Sang-Gon Park

Comparison of laboratory characteristics between acute promyelocytic leukemia and other subtypes of acute myeloid leukemia with disseminated intravascular coagulation

Background Acute promyelocytic leukemia (APL) is an acute myeloid leukemia (AML) subtype with distinctive cell morphology, molecular presentation, clinical course, and treatment. About 90% of APL patients present with hemorrhagic complications due to disseminated intravascular coagulation (DIC). When APL is suspected, all-trans retinoic acid (ATRA) treatment is recommended even before confirmation by molecular tests. Specific criteria for differentiating unconfirmed APL from other AML subtypes with DIC are currently lacking. We aimed to achieve the early diagnosis of APL from other AML types with DIC by restricting the DIC criteria. Methods We retrospectively analyzed 29 patients newly diagnosed with AML accompanied by DIC from January 2005 to January 2013. Results Fibrin degradation products (FDP) (77.7 µg/mL vs. 23.7 µg/mL, p=0.026), D-dimer (7,376.2 ng/mL vs. 1,315.2 ng/mL, p=0.018), and TIBC (264.4 µg/dL vs. 206.8 µg/dL, P=0.046) were higher, while fibrinogen (133.8 mg/dL vs. 373.2 mg/dL, p<0.001), WBC (14.988×109/L vs. 70.755×109/L, p=0.015), and ESR (7.1 mm/h vs. 50.0 mm/h, p <0.001) were lower in APL patients than in the patients with other AML subtypes. FDP ≥27 µg/mL, D-dimer ≥2,071 ng/mL, and fibrinogen ≤279 mg/dL were our threshold values. These markers may be characteristic to APL and helpful in presumptive diagnosis. Conclusion APL may be differentiated from other AML subtypes by core markers of DIC (FDP, D-dimer, and fibrinogen). We suggest that clinicians set new diagnostic thresholds by restricting the DIC criteria. These findings support the early initiation of ATRA, prior to confirmation by PML-RARA molecular testing.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum

Background/Aims Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. Methods Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. Results Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). Conclusions Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Bowel perforation associated sunitinib therapy for recurred gastric gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Several recent findings that there are activating mutations in the KIT and PDGFRA (platelet-derived growth factor receptor-α) genes of GISTs provide the rationale for using targeted therapies such as imatinib or sunitinib. Sunitinib, an oral multitargeted receptor tyrosine kinase inhibitor that inhibits kinases such as KIT, PDGFR (platelet-derived growth factor recepter), and VEGFR (vascular endothelial growth factor receptor), was recently approved for the treatment of imatinib-refractory GIST. Sunitinib is generally well tolerated and has an acceptable toxicity profile; an adverse event such as bowel perforation is rare. We present a patient with imatinib-refractory GIST who was successfully treated using sunitinib, but developed bowel perforation. The mechanism involved in bowel perforation associated with sunitinib is unknown. However, we presume that in our patient, the dramatic reduction in disseminated peritoneal metastases and bowel invasion of recurrent GIST during sunitinib treatment might have resulted in the bowel perforation.

Health-related Quality of Life Among Cancer Survivors in Korea: The Korea National Health and Nutrition Examination Survey

OBJECTIVE The purpose of this study was to investigate the quality of life among cancer survivors compared with individuals without a history of cancer (noncancer controls) using the Korea National Health and Nutrition Examination Survey. METHODS The study subjects were 783 adult cancer survivors and 36 456 noncancer controls who participated in the third, fourth and fifth Korea National Health and Nutrition Examination Survey. Demographic factors, health-related behavior, clinical characteristics and health-related quality of life were assessed with self-reported questionnaires. The EuroQoL-5Dimension was used to evaluate health-related quality of life. Descriptive statistics and multiple regression analysis were used to compare health-related quality of life between cancer survivors and noncancer controls. RESULTS About 67% were women and the mean age of the cancer survivors was 60.9 ± 12.4 years. About 52% of survivors were diagnosed with cancer between 45 and 64 years, and more than half of cancer survivors were diagnosed 5 years or less before the interview. The pain/discomfort dimension was the highest reported problem: 43.6% for cancer survivors. The proportion of any reported problem was significantly higher among cancer survivors compared with noncancer controls in terms of mobility (adjusted odds ratio (aOR), 1.56, 95% confidence interval, 1.24-1.97), usual activities (aOR, 1.45, 95% confidence interval, 1.11-1.89), pain/discomfort (aOR, 1.26, 95% confidence interval, 1.04-1.52) and anxiety/depression (aOR, 1.61, 95% confidence interval, 1.29-2.01). CONCLUSIONS Cancer survivors had a significantly lower quality of life compared with noncancer controls. The pain/discomfort dimension was the highest reported problem in cancer survivors.

Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report.

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.

Spontaneous tumor lysis syndrome with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma unspecified

Tumor lysis syndrome is a well-described, serious complication of chemotherapy administered to treat malignancies. However, a very rare event resulting in the spontaneous necrosis of a tumor prior to therapy can also occur, which is termed spontaneous tumor lysis syndrome (STLS). We present a case of a 27-year-old male who presented to the hospital with epistaxis, dyspnea, and cervical lymphadenopathy. Laboratory findings included progressive pancytopenia, hyperuricemia, and acute renal failure. Bone marrow biopsy showed a T cell lymphoid neoplasm that had entirely infiltrated the marrow stroma. The patient was diagnosed with STLS in the setting of a T cell lymphoma with bone marrow infiltration. The patient was immediately treated with a blood transfusion and hemodialysis. After this urgent treatment, the patient’s pancytopenia resolved and the lymphadenopathy disappeared spontaneously. One month post-treatment, the patient’s cervical lymphadenopathy recurred and peripheral T cell lymphoma, not otherwise specified, was confirmed. STLS has previously been reported, however, most known cases of STLS did not show a decreased tumor burden resulting from massive tumor cell death. We present a rare case of STLS with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma not otherwise specified.

Evaluation of the prevalence and clinical impact of toxocariasis in patients with eosinophilia of unknown origin.

Background/Aims Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin. Methods We performed a retrospective chart review. After evaluation of cause of eosinophilia, the patients suspected of eosinophilia of unknown origin performed immunoglobulin G antibody specific assay for the Toxocara canis larval antigen by enzyme-linked immunosorbent assay. Results This study evaluated 113 patients, 69 patients (61%) were suspected of eosinophilia of unknown origin. Among these 69 patients, the frequency of T. canis infection was very high (45 patients, 65.2%), and albendazole treatment for 45 eosinophilia with toxocariasis was highly effective for a cure of eosinophilia than no albendazole group regardless of steroid (82.3%, p = 0.007). Furthermore, among the nonsteroid treated small group (19 patients), albendazole treatment for eosinophilia were more effective than no albendazole group, too (83.3% vs. 28.6 %, p = 0.045). Conclusions The prevalence of toxocariasis was high among patients suspected of eosinophilia of unknown origin; therefore, evaluation for T. canis infection is recommended for patients with eosinophilia of unknown origin. Furthermore, for patients suspected of eosinophilia of unknown origin who have positive results for T. canis, albendazole treatment may be considered a valuable treatment option.

Rare complication of bronchoesophageal fistula due to pulmonary mucormycosis after induction chemotherapy for acute myeloid leukemia: a case report

BackgroundMucormycosis is a rare and life-threatening invasive fungal infection. Pulmonary mucormycosis commonly occurs in patients with severe neutropenia. Typically, pulmonary mucormycosis causes tissue necrosis resulting from angioinvasion and subsequent thrombosis, so most cases can occur with necrotizing pneumonia and/or hemoptysis. Some complex cases may invade adjacent organs, such as the mediastinum, pericardium, and chest wall. However, to the best our knowledge there is little known regarding bronchoesophageal fistula due to pulmonary mucormycosis after induction chemotherapy for acute myeloid leukemia. We present a case report about this unusual presentation.Case presentationA 51-year-old Korean man was diagnosed as having acute myeloid leukemia and received induction chemotherapy. After prolonged severe neutropenia, he complained of coughing with aspiration. Imaging showed a bronchoesophageal fistula with extensive necrotizing pneumonia in the middle and lower lobes of his right lung. Bronchoscopy showed near total tissue necrosis in the middle lobe of his right lung, creating an orifice. A bronchial scope was passed through and was able to be connected with his esophagus; a bronchial wall biopsy was performed. Esophagoscopy revealed a large linear defect of his esophageal wall 30 cm from the incision that may have connected with the bronchus. A bronchial biopsy showed typical hyphae with necrotic tissue, indicating pulmonary mucormycosis. He was given amphotericin B, and a wide excision of lung and esophagus was planned. However, he suddenly died due to massive hemoptysis.ConclusionHere we present an extremely rare case of bronchoesophageal fistula with severe necrotizing pneumonia due to pulmonary mucormycosis.

Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy

Thymidylate synthase (TS) gene polymorphisms such as tandem repeat (TR) polymorphisms and single-nucleotide polymorphisms (SNPs) affect transcriptional efficiency of the TS gene and may be prognostic markers for fluoropyrimidine-based therapy in various gastrointestinal cancers. However, data for TS polymorphisms on clinical outcomes in advanced small bowel adenocarcinoma (SBA) are limited. We retrospectively enrolled 58 locally advanced/metastatic SBA patients treated with first-line fluoropyrimidine-based chemotherapy and analyzed the relationship between TS genotypes and clinical outcomes in 30 patients who were available for tumor tissue. Based on TR polymorphisms and a G>C SNP in the promoter region of the TS gene, 74% of patients had high TS expression genotypes (2R/3RG, 3RG/3RC, 3RG/3RG); the remainder had low TS expression genotypes (2R/2R, 2R/3RC, 3RC/3RC). After a median follow-up of 48.8 months, median progression-free survival (PFS) and overall survival (OS) in all patients were 6.0 and 11.3 months, respectively. However, patients with low TS expression genotypes had better median PFS (12.8 vs. 4.3 months, P=0.027) and OS (28.8 vs. 8.9 months, P=0.025) than those with high TS expression genotypes. In multivariate analysis, poor Eastern Cooperative Oncology Group performance status [hazard ratio (HR), 2.85; 95% CI, 1.02-7.93] and high TS expression genotypes (HR, 3.49; 95% CI, 1.13-10.78) were independent prognostic factors for worse OS. Therefore, TS genotypes, based on a G>C SNP in the TR sequence of the TS gene, may be a useful biomarker for predicting outcomes for fluoropyrimidine-based chemotherapy in patients with locally advanced/metastatic SBA.

The oncogenic effects of p53-inducible gene 3 (PIG3) in colon cancer cells

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.