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Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoaggluti nin test. HLA mismatch was 0 and he received a single 325 mg/m2 dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop ste roid treatment despite the risk of rejection after withdrawal. Steroid tapering was initi ated at 20 months and accomplished at 26 months after KT. At that time, serum creati nine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respec tively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients.

Esophageal cancer is one of the lethal malignant tumors because it is often diagnosed in the advanced stage with lymph node or distant metastasis. The recurrence rate of esophageal cancer is known to be about 40% to 50% even in the patients who underwent curative esophageal resection. Most frequent sites of metastases are known to be the liver. Furthermore, other distant metastases also could be developed in lung, bone, brain, kidney, adrenal, abdominal cavity, and skin. However, ampulla of Vater (AoV) metastasis rarely occurs from esophageal cancer. Therefore, we report herein a case of AoV metastasis from squamous cell carcinoma of the esophagus.

Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery (P = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity., Cancer: Tell-tale signs of recurrence Fragments of tumor DNA, or circulating tumor DNA (ctDNA), in blood can help predict stomach cancer recurrence within 12 months of surgery. Kyeong-Man Hong at the National Cancer Center, in Goyang-si, South Korea, and colleagues, carried out whole genome sequencing of stomach tumor samples from 25 patients to identify personalized cancer-specific rearranged DNA sequences. When they used this information to monitor ctDNA in blood samples obtained after surgical removal of the tumor, they found a significant correlation between the presence of ctDNA and cancer recurrence. In most cases, ctDNA was detected around four months prior to clinical recurrence, highlighting the potential usefulness of ctDNA monitoring. The lack of correlation between ctDNA levels and tumor size suggests that further research into the factors determining ctDNA levels is needed.

Background Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis. Methods We evaluated calretinin, WT1, and mesothelin expression by immunohistochemical staining in 117 gastric adenocarcinomas. Results Mesothelin was positively stained in 30 cases (25.6%). Mesothelin expression was related to increased depth of invasion (p = .002), lymph node metastasis (p = .013), and presence of lymphovascular (p = .015) and perineural invasion (p = .004). Patients with mesothelin expression had significantly worse disease-free survival rate compared with that of nonmesothelin expression group (p = .024). Univariate analysis showed that mesothelin expression is related to short-term survival. None of the 117 gastric adenocarcinomas stained for calretinin or WT1. Conclusions Mesothelin expression was associated with poor prognosis. Our results suggest that mesothelin-targeted therapy should be considered as an important therapeutic alternative for gastric adenocarcinoma patients with mesothelin expression.

Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the unique feature of Kap123 that possesses two discrete lysine-binding pockets for NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at least one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are mutually exclusive. Additionally, acetylation of key lysine residues at NLS, particularly H4-NLS diacetylation, weakens the interaction with Kap123. These data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex nuclear translocation.

Multiple wasp stings can induce multiple organ dysfunction by toxic reactions. However, acute pancreatitis is a rare manifestation in wasp sting injury. A 74-year-old woman visited the emergency department by anaphylactic shock because of multiple wasp stings. Acute kidney injury, rhabdomyolysis, hepatotoxicity, and coagulopathy were developed next day. Serum amylase and lipase were elevated and an abdominal computed tomography revealed an acute pancreatitis. Urine output was recovered after 16 days of oliguria (below 500 ml/day). Her kidney, liver, and pancreas injury gradually improved after sessions of renal replacement therapy.

Background Recently, we reported cytoskeleton-associated protein2 (CKAP2) as a possible new prognostic breast cancer marker. However, it has not yet been applied in clinic. Therefore, clinical significance of CKAP2 was evaluated in comparison with that of Ki-67 in a cohort of breast cancer patients, and the expression difference was analyzed in cell cycle-arrested cancer and fibroblast cells. Methods A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital in Korea between 2001 and 2005 were accrued. CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67LI) were evaluated by immunohistochemcal staining. The immunocytochemical staining patterns of CKAP2 and Ki-67 were analyzed in HeLa and human fibroblast cells after synchronization by double thymidine block. Results Although there was a significant correlation (R = 0.754, P < 0.001) between CPCC and Ki-67LI, only CPCC was correlated with DFS in overall population (HR, 2.029; 95% CI, 1.012–4.068; P = 0.046) and HER2-negative luminal subgroup (HR, 3.984; 95% CI, 1.350–11.762; P = 0.012) by multivariate analysis. In immunocytochemical staining, more than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low CKAP2-positivity, which might explain the prognostic difference between CPCC and Ki-67LI. Conclusions The current study showed that CPCC but not Ki-67LI is an independent prognostic indicator in early breast cancer, more specifically in HER2-negative luminal breast cancer. The difference between two markers may be related to the lower background expression of CKAP2 in cancer cells.

Malakoplakia, meaning soft (malako) plaque (plakia), is a rare benign inflammatory lesion. The disease was initially described in the bladder by Michaelis and Gutmann [1] in 1902 and named by von Hansemann [2] in 1903. Since its initial description, many cases have been described in numerous anatomic locations including the genitourinary tract, gastrointestinal tract, pancreas, liver, oropharynx, retroperitoneum, thyroid gland, lymph nodes, lung, bone/joint, brain, skin, and other tissues [3-5]. To our knowledge, this is the first case of malacoplakia affecting the umbilical cord.

Granular cell astrocytoma is a rare infiltrative malignant glioma with prominent granular cell change. Granular cell astrocytomas are biologically aggressive compared with conventional infiltrating astrocytomas of similar grades, but their genetic alterations are poorly known. We report a case of granular cell glioblastoma and its genetic and molecular features. Histologically, the tumor not only showed features typical of granular cell astrocytoma but also demonstrated frequent mitoses, pseudopalisading necrosis, and vascular endothelial hyperplasia, compatible with glioblastoma. Array-based comparative genomic hybridization and focused molecular genetic analyses demonstrated gain of chromosome 7; losses of chromosome 1p, 8p, 9p, 10, 13q, and 22q; amplification of epidermal growth factor receptor; and homozygous deletion of CDKN2A as well as MGMT promoter methylation. However, neither isocitrate dehydrogenase 1 mutation nor codeletion of 1p/19q was found. Our results indicate that granular cell glioblastomas, despite having its peculiar granular cell changes, share common molecular genetic features with conventional glioblastoma, especially the classical subtype.

A 53-year-old man presented with right flank pain for 6 days. Computerized tomography revealed a 3 cm long segment of ureteral narrowing with wall thickening and hydronephrosis, suspicious for ureteral cancer. Under the clinical diagnosis of ureteral carcinoma a right nephroureterectomy was performed. The wall of the distal ureter, 2.5 cm from the bladder cuff, had a luminal-narrowing, firm mass-forming lesion with abrupt transition from the adjacent ureter. Histologically, the resected ureteral mass showed transmural fibrosing, chronic inflammation with numerous plasma cells, epithelioid granulomas, and obliterative phlebitis. Histological findings were consistent with idiopathic segmental ureteritis (ISU) with differential diagnoses of IgG4-related sclerosing disease, including lymphoplasmacytic inflammatory pseudotumor (IPT) and idiopathic retroperitoneal fibrosis. IgG4 immunostaining in this case was barely positive, excluding the possibility of IgG4-related IPT. Although the majority of luminal obliterated segmental lesions of the ureter are neoplastic in nature, non-neoplastic inflammatory processes as seen in this case may occur in the ureter, causing diagnostic confusion with true neoplasms. Herein we report a rare case of ISU that was clinically misdiagnosed as malignancy preoperatively. ISU of the current case may be an IgG4-unrelated subtype of IPT.

Selective IgA deficiency is the most common primary immunoglobulin deficiency. The clinical manifestations of selective IgA deficiency, including gastrointestinal (GI) complications, are rare and typically milder than those seen with common variable immunodeficiency or X-linked agammaglobulinemia. We present a rare case of selective IgA deficiency that shows a number of interesting histological features in the GI tract, including diffuse nodular lymphoid hyperplasia involving the entire small and large intestine, celiac disease-like and collagenous sprue-like changes in the small intestine, as well as lymphocytic colitis pattern. However, this patient had no particular GI symptoms suggestive of celiac sprue or microscopic colitis. These findings suggest that the GI tract in patients with selective IgA deficiency can show peculiar histologic changes that mimic celiac disease, collagenous sprue, or lymphocytic colitis, which may be a pattern of injury related to infection or immunoglobulin immunodeficiency-associated autoimmune phenomena.

Clear cell sarcoma (CCS) is a distinctive soft tissue sarcoma that shows melanocytic differentiation. Primary gastrointestinal (GI) CCSs have been rarely reported, but to our knowledge, no association between GI CCSs and immunoglobulin G4 (IgG4)-related sclerosing disease has been described in the literature. We experienced 2 cases of CCS that arose in the small intestine and metastasized to the liver. Histologic features and immunophenotype were typical of CCS. One of them showed a unique peritumoral sclerosing inflammatory reaction, which was highly reminiscent of IgG4-related sclerosing inflammatory disease. Dense lymphoplasmacytic infiltration with extensive sclerosis and obliterative phlebitis was observed in the immediate vicinity of the primary and metastatic tumors, but not in the distant areas from the tumor. The average number of IgG4-positive plasma cells was more than 50 per high-power field. We report 2 cases of primary GI CCS with one case showing a unique peritumoral IgG4-related lymphoplasmacytic sclerosing inflammation.

Background and aim: Although morphological criteria are important for diagnosis of cervical intraepithelial neoplasia, it is not possible to differentiate those that will regress from those that will progress into invasive cancer. We evaluate the usefulness of p16, cyclin D1, and human telomerase reverse transcriptase (hTERT) as diagnostic and prognostic biomarkers in cervical lesions. Methods: We studied 12 cases of benign lesion, 15 cases of low-grade squamous intraepithelial lesion, 46 cases of high-grade squamous intraepithelial lesion, and 13 cases of squamous cell carcinoma by immunohistochemistry. Results: The p16 expression was significantly correlated with high risk-human papillomavirus (HR-HPV) status, lesion grade, and decreased cyclin D1 expression. The decreased cyclin D1 expression was significantly correlated with HR-HPV status, lesion grade, and p16 expression. The positive predictive values for high grade lesion of p16 expression, HR-HPV status, and decreased cyclin D1 expression were 93.8%, 81.3%, and 51.2%, respectively. The distribution pattern of hTERT positive cells was correlated with morphologically dysplastic cells. Conclusions: A good correlation was observed between cervical lesion grade and p16 expression, decreased cyclin D1 expression, and HR-HPV status. p16 expression could be used as a diagnostic and prognostic biomarker for risk of developing cervical cancer in women infected with HPV.

The aims of this study were to evaluate the clinicopathologic features of Helicobacter heilmannii-associated gastritis and to compare H. heilmannii-associated gastritis with H. pylori-associated gastritis. We reviewed 5,985 consecutive gastric biopsy specimens. All cases of chronic gastritis with Helicobacter infection were evaluated with the Updated Sydney System, and the grades of all gastritis variables were compared between H. heilmannii-associated gastritis and H. pylori-associated gastritis groups. There were 10 cases of H. heilmannii-associated gastritis (0.17%) and 3,285 cases of H. pylori-associated gastritis (54.9%). The organisms were superficially located within the mucous layer without adhesion to epithelial cells. Interestingly, in one case many intracytoplasmic H. heilmannii organisms were observed in parietal cells with cell damage. A case of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma concomitant with H. heilmannii infection was detected. Compared to H. pylori-associated gastritis, H. heilmannii-associated gastritis showed less severe neutrophilic activity (p

OBJECT In this study the authors sought to evaluate clinical outcomes after using stereotactic radiosurgery (SRS) to treat benign and malignant spinal neurogenic tumors. METHODS The authors reviewed a total of 66 procedures of spinal SRS performed between 2001 and 2013 for 110 tumors in 58 patients with spinal neurogenic tumors, which included schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNSTs). The clinical and radiological findings were evaluated in patients with benign neurogenic tumors. For the 4 patients with MPNSTs, the authors reported overall survival and results of additional immunohistochemical staining to predict the survival difference among the patients. RESULTS Of the 92 benign neurogenic tumors, 65 tumors that were serially followed up using MRI after SRS showed significant change in mean tumor volume, from a mean of 12.0 ± 2.6 cm3 pre-SRS to 10.8 ± 2.5 cm3 post-SRS (p = 0.027), over an average of 44 months. The local control rate of benign neurogenic tumors was 95.4%. The 34 patients who presented with clinical symptoms of pain showed a significant symptomatic improvement. The initial mean visual analog scale (VAS) score was 6.0 and decreased dramatically to 1.0 after SRS during an average follow-up period of 10.9 months (median of 8.1 months). Although the proportions of transient swelling and loss of intramural enhancement were significantly different among the groups, there was no statistically significant correlation between those 2 factors and local tumor control (p = 0.253 and 0.067, respectively; Fisher’s exact text). Cross-table analysis also indicated that there was no statistically significant relationship between groups with loss of intramural enhancement and transient swelling. The median survival of neurofibromatosis Type 1 (NF1)-related and sporadic MPNSTs was 1.13 and 5.8 years, respectively. Immunohistochemical results showed that S100 was expressed in a sporadic MPNST or neurofibroma, whereas topoisomerase-IIa was expressed in NF1-related MPNSTs. CONCLUSIONS SRS is an effective treatment modality for benign neurogenic tumors, while MPNSTs showed heterogeneity in their responses to SRS.

Background: The epithelial cell adhesion molecule (Ep-CAM) is widely associated with human carcinomas. However, the expression and distribution of Ep-CAM in gastric premalignant and malignant lesions are not well known. Method: We examined the expression of Ep-CAM in 99 cases of gastric adenocarcinoma and associated uninvolved gastric mucosa, 39 cases of gastric biopsy specimens with chronic gastritis (CG) with or without intestinal metaplasia (IM) (25 cases) and gastric epithelial dysplasia (GED) (14 cases) by immunohistochemical staining. In gastric adenocarcinoma, we correlated the results with established prognostic factors, and in IM and GED, with Hepatocyte paraffin 1 (Hep Par 1) expression, introduced as a marker of IM. Results: Ep-CAM overexpression was noted in 0% of normal epithelia, 93.9% of IM, 42.9% of GED and 34.3% of adenocarcinoma. The average immunostaining score of normal epithelia, IM, GED and gastric adenocarcinoma was 0.14 (± 0.26), 7.18 (± 1.93), 5.67 (± 2.29) and 4.09 (± 1.89), respectively. There were significant differences among the groups. Ep-CAM overexpression in adenocarcinoma correlated with Lauren classification and histologic grade, but not with tumor stage, lymph node metastasis and p53 expression. Both Ep-CAM and Hep Par 1 expressions showed excellent correlations with IM (P

A 41-year-old male presented with an ill-demarcated mass involving the left fronto-temporal lobe and the basal ganglia. Light microscopically the tumor was diagnosed as an anaplastic oligoastrocytoma. Electron microscopy revealed several cytoplasmic crystalline inclusions in tumor cells of oligodendroglial lineage. No crystalline inclusions were membrane bound. The morphologic features with unique ultrastructural findings are presented.

In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting mammary epithelium. The exact mechanism and the effect of the down regulation of the Bcl2 expression on breast cancer cells are not clearly defined. We compared down regulation as well as the persistent expression of Bcl2 with ER, PR, p53, and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in 11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR immunoreactive ones and 71.9 % of c-erb-B2 immnonegative ones. Seventeen cases of Bcl2 down regulated IDC had a significant correlation with ER negativity (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and histological grade (76% is grade III). However, in DCIS, no significant correlation between the Bcl2 expression and various parameters were obtained, probably due to small sample size. In conclusion, the Bcl2 expression was both ER and PR dependent and down regulation of Bcl2 in IDC was significantly correlated with poor prognostic factors.

We studied Fas/FasL, Bcl-2, and M30 CytoDeath in five cases of normal thymus and 41 cases of thymic epithelial tumors (TETs). In normal thymus, Fas was expressed in all epithelial cells, but not in thymic lymphocytes; FasL was weakly expressed only in medullary epithelium and Hassal's corpuscles. In TETs, Fas was expressed in all epithelial cells and lymphocytes, while FasL was differently expressed in epithelial cells of different subtypes of TETs, i.e., type A (2/2), AB (12/12), B1 (0/9), B1/B2 (0/3), B2 (0/1), B2/B3 (1/3), B3 (6/10) and C (1/1), but not in lymphocytes. Bcl2 protein was strongly expressed in medullary-derived lymphocytes of normal thymus and TETs, and weakly expressed only in medullary (spindle) epithelium of TETs. On M30 CytoDeath immunostaining, apoptotic indices were very low in all TETs (0-1.2). In conclusion, since FasL was expressed on the epithelial cells of lymphocyte-depleted (LD) areas of type B2/B3 and/or LD subtypes (type A, AB, B3, C), FasL expression could be relevant for the intracytoplasmic processes of T-cell selection and the regulation of the lymphoid cells inside the tumor, at least partly. However, tumorigenesis of TETs is not necessarily induced by abrogation of apoptosis.

BACKGROUND: The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). METHODS: This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. RESULTS: After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR] = 4.10 (95% CI: 1.64-10.29) for group 2; HR = 4.35 (95% CI: 2.04-10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR = 2.05 (95% CI: 0.94-4.65) for group 2; HR = 2.35 (95% CI: 1.09-5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. CONCLUSIONS: Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.

We performed the immunohistochemical staining for six G1 check point cell cycle proteins to study their expression patterns and roles in the gastric carcinogenesis. We studied 76 cases of paraffin blocks that included the sections of 18 tubular adenomas (TA), 38 early gastric carcinomas (EGC) (20 cases of mucosal type, nine cases of submucosal type with no nodal metastasis, nine cases of submucosal type with nodal metastasis), 20 advanced gastric carcinomas (AGC) (ten cases with no nodal metastasis, ten cases with nodal metastasis). We found that abnormal expression of p16 and p27 increased with the progression of tubular adenomas to advanced gastric cancers. Inverse relationship between pRb and p16 proteins was found in a small portion of the gastric tumors. Expressions of pRb and cdk4 were consistently high in benign and malignant gastric tumors. Expression of cyclin D1 and cyclin E rather decreased with the tumor progression. In conclusion, losses of p16 and p27 seem to play a significant role during the gastric carcinogenesis, and the G1 checkpoint cell cycle proteins such as pRb, cdk4, cyclin D1, and cyclin E variably participate in the gastric carcinogenesis and metastasis by the mechanisms which are yet unknown; thus, further studies need to be performed to elucidate the mechanisms.

Aims/Background: In hepatitis B virus-related hepatocellular carcinoma(HCC), at least 20–40 years of continuous necro-inflammation is necessary for the hepato-carcinogenesis to occur. However, HCC in childhood shows an unusually short latent period and rapid progression. In our previous report, mutation of c-met was found only in childhood HCC, but not in adult HCC. In order to determine the specific biological tumorous features of childhood HCC, a comparison study of childhood and adult HCC was performed. Methods: Eighteen cases of HBV positive HCC (nine children and nine adults aged more than 40 years) were selected. The expression of G1 phase regulatory proteins (cyclin D1, cyclin E and cdk4) was studied using immunohistochemical methods. Loss of heterozygosity (LOH) on chromosomal arms 8p, 13q and 17p was analyzed. Results: Cyclin D1 expression was significantly lower in childhood HCC than in adult HCC (cases of cyclin D1 expression under 3+: childhood 5/9 vs. adult 1/9, p=0.046). No difference in cyclin E and cdk4 expression was found between childhood and adult HCC. LOH frequency on 13q was relatively higher in childhood than in adult HCC (66.7% vs. 22.2%, p=0.058). LOH frequency on 8p and 17p was 44.4% and 33.3% in childhood HCC and 44.4% and 75% in adult HCC with no statistical significance between the two groups. Conclusion: Our data suggest that childhood HCC may be less dependent on cyclin D1 protein for tumor growth and progression than adult HCC, and that the LOH on 13q may be an important feature of childhood HCC.

Abnormality of the cyclin D1/cdk4/p16INK4a/pRb pathway during tumorigenesis has recently been reported. Hepatoblastoma is a rare malignant liver tumor of childhood, but underlying abnormalities of cell-cycle regulating protein remain to be elucidated. The expression of cyclin D1, cdk4, p16 and retinoblastoma gene product (pRb) was studied by immunohistochemistry in 17 paraffin-embedded tissues consisting of both tumor and corresponding non-neoplastic tissues. Tumor tissues showed overexpression of cyclin D1 (13/17, 76%) and cdk4 (15/17, 88%). Eleven cases showed co-overexpression of both cyclin D1 and cdk4. No abnormal p16 or pRb expression was noted. In the group with a high score (+4) for cyclin D1 expression, a positive correlation with tumor recurrence was noted (P = 0.043). These data suggest that overexpressed cyclin D1 and cdk4 protein might play an important role in the tumorigenesis of hepatoblastoma and that in the group with high cyclin D1 expression, tumor recurrence may be more frequent.

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Graft-versus-host disease (GvHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Recent literature demonstrates a potential benefit of human mesenchymal stromal cells (MSC) for the treatment of refractory GvHD; however, the optimal dose remains uncertain. We set out to develop an animal model that can be used to study the effect of MSC on GvHD.A GvHD mouse model was established by transplanting C3H/he donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. MSC were obtained from C3H/he mice and the C3H/10T1/2 murine MSC line.The mRNA expression of Foxp3 in regional lymph nodes (LN) localized with T cells was markedly increased by the addition of C3H10T1/2 cells in a real-time polymerase chain reaction (PCR). Using a mixed lymphocyte reaction, we determined the optimal splenocyte proliferation inhibition dose (MSC:splenocyte ratios 1:2 and 1:1). Three different C3H10T1/2 cell doses (low, 0.5 x 10(6), intermediate, 1 x 10(6), and high, 2 x 10(6)) with a consistent splenocyte dose (1 x 10(6)) were evaluated for their therapeutic potential in an in vivo GvHD model. The clinical and histologic GvHD score and Kaplan-Meier survival rate were improved after MSC transplantation, and these results demonstrated a dose-dependent inhibition.We conclude that MSC inhibit GvHD in a dose-dependent manner in this mouse model and this model can be used to study the effects of MSC on GvHD.

Background We sought to identify the role of serum CA-125 levels in early-stage epithelial ovarian cancer (EOC) on preoperative CT and MRI. Methods Clinical data of 101 patients with early-stage EOC on preoperative CT and MRI were collected between January 2000 and December 2007. Clinical stage I ( n = 59) was defined as tumor limited to the ovaries with or without ascites, whereas clinical stage II ( n = 42) was defined as tumor within the pelvis with or without ascites. The primary endpoint was to investigate the efficacy of serum CA-125 levels for the prediction of advanced-stage disease, and secondary endpoints were to evaluate the accuracy of preoperative CT and MRI, and to examine the role of serum CA-125 levels as a prognostic factor for survival. Results The results of preoperative CT and MRI were concordant with no peritoneal implants outside the pelvis in 50/101 (50%) and no lymph node metastasis in 71/101 (70%) patients. The receiver operating characteristic curves showed that best cut-off values of serum CA-125 levels were 320 U/ml (71% sensitivity, 84% specificity) and 510 U/ml (67% sensitivity, 80% specificity) for the prediction of peritoneal implants outside the pelvis and lymph node metastasis. The serum CA-125 level (≥320 U/ml) was a significant factor for the prediction of advanced-stage disease (adjusted OR, 7.43; 95% CI, 2.39–23.04). However, it was not an independent prognostic factor for survival. Conclusions Serum CA-125 levels may be very useful for the prediction of advanced-stage disease in early-stage EOC on preoperative CT and MRI.

Thyroid nodules are uncommon in children and adolescents compared with adults, but the risk of malignancy is much higher. In adults, fine needle aspiration biopsy (FNAB) has been used extensively to select patients for surgical exploration with a high degree of reliability. The purpose of this study was to assess the utility of FNAB for the management of thyroid nodules in children and adolescents. We reviewed our experience with 60 FNABs of thyroid nodules in 51 children and adolescents. Of the 60 aspirates, 45 aspirates (74%) were diagnosed as "benign", 5 aspirates (8%) as "suspicious for malignancy", and 6 aspirates (10%) as "malignant", and 4 aspirates (7%) as "unsatisfactory". Thyroidectomy was performed in 17 patients, and 5 with a cytological diagnosis of "benign" revealed nodular hyperplasia in three and follicular adenoma in two; 5 with a cytological diagnosis of "suspicious" revealed nodular hyperplasia in one, follicular adenoma in two, and papillary carcinoma in two; and 6 with a cytological diagnosis of "malignant" revealed papillary carcinoma. One patient with a cytological diagnosis of "unsatisfactory" revealed papillary carcinoma. The diagnostic accuracy was 81% with 100% sensitivity and 63% specificity. The positive and negative predictive values of FNAB were 73% and 100%, respectively. We conclude that FNAB is a good screening test for thyroid nodules in children and adolescents because of its high sensitivity.

A scalp mass surgically excised from a 4-year-old Korean boy was identified as a tick through histological observations. In sections of the mass, characteristic features of a tick, including its gross contour, cuticular structures, well developed musculature and salivary glands, and the capitulum, were discovered. In particular, the capitulum is anteriorly protruded, which strongly suggests that the specimen be a hard tick of family Ixodidae. However, the present histological features were not enough to determine the genus and species of the tick, because information on sectional morphologies of different tick species is unavailable. This is a rare case of tick infestation on the scalp diagnosed in histological sections.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.

The chronic hepatotoxic effects of carbon tetrachloride (CCl(4)) in heat-shock protein (HSP) 70 knock out (HSP70-/-) mice were examined. After repeated intraperitoneal injections of CCl(4) for six weeks, the level of ALT and weight ratio of the liver to body were lower in HSP70-/- mice than in the control (WT) mice. The levels of HSP25 and HSP47 were lowered in HSP70-/- mice as compared with WT mice. The grades of hepatic necrosis and neutrophil infiltration were not significantly different between HSP70-/- and WT mice. The collagen content was not affected significantly by CCl(4) treatment.

Aim: The application of sentinel node (SN) biopsy in gastric cancer remains controversial. In this study, detection rate and predictive values of SN biopsy were determined to evaluate its feasibility in gastric cancer. Various clinicopathologic features were also analysed to determine the factors affecting the detection rate and predictive values. Methods: Seventy-one gastric adenocarcinoma patients without serosal invasion and distant metastasis, were studied. One percent isosulfan blue stained nodes were defined as SNs, and standard gastrectomy with D2 lymphadenectomy was performed. All lymph nodes were studied by hematoxylin and eosin staining. Results: SNs were identified in 65 of 71 patients and average number of SNs per patient was 2.5 (range 1–8). Among the 65 patients with SNs, metastatic SNs were found in 11 and the remaining 54 were free of metastasis. In eight of the 11 patients with metastasis of the SNs, metastases were also identified in non-SNs. Conclusions: SN biopsy is feasible in early stage gastric cancer. However, complementary procedures may be needed to improve the detection rate and predictive values. SNs biopsy results should be treated with caution in male patients and for tumours at the upper part of stomach due to the low detection rate.

Background/Aims Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney. Methods PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1α in renal tubule cells. Results PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1α, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1α and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1α protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1α protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 µM), which enhanced HIF-1α mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1α expression. Conclusions PTX attenuates tubular hypoxia in the diabetic kidney.

Renal infiltration is common in chronic lymphocytic leukemia (CLL), but renal impairment caused by leukemic infiltration is rare. This report describes the case of a 38-year-old man with CLL who required no medical treatment for 1 year and was admitted with nonoliguric renal insufficiency (proteinuria > 2,000 mg/day). A renal biopsy subsequently revealed leukemic infiltration by CLL. Treatment with fludarabine plus cyclophosphamide resulted in the improvement of renal function. Leukemic infiltration should be considered in the differential diagnosis of a patient with CLL and impaired renal function because renal impairment often responds well to chemotherapy. (Korean J Med 2012;83:132-135)

Carcinoma showing thymus-like differentiation (CASTLE) is a rare carcinoma of the thyroid or adjacent soft tissue of the neck with a histologic resemblance to thymic epithelial tumors. Although the fine-needle aspiration (FNA) plays a central role in the initial evaluation of thyroid nodules, few reports about the cytologic findings of CASTLE have been found according to a review of literatures. We report cytologic findings of a case of CASTLE. A 34-year-old woman presented with a 2-month history of sore throat. The FNA showed that the smear was composed of three dimensional clusters and sheets. The tumor cells were round to ovoid with high nuclear : cytoplasmic ratios. The nuclei were vesicular with small nucleoli. There were some tumor cells showing keratinization. Some lymphocytes were found on the background and within clusters. The presence of poorly-differentiated tumor cells with a focal keratinization and a lymphocytic background on the FNA is suggestive of CASTLE.

Myxoma of the aortic valve is an exceedingly uncommon condition. In this article, we report the case of a 72-year-old man with myxoma arising from the aortic valve. We extirpated the mass and repaired the aortic valve with the patient under cardiopulmonary bypass. The postoperative course was uneventful. Histological examination confirmed that the mass was a myxoma.

Human Gnathostoma hispidum infection is extremely rare in the world literature and has never been reported in the Republic of Korea. A 74-year-old Korean man who returned from China complained of an erythematous papule on his back and admitted to our hospital. Surgical extraction of the lesion and histopathological examination revealed sections of a nematode larva in the deep dermis. The sectioned larva had 1 nucleus in each intestinal cell and was identified as G. hispidum. The patient recalled having eaten freshwater fish when he lived in China. We designated our patient as an imported G. hispidum case from China.

Background/aims Cell cycle regulating proteins are known to have close relation with the proliferation of the mammalian cells. In injured liver, number of hepatic stellate cells is increased from proliferation. However, the expression of cell cycle proteins of hepatic stellate cells during proliferation remains unevaluated. Therefore, cell cycle protein profiles of hepatic stellate cells were studied in dimethylnitrosamine (DMN)-induced rat liver fibrosis model. Methods Six-week male Sprague-Dawley rats (n=19) were intraperitoneally injected with 10 μg/kg DMN and the animals were sacrificed at the end of 1st, 2nd, 3rd, and 4th week. Hepatic stellate cells were separated according to the original method of Alpini and the number of the cells in S phase was counted to evaluate the cell proliferation by flowcytometry. The expression of cyclin A, cyclin B, cyclin D1, cdk2, cdk4, cdc2, proliferating cell nuclear antigen (PCNA), p21, and p27 was examined with immunoblotting analysis. Results Portion of S-phase cells showed its peak on the 7th day. After 1st week, cyclin A, and PCNA showed significant increment in hepatic stellate cells compared to untreated hepatic stellate cells (114% and 116%, respectively, P Conclusion The increment of cyclin A, and PCNA and the decrement of p21 seem to play important roles in the proliferation of HSCs during the early period of DMN-induced rat hepatic fibrosis.

In an attempt to better define the cytologic characteristics of schwannomas, we have reviewed aspirates and corresponding histologic sections from 23 schwannomas. Of this number, the original cytologic diagnoses were: schwannoma in 14 cases (61%), benign soft tissue tumor in 2 cases (9%), and insufficient specimen in 7 cases (30%). The cytologic findings common to all cases of schwannoma included fragments of tightly cohesive fascicles with variable cellularity and corresponding Antoni type A area. The Antoni type B area, consisting of scattered spindle cells and some histiocytes and lymphocytes against a myxoid background, was seen in 14 cases. Fibrillary stroma was seen in 12 cases. The tumor cells had spindle- or ovalshaped nuclei, with pointed ends and indistinct cell borders. Nuclear palisading was seen in 10 cases, and distinctive Verocay bodies were seen in 5 cases. In ancient schwannomas, there were no Verocay bodies. Most schwannomas have distinct cytomorphologic features that allow correct diagnosis. The major problem with fine needle aspiration cytology of these tumors is the high frequency of poor cellularity, particularly in lesions with cystic degeneration. Of 7 cases with insufficient specimen, 4 showed marked cystic changes and 1 showed marked hyaline changes on histologic sections. In conclusion, we believe that if cytopathologist reminds the situation such as cystic degeneration or hyaline degeneration, the correct diagnosis of the schwannoma will be easily made.

Gastrointestinal stromal tumors (GISTs) are rarely noted in association with neurofibromatosis-1 (NF-1, von Recklinghausen disease) as an individual gastrointestinal manifestation. We report here a case of multiple GISTs with an abundant skeinoid fiber in the jejunum of a 43-year-old woman diagnosed as NF-1. Histologically, the tumors were composed of uniform spindle-shaped cells with a fascicular pattern, almost indistinguishable from the histology characteristic of usual GISTs. However, multiple synchronous tumor occurrence, abundant skeinoid fiber, and presence of microscopic miniatures of stromal tumors are additional characteristic features of this case.