Comparison of three risk stratification models for non-clear cell renal cell carcinoma patients treated with temsirolimus as first-line therapy

Background/Aims@#For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. @*Methods@#This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. @*Results@#Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). @*Conclusions@#All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Freezing and Washing of Red Blood Cells Using Haemonetics ACP 215 / 대한수혈학회지

BACKGROUND: The use of a functionally closed system for the glycerolization and deglycerolization of red blood cells (RBCs) allows for prolonged post-thaw storage for more than 24 hours. The aim of this study was to assess glycerolization and deglycerolization processing for RBCs using a high glycerol method in the automated, closed system provided by Haemonetics ACP 215. METHODS: Thirty-five packed RBCs were glycerolized using the ACP 215 to a final concentration of 40% (wt/vol). The units were either frozen as such (n=30) or excess glycerol was removed (n=5) before freezing. After storage at −80℃, the units were thawed, deglycerolized and resuspended in SAG-M. The frozen-thawed RBCs were stored at 4℃, and analyzed for their stability and in vitro quality. RESULTS: No prefreeze excess glycerol removal units showed significantly less potassium leakage during post-thaw storage compared to the prefreeze excess glycerol removal units. All measurements of the stability and in vitro quality of thawed RBCs prepared from frozen RBCs without the prefreeze removal of excess glycerol during post-thaw storage at 4℃ for 7 days were acceptable to the American Blood Bank Association's standards and European standards. CONCLUSION: RBCs frozen without prefreeze removal of excess glycerol and the ACP 215 simplifies cryopreservation procedure and increases the stability of frozen-thawed RBCs. This increases the practical applicability of cryopreserved RBCs in blood transfusion practice.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

The measurement of serum corticosteroid level in atopic dermatitis patients associated with application of topical corticosteroids

PURPOSE: Most of the atopic dermatitis (AD) patients and their parents refuse topical treatment because of concern about generalized side effect due to systemic absorption of topical corticosteroids. Therefore, a large number of studies reported difficulty in properly controlling in AD. However, investigations of the percutaneous absorption of topical corticosteroids are still insufficient. METHODS: One hundred nine patients who visited our atopy clinic and diagnosed as AD by a physician from January 2005 to January 2012 were enrolled. We examined serum corticosteroid (clobetasol propionate, hydrocortisone) level by liquid chromatography (LC) coupled with a tandem mass spectrometric (MS/MS) method. RESULTS: We developed the LC-MS/MS method to determine corticosteroids (clobetasol propionate, hydrocortisone) in sera of AD patients. Also, we confirmed precision, accuracy, limit of detection, limit of quantification, absolute recovery, and relative recovery of the experimental methods. We could not detect clobetasol propionate or hydrocortisone in sera of 109 AD patients using the newly developed LC-MS/MS method. CONCLUSION: Regardless of age, the severity and illness duration of AD, clobetasol and hydrocortisone were not detected in sera. Although there are many other factors of determining systemic absorption of topical medications, our results showed that topical corticosteroids applied for several years in AD patients may be under the limit of detection in their sera by the LC-MS/MS method.

Transfusion Strategy of RhD-negative/variant Patients in the Korean Population

The prevalence of RhD-negative individuals in the Korean population is approximately 0.15-0.30% and the supply of RhD-negative blood often faces potential shortage. Furthermore, 15-17% of serologically RhD-negative Korean individuals were revealed to be DEL variants and should be treated as RhD-positive when being considered as blood donors. This change is expected to result in a further shortage of RhD-negative blood supply, whereas surplus DEL variant blood stock is created. Therefore, it is now required to amend blood donation and supply policies, and transfusion strategies. In this review, a new transfusion strategy for patients with RhD-negative or variant blood in Korea is discussed, with particular interest in women of child-bearing age, patients with anti-D, and Asia type DEL (c.1227G>A) variants.

Factors Associated with Cognitive Function in Breast Cancer Patients Complaining Cognitive Decline / 정신신체의학

OBJECTIVES: Cognitive complaints are reported frequently after breast cancer treatments. The causes of cognitive decline are multifactorial, a result of the effect of cancer itself, chemotherapy, and psychological factors such as depression and anxiety. However, cognitive decline does not always correlate with neuropsychological test performance. The purpose of this study was to examine the relationship of subjective cognitive decline with objective measurement and to explore associated factors of cognitive function in breast cancer survivors. METHODS: We included 29 breast cancer survivors who complain cognitive decline at least 6 months after treatment and 20 age-matched healthy controls. Neuropsychological tests were performed in all participants. Multivariable regression analysis evaluated associations between neuropsychological test scores and psychological distress including depression and anxiety, also considering age, education, and comorbidity. RESULTS: There were no statistically significant differences in neuropsychological test performances. However, the breast cancer survivors showed a significantly higher depression(p=0.002) and anxiety(p < 0.001) than the healthy controls did. Among the cancer survivors, poorer executive function was strongly associated with higher depression(β=−0.336, p=0.001) and anxiety(β=−0.273, p=0.009), after controlling for age, education, and comorbidity. In addition, poorer attention was also significantly related with depression(β=−0.375, p=0.023) and anxiety (β=−0.404, p=0.013). CONCLUSIONS: The results of this study showed the discrepancies between subjective complaints and objective measures of cognitive function in breast cancer survivors. It suggests that subjective cognitive decline could be indicators of psychological distress such as depression and anxiety.

Myelodysplastic Syndrome and Minimal Change Nephrotic Syndrome treated with Steroid Challenge / 대한내과학회지

Glomerulonephritis associated with malignancy is deemed to be paraneoplastic glomerulonephritis. Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by impaired hematopoietic cell differentiation and cytopenia. The pathophysiology of MDS is thought to be immune-mediated in part. A few reports have documented various forms of glomerulonephritis in patients with MDS and suggested that immune dysregulation is important in the development of paraneoplastic glomerulonephritis. Here, we report a patient with MDS and refractory anemia with excess blast-2 accompanied by minimal change nephrotic syndrome. The patient was treated with prednisolone, and the nephrotic-range proteinuria and pancytopenia improved markedly.

A Case of Primary Anti-D Alloimmunization by RHD (c.1227G>A) DEL Red Blood Cell Transfusion / 대한수혈학회지

The Rh blood group D antigen is the most immunogenic of all antigens, next to ABO antigens. Anti-D immunization is clinically important since it may cause clinical problems, such as severe hemolytic transfusion reactions and hemolytic disease of the newborn. DEL is an extremely weak D variant that cannot be detected by basic serologic typing and is typed as D-negative without the absorption-elution techniques and RHD genotyping. Of the DEL phenotype, RHD (c.1227G>A) allelic variant is the most common in Korea. The DEL phenotype has been considered to carry only a few D antigens to induce anti-D immunization, but a few cases have reported that this allelic variant is capable of inducing anti-D immunization in a D-negative recipient, for which it is clinical significant. Herein, we present a case of primary anti-D alloimmunization in a RhD negative patient after receiving RHD (c.1227G>A) DEL red cell transfusion identified by serological and molecular tests, including RHD genotyping.

Korean Red Cross HLA-Matched Platelet Donor Registry / 대한수혈학회지

BACKGROUND: Transfusion of HLA-matched platelets is required when development of platelet refractoriness occurs after repeated platelet transfusion. This study was conducted to establish a HLA-matched platelet donor registry to supply matched platelets to patients who develop platelet refractoriness. METHODS: HLA-matched platelet donors were recruited among plateletpheresis donors. HLA-A and HLA-B antigen types of recruited donors were tested using a polymerase chain reaction-sequence specific oligonucleotide probe method. RESULTS: A total of 1,029 plateletpheresis donors were recruited. HLA-A and HLA-B antigen frequencies of recruited donors were similar to those of previously reported HLA antigen frequencies of Koreans. During the study period, a patient with platelet refractoriness recovered after receiving six units of HLA-matched platelets. CONCLUSION: During this study 1,029 donors were registered as HLA-matched platelet donors and a patient with platelet refractoriness received HLA-matched platelets using this registry. Supply of HLA-matched platelets will be facilitated by continuous expansion of the number of registered HLA-matched platelet donors, development of a program for management and searching for HLA-matched donors, and establishment of a request-supply system between hospitals and the Korean Red Cross through further studies.

A Case of Pseudohyperphosphatemia in a Patient with Multiple Myeloma / 대한내과학회지

Hyperphosphatemia develops when there is impaired renal phosphate excretion or massive extracellular fluid phosphate load. For example, renal insufficiency, hypoparathyroidism, exogenous phosphate administration, and extensive cellular injury induce a hyperphosphatemic state. In patients with multiple myeloma, renal insufficiency occurs as a result of hypercalcemia, light chain tubulopathy, urate nephropathy or infection, and hyperphosphatemia usually results from renal failure. We report here a case of a patient with multiple myeloma who had an elevated serum phosphate level measured by the phosphomolybdate UV method without significant renal insufficiency and was finally diagnosed with pseudohyperphosphatemia.

A Case of Anaplastic Lymphoma Kinase-Negative Primary Gastric Anaplastic Large Cell Lymphoma / 대한내과학회지

Primary malignant lymphoma of the stomach comprises 1 to 7% of all gastric malignancies and is mostly B-cell type. Anaplastic large cell lymphoma (ALCL) of the stomach is very rare and regarded to have a poor prognosis. A 66-year-old man complained of dyspepsia for 3 days. A esophagogastroduodenoscopic examination revealed a flat, depressed ulcer at the distal antrum. Biopsy of the lesion showed diffuse infiltration of large pleomorphic lymphoid cells that were positive for CD3 and CD30 and negative for cytokeratin and anaplastic lymphoma kinase (ALK). We diagnosed the patient with ALK-negative primary gastric ALCL with multiple lymphadenopathies, and he received systemic chemotherapy. CHOP-like regimens followed by consolidation therapy have been widely used for ALK-negative ALCL. However, the patient maintained complete remission for 36 months with only induction chemotherapy. This case suggests that heavy treatment for ALK-negative ALCL is not required for all patients.

Effect of Korean Red Ginseng on Sleep: A Randomized, Placebo-Controlled Trial / 수면정신생리

OBJECTIVES: Ginseng has a long history of being used in insomnia treatment and there is some evidence from animal studies of its sleep-enhancing property. From this, it can be assumed that ginseng has sleep-promoting effect in humans. The purpose of this study was to investigate the effect of Korean red ginseng on change of sleep architecture in humans. METHODS: A total of 20 healthy young males with regular sleep and wake habits and without any psychiatric nor cognitive problems were selected based on review of sleep questionnaires and sleep diaries they completed followed by an interview with a board-certified psychiatrist. The subjects were randomly assigned to red ginseng or placebo for 2 weeks of trial. The total daily dose of ginseng was 4,500 mg. The polysomnographic recordings were made at baseline and at 2 weeks after. The effects of red ginseng and placebo on sleep were assessed by comparing the changes in polysomnographic variables between the two groups. RESULTS: A total of 15 subjects, 8 from red ginseng group and 7 from placebo group, were included to undergo polysomnographic procedures. The red ginseng group showed tendencies to increase stage 3 sleep (p=0.087) and to decrease stage 2 sleep (p=0.071) from the baseline compared with the placebo group. CONCLUSION: Korean red ginseng tends to increase deep sleep and decrease shallow sleep. Our result is in line, at least in part, with previous findings that Korean red ginseng increased total and NREM sleep in rats. Further studies with higher ginseng dosage, larger sample size and longer trial duration should be conducted to confirm the sleep stabilizing and balancing effects of Korean red ginseng.

Detection of Allergen Specific IgE by AdvanSure Allergy Screen Test / 대한진단검사의학회지

BACKGROUND: In vitro serum allergen-specific IgE tests have been routinely used in the clinical diagnosis of allergic diseases. We evaluated the clinical usefulness of a newly introduced multiple antigen screen test, Advansure Allergy Screen (LG Life Science, Korea) (LG-Screen) for the detection of allergen specific IgE. METHODS: A total of 180 sera (80 for inhalant and 100 for food panels) were tested by LG-Screen and RIDA Allergy Screen (R-biopharm, Germany) (RIDA-Screen) assays. According to the 58-60 specific allergens or allergen groups, the positive rates and agreement rates were analyzed using the cut off levels of class 2. For the quantitation of total IgE and specific IgE, nephelometry and ImmunoCAP test were performed in the sera showing discrepant results between the two allergy screen assays. RESULTS: The agreement rate and kappa value (k) of total IgE between the two allergy screen assays was 73.9% and 0.333. LG-Screen showed higher agreement rate with nephelometry than RIDA-Screen. The positive rates to common outdoor inhalant and food allergens were significantly higher in RIDA-Screen. Overall agreement rate of specific IgE between the two allergy screen assays for 58 allergens was 86.7% (6,086/7,020) (k, 0.293). In samples showing discrepant results between the two allergy screen assays, concordance rate of allergy screen assay with ImmunoCAP assay was 70.9% (449/633) for LG-Screen (k, 0.585) and 29.1% (184/633) for RIDA-Screen (k, -0.303). CONCLUSIONS: LG-Screen showed a favorable agreement with RIDA-Screen and ImmunoCAP assays, and it could be used for the detection of allergen specific IgE in the clinical laboratory.

A case of micropapillary breast cancer with endometrial metastasis / 대한내과학회지

Breast cancer is one of the most common cancers in women. Even if appropriate treatments are applied, metastasis can occur in any organ of the body. Uterine metastasis from an extrapelvic tumor such as breast cancer is very rare. A 62-year-old woman with breast cancer was treated with modified radical mastectomy after neoadjuvant chemotherapy and adjuvant chemoradiotherapy. A single lung metastasis developed at 2 years after surgery, and the patient underwent wedge resection followed by capecitabine chemotherapy. Afterwards, the patient was treated with gemcitabine/vinorelbine chemotherapy for skin metastasis. Recently, she complained of vaginal spotting for 3 weeks. MRI of the uterus revealed a 1.1 cm endometrial tumor with myometrial invasion. Biopsy confirmed papillary carcinoma that originated from previous breast cancer. Although she was treated by palliative radiotherapy to the uterus, docetaxel/cyclophosphamide and trastuzumab, disease progression was observed.

A Case of t(3;3)(q21;q26.2) Associated with Severe Multilineage Dysplasia and Multi-drug Resistance in Blastic Crisis of Chronic Myelogenous Leukemia / 대한진단검사의학회지

The t(3;3)(q21;q26.2) is known to be mainly observed in hematologic myeloid malignancies, as a form of 3q21q26 syndrome. Cytogenetic abnormalities of 3q21q26 syndrome result in RPN1-EVI1 fusion transcripts involving ecotropic viral integration site-1 (EVI1) at 3q26.2 and ribophorin I (RPN1) at 3q21, and the fusion transcripts play an important role in leukemogenesis and disease progression. They are usually associated with dysplasia, especially of megakaryocytes. Patients with these cytogenetic abnormalities show extremely poor prognosis even with aggressive anti-leukemic therapy. We report a case of blastic crisis of CML with both t(3;3)(q21;q26.2) and t(9;22)(q34;q11.2) and associated severe multilineage dysplasia. The patient showed a poor response to imatinib, dasatinib and aggressive induction therapy. When both t(3;3)(q21;q26.2) and t(9;22)(q34;q11.2) are observed in cases of leukemia with increased blasts, they are best considered as aggressive phases of CML with t(3;3)(q21;q26.2), rather than AML with t(9;22)(q34;q11.2) by 2008 WHO classification.

A Case of Intravesical Cidofovir Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Peripheral Blood Stem Cell Transplantation / 영남의대학술지

Hemorrhagic cystitis (HC) is a common complication after allogeneic transplantation. Early posttransplant HC occurs in association with cyclophosphamide, while later on HC results from viral infections such as polyomavirus BK (BKV) and adenovirus. We report here the case of a 57-year-old woman who received an instillation of cidofovir into the bladder for the treatment of hemorrhagic cystitis after allogeneic peripheral stem cell transplantation for her acute myeloid leukemia. Cyclophosphamide and busulfan were used as conditioning treatments. Cyclosporin was administered daily. On the 71st day after transplantation, the patient developed acute severe hemorrhagic cystitis, and BK virus was demonstrated in the urine samples using polymerase chain reaction. Her urinary symptoms did not improve in spite of palliative treatment, but a response was evident after intravesical cidofovir treatment.

Microscopic Colitis: The Pathologic Features of 24 Korean Patients

BACKGROUND: The clinical presentation of microscopic colitis (MC) consists of chronic non-bloody watery diarrhea for weeks or months at a time, abdominal pain, and changes in bowel habits with a normal mucosal appearance upon performing colonoscopy. MC includes two relatively well established histopathologic entities: collagenous colitis (CC) and lymphocytic colitis (LC) as well as atypical forms. The recognition of the microscopic findings of this heterogeneous entity is very important for making the correct diagnosis and providing proper treatment. METHODS: We studied the colonoscopic biopsy specimens that were obtained from 26 patients who had clinical findings that were suggestive of MC. RESULTS: Fifteen patients (M:F=9:6) and 9 patients (M:F=5:4) showed the microscopic features of LC and MC, not otherwise specified, respectively. CONCLUSIONS: The clinicopathologic findings (the incidence of the subtypes, the patients' ages and the male/female ratio) of the 24 cases of MC in this study showed differences from the previously reported findings from other countries. Further studies with a sufficient number of patients from multi-centers would be necessary to confirm the regional or ethnic influence.

Metaplastic Squamous Carcinoma of the Breast: Clinicopathologic Analysis of 17 Cases

BACKGROUND: Squamous cell carcinoma of the breast is very rare and it is considered to arise from metaplastic change of ductal carcinoma. Metaplastic squamous cell carcinoma (MSC) of the breast includes pure squamous cell carcinoma, metaplastic adenosquamous carcinoma and low grade adenosquamous carcinoma. Most of the cases of MSC of the breast were reported to have lymph node metastasis and this has a worse prognosis than that of conventional invasive ductal carcinoma. METHODS: We collected 17 cases of MSC of the breast from 1,173 cases of breast cancer and analyzed the clinicopathological characteristics. RESULTS: The age range was 31 to 69 years (mean age: 47.2). The mean tumor size was 3.6 cm. Twelve cases (70.6%) had a negative nodal status. The majority of the cases were of a high nuclear grade (grade III: 76.5%), and a high histologic grade (grade III: 88.2%). All the cases had no amplification of HER2, and they were negative for hormonal receptors, except for 2 cases with weak positivity. All the cases showed positivity for EGFR (3+: 14 cases, 1+: 3 cases). Clinical relapse was found in 3 patients on follow up and two of them expired due to lung and bone metastasis. CONCLUSIONS: MSC is associated with high nuclear and histologic grades, a high EGFR expression and they are triple negative for ER, PR, and HER2. The EGFR immunopositivity of MSC suggests a basal-like subtype.

The prognostic significance of FDG-PET in advanced non-small cell lung cancer / 대한내과학회지

BACKGROUND/AIMS: Lung cancer is the leading cause of cancer-related death in Korea. Non-small cell lung cancer (NSCLC) comprises 80~85% of lung cancer. Positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with NSCLC. This study determined whether the standardized uptake value (SUV) of FDG uptake by PET is a prognostic factor for advanced NSCLC. METHODS: FDG-PET was performed in 59 patients with stage IIIb and IV NSCLC. The SUV was calculated for each patient. Overall survival (OS) and time to progression were calculated using the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed using univariate and multivariate analyses. RESULTS: A cutoff of 7 for the SUV gave the best criminative value. In the univariate analysis, performance status (p=0.02) and SUV (p=0.03) were significant predictors of OS. The patients with low SUVs (7, p=0.04). A multivariate Cox analysis identified performance status and the SUV as important for the prognosis. CONCLUSIONS:These results suggest that SUV is a significant prognostic factor in patients with advanced non-small cell lung cancer.

Brown Bowel Syndrome that Developed after Total Gastrectomy: A Case Report

The brown bowel syndrome (BBS) is an uncommon disorder, which is characterized by brown pigmentation of the intestine due to the accumulation of lipofuscin in the smooth muscle cells. Vitamin E deficiency has generally been considered as the cause of this malady. BBS has been reported in a wide variety of malabsorptive diseases involving the pancreas, liver and gastrointestinal tract. We report here on a case of brown bowel syndrome that occurred in a 73-year-old man who had undergone total gastrectomy 11 years ago for gastric adenocarcinoma. He has complained about intestinal obstructive symptoms for several years, and these symptoms were recently aggravated. He showed a low serum concentration of total protein, albumin and cholesterol, and he had been treated for megaloblastic anemia due to vitamin B12 and folate deficiency several months ago. The resected small bowel showed lipofuscin deposition in the muscle layer of the intestine and large vessels. The electron microscopic examination revealed multiple electron dense lipofuscin deposits with irregular shapes and sizes in the cytoplasm.