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Little has been determined regarding the association between patients’ and families’ illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients’ illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.

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.

Background: Positive attitudes for end-of-life (EOL) care along with adequate education are key factors for the provision of quality EOL care. This national study was conducted to identify the factors that influence attitudes toward EOL care on medical students. Method: An anonymous survey was designed and administered to fourth-year medical students at all 41 medical schools in Korea. Topics related to EOL care were assessed in classroom teaching, bedside teaching, and feedback experiences during clinical clerkships. Seven questions for self-rated attitudes and affecting factors were analyzed toward EOL care. Results: With a response rate of 49.2%, the median number of topics recognized by the students as having been delivered was 5 of 11 topics in classroom lectures and 1 of 8 topics in clinical experience. Although few (21.2%) participants indicated that they felt ready for EOL care practice, nevertheless, most felt that they should have adequate knowledge of and preparation for clinical competency in EOL care. Several parameters including respondent’s demographics and exposure to EOL care topics in classroom and in bedside teaching influenced the responses to all 7 attitude questions. However, having more than 1 bedside experience was the only factor positively affecting all attitudinal measures. Conclusions: Clinical experience related to EOL care seems to be the utmost priory in fostering positive attitudes and competency among medical students.

Aim To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). Patients and methods Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial-mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. Results The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). Conclusion Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.

Context To respect a patient's wish for end-of-life care, “the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life” was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically. Objectives The objective of this study was to investigate awareness and attitudes toward ACP in South Korea. Methods A multicenter, nationwide cross-sectional study was conducted a survey regarding ACP among four groups that would have different positions and experiences: 1,001 cancer patients, 1,006 family caregivers, 928 physicians, and 1,005 members of the general public. Results A total of 16% of the general population, 33% of the patients and caregivers, and 61% of the physicians had knowledge of advance directives. More than 63% of the general population, above 72% of the patients and caregivers, and 97% of the physicians were willing to do so when the disease status was aggravated or terminal. The possibility for changing the plan, uncertainty as to whether directives would actually be followed, and psychological discomfort were common reasons for not wanting to engage in ACP. Routine recommendations for a specific medical condition, heightened accessibility, and health insurance support were common factors that could help facilitate ACP. Conclusion Our findings suggest that strategies for promoting ACP should reflect different perspectives among the general public, patients, family caregivers, and physicians. Public advocacy, resources for approaching and integrating ACP into routine health care, as well as systematic support provisions are needed.

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., Graphical Abstract

We conducted a phase II trial of 5-fluorouracil and oxaliplatin combination chemotherapy as a second-line treatment in unresectable/metastatic biliary tract cancer patients who had failed gemcitabine-based chemotherapy. Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m2 (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m2 (days 1, 2) every 2 weeks. Between March 2010 and June 2012, a total of 30 patients were enrolled in this study. Twenty-eight patients were measurable for treatment response. One achieved complete response, and one a partial response was observed. Overall response rate was 7.1 % (95 % confidence interval 0.9–23.5 %). The median progression-free survival was 1.6 months, and the median overall survival was 4.4 months. Grade 3–4 hematologic toxicities included neutropenia (6.7 %) and thrombocytopenia (3.4 %). The most common non-hematologic toxicity was neuropathy (22.2 %). However, the most common grade 3–4 non-hematologic toxicity was hyperbilirubinemia (5.0 %). There was one treatment-related death due to neutropenic infection. mFOLFOX3 as a second-line regimen has modest effect and tolerable toxicity in unresectable/metastatic biliary tract cancer patients who have been treated previously via gemcitabine-based chemotherapy.

Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients. One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G. With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4–15.6 months] of the G group, which was not significantly different for the median OS of 11.0 months (95 % CI 9.7–12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485). There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC patients.

Background & Aims The CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL). Methods We analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point was disease-free survival. DNA isolated from available tumor samples (n = 615) was used to determine CIMP status based on methylation patterns at the CACNA1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF , KRAS , and mismatch repair (MMR) status were also investigated. Results Of the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio = 1.36; 95% confidence interval: 1.01–1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio = 0.62; 95% CI: 0.37–1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00–1.89; P = .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P = .01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease-free survival times were comparable among all analyses. Conclusions Patients with stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin.

The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy.Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry.Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy.We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.

Objective: To generate a map of local recurrences after pancreaticoduodenectomy (PD) for patients with distal extrahepatic cholangiocarcinoma (DEHC) and to evaluate the adequate target volume coverage encompassing the majority of local recurrences when the clinical target volume (CTV) for pancreatic cancer was applied. Methods: We retrospectively reviewed the records of DEHC patients who underwent pancreaticoduodenectomy and had postoperative CT scans acquired between 1991 and 2015 available. The sites of local recurrence were delineated on individual CT scans, and then, mapping was manually performed onto template CT images. Coverage of each site of local recurrence was evaluated by applying the CTV defined according to Radiation Therapy Oncology Group (RTOG) consensus guidelines (CTVRTOG ) for target delineation in the postoperative treatment of pancreatic head cancer. Results: Of the 99 patients, 36 patients had a total of 62 local relapses identifiable by postoperative CT scans; the relapses were the most frequent in the choledochojejunostomy (CJ) site, 11 sites (17.7%); para-aortic area, 10 sites (16.1%), superior mesenteric artery area, 10 sites (16.1%); and portal vein area, 9 sites (14.5%). 21 sites (33.9%) were not covered by the CTVRTOG, and the most common site of local recurrence outside the CTVRTOG was the CJ site. Conclusion: When mapping of local relapses was evaluated according to the CTVRTOG, the choledochojejunostomy site was identified as a high-risk area of local recurrence but was insufficiently covered within the CTVRTOG. These findings may help construct a target volume for postoperative radiotherapy in DEHC. Advances in knowledge: Mapping local recurrences can aid in defining appropriate target volume for postoperative radiotherapy in DEHC.

To investigate the significance of carbohydrate antigen 19-9 (CA19-9) levels for survival in locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT).We retrospectively reviewed data from 97 LAPC patients treated with CCRT between 2000 and 2013. CA19-9 levels (initial and post-CCRT) and their changes [{(post-CCRT CA19-9 level - initial CA19-9 level)/(initial CA19-9 level)} × 100] were analyzed for overall survival. A cut-off point of 37 U/mL was used to analyze initial and post-CCRT CA19-9 levels. In order to define an optimal cut-off point for change in CA19-9 level, the maxstat package of R was applied.Median overall survival was 14.7 months (95% CI 13.4-16.0), and the 2-year survival rate was 16.5%. The estimated optimal cut-off point of CA19-9 level change was 94.4%. On univariate analyses, CA19-9 level change between initial and post-CCRT was significantly correlated with overall survival (median survival time 9.7 vs 16.3 months, p 0.001). Multivariate analyses confirmed that CA19-9 level change from initial to post-CCRT was the only prognostic factor (p 0.001).Change in CA19-9 level between initial and post-CCRT was a significant prognostic marker for overall survival in LAPC treated with CCRT. A CA19-9 level increase94.4% might serve as a surrogate marker for poor survival in patients with LAPC undergoing CCRT, and the prognostic power surpassed other CA19-9 variables including initial and post-CCRT values.

ObjectivesThis study determined attitudes of four groups—Korean patients with cancer, their family caregivers, physicians and the general Korean population—towards five critical end-of-life (EOL) interventions—active pain control, withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active euthanasia and physician-assisted suicide.Design and settingWe enrolled 1001 patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241 members of the general population and 928 physicians from each of the 12 hospitals and the Korean Medical Association. We analysed the associations of demographic factors, attitudes towards death and the important components of a ‘good death’ with critical interventions at EoL care.ResultsAll participant groups strongly favoured active pain control and withdrawal of futile LST but differed in attitudes towards the other four EoL interventions. Physicians (98.9%) favoured passive euthanasia more than the other three groups. Lower proportions of the four groups favoured active euthanasia or PAS. Multiple logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to 2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with preference for active pain control. Attitudes towards death, including belief in being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling ‘life was meaningful’ (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to 4.15). Believing ‘freedom from pain’ negatively predicted preference for passive euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, ‘not being a burden to the family’ was positively related to preferences for active euthanasia (aOR 1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89).ConclusionGroups differed in their attitudes towards the five EoL interventions, and those attitudes were significantly associated with various attitudes towards death.

This study evaluated the outcome of salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer.We performed a retrospective review of 23 extrahepatic bile duct cancer patients who underwent radiotherapy with or without concomitant chemotherapy for isolated locoregional recurrence after radical surgery between August 2001 and September 2013. The median disease-free interval was 11.8 months. Salvage radiotherapy was delivered to the recurrent tumour with or without initial operation bed up to a median dose of 54 Gy (range, 45-60). 18 patients received concomitant chemotherapy.The median follow-up period was 14.2 months for all patients, and 48.8 months for survivors. The median overall survival and progression-free survival (PFS) were 18.4 (range, 4.4-114.6) and 15.5 months (range, 1.6-114.6), respectively. On multivariate analysis, the use of concomitant chemotherapy was a favourable prognostic factor for PFS (p = 0.027), and prolonged disease-free interval (≥1 year) was associated with a significantly poor overall survival (p = 0.047). Grade 3 or higher toxicities did not occur in follow-up period.Salvage radiotherapy showed promising survival outcomes in locoregional recurrence of extrahepatic bile duct cancer. Our results indicated that concomitant chemotherapy was associated with improved PFS. Concurrent chemoradiotherapy can be a viable salvage treatment option in selected patients. Advances in knowledge: Locoregional recurrence is the most common pattern of failure after radical resection in extrahepatic bile duct cancer. In this study, salvage radiotherapy showed favourable survival outcomes without severe complications in locoregionally recurrent extrahepatic bile duct cancer patients.

SummaryEvaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients’ diagnoses were essential thrombocythemia (ET n=146), polycythemia vera (PV n=120), primary myelofibrosis (n=12), and unclassifiable MPN (MPNu n=5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p=0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p=0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

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 37°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. (Korean J Lab Med 2008;28:258-61)

Objective. To evaluate the efficacy of intravenous lorazepam as premedication for bone marrow aspiration and biopsy (BMAB). Design. Randomized, double-blind, placebo-controlled. Patients. One hundred and thirty-eight consenting patients planned to receive BMAB. Intervention. Patients were randomly assigned to receive either intravenous lorazepam 1 mg or placebo just prior to BMAB. Setting. Tertiary referral center, inpatient setting. Outcome Measures. A questionnaire was used to determine the patient perception about the procedure and pain at baseline, which was completed just after the procedure, and the next day after the BMAB. Pain was rated using a 10-cm linear visual analog scale (VAS). Results. The mean VAS scores measured during the BMAB examination were 6.0 for lorazepam vs 6.2 for placebo. Few adverse events were noted during intravenous lorazepam administration. The patients in the lorazepam group were more likely to accept the next BMAB (P = 0.044). Conclusion. Intravenous lorazepam was safe in patients undergoing BMAB and was more effective than placebo in enhancing cooperation during BMAB and willingness to undergo another procedure. However, use of lorazepam 1 mg provided no reduction in the pain associated with BMAB. Further studies should focus on providing appropriate analgesia for this potentially painful procedure.

Mapping of brain perfusion using bolus tracking methods is increasingly used to assess the amount and severity of cerebral ischemia in acute stroke. Using relative perfusion maps, however, it is difficult to identify the tissue at risk-maximum (TARM) of infarction with sufficient reliability and reproducibility.We analysed 76 perfusion computed tomography (PCT) derived maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) in 40 acute stroke patients using multidetector row technology and standard software (Somatom VolumeZoom, Siemens, Germany). 'Window narrowing' of the color maps was performed until color homogenisation of the contralateral unaffected hemisphere was reached. Tissue still depictable on the affected hemisphere after sufficient window narrowing was defined as the TARM. We analysed presence and size of the TARM on PCT maps, its relative perfusion values by comparison with contralateral, mirrored tissue, and its correlation with occurrence and final size of cerebral infarction on follow-up imaging.An ischemic area was visible in 64, 58.9 and 72.6% on the conventional CBF, CBV and TTP maps, respectively. After window narrowing, a TARM was present in 56.8, 54.1 and 63.0% of slices comprising 11.9, 11.6 and 21.1% of the ipsilateral hemisphere (CBF, CBV and TTP), respectively. The relative perfusion values were 38.7 (CBF) and 43.0% (CBV) for the entire ischemic area and 11.3 (CBF) and 13.3% (CBV) for the TARM. Definite cerebral infarction was visible on 68.1% of the target slices comprising 23.7 +/- 22.9% of the ipsilateral hemisphere. The size of the TARM correlated slightly better with the final infarction size (r=0.74-0.82) than the entire ischemic area (r=0.61-0.79). With respect to the occurrence of cerebral infarction, the presence of a TARM on CBF maps showed the best positive (97.9%) and negative (72.7%) predictability.On PCT maps, window narrowing provides a standardized display of the TARM in peracute stroke. The severely reduced values of relative CBF and CBV suggest the TARM to indicate tissue most prone to infarction.

The objective of this retrospective study was to investigate clinical features and treatment outcomes in patients with angioimmunoblastic T-cell lymphoma (AITL), data of which were collected over a 15-year period. Sixty-five patients diagnosed with AITL were included in the study. About half of the patients (46.2%) presented with poor performance status (ECOGor = 2); 72.3% of patients belonged to high intermediate or high-risk of IPI and same proportion belonged to Class 2 of PIT (Prognostic index for PTCL-U), and most patients (95.4%) were diagnosed at an advanced stage. At diagnosis, 27 patients (41.5%) presented with malignant pleural effusion, and 22 patients (33.8%) had skin involvement. Most of the initial chemotherapy regimens were anthracycline-based (88.2%). Overall response rate to initial chemotherapy was 86.2% (64.7% of complete response, 21.5% of partial response). The median progression-free survival and overall survival of all patients was 7.1 months (95% CI, 2.8 - 11.4) and 15.1 months (95% CI, 6.7 - 23.5), respectively. Age, performance status, and PIT scores were predictive prognostic factors for survival. In conclusion, although AITLs showed a good response to the initial chemotherapy, their response durations were short; therefore, chemotherapy for AITL should be modified or intensified as in high-dose chemotherapy.

Nodal marginal zone B-cell lymphoma (NMZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and the optimal treatment modality have not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of NMZL. Thirty-six patients who were histologically diagnosed as NMZL were included in the analysis. Fifty-three percent of the patients had localized disease (stages I and II), and 21.2% (7/33) had bone marrow involvement at presentation. B symptom was present in only three patients (8.3%). Most patients were categorized as low or low-intermediate risk group by international prognostic index (IPI) (77.1%). Majority (94.4%) of the patients with localized disease achieved complete remission (CR) after the initial treatment. Of the seven patients with disseminated disease, who were treated with anthracycline-based chemotherapy, four patients achieved CR. Of the seven patients who received nonanthracycline-based chemotherapy, no patient achieved CR. After the median follow-up duration of 36 months, the median progression-free survival (PFS) was 3.9 (95% CI; 2.9-5.6) years, and the estimated 5-year PFS and overall survival rates were 47.2 and 82.7%, respectively. The significant predictive factors for PFS were performance status, advanced stage, and follicular lymphoma IPI (FLIPI) in this study. This clinical feature is similar to FL rather than to MZL-MALT type.

The selection of chemotherapeutic regimens is challenging for metastatic breast cancer (MBC) patients whose diseases have failed to respond to anthracyline and taxane. Capecitabine has advantages of oral administration and favorable toxicity profiles. This study was conducted to evaluate the efficacy of capecitabine and to identify the subgroup of patients who would potentially have benefit from capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC. Female patients with MBC who had been previously treated with anthracycline and taxane received oral capecitabine 2500 mg/m(2) divided in two doses daily for 2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total of 38 patients were enrolled. Among the 36 evaluable patients, one patient achieved a complete response (CR), 9 patients had partial responses (PRs), and 13 patients had stable diseases (SDs). Response rate was 26% [95% confidence interval (CI), 12-40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95% CI, 45-77%). The median follow-up duration was 27.8 mo. The median duration of response was 8.9 mo, the median time to progression was 4.6 mo, and the median overall survival was 18.1 mo. The major toxicities were hand-foot syndrome, diarrhea, and emesis. There was no treatment-related death. The predictors of better overall survival were positivity of hormone receptor, disease-free survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number (

Combined chemoradiotherapy (CRT) is the standard treatment modality for limited-stage small-cell lung cancer (LSCLC), but the optimal timing of radiation is controversial. Prolonged oral etoposide has the advantage of prolonged exposure, which possibly leads to improved clinical outcome. We conducted a phase II trial of early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy for previously untreated LSCLC.Chemotherapy was given for six cycles, each consisting of oral etoposide (50 mg/m(2) daily from day 1 to 14) and intravenous cisplatin (75 mg/m(2) on day 1), every 3 weeks. Thoracic radiation therapy was given from day 1 of the first cycle of chemotherapy, administered at 2.0 Gy in 22 daily fractions to a total dose of 44 Gy.Forty-four patients were enrolled. The median age was 60 years (range, 42-77 years), including 15 patients (34%) over 65 years-of-age. We observed a complete response rate of 52% (95% CI, 37-67%), and an overall response rate of 88% in an intent-to-treat (ITT) analysis. Median overall survival was 14.9 months (95% CI, 11.4-18.3 months) and the median time to progression was 10.8 months (95% CI, 9.3-12.4 months) for the ITT population. In 220 cycles, grade 3-4 neutropenia was observed in 48% of cycles and grade 3-4 thrombocytopenia in 30% of cycles. Neutropenic fever was observed in 18 patients (41%).Early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy with prolonged oral etoposide and cisplatin failed to show any improvement in survival compared with other CRT regimens.

Clinically silent circulating microembolic signals (MES) can be identified by transcranial Doppler ultrasound (TCD). It is not yet clear whether their occurrence is always linked to the presence of embolic sources. 24 terminally ill patients (7 women, 17 men; mean age 68 years) were investigated by TCD of the middle cerebral arteries. These findings were correlated with a complete post-mortem examination of potential embolic pathways. Four patients out of the 24 under investigation showed MES, 2 of them bilaterally. All these 4 MES-positive patients had a definite embolic source, i. e. bilateral carotid artery occlusive disease, endocarditis with thrombotic valvular adhesions and severe plaques in the aortic arch, dilated left atrium and a patent foramen ovale, or severe plaques in the aortic arch and a dilated left atrium, respectively. In the investigated patient group, we could demonstrate that MES can only be found when an embolic source is present. The finding of MES justifies an extensive clinical and laboratory search for potential embolic sources including extracranial and intracranial colour-coded duplex ultrasound, ECG, Holter-ECG, and TEE.

Carotid bruits are supposed to indicate the presence of high-grade common carotid or extracranial internal carotid artery stenosis in a large proportion of patients. Using a stethoscope, we prospectively auscultated 273 carotid arteries of 145 patients blinded to the results of a complete extracranial and intracranial Doppler investigation including extracranial color-coded duplex ultrasound. Fifty-four arteries showed stenosis of > or = 50%-99%, or occlusion of the extracranial internal or the common carotid artery. In 25 of these arteries, a bruit was present. In 9 out of 16 patients with extracranial stenosis from 70%-99%, a bruit was detected. In one additional patient with a middle-grade external carotid artery stenosis, a bruit was also present. In seven additional patients, a bruit was present in the absence of any carotid artery stenosis, cardiac vitium or goiter. The sensitivity of carotid auscultation for the detection of a 70%-99% stenosis of the common or extracranial internal carotid artery was 56% and specificity was 91%. The positive predictive value of a bruit found during carotid auscultation was 27%, and the negative predictive value of a normal auscultation was 97%. Carotid auscultation is a useful screening procedure in the detection of carotid stenosis or occlusion, but requires confirmation by carotid ultrasound.

To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer.From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45-61 Gy).With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100-0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219-1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051-18.344; and HR for R2 18.551, 95% CI 3.680-93.520; p 0.001) and OS (HR for R1 1.816, 95% CI 0.853-3.867; and HR for R2 3.564, 95% CI 1.175-10.809; p = 0.054).RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group.

The aim of the present study is to evaluate the kinetics of CD34(+) cells and investigate the potential modulation of CD44 and CD31 expression on CD34(+) cells during continuous i.v. administration of G-CSF, thus to elucidate the possible mechanism of peripheral blood progenitor cell (PBPC) mobilization. Fifteen healthy donors were enrolled in this study. G-CSF (10 microg/kg/day) was administered for four consecutive days through continuous 24-h i.v. infusion. For measurement of complete blood counts, CD34(+) cell levels and their expression of CD44 and CD31, PB sampling was performed immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, and 120 h of G-CSF administration. The percentage and absolute number of CD34(+) cells significantly increased at day 3 (0. 55 +/- 0.09%, 51.12 +/- 24.83 x 10(3)/ml) and day 4 (0.47 +/- 0.09%, 46.66 +/- 24.93 x 10(3)/ml), compared to the steady-state level (0. 06 +/- 0.09%, 2.03 +/- 5.69 x 10(3)/ml). At day 3 to day 5 following the onset of G-CSF administration, a strong decrease of CD44 and CD31 expression was observed on mobilized CD34(+) cells compared to controls: the relative fluorescence intensity of CD44 and CD31 was, respectively, 50%-70% and 40%-90% lower than that of controls. We conclude that continuous i.v. administration of G-CSF apparently results in more rapid mobilization of CD34(+) cells, and downregulation of CD44 and CD31 on CD34(+) cells is likely to be involved in the mobilization of PBPC after treatment with G-CSF.

Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer.Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP).Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis.Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.

Purpose When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons. Patients and Methods Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC—either docetaxel 60 mg/m2 every 3 weeks or irinotecan 150 mg/m2 every 2 weeks—was left to the discretion of investigators. Primary end point was overall survival (OS). Results Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116). Conclusion To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.

S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.

To examine the current practices relating to do-not-resuscitate (DNR) orders for terminal patients with cancer at teaching hospitals in Korea.The records of 387 deaths from January 1 to December 31, 2005 at four cancer centers were identified and reviewed to assess the DNR delineation. Basic demographics, circumstances surrounding the establishment of the DNR directive, the percentage of orders for identified populations, and the time interval between DNR consent and death were evaluated.An order of DNR consent was obtained from 296 patients (76%) of a total of 387 patients. All DNR consents were made between the physician and family, without involving the patient. Written preprinted DNR consent forms were used in 169 (57%) cases and 127 patients (43%) had verbal DNR permission. DNR consent was interpreted in two ways: one forbade resuscitation in two hospitals and the other implied limited care in two other hospitals. A unilateral physician decision to withhold cardiopulmonary resuscitation (CPR) was decided for 62 (16%) patients. Terminal CPR was performed on 29 (7%) patients. DNR discussion was made within 7 days of the day of death on 228 (77%) patient among the 296 DNR consenting patients.From our teaching-hospital-based analysis of terminal cancer patients in Korea, consent for a DNR order was common. However, DNR order forms were not standardized and lacked room to document patient involvement in the decision. Usually the DNR decision was made within last days of the patient's life. Our results reflect the need for the improvement of end-of-life care decisions in Korea.

CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37–86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211–.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630–3.393; P = .377) had no prognostic significance for survival. CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

Intestinal marginal zone B-cell lymphoma of the MALT type (I-MZL) is a relatively uncommon form of lymphoma. Twenty-seven patients with histologically-confirmed I-MZL were analyzed. The patients initially presented with abdominal pain (62.9%), and diarrhea (22.2%). The most common involved site was the ileo-caecal area (40.7%). Musshoff's stage I(E), II(E)1, II(E)2, III(E) and IV were present in 44%, 15%, 11%, 7.4% and 22% respectively. Sixty-three percent were in the low-risk group according to the Follicular Lymphoma International Prognostic Index. Complete response and partial response were achieved in 82% and 4% patients. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were 86% and 54%. Stage > or = II(E)2 was determined to be a poor prognostic factor for PFS and OS. I-MZL commonly manifests in an early-stage, low-risk state and tends to respond well to local and systemic treatment with favorable prognosis. I-MZL tends to be an indolent disease - characterized by prolonged survival with frequent relapses, similarly to other site MZLs.

Neurofibromatosis type 1 (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous disorder characterized by abnormal skin pigmentation (café au lait spots and axillary freckling), cutaneous and plexiform neurofibromas, skeletal dysplasias, and Lisch nodules (pigmented iris hamartomas). Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesenchymal origin in the gastrointestinal tract, mesentery, omentum, and retroperitoneum. Here, we report a case of GIST in the ileum of a 76-year-old woman previously diagnosed as NF-1. She was admitted due to sudden onset of abdominal pain. Contrast enhanced CT scan revealed a moderately defined, peripherally enhanced soft tissue mass of about 8.8 x 7.3cm, originating from the small bowel in the left of the abdomen. Surgical excision was performed and the tumor was found to be composed of tumor cells that were positive for c-kit protein. The patient started imatinib treatment a month later, but stopped medication due to dyspepsia after a few months and eventually progressed after 18 months.

To assess detection of stroke and prediction of extent of infarction with multimodal computed tomographic (CT) evaluation (unenhanced CT, perfusion CT, and CT angiography) in patients suspected of having acute stroke.Forty-four consecutive patients with a mean National Institutes of Health Stroke Scale score of 10.45 and suspected of having ischemic stroke of the anterior circulation were examined with multi-detector row CT within 8 hours (mean, 3.05 hours) of onset of symptoms. All evaluations were performed with the knowledge that acute stroke was suspected but without detailed clinical information. The extent of ischemia or final infarction on the baseline unenhanced CT scan and follow-up images was assessed with the Alberta Stroke Program Early CT score. Different perfusion maps and follow-up images were assessed to determine the percentage of the ischemia-affected hemisphere. Each component, as well as the multimodal CT evaluation, was compared with follow-up unenhanced CT scans or magnetic resonance images after a mean time of 2.32 days.Multimodal CT revealed true-positive findings in 30 of 41 patients and true-negative findings in three, resulting in a sensitivity of 78.9%. Unenhanced CT, CT angiography, and perfusion CT showed sensitivities of 55.3%, 57.9%, and 76.3%, respectively. In eight patients, small infarctions (mean size, 1.47 cm) that were proved at follow-up were missed with all modalities at initial multimodal CT. With perfusion CT, four of these small infarctions were missed within the white matter of the section levels. Maps of cerebral blood flow showed the best correlation with the final size of infarction with an r(2) value of 0.71.The presented multimodal CT evaluation improves detection rate and prediction of the final size of infarction in comparison with unenhanced CT, CT angiography, and perfusion CT alone.

Background: Extrapulmonary small-cell carcinoma (EPSCC) has been recognized as a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. This study aimed to review the clinical features, therapy and natural course of patients with EPSCC in Oriental single-institution series. Methods: We retrospectively reviewed the medical records of patients with SCC between September 1995 and December 2002. Study eligibility required that patients had pathologically proven SCC in sites other than lung and normal radiological findings of the chest and normal sputum cytology or negative bronchoscopic findings. Results: Twenty-four patients with EPSCC were identified and primary sites were various: uterine cervix in seven (29%), urinary bladder in five, colon or rectum in three, kidney in two and stomach, esophagus, pancreas, common bile duct, larynx, parotid gland, thymus in one each. Sixteen patients (66.7%) had limited disease (LD) and eight had extensive disease (ED). Patients with ED received mostly platinum-based chemotherapy, for which the response rate was 57%, but showed an aggressive natural history, with median overall survival (OS) of 9.2 months. Patients with LD were treated with a variety of therapeutic modalities. LD SCC of the cervix showed a favorable clinical course, with five patients being disease-free with a median follow-up of 28.4 months. Patients with LD SCC of sites other than cervix had an aggressive course with a median OS of 9.6 months. Conclusion: EPSCC was identified in various sites, with the most common primary site being the uterine cervix. Regardless of the primary site or disease stage, EPSCC of sites other than cervix was usually a fatal disease with a discouraging outcome for various treatment modalities.

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

Background and Purpose— With new CT technologies, including CT angiography (CTA), perfusion CT (PCT), and multidetector row technique, this method has regained interest for use in acute stroke assessment. We have developed a score system based on Multimodal Stroke Assessment Using CT (MOSAIC), which was evaluated in this prospective study. Methods— Forty-four acute stroke patients (mean age, 63.8 years) were enrolled within a mean of 3.0±1.9 hours after symptom onset. The MOSAIC score (0 to 8 points) was generated by results of the 3 sequential CT investigations: (1) presence and amount of early signs of infarction on noncontrast CT (NCCT; 0 to 2 points), (2) stenosis (>50%) or occlusion of the distal internal carotid or middle cerebral artery on CTA (0 to 2 points), and (3) presence and amount of reduced cerebral blood flow on 2 adjacent PCT slices (0 to 4 points). The predictive value of the MOSAIC score was compared with each single CT component with respect to the final size of infarction and the clinical outcome 3 months after stroke by use of the modified Rankin Scale (mRS) and the Barthel Index (BI). Results— Among the CT components, PCT showed the best correlation to infarction size ( r =0.75) and clinical outcome ( r =0.60 to 0.62) compared with NCCT ( r =0.43 to 0.58) and CTA ( r =0.47 to 0.71). The MOSAIC score showed consistently higher correlation factors ( r =0.67 to 0.78) and higher predictive values (0.73 to 1.0) than all single CT components with respect to outcome measures. A MOSAIC score Conclusions— The MOSAIC score based on multidetector row CT technology is superior to NCCT, CTA, and PCT in predicting infarction size and clinical outcome in hyperacute stroke.

A phase II study was performed to evaluate the clinical efficacy and toxicity of oxaliplatin combined with uracil and tegafur (UFT) in patients with advanced colorectal cancer previously treated with a fluoropyrimidine-based regimen. From January to December 1999, 34 patients were enrolled in this study. Patients received intravenous oxaliplatin 130 mg/m2 on day 1 and daily oral UFT 350 mg/m2 in 3 divided doses for 21 days and repeated every 21 days. Thirty-one of 34 patients were assessable for response and 32 patients for toxicity. Partial response was observed in four patients and stable disease in six patients. The response rate was 12.9% (95% CI, 3.6-29.8%) and median duration of response was 17 weeks. The median overall survival and progression-free survival of all patients were 26 weeks (range, 3-90+ weeks) and 9 weeks (range, 3-56 weeks), respectively. Sensory neuropathy was the most common toxicity, but there was no severe toxicity (>grade II) except for a case of grade III neutropenia. We conclude that oxaliplatin and UFT combination chemotherapy was well tolerated without significant toxicities. The results of this trial will serve as the basis for designing new clinical trials with a different dose or schedule.

Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC.Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles.Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months.Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.

Cardiac right-to-left shunts (RLS) can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents, such as Echovist-200 or Echovist-300 in conjunction with a Valsalva maneuver (VM) as provocation procedure. Both Echovist preparations are in use. Currently, the appropriate timing of the VM is still under debate.Sixty-four patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) no VM, (2) VM for 5 s starting with the beginning of Echovist-300 injection, (3) VM for 5 s starting 5 s after the beginning of Echovist-300 injection, (4) VM for 5 s starting 10 s after the beginning of Echovist-300 injection, and (5) VM for 5 s starting 5 s after the beginning of Echovist-200 injection.In 27 patients, an RLS was demonstrated by both TEE and contrast TCD (shunt-positive). Twenty-two patients were negative in both investigations, no patient was positive on TEE but negative on TCD, 15 patients were only positive on at least one TCD investigation but negative on TEE. Tests 3 and 5 were the most appropriate ones; test 3 was slightly superior to test 5.TCD using Echovist-300 or Echovist-200 is a sensitive method to identify TEE-proven cardiac RLS. To achieve the best diagnostic accuracy, the VM should be performed for a duration of 5 s starting at 5 s following the beginning of contrast injection.

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.

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.