Identification of risk factors for post-induction hypotension in patients receiving 5-aminolevulinic acid: a single-center retrospective study.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) is useful as a photodynamic agent, but its use commonly leads to hypotension. Although avoiding a mean arterial pressure (MAP) < 60 mmHg is important, the incidence of MAP < 60 mmHg when using 5-ALA is unclear. Therefore, we conducted a retrospective study to assess the incidence of post-induction hypotension and identified risk factors of this phenomenon. METHODS: One-hundred and seventy-two consecutive patients who underwent transurethral resection of the bladder tumor or craniotomy with the use of 5-ALA were enrolled. The primary outcome was the incidence of post-induction hypotension, defined as MAP < 60 mmHg during the first 1 h after anesthesia induction. We divided participants into the normal blood pressure group (group N) and the hypotension group (group L). RESULTS: The incidence of post-induction hypotension was 70% (group L = 121, group N = 51). Multivariate analysis revealed that female sex was an independent factor of post-induction hypotension (odds ratio [OR] 3.95; 95% confidence interval [CI] 1.21-12.97; p = 0.02). Systolic blood pressure < 100 mmHg before anesthesia induction and general anesthesia were also identified as significant independent factors (OR 13.30; 95% CI 1.17-151.0; p = 0.04 and OR 25.84; 95% CI 9.80-68.49; p < 0.001, respectively). CONCLUSIONS: The incidence of post-induction hypotension was 70% in patients using 5-ALA. Female sex, systolic blood pressure < 100 mmHg before anesthesia induction, and general anesthesia might be independent factors of post-induction hypotension when using 5-ALA.

In-vitro proliferation assay with recycled ascitic cancer cells in malignant pleural mesothelioma: A case report.

BACKGROUND: We report the first case, to the best of our knowledge, of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy (KM-CART). The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to investigate anticancer drug susceptibility. CASE SUMMARY: A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites; more than 4000 mL of ascitic fluid was removed, filtered, and concentrated using KM-CART, and the cell-free ascitic fluid was reinfused into the patient to improve quality of life. Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine. Treatment with gemcitabine maintained stable disease for 4 mo. CONCLUSION: The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.

Indocyanine green fluorescence/thermography evaluation of intercostal muscle flap vascularization.

BACKGROUND: During anatomical lung resection in high-risk patients, the bronchial stump is covered with tissue flaps (e.g. pericardial fat tissue and intercostal muscle) to prevent bronchopleural fistula development. This is vital for reliable reinforcement of the bronchial stump. We evaluated the blood supply of the flap using indocyanine green fluorescence (ICG-FL) and thermography intraoperatively in 27 patients at high risk for developing a bronchopleural fistula. METHODS: Before reinforcing the stump with a flap, the fluorescence agent was intravenously injected and the blood supply was evaluated. The surface temperature of the flap was measured with thermography. The two modalities were then compared. RESULTS: ICG-FL intensity and surface temperature on the distal compared to the proximal side of the flap decreased by 32.6 ± 29.4% (P < 0.0001) and 3.5 ± 2.0°C (P < 0.0001), respectively. In patients with a higher ICG-FL intensity value at the tip than the median, the surface temperature at the tip decreased by 2.7 ± 1.7°C compared to the proximal side. In patients with a lower ICG-FL value at the tip, the surface temperature decreased by 4.6 ± 1.7°C (P = 0.0574). The bronchial stump reinforced the part of the flap with adequate blood supply; none of the patients developed a bronchopleural fistula. CONCLUSIONS: ICG-FL confirmed variation in the blood supply of the intercostal muscle flap, even if prepared using the same surgical procedure. Thermography analysis tends to correlate with the fluorescence method, but may be influenced by the state of flap preservation during surgery.

Correction: In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0152665.].

In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI) test and collagen gel droplet embedded culture drug sensitivity test (CD-DST) are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs. METHODS: The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status. RESULTS: HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003). The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026) in CD-DST. CONCLUSIONS: In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

Asymptomatic primary tuberculous pleurisy with intense 18-fluorodeoxyglucose uptake mimicking malignant mesothelioma.

BACKGROUND: The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by mycobacterial proliferation. Although it has been shown that pulmonary tuberculosis induces 18-fluorodeoxyglucose (FDG) uptake in active lesions, little is known about the application of FDG positron emission/computed tomography (FDG PET/CT) to the management of primary tuberculous pleurisy. CASE PRESENTATION: We report a case of asymptomatic primary tuberculous pleurisy presenting with diffuse nodular pleural thickening without distinct pleural effusion and parenchymal lung lesions mimicking malignant mesothelioma. An initial FDG PET/CT scan demonstrated multiple lesions of intense FDG uptake in the right pleura and thoracoscopic biopsy of pleural tissue revealed caseous granulomatous inflammation. The patient received antituberculous therapy for 6 months, with clearly decreased positive signals on a repeated FDG PET/CT scan. CONCLUSION: FDG PET/CT imaging may be useful for evaluating disease activity in tuberculous pleurisy patients with an unknown time of onset.

Comparison of epidermal growth factor receptor mutation analysis results between surgically resected primary lung cancer and metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Lung cancers with mutations in the epidermal growth factor receptor (EGFR) gene respond well to treatment with EGFR inhibitors. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered a useful modality to obtain samples from the mediastinal and hilar lymph nodes. However, the EGFR gene status of EBUS-TBNA samples may not always match that of primary tumors. METHODS: In 14 node-positive patients diagnosed by EBUS-TBNA, EGFR mutation analysis results were compared between EBUS-TBNA samples and surgically removed primary tumors. EGFR mutation was screened with peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp followed by direct sequence analysis. For one controversial case, gene mutation analyses were performed for the multiple micro-fractions of a metastatic lymph node, which exhibited the heterogeneous immunohistochemical features. RESULTS: EBUS-TBNA diagnosed one case of exon 21 point mutations, one case of exon 19 deletion, and 12 cases of wild-type EGFR. Results were consistent with those of surgically removed primary tumors in 13 of 14 cases. One case of wild-type EGFR diagnosed by EBUS-TBNA exhibited exon 21 point mutation in the surgically removed primary tumor. The metastatic lymph node targeted by EBUS-TBNA mostly consisted of cancer cells with wild-type EGFR; however, a minor component positive for thyroid transcription factor-1 (TTF-1) and surfactant-associated protein A (PE-10) exhibited EGFR mutation. CONCLUSION: The combination of EBUS-TBNA and PNA-LNA clamp is useful for EGFR mutation analysis. However, EGFR mutation status in EBUS-TBNA samples may not be consistent with that of the primary tumor when the tumor contains few EGFR mutations.

Thymic mucosa-associated lymphoid tissue lymphoma with immunoglobulin-storing histiocytosis in Sjögren's syndrome.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the thymus is extremely rare. Only 33 cases of thymic MALT lymphoma have been reported to date. We present the case of a 53-year-old Japanese woman with Sjögren's syndrome who was diagnosed with thymic MALT lymphoma. In addition, the patient had the characteristic clinical and pathological features of thymic MALT lymphoma, as found in most of the 33 previous cases, except that there was an immunoglobulin G (IgG) phenotype, i.e. Sjögren's syndrome, epithelial cysts, lymphoepithelial lesions, and marked plasmacytic differentiation. The serum IgA levels were also elevated with IgA kappa M protein. This hypergammaglobulinemia remained unchanged after operation. The serological abnormalities may not arise from MALT lymphoma itself and may arise from the immune system hyper-reactivity evoked by Sjögren's syndrome. Of further interest were marked accumulations of CD68-positive histiocytes containing abundant eosinophilic globular inclusions in their cytoplasm. These inclusions were immunopositive for IgG-kappa, suggesting immunoglobulin inclusion bodies. The globular immunoglobulin inclusion bodies have been reported in non-crystallized immunoglobulin-storing histiocytosis in only one patient with multiple myeloma. To our knowledge, this is the first case of thymic MALT lymphoma with marked accumulation of histiocytes with immunoglobulin inclusions in a patient with Sjögren's syndrome.

Establishment and molecular cytogenetic characterization of non-small cell lung cancer cell line KU-T1 by multicolor fluorescence in situ hybridization, comparative genomic hybridization, and chromosome microdissection.

A human lung adenocarcinoma cell line, designated KU-T1, was established from a Japanese man in Kochi Medical School. Conventional banding and multicolor fluorescence in situ hybridization (M-FISH) analyses of KU-T1 cells revealed a hyperdiploid chromosomal constitution and complex karyotypes. Comparative genomic hybridization showed several chromosomal copy number changes, and five regions that were highly amplified. Two of the five highly amplified regions, 1q and 3q, were identified from distributions of DNA sequences on a metaphase cell by FISH using chromosome microdissection-generated probes hybridized to 1q32 approximately q34 and 3q26 approximately q28, respectively. The 3q probe depicted a homogeneously staining region (hsr) in a derivative chromosome 3 of KU-T1. An hsr probe was regenerated by chromosome microdissection and was hybridized back to KU-T1 and normal metaphases. This hybridization experiment confirmed the probe derived from an hsr and indicated original locations of DNA sequences of hsr on normal chromosome 3. Intense hybridized signals shown at three loci (3p12, 3q26.3, and 3q28) suggests that oncogenes may be involved in the hsr formation. The present study provides a comprehensive analysis of the chromosomal abnormalities, including hsr formation and related oncogenes, in the KU-T1 cell line.