Wankyu Eo

Rhus verniciflua stokes extract as a potential option for treatment of metastatic renal cell carcinoma: report of two cases.

A 50-year-old man presented with hematuria in July 2006. Abdominal computed tomography (CT) scan revealed a 12-cm right renal mass, and a right radical nephrectomy was carried out. Pathologic study revealed the clear cell type of renal cell carcinoma (RCC; Fuhrman grade II). Four months after nephrectomy, a chest CT revealed multiple pulmonary nodules (Figure 1A). With a clinical diagnosis of unresectable metastatic RCC, immunotherapy was recommended, but he refused. Instead, treatment with aRVS extract 450-mg capsules orally three times a day was initiated in December 2006 after his informed consent. After 4 months of treatment, CT scan showed a complete response in all pulmonary metastases including resolution of right pulmonary artery thrombosis (Figure 1B). Follow-up CT scans continued to demonstrate a complete response, which has lasted over 31 months since the initiation of aRVS therapy.

Necrotizing Fasciitis versus Pyomyositis: Discrimination with Using MR Imaging

Objective We wanted to evaluate the MR findings for differentiating between necrotizing fasciitis (NF) and pyomyositis (PM). Materials and Methods The MR images of 19 patients with surgically confirmed NF (n = 11) and pathologically confirmed PM (n = 8) were retrospectively reviewed with regard to the presence or absence of any MRI finding criteria that could differentiate between them. Results The patients with NF had a significantly greater prevalence of the following MR findings (p < 0.05): a peripheral band-like hyperintense signal in muscles on fat-suppressed T2-weighted images (73% of the patients with NF vs. 0% of the patients with PM), peripheral band-like contrast enhancement (CE) of muscles (82% vs. 0%, respectively) and thin smooth enhancement of the deep fascia (82% vs. 13%, respectively). The patients with PM had a significantly greater prevalence of the following MRI findings (p < 0.05): a diffuse hyperintense signal in muscles on fat-suppressed T2-weighted images (27% of the patients with NF vs. 100% in the patients with PM), diffuse CE of muscles (18% vs. 100%, respectively), thick irregular enhancement of the deep fascia (0% vs. 75%, respectively) and intramuscular abscess (0% vs. 88%, respectively). For all patients with NF and PM, the superficial fascia and muscle showed hyperintense signals on T2-weighted images and CE was seen on fat-suppressed CE T1-weighted images. The subcutaneous tissue and deep fascia showed hyperintense signals on T2-weighted images and CE was seen in all the patients with NF and in seven (88%) of the eight patients with PM, respectively. Conclusion MR imaging is helpful for differentiating between NF and PM.

Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients

AIM To investigate the impact of systemic inflammation-based prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer (mCRC) patients. METHODS To investigate prognostic markers in mCRC patients, this study was performed with patients who have experienced relapsed/refractory mCRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status, age, or comorbidity. We reviewed the medical records of 177 mCRC patients managed with Korean Medicine (KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics, laboratory test, the systemic inflammation markers including the modified Glasgow prognostic score (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), and prognostic nutritional index (PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers, the hazard ratio (HR) of mGPS, NLR, PLR, LMR, and PNI for overall survival were evaluated with the Cox proportional hazards regression. RESULTS The majority of mCRC patients had relapsed/refractory to standard chemotherapy; 128 patients (72.3%) had undergone more than second line chemotherapy, and the median time from diagnosis of mCRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses, the inflammation markers of higher mGPS (P < 0.001), NLR ≥ 5 (P < 0.001), PLR > 300 (P = 0.004), LMR ≤ 3.4 (P < 0.001), and PNI ≤ 45.3 (P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model, mGPS at 2 vs 0 (HR = 3.212, 95%CI: 1.437-7.716, P = 0.004), and LMR ≤ 3.4 (HR = 1.658, 95%CI: 1.092-2.518, P = 0.018) as independent predictors associated with poor overall survival along with carbohydrate antigen 19-9 (HR = 1.482, 95%CI: 1.007-2.182, P = 0.046), AST ≥ 40 (HR = 2.377, 95%CI: 1.359-4.155, P = 0.002), and the treatment duration for KM less than 2.9 mo (HR = 1.718, 95%CI: 1.160-2.543, P = 0.007). CONCLUSION These results indicate that the inflammatory markers, mGPS and LMR are independent prognostic factors for predicting overall survival in relapsed/refractory mCRC patients.

DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers.

DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

Efficacy and Safety of Standardized Allergen-Removed Rhus verniciflua Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.

Serum Ferritin as a Prognostic Biomarker for Survival in Relapsed or Refractory Metastatic Colorectal Cancer.

Background: This study investigated the prognostic impact of serum ferritin for survival in patients with relapsed or refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort study reviewed clinicopathological characteristics and laboratory biomarkers in 120 mCRC patients being treated with Korean Medicine (KM). The overall survival (OS) of patients was calculated using the Kaplan-Meier method, and statistical significance was assessed using the log-rank test. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival in relapsed or refractory mCRC patients. Results: Of the patients, 62.5% had liver metastases, 74.1% underwent greater than second-line chemotherapy, and 80.8% underwent surgery. Median OS was 7.6 months for all patients after the initiation of KM treatment, which was begun 13.7 months, on average, after mCRC diagnosis. Concerning prognostic factors such as the presence of liver metastasis (p = 0.024), high carcinoembryonic antigen level (CEA > 5 ng/mL, p = 0.044), elevated C-reactive protein (CRP ≥ 10.0 mg/L, p = 0.000), high absolute monocyte count (AMC > 413.3 cells/μL, p = 0.034), elevated serum ferritin (ferritin ≥ 150 ng/mL, p = 0.002), low hemoglobin level (Hb < 12 g/dL, p = 0.026) and low albumin (albumin < 3.5 g/dL, p = 0.003) were associated with increased hazard ratios and poor survival. According to the multivariate proportional hazards model with backward and forward manners, albumin (albumin < 3.5 g/dL; hazard ratio (HR) 2.218, 95% confidence interval (CI) 1.135 - 3.990, p = 0.019), CRP (CRP ≥ 10.0 mg/L; HR 2.506, 95% CI 1.644 - 3.822, p = 0.000), CEA (CEA > 5 ng/mL; HR 2.040, 95% CI 1.203 - 3.460, p = 0.008), and serum ferritin (ferritin ≥ 150 ng/mL; HR 1.763, 95% CI 1.169 - 2.660, p = 0.007) were independent prognostic biomarkers of survival in mCRC patients. Conclusions: These results indicate that serum ferritin acts as an independent prognostic biomarker for survival in relapsed or refractory mCRC patients.

Impact of Standardized Allergen-Removed Rhus verniciflua Stokes Extract on Advanced Adenocarcinoma of the Ampulla of Vater: A Case Series

Background. Adenocarcinoma of the ampulla of Vater (AAV) is a rare malignancy that has a better prognosis than other periampullary cancers. However, the standard treatment for patients with relapsed or metastatic AAV has not been established. We investigated the clinical feasibility of standardized allergen-removed Rhus verniciflua stokes (aRVS) extract for advanced or metastatic AAV. Patients and Methods. From July 2006 to April 2011, we retrospectively reviewed all patients with advanced AAV treated with aRVS extract alone. After applying inclusion/exclusion criteria, 12 patients were eligible for the final analysis. We assessed the progression-free survival (PFS) and overall survival (OS) of these patients during the follow-up period. Results. The median aRVS administration period was 147.0 days (range: 72–601 days). The best tumor responses according to Response Evaluation Criteria in Solid Tumors were as follows: two with complete response, two with stable disease, and eight with progressive disease. The median OS was 15.1 months (range: 4.9–25.1 months), and the median PFS was 3.0 months (range: 1.6–11.4 months). Adverse reactions to the aRVS treatment were mostly mild and self-limiting. Conclusions. Prolonged survival was observed in patients with advanced AAV under the treatment of standardized aRVS extract without significant adverse effects.

Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma

BACKGROUND Malignant ovarian tumor is one of the leading causes of worldwide cancer death. It is usually characterized by insidious onset and late diagnosis because of the absence of symptoms, allowing ovarian cancer cases to progress rapidly and become unresectable. The tumor suppressor, p53, plays an important role in regulating cell cycles and apoptosis. p53 is regulated by several molecules, and it interacts with other apoptotic proteins. OBJECTIVES To compare the prognosis of ovarian serous carcinoma and evaluate the expression of DNA-PKcs, Akt3, GSK-3β, and p53 in cancerous cells. MATERIAL AND METHODS DNA-PKcs, Akt3, GSK-3β, and p53 expression levels were scored using immunohistochemistry staining of tissue samples from 132 women with ovarian serous adenocarcinoma. Expression was confirmed by real-time RT-PCR. Analyses were stratified by age, tumor grades, cancer stages and serum CA 125 levels. RESULTS Significant differences in DNA-PKcs, Akt3, and p53 expression were observed between participants with different stages and tumor grades of ovarian serous adenocarcinoma. DNA-PKcs and p53 expression increased along with increasing tumor grade. Meanwhile, DNA-PKcs, Akt3, and p53 expression increased along with increasing cancer stage, and with a decrease in 5-year overall survival rate. CONCLUSIONS This study shows that elevated expression of DNA-PKcs, Akt3, and p53 in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis.

The Relationship Between Health-Related Quality of Life and Survival in Metastatic Colorectal Cancer Patients Treated With Korean Medicine

Objectives. This study aimed to identify the relationship between health-related quality of life (HRQoL) measured by the Functional Assessment Cancer Therapy–General (FACT-G) and survival in metastatic colorectal cancer (mCRC) patients. Methods. The clinical characteristics and FACT-G scores were retrospectively reviewed in mCRC patients who visited the Cancer Center of Korean Medicine. The overall survival (OS) was calculated and compared using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed based on clinical characteristics and FACT-G scores. To identify significant differences in answer frequency, χ2 tests and Fisher’s exact tests were used. Results. A total of 58 patients were reviewed. The proportion of patients who had an Eastern Cooperative Oncology Group–Performance Status ≥ 2 was 43.1%, multiple distant metastatic sites was 77.6%, liver metastases was 43.1%, been previously treated was 89.7%, and received more than the second-line chemotherapy was 75.5%. The mean total FACT-G score was 65.3 (median 65.6). The median OS was 7 months. There was no significant difference in OS between the 2 groups divided by the median values of FACT-G total and subscores. In univariate analyses, functional well-being (FWB) score had a significant impact on survival. In multivariate analyses, presence of liver metastasis, FACT-G total score, and FWB score were significant prognostic predictors of survival. No statistically different answer frequency was observed for any question regarding FWB. Conclusions. This study found that FACT-G total and FWB scores were potential prognostic factors for predicting OS in relapsed or refractory mCRC patients treated with Korean Medicine.