Dae Young Kang

Prognostic significance of p53, mTOR, c-Met, IGF-1R, and HSP70 overexpression after the resection of hepatocellular carcinoma.

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.

Amiodarone-induced hepatitis and polyneuropathy.

Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication thats been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.

Inhibitory effects of rapamycin on the different stages of hepatic fibrosis.

AIMnTo investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.nnnMETHODSnWe performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL(+)/Rapa(-) group (un-treated control, n = 4), the BDL(+)/Rapa(+) group (treated 14 d after BDL, n = 8), the BDL(+)/Rapa(++) group (treated on the day after BDL, n = 8), and the BDL(-)/Rapa(-) group (un-treated, sham -operated control, n = 4). The BDL(+)/Rapa(+) and BDL(+)/Rapa(++) groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin.nnnRESULTSnThe liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL(+)/Rapa(++)group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL(+)/Rapa(++)group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001).nnnCONCLUSIONnThe results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.

A Phase II Study of Additional Four-Week Chemotherapy With Capecitabine During the Resting Periods After Six-Week Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

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.

TisN0M1 Sigmoid Colon Cancer: A Case Report

Distant metastasis of a colon carcinoma in situ has not yet been reported. We experienced a case of a sigmoid colon carcinoma in situ with common hepatic lymph node metastasis. After the first operation, we diagnosed dual intramucosal adenocarcinomas of the sigmoid colon without any regional lymph node metastasis. After the second operation, a metastatic adenocarcinoma was found in the common hepatic lymph nodes. We suggest that metastasis in cases of a colonic carcinoma in situ is rare, but possible. The parallel progression model of tumors can explain this early metastasis.

Distal Cholangiocarcinoma with Gastric Metastasis Mimicking Early Gastric Cancer

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 Whippless 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.

The polypoid ganglioneuroma associated with hyperplastic polyposis

To the Editor, n nGanglioneuroma (GN) of the gastrointestinal (GI) tract is rare tumor composed of ganglion cells, nerve fibers, and supporting cells of the enteric nervous system. Diffuse ganglioneuromatosis is associated with multiple endocrine neoplasia IIB (MEN IIB), neurofibromatosis type I (NF1, also known as von Recklinghausen disease), multiple cutaneous or GI tract neurofibromatosis, and neurogenic sarcoma of the GI tract [1]. However, usual presentation of GN is small mucosal polyp < 1 to 2 cm, or sometimes multiple polyps. Few cases of solitary polypoid GN were reported in the literature, and colonic mucosal GN associated with colonic polyps is a very unusual finding. We report here a case of polypoid GN associated with hyperplastic polyposis and discuss the important pathological features and clinical issues. n nA 51-year-old Korean woman underwent colonoscopy for health checkup. The patient denied abdominal pain, diarrhea, or weight loss. She and her family had no history of familial adenomatous polyposis, MEN IIB, NF1, juvenile polyposis, or Cowden syndrome. During colonoscopy, numerous small sessile polyps were observed in the transverse colon, sigmoid colon, and rectum (Fig. 1A). The polyps were mainly located in rectosigmoid area. The colonoscpic biopsy was performed in polyps in size from 2 to 5 mm. Pathologic examination of 3 polyps in cecum, 1 polyp in ascending colon, 1 polyp in hepatic fracture, 2 polyps in sigmoid colon revealed hyperplastic polyps. Pedunculated polyp in sigmoid colon showed irregular lobulation with redness, measuring 3.0 × 1.5 cm in greatest dimensions (Fig. 1B). The endoscopic finding suggested differential diagnosis for hamartomatous polyp. The polypectomy was done after injection of normal saline and indigo carmine solution into the submucosal layer. The polyp was removed clearly by endoscopic mucosal resection. Microscopically, at low magnification the polyp showed disturbed crypt architecture with cystic glands, expanded lamina propria, and a smooth surface epithelium. Nerve ganglion and stromal cells were also noted in the lamina propira (Fig. 2A). Under closer inspection at higher magnification, collection of spindle cells in fibrillar matrix and irregular groups and nest of ganglion cells were observed specifically within the lamina propria (Fig. 2B). Immunohistochemically, the ganglion cells were positive for neuron specific enolase (NSE) (Fig. 2C) and S-100 protein (Fig. 2D). As a result of the colonoscopy, the patient also underwent esophagogastroduodenoscopy. Inner cavity of the stomach was covered with numerous sessile polyps were identified and biopsied (Fig. 1C). Pathologic examination of multiple gastric biopsies revealed hyperplastic polyps. n n n nFigure 1. n n(A) The colonoscpic finding revealed numerous small sessile polyps. (B) Polypoid ganglioneuroma presented as pedunculated polyp, measuring 3.0 × 1.5 cm

A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

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.

Recurrent Renal Leiomyosarcoma Mimicking a Colonic Submucosal Tumor: A Case Report

A primary leiomyosarcoma of the kidney is a rare, but highly aggressive, neoplasm, accounting for only 0.1% of all invasive renal tumors. Local or systemic recurrence is common, but a leiomyosarcoma is difficult to diagnose preoperatively. We recently encountered an interesting case of an unusual recurrence of a renal leiomyosarcoma. A 57-year-old woman visited our hospital complaining of lower abdominal pain. Four years previously, she had undergone a left nephrectomy. She had a primary leiomyosarcoma of the kidney that had been misdiagnosed as a renal cell carcinoma. Colonoscopy revealed the presence of a lesion similar to a submucosal tumor in the descending colon. Postoperative pathologic examination confirmed that the mass was a recurrent leiomyosarcoma. We report this unusual case and present a review of the literature.

Clear cell carcinoid of the appendix: Report of two cases with literature review.

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.