A Case of Paraneoplastic Limbic Encephalitis Associated with Primary Adenocarcinoma of Lung / 결핵및호흡기질환

Paraneoplastic limbic encephalitis is a rare disorder that is characterized by personality changes, irritability, depression, seizures, memory loss and dementia, and is commonly associated with small cell lung cancer. The cause is unknown but it is believed to be an autoimmune disorder that develops secondary to a carcinomatous process. We report a patient with the clinical feature consistent with limbic encephalitis. A 64-year-old women developed disorientation, memory loss and general weakness. She was diagnosed with NSCLC (adenocarcinoma) with a brain metastasis 1 year earlier and was treated with radiation and chemotherapy. Although the lung mass and brain metastatic lesions had improved, the brain T2-weighted MRI showed high signal intensity in the right temporal region. This lesion consisted of with limbic encephalitis and was negative to the other viral and immune markers. The patient's symptoms did not improve after steroid treatment. Our case demonstrated that a NSCLC (adenocarcinoma) also can be associated with paraneoplastic limbic encephalitis.

Tumor Lysis Syndrome in Lymphoblastic Crisis of CML

Tumor lysis syndrome (TLS) defines the metabolic derangements that occur with tumor breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular materials and their metabolites into the extracellular space. The syndrome causes hyperuricemia, hyperkalemia, hyperphosphatemia, secondary hypocalcemia and uremia. It can result in acute renal failure and be fatal. Early recognition of patient at risk and preventive measures are important. There is a high incidence of TLS in tumors with high proliferative rates and large burden such as acute lymphoblastic leukemia and Burkitt's lymphoma. It less commonly occurs in solid tumors such as testicular cancer, breast cancer and small cell lung cancer. There are only a few reports on TLS complicated in CML in blast crisis. So we report a 45-yr-old woman presenting with TLS associated with CML in lymphoblastic crisis after the initiation of cytotoxic chemotherapy.

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as Second Line Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy. MATERIALS AND METHODS: Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m2 on day 1; LV 200 mg/m2 on days 1 and 2; and 5-FU 400 mg/m2 bolus IV with 600 mg/m2 with a 22-hour infusion on days 1 and 2 every 2 weeks. RESULTS: The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/ vomiting (23.6%/18.5%). There was no life-threatening toxicity. CONCLUSION: The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.

Epstein-Barr virus-associated Hodgkin's disease following renal transplantation

Post-transplant lymphoproliferative disorders (PTLD) have been recognized as a complication of immunosuppression and occur with a reported incidence of 1 to 8% of recipients receiving solid organ transplantation. PTLD are classified into two major categories, polymorphic and monomorphic PTLD. The majority of the monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. Hodgkin's disease is not part of the typical spectrum of PTLD; however, it has been rarely reported. We describe a case of Hodgkin's disease following renal transplantation. A 41-year-old man developed right cervical lymphadenopathy following renal transplantation 116 months previously for chronic renal failure of unknown origin. He had been taking cyclosporine, mycophenolate mofetil and prednisone. A lymph node biopsy revealed mixed cellularity Hodgkin's disease. Immunohistochemical staining was positive for CD30 and EBV-latent membrane protein-1. No other site of disease was identified. The immunosuppressive agents were reduced (mycophenolate mofetil was discontinued, cyclosporine dose reduced from 200 mg to 150 mg and prednisone continued at 5 mg). After 2 cycles of ABVD followed by radiation therapy (3600 cGy), he achieved complete remission.

Comparison of WHO and RECIST Criteria for Response in Metastatic Colorectal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study compared the WHO criteria with the response evaluation criteria in solid tumors (RECIST) in the same patients with metastatic colorectal cancer in order to determine the significance of the RECIST. In addition, this study compared the estimations of medical oncologists with those of a radiologist. MATERIALS AND METHODS: Between 2002 and 2005, a total of 48 patients (male: female ratio, 29: 19; median age, 58 years) with measurable lesions receiving chemotherapy for metastatic colorectal carcinoma were enrolled in this study. Two medical oncologists and one radiologist, who were blinded to the patients' condition, independently reviewed all the CT images. The results were compared using a kappa test. RESULTS: The kappa test for concordance between the WHO and RECIST criteria of the medical oncologists and the radiologist were 0.908 and 0.841, respectively. The level of concordance between the investigators using the WHO and RECIST were 0.722 and 0.753, respectively. CONCLUSIONS: The RECIST criteria are comparable to the WHO criteria in evaluating the response of colorectal carcinoma, but have simple and reproducible guidelines. The use of RECIST is recommended for evaluating the treatment efficacy in clinical trials and practice.

A Case of Erythema Nodosum and Serositis Associated with Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a heterogenous group of stem cell disorders usually characterized by progressive refractory cytopenias, which could progress to acute myeloid leukemia. MDS may be associated with a wide spectrum of skin lesions, including neoplastic cell infiltration, Sweet's syndrome, pyoderma gangrenosum, erythema elevatum diutinum, vasculitis, and panniculitis. However, erythema nodosum is rarely associated with MDS. Unusual rheumatologic manifestations in patients with MDS also have been reported, which range from asymptomatic serological abnormalities to classic connective tissue disorders such as Sjogren's syndrome, relapsing polychondritis, systemic lupus erythematosus, rheumatoid arthritis and mixed connective tissue disease. However, concurrent erythema nodosum and serositis has rarely been reported. We describe a case of MDS with erythema nodosum and immune-mediated pericardial effusion in a 34-year-old woman.

Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival. MATERIALS AND METHODS: The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M: F=25: 20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated. RESULTS: Thirty-seven patients were treated with 5-FU/ LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy. CONCLUSION: These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Clinical Aspects of Pregnancy and Delivery in Patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP)

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder. METHODS: We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003. RESULTS: Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70, 040/mm3, 83, 960/mm3, and 62, 680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage. CONCLUSION: Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications.

Combination Chemotherapy of Heptaplatin, Paclitaxel and 5-Fluorouracil in Patients with Advanced Gastric Cancer: a Pilot Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. MATERIALS AND METHODS: Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m(2) iv on day 1, heptaplatin 400 mg/m(2) iv on day 2 and 5-fluorouracil 800 mg/m(2) on day 2~4 were administered and the regimen was repeated every 3 weeks. RESULTS: The median age of the patients was 60 years (range: 32~74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26~8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48~6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26~17.44). A median of 3 cycles (range: 1~7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life- threatening complication of pneumonia. CONCLUSION: The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.

Phase II Study of Irinotecan, 5-Fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as First-line Therapy / Journal of the Korean Cancer Association, 대한암학회지

BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer. MATERIALS AND METHODS: Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m2 on days 1 and 15; 5-FU 400 mg/m2 bolus IV with 600 mg/m2 by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m2 on days 1, 2, 15 and 16, every 4 weeks. RESULTS: The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty- two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/ 18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity. CONCLUSION: The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.

Radiofrequency Ablation for Metastatic Hepatic Tumor in Colorectal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to assess the efficacy and safety of radiofrequency ablation (RFA) to treat hepatic metastasis in patients with colorectal carcinoma. MATERIALS AND METHODS: Between May 1999 and July 2002, a total of 45 tumors in 24 patients with colorectal cancer were treated with RFA. Thirteen patients received systemic chemotherapy after the RFA procedure. The ablation was performed percutaneously under ultrasound guidance using cool-tip or expandable electrodes and an RF generator. The medical records as well as the CT scan results taken every 3 months were retrospectively reviewed. RESULTS: The median follow-up duration of the surviving patients was 11.7 months (4.6~32.2 months). Complete tumor necrosis was achieved in 17 patients (70.8%) on an immediate (<24 hrs) CT scan. The median survival was 17.1 months. The 1- and 2-year survival rates were 80.5 and 25.8%, respectively. In a univariate analysis, complete necrosis, tumor size and post-RFA chemotherapy were significant factors for survival. Nineteen of the 24 patients developed a recurrence or progressed (79.2%). The median progression free survival was 5.5 months. There were no treatment related deaths or serious adverse effects, with the exception of one case of respiratory failure. CONCLUSION: These results suggest that RFA is a well-tolerated and effective method to treat hepatic metastasis in colorectal carcinomas.

Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS: Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement. RESULTS: Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION: This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients.

Combination Chemotherapy of Oxaliplatin and Capecitabine in Patients with Metastatic Colorectal Cancer: a Pilot Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin and capecitabine in patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between December 2001 and April 2003, fourteen patients were enrolled in this study. Oxaliplatin, 80 mg/m(2), was administered intravenously on day 1, and capecitabine, 1, 250 mg/m(2) bid po (total daily dose 2, 500 mg/m(2)), was given on days 1~14 of 3 week cycles. RESULTS: The median age of the patients was 57 years (range: 41~74), and the most common sites of metastasis were liver, lung or lymph node. Of the 12 evaluable patients, the overall response rate was 41.7%, but with no complete response. The median response duration and median progression free survival of 12 patients were 42 and 24.4 weeks, respectively. The median overall survival was not reached. A median 6 (range: 1~9), and a total 80, cycles were administered to 14 patients. 80 cycles were evaluable for toxicity. The most common hematological toxicities were NCI grades I/II anemia (45%), leucopenia (33.75%) and thrombocytopenia (17.5%). The most common non-hematological toxicities were nausea/ vomiting (28.75/5%) and neurotoxicity (8.75%). Hand and foot syndrome was noted in only 3.75%. There was no life-threatening toxicity. CONCLUSION: Oxaliplatin and oral capecitabine combination chemotherapy showed significant activity and favorable toxicity in patients with metastatic colorectal cancer. Further studies, with larger numbers of patients and long-tern follow-up will be needed.

Clinical significance of microvessel density in multiple myeloma patients

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.

Detection of Malignant Cells in Pleural Fluid or Ascites by CD44v8-10/CD44v10 competitive RT-PCR

BACKGROUND: CD44 is a cell surface adhesion molecule which has been implicated in various biologic functions as lymphocyte homing and activation, cellular migration and extracellular matrix adhesion. Over-expression of CD44v8- 10 has been found in several cancers and is considered to be associated with tumor progression and metastasis. Recently, a novel molecular method, CD44v8- 10/CD44v10 competitive reverse transcription-polymerase chain reaction(RT-PCR) has been developed for detecting cancer cells over-expressing CD44v8-10. METHODS: We analyzed from benign and malignant pleural effusion and ascites by CD44 competitive RT-PCR and compared to the conventional cytology. RESULTS: The CD44 competitive RT-PCR analysis showed that all the 24 samples associated with benign disease presented a predominant expression of the CD44v10 transcript (v8-10/v10 ratio: 0.126-0.948), whereas 6 of 7 malignant pleural samples associated with cytology positive cancer expressed the CD44v8-10 transcript (v8-10/v10 ratio > 1.00). CONCLUSION: These results indicate that CD44 competitive RT-PCR assay is a useful and adjunct to cytological examination in cancer diagnosis, especially in detecting exfoliated cancer cells in pleural effusion.

Clinical Impacts of Tumor Cell Contamination of Hematopoietic Stem Cell Products in Metastatic Breast Cancer Patients undergoing Autologous Peripheral Blood Stem Cell Transplantation: Multicenter Trial

To determine whether the tumor cell contamination of peripheral blood stem cells influences clinical impacts on high-dose chemotherapy in patients with metastatic breast cancer, we analyzed carcinoembryonic antigen (CEA) mRNA in the apheresis products by nested RT-PCR (reverse transcriptase-polymerase chain reaction). A total of 38 metastatic breast cancer patients and ten normal healthy subjects as a negative control were included. Twenty out of 38 (51.3%) apheresis products from patients with metastatic breast cancer were positive for CEA mRNA. CEA mRNA was noted in 54.8% (17/31) of patients mobilized with chemotherapy plus G-CSF and 42.8% (3/7) of patients with G-CSF alone. There was no significant difference in age, estrogen receptor, menopausal status, mobilization method, disease free interval, or number of metastasis sites (1 vs >/=2) between positive and negative groups. The presence of CEA mRNA in apheresis products did not influence the time to progression and overall survival in both groups. However, both the univariate and the multivariate analysis disclosed that the number of metastasis was associated with survival significantly. We suggest that the tumor cell contamination does not predict poor treatment outcome in patients with metastatic breast cancer.

A Case of Primary Intestinal T-Cell Lymphoma Involving Entire Gastrointestinal Tract: Esophagus to Rectum

Primary intestinal T-cell lymphoma is a rare disease entity, which is approximately 10% to 25% of intestinal lymphomas, and most of the lymphomas occur in the small intestine. We report here a case of a 56-year-old woman who has been suffering from chronic diarrhea and weight loss for 6 months. Abdominal CT scan and small bowel series showed diffuse wall thickening of the small bowel. Gastroscopic examination showed diffuse erythematous lesions on the esophagus and small gastric ulcerations on the antrum of the stomach, and colonoscopic examination also showed multiple punched-out ulcerations and erosions on the entire colon, including the sigmoid colon to the terminal ileum. Diffuse infiltration of CD 3 positive lymphoma cells was found on biopsy. The patient was diagnosed as primary intestinal T-cell lymphoma with diffuse involvement of the entire gastrointestinal tracts from the esophagus to the rectum. Although the patient received systemic combination chemotherapy and achieved partial response initially, the lymphoma relapsed repeatedly.