Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Posterior Screw Fixation in Previously Augmented Vertebrae with Bone Cement: Is It Inapplicable?

OBJECTIVE: The purpose of this study was to determine the feasibility of screw fixation in previously augmented vertebrae with bone cement. We also investigated the influence of cement distribution pattern on the surgical technique. METHODS: Fourteen patients who required screw fixation at the level of the previous percutaneous vertebroplasty or balloon kyphoplasty were enrolled in this study. The indications for screw fixation in the previously augmented vertebrae with bone cement included delayed complications, such as cement dislodgement, cement leakage with neurologic deficits, and various degenerative spinal diseases, such as spondylolisthesis or foraminal stenosis. Clinical outcomes, including pain scale scores, cement distribution pattern, and procedure-related complications were assessed. RESULTS: Three patients underwent posterior screw fixation in previously cemented vertebrae due to cement dislodgement or progressive kyphosis. Three patients required posterior screw fixation for cement leakage or displacement of fracture fragments with neurologic deficits. Eight patients underwent posterior screw fixation due to various degenerative spinal diseases. It was possible to insert screws in the previously augmented vertebrae regardless of the cement distribution pattern; however, screw insertion was more difficult and changed directions in the patients with cemented vertebrae exhibiting a solid pattern rather than a trabecular pattern. All patients showed significant improvements in pain compared with the preoperative levels, and no patient experienced neurologic deterioration as seen at the final follow-up. CONCLUSION: For patients with vertebrae previously augmented with bone cement, posterior screw fixation is not a contraindication, but is a feasible option.

Posterior Screw Fixation in Previously Augmented Vertebrae with Bone Cement: Is It Inapplicable?

OBJECTIVE: The purpose of this study was to determine the feasibility of screw fixation in previously augmented vertebrae with bone cement. We also investigated the influence of cement distribution pattern on the surgical technique.METHODS: Fourteen patients who required screw fixation at the level of the previous percutaneous vertebroplasty or balloon kyphoplasty were enrolled in this study. The indications for screw fixation in the previously augmented vertebrae with bone cement included delayed complications, such as cement dislodgement, cement leakage with neurologic deficits, and various degenerative spinal diseases, such as spondylolisthesis or foraminal stenosis. Clinical outcomes, including pain scale scores, cement distribution pattern, and procedure-related complications were assessed.RESULTS: Three patients underwent posterior screw fixation in previously cemented vertebrae due to cement dislodgement or progressive kyphosis. Three patients required posterior screw fixation for cement leakage or displacement of fracture fragments with neurologic deficits. Eight patients underwent posterior screw fixation due to various degenerative spinal diseases. It was possible to insert screws in the previously augmented vertebrae regardless of the cement distribution pattern; however, screw insertion was more difficult and changed directions in the patients with cemented vertebrae exhibiting a solid pattern rather than a trabecular pattern. All patients showed significant improvements in pain compared with the preoperative levels, and no patient experienced neurologic deterioration as seen at the final follow-up.CONCLUSION: For patients with vertebrae previously augmented with bone cement, posterior screw fixation is not a contraindication, but is a feasible option.

Cement Leakage into Adjacent Vertebral Body Following Percutaneous Vertebroplasty

Percutaneous vertebroplasty (PV) is a minimally invasive procedure for osteoporotic vertebral compression fractures that fail to respond to conventional conservative treatment. It significantly improves intolerable back pain within hours, and has a low complication rate. Although rare, PV is not free of complications, most of which are directly related to cement leakage. Because of its association with new adjacent fracture, the importance of cement leakage into the adjacent disc space is paramount. Here, we report an interesting case of cement leakage into the adjacent upper vertebral body as well as disc space following PV. To the best of our knowledge, there has been no report of cement leakage into the adjacent vertebral body following PV. This rare case is presented along with a review of the literature.

Rapid Resolution of Traumatic Pneumatocyst in the Cervical Spine: A Case Report

Intraosseous pneumatocyst is a benign, gas-filled, cystic lesion, and is commonly encountered in iliac bone or sacrum. Other locations of this lesion following trauma are rare, and only a handful of isolated cases have been reported. The pathogenesis and etiologies of this uncommon entity are various and it can present a diagnostic challenge. Only four previous cases have described the natural course of intravertebral pneumatocysts. Here, the authors report a rare case of traumatic pneumatocyst, which resolved rapidly without further complication. Possible pathogenic mechanisms are discussed and reviews of literatures are included.

Successful Erythropoietin Therapy after Alemtuzumab and Cyclosporin a Treatment for Epoetin-Induced Pure Red Cell Aplasia / 대한내과학회지

Pure red cell aplasia (PRCA) in adults is usually idiopathic, although some underlying conditions can cause PRCA. Immunosuppressive therapy (IST) is used to treat PRCA, but IST has side effects and may fail. The anti-CD52 monoclonal antibody alemtuzumab (ALM) was recently used to successfully treat therapy-resistant PRCA. We herein report successful treatment of secondary PRCA after erythropoietin therapy using ALM and cyclosporin A (CsA) in one patient. The total dose of ALM was 60 mg over 3 days (10, 20, and 30 mg, respectively) plus CsA for at least 6 months. The patient achieved a complete response 18 months after ALM-CsA treatment and his treatment could be changed to a different erythropoietin-stimulating agent.

Clinical significance of PML/RAR alpha isoforms in acute promyelocytic leukemia / 대한내과학회지

BACKGROUND/AIMS: There are three types of PML-RAR alpha mRNA fusion transcripts associated with acute promyelocytic leukemia (APL): the short (S)-form, the long (L)-form and the variable (V)-form. No study on the Korean population has addressed the clinical significance of the specific types of PML-RAR alpha mRNA fusion transcripts for APL patients who receive the combination therapy of all-trans-retinoic-acid and idarubicin (AIDA regimen). METHODS: We performed a retrospective analysis on 94 patients with APL to evaluate differences in the therapeutic outcomes, such as the response rate, an event-free survival (EFS), and overall survival (OS), after remission following the induction of chemotherapy. We also analyzed whether differences in the pretreatment clinical characteristics depend on the PML-RAR alpha isoform. RESULTS: The median age of the patients was 41 years (range 15-85). Among the 94 patients, there were 58 L-form cases (62.1%), 32 S-form cases (34.0%), and 4 V-form cases (4.3%). The CR rate following remission induction treatment was 84.9%. The CR rate was higher in patients with an initial WBC <10.0x109/L, as compared to patients with an initial WBC higher than 10.0X109/L (93.5% vs. 65.4%, p=0.001). The AIDA induction regimen was associated with a better EFS than non-AIDA induction regimens (81.9% vs. 49.6%, p=0.006). The induction group was also a significant prognostic factor for EFS in the multivariate analysis (p=0.020). There were no differences in OS and EFS in patients with either isoform L or isoform S in the AIDA induction group. CONCLUSIONS: This retrospective study demonstrated that pretreatment clinical characteristics and treatment outcomes were not significantly different among patients with varying PML-RAR alpha isoform types in the AIDA induction group.

Anorectal and gastric peripheral T-cell lymphoma, unspecified in a non-AIDS patient

Anorectum is a rare location for malignant lymphoma. Involvement of is rare even for the lymphoma associated with acquired immune deficiency syndrome (AIDS), and AIDS has a relatively increased frequency of anorectal lymphoma. Most lymphomas in AIDS patients are of a B-cell origin, and T-cell lymphoma of the gastrointestinal tract is extremely rare. We report here on a case of anorectal and gastric peripheral T-cell lymphoma, unspecified (PTCLu) in a non-AIDS patient. A previously healthy 29-year-old man presented with hematochezia and tenesmus that he had suffered with for the previous 2 months. Sigmoidoscopy showed anal and rectal submucosal tumor. Multiple round-shaped, flat and elevated lesions were noted on the gastric antrum and body as well. He underwent excisional biopsy for the anal mass and the diagnosis was PTCLu. Biopsies of the gastric lesions gave the same diagnosis. There was no lymphoma involved in the bone marrow. At admission, no antibodies against human immunodeficiency virus were detected. He underwent systemic chemotherapy and upfront autologous stem cell transplantation.

Cutaneous Polyarteritis Nodosa Presented with Digital Gangrene: A Case Report

Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of vasculitis involving small and medium sized arteries of unknown etiology. The disease can be differentiated from polyarteritis nodosa by its limitation to the skin and lack of progression to visceral involvement. The characteristic manifestations are subcutaneous nodule, livedo reticularis, and ulceration, mostly localized on the lower extremity. Arthralgia, myalgia, peripheral neuropathy, and constitutional symptoms such as fever and malaise may also be present. We describe a 34-yr-old woman presented with severe ischemic change of the fingertip and subcutaneous nodules without systemic manifestations as an unusual initial manifestation of CPAN. Therapy with corticosteroid and alprostadil induce a moderate improvement of skin lesions. However, necrosis of the finger got worse and the finger was amputated.

Two Cases of Cytomegalovirus Pneumonia after CD34 Selected Autologous Stem Cell Transplantation

Cytomegalovirus (CMV) pneumonia is an important cause of treatment related mortality after allogeneic stem cell transplantation (SCT) and autologous SCT, particularly in a CD34 selected setting. There is little known about the immune reconstitution pertaining to the CMV after CD34 selected SCT. However, several studies have suggested there is more profound immunodeficiency early in the CD34 selected population compared with the unselected population. We encountered two fatal cases of CMV pneumonia at the CD34 selected SCT for T-cell lymphoblastic lymphoma and high-risk breast cancer that was confirmed through a lung biopsy and bronchoalveolar lavage. In conclusion, autologous CD34 selected CMV seropositive recipients need to be monitored in a similar manner to allogeneic recipients.

Combination Chemotherapy with 5-Fluorouracil and Heptaplatin as First-line Treatment in Patients with Advanced Gastric Cancer

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

A Less Intensive Combination of Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer Patients who Have Aged 60 Years or More and Has a Poor Performance Status

BACKGROUND: The aim of this study was to evaluate the response, survival, and toxicities of a less intensive combination of paclitaxel and carboplatin, which is used in advanced non-small cell lung cancer (NSCLC) patients older than 60 years of age including those with a poor performance status. METHODS: Thirty patients received 135 mg/m2 of paclitaxel on day 1, and carboplatin was administered to the patients on day 1 every 4 weeks over an area under the concentration-time curve of 6. RESULTS: The response rate was 40%, the median overall survival was 9.1 months (95% CI, 4.2 to 14 months), and the 1 year survival rate was 31%. The median progression-free survival was 7.7 months (95% CI, 3.1 to 12.2 months). In addition, the toxicities were generally mild and reversible. CONCLUSION: This study demonstrates that a less intensive combination of paclitaxel/carboplatin is active and well tolerated in advanced NSCLC patients who are older than 60 years including those with a poor PS 3~4.

The Role of Bile Carcinoembryonic Antigen in Diagnosing Bile Duct Cancer

It is known that the fluids bathing tumors might contain a higher level of the carcinoembryonic antigen (CEA) than those found in the blood. Therefore, we evaluated the role of bile CEA in diagnosing bile duct cancer. One hundred and thirty two patients were prospectively studied. The patients were divided into 3 groups: the bile duct cancer (n=32), pancreatic cancer (n=16), and benign biliary diseases (n=84) groups. Bile samples were obtained on the next day of the biliary drainage procedures. The mean bile CEA level in those with bile duct cancer (120.6+/-156.9 ng/mL) was significantly higher than those with pancreatic cancer and benign biliary diseases (32.0+/-28.5 ng/mL, 29.3+/-56.3 ng/mL). Using the level of 20 ng/mL, the sensitivity and specificity of bile CEA in the diagnosis of bile duct cancer from benign biliary diseases were 65.6% and 66.7%, respectively. Both the bile CEA and total bilirubin level were found to be an independent factor linked to bile duct cancer. This study result suggests that bile CEA level is a useful supplementary test for diagnosing bile duct cancer.

A Case of Thrombotic Thrombocytopenic Purpura Achieved Complete Remission with 54 Plasma Exchanges / 대한혈액학회지

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, renal disorder and neurologic signs. Its clinical course is rapid and its mortality rate is very high. However, the prognosis has much improved after plasma exchange was introduced as a therapeutic modality. We report a 31-year-old multipara pregnant woman with refractory TTP, who achieved complete remission after 54 plasma exchanges.

Diagnostic Usefulness of Intradermal Test for Clonorchiasis in Patients with Pancreatobiliary Diseases / 대한소화기학회지

BACKGROUND/AIMS: The diagnosis of clonorchiasis is based on demonstrating eggs in stool or bile. It is believed that bile examination is the most precise method for detecting eggs. We evaluated diagnostic usefulness of intradermal test (IDT) by comparing it with the result of bile examination. METHODS: For 88 patients with pancreatobiliary diseases, we examined Clonorchis sinensis eggs in bile and performed IDT for clonorchiasis. The bile was obtained from endoscopic nasobiliary or percutaneous transhepatic biliary drainage tubes. RESULTS: We calculated ROC curve to decide the cut-off value of IDT in determining diagnostic accuracy on the basis of bile examination. We chose a value of 40 mm2, which significantly improved the sensitivity, without reducing the specificity. With a cut-off value of 40 mm2, the sensitivity, specificity, positive and negative predictive values of IDT were 81.5%, 67.2%, 52.4%, and 89.1%, respectively. The value of IDT was not affected by age and showed no difference between benign and malignant diseases. However, in egg-positive patients, the mean value was lower in malignant diseases than in benign diseases. CONCLUSIONS: In patients with pancreatobiliary diseases, IDT with a cut-off value of 40 mm2 seems to be a valuable supplementary diagnostic test for clonorchiasis in view of its high sensitivity.

Diagnostic role of biliary carcinoembryonic antigen in patients with pancreatobiliary diseases / 대한내과학회지

BACKGROUN: Recently there has been notion that fluids bathing tumors might contain higher levels of carcinoembryonic antigen (CEA) than those found in the blood. Thus, we evaluated the diagnostic role of biliary CEA in patients with pancreatobiliary diseases. METHODS: One hundred and twenty one patients were prospectively studied. The patients were grouped as control (n=21), benign diseases (n=57), and malignant diseases (n=43). All patients underwent endoscopic or percutaneous biliary drainage. Bile was obtained and analyzed for CEA concentration on the next day of biliary drainage procedure. RESULTS: The mean biliary CEA were significantly different among the groups: control, 3.6 +/- 6.5 ng/mL; benign diseases, 35.4 +/- 59.2 ng/mL; malignant diseases, 77.9 +/- 126.6 ng/mL. But, there was considerable overlap among the groups. With a cut-off level of 22 ng/mL, the sensitivity and specificity were 58.1% and 60.5%, respectively. Among the variables, biliary CEA, total bilirubin, and gamma-GT were directly correlated with presence of malignancy. However, multivariate analysis revealed that biliary CEA was not enough to differentiate malignant diseases from benign diseases. CONCLUSION: Although biliary CEA levels might be predictive of malignancy, it is very difficult to differentiate with fair certainty between the two diseases because of the considerable overlap. Thus, biliary CEA appears to have a limitation for routine clinical application in distinguishing between benign and malignant diseases.

A Case of Chronic Pancreatitis Associated with Liver Infarction and Acrodermatitis Enteropathica

Liver infarction and acrodermatitis enteropathica are rare complications of chronic pancreatitis. This report shows the case of a 56-year-old man who developed liver infarction due to portal vein thrombosis from chronic pancreatitis and acrodermatitis enteropathica during the course of his treatment. The rare combination of these complications in a patient with chronic pancreatitis has never previously been reported in the literature.

Gemcitabine Therapy in Patients with Advanced Pancreatic Cancer

BACKGROUND: Advanced, unresectable pancreatic cancer is an extremely aggressive disease. The 5-year survival rate for pancreatic cancer is only less than 5%. Current therapeutic options for patients with locally advanced or metastatic disease are limited. This analysis is a retrospective evaluation of the efficacy and toxicity of gemcitabine regimen as first-line chemotherapy in patients with advanced pancreatic cancer. METHODS: Seventeen chemotherapy-na ve patients with advanced or recurred pancreatic cancer were consecutively treated. Gemcitabine was diluted in normal saline and administered intravenously over 1 hour. Gemcitabine 1,000 mg/m2 was administered once weekly for 3 out of every 4 weeks. RESULTS: The median age of patients was 55 years (range 44~82 years). Based on RECIST criteria, there were 5 cases of stable disease (45%) and 6 cases of progressive disease (55%) among the 11 assessable patients. The median survival time was 189 days (range, 84 to 409 days), the 1 year survival rate was 18% in all 17 patients. Grade 3~4 toxic side effect was leucopenia only (29%) and was easily managed without infection. CONCLUSION: Gemcitabine is well tolerated, but has no objective response in advanced pancreatic cancer.

Prevalence and risk factors of the osteoporosis of perimenopausal women in the community population / 대한내과학회지

BACKGROUND: Osteoporotic fractures pose a major public problem, not only in Western populations but also of increasing significance in Asian populations. However, most previous studies for the prevalence of osteoporosis in Korea were carried out from the data of hospitalized or out-patient based subjects, hospital staff, healthy volunteers and so forth. The purpose of present study was to evaluate the normative data of bone mineral density (BMD) in Korean young and perimenopausal women and to determine the prevalence and risk factors of low bone mass, including osteoporosis and osteopenia in a community-based population. METHODS: In 1999, a baseline survey was carried out in the Dong-gu of Ulsan city, a urban area but located in seashore of southeastern Korea. The selected community sample of 3,822 inhabitants (all were women aged 49~54 years) were chosen. We studied 1,629 women among them and 127 healthy women aged 20~35 years. BMD of lumbar spine and femur was measured using dual-energy X-ray absorptiometry. For analysis of risk factors, those were excluded who was the current or recent user of estrogen and who had osteoporosis related disease or unknown menopause due to previous hysterectomy. Thus, 1,020 subjects were analysed for the association of low BMD and risk factors. Significant determinants of BMD were investigated using univariate and multiple regression analysis. RESULTS: When our young normal data were used, 9.8% for the lumbar spine and 1.4% for the femoral neck of our study population (n=1,629) were classified as osteoporosis. Among them, the menopausal status of above 1,020 subjects had independent association with low BMD (T-score<-1.0) of both lumbar spine (odds ratio=4.71 in postmenopause, p<0.001) and femoral neck (odds ratio=2.86 in postmenopause, p<0.001). In premenopausal women (n=507), weight and age of menarche were associated independently with low bone mass, including osteoporosis and osteopenia of both lumbar spine and femoral neck. In postmenopausal women (n=513), weight and duration since menopause were associated independently with low bone mass of both lumbar spine and femoral neck. Also, daily amount of calcium intake had significant association (regression coefficient=0.047; p<0.05) independently with BMD of femoral neck. CONCLUSION: The results of this population-based study suggest that it is important to prevent bone loss and screen the BMD in women aged 49~54 years with menopause, low body weight, late menarche, prolonged duration since menopause, low calcium intake.

Expression of a Novel 90 kDa Heat Shock Protein in Colorectal Tumor

PURPOSE: When cells are subjected to a wide variety of stressful stimuli, they respond by increasing the synthesis of specific stress proteins. Stresses include heat shock, nutrient deprivation, oxygen radicals, toxic metal and viral infection. Major stress proteins are Hsp 27, Hsp 60, Hsp 70 (9), Hsp 90 (3) and Hsp 100 (1). Previously a novel 90 kDa stress protein has been reported to be induced in fish cells by virus infection. The novel 90 kDa stress protein is different from well-known major stress protein in size, antigenicity, cellular localization. The novel 90 kDa stress protein was found to be present in various kinds of cells including human cells and its expression was increased in human carcinomas. The purpose of this study is to evaluate the expression of the novel 90 kDa stress protein in human colonic mucosa of normal tissue, adenoma and adenocarcinoma using immunohistochemical method. METHODS: 85 colon tissues were screened for the expression of the novel 90 kDa stress protein; 85 normal colonic mucosa, 20 colonic adenoma and 65 colonic adenocarcinoma. The tissues were stained with monoclonal antibody against the novel 90 kDa stress protein. In scoring system, tissue sections with immunostained area above 10 % were decided to be positive and, among the positive, the tissue sections were divided into three score, 1, 2, and 3, based on the staining intensity and positive area proportion. The tissue sections with immunostained area below 10% were decided to be negative and grouped into 0 score. Correlation of immunohistochemical expression was analysed by using SPSS version 10.0 statistically. RESULTS: The expression of the 90 kDa stress protein was significantly different among normal colonic mucosa, colonic adenoma, and colonic adenocarcinoma and the percentage of positive samples were 14.1%, 80.5%, and 95.4% respectively. This result suggests that the expression level of the novel 90 kDa stress protein was extremely low in normal tissue but increased significantly in adenocarcinomatous tissues. CONCLUSIONS: The expression of the novel 90 kDa stress protein was increased significantly with transformation of the normal colon tissue to malignancy. This suggests the possibility that this novel 90 kDa stress protein play some role in cancerous transformation of colon tissue.