Wan Kyu Eo

Efficacy and Safety of Rhus verniciflua Stokes Extracts in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer

Background: Systemic treatments for advanced non-small cell lung cancer (NSCLC) have modest survival benefits but high toxicity. Rhus verniciflua Stokes (RVS), the lacquer tree, is an ancient traditional medicine being used for the treatment of cancer. We investigated the efficacy and safety of allergen-removed RVS extract (aRVS) for the prolongation of survival in NSCLC after the failure of first-line or secondline chemotherapy. Patients and Methods: We reviewed the medical records of 40 patients who were treated with aRVS for previously treated, advanced NSCLC at the M×µ Integrative Cancer Center, Korea, between June 2006 and June 2009. The primary objective of this study was to assess overall survival. Secondary objectives included assessments of disease control rates, progression-free survival, and the safety of aRVS treatment. Results: The median survival time was 8.4 months with a 1-year survival of 40%. The disease control rate was 63.6%, and the median progression-free survival interval was 3.9 months. Patients who had better performance status and adenocarcinoma experienced more favorable outcomes in terms of overall survival. in aRVS treatment were negligible, with the most common drug-related adverse events being mild epigastric pain and itching skin. Hematologic toxicity was absent. Conclusions: Survival data and favorable levels of tolerability suggest the potential of aRVS treatment in previously treated patients with advanced NSCLC. Treatment with aRVS might be a viable alternative in patients for whom chemotherapy is not feasible, or who refuse chemotherapy.

The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer.

Objective: To measure the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively examined the LMR as a prognosticator in a cohort of 234 patients with EOC who underwent surgical resection. Patients were categorized into two different groups based on the LMR (LMR-low and LMR-high) using cut-off values determined by receiver operating characteristic (ROC) curve analysis. The objective of the study was to assess the effect of the LMR on progression-free survival (PFS) and overall survival (OS), and to validate the LMR as an independent predictor of survival. Results: Using the data collected from the whole cohort, the optimized LMR cut-off value selected on the ROC curve was 2.07 for both PFS and OS. The LMR-low and LMR-high groups included 48 (20.5%) and 186 patients (79.5%), respectively. The 5-year PFS rates in the LMR-low and LMR-high groups were 40.0 and 62.5% (P < 0.0001), respectively, and the 5-year OS rates in these two groups were 42.2 and 67.2% (P < 0.0001), respectively. On multivariate analysis, we identified age, International Federation of Gynecology and Obstetrics (FIGO) stage, and cancer antigen 125 levels to be the strongest valuable prognostic factors affecting PFS (P = 0.0421, P = 0.0012, and P = 0.0313, respectively) and age, FIGO stage, and the LMR as the most valuable prognostic factors predicting OS (P = 0.0064, P = 0.0029, and P = 0.0293, respectively). Conclusion: The LMR is an independent prognostic factor affecting the survival of patients with EOC.

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer

AIM To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.

A case of recurred hepatocellular carcinoma refractory to doxorubicin after liver transplantation showing response to herbal medicine product, Rhus verniciflua Stokes extract.

There is no established protocol proven to be beneficial for treatment of hepatocellular carcinoma recurrence after liver transplantation. Only a few reports have shown direct treatment by surgery or ablation to be independent predictors of survival for localized recurrence. Moreover, the necessity of immunosuppression to prevent allograft rejection makes many physicians hesitate to administer systemic chemotherapy. This case report documents a case in which the administration of an herbal product, an extract of the lacquer tree, Rhus verniciflua Stokes, was associated with a decrease in the size of lung metastases in a patient with recurrent hepatocellular carcinoma after liver transplantation refractory to doxorubicin. This patient experienced prolonged survival compared with average survival times and little toxicity.There is no established protocol proven to be beneficial for treatment of hepatocellular carcinoma recurrence after liver transplantation. Only a few reports have shown direct treatment by surgery or ablation to be independent predictors of survival for localized recurrence. Moreover, the necessity of immunosuppression to prevent allograft rejection makes many physicians hesitate to administer systemic chemotherapy. This case report documents a case in which the administration of an herbal product, an extract of the lacquer tree, Rhus verniciflua Stokes, was associated with a decrease in the size of lung metastases in a patient with recurrent hepatocellular carcinoma after liver transplantation refractory to doxorubicin. This patient experienced prolonged survival compared with average survival times and little toxicity.

Toxic epidermal necrolysis following thalidomide and dexamethasone treatment for multiple myeloma: a case report

Dear Editor, Toxic epidermal necrolysis (TEN) is a life-threatening idiosyncratic adverse drug reaction characterized by fullthickness epidermal necrosis and eventual development of subepidermal bullae [1, 2]. Carbamazapine, phenytoin, and allopurinol are frequent causes of TEN in Asia [1]. Although thalidomide has been suggested as a cause of TEN, to the best of our knowledge, only two cases had been reported worldwide [3, 4]. We present the case of a 65-year-old male patient who was initially diagnosed with Immunoglobulin G-κ (IgG-κ) multiple myeloma stage IIIA, and had been treated with combination chemotherapies including a VAD (vincristine, doxorubicin, and dexamethasone) regimen as well as an MP (melphalan and prednisone) regimen. About 3 years after finishing MP treatment, the patient presented with bone pain and a serum monoclonal protein level of 4,170 mg/dl. We initiated treatment with 200 mg thalidomide per day for 12 days and 40 mg dexamethasone per day for 4 days, and the dose of thalidomide was then increased to 400 mg per day. Eleven days after the boost, the patient’s course was complicated by the development of sloughing from the periorbital and perioral regions. Three days after the onset of the initial event, the patient was admitted to the emergency department with fever, dysphagia, and itching. The same day, oral mucositis, angioedema of lips and eyebrow, and diffuse erythematous to purpuric patches and plaques appeared on the face, neck, trunk, and extremities. On the third day of hospitalization, a skin biopsy showed subepidermal bullous change with an infiltration of lymphocytes and polymorphonuclear cells in the epidermis which suggested TEN (Fig. 1). On the fifth day, the clinical course was complicated by the worsening rash over the entire trunk, and the patient was started on 400 mg/kg intravenous immunoglobulin (IV-Globulin S®, Green Cross Inc., Korea) per day for five consecutive days. In addition, the patient was intensively treated as a burn patient. On the sixth day, focal skin detachment was noticed and, after 2 days, was followed by generalized detachment from the face to the lower extremities. The patient’s severity-ofillness score for TEN (SCORTEN) was 4 with an expected W. K. Eo : S. H. Cheon : S. H. Lee : J. S. Jeong Integrative Cancer Center, Kyung Hee University, East-West Neo Medical Center, Seoul, South Korea

Bone Density in Patients with Cervical Cancer or Endometrial Cancer in comparison with Healthy Control; According to the stages.

Objective: To evaluate the bone mineral density (BMD) in the lumbar spine and femur in postmenopausal women with cervical cancer and endometrial cancer without bone metastasis in comparison with that in healthy control postmenopausal women, and to assess the loss of BMD according to the cancer stage. Materials and methods: We analyzed the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry (DXA) in 218 patients with cervical cancer, 85 patients with endometrial cancer, and 259 healthy controls. The serum levels of calcium (Ca), phosphorus (P), osteocalcin (OSC), and total alkaline phosphatase (ALP), and urine deoxypyridinoline(DPL) were measured in all participants. Results: Age, body mass index, parity, and time since menopause were not significantly different between the three groups. Serum Ca level was higher in the cervical cancer group (p = 0.000), however, urine DPL was lower in endometrial cancer group (p = 0.000). The T-scores of basal BMD at the second and fourth lumbar vertebra (L2, L4) were significantly lower in patients with cervical cancer (p = 0.038, 0.000, respectively) compared to those in the healthy control groups. Additionally, the incidence of osteoporosis and osteopenia basal status of bone mass was significantly higher in patients with cervical cancer compared to that in controls (p = 0.016). No differences in basal BMD of the lumbar spine and femur were observed between patients with cervical cancer according to their stages. Conclusion: Our results suggest that postmenopausal women with cervical cancer have a lower BMD and are at increased risk of osteoporosis in the lumbar spine before receiving anticancer treatment compared with postmenopausal women with endometrial cancer.

Diagnostic accuracy of inflammatory markers for distinguishing malignant and benign ovarian masses

Objective: To evaluate the role of inflammatory markers for distinguishing malignant and benign ovarian masses. Methods: Preoperative demographic, clinicopathologic, and laboratory variables were reviewed in patients with an ovarian mass that was subsequently diagnosed as either epithelial ovarian cancer (EOC) or a benign ovarian mass on histologic analysis. The differences between variables of the two groups were further evaluated. Logistic regression analysis was applied to evaluate variables to predict the presence of EOC. Results: According to the analysis of 229 patients with EOC, 120 (52.4%) patients had serous adenocarcinoma. Of the 229 patients, 110 (48.1%) patients had stage I or II disease and 119 (52.0%) had stage III or IV disease. There was a significant difference between EOC and benign ovarian mass in median values of variables such as age, white blood cell (WBC) count, hemoglobin concentration, platelet count, cancer antigen 125 (CA125) levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (all P < 0.001, except for WBC count [P = 0.009]). In addition, there was significant difference in median values of these continuous variables among early-stage EOC, advanced-stage EOC, and benign ovarian mass (P < 0.001 for all variables). On multivariate logistic regression analysis, age (odds ratio [OR] = 4.14, P < 0.001), CA125 levels (OR = 9.87, P < 0.001), NLR (OR = 1.76, P = 0.049), PLR (OR = 2.41, P = 0.004), and LMR (OR = 0.51, P = 0.024) were found to significantly predict the presence of EOC. Conclusion: The three LMR, NLR, and PLR markers were found to be predictors for the presence of EOC. Further prospective studies to assess these markers as screening tools for the presence of EOC are required.

Monocytosis as a prognostic factor for survival in stage IB and IIA cervical cancer

Objective: To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. Methods: We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Results: Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; P <0.001) and tumor size (HR, 5.41; P = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; P <0.001), tumor size, (HR, 5.27; P = 0.033), and lymph node involvement (HR, 3.90; P = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Conclusions: Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.

Long interspersed element-1 open reading frame 1 protein expression profiles in ovarian cancers

Long interspersed element-1 (LINE-1) retrotransposons are autonomous mobile DNA elements with unique activity that account for about one-fifth of the human genome. Recently, it has been reported that the expression of LINE-1 is closely related to cancer prognosis, and LINE-1 hypomethylation might contribute to the acquisition of aggressive tumor behavior. Despite the importance of LINE-1 expression in cancers, research on the expression of LINE-1 open reading frame (ORF) proteins is very limited. Here, we investigated the expression profiles of LINE-1 ORF1p in ovarian cancer tissue microarrays containing 100 surgical specimens including adjacent normal ovary tissue, primary ovarian cancers, and metastatic ovarian cancers in lymph node. The tissue microarray was stained with mouse monoclonal antibody to LINE-1 ORFp1 for immunofluorescence analysis, and expression levels were evaluated by image analysis. LINE-1 ORFp was significantly overexpressed in ovarian cancers compared with normal tissues and especially upregulated in metastatic ovarian cancers. In addition, the expression of LINE-1 ORF1p was significantly higher in older ovarian cancer patients compared with young patients. These results indicate that expression of LINE-1 ORF1p is related to the progression of ovarian cancers and, in particular, to the age of the patient and the metastatic potential of the cancer.