Clinical Practice Guideline for Care in the Last Days of Life / 한국호스피스완화의료학회지

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients’ physical and mental symptoms, psychological support, appropriate deci-sion-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world. This guideline should be applied in a way that takes into account specific health care environments, including the resources of medical staff and differences in the available resources of each institution. This guideline can be used by all medical institutions in South Korea.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of Ethics Statement: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

The approval number of Institutional Review Board (IRB) was wrong in the article.

The impact of primary tumor location in patients with metastatic colorectal cancer: a Korean Cancer Study Group CO12-04 study

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

Do Korean Medical Schools Provide Adequate End-of-Life Care Education? A Nationwide Survey of the Republic of Korea's End-of-Life Care Curricula / 한국호스피스완화의료학회지

PURPOSE: Physician competency in end-of-life (EOL) care is becoming increasingly important. This study investigated the EOL care curricula in Korean medical schools.METHODS: Questionnaires were issued to the faculty members responsible for the EOL care curricula at each of the medical schools. These included questions on the structure and content of the curricula, teaching methods, and faculty members' attitudes to the curricula.RESULTS: Characteristics of the EOL care curricula were compiled from 27 (66%) of the 41 medical schools. All of the medical schools taught essential aspects of the EOL care curriculum either as a separate course or embedded within other medical education courses. The mean time spent on EOL care teaching was 10 hrs (range, 2~32 hrs). The most frequently taught topics were delivering bad news (100%) and symptom management (74%). When the palliative care education assessment tool (PEAT) was used to evaluate the curricula, a median of 11 PEAT objectives was met (range, 2~26; maximum, 83). More than two teaching methods were used in most of the curricula. However, lectures were the only teaching method used by three medical schools. 78% of faculty members who were responsible for curriculum reported dissatisfaction with it, whereas 18% believed that the time allotted to it was adequate. Only 7% of these faculty members believed that their students were adequately prepared to practice EOL care.CONCLUSION: There is a need to improve EOL care education in basic medical curricula and to take a more systematic approach to achieving learning outcomes.

Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

BACKGROUND: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea. METHODS: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea. RESULTS: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children. CONCLUSION: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis.

End-of-Life Care Practice in Dying Patients with Do-Not-Resuscitate Order: A Single Center Experience / 한국호스피스완화의료학회지

PURPOSE: End-of-life (EoL) decisions are challenging and multifaceted for patients and physicians. This study was aimed to explore how EoL care is practiced for patients with a do-not-resuscitate (DNR) order. METHODS: We retrospectively analyzed medical records of patients who died after agreeing to a DNR order in 2016 at a university hospital. Characteristics including cause of death, intensity of EoL care, and other factors were reviewed and statistically analyzed. RESULTS: Of total 375 patients, 170 patients (45.3%) died with malignancies, and 205 patients (54.6%) with other causes involving the central nervous system (19.2%), pulmonary (14.7%), cardiologic (6.7%) and infectious (6.4%) conditions. Both the cancer and non-cancer patient groups showed a short duration from DNR to death (median 3 days vs 2 days, P=0.629). An intensive care group comprising patients who received one or more intensive treatments such as ventilator (n=205) showed a higher number of non-cancer patients and a shorter duration from DNR to death than a group that withheld treatment before DNR (P < 0.05). CONCLUSION: EoL decisions were made very late by both cancer and non-cancer patients. About half of the patients did not have cancer, and two-thirds of them decided DNR during intensive treatment. To make a good EoL decision, a shared decision making with patients should be done at an earlier stage.

The Necessity for End-of-Life Care Education: A Preliminary Analysis with Interns at Two University Hospitals / 한국호스피스완화의료학회지

PURPOSE: This study was performed to explore the current state of end-of-life (EoL) care education provided to new interns at two university hospitals. METHODS: A questionnaire was given to incoming interns (N=64). The levels of acquired knowledge and experience of clinical observation were measured. Seven areas for self-assessment questions were identified and used to analyze the interns' attitudes towards EoL-related education and practice. RESULTS: On average, participants learned five elements (nine in total) from EoL-related classes and two (seven in total) from clinical observation. The most frequently educated element was how to deliver bad news (96.9%) in the classroom setting and how to control physical symptoms (56.5%) in clinical observation. Less than 20% received training on EoL care communication, including discussion of advanced directives. Compared with participants who had no EoL training, those who had EoL training showed positive attitudes in all seven categories regarding overall satisfaction, interest and preparedness in relation to EoL-care classes and practice. CONCLUSION: Although interns are responsible for caring of dying patients, their EoL training in classroom and clinical settings was very insufficient. Further research should be conducted to establish an education system that provides sufficient knowledge and training on EoL care.

Recent advances in the treatment of patients with colorectal liver metastases / 대한내과학회지

Colorectal cancer (CRC) is 2nd to 3rd common cancer and the annual incidence of CRC is increasing in Korea. The liver is the most frequent metastatic site of colorectal cancer and approximately one forth of patients presents with liver metastasis at initial diagnosis. Without treatment, patients with colorectal liver metastasis (CRLM) have a poor prognosis; however, long-term survival benefits and even cure have been reported in a portion of patients undergoing surgical resection of liver metastasis. In addition, advances in chemotherapeutic agents, imaging, and surgical techniques can increase the number of patients who are eligible for curative resection. In the past 10 years, combination chemotherapy with 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin or irinotecan was becoming the standard chemotherapy of treatment for metastatic CRC including CRLM. Furthermore, the combined use of targeted agents, such as cetuximab and bevacizumab, plus standard chemotherapeutics revealed more improvements in response rates and survival. Even in patients with resectable CRLM, perioperative chemotherapy with surgical resection could improve in progression free survival. However, the curable portion of patients with CRLM was still less than 20~30%, more detail management based on multidisciplinary team approaches should be needed.

Cancer of Unknown Primary Finally Revealed to Be a Metastatic Prostate Cancer: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.

A Case of Wernicke's Encephalopathy Following Fluorouracil-based Chemotherapy

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.

A Case of Type 2N von Willebrand Disease with Homozygous R816W Mutation of the VWF Gene in a Nepalese Woman / 대한진단검사의학회지

Type 2N von Willebrand disease (vWD) can be confused with hemophilia A due to decreased factor VIII levels and a bleeding tendency, and differential diagnosis is of importance for providing the optimal treatment and genetic counseling. For the accurate diagnosis of type 2N vWD, von Willebrand Factor (vWF) function tests, multimer assay and gene mutation analysis are needed. The patient was a 38-yr-old Nepalese woman with a history of bleeding manifestations from childhood, such as hemarthrosis, intramuscular hematoma, and menorrhagia. Family history revealed that her mother and elder brothers also had bleeding manifestations from childhood. When she had a laparotomy in 1991, she was diagnosed as hemophilia A with factor VIII level of 3.6% and was transfused with whole blood, factor VIII and cryoprecipitates. In June 2007, she was admitted to our hospital for further evaluation of bleeding tendency. Blood tests revealed normal CBC; bleeding time, 2 min; PT, 14.9 sec (11-14 sec); aPTT, 51.2 sec (24-38 sec); and factor VIII, 4.9% (50-150%). The prolonged aPTT was corrected by 1:1 mixing test to the levels of 106% and 84%, respectively, before and after 2 hr-incubation at 37degrees C. No abnormalities were found in the vWF antigen level (71.3%), ristocetin cofactor assay (130.4%), and multimer assay. Direct DNA sequencing of the VWF gene revealed homozygous missense mutation located in exon 19, c.2446C>T (p.Arg816Trp), confirming the diagnosis of type 2N vWD.

The Results of Danazol Therapy in Patients with Chronic Immune Thrombocytopenic Purpura Who Failed with Corticosteroid Therapy / 대한혈액학회지

BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.

Diagnostic Usefulness of the Janus Kinase 2 Mutation in non BCR/ABL Myeloproliferative Disorders

BACKGROUND: We investigated the Janus kinase 2 (JAK2) mutation and its diagnostic value in patients suffering with non BCR/ABL myeloproliferative diseases (nMPD) or other reactive conditions. METHODS: We reviewed the clinical records of 83 patients who underwent bone marrow (BM) examinations with suspect of nMPD. The diagnoses of nMPD were made based on the WHO criteria since 2001 and the PVSG criteria before 2001. The JAK2 mutation was examined by PCR in 54 patients whose BM samples were available. RESULTS: The JAK2 mutation was detected in 25 patients (46%); 12 of 26 patients with essential thrombocythemia (ET), 9 of 12 patients with polycyhtemia vera (PV), one of 7 patients with chronic idiopathic myelofibrosis (CIM) and one patient with unclassifiable MPD. Additionally, JAK2 mutation was detected in each one patient with secondary polycythemia and reactive thrombocytosis. These two patients and two other patients among the JAK2 mutated ET did not meet the WHO PV criteria due to their initial low hemoglobin levels. These patients had liver cirrhosis and hypersplenism due to Budd-Chiari syndrome (1), gastrointestinal bleeding (1) or the initial hemoglobin level was slightly below the level as provided by the criteria, but the level showed a rising pattern despite cytoreductive therapy (2). With the results of the JAK2 mutation available, 4 patients' disease could be re-diagnosed as PV. Finally, the positive rate of the JAK2 mutation was 81% in PV, 48% in ET and 14% in CIM. The presence of JAK2 mutation closely correlated with PV (p=0.001), leukocytosis (p=0.001) and an increased cellularity of BM (p=0.024). CONCLUSIONS: The JAK2 mutation may help differentiate nMPD from secondary cytosis. Therefore, it should be incorporated into the guidelines for the nMPD work-up for making a more accurate diagnosis and administering proper treatment.

Adenocarcinoma of Unknown Primary Site

BACKGROUND: Metastatic cancer of unknown primary site occupies 0.5~10% of all diagnosed cancer patients and includes various tumors with diverse responses to systemic chemotherapy. Adenocarcinoma of unknown primary site (ACUPS), the most common subtype, has no standard treatment, rarely responds to conventional treatment and has a poor survival rate. METHODS: The retrospective study was performed to investigate the clinical characteristics and the treatment outcomes of ACUPS. RESULTS: Eighty-one patients with ACUPS diagnosed at Samsung Medical Center from May 1995 to July 1999 were included. The median age was 58 years (range, 29~77). The common sites of metastases were the lymph node, liver, lung and bone in order. In 49 of 81 patients (60.5%), the dominant tumor location was below the diaphragm. The majority of patients (76 of 81) were initially treated with systemic chemotherapy including cisplatin. Responses were evaluable in 70 of 76. Eighteen of 70 patients (25.7%) responded to chemotherapy and complete remission was observed in 6 patients. The overall median survival of 81 patients was 5.6 months. The median survival of the responding patients was 18.3 months but the median survival of the nonresponding patients was 4.6 months (p<0.01). In univariate and multivariate analysis, age, performance status and response to initial chemotherapy were significant prognostic factors for overall survival. CONCLUSION: We observed poor response to the treatment and survival rate in ACUPS, but complete remission and long-term survival were observed in a small number of patients.

A Case of Chronic Neutrophilic Leukemia Associated with Increased Respiratory Burst Activity of Neutrophils / 대한혈액학회지

Chronic neutrophilic leukemia is a rare myeloproliferative disorder. We have experienced a typical case of chronic neutrophilic leukemia in a 76-year-old man who complained abdominal distension due to hepatosplenomegaly. White blood cell count of peripheral blood was 50,500/nL with 90% segmented neutrophils. The underlying disease for a leukemoid reaction had not been detected. Leukocyte alkaline phosphatase score and the serum levels of vitamin B12 and uric acid were elevated. Chromosome study showed a normal karyotype without Philadelphia chromosome or bcr/abl rearrangement. Phorbol myristate acetate-activated respiratory burst activity of neutrophils measured with chemiluminescence showed increased activity.

Expression of Vascular Endothelial Growth Factor and Interleukin-6 in Multiple Myeloma / 대한혈액학회지

BACKGROUND: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine involved in angiogenesis as selective mitogen for endothelial cells as well as potent permeability factor. And interleukin-6 (IL-6) is also known to be a growth factor of myeloma cells. To determine the role of angiogenesis, VEGF and IL-6 in the patients with multiple myeloma, the relationship between the level of VEGF expression, microvessel count (MVC), IL-6 expression in the bone marrow specimen of multiple myeloma patients and stage, response, survival duration were evaluated in 18 patients with multiple myeloma who underwent bone marrow biopsy. METHODS: VEGF expression, MVC and IL-6 expression were assessed by immunohistochemical stain with polyclonal antibody to VEGF, factor VIII related antigen and IL-6 respectively. RESULTS: VEGF expression was higher in multiple myeloma than that of control (61.4+/-34.4% vs 19.0+/-25.9%, P<0.001), and MVC was also higher in multiple myeloma than that of control (11.7+/-6.1 vs 6.2+/-3.8, P=0.005). IL-6 was expressed in 66.7% of multiple myeloma but not in control (P<0.001). Between high VEGF expression group and low VEGF expression group, there were no significant differences in the stage, response or survival. There were no significant differences between hypervascular group and hypovascular group. Also IL-6 expression was not a prognostic indicator. After treatment, VEGF expression, MVC and IL- 6 expression were decreased in the responder, but these differences were not statistically significant (P=0.23, P=0.07, P=0.06), probably due to limited number of cases. CONCLUSION: VEGF, angiogenesis and IL-6 can play a role in the pathogenesis of multiple myeloma. But we cannot confirm the prognostic role of those parameters. Further study with more cases in longer duration as well as prospective study would be necessary for the establishment of relationship between VEGF expression, neovascularization, IL-6 expression and disease severity and prognosis of multiple myeloma.

Clinical investigation of gastric MALT lymphoma / 대한내과학회지

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori (H. pylori) infection. Characteristics and treatment outcomes of 57 patients with gastric MALT lymphoma were analyzed. METHODS: Retrospective analysis of 57 cases of gastric MALT lymphoma who underwent treatment with various modalities at Samsung Medical Center from Mar. 1995 to Jul. 2000 was performed. RESULTS: The median age of the patients was 47 years (ranged from 22 to 75 years) and the ratio of males to females was 1.1:1. The presenting symptoms were abdominal pain, indigestion and GI bleeding. By Modified Ann Arbor system, stage IE accounted for 70.2%, stage II1E 14.0%, stage II2E 14.0%, and stage IV 1.8%, respectively. H. pylori had been evaluated histologically in 49 cases of which 81.6% was positive. Low grade histology accounted for 71.9% and high grade histology 28.1%. Treatment modalities included H. pylori eradication, surgery, chemotherapy, radiotherapy and their combination therapy. In one case, the patient was observed without treatment. Complete remission rate was 98.2%. H. pylori eradication alone resulted in lymphoma regression successfully in 20 out of 23 patients. With median follow-up of 33 months (3-61 months), median survival was not reached. Overall 3 year survival rate was 94.7%. CONCLUSION: Regardless of treatment modality, high survival rate (3 year survival rate 94.7%) was obtained. H. pylori eradication was feasible and safe in the cases of low grade, stage I, and H. pylori-positive lymphoma, and allowed stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy and side effects of H. pylori eradication.