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Purpose The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). Materials and Methods Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. Results Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. Conclusion This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Objective:Cultures obtained from pre-operative middle-ear swabs from patients with chronic otitis media have traditionally been used to guide antibiotic selection. This study investigated changes in the bacterial strains of the middle ear during chronic otitis media surgery.Methods:Pre-operative bacterial cultures of otorrhoea, and peri-operative cultures of the granulation tissue in either the middle ear or mastoid cavity, were obtained. Post-operative cultures were selectively obtained when otorrhoea developed after surgery.Results:Bacterial growth was observed in 45.5 per cent of pre-operative cultures, 13.5 per cent of peri-operative cultures and 4.5 per cent of post-operative cultures. Methicillin-resistant Staphylococcus aureus was identified as the most common bacteria in all pre-operative (32.4 per cent), peri-operative (52.4 per cent) and post-operative (71.4 per cent) tests, and the percentage of Methicillin-resistant S aureus increased from the pre- to the post-operative period.Conclusion:The bacterial culture results for post-operative otorrhoea showed low agreement with those for pre-operative or peri-operative culture, and strain re-identification was required.

Hospice palliative care (HPC) in Korea has developed steadily since its introduction in 1965. Currently, HPC in Korea is targeted only towards terminal cancer patients and their families, and the national health insurance scheme covers only inpatient hospice care for said patients. In recent years, healthcare professionals and policy makers began to recognize the need for HPC services in diverse settings including outside hospital boundaries, and for all terminally-ill patients. A law on HPC passed in January 2016 allows terminally-ill patients to refuse life-sustaining treatments, and will likely facilitate further development of HPC services. It is critical for the government and all interested parties in the medical, academic and social sectors to collaborate to ensure its success once it takes effect in 2017. This article will briefly review the half-century history of HPC in Korea, and discuss how to prepare for and cope with death and, thereby, improve the quality of death.

10106 Background: A decision aid (DA) increases knowledge, decreases decisional conflicts and regrets and improves post-decision satisfaction, emotional distress. However, few DA trials have revealed whether decisional role preferences have an impact on patient-reported outcomes by decision making. The objective of this study was to investigate the impact of caregiver’s decisional role preference on decisional conflicts and psychiatric distresses in decision making. Methods: 406 of 444 caregivers of terminally ill cancer patients enrolled onto a previous trial determining the efficacy of the decision aid about disclosure of terminal disease status were included in this analysis. The analysis outcomes were change score of decisional conflicts using the Decision Conflict Scale (DCS) and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) at 1 and 3 months from baseline. Participants were divided into 4 groups: active caregiver who received DA (active-DA), active caregiver in control group (active-control), passive caregiver who received DA (passive-DA), and passive caregiver in control group (passive-control). Linear mixed model was conducted to find out the impact of caregiver’s decisional role preference on the DCS and the HADS. Results: Among 406 caregivers, 137 (33.7%) showed active role preference, and 269 (66.3%) showed passive role preference. In post-hoc analysis of adjusted differences of change scores between passive-DA and active-DA groups, non-significant differences were observed in DCS. However, at 3 months, change scores of HADS depression subscale increased as 4.43 (95% confidence interval (CI), 0.78-8.07; P< 0.007; effect size (ES) 0.71) and those of HADS anxiety subscales increased as 4.14 (95% CI, 0.37-7.91; P= 0.021; ES 0.61) in passive-DA group than in active-DA group, showing moderate to large difference. Conclusions: These findings suggest that information about decision making might be provided with tailored format for how much individual wish to involve in decision making.

Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10(7) LMP1/2a CTLs/m(2). Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.

Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP). Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen. Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS. In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.

Purpose To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. Materials and Methods A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. Results CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). Conclusion In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

A Korean advance directive (K-AD) draft was developed for establishment of a unified and evidence-based form of AD in Korea. Yet, it remains unknown whether this K-AD is culturally and practically compatible for employment in a clinical environment. Therefore, the aim of this study was to solicit professional opinions regarding this K-AD draft. Using a panel of experts in hospice and end-of-life (EOL) care, a 3-round Delphi study was conducted for evaluation of K-AD, composed of 16 specifics in 5 components, including introduction, a value statement, treatment options, proxy appointment, and stakeholders’ signatures. A consensus was determined: An item scored as important (≥4 on a 5-point Likert scale) among 75% of experts or content validity ratio of 0.59 or greater. Forty experts, 35% (n = 14) and 79% (n = 11) of previous-round participants, completed each round. Item evaluation did not differ across 3 rounds (Friedman χ2 = 0.00-6.00, P = .05-1.00). Experts reached a consensus on 5 K-AD components, all-encompassing. Among EOL treatment options, cardiopulmonary resuscitation, artificial ventilation, artificial feeding, and hospice care were determined for inclusion of the K-AD. Important-item content validity ratios ranged from 0.64 to 1.00. In conclusion, K-AD could be used as a vehicle to facilitate the decision-making process for EOL care.

Castleman's disease (CD) is thought to be related with an initially benign viral disease with cytokine-driven propagation and malignant transformation. This paper reports the first case of a simultaneous discordant lymphoma consisting of lymphocyte-depleted classical Hodgkin's lymphoma (LDCHL) and peripheral T-cell lymphoma (PTCL) arising in a patient with multicentric CD (MCD). PTCL occurred 4 years after the diagnosis of MCD, and LDCHL was developed 6 years after the treatment of PTCL, sequentially. The following year, the patient presented with a relapse of a simultaneous discordant lymphoma. On excisional cervical LN biopsy, immunohistochemical stain pattern was identical with previously diagnosed LDCHL, which expressed CD30, CD15, PAX5, and Epstein-Barr virus (EBV)-encoded RNA. PTCL was positive for CD3, CD4, CD5, CD10, and CD56, and showed identical TCRB and TCRG gene rearrangements to those detected initially. MCD was thought to be the major contributing factor leading to initial PTCL, while EBV-positive LDCHL is thought to have promoted the development of PTCL, as a persistently abnormal immune microenvironment may induce the recurrence of PTCL. MCD runs a more aggressive course and can progress to Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or combined HL/NHL. Due to its malignant potential, prompt recognition and therapy is critical for these situations, which may be life threatening.

Purpose Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. Methods Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. Results A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5–39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p

Few studies of systemic chemotherapy have focused on gastric cancer with peritoneal carcinomatosis (PC) without measurable lesions. In the present study, we characterized the outcomes of systemic chemotherapy and prognostic factors for gastric cancer with PC, particularly in patients without measurable disease.Clinical data from 211 gastric cancer patients with PC (137 without and 74 with measurable disease) who had received systemic chemotherapy between January 2003 and December 2010 at a single center were reviewed.The median overall survival (OS) rate of gastric cancer patients with PC with no measurable disease was significantly longer than that of patients with measurable disease (18.0 vs. 11.6 months, p = 0.010). On multivariate analysis, poor performance status [hazard ratio (HR) = 2.15, p 0.001], the presence of metastatic lymphadenopathy (HR = 2.17, p 0.001), and high-grade PC (HR = 1.83, p = 0.001) were associated with significantly decreased OS. When patients with low-grade PC were stratified by clinical PC grade, the median OS of those without measurable disease was 19.6 months. The median OS of patients with low-grade PC with no measurable disease was longer than those of patients with high-grade PC without measurable disease, patients with low-grade PC with measurable disease, and patients with high-grade PC with measurable disease (p = 0.001, p = 0.029, and p 0.001, respectively). Among the patients with low-grade PC, patients who received a gastrectomy had longer survival than patients who did not receive a gastrectomy (p 0.001).In our study, clinically low-grade PC without measurable disease was associated with better outcomes of systemic chemotherapy than the outcomes in the other groups examined. Clinical trials in patients with gastric cancer with PC should be stratified according to PC grade.

Purpose We tested whether a decision aid explaining how to discuss the approach of death with a family member with cancer would help family caregivers decide to discuss a terminal prognosis. Patients and Methods We randomly assigned caregivers of terminally ill patients with cancer to a group that received a video and a companion workbook that showed either how they can discuss the prognosis with their patient (experimental arm) or how cancer pain can be controlled (control arm). At baseline and 1 month, we evaluated the decision to discuss terminal prognosis as the primary outcome. At 0, 1, 3, and 6 months, we assessed the caregivers' decisional conflict and satisfaction as secondary outcomes using a Decision Conflict Scale (DCS). Results We found no difference in changes in the decision to discuss terminal prognosis between the two groups. Conflict (P = .003), uncertainty (P = .019), and value clarity (P = .007) subscale scores and total DCS score (P = .008) improved from baseline to 1 month significantly more in the experimental arm than in the control arm. Over 6 months, the significant between-group differences continued for the conflict (P = .031), uncertainty (P = .014), and value clarity (P = .039) subscale scores and total DCS score (P = .040). Conclusion Decision aids can help caregivers, with the aid of trained professionals, to communicate with patients about their terminal illness.

Korean hospice care has been greatly developed in a short period of time, thanks to help of foreign specialists and aids from developed countries. With enormous growth in economy, Korea which once received foreign aids now give help to other countries. It is the time for the Korean hospice society to consider ways to make an international contribution. That way, Korea could help terminal patients both in Korea and neighboring countries overcome sufferings, maintain their dignity as human beings until the end of their lives and have a comfortable moment of death. Thus, we need to think about ways to contribute to the international hospice society and make related plans. (Korean J Hosp Palliat Care 2011;14:138-143)Key Words: Hospices, International cooperation, Gift giving서 론한국의 호스피스는 1964년에 한국에 진출한 호주의 ‘마리아의 작은 자매회’ 수녀들이 1965년에 강릉에서 시작한 갈바리 의원을 효시로 한다(1). 현재는 약 160여 개의 호스피스 기관이 활동하고 있는 것으로 알려져 있으며 호스피스ㆍ완화의료의 제도화를 위한 수가 시범사업을 통해 정부와 민간이 모두 적극적인 관심을 가지고 노력을 하고 있으며 호스피스와 관련된 윤리적 문제를 해결하고 대책을 정리하기 위한 논의도 활발하다.호스피스ㆍ완화의료에 대한 학문적 접근도 활성화 되어 매년 국제적인 학술잡지에 많은 논문이 발표되고 있고 국제적인 호스피스ㆍ완화의료 학술대회에서 발표되는 초록이나 참가자의 수가 매년 늘어나고 있고 호스피스ㆍ완화의료와 관련된 국제 학회에서 한국 전문가들의 활동도 점차 늘어나고 있다.한국은 세계 역사상 가장 짧은 기간에 경제 부흥을 이룬 나라로 인정되고 있으며, 원조를 받던 빈곤 국가에서 이제는 원조를 주는 경제 강국으로 탈바꿈한 유일한 국가로 국제사회에서 알려져 있고 기능하고 있다.한국의 호스피스가 자리를 잡아가면서 같은 시기에 세계적으로는 아시아 태평양 호스피스 네트워크(Asia Pacific Hospice Palliative Care Network, APHN), 국제 호스피스ㆍ완화의료 연합(International Association for Hospice and Palliative Care, IAHPC), 유럽 완화의료 연합(European Association for Palliative Care, EAPC) 등이 시작되었고, 2000년대 중반부터는 세계 완화의료 연맹(World Palliative Care Alliance, WPCA) 등이 발족되어 활동하고 있다. 한국은 초창기에 개인적인 입장에서 몇몇 전문가들이 이 활동에 참여를 했고, 아시아 태평양 지역의 대표적 호

Although Epstein-Barr virus (EBV) is associated with 6-16% of the gastric carcinoma (GC) cases, the effect of EBV infection on the tumorigenesis process and the responsiveness to chemotherapy remain unclear. We compared chemosensitivity of the EBV-positive GC (AGSEBV) and EBV-negative GC (AGS) cells to 5-fluorouracil (5-FU). Although 5-FU inhibited the growth of both cell lines in a dose- and time-dependent manner, the sensitivity of EBV-positive GC cells to 5-FU was lower than that of EBV-negative GC cells. The cleavage of PARP and caspase-3 was also lower in AGS-EBV cells than in AGS cells following 5-FU treatment. Both the level of Bcl-2 expression and the ratio of Bcl-2/Bax were higher in AGS-EBV than in AGS cells not only at basal state but also following 5-FU treatment. Moreover, p53 and p21 expression was enhanced further by 5-FU in AGS than in AGS-EBV cells. Immunofluorescence assay and Western blot showed that 5-FU induced the expression of EBV-lytic genes including BZLF1, BRLF1, BMRF1 and BHRF1. Our results suggest that latent and lytic EBV infection contributes to the chemoresistance to 5-FU in gastric carcinoma by modulating apoptosis related cellular genes.

In Korea, many health care professionals have shown increased concern about the management of cancer pain. Five years after a pain management guideline was distributed to Korean physicians, the Korean Society of Hospice and Palliative Care evaluated the change in cancer pain management. The period evaluated was between 2001 and 2006.We did a prospective, cross-sectional cancer pain survey on the change of the pain prevalence and pain intensity, its impact on daily activities and the adequacy of pain management between 2001 and 2006.Overall, 7565 patients were enrolled from 72 cancer hospitals in the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals in the 2006 cancer pain survey. The overall prevalence of cancer pain and the percentage of patients reporting a negative pain management index were significantly decreased in the 2006 cancer pain survey compared with the 2001 cancer pain survey (44.9% vs. 52.1%, P0.0001 and 41.6% vs. 45.0%, respectively, P=0.0005). However, in 2006, physicians did not prescribe analgesics to 25.8% of the patients with severe pain and they did not adjust the prescribed analgesics properly in 47.4% of the patients with severe pain.Some improvement in cancer pain management was noted during the five years between 2001 and 2006. However, all of the physicians who care for cancer patients should pay more attention to cancer pain management, and an educational program for cancer pain management should be distributed to all of the physicians who care for cancer patients.

We investigated the impact of perception of socioeconomic burden on beliefs regarding a patient’s autonomy in end-of-life (EOL) decision making. We also sought to identify the characteristics of individuals who advocate patient autonomy and their attitudes toward other EOL issues. A total of 1055 individuals from the Korean general population were interviewed through a telephone survey using a structured questionnaire that was designed to investigate public attitudes toward various EOL issues. Of 1019 individuals included in the analysis, 635 (62.3%) specified the patient and 221 (21.7%) the family, when asked who is the appropriate decision maker in terms of EOL decisions in the absence of perception of socioeconomic burden. In contrast, the numbers were 458 (44.9%) and 500 (49.1%), respectively, if substantial burden was assumed. Respondents who favoured the patient’s right to make decisions regardless of perception of socioeconomic burden numbered only 312 (30.6%) and were likely to be younger and have knowledge of hospice than who favoured family decision. Former group also favoured the disclosure of terminal illness to patients, withholding life-sustaining treatment, and preparation of advanced directives. Societal attitudes toward patient autonomy were significantly influenced by perception of socioeconomic burden. Open and balanced discussion about burden to family and adequate welfare support are thus suggested.

PURPOSE The potential therapeutic application of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS Using TRAIL-sensitive (RPMI- 8226) and TRAIL-resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells.

Cyclooxygenase-2 (COX-2) contributes to invasiveness of cancer through activation of several matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme that degrades the extracellular matrix, and has been linked to invasion and metastasis. This study aims to assess the correlation of the COX-2 expression and the MMP-2 expression in patients with non-small cell lung cancer (NSCLC).We analyzed the protein expressions of COX-2 and MMP-2 by immunohistochemical staining on the tissue array specimens from 204 patients with completely resected NSCLC. A10% immunostaining of the cancer cells was considered negative, while10% was considered positive.The COX-2 expression was positive in 68.1% and that of the MMP-2 was positive in 45.6%. The positive expression rate of MMP-2 (52.5%) in the positive COX-2 group was higher than that in the negative COX-2 group (30.8%, P = 0.004). Furthermore, the MMP-2 expression was associated with lymph node involvement, the tumor stage and the histological type. The patients with a positive MMP-2 expression showed a reduced survival (P = 0.048).The COX-2 expression is associated with the MMP-2 expression in NSCLC patients: the latter may also be associated with tumor progression and reduced survival in NSCLC patients.

Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin’s lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient’s T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 X 107 cells/m2, and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lym-phoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.

Background: This study was undertaken to identify predictors of the prescription of strong opioids, which are important for the management of severe cancer pain, by Korean physicians. Methods: A questionnaire based on a hypothetical case designed to assess the prescription of morphine by physicians was administered to 800 specialists in the Korea Cancer Association, of whom 147 (18.4%) responded, and to 2200 specialists in the Korean Academy of Family Medicine, of whom 388 (17.6%) responded. We used a multidimensional approach to identify the predictors of prescription of morphine by physicians. Results: In the hypothetical case scenario, only 16.5% of the respondents stated that they would prescribe morphine for severe cancer pain. Multiple logistic regression analysis showed that physicians with a positive attitude regarding opioid addiction [odds ratio (OR) 2.62; 95% confidence interval (CI) 1.54 ‐ 4.46], experience of pain assessment (OR 2.09; 95% CI 1.13 ‐ 3.87), recent residency training (OR 2.27; 95% CI 1.30‐ 4.0) and positive self-evaluation as an oncology specialist (OR 2.60; 95% CI 1.41 ‐4.78) were more likely to prescribe morphine. None of the 13 variables in the knowledge dimension significantly predicted prescription of morphine for severe cancer pain. Conclusions: The results of the survey suggest that we need to develop strategies to develop a positive attitude toward opioids, to increase experience in pain assessment and to improve cancer pain

Objectives: We conducted this study to identify factors influencing the burdens cancer brings to a patient’s family and to evaluate the association between the burdens and the caregiver’s quality of life (QOL). Methods: Participants were drawn from the primary family caregivers of cancer patients at 6 university hospitals and the National Cancer Center in Korea. Of the 738 eligible caregivers, 704 (95.4%) completed the questionnaire packets (Family Impact Questions and Caregiver’s QOL-Cancer). Results: Caregivers, who were poor (OR, 2.11; 95% CI, 1.44–3.10), whose health status was poor (OR, 1.87; 95% CI, 1.29–2.70), who were married (OR, 1.75; 95% CI, 1.12–2.72), who provided care for a long time (OR, 2.29; 95% CI, 1.59–3.28), who cared for patients with poor performance status (OR, 1.35; 95% CI, 1.00–1.82), and who paid high medical expenses (OR, 1.70; 95% CI, 1.21–2.40), were more likely to lose their family savings. In multiple regression analysis, most burden variables – including requiring caregiving assistance, major life change, inability to function normally, loss of savings, loss of income, and altered educational plans – were associated with caregiver QOL. Loss of family income, which was related to economic issues, was most strongly associated with it (16.0%). Conclusions: Our study suggests that to improve caregiver QOL, we should give priority to decreasing the economic burden that cancer places on patient’s family.

Background: Intrahepatic cholangiocarcinoma is a chemoresistant cancer for which effective chemotherapy is not yet available. We investigated the efficacy and toxicity of the combination of gemcitabine and cisplatin as second-line chemotherapy in four patients with advanced, progressive intrahepatic cholangiocarcinoma. Methods: Four patients were enrolled who had previous chemotherapy with epirubicin, cisplatin and protracted infusion of 5-FU. All these patients treated with gemcitabine 1000 mg/m 2 intravenously (i.v.) on days 1 and 8 for 30 min, cisplatin 75 mg/m 2 i.v. on day 1 for 90 min, given every 21 days. Results: Two patients had partial response (PR), and two had stable disease (SD), with one of the latter showing a decrease in tumor size of 35%. Median time to progression was 5 months (range, 3-9 months) and median survival was 9 months (range, 8-16 months). Toxicity was mild and tolerable. Conclusions: Gemcitabine and cisplatin combination chemotherapy may be an effective regimen for advanced intrahepatic cholangiocarcinoma. Further study is warranted to determine the efficacy of this combination regimen.

Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.On day 1, epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered i.v., repeated every 21 days. 5-FU (200 mg/m(2)/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.

Background : Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders and nasopharyngeal carcinoma. Recently some of the tumor cells of gastric cancer were observed to contain EBV sequence. We detected EBV using PCR to determine the frequency of EBV associated gastric cancer, which is the most common cancer in Korea. We also performed immunohistochemical staining for the latent membrane protein (LMP1), p53 and CD44 to investigate the possible mechanism in EBV-associated gastric cancer. Methods : Eighty-seven formalin-fixed and paraffin-embedded blocks (40 gastric adenocarcinomas, 34 adjacent normal tissues, 13 metastatic lymph nodes) from 40 surgically resected gastric specimens were studied. All patients were diagnosed as having gastric cancer at the Kang-Nam St. Mary's Hospital during the period of April 1995 to April 1997. DNA was extracted from each paraffin block and then we performed PCR and immunohistochemical staining for the LMP1, p53 and CD44. We reviewed the patients' chart for clinical information. Results : EBV was detected in 4 cases (10%) by EBV-PCR among the 40 patients. It was also detected in a metastatic lymph node in 1 patient. The immunohistochemical staining for the LMP1, p53 and CD44 was negative in all the EBV-positive cancer patients. Of the patients having these cancers, 2 had a poorly differentiated adenocarcinoma with a lymphoepithelioma-like morphology. Conclusion : The frequency of EBV-associated gastric cancer may be about 10% in Korea. Considering the negative result of the immunohistochemical staining for the LMP1, p53 and CD44, EBV-associated gastric cancer seems to have a different mechanism of tumorigenesis from ordinary gastric cancer or other EBV-associated cancers. This must be determined by further large scale studies.

Purpose To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. Patients and Methods We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. Results 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P < .001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). Conclusion Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71–89) in the single regimen group (SG, 70 patients) and 73 years (range 71–81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85–5.95) and 4.1 months (95 % CI 2.62–5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17–9.08) and 7.6 months (95 % CI 5.50–9.69; P = 0.782), respectively. Hematologic (P

OBJECTIVES Hemophagocytic syndrome (HS) is a fatal complication of nasal angiocentric lymphoma (AL) and difficult to distinguish from malignant histiocyosis. Epstein-Barr virus (EBV)-associated HS is frequently observed in lymphoma of T-cell lineage and EBV is highly associated with nasal AL. Clinicopathologic features of 10 nasal ALs with HS were reviewed to determine the clinical significance and the pathogenetic association with EBV. METHODS Ten patients of HS were identified from a retrospective analysis of 42 nasal ALs diagnosed from 1987 to 1996. Immunohistochemical study and in situ hybridization were performed on the paraffin-embedded tumor specimens obtained from 10 patients. Serologic study of EBV-Ab was performed in 3 available patients. RESULTS Five patients had HS as initial manifestation, 3 at the time of relapse and 2 during the clinical remission of AL. Four patients were treated by combination chemotherapy (CHOP) and others had only supportive care. The median survival of all patients with HS was 4.1 months (range 2 days-36.5 months) and all had fatal outcome regardless of the treatment-modality. All cases were positive for UCHL1 (CD45RO) and EBV by EBER in situ hybridization. The data of serologic tests indicated the active EBV infection. CONCLUSIONS HS is a fatal complication of nasal AL and has a high association with EBV. Reactivation of EBV may contribute to HS and further investigation of predictive factors and effective treatment of HS should be pursued in the future.

Background Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. Methods From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. Results The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). Conclusions MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.

Objectives: Terminal cancer patients and their caregivers often experience traumatic stress and need many types of assistance. In the present study we interviewed terminally ill cancer patients and caregivers to determine how much burden they experienced and to find out what factors are most important for satisfaction. Design: We constructed a questionnaire including overall care burden and needs experienced, and administered it to 659 terminal cancer patients and 659 important caregivers at 11 university hospitals and 1 national cancer center in Korea. Results: Finally, 481 terminal cancer patients and 381 caregivers completed the questionnaire. Care burden was not insubstantial in both and the caregiver group felt more burden than the patient group (P

PURPOSE It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. MATERIALS AND METHODS We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. RESULTS During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. CONCLUSION Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives.

4016Background: Paclitaxel is currently only available as an IV formulation. DHP107 is a novel oral formulation composed of lipid ingredients and paclitaxel. DHP107 has demonstrated comparable effi...

Homeobox genes code for transcription factors and are arranged in clusters, named A, B, C and D, found on four separate chromosomes in vertebrates. They contain a homeobox DNA sequence which codes for the homeodomain, a region of amino acids responsible for the DNA binding exhibited by these proteins. During embryonic development, the homeobox genes are both spatially and temporally regulated. In teratocarcinoma cell cultures, homeobox genes are regulated by retinoic acid (RA). The cDNAs from the first gene in the human HOX A cluster, HOX A1 (1.6), were cloned and the nucleotide sequence of a full-length cDNA was determined. It is highly homologous to its murine counterpart. Another HOX A1 cDNA was cloned, corresponding to an alternatively spliced form. In vitro translation of the full-length cDNA clone gave rise to a protein of 36 kDa. In PA-1 human teratocarcinoma cells HOX A1 is the earliest HOX A gene to be expressed after treatment with RA. To test whether HOX A1 could function as a early regulator of other HOX A cluster genes, we cotransfected into PA-1 human teratocarcinoma cells sense and antisense HOX A1 cDNAs expressed from an SV40 promoter with a 5.4-kb RA-sensitive HOX A4 (1.4) promoter-cat reporter. We found no effect of HOX A1 on the HOX A4 promoter. However, cotransfection of HOX A5 (1.3) was able to inhibit the HOX A4 promoter activity.

Context The Edmonton Symptom Assessment System (ESAS) is a brief, widely adopted, multidimensional questionnaire to evaluate patient-reported symptoms. Objectives To develop a Korean version of the ESAS (K-ESAS) and to perform a psychometric analysis in Korean patients with advanced cancer. Methods We tested the K-ESAS in two pilot studies with 15 patients each. We assessed internal consistency, test-retest reliability, and concurrent validity in 163 Korean patients, who completed the K-ESAS along with the Korean versions of the M. D. Anderson Symptom Inventory (K-MDASI) and the Hospital Anxiety and Depression Scale (K-HADS) twice. A total of 38 patients completed the questionnaires again seven days later to assess responsiveness. Results The K-ESAS scores had good internal consistency, with a Cronbach's alpha coefficient of 0.88, indicating that no questions had undue influence on the score. Pearson correlation coefficients for K-ESAS symptom scores between baseline and after two to four hours ranged from 0.72 (95% CI 0.64–0.79) to 0.87 (95% CI 0.82–0.90), indicating strong test-retest reliability. For concurrent validity, Pearson correlation coefficients between K-ESAS symptom scores and corresponding K-MDASI symptom scores ranged from 0.70 (95% CI 0.62–0.77) to 0.83 (95% CI 0.77–0.87), indicating good concurrent validity. For the K-HADS, concurrent validity was good for anxiety ( r =0.73, 95% CI 0.65–0.79) but moderate for depression ( r =0.4, 95% CI 0.26–0.52). For responsiveness, changes in K-ESAS scores after seven days were moderately correlated with changes in K-MDASI scores but weakly correlated with changes in K-HADS scores. Conclusion The K-ESAS is a valid and reliable tool for measuring multidimensional symptoms in Korean patients with cancer.

Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (CDH1, CTNNB1, ERBB2, KRAS, MLH1, PIK3CA, SMARCB1, and TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

Objectives: To investigate in depth the use of complementary and alternative medicines (CAMs) by cancer patients at the end-of-life (EOL) and how they communicate with physicians about them. Design and location: In 17 hospitals in Korea between January and December 2004 we identified 4,042 families of cancer patients. Results: The prevalence of CAM use among cancer patients at the EOL was 37.0%, and 93.1% had used pharmacologic types of agents. The most frequent motive for CAM use was the recommendation of friends or a close relative (53.4%) or a physician (1.6%). Only 42.5% discussed CAM use with their physicians. Satisfaction with CAMS was recalled for 37.1% . The most common reason given for that satisfaction was improvement of emotional or physical well-being, while ineffectiveness was the most common reason given for dissatisfaction. The average cost of CAM during the last month of life was $US 900. CAM use was associated with longer disease periods, primary cancers other than liver, biliary, and pancreatic, and need of support from physicians or religion. Conclusions: CAM use among cancer patients at the EOL was common, not discussed with physicians, and associated with expectation of cure. Expectations were generally unmet while the treatments were a financial burden. Further studies evaluating the effects of CAM at the EOL and factors that enhance communication with the physician are needed.

The aims of this study were to evaluate the differences in cancer prevalence and pain management between young and elderly patients. The patients were grouped into 3 groups. The prevalence of cancer pain was 50.0% in those younger than 65 years, 55.9% in those aged between 65 and 75, and 58.3% in those older than 75 years. The prevalence of cancer pain was higher for patients in advanced stages and with poor performance status. Using logistic regression analysis, we found that performance status has a significant correlation with cancer pain. Severe cancer pain occurred in 8.0% of the patient and was most prevalent in the advanced stage. Side effects of analgesics were observed in 24.5%. Cancer pain correlates with performance status and cancer stage but not significantly with age.

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35 mg/m(2)) intravenously on day 1 and 8 plus oxaliplatin (100 mg/m(2)) intravenously on day 1 every 3 weeks until disease progression or unacceptable toxicity.A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6 months (range, 1-48 months) were enrolled in this trial; 22 (64.7 %) patients had been exposed to both agents. Their median age was 58 years (range, 50-68 years). The overall response rate was 55.9 % (95 % confidence interval (CI), 38.3-73.5 %), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5 months (range, 9.2-50.7 months), the median progression-free survival for all patients was 5.3 months (95 % CI, 4.4-6.1 months) and the median overall survival was 13.8 months (95 % CI, 11.1-16.4 months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1 %) and diarrhea (17.6 %), respectively. Five patients (14.7 %) experienced febrile neutropenia.Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m(2) in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 400 mg/m(2) as a bolus followed by 600 mg/m(2) as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Four types of human hyaluronidases (rHuHyal-1, -2, -3 and -4) were transiently expressed and purified from Nicotiana benthamiana, and their biochemical characteristics were analyzed. The recombinant HuHyals were expressed via agrobacteria-mediated infiltration and generated and expressed in terms of micrograms per 5 leaves of N. benthamiana. Expressed recombinant HuHyals were purified using a His(6) tagging system and Ni column chromatography, respectively, at pH 8.0, after which the purified rHuHyals were concentrated for additional biochemical analyses. The four types of rHuHyals were allowed to react with hyaluronic acids and chondroitin sulfates. The biochemical properties of rHuHyal-1 fit those of the commercially available Hyal, PH-20, which was extracted from animal testes under acidic conditions (pH 3.5). However, rHuHyal-1 evidenced activity levels 2 to 6-fold greater than the three other rHuHyals (rHuHyal-2, -3 and -4) at pH 3.5. However, only rHuHyal-4 exhibited chondroitinase activity with both 6-S-chondroitin sulfate (chondroitin sulfate C) and 4-S-chondroitin sulfate (chondroitin sulfate A) as standard substrates. The results of zymography demonstrated that recombinant HuHyal 1 was modified by glycosylation, but Escherichia coli Hyal was not. This result demonstrated that plant-based rHuHyal was functionally active and evidenced biochemical characteristics and post-translational protein modifications similar to those of animal testis-derived Hyal.

Aim: Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms. Methods: We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea. Results: Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal-type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3- and 5-year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow-up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco-regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3- and 5-year disease-free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high-grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005). Conclusion: High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.

Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease.

Chemotherapy failure remains a significant medical problem in the treatment of neoplastic disease and is thought to be due to many different factors including membrane transport, p-glycoprotein in multidrug resistance, glutathione and its related enzymes, topoisomerase II and DNA repair. Glutatione is a major constituent of non-protein thiol and participates in detoxification of chemotherapy and radiation. Thus, glutathione concentration is correlated with sensitivity to alkylating agents and radiation, and increased in resistant cell lines. Buthionine sulfoximine (BSO) is an inhibitor of glutathione biosysthesis and may increase cytotoxicities of alkylating agents, including melphalan and cisplatin, and radiation in sensitive and resistant cell lines. We studied effects on cellular glutathione levels and cytotoxicites of cisplatin, carboplatin and radiation by BSO treatment in human stomach cancer cell line (SNU-1) and ovarian cancer cell line (OVCAR-3). The results were as follow: 1) After BSO treatment of 1 mM and 2 mM for 2 days, the intracellular thiol concentration was depleted to 75.7% and 76.2% in SNU-1, and 74.1% and 63.0% in OVCAR-3, respectively. 2) The intracellular thiol concentration in SNU-1 was depleted to 33.4% after BSO 2 mM for only 2 hours incubation and 71.5% after small amount of BSO (0.02 mM) for 2 days. 3) The recovery of intracellular thiol concentration required more than 3 days after BSO removal. 4) BSO inhibited partially the growth of SNU-1 and OVCAR-3. 5) The cytotoxicities of cisplatin and carboplatin were markedly enhanced both in SNU-1 and OVCAR-3 by BSO treatment. 6) The cytotoxicities of radiation was inceased in OVCAR-3 and SNU-1 by BSO treatment. Therefore, it is concluded that BSO can deplete effectively the intracellular thiol concentration and enhance the cytotoxicities of cisplatin, carboplatin and radiation.