Joo Han Lim

Palliative chemotherapy for patients with recurrent hepatocellular carcinoma after liver transplantation

Background and Aim:  The majority of patients with post‐transplantation recurrence of hepatocellular carcinoma (HCC) have extrahepatic metastases and multifocal lesions. Therefore, they have few treatment options and may not be amenable for local therapy. The safety and efficacy of palliative chemotherapy in this population has not been reported.

Irinotecan Combined with 5-Fluorouracil and Leucovorin as Second-line Chemotherapy for Metastatic or Relapsed Gastric Cancer

OBJECTIVE We analysed the efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) chemotherapy as second-line treatment for metastatic or relapsed gastric cancer (MRGC) in a clinical practice setting. Factors to select patients who may benefit from salvage chemotherapy was also analysed. METHODS Patients with MRGC with progression on or within 6 months after discontinuing platinum-based chemotherapy received FOLFIRI as second-line therapy. The FOLFIRI regimen consisted of irinotecan (180 mg/m(2); day 1) combined with leucovorin (200 mg/m(2)), followed by 5-fluorouracil (400 mg/m(2)) as a bolus and 600 mg/m(2) as a 22-h infusion on days 1 and 2 every 2 weeks. RESULTS Fifty-one patients received a total of 282 courses of chemotherapy. No patients had complete remission (CR), but 9 patients achieved partial remission (PR). Stable disease (SD) was documented in 15 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.2 and 9.1 months, respectively. Toxicities were tolerable and grade 3/4 neutropenia was observed in 49 cycles (17%). In multivariate analysis, patients with less organ involvement by metastasis and good performance status (PS) were independently associated with a longer PFS and OS (P < 0.05). Disease control (CR, PR or SD) after first-line chemotherapy were related to a longer PFS (P = 0.02), but had no effect on OS. CONCLUSIONS FOLFIRI was tolerable and showed modest activity as a second-line therapy in MRGC. Less organ involvement by metastasis or good PS may be optimal selection criteria for patients with MRGC who are suitable for second-line chemotherapy.

Mesenchymal stromal cells for steroid-refractory acute graft-versus-host disease: a report of two cases

Severe graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, there have been only a few limited therapeutic options for the treatment of GVHD. Here we have reported two cases of the patients with acute steroid-refractory GVHD who underwent allogeneic HSCT. These patients received infusions of third-party clonal mesenchymal stem cells (cMSCs), which were isolated by a subfractionation culturing method (SCM) developed recently by our group, and showed marked improvement of the disease. MSCs represent a new potential therapeutic option in the treatment of steroid-refractory acute GVHD. They showed safety and improved clinical findings of the acute GVHD patients. However, further investigations are needed to understand the accurate mechanisms of MSCs and larger well-designed human clinical trials are necessary to prove further the safety and efficacy of the cMSCs for the treatment of acute GVHD patients.

Plasmablastic Lymphoma in the Anal Canal

Plasmablastic lymphoma (PBL) of the oral cavity is an acquired immunodeficiency syndrome-related lymphoma. The immunophenotype of this disease is associated with poor expression of B-cell markers but a positive reactivity for plasma cell markers. PBL is highly aggressive and responds poorly to treatment. Although originally described in the oral cavity, this disease can occur in other body niches. Here, we describe a very rare case of PBL in the anal canal of a 40-year-old woman with human immunodeficiency virus infection. The malignant cells were positive for Epstein-Barr virus and human herpes virus 8.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Initially Mimicking Cutaneous Lupus Erythematosus

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease. The prognosis is poor in most cases with rapid progression despite administering chemotherapy. A 67-year-old man complained of skin rashes on his back and this spread to the trunk, face, arms and thighs, and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy. The skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months. Repeated skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei, positive for CD4 and CD56, negative for Epstein-Barr virus (EBV), indicating a diagnosis of BPDCN. Further workups confirmed stage IVA BPDCN involving the skin, multiple lymph nodes, the peripheral blood and the bone marrow. He was treated with six cycles of combination chemotherapy consisting of ifosphamide, methotrexate, etoposide, prednisolone and L-asparaginase, and he achieved a partial response. Herein we report on a rare case of BPDCN that was initially misinterpreted as cutaneous lupus erythematosus.

HS-173, a novel PI3K inhibitor suppresses EMT and metastasis in pancreatic cancer

Pancreatic cancer is one of the most aggressive solid malignancies prone to metastasis. Epithelial-mesenchymal transition (EMT) contributes to cancer invasiveness and drug resistance. In this study, we investigated whether HS-173, a novel PI3K inhibitor blocked the process of EMT in pancreatic cancer. HS-173 inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Moreover, it significantly suppressed the TGF-β-induced migration and invasion, as well as reversed TGF-β-induced mesenchymal cell morphology. Also, HS-173 reduced EMT by increasing epithelial markers and decreasing the mesenchymal markers by blocking the PI3K/AKT/mTOR and Smad2/3 signaling pathways in pancreatic cancer cells. In addition, HS-173 clearly suppressed tumor growth without drug toxicity in both xenograft and orthotopic mouse models. Furthermore, to explore the anti-metastatic effect of HS-173, we established pancreatic cancer metastatic mouse models and found that it significantly inhibited metastatic dissemination of the primary tumor to liver and lung. Taken together, our findings demonstrate that HS-173 can efficiently suppress EMT and metastasis by inhibiting PI3K/AKT/mTOR and Smad2/3 signaling pathways, suggesting it can be a potential candidate for the treatment of advanced stage pancreatic cancer.

Risk factors for bacterial pneumonia after cytotoxic chemotherapy in advanced lung cancer patients.

The purpose of this study was to demonstrate the prevalence of and risk factors for pneumonia after cytotoxic chemotherapy in advanced lung cancer patients. We retrospectively reviewed 193 out of 215 advanced lung cancer patients who were consecutively treated with cytotoxic chemotherapy at Seoul National University Hospital in 2005. The mean age was 61 years (range, 31-85 years). A total of 41 patients (21%) had Eastern cooperative oncology group (ECOG) performance status 2-3. Among 135 patients with pulmonary function test (PFT), 34% (n=46) of patients demonstrated an obstructive pattern of lung function. Pneumonia occurred in a total of 10 patients (5%). Occurrence rate was significantly higher in older patients (>70 years) than in younger ones (13% vs. 4%, p=0.05), higher in patients with ECOG 2-3 compared with those with ECOG 0-1 (15% vs. 3%, p<0.01), and higher in patients with an obstructive pattern of lung function compared with those without (11% vs. 1%, p=0.02). Pneumonia occurrence rate in patients with all three risk factors was 25%. Six out of 10 pneumonia patients required hospitalization, and one patient died from respiratory failure. We identified this high-risk group as a candidate for antibacterial prophylaxis after cytotoxic chemotherapy in advanced lung cancer patients.

The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma

Background Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC). Methods A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis. Results The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival. Conclusions These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

Central Pontine Myelinolysis in a Patient with Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation : A Case Report

We describe a 37-yr-old man who developed central pontine myelinolysis (CPM) after allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After HSCT, desquamation developed on the whole body accompanied by hyperbilirubinemia. The liver biopsy of the patient indicated graft-versus-host disease-related liver disease, and the dose of methylprednisolone was increased. Then, the patient developed altered mentality with eye ball deviation to the left, for which electroencephalogram and magnetic resonance imaging (MRI) scans were done. Brain MRI scan demonstrated the imaging findings consistent with central pontine myelinolysis and extrapontine myelinolysis. He did not have any hyponatremia episode during hospitalization prior to the MRI scan. To the best of our knowledge, presentation of CPM after allogeneic HSCT is extremely rare in cases where patients have not exhibited any episodes of significant hyponatremia. We report a rare case in which hepatic dysfunction due to graft-versus-host disease has a strong association with CPM after HSCT.

Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma.

Background: Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.