The optimal sequence of bronchial brushing and washing for diagnosing peripheral lung cancer using non-guided flexible bronchoscopy.

The optimum sequence of bronchial brushing and washing for diagnosing peripheral lung cancer, defined as an invisible endobronchial tumour, is not clear and requires further study. We prospectively obtained washing samples after brushing in patients with peripheral lung tumours during non-guided flexible bronchoscopy (FB) to investigate the diagnostic yield of these samples and conducted a retrospective review of the prospectively collected data. The study included 166 patients who met the inclusion criteria. The overall diagnostic yield of bronchial brushing and washing for peripheral lung cancer was 52.4%. The diagnostic yields of brushing and washing were 37.3% and 46.4%, respectively, and that of washing was superior according to McNemar's test (p = 0.017, κ = 0.570). Furthermore, washing was diagnostic, whereas brushing was not, in 15.1% of all cases. Comparison of positive washing cytology (brushing) with the respective pathological diagnosis yielded a concordance rate of 88.3% (90.3%), with κ = 0.769 (0.801) (p < 0.001). Performing washing after brushing during non-guided FB is a very safe, cost-effective procedure that may help improve the diagnostic yield in patients with suspected peripheral lung cancer. Our information will also benefit clinicians performing diagnostic bronchoscopy in patients with suspected peripheral lung cancer when fluoroscopic guidance or advanced bronchoscopy techniques are not available.

Comparison of PANAMutyper and PNAClamp for Detecting KRAS Mutations from Patients With Malignant Pleural Effusion.

BACKGROUND/AIM: KRAS is one of the frequently mutated genes in human cancers and often relates with drug resistance and poor prognosis. PANAMutyper™ is a novel technology that integrates PNAClamp™ and PANA S-Melting™. In the present study, PANAMutyper™ and PNAClamp™ were compared for the detection of KRAS mutations using different samples of patients with malignant pleural effusion. PATIENTS AND METHODS: A total of 103 patients (including 56 lung adenocarcinoma, 10 lung squamous carcinoma, 17 small cell lung cancer, 3 large cell lung cancer, 3 stomach cancer, 2 ovarian cancer, and others) with malignant pleural effusion were investigated using matched tumor tissue, cell block, and pleural effusion samples. The diagnostic performance of these two methods was compared. RESULTS: KRAS mutations were detected in 18 (17.5%) of 103 patients using tissue, cell block, and pleural effusion samples. All 18 patients with KRAS mutations were detected by PANAMutyper™ using any sample type, however, only 7 cases were detected by PNAClamp™. Among the subtypes of KRAS mutations, substitution in codon 12, 35G>T was the most frequent, followed by substitution in codon 12, 35G>A and codon 12, 34G>A. In pleural effusion specimens, PANAMutyper™ showed a better diagnostic performance compared to PNAClamp™. CONCLUSION: PANAMutyper™ had a diagnostic superiority for the detection of KRAS mutations in patients with malignant pleural effusion compared to PNAClamp™, although there was a concordance between PANAMutyper™ and PNAClamp™ results. Therefore, PANAMutyper™ can be used for a more sensitive and accurate detection of KRAS mutations.

Comparison of PNA Clamping-assisted Fluorescence Melting Curve Analysis and PNA Clamping in Detecting EGFR Mutations in Matched Tumor Tissue, Cell Block, Pleural Effusion and Blood of Lung Cancer Patients With Malignant Pleural Effusion.

BACKGROUND/AIM: This study compared the efficacy of PANAMutyper™, a novel technology that integrates PNAClamp™ and PANA S-Melting™, and PNAClamp™ alone for the detection of EGFR mutations in lung cancer patients. MATERIALS AND METHODS: PANAMutyper™ and PNAClamp™ were used to assess the EGFR mutation status in tissue, cell block, pleural effusion, and blood samples of 90 lung cancer patients with malignant pleural effusion. RESULTS: PANAMutyper™ detected more EGFR mutations than PNAClamp™, especially in body fluids (pleural effusion and serum). Patients with additional EGFR mutations detected using PANAMutyper™ had a favorable response to EGFR-tyrosine kinase inhibitor (TKI) treatment. CONCLUSION: The diagnostic performance of PANAMutyper™ was superior to that of PNAClamp™ for the detection of EGFR mutations. It was also better at identifying lung cancer patients with malignant pleural effusion who were likely to benefit from EGFR-TKI treatment.

Small-cell Lung Cancer Presenting as Fatal Pulmonary Hemorrhage.

Small-cell lung cancer (SCLC) is a lung cancer histological subtype unusual in its favorable response to cytotoxic chemotherapy. Life-threatening manifestations at presentation are rarely reported and should be an important clinical concern. We report a case of a 63-year-old man presenting with rapid-onset refractory severe thrombocytopenia, development of massive hemoptysis, and death from respiratory failure. This case provides clinicians a reference for this unusual presentation and carries clinical implications for managing SCLC patients.

Dramatic response of acute disseminated intravascular coagulation to erlotinib in a patient with lung adenocarcinoma with activating EGFR mutation.

Disseminated intravascular coagulation (DIC) is a commonly encountered clinical situation characterized by thrombotic occlusion or bleeding in patients with lung cancer. DIC in patients with cancer is usually asymptomatic, taking a chronic form as a compensatory mechanism. Although acute DIC in patients with lung cancer is rarely reported, it can be fatal. We herein describe a patient with lung adenocarcinoma with an activating mutation of the epidermal growth factor receptor (EGFR) gene who developed acute DIC after minor surgical excision. The patient's condition dramatically improved immediately after administration of erlotinib. This report alerts physicians to the occurrence of acute DIC and serves as a reference in treating EGFR mutation-positive lung cancer in patients with DIC.

Late-onset distant metastatic upper urinary tract urothelial carcinoma mimicking lung adenocarcinoma.

Urothelial carcinomas (UCs) can occur in the upper urinary tract or lower urinary tract. Upper urinary tract urothelial carcinoma (UUT-UC) is relatively a rare disease and accounts for only about 5% of UC cases. Sporadic cases of late-onset metastasis, associated with UC of the bladder, have occasionally been reported. In contrast, no late-onset distant metastatic UUT-UC without local recurrence has, to the best of our knowledge, been reported in the English literature. We report an extremely rare case of distant metastatic UC, mimicking lung adenocarcinoma that originated from UUT-UC 12 years previously.

Erlotinib induced trichomegaly of the eyelashes.

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.

Gender differences in susceptibility to smoking among patients with lung cancer.

BACKGROUND/AIMS: To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. METHODS: Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer who were smokers or had a history of smoking. Differences in individual susceptibility to smoking were estimated using a susceptibility index formula. RESULTS: Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV(1), liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 ± 19.2 vs. 42.9 ± 21.7 for pack-years; 1.4 ± 0.5 vs. 2.0 ± 0.6 for FEV(1); 3.0 ± 0.7 vs. 2.0 ± 0.6 for FVC; 4.5 ± 0.8 vs. 5.7 ± 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 ± 4.1 vs. 0.7 ± 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). CONCLUSIONS: The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.

Complete atrioventricular block secondary to bortezomib use in multiple myeloma.

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared.

High-resolution analysis of condition-specific regulatory modules in Saccharomyces cerevisiae.

We present an approach for identifying condition-specific regulatory modules by using separate units of gene expression profiles along with ChIP-chip and motif data from Saccharomyces cerevisiae. By investigating the unique and common features of the obtained condition-specific modules, we detected several important properties of transcriptional network reorganization. Our approach reveals the functionally distinct coregulated submodules embedded in a coexpressed gene module and provides an effective method for identifying various condition-specific regulatory events at high resolution.

[Incidence and risk factors of acute hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma].

BACKGROUND/AIMS: Although transcatheter arterial chemoembolization (TACE) is a major treatment modality for unresectable hepatocellular carcinoma (HCC), acute hepatic failure after TACE is not rare. However, reports dealing with this important complication are not good enough and results are often variable. The purpose of this study was to evaluate the incidence and associated risk factors of acute hepatic failure after TACE. METHODS: From January 2001 to November 2004, six hundred and thirty-two TACE sessions were performed in 377 patients (294 men and 83 women). Adriamycin mixed lipiodol solution and gelfoam were used for TACE. Various clinical and radiological factors before and after the procedure were reviewed retrospectively. Univariate and multivariate analyses were performed to evaluate the risk factors associated with the development of acute hepatic failure after TACE. RESULTS: Acute hepatic failure occurred in 76 (12.0%) of the 632 TACE sessions within 14 days. Univariate analysis revealed that Child-Pugh class, 1st TACE, total bilirubin level, number of involved segments, total size of tumor, presence of right portal vein thrombosis (PVT) or main PVT, involvement of segment 1, 5, 6, 7, modified UICC stage, and doses of chemotherapeutic agent were significantly different between the patients with or without hepatic failure after TACE. Among them, elevated total bilirubin (p=0.001, E (beta)=1.449), presence of right (p=0.035, E (beta)=2.109) or main (p=0.011, E (beta)=4.067) PVT were independently associated factors in multivariate analysis. CONCLUSIONS: The incidence of acute hepatic failure after TACE was 12.0%. Elevated bilirubin level and portal vein thrombosis could be considered as the predictive factors for acute hepatic failure after TACE in HCC patients.

Surgical treatment of malignant mediastinal neurogenic tumors in children.

INTRODUCTION: The aim of this study was to identify the role of surgical resection in the treatment of malignant mediastinal neurogenic tumors in children. MATERIALS AND METHODS: Thirty-eight consecutive children, who underwent surgical resection of a malignant mediastinal neurogenic tumor between 1986 and 2004, were included in this study. The tumor cell types were neuroblastoma in 23 patients (60.5%), ganglioneuroblastoma in 14 (36.8%), and malignant neuroepithelioma in 1 (2.6%). Surgery was performed for curative resection in localized tumors and salvage resection of residual mediastinal masses after chemotherapy in stage IV tumors. Of the 16 patients (42.1%) who underwent salvage resection, 14 had neuroblastoma and 2 ganglioneuroblastoma. RESULTS: Mean patient age was 3.4+/-3.0 years (1 month-13 years) and 26 patients (68.4%) were symptomatic at presentation. Adjacent structure invasion was found in eight patients (21.1%), invasion of chest wall in four, heart and vena cava in two, lung in one, and chest wall and lung in one. Complete gross resection was possible in 30 patients (78.9%) and there was no surgical mortality. Surgical morbidity occurred in 10 patients (26.3%) and Horner's syndrome was the most frequent complication (n=7). The 5-year survival was 95.2% for a localized tumor and 52.5% for a stage IV tumor (p=0.004). The significant risk factors of long-term survival were adjacent structure invasion (p=0.002) and a stage IV tumor (p=0.002) by multivariate Cox regression analysis. CONCLUSIONS: Surgical resection of localized malignant mediastinal neurogenic tumor in children showed good long-term survival, and salvage operations after chemotherapy showed acceptable long-term survival.

Lymphadenectomy extent is closely related to long-term survival in esophageal cancer.

OBJECTIVE: The optimal extent of lymphadenectomy during esophagectomy for esophageal cancer remains debatable. The aim of this study was to identify the effect of the extent of lymphadenectomy on survival and recurrence after esophagectomy in esophageal cancer. MATERIALS AND METHODS: Two hundred thirty-three patients who were operated on between January 1995 and December 2003 due to esophageal cancer were included. The study subjects were stage I, II, and III esophageal squamous cell carcinoma patients who had undergone curative resection without neoadjuvant chemotherapy or chemoradiation therapy. To analyze the extent of lymphadenectomy, lymph node stations were classified into three regions, namely, paraesophageal, upper thoracic, and abdominal regions, and patients were allocated to one of three groups, i.e., group 1 received lymphadenectomy in one region only, group 2 in two regions, and group 3 in three regions. RESULTS: The pathologic stages were stage I in 57 (24.5%), IIA in 69 (29.6%), IIB in 27 (11.6%), and III in 80 (34.3%). There were 67 patients in group 1, 102 in group 2, and 64 in group 3. The operative mortality rate was 2.1%. Postoperative morbidity rates and hospital stay periods were no different for the three groups. The overall 5-year survivals in groups 1, 2, and 3 were 21.2, 36.3, and 53.7%, respectively, and there were statistically significant differences between groups (p=0.019). Overall 5-year survival for those with N0 disease was different significantly in the groups (26.7, 56.8, and 74.4% in groups 1, 2, and 3, respectively; p=0.001). However, overall 5-year survival differences for N1 disease were not significant. Group 1 showed more frequent locoregional recurrence than groups 2 and 3 (34.3 vs 12.7% and 15.6%, p=0.002). However, distant recurrence was no different in the three groups. CONCLUSIONS: A wider extent of lymphadenectomy in esophageal cancer was associated with better long-term survival than limited lymphadenectomy, especially in N0 patients. In addition, increased survival was found to be inversely associated with locoregional recurrence.

[A case of intraluminal gallbladder hematoma after percutaneous liver biopsy].

Percutaneous liver biopsy is valued in the diagnosis of diffuse or localized liver disease. Serious complications after ultrasonography-guided liver biopsy are rare. We report a case of a 69-year-old man who underwent a percutaneous liver biopsy for the evaluation of his underlying liver disease with subsequent late complication of intraluminal gallbladder hematoma.