Dimitrios Nasioudis

Neutrophil gelatinase-associated lipocalin and innate immune responses to bacterial infections

Neutrophil gelatinase-associated lipocalin (NGAL), an essential component of the antimicrobial innate immune system, is present in neutrophils and multiple other tissues. It prevents iron acquisition by microorganisms by sequestering iron-loaded bacterial siderophores. NGAL also modulates neutrophil functions. Its production is inducible following Toll-like receptor 4 activation and release of pro-inflammatory cytokines. NGAL is employed clinically in the diagnosis of acute kidney injury and may be useful in general in the differential diagnosis of a bacterial-mediated infectious process. Elevated levels of NGAL have been detected in the blood of patients with bacterial urinary tract infection, community-acquired pneumonia, sepsis, as well as in the cerebrospinal fluid and peritoneal fluid of patients with bacterial meningitis and peritonitis. Some bacteria have developed resistance to NGAL-mediated iron sequestration by production of modified siderophores that are not recognized by NGAL.

α-Amylase in Vaginal Fluid: Association With Conditions Favorable to Dominance of Lactobacillus.

Vaginal glycogen is degraded by host α-amylase and then converted to lactic acid by Lactobacilli. This maintains the vaginal pH at ≤4.5 and prevents growth of other bacteria. Therefore, host α-amylase activity may promote dominance of Lactobacilli. We evaluated whether the α-amylase level in vaginal fluid is altered in women with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) and whether its concentration was associated with levels of lactic acid isomers and host mediators. Vaginal fluid was obtained from 43 women with BV, 50 women with VVC, and 62 women with no vulvovaginal disorders. Vaginal fluid concentrations of α-amylase, secretory leukocyte protease inhibitor (SLPI), hyaluronan, hyaluronidase-1, β-defensin, and elafin were measured by enzyme-linked immunosorbent assay (ELISA). Vaginal concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 8, and d- and l-lactic acid levels in these patients were previously reported. The median vaginal fluid α-amylase level was 1.83 mU/mL in control women, 1.45 mU/mL in women with VVC, and 1.07 mU/mL in women with BV. Vaginal levels of α-amylase were correlated with d-lactic acid (P = .003) but not with l-lactic acid (P > .05) and with SLPI (P < .001), hyaluronidase-1 (P < .001), NGAL (P = .001), and MMP-8 (P = .005). The exfoliation of glycogen-rich epithelial cells into the vaginal lumen by hyaluronidase-1 and MMP-8 may increase glycogen availability and promote α-amylase activity. The subsequent enhanced availability of glycogen breakdown products would favor proliferation of Lactobacilli, the primary producers of d-lactic acid in the vagina. Concomitant production of NGAL and SLPI would retard growth of BV-related bacteria.

Bacterial vaginosis: a critical analysis of current knowledge.

Bacterial vaginosis (BV), the change from a Lactobacillus‐dominant vaginal microbiota to an anaerobic and facultative bacterial dominance, is associated with pathological sequelae. In many BV‐positive women their microbiota is in fact normal and unrelated to pathology. Whether or not the dominance of BV‐associated bacteria persists depends upon interactions between host and bacterial factors. Inconsistencies in diagnosis and erroneous associations with pathology may be due to a failure to differentiate between sub‐populations of women. It is only in those women with a BV diagnosis in which the identified bacteria are atypical and persist that BV may be a clinical problem requiring intervention.

Prognostic significance of lymphadenectomy and prevalence of lymph node metastasis in clinically-apparent stage I endometrioid and mucinous ovarian carcinoma.

OBJECTIVE The aim of the present study was to investigate the prevalence of lymph node (LN) metastasis in women with apparent stage I ovarian carcinoma of endometrioid or mucinous histology and to examine the prognostic significance of LN sampling/dissection (LND) on patient survival. METHODS The National Cancer Institutes Surveillance, Epidemiology, and End Results database was accessed and a cohort of surgically-staged women, diagnosed between 1988 and 2013, with apparent stage I ovarian carcinoma of mucinous or endometrioid histology was selected. Information derived from the histopathology report was employed to determine whether LND was performed and the status of harvested LNs. Five-year cancer-specific survival (CSS) rate was calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank test. Cox proportional hazard models were constructed to evaluate the effect of LND on survival. RESULTS A total of 3354 and 2855 women with endometrioid and mucinous tumors who met the inclusion criteria were identified. LND was performed in 2307 (68.8%) and 1602 (56.1%) of them (p<0.001), respectively. The rate of histopathologically confirmed LN metastasis was 2.1% and 1.7%, respectively. By multivariate analysis LND was associated with superior cancer-specific mortality only for women with endometrioid carcinoma. CONCLUSIONS Lymph node involvement in women with mucinous and endometrioid ovarian carcinoma grossly confined to the ovary is infrequent. LND is associated with a survival advantage for those with endometrioid carcinoma.

Laparoscopic cholecystectomy during pregnancy: A systematic review of 590 patients

BACKGROUND The incidence of symptomatic biliary disease during pregnancy ranges from 0.05 to 8%. Cholecystectomy is one of the common operations performed during pregnancy and laparoscopic approach has gained popularity as an attractive alternative to open surgery. METHODS In order to evaluate the safety, feasibility, outcomes and technical aspects of laparoscopic cholecystectomy during pregnancy a comprehensive search of Medline and Cohrane Library databases was conducted. RESULTS Fifty-one studies were deemed eligible, in which laparoscopic cholecystectomy was attempted in 590 patients. The majority of the procedures (70.7%) were performed during the second trimester. Intraoperative and postoperative complications were observed in 3.5% and 4% of the study population. Conversion rate to open surgery was 2.2%. Fetal loss rate and preterm delivery rate were 0.4% and 5.7% respectively. CONCLUSION Laparoscopic cholecystectomy seems to be a safe alternative to open surgery during pregnancy.

Epidemiology and outcomes of squamous ovarian carcinoma; a population-based study.

OBJECTIVE Squamous ovarian carcinoma (SOC) is a rare tumor. Scarcity of information about the epidemiology and prognosis of SOC hinders attempts at optimal patient management. This retrospective study of a large cohort details the clinicopathological and demographic characteristics and prognosis of women with SOC. METHODS A cohort of patients drawn from the National Cancer Institutes Surveillance Epidemiology and End Results (SEER) database who were diagnosed with SOC between 1988 and 2012 were analyzed. Observed and disease-specific survival was estimated by Kaplan-Meier plots in women who underwent surgery as part of their cancer-related treatment. A Cox hazard regression analysis was performed to determine independent predictors of cancer-specific survival in patients with SOC. RESULTS We identified 341 patients with SOC with a median age at diagnosis of 55 years. Stage I, II, III and IV tumors were noted in 34%, 15%, 20.5% and 24.9% of patients, respectively. Five-year cancer-specific survival was 86% for stage I, 54.3% for stage II, 36.3% for stage III and 2.8% for stage IV disease patients. Observed and cancer-specific survival was better for patients that underwent lymphadenectomy (p=0.031). Postoperative radiotherapy was not associated with improved survival. In a multivariate analysis, independent predictors of improved cancer-specific survival were younger age, lower disease stage and lymphadenectomy. CONCLUSIONS SOC is typically a unilateral malignancy with a tendency toward loco-regional spread. Stage I patients have a relatively high survival rate; however, the prognosis is poor for women with abdominal or distant spread. Lymphadenectomy, but not postoperative radiotherapy, is associated with improved survival.

Laparoendoscopic single-site surgery (LESS) for major urological procedures in the pediatric population: A systematic review

BACKGROUND Improvements in laparoscopic surgery have led to the introduction of laparoendoscopic single-site surgery (LESS) as an alternative to conventional laparoscopy conferring a number of possible advantages. In this review, we aim to elucidate the aspects of LESS for major urological procedures in the pediatric population. MATERIALS AND METHODS An in-depth search of the literature was performed in the databases of PubMed and Scopus, for studies investigating the technical aspects and clinical outcomes of partial nephrectomies, nephrectomies, nephroureterectomies, varicocelectomies and pyeloplasties in children. Data on parameters such as operation time, instrumentation, perioperative complications, hospital stay and follow up period were collected and further analyzed cumulatively. RESULTS Twenty nine studies met the inclusion criteria incorporating 386 patients who underwent 401 procedures. There were no major intraoperative complications, with only 19 patients (4.73%) facing postoperative complications. No perioperative deaths were reported. CONCLUSIONS In the hands of experienced surgeons LESS seems a feasible, efficient and less invasive alternative to standard laparoscopy in the field of pediatric urology. There is an eminent need of well-designed randomized controlled trials comparing the two techniques.

Prevalence of lymph node metastasis and prognostic significance of lymphadenectomy in apparent early-stage malignant ovarian sex cord-stromal tumors

OBJECTIVE The aim of this retrospective population-based study was to investigate the prevalence of lymph node metastasis in patients with apparent early stage malignant sex cord-stromal tumors (SCSTs) and the effect of regional lymph node sampling/lymphadenectomy (LND) on their survival. METHODS A cohort of patients diagnosed with malignant SCSTs between 1988 and 2012 was drawn from the National Cancer Institutes Surveillance, Epidemiology, and End Results database. Overall and Cancer Specific Survival, stratified by performance of LND, were calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank and Breslow tests. A multivariate Cox proportional analysis was performed to determine the effect of LND on overall mortality. RESULTS A total of 1156 patients with SCST met the inclusion criteria; 1000 (86.5%) and 156 (13.5%) patients had apparent stage I and II disease, respectively. LND was performed in 572 (49.5%) patients. Lymph node metastases were pathologically confirmed in 19 patients (3.3%). Five-year cancer specific survival (CSS) was similar, 92.7% and 94.7%, for patients who did or did not undergo LND, respectively. According to multivariate analysis overall mortality did not differ between the two groups after controlling for age, histology and apparent stage. CONCLUSIONS Regional lymphatic mode metastasis in patients with apparent early stage SCSTs is uncommon and lymphadenectomy did not confer a survival benefit in this cohort.

Properties of Epithelial Cells and Vaginal Secretions in Pregnant Women When Lactobacillus crispatus or Lactobacillus iners Dominate the Vaginal Microbiome

Objective: Our objective was to determine differences in properties of vaginal epithelial cells and the composition of vaginal secretions when Lactobacillus crispatus or Lactobacillus iners are numerically dominant in the vaginal microenvironment of pregnant women. Methods: The vaginal microbiomes of 157 first-trimester pregnant women were identified by classifying partial 16S gene sequences amplified from the V1 to V3 region of bacterial ribosomal 16S RNA genes. The extent of autophagy and cell stress in vaginal epithelial cells was determined by measuring the intracellular levels of p62 and the inducible 70-kDa heat shock protein (hsp70). Vaginal secretions were analyzed using a colorimetric assay for d- and l-lactic acid and by enzyme-linked immunosorbent assay for matrix metalloproteinase 8, neutrophil gelatinase-associated lipocalin, α-amylase, hyaluronan, calprotectin, S100A8, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results: L. crispatus was dominant in 69 (43.9%) women, while L iners dominated in 23 (14.6%) women. The median epithelial p62 levels were 0.41 and 4.26 ng/mL in women with L crispatus or L iners dominance, respectively (P = .0035). The corresponding median hsp70 levels were 4.24 and 14.50 ng/mL, respectively (P < .0001). The d-lactic acid concentration in vaginal fluid was highest in association with L crispatus dominance, while all other vaginal fluid compounds except for EMMPRIN were highest when L iners was dominant (P < .03). Conclusion: Epithelial cells exhibit a higher level of autophagy, lower induction of stress-related hsp70, and release lower level of mediators when L crispatus is most abundant as compared to when L iners dominates the vaginal microbiota.

Malignant urachal neoplasms: A population-based study and systematic review of literature

OBJECTIVES To examine patient and clinicopathological features of malignant urachal neoplasms (MUN) in a population-based cohort, to investigate survival outcomes, and to review the current evidence that exists in the literature. MATERIAL AND METHODS The Surveillance, Epidemiology, and End Results database was used to identify microscopically confirmed MUN cases diagnosed between 1988 and 2012. Kaplan-Meier analysis was used to determine median and 5-year overall survival (OS) as well as cancer-specific survival (CSS) rates. Cox proportional hazards model was employed to identify variables independently associated with cancer-specific mortality. A systematic literature review was conducted in line with the PRISMA statement. RESULTS A total of 420 patients with MUNs were identified. The majority were white (77.6%) and male patients (59%) who presented with low-grade (62.1%), mucinous, noncystic adenocarcinomas (42.9%). From the cohort, 19%, 15.2%, 29.5%, and 30.5% of the patients presented with American Joint Committee on Cancer Stage I to IV disease, respectively. Cancer-directed surgery was performed in 86.5% of the patients. The most common procedure performed was partial cystectomy (52.4%) followed by local tumor excision (20.7%). Median OS was 57 months (95% CI: 41.6-72.4), and median CSS was 105 months (95% CI: 61.5-148.5). Five-year OS and CSS rates were 51% and 57%, respectively. Grade and stage were independently associated with cancer-specific mortality. Mortality rates did not differ between patients who underwent partial cystectomy and radical cystectomy/exenteration (P = 0.165), even after controlling for tumor stage. A total of 16 studies reporting on 585 patients were systematically reviewed, and relevant outcomes were summarized in the Supplemental material. CONCLUSIONS MUNs are usually low-grade, mucinous, noncystic adenocarcinomas diagnosed at advanced stages. Overall, the prognosis is poor, and high-grade and disease stage are independently associated with cancer-specific mortality.