Kyung Han Nam

c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer

Background The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC). Methods The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations. Results In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453–3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS. Conclusions c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients’ outcome and for managing CRC patients.

Concomitant Drug Reaction with Eosinophilia and Systemic Symptom Syndrome from Ethambutol and Autoimmune Hepatitis from Isoniazid

Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen.

Clinical significance of midkine expression in sporadic desmoid tumors

The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors.

Childhood colon cancer in a patient with ataxia telangiectasia

BACKGROUND Ataxia-telangiectasia (AT) is a rare autosomal recessive disease characterized by progressive neurologic impairment and cerebellar ataxia. In addition, patients with this disease are known to have an inherent increased susceptibility to the development of cancer, predominantly hematologic malignancies. METHODS We report the case of a young boy with AT from Russia, who had abdominal pain. Laboratory tests and radiologic examinations were performed to him. RESULTS After abdominal computed tomography (CT), colonoscopy and surgical interventions, the young boy was diagnosed with colon cancer that had signet ring cell features. CONCLUSIONS It is known that the patient with AT appeared to be predisposed to various tumors, including leukemia or lymphoma, which are more common in childhood. Even if the patient with AT could have solid tumor such as stomach cancer or breast cancer, it is less likely to have colon cancer, especially signet ring cell type. Actually, no case of colon cancer has ever been reported, especially in young patient and hence, we have focused on this point and are hereby reporting this unique case.

A Case of Advanced Gastric Cancer Concomitant with Pyogenic Liver Abscess in the Patient with Subtotal Gastrectomy

The hematogenous spreading of an infectious pathogen via the portal vein from a mucosal injury in the gastrointestinal tract has been considered as one of the pathologic mechanisms of pyogenic liver abscess. Several studies have presented the association between colorectal cancer and pyogenic liver abscess. However, the cases of stomach cancer concomitant with pyogenic liver abscess have rarely been reported in the world. Herein, we present a case of advanced gastric cancer concomitant with pyogenic liver abscess in a patient who previously underwent subtotal gastrectomy due to peptic ulcer perforation.

Predictive value for lymph node metastasis of epithelial-mesenchymal transition and cancer stem cell marker expression in early gastric cancer

BACKGROUND Minimally invasive therapies, including endoscopic mucosal resection or sentinel node navigation surgery, have been widely applied in early gastric cancer because of their benefits in promoting patient quality of life. However, lymph node dissection is beyond the capability of endoscopic therapy, and in sentinel node navigation surgery, the potential for skip metastasis is not negligible. Therefore, the possibility of lymph node metastasis is the most important factor to consider when deciding whether to apply the minimally invasive therapies. In the present study, the significance of epithelial mesenchymal transition and stem cell marker expression in lymph node metastasis in early gastric cancer was investigated. METHODS We evaluated the significance of the expression of 5 epithelial mesenchymal transition-related markers (E-cadherin, MMP7, S100A, Snail-1, and HGF) and 6 stem cell markers (ALDH1, SOX2, CD24, CD44, CD54, and CD133) in 119 early gastric cancer specimens using immunohistochemistry. Because protein expression is heterogeneous in gastric cancer, we analyzed the expression of these markers in two selected regions (one each at the superficial zone and the deep invasive front). RESULTS Expression of E-cadherin, MMP7, HGF, and CD133 at the deep invasive front was associated with the absence of lymph node metastasis (P=0.013, 0.018, <0.001, and 0.026, respectively). Presence of diffuse-type component, lymphatic invasion, and lack of expression of HGF and CD133 at the deep invasive front were independent predictive markers of lymph node metastasis (P=0.019, <0.001, 0.015, and 0.047, respectively). CONCLUSIONS Lymph node metastasis is strongly associated with expression status of HGF and CD133 at the deep invasive front, suggesting the usefulness of these proteins as independent predictive markers of lymph node metastasis in early gastric cancer.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites

ABSTRACT Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach–Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

Primary adenosquamous carcinoma of the liver: a case report

Adenosquamous carcinoma of the liver is a rare variant of cholangiocarcinoma. It is known to be a highly aggressive tumor with a poor prognosis, but its pathogenesis remains unclear owing to limited data in the literature. We report a case of 56-year-old woman who presented with a 1-week history of epigastric pain. Magnetic resonance imaging revealed a 6.5-cm ill-defined mass with low signal intensity in the left lobe of the liver, which was suspicious of cholangiocarcinoma. The patient underwent left hemihepatectomy. Microscopically, the tumor consisted of malignant glandular and squamous components and staged as pT2aN1. Despite postoperative chemoradiation, the patient had recurrence 8 months after surgery.