Allopurinol hypersensitivity syndrome in patients with hematological malignancies: characteristics and clinical outcomes

BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.

High Expression of Ribonucleotide Reductase Subunit M2 Correlates with Poor Prognosis of Hepatocellular Carcinoma

BACKGROUND/AIMS: Ribonucleotide reductase subunit M2 (RRM2) catalyzes the production of deoxynucleotide triphosphates, which are necessary for DNA synthesis. RRM2 has been reported to play an active role in tumor progression, and elevated RRM2 levels have been correlated with poor prognosis for colorectal cancer patients. This study aimed to elucidate the prognostic significance of RRM2 protein expression in hepatocellular carcinoma after surgery. METHODS: RRM2 protein expression was evaluated using immunohistochemistry in tumor tissues from 259 hepatocellular carcinoma patients who underwent curative hepatectomy. RESULTS: High RRM2 expression was observed in 210 of 259 patients (81.1%) with hepatocellular carcinomas. High RRM2 expression was significantly associated with viral etiology (p=0.035) and liver cirrhosis (p=0.036). High RRM2 expression was correlated with early recurrence (p=0.004) but not with late recurrence (p=0.144). Logistic regression analysis revealed that high RRM2 expression (p=0.040) and intrahepatic metastasis (p<0.001) were independent predictors of early recurrence. High RRM2 expression unfavorably influenced both shorter recurrence-free survival (p=0.011) and shorter disease-specific survival (p=0.002) and was an independent predictor of shorter disease-specific survival (p=0.008). CONCLUSIONS: High RRM2 protein expression might be a useful marker for predicting early recurrence and may be a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy.

KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing

BACKGROUND: KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required in order to accurately test for KRAS status. METHODS: We compared direct Sanger sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method in 134 NSCLCs and explored associations with clinicopathological factors. Next-generation sequencing (NGS) was used to validate the results of discordant cases. To increase the resolution of low-level somatic mutant molecules, PNA-mediated PCR clamping was used for mutant enrichment prior to NGS. RESULTS: Twenty-one (15.7%) cases were found to have the KRAS mutations using direct sequencing, with two additional cases by the PNA-mediated PCR clamping method. The frequencies of KRAS mutant alleles were 2% and 4%, respectively, using conventional NGS, increasing up to 90% and 89%, using mutant-enriched NGS. The KRAS mutation occurs more frequently in the tumors of smokers (p=.012) and in stage IV tumors (p=.032). CONCLUSIONS: Direct sequencing can accurately detect mutations, but, it is not always possible to obtain a tumor sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide results with sufficient sensitivity.

Micropapillary Mucinous Adenocarcinoma of the Lung: A Brief Case Report

No abstract available.

Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma

BACKGROUND: The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma. METHODS: We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma. RESULTS: Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus. CONCLUSIONS: The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).