Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

激素治疗增加绝经后健康妇女尿失禁的发病率和严重程度

问题：在绝经后健康妇女中，激素治疗（hormone therapy，HT）对尿失禁（urinary incontinence，UI）的效果如何？     

Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer

BACKGROUND: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS: Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.     

Target visualisation and microwave hyperthermia monitoring using nanoparticle-enhanced transmission ultrasound (NETUS)

Purpose: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment.

Methods: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored.

Results: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5?°C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p?Conclusions: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast.     

Rheumatoid arthritis synovial macrophages express the Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein and are refractory to Fas-mediated apoptosis

OBJECTIVE: The chronic inflammation and progressive joint destruction observed in rheumatoid arthritis (RA) are mediated in part by macrophages. A paucity of apoptosis has been observed in RA synovial tissues, yet the mechanism remains unknown. The present study sought to characterize the expression of Fas, Fas ligand (FasL), and Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP), and to quantify the apoptosis induced by agonistic anti-Fas antibody, using mononuclear cells (MNC) isolated from the peripheral blood (PB) and synovial fluid (SF) of RA patients. METHODS: The expression of Fas, FasL, and FLIP and apoptosis induced by agonistic anti-Fas antibody in MNC from the PB and SF of RA patients were determined by flow cytometry. Immunohistochemistry employing a monospecific anti-FLIP antibody was performed on RA and osteoarthritis (OA) synovial tissue. RESULTS: CD14-positive monocyte/macrophages from normal and RA PB and from RA SF expressed equivalent levels of Fas and FasL. Furthermore, unlike the CD14-positive PB monocytes, RA SF monocyte/macrophages were resistant to the addition of agonistic anti-Fas antibody. In contrast, both CD14-positive PB and SF monocyte/macrophages were sensitive to apoptosis mediated by a phosphatidylinositol 3-kinase inhibitor. Intracellular staining of the caspase 8 inhibitor, FLIP, in CD14-positive SF monocyte/macrophages revealed a significant up-regulation of FLIP compared with normal and RA PB monocytes. Immunohistochemical analysis of synovial tissue from RA and OA patients revealed increased FLIP expression in the RA synovial lining compared with the OA synovial lining. Furthermore, FLIP expression was observed in the CD68positive population in the RA synovial lining. Forced reduction of FLIP by a chemical inhibitor resulted in RA SF macrophage apoptosis that was enhanced by agonistic anti-Fas antibody, indicating that FLIP is necessary for SF macrophage survival. CONCLUSION: These data suggest that up-regulation of FLIP in RA macrophages may account for their persistence in the disease. Thus, the targeted suppression of FLIP may be a potential therapeutic strategy for the amelioration of RA.