Injectable Poloxamer Hydrogel Formulations for Intratympanic Delivery of Dexamethasone

Background@#In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX). @*Methods@#DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements. @*Results@#The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation. @*Conclusion@#P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release.

Chemotherapy in Advanced Gastric Cancer Patients Associated with Disseminated Intravascular Coagulation / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Little is known about the clinical features of advanced gastric cancer (AGC) combined with disseminated intravascular coagulation (DIC). The main objective of this study was to determine the clinical outcome of patients with AGC complicated by DIC. MATERIALS AND METHODS: We conducted a retrospective review of 68 AGC patients diagnosed with DIC at four tertiary medical centers between January 1995 and June 2010. RESULTS: Sixty eight patients were included. The median age was 55 years (range, 25 to 78 years). Nineteen patients received chemotherapy, whereas 49 patients received only best supportive care (BSC). The median overall survival (OS) of the 68 patients was 16 days (95% confidence interval [CI], 11 to 21 days). Significantly prolonged OS was observed in the chemotherapy group, with a median survival of 61 days compared to 9 days in the BSC group (p or =65 vs. <65; hazard ratio [HR], 0.38; 95% CI, 0.18 to 0.78; p<0.001), chemotherapy (BSC vs. chemotherapy; HR 0.31; 95% CI, 0.15 to 0.63; p<0.001), and previous chemotherapy (yes or no; HR, 0.49; 95% CI, 0.25 to 0.98; p<0.045) were consistently independent prognostic factors that impacted OS. CONCLUSION: Our study showed that patients with AGC complicated by DIC had very poor OS, and suggested that chemotherapy might improve OS of these patients.

Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. MATERIALS AND METHODS: One hundred twenty cancer patients with pain (numeric rating scale [NRS] > or = 4) and sleep disturbance (NRS > or = 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator\'s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. RESULTS: A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea. CONCLUSION: HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

The Effect of Bilaterally Alternating Auditory Stimulations on the Episodic Memory Retrieval / 신경정신의학

OBJECTIVES: Previous research has shown that bilaterally alternating eye movements enhance episodic memory retrieval. This effect has been considered an important mechanism of the therapeutic effects of eye movement desensitization and reprocessing (EMDR) treatment. We conducted this study in order to test the hypothesis that bilaterally alternating auditory stimuli would also have similar effects on episodic memory retrieval. METHODS: Thirty eight right-handed subjects participated in this study. Subjects learned words, and then received bilaterally alternating auditory stimuli (as experimental stimuli) or unilateral auditory stimuli (as control stimuli). Subsequently, they performed recognition memory task. Recognition accuracy, response bias, and mean response to hits were used for evaluation of episodic memory retrieval. Repeated measures analysis of variance was performed for statistical analysis. RESULTS: There was no significant effect of experimental conditions in recognition accuracy, the response bias, and mean response time to hits. CONCLUSION: Unlike the previous positive results of bilaterally alternating eye movements, we did not observe an enhancing effect of bilaterally alternating auditory stimuli compared to unilateral auditory stimuli on episodic memory retrieval. This result suggests the possibility that the therapeutic mechanisms of EMDR might differ according to modalities of bilateral stimulation.

Should we still use Camitta's criteria for severe aplastic anemia? / 대한혈액학회지

BACKGROUND: The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria. METHODS: 117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS). RESULTS: Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/microL, 12,000/microL, and 0.39%, respectively. In multivariate analyses, ANC or =500/microL (P=0.015, HR 2.694, 95% CI: 1.20-6.01) and age (P=0.015, HR 1.022, 95% CI: 1.00-1.04) were the significant factors for OS. CONCLUSION: ANC could be an essential, not an optional criterion for diagnosing SAA. This study suggests the possibility that the Camitta's criteria be modified. Studies in large cohorts are needed to transform the Camitta's criteria.

Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome / 대한혈액학회지

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

Patient Perception of Natural Orifice Transluminal Endoscopic Surgery in an Endoscopy Screening Program in Korea

PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new method of accessing intracavitary organs in order to minimize pain by avoiding incisions in the body wall. The aim of this study is to determine patients' acceptance of NOTES in Korea and to compare their views about laparoscopic surgery and NOTES for benign and malignant diseases. MATERIALS AND METHODS: The target number of total subjects was calculated to be 540. The subjects were classified into 18 sub-groups based on age groups, gender, and history of prior surgery. The questionnaire elicited information about demographic characteristics, medical check-ups, diseases, endoscopic and surgical histories, marital status and childbirth, the acceptance of NOTES, and the preferred routes for NOTES. In addition, the subjects chose laparoscopic surgery or NOTES for a hypothetical cholecystectomy and rectal cancer surgery, and responded to questions regarding the acceptable complication rate of NOTES, the appropriate cost of NOTES, and the reason(s) why they did not select NOTES. RESULTS: 486 of 540 patients (90.0%) who agreed to participate in this study completed the questionnaire. NOTES was preferred by the following patients: elderly; a history of treatment due to a disease; having regular check-ups; and a history of an endoscopic procedure (p<0.05). The most preferred route for NOTES was the stomach (67.1%). Eighty-four percent of the patients choosing NOTES responded that the complication rate of the new surgical method should be the same or lower than laparoscopic surgery. Vague anxiety over a new surgical method was the most common reason why NOTES was not selected in benign and malignant diseases (64% and 73%), respectively. CONCLUSION: Patients appear to be interested in the potential benefits of NOTES and would embrace it if their concerns about safety are met. We believe that qualified surgical endoscopists can meet these safety concerns, and that NOTES development has the potential to flourish.

The Influence of Bilateral Eye Movement on Recognition Memory Task Performance / 신경정신의학

OBJECTIVES: Recently, Interest has been increase on the cognitive and emotional effects of bilateral eye movement. However, there is little research related to the subject in Korea. In this study, we evaluated the effects of bilateral eye movement to memory. METHODS: There were a total of 24 subjects between the ages of 18 and 45. All were right-handed. The subjects first studied words, and then performed recognition memory task about the words after bilateral eye movement and eye fixation. The results (recognition accuracy, response bias, mean response to hits) were compared and analyzed. In addition, We evaluated whether the results differ according to the type of word. Repeated measure analysis of variance was performed for statistical analysis. RESULTS: The main effects on condition [F(1, 23)=9.39, p<0.05] and word type [F(1, 23)=33.727, p<0.05] in recognition accuracy were statistically significant. Also main effect of mean response time to hits was observed [F(1, 23)=66.482, p<0.05]. CONCLUSION: These results suggest that bilateral eye movement enhance recognition accuracy than eye fixation. In this study, bilateral eye movement that affects cognition were investigated.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin. MATERIALS AND METHODS: CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals. RESULTS: Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival. CONCLUSION: The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.

Prognostic implication of metastatic lymph node ratio in node-positive rectal cancer / 대한외과학회지

PURPOSE: The aim of this study was to evaluate the prognostic significance of the ratio between metastatic and examined lymph nodes (LNs) in patients with stage III rectal cancer. METHODS: A review was made of 175 (male, 98) patients with stage III rectal cancer of R0 resection. LN disease was stratified both by the American Joint Committee on Cancer/International Union Against Cancer nodal classification (pN) and by quartiles of the lymph node ratio (LNR). Disease-free survivals (DFS) were made using Kaplan-Meier curves and assessed by the log rank test and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Patients ranged in age from 29 to 83 (median, 60) years with median follow-up of 47 months (range, 13 to 181 months). months. There was a significant correlation between the number of metastatic LNs and the LNR (r = 0.8681, P < 0.0001). Cut-off points of LNR quartiles best to separate patients with regard to 5-year DFS were between quartile 2 and 3, and between 3 and 4 (LNR1, 2, and 3); the 5-year DFS according to such stratification was 89.6%, 55.8%, and 18.2% in LNR1, 2, and 3, respectively (P < 0.0001). Cox model identified the LNR as the most significant independent prognostic covariate; LNR2 showed 3.6 times (95% confidence interval [CI], 1.682 to 7.584; P = 0.0009) and LNR3, 18.7 times (95% CI, 6.872 to 50.664; P < 0.0001) more risky than LNR1. CONCLUSION: This study suggests that ratio-based LN staging, which reflects the number of LNs examined and the quality of LN dissection, is a simple and reliable system for prognostic LN stratification in patients with stage III rectal cancer.

Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes / 한국유방암학회지

PURPOSE: The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes. METHODS: Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes). RESULTS: The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade > or =3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred. CONCLUSION: These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.

Incidence and clinical characteristics of clonal cytogenetic abnormalities of acquired aplastic anemia in adults / 대한혈액학회지

BACKGROUND: Cytogenetic abnormalities (CAs) have been reported frequently in patients with otherwise typical aplastic anemia (AA), but their implications in the prognosis and in the evolution to hematologic malignancies are controversial. METHODS: We retrospectively analyzed 127 adult AA patients who had successful cytogenetic analysis at initial diagnosis. RESULTS: The patients were classified into 3 groups according to the initial and follow-up results of cytogenetic profiles. Group 1 included patients who had persistent AA with normal cytogenetic profiles (N=117); Group 2, those who had a normal cytogenetic profile at initial diagnosis but later acquired CA (N=4, 3.1%); and Group 3, those who had CA at the initial diagnosis, regardless of follow-up cytogenetic status (N=6,4.7%). In Group 2, 2 patients later developed CA without progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); the other 2 patients later progressed to AML. None of the patients in Group 3 progressed to AML or MDS. There was no significant difference in overall survival between Groups 1 and 3. CONCLUSION: AA patients with CA at initial diagnosis or follow-up may not be at greater risk for evolution to AML or MDS, or show shorter survival periods. Prospective studies and a larger patient samples are needed to establish the clinical relevance of CA.

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide / 대한혈액학회지

BACKGROUND: A combination of busulfan (Bu) and cyclophosphamide (Cy) has been used as a standard myeloablative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). Recent studies postulate that fludarabine (Flu) is a less toxic substitute for Cy. METHODS: Forty-two patients who were diagnosed with acute leukemia or myelodysplastic syndrome and received BuFlu (n=17) or BuCy (n=25) from August, 1999 to July, 2009 at Dong-A University Medical Center were retrospectively analyzed. RESULTS: The median follow-up duration was 39.75 months. The BuFlu group showed a lower incidence of mucositis (P=0.005), but there was no significant intergroup difference in the time of engraftment, nausea/vomiting, acute/chronic graft-versus-host disease, hepatic veno-occlusive disease, or hemorrhagic cystitis. Moreover, the 2 groups showed no significant difference in the cumulative risk of relapse, event-free survival, or overall survival. CONCLUSION: BuFlu administration can be employed as a preparative regimen for allogeneic HSCT and shows efficacy and transplant-adverse effects comparable to those of BuCy. However, randomized prospective studies in more patients are warranted.

A Case of 5-Fluorouracil Induced Encephalopathy / Journal of the Korean Cancer Association, 대한암학회지

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.

A Case of Pathologic Splenic Rupture as the Initial Manifestation of Acute Myeloid Leukemia M2

A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy.

Clinical Outcomes in Patients with Triple-negative Breast Cancer and Brain Metastases / 한국유방암학회지

PURPOSE: Patients with triple-negative breast cancer (TNBC) are known to carry an increased risk of distant metastasis and poor survival. The principal objective of this study was to investigate survival after brain metastases in patients with TNBC. METHODS: The authors retrospectively evaluated clinical data obtained from 66 patients who had been diagnosed with breast cancer and brain metastasis from 2003 to 2009. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were determined via immunohistochemical staining. TNBCs were defined as those that were ER-negative, PR-negative, and HER2-negative. The time interval from initial diagnosis to brain metastasis and overall survival after brain metastasis was evaluated via the Kaplan-Meier method. RESULTS: Twenty four (40.0%) of 60 patients were diagnosed with TNBC. The clinicopathologic characteristics did not differ between the TNBC and non-TNBC patients. The disease-free survival durations of the TNBC and non-TNBC subjects were 17.9 and 25.6 months, respectively (p=0.135). The time intervals from initial diagnosis to brain metastasis were 25.5 and 43.7 months, respectively (p=0.027). The time intervals from distant metastasis to brain metastasis were 8.4 and 19.5 months, respectively (p=0.006). Overall survival durations from brain metastasis to death were 4.3 and 7.6 months, respectively (p=0.046). CONCLUSION: Patients with TNBC were more likely to develop brain metastasis earlier, and exhibit poor overall survival. Triple receptor status may be utilized as a prognostic marker for breast cancer patients with brain metastasis.

Use of Antidepressants in Patients with Breast Cancer Taking Tamoxifen / 한국유방암학회지

Tamoxifen, a selective estrogen modulator has been used for more than three decades to treat all stages of estrogen receptor (ER)-positive breast cancer and to prevent the disease. Tamoxifen is a pro-drug that requires metabolic activation to 4-hydroxytamoxifen and 4-hydroxy-N-desmethyltamoxifen (endoxifen) to elicit its pharmacological activity. Endoxifen has identical properties and potency with 4-hydroxytamoxifen, but is present in concentrations up to 10-fold higher than 4-hydroxytamoxifen. The cytochrome P450 2D6 (CYP2D6) enzyme plays a key role in converting tamoxifen into its active metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Genetic variants in the CYP2D6 gene may result in CYP2D6 enzymes with reduced or null activity, thereby decreasing the anti-cancer effect. In addition to genetic inactivation of CYP2D6, inhibitors of CYP2D6, including some antidepressants to treat hot flashes or depression in patients with breast cancer, may also alter enzyme activity and negatively affect the outcomes of patients receiving adjuvant tamoxifen. This article reviews and discusses the following issues: tamoxifen metabolism, antiproliferative effects of tamoxifen and its metabolites, CYP2D6 genetic polymorphisms, treatment for hot flashes and depression in breast cancer, and the pharmacological interactions between tamoxifen and antidepressants via CYP2D6. Although routine CYP2D6 testing is not recommended yet, coadministration of potent or intermediate CYP2D6 inhibitors in women taking tamoxifen should be avoided.