Samyong Kim

Experiences and Attitudes of Patients With Terminal Cancer and Their Family Caregivers Toward the Disclosure of Terminal Illness

PURPOSE We investigated the experiences of cancer patients and their family caregivers who became aware that the cancer was terminal, how they became aware, and how they felt about disclosure of the information. PATIENTS AND METHODS In this cohort study, we administered questionnaires to 619 consecutive patients determined by physicians to be terminally ill and to their family caregivers. RESULTS A total of 481 patients and 381 family caregivers completed the questionnaire. A majority of patients (58.0%) and caregivers (83.4%) were aware of the patients terminal status. Approximately 28% of patients and 23% of caregivers reported that they guessed it from the patients worsening condition. The patient group was more likely than the caregiver group (78.6% v 69.6%) to prefer that patients be informed of their terminal status. Patients informed of their terminal diagnosis had a significantly better quality of life and fewer symptoms and had a lower rate of emotional distress than patients who guessed it from their worsening condition. Younger patients and patients who paid the treatment costs themselves were significantly more likely to want to be told when their illness was terminal. If the patient paid the treatment cost and was employed at the time of the cancer diagnosis, the family caregivers were more likely to prefer disclosure of terminal illness. CONCLUSION Most patients with terminal cancer and their family caregivers preferred disclosure, and patients who knew of their terminal diagnosis had a lower rate of emotional distress and a higher health-related quality of life.

A Comparative Trial of a Single Dose of Azithromycin versus Doxycycline for the Treatment of Mild Scrub Typhus

BACKGROUND Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments. METHODS We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens. RESULTS A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period. CONCLUSION The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.

Chemotherapy use and associated factors among cancer patients near the end of life.

Objectives: We investigated the frequency of chemotherapy use and its associated factors in patients in all age groups in the last year of life. Methods: We identified cancer patients who died in 2004 in any of 17 hospitals. We used demographic and treatment characteristics by computerized hospital information systems and by linking the identification numbers to the 2004 death registry. Results: 48.7% of patients in the last 6 months of life, 43.9% in the last 3 months, and 30.9% in the last month of life received chemotherapy. The frequency of chemotherapy use was lower for older patients. In those ≧65 years old, there was no difference between women and men in the proportion that received chemotherapy. For patients <65 years of age, a larger proportion of women than men received chemotherapy, and chemotherapy use was significantly less frequent for patients with refractory disease than for those with responsive disease. Patients dying at a relatively small hospital without a hospice inpatient unit were significantly more likely to receive chemotherapy. Conclusions: Despite the fact that most cancer patients are resistant to chemotherapy at the end of life, it was administered often to all age groups.

Impact of caregivers’ unmet needs for supportive care on quality of terminal cancer care delivered and caregiver’s workforce performance

Goals of workFamily caregivers play an important role in caring for cancer patients, but the impact of caregivers’ unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood.Patients and methodsWe identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL).ResultsCompared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P < 0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80–15.00), psychosocial support (aOR = 6.24; 95% CI 2.95–13.05), symptom management (aOR = 3.21; 95% CI 2.26–4.54), community support (aOR = 3.82; 95% CI 2.38–6.11), or religious support (aOR = 4.55; 95% CI 1.84–11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00–1.47), psychosocial support (aOR = 1.99; 95% CI 1.37–2.88), and religious support (aOR = 1.73; 95% CI 1.08–2.78) than those of patients receiving palliative hospice care.ConclusionsCaregivers’ unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.

Hyperfractionated radiotherapy with concurrent chemotherapy for para-aortic lymph node recurrence in carcinoma of the cervix.

PURPOSE To evaluate efficacy, toxicity, and patterns of relapse in patients treated with hyperfractionated radiotherapy (HFRT) with concurrent chemotherapy for para-aortic lymph node (PALN) recurrence of cervical carcinoma. METHODS AND MATERIALS Between September 1997 and October 2000, 12 cervical carcinoma patients with isolated PALN recurrence who had previously received radical or postoperative radiotherapy were treated with HFRT and concurrent chemotherapy. The initial FIGO stage was Stage IB in 4 (33%) patients, Stage IIA in 2 (17%), and Stage IIB in 6 (50%). The radiation field encompassed the gross recurrent PALN with the superior margin at the upper end of the T12 body and the inferior margin between L5 and S1. The fractionated dose was 1.2 Gy in 2 daily fractions, and the median total dose was 60 Gy. The weekly concurrent chemotherapy consisted of paclitaxel in 11 patients and cisplatin in 1. The median number of cycles of chemotherapy was 5. RESULTS The latent period to PALN recurrence from the time of initial treatment for all patients ranged from 2 to 92 months (median: 12 months). One month after treatment, the clinical tumor response evaluated was complete in 33% (4/12) and partial in 67% (8/12). The 3-year overall survival rate and median survival were 19% and 21 months, respectively. The latent period to PALN recurrence was the only significant prognostic factor; the median survival of patients who relapsed in < or =24 months from the initial treatment of cervical carcinoma was 13 months vs. 45 months for those relapsed at >24 months (p = 0.026). Grade 3-4 hematologic toxicity developed in 2 patients. Six (50%) patients experienced Grade 2 nausea. There were no late gastrointestinal or neurologic complications during the follow-up period. Subsequent distant metastases after PALN treatment developed in 58% (7/12). CONCLUSION HFRT of 60 Gy to PALN with concurrent chemotherapy could be regarded as an effective treatment modality without significant acute or late toxicity. Patients with a latent period >24 months until PALN recurrence had a more favorable survival rate than those with a latent period </=24 months. Subsequent distant metastasis after PALN recurrence was the main cause of death and is a problem to overcome in the future.

CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targeting

Gastric cancer is the fourth most common cancer, and the second-highest cause of cancer-related deaths worldwide. Despite extensive research to identify novel diagnostic and therapeutic agents, patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis, and treatment is dependent mainly on conventional cytotoxic chemotherapy. To improve the quality of life and survival of gastric cancer patients, a better understanding of the underlying molecular pathologies, and their application towards the development of novel targeted therapies, is urgently needed. Chemokines are a group of small proteins associated with cytoskeletal rearrangements, the directional migration of several cell types during development and physiology, and the host immune response via interactions with G-protein coupled receptors. There is also growing evidence to suggest that chemokines not only play a role in the immune system, but are also involved in the development and progression of tumors. In gastric cancer, CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment. CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion and metastasis, as well as indirectly by regulating angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on the roles of CXC chemokines and their receptors in the development, progression, and metastasis of gastric tumors, and discuss their therapeutic potential for gastric cancer.

The CXCR4 Antagonist AMD3100 Has Dual Effects on Survival and Proliferation of Myeloma Cells In Vitro.

Purpose AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro. Materials and Methods The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay). Results AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions. Conclusion AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.

Direct and Indirect Effects of Androgens on Survival of Hematopoietic Progenitor Cells In Vitro

Androgens remain a common treatment for certain type of anemia, based upon its myelostimulating effects; however, it has not been established whether androgens affect apoptosis of hematopoietic progenitor cells (HPCs). We investigated the effects of the androgens, such as testosterone, 5β-dihydrotestosterone (5-DHT), and oxymetholone, on apoptosis of normal hematopoietic progenitor cells in vitro. Androgens did not rescue normal bone marrow (BM) CD34+ cells and colony-forming cells (CFCs), other than mature erythroid CFCs, from apoptosis induced by serum- and growth factor deprivation. Oxymetholone did not affect growth factor-mediated survival of normal CD34+ cells or its inhibition by interferon-gamma (IFN-γ). In a standard methylcellulose clonogenic assay, low concentrations of oxymetholone and 5-DHT stimulated the clonal growth of colony-forming unit (CFU)-erythroid, but did not affect growth of CFU-granulocyte/macrophage or burst-forming unit-erythroid. Oxymetholone and 5-DHT stimulated the production of stem cell factor in normal bone marrow stromal cells (BMSCs) via transcriptional regulation. In agreement with this, oxymetholone-treated BMSCs better supported the survival of HPCs. These data indicate that survival-enhancing or growth-stimulatory effects of androgens on hematopoietic progenitor cells are minimal and mostly restricted to mature erythroid progenitors, and its myelostimulating effects could be attributed, at least in part, to the stimulation of production of hematopoietic growth factors in BMSCs.

Human rotavirus genotypes in hospitalized children, South Korea, April 2005 to March 2007.

Availability of new rotavirus vaccines highlights the need to maintain and enhance rotavirus strain surveillance. We collected stool samples from children with gastroenteritis admitted to eight hospitals in South Korea from April 2005 to March 2007. Of the 6057 samples collected, 1337 (22%) were positive for rotavirus by one of several antigen detection assays. G and P genotypes were identified for 1299 (97%) of rotavirus-positive specimens. G1P[8] (36%) was the most prevalent strain, followed by G3P[8] (16%), G4P[6] (8.9%) and G1P[6] (8.2%). G1P[8] was also the most prevalent strain in each hospital. Seasonal peaks of rotavirus infection were noted from November 2005 to April 2006 and January to March 2007. This large-scale surveillance study provides important insights into rotavirus genotype distribution and pattern changes in South Korea.

Adenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity

We report here that gene transfer using recombinant adenoviruses encoding interleukin (IL)-18 mutants induces potent antitumor activity in vivo. The precursor form of IL-18 (ProIL-18) is processed by caspase-1 to produce bioactive IL-18, but its cleavage by caspase-3 (CPP32) produces an inactive form. To prepare IL-18 molecules with an effective antitumor activity, a murine IL-18 mutant with the signal sequence of murine granulocyte-macrophage (GM)- colony stimulating factor (CSF) at the 5′-end of mature IL-18 cDNA (GMmIL-18) and human IL-18 mutant with the prepro leader sequence of trypsin (PPT), which is not cleaved by caspase-3 (PPThIL-18CPP32−), respectively, were constructed. Adenovirus vectors carrying GMmIL-18 or PPThIL-18CPP32− produced bioactive IL-18. Ad.GMmIL-18 had a more potent antitumor effect than Ad.mProIL-18 encoding immature IL-18 in renal cell adenocarcinoma (Renca) tumor-bearing mice. Tumor-specific cytotoxic T lymphocytes, the induction of Th1 cytokines, and an augmented natural killer (NK) cell activity were detected in Renca tumor-bearing mice treated with Ad.GMmIL-18. An immunohistological analysis revealed that CD4+ and CD8+ T cells abundantly infiltrated into tumors of mice treated with Ad.GMmIL-18. Huh-7 human hepatoma tumor growth in nude mice with a defect of T cell function was significantly inhibited by Ad.PPThIL-18CPP32− compared with Ad.hProIL-18 encoding immature IL-18. Nude mice treated with Ad.PPThIL-18CPP32− contained NK cells with increased cytotoxicity. The results suggest that the release of mature IL-18 in tumors is required for achieving an antitumor effect including tumor-specific cellular immunity and augmented NK cell-mediated cytotoxicity. These optimally designed IL-18 mutants could be useful for improving the antitumor effectiveness of wild-type IL-18.