Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).

OBJECTIVE: To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells. DESIGN: Molecular analysis in human samples and a cell line. SETTING: Two university hospitals and a private clinic. PATIENT(S): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy. INTERVENTION(S): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies. MAIN OUTCOME MEASURE(S): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA). RESULT(S): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release. CONCLUSION(S): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.

Sonication of catheter tips for improved detection of microorganisms on external ventricular drains and ventriculo-peritoneal shunts.

The diagnosis of infections involving internal or external neurosurgical drainage devices is challenging, and to our knowledge no single reliable microbiological test exists. We used sonication to study bacterial colonization in 14 explanted external ventricular drains (EVD) and 13 ventriculo-peritoneal shunt (VPS) devices. This technique dislodges biofilm bacteria from the surface of implanted materials before culture. Removed devices were sonicated in saline (40 kHz, 1 minute, 0.25 W/cm(2)), the resulting fluid was cultured aerobically and anaerobically at 37°C, and bacterial growth was counted. Ventricular cerebrospinal fluid (CSF) was cultured separately. In the EVD group, sonication cultures grew significantly more bacteria (64%, 9/14) than cultures of aspirated ventricular CSF (14%, 2/14). In the VPS group the difference was not significant. Positive sonication cultures of EVD catheters yielded a median of >100 colony forming units (CFU) (range, 60-800). For positive sonication cultures of VPS, the median was 1000 CFU (range, 20-100,000). All patients with bacteria in their CSF also had positive sonication cultures from the removed device. Of the five patients with sterile or presumably contaminated CSF cultures but positive sonication cultures of removed shunts, one became afebrile after removal of the EVD, two developed meningitis and two remained asymptomatic. Sonication culture of EVD appears to improve the microbiological assessment of device-related infection and it corroborates with CSF cultures of revision surgery for VPS. Sonication of the removed EVD tip may raise awareness for the onset of meningitis.

Peritoneal carcinomatosis due to ovarian cancer: comparison between MDCT, MRI and positron emission tomography-computed tomography with F18-fluorodeoxyglucose

Purpose: To compare MDCT, MRI and 18F-FDG PET/CT for the detection of peritoneal carcinomatosis due to ovarian cancerMethods and Materials: Fifteen women (mean age 65±) with clinical suspicion of ovarian cancer and peritoneal carcinomatosis underwent MDCT, MRI and 18F-FDG PET/CT, simultaneously and shortly performed before surgery (delay 8.1± days). According to the peritoneal cancer index nine abdominopelvic regions were defined. We applied four scores of lesion size on MDCT and MR images, while the maximal standard uptake value (SUVmax) was measured on 18F-FDG PET/CT. Three sites of lymphadenopathy and posterobasal pleural carcinomatosis were also analyzed. First, one radiologist blindly and separately read MDCT and MR images, while one nuclear physician blindly read PET/CT images grading each lesion according to four diagnostic certitudes. Secondly, all the images were reviewed jointly and compared with histopathology. Receiver operating characteristics (ROC) analysis was performed.Results: Peritoneal implants were proven in ten women (75%). Altogether, 228 abdominopelvic sites were compared. Sensitivity and specificity for MDCT was 90.2% and 90.6%, for MRI 93.5% and 86.3%, and for 18F-FDG PET/CT 92.7% and 95.7%, respectively. ROC area under the curve were 0.93 for MDCT and MRI, and 0.96 for 18F-FDG PET/CT respectively. No significant differences (p=0.11) were found between the three modalities.Conclusion: Although MRI revealed to be the most sensitive and 18F-FDG PET/CT the most specific modality, no significant differences were shown between the three techniques.

Effect of oxidized cholesterol on age-associated changes to immune parameters in spleen lymphocytes and peritoneal exudate cells derived from rats

The effects of oxidized cholesterol on immune parameters were examined by using spleen lymphocytes and peritoneal exudate cells (PEC) derived from 5-week- (Young) and 9-month-old (Adult) rats. The immunoglobulin (Ig) G and IgM production was inhibited by oxidized cholesterol in the rats of both ages when lymphocytes were exposed to 30 micrograms/ml of oxidized cholesterol for 24 hr. The intracellular IgA level was also lowered by 30 micrograms/ml of oxidized cholesterol, irrespective of age. In contrast, IgE production was significantly increased by the addition of 30 micrograms/ml of oxidized cholesterol in only young lymphocytes. Moreover, oxidized cholesterol enhanced the intracellular histamine accumulation in only adult PEC, although the total histamine level produced by PEC was similar in the rats of both ages. These results thus suggest the possibility that oxidized cholesterol can have different effects on the age-related modulation of immune functions such as Igs production and histamine release.

Péritonite infectieuse en dialyse péritonéale: une complication trop redoutée [Infectious peritonitis in peritoneal dialysis: an over-emphasized complication].

Peritoneal dialysis is an extrarenal epuration modality which uses physiological properties of peritoneum as a dialysis membrane. Despite the improvement of peritoneal dialysis techniques in the last ten years, peritonitis remains one of the most redoubt complications. Peritonitis may sometimes lead to technical failures, which need catheter removing, but rarely lead to death. Our retrospective study at the dialysis center of CHUV has analyzed factors which can predict this kind of complication. It calculates peritonitis rate and median peritonitis free-survival for different groups of patients. It also describes causatives organisms and their sensitivity to antibiotics.

Peritoneal carcinomatosis due to ovarian cancer: comparison between MDCT, MRI and 18F-FDG PET/CT

Purpose: To compare MDCT, MRI and 18F-FDG PET/CT for the detection of peritoneal carcinomatosis due to ovarian cancerMethods and Materials: Fifteen women (mean age 65±) with clinical suspicion of ovarian cancer and peritoneal carcinomatosis underwent MDCT, MRI and 18F-FDG PET/CT, simultaneously and shortly performed before surgery (delay 8.1± days). According to the peritoneal cancer index nine abdominopelvic regions were defined. We applied four scores of lesion size on MDCT and MR images, while the maximal standard uptake value (SUVmax) was measured on 18F-FDG PET/CT. Three sites of lymphadenopathy and posterobasal pleural carcinomatosis were also analyzed. First, one radiologist blindly and separately read MDCT and MR images, while one nuclear physician blindly read PET/CT images grading each lesion according to four diagnostic certitudes. Secondly, all the images were reviewed jointly and compared with histopathology. Receiver operating characteristics (ROC) analysis was performed.Results: Peritoneal implants were proven in ten women (75%). Altogether, 228 abdominopelvic sites were compared. Sensitivity and specificity for MDCT was 90.2% and 90.6%, for MRI 93.5% and 86.3%, and for 18F-FDG PET/CT 92.7% and 95.7%, respectively. ROC area under the curve were 0.93 for MDCT and MRI, and 0.96 for 18F-FDG PET/CT respectively. No significant differences (p=0.11) were found between the three modalities.Conclusion: Although MRI revealed to be the most sensitive and 18F-FDG PET/CT the most specific modality, no significant differences were shown between the three techniques.

Peritoneal Carcinomatosis in Primary Ovarian Cancer Staging: Comparison Between MDCT, MRI, and 18F-FDG PET/CT.

PURPOSE: The aim of this study was to compare multidetector CT (MDCT), MRI, and FDG PET/CT imaging for the detection of peritoneal carcinomatosis (PC) in ovarian cancer. PATIENTS AND METHODS: Fifteen women with ovarian cancer and suspected PC underwent MDCT, MRI, and FDG PET/CT, shortly before surgery. Nine abdominopelvic regions were defined according to the peritoneal cancer index. We applied lesion size scores on MDCT and MR and measured FDG PET/CT standard uptake. We blindly read MDCT, MR, and PET/CT before joint review and comparison with histopathology. Receiver operating characteristics analysis was performed. RESULTS: Ten women had PC (67%). Altogether, 135 abdominopelvic sites were compared. Multidetector CT, MRI, and FDG PET/CT had a sensitivity of 96%, 98%, and 95%, and specificity was 92%, 84%, and 96%, respectively. Corresponding receiver operating characteristics area was 0.94, 0.90, and 0.96, respectively, without any significant differences between them (P = 0.12). FDG PET/CT detected supradiaphragmatic disease in 3 women (20%) not seen by MDCT or MRI. CONCLUSIONS: Although MRI had the highest sensitivity and FDG PET/CT had the highest specificity, no significant differences were found between the 3 techniques. Thus, MDCT, as the fastest, most economical, and most widely available modality, is the examination of choice, if a stand-alone technique is required. If inconclusive, PET/CT or MRI may offer additional insights. Whole-body FDG PET/CT may be more accurate for supradiaphragmatic metastatic extension.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.

Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.

Burkitts's lymphoma - an atypical presentation.

BACKGROUND: In female adolescents and young adults, malignancies of the genital tract are the most frequent type of cancer, closely followed by Hodgkin's and non-Hodgkin's lymphomas. CASE PRESENTATION: We report an unusual case of sporadic Burkitt's lymphoma (BL) presenting with massive bilateral ovarian infiltration, peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by endoscopy of the upper gastrointestinal tract. With intensive chemotherapy, complete remission was rapidly achieved, without life-threatening tumor lysis syndrome. CONCLUSION: Besides metastatic gastric adenocarcinoma, BL is an important differential diagnosis in adolescents presenting with Krukenberg tumor.

Macrophages induce neutrophil apoptosis through membrane TNF, a process amplified by Leishmania major.

Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (MPhi) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of MPhi. Extent of neutrophil apoptosis positively correlated with the number of MPhi added. This process was strictly dependent on TNF because MPhi from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using MPhi derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with MPhi was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate MPhi-induced apoptosis of neutrophils, but BALB/c MPhi were not as potent as C57BL/6 MPhi in this induction. Our results emphasize the importance of MPhi-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation.