UMG1-2 cells compared with U373MG controls. The amplified phenotype in UMG1-2 cells was effectively suppressed by roscovitine in addition to inhibitors of viral replication. This is the first study to provide histological evidence of the contribution of HCMV IE1 protein to enhanced cytopathogenic responses in active HSV-1 infection.

Detection of JC virus type 1 in peripheral lymphocytes, brain and cerebrospinal fluid from two Korean AIDS patients with progressive multifocal leukoencephalopathy.

The human polyomavirus JC virus (JCV) is the etiologic agent of the fatal demyelinating central nervous system disease progressive multifocal leukoencephalopathy (PML), which occurs in 4-7% of AIDS patients. Two Korean AIDS patients with PML were assayed for JCV, and the virus was genotyped by polymerase chain reaction, DNA sequencing and phylogenetic analysis. Using immunohistochemical analysis, we also examined the distribution of JCV antigen in the brains of the patients. The JCV genome was detected in peripheral lymphocytes, brain and cerebrospinal fluid from these Korean PML patients. Although type 2 is the most common genotype in Asia, the genotype of the JCV in these two AIDS patients was characterized as type 1, which is of European origin. We found that JCV antigen was selectively detected in oligodendrocytes and astrocytes of the brains from these patients. Compared to the prototype type 1 (Mad-1), two different nucleotides (G-->C) in the KOR-1 strain identified here were found at positions 2488 and 2490 of the major capsid protein VP1 gene. In summary, this is the first report of PML in Korean AIDS patients; it is also the first isolation of JCV type 1 in PML in East Asians.