Young Jin Yuh

Clinical heterogeneity of extranodal NK/T-cell lymphoma, nasal type: a national survey of the Korean Cancer Study Group

BACKGROUND This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity. PATIENTS AND METHODS Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset. RESULTS NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset. CONCLUSION NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.

Multiple gastrointestinal stromal tumors with a germline c-kit mutation

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder; thus far, only seven families have been reported with c‐kit germline mutations. Presented herein is a case of multiple intestinal GIST in a 38‐year‐old man with a germline mutation of the c‐kit gene. Operative specimens of the jejunal segment and multiple wedge resection specimens included approximately 30 masses, ranging in size from 1.0 to 6.0 cm. Microscopically, the tumors were composed of CD117‐positive spindle/epitheloid cells with variable numbers of mitotic counts, a characteristic of GIST. The mitotic rate increased to more than 5/50 high‐power fields. Interestingly, marked hypertrophy of the myenteric plexus with CD117‐positive cells was identified in the intestinal segment. By polymerase chain reaction–single‐strand conformation polymorphism analysis and direct DNA sequencing, a heterozygous c‐kit missense mutation at nucleotide 1676 of codon 559 (T → C, Val → Ala), part of the juxtamembrane domain, was detected in the normal tissue. The same mutation was homozygous in the tumor samples. The present case is the first proven case of multiple GIST with a c‐kit germline mutation in Korea and is distinguishable from other reported germ‐line c‐kit mutations because the same 1676 T → C missense mutation occurs in the normal allele as well as the affected allele, although the significance of the identical mutations remains to be investigated.

Primary Cardiac Lymphoma Presenting With Atrioventricular Block

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan.

Korean patients with superwarfarin intoxication and their outcome.

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

Gemcitabine and Carboplatin Combination Chemotherapy for Elderly Patients with Advanced Non-small Cell Lung Cancer: A Feasibility Study

PURPOSE Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients. MATERIALS AND METHODS THE ELIGIBILITY CRITERIA WERE AS FOLLOWS: pathologically confirmed NSCLC, an age >or=65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m(2) was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration. RESULTS From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65 approximately 75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4 approximately 64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy. CONCLUSIONS Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

Phase II trial of combination chemotherapy with gemcitabine, 5-fluorouracil and cisplatin for advanced cancers of the bile duct, gallbladder, and ampulla of Vater

AIMS AND BACKGROUND For advanced cancers of the bile duct, gallbladder and ampulla of Vater, there are only a few treatment options. We explored the efficacy of the combination of gemcitabine, 5-fluorouracil and cisplatin for advanced biliary cancers. METHODS From September 2003 to April 2010, 28 patients with recurrent or metastatic biliary tract cancer were enrolled. A treatment regimen consisting of gemcitabine (800 mg/m² at a fixed dose rate on days 1 and 8), 5-fluorouracil (1 g/m²/day continuous infusion for 4 days) and cisplatin (60 mg/m² on day 2) was repeated every 3 weeks. RESULTS One (3.6%) patient showed complete response, 8 (28.6%) partial response, 14 (50%) stable disease and 5 (17.9%) disease progression. Overall, the objective response rate was 32.1% (95% CI, 17.9-50.6%) and the disease control rate was 82.1% (95% CI, 64.4-92.1%). Median progression-free survival and overall survival were 7.6 months (95% CI, 5.5-9.7) and 11.2 months (95% CI, 6.8-15.5), respectively. G3/4 neutropenia was observed in 44 (24.3%) of 181 cycles and G3/4 thrombocytopenia in 48 (26.5%) of 181 cycles. There was no treatment-related mortality. CONCLUSIONS The combined regimen of gemcitabine, 5-fluorouracil and cisplatin has comparable activity for patients with advanced cancer of the bile duct, gallbladder and ampulla of Vater. Toxicity was tolerable but substantial.

A Phase II Study of Ifosfamide, Methotrexate, Etoposide, and Prednisolone for Previously Untreated Stage I/II Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Multicenter Trial of the Korean Cancer Study Group

BACKGROUND Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL). METHODS Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT). RESULTS Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively. CONCLUSION Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.

A Phase II Trial of Paclitaxel, 5-fluorouracil (5-FU) and Cisplatin in Patients with Metastatic or Recurrent Gastric Cancer

PURPOSE We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer. MATERIALS AND METHODS Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m(2) on day 1, 5-FU 1 g/m(2)/day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m(2) on day 1 were administered. This regimen was repeated every 3 weeks. RESULTS A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0 approximately 77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed. CONCLUSIONS The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and acceptable toxicity for treating metastatic gastric cancer.

A Case of Invasive Thymoma with Endotracheal Polypoid Growth

Thymomas are one of the most common neoplasms of the mediastinum derived from thymic epithelium. It is common that invasive thymoma invades the lung, pericardium, and great vessels. Airway compression by mass effect also occurs, but direct polypoid tumor growth into the airway is extremely rare. Only 20 cases of invasive thymoma with endobronchial polypoid growth have previously been reported globally. However, there is no case report of invasive thymoma with endotracheal growth. Herein, we report a rare case of invasive thymoma with endotracheal polypoid growth in a 28-year-old woman.

actate Dehydrogenase (LDH) as a Tumor Marker for Non-small Cell Lung Cancer

PURPOSE To determine the prognostic value of pre- treatment serum LDH levels and the LDH isoenzyme pattern for non-small cell lung cancer, and to determine the relationship between the response to chemotherapy and the changes in serum LDH levels following chemotherapy. MATERIALS AND METHODS Patients with pathologically confirmed non-small cell lung cancer were entered onto this study. Their serum LDH levels were assessed prior to chemotherapy, with the LDH isoenzyme being assessed in patients with high initial serum LDH levels. The serum LDH levels were re-assessed following 2 cycles of chemotherapy. The relationship between the response to chemotherapy, pre-treatment serum LDH levels and LDH isoenzyme pattern and the changes in serum LDH levels, following chemotherapy, were evaluated. RESULTS 49 patients were entered onto this study. The pre-treatment serum LDH levels were normal in 26 patients, and elevated in 23. The LDH isoenzyme was evaluated in 15 patients, with LDH2 being elevated the most frequently. The response rate to chemotherapy was 42.9% in all 42 patients able to be evaluated, 45.8% in patients with normal serum LDH levels and 41.2% in patients with elevated serum LDH levels. This difference was not statistically significant (p=0.767). The median survival was 37 weeks in all patients able to be evaluated, 38 weeks in those with normal serum LDH levels and 31 weeks in those with elevated serum LDH levels. These differences were not statistically significant (p=0.202). The patients with normal serum LDH levels following chemotherapy were more responsive to chemotherapy than those with elevated serum LDH levels following chemotherapy (response rate 51.4% vs. 0%, p=0.027). CONCLUSION The LDH2 are most commonly elevated in non small cell lung cancer patients. The pre-treatment serum LDH levels do not reflect the prognosis accurately. The serum LDH levels following chemotherapy are associated with the response to chemotherapy.