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Dasatinib is a potent and effective second‐generation oral tyrosine kinase inhibitor that is clinically indicated for the treatment of imatinib‐resistant or imatinib‐intolerant breakpoint cluster region‐Abelson (BCR‐ABL)‐positive chronic myeloid leukaemia (CML) or for Philadelphia chromosome‐positive acute lymphocytic leukaemia. The most common adverse events associated with dasatinib therapy are skin rash, gastrointestinal upset, pancytopenia, pulmonary hypertension, and fluid retention, including pleural effusion. However, chylothorax secondary to dasatinib administration has rarely been reported. Although the underlying mechanism leading to dasatinib‐induced chylothorax is uncertain, the preferred treatment options are usually supported with diuretics or systemic steroids. Moreover, the discontinuation of the drug is mandatory in refractory cases. Here, we present the case of a patient with dasatinib‐induced chylothorax, and review the previously reported cases in the literature., Chylothorax is a rare adverse event of dasatinib treatment, and it is often diminished after the cessation of the offending drug.

Kidney failure is a possible but rare complication in lung cancer patients that may be caused by massive tumor lysis or a paraneoplastic effect. Clinical case reports have documented pathological characteristics of paraneoplastic syndrome in glomeruli, but are short of molecular details. When Lewis lung carcinoma 1 (LLC1) cells were implanted in mice lungs to establish lung cancer, renal failure was frequently observed two weeks post orthotopic xenograft. The high urinary albumin-to-creatinine ratio (ACR) was diagnosed as paraneoplastic nephrotic syndrome in those lung cancer mice. Profiling the secretome of the lung cancer cells revealed that the secretory proteins were potentially nephrotoxic. The nephrotoxicity of lung cancer-derived secretory proteins was tested by examining the pathogenic effects of 1 &times, 106, 2 &times, 106, and 5 &times, 106 LLC1 cell xenografts on the pathogenic progression in kidneys. Severe albuminuria was present in the mice that received 5 &times, 106 LLC1 cells implantation, whereas 106 cell and 2 &times, 106 cell-implanted mice have slightly increased albuminuria. Pathological examinations revealed that the glomeruli had capillary loop collapse, tumor antigen deposition in glomeruli, and renal intratubular casts. Since IL-6 and MCP-1 are pathologic markers of glomerulopathy, their distributions were examined in the kidneys of the lung cancer mice. Moderate to severe inflammation in the kidneys was correlated with increases in the number of cells implanted in the mice, which was reflected by renal IL-6 and MCP-1 levels, and urine ACR. TGF-&beta, signaling-engaged renal fibrosis was validated in the lung cancer mice. These results indicated that lung cancer cells could provoke inflammation and activate renal fibrosis.

Background Afatinib is a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Compared to cytotoxic chemotherapy, afatinib has been shown to have better efficacy in the treatment of non-small cell lung cancer harboring EGFR mutations. However, 40 mg daily as the initial dose is often accompanied by serious adverse drug reactions (ADRs) and 28 to 53.3% of patients required a dose reduction. No previous study has compared the clinical efficacy and ADRs of different initial doses (40 mg vs. 30 mg daily) of afatinib in lung cancer treatment. Methods Patients with stage IV lung adenocarcinoma diagnosed and treated in two Kaohsiung Medical University-affiliated hospitals in Taiwan between May 2014 and August 2016 were identified and followed until December 2016. Demographic characteristics, responses, progression-free survival (PFS), overall survival (OS), and ADRs were recorded. Result A total of 48 patients with stage IV lung adenocarcinoma harboring susceptible EGFR mutations who received afatinib as their first-line therapy were enrolled. Patients using 30 mg daily as the initial dose tended to be older and female and have a smaller body size. The patients using 30 mg of afatinib daily as their initial dose had a similar response rate to those receiving 40 mg daily (76% vs. 95%, p = 0.0862) and the same disease control rate (100% vs. 100%, p = 0.1486). The PFS was similar between the patients receiving 30 mg or 40 mg of afatinib daily (median PFS: 469 vs. 443 days, log-rank p = 0.8418). Patients receiving 30 mg daily had a significantly lower incidence of diarrhea than those using 40 mg daily (41% vs. 100%, p

An abscopal effect refers to distant tumor regression after localized irradiation. The mechanism is thought to be via local radiotherapy triggering the immune system which then attacks distant tumor sites. Only several cases of solid tumors with an abscopal effect have been reported in the past few decades, and whether an abscopal effect can cross the blood-brain barrier is still unknown. Herein, we present a female patient who was admitted due to unsteady gait and dyspnea. Chest X-ray (CXR) and chest CT showed a huge lung mass with left lung collapse and multiple liver masses. Brain MRI also showed multiple brain metastases. A bronchoscopic biopsy proved metastatic adenocarcinoma from colorectal cancer based on immunohistochemical staining. She therefore received 30 Gy (10 fractions) for the brain metastases; however, she refused to receive any systemic therapy for her lung mass and asked for hospice care. She was therefore transferred to a nursing home and was lost to follow-up. She returned 2 months later due to right pneumonia with fever and productive cough. Surprisingly, her left lung mass had markedly regressed even though she had not received any additional systemic anticancer therapy. This may be the first case of an abscopal effect after receiving whole brain irradiation for brain metastases.

Primary adrenal non-Hodgkin lymphoma is an extremely rare disease confined wholly or chiefly to extranodal involvement. We report the case of an old woman who presented with progressive malaise and was diagnosed with primary adrenal diffuse large B-cell lymphoma pathology using laparoscopic adrenalectomy. Enhanced computed tomography and positron emission tomography revealed bilateral adrenal involvement.

Purpose Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. Methods We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. Results Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. Conclusions Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Background Influenza B virus infection is generally considered to be mild and is rarely associated pulmonary cardiovascular involvement in adults. However fatal complications may occur. Case presentation A 43-year-old previously healthy Taiwanese male came to our emergency department due to high fever, chills, general malaise and myalgia for about 4 days. An influenza rapid test from a throat swab was negative. Chest radiography showed mild left lung infiltration and levofloxacin was prescribed. However, progressive shortness of breath and respiratory failure developed 48 h later after hospitalization. Emergent intubation was performed and he was transferred to the intensive care unit where oseltamivir (Tamiflu, Roche) 75 mg orally twice daily was given immediately. In the intensive care unit, cardiac catheterization revealed normal coronary arteries. However, a markedly elevated cardiac enzyme level (Troponin I level was up to 71.01 ng/ml), a positive cardiac magnetic resonance imaging findings and no coronary artery stenosis led to the diagnosis of acute myocarditis. Subsequent real-time polymerase chain reaction of endotracheal aspirates was positive for influenza B. His condition gradually improved and he was successfully weaned from the ventilator on day 22. He was discharged without prominent complications on day 35. Conclusion Influenza B infection is not always a mild disease. Early detection, early administration of antiviral agents, appropriate antibiotics and best supportive care, is still the gold standard for patients such as the one reported.

Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Recent studies have demonstrated that expression of some circadian clock genes displays daily oscillation in peripheral tissues including peripheral blood and bone marrow. Circadian rhythms regulate various functions of human body, and the disruption of circadian rhythm has been associated with cancer development and tumor progression. However, the direct links between aberrant circadian clock gene expression and human disorders remain largely unknown. In this study, comparisons were made between the expression profiles of 9 circadian clock genes from peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) from 18 healthy volunteers. Peripheral blood (PB) total leukocytes from 54 healthy volunteers and 95 patients with chronic myeloid leukemia (CML) were also investigated. Similar expression profiles of all 9 circadian clock genes were observed in PBMCs and PMNs of healthy individuals. In PB total leukocytes of healthy individuals, the daily pattern of PER1, PER2, PER3, CRY1, CRY2, and CKIε expression level peaked at 0800 h, and BMAL1 peaked at 2000 h. Daily pattern expression of these 7 genes was disrupted in newly diagnosed pre—imatinib mesylate—treated and blast crisis—phase patients with CML. Partial daily pattern gene expression recoveries were observed in patients with CML with complete cytogenetic response and major molecular response. The expression of CLOCK and TIM did not show a time-dependent variation among the healthy and patients with CML. These results indicate a possible association of the disrupted daily patterns of circadian clock gene expression with the pathogenesis of CML.

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty-four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p

SummaryThe aim of the present study was to investigate the epidemiology of Legionnaires’ disease (LD) caused by Legionella longbeachae in Taiwan during 2006–2010. A total of six cases were identified prospectively, accounting for 1.6% of all laboratory-confirmed LD cases and 4.4% of culture-positive LD cases. All six cases occurred between April and August. The male to female ratio was 0.5. These six LD patients had a higher median age than those with LD due to Legionella pneumophila. Four of the six patients presented with pleural effusion and five survived the infection episode. Only two patients had a potential soil contact history prior to LD onset. The patients resided in divergent geographical areas without a common exposure history. The individual genomic DNA banding patterns of the six L. longbeachae isolates analyzed by pulsed-field gel electrophoresis (PFGE) were unique, supporting the hypothesis that the L. longbeachae infections occurred sporadically.

Primary liver lymphoma is extremely rare. The diagnosis depends on the physician's suspicions and histological examination. We report the case of a man aged 38 years who suffered from abdominal discomfort and hypercalcemia. Sonography showed a huge, solid liver tumor, and magnetic resonance imaging showed the tumor had characteristics of hypointensity on T1-weighted and hyperintensity on T2-weighted imaging. Primary liver lymphoma was diagnosed by histological examination from biopsy. We report this rare type of liver tumor and review the clinical presentation and treatment of the disease.

Background Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. Methods We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. Results A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95 % confidence interval (CI), 1.688–29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179–4.564), p = 0.0148), and lung cancer (HR = 5.807 (95 % CI, 2.946–11.447), p 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

Abstract 4613 Circadian rhythms regulate various functions of human body and disruption of circadian rhythm has been associated with cancer development and tumor progression. Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Many transcriptional regulators are histone acetyltransferases (HAT) or histone deacetylases (HDAC). As clock function and integration of inputs rely on transcriptional regulation, it is possible that chromatin is remodeled during circadian cycles and in response to signals that regulate the clock. SIRT1 (sirtuin 1) is a HDAC that has recently been identified as a crucial modulator of the circadian clock machinery. To date, at least 7 SIRT genes (SIRT1–7) have been identified. In our previous report we have demonstrated the daily expression patterns of PER1, PER2, PER3, CRY1, CRY2, and CKIe in peripheral blood (PB) of healthy individuals were abolished in chronic myeloid leukemia (CML) patients and partial recoveries of daily patterns were observed in CML patients with complete cytogenetic response (CCyR) and major molecular response (MMR) post-imatinib treatment [J Biol Rhythms 2011]. In this study we further investigated the expression profiles of the 7 SIRT genes (SIRT1–7) in PB total leukocytes from 49 CML and 22 healthy volunteers. Collection of PB was carried out at four time points: 2000 h, 0200 h, 0800 h, and 1400 h, respectively. In PB total leukocytes of healthy individuals, the daily pattern of SIRT1 (p < 0.01) and SIRT5 (p < 0.05) expression level peaked at 0200 h, and SIRT2 (p < 0.01) peaked at 0800 h. Daily pattern expression of these 3 genes was abolished in newly diagnosed pre-imatinib mesylate treated and blast crisis-phase CML patients. Partial daily patterns of gene expression recoveries were observed in CML patients with CCyR and MMR. In some serial monitored individual patients, the recoveries of oscillations of SIRT1, 2, and 5 genes expression accompanied with the disappearance of BCR-ABL transcripts were also noted. The expression of SIRT3, 6, and 7 did not show a time-dependent variation among the healthy and CML patients. SIRT4 expression was undetectable both in the healthy and CML patients. Updated in vitro study results of the regulation of SIRT1, 2, and 5 genes on circadian clock genes expression will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Abstract 3633 Circadian rhythm is present in human and all eukaryotes with a 24-hour cycle. Circadian genes use transcriptional-translational feedback loops to control circadian rhythms. Therefore, the marked characteristic of circadian systems is the strong daily cycling of clock gene mRNA, clock protein, and clock-controlled gene RNA and protein. Recent studies have demonstrated that expression of some of the circadian genes display daily oscillation in peripheral tissues including liver, eye, lung, heart, spleen, kidney, peripheral blood and bone marrow. Circadian rhythms regulate various functions of human body and disruption of circadian rhythm has been associated with cancer development and tumor progression. In this study the expression profiles of the 9 circadian genes (hPER1, hPER2, hPER3, hCRY1, hCRY2, hCLOCK, hBMAL1, hCK1e and hTIM) in peripheral blood (PB) total leukocytes from 95 chronic myeloid leukemia (CML) and 54 healthy volunteers were investigated. For comparison of circadian gene expression between PB mononuclear cells (PBMCs) and polymorphonuclear cells (PMNLs), another group of 10 healthy volunteers were also investigated. Collection of PB was carried out at four time points: 20:00, 02:00, 08:00, and 14:00, respectively. In healthy individuals, the daily oscillation was shown for hPER1, hPER2, hPER3, and hCRY2 with peak expression levels at 8:00AM, and the expression of the nine genes displayed similar profile both in PBMCs and in PMNs. In contrast, oscillations of these four genes were abolished in newly diagnosed pre-imatinib mesylate treated and blast crisis-phase CML patients and partial recoveries of oscillations were observed in CML patients with complete cytogenetic response and major molecular response. In some serial monitored individual patients, the recoveries of oscillations of circadian gene expression accompanied with the disappearance of BCR-ABL transcripts were also noted. Expression of hCRY1, hCLOCK, hBMAL1, hCK1e and hTIM did not oscillate both in healthy individuals and CML patients. Updated results on more healthy volunteers and serial monitored CML patients will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Background Infectious agents have been shown to contribute to the development of lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in Asian populations. Herpes zoster infection, commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies in retrospective case–control studies from Western populations, but the results are controversial and large-scale prospective studies from Asian populations are lacking. Methods A nationwide population-based matched-controlled prospective study on Taiwanese patients was performed using the National Health Insurance Research Database from 1996 to 2007. Herpes zoster and malignancies were defined by compatible ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) codes. Patients who had been diagnosed with any malignancies before herpes zoster, with known viral infections including human immunodeficiency virus, and duration from herpes zoster to diagnosis of malignancies less than 6 months were excluded. Results Of 42,498 patients with herpes zoster prior to the diagnosis of any malignancies, the cumulative incidence for lymphoid malignancies was 0.11% (n = 48), compared with 0.06% (n = 106) in 169,983 age- and gender-matched controls (univariate hazard ratio (HR): 1.82, 95%CI: 1.29-2.55). The most common lymphoid malignancy was non-Hodgkin’s lymphoma (60.4%, n = 29), followed by multiple myeloma (27.1%, n = 13). Risk for developing lymphoid malignancies is significantly higher in herpes zoster patients (log rank P = 0.005). After adjusting for presence of any comorbidities in Charlson comorbidity index, time-dependent covariate for herpes group, and income category using Cox proportional hazard regressions, herpes zoster patients had an increased risk of developing lymphoid malignancies (adjusted HR: 1.68, 95%CI: 1.35-2.42, P = 0.0026), but did not have an increased risk of developing non-lymphoid malignancies (adjusted HR: 1.00, 95%CI: 0.91-1.05, P = 0.872). Conclusion Preceding herpes zoster infection is an independent risk marker for subsequent lymphoid malignancies in Taiwanese subjects. Further studies are warranted for pathogenesis exploration and preventive strategies in Asian populations.