Spirulina (Arthrospira platensis) Improved Nonalcoholic Fatty Liver Disease Characteristics and Microbiota and Did Not Affect Organ Fibrosis Induced by a Fructose-Enriched Diet in Wistar Male Rats.

Spirulina (Arthrospira platensis) is reported to play a role in improving nonalcoholic fatty liver disease (NAFLD) and intestinal microbiota (IM). To study spirulina's effects in the improvement of NAFLD characteristics, IM, and pancreatic-renal lesions induced by a fructose-enriched diet, 40 Wistar healthy male rats, weighing 200-250 g, were randomly divided into four groups of 10, and each rat per group was assigned a diet of equal quantities (20 g/day) for 18 weeks. The first control group (CT) was fed a standardized diet, the second group received a 40% fructose-enriched diet (HFr), and the third (HFr-S5) and fourth groups (HFr-S10) were assigned the same diet composition as the second group but enriched with 5% and 10% spirulina, respectively. At week 18, the HFr-S10 group maintained its level of serum triglycerides and had the lowest liver fat between the groups. At the phylae and family level, and for the same period, the HFr-S10 group had the lowest increase in the Firmicutes/Bacteroidetes ratio and the Ruminococcaceae and the highest fecal alpha diversity compared to all other groups (p < 0.05). These findings suggest that at a 10% concentration, spirulina could be used in nutritional intervention to improve IM, fatty liver, metabolic, and inflammatory parameters associated with NAFLD.

PD-L1 protein expression by Combined Positive Score (CPS) in patients with muscle invasive or advanced urothelial carcinoma: a single institution experience.

INTRODUCTION: Immune checkpoint inhibitors have revolutionized the treatment of patients with advanced urothelial carcinoma (UC) in the frontline and relapsed settings. Lebanon has one of the highest incidence of UC worldwide, yet no data exists regarding the expression of PD-L1 by Combined Positive Score (CPS) in advanced disease. METHODS: We reviewed all patients treated at our institution for high grade UC, stage pT2 and above, between January 2017 and March 2021. We assessed the expression of PD-L1 by immunohistochemistry using 22C3 clone, and analyzed the association between PD-L1 expression and clinicopathological characteristics. PD-L1 positivity was defined as CPS score ≥ 10. RESULTS: A total of 101 patients with advanced UC were included, with a median age of 71 years (range, 38 to 96 years); 78% were ever-smokers. Ninety-three of 101 patients (92%) had conventional UC and 43 patients (43%) had positive PD-L1 expression, with 12 patients having CPS of 100. The analysis by molecular subtype showed that patients with maximal CPS of 100 were enriched in "basal" molecular subtype. However, no association was found between PD-L1 expression (positive versus negative) and clinicopathological characteristics. CONCLUSION: The positivity of PD-L1 expression as assessed by CPS using the 22C3 clone in our population was almost comparable to the results reported in the occidental literature. Therefore, PD-L1 expression, as a potential predictor of response to immunotherapy, concerns the same percentage of the Lebanese UC patients.

Epidemiology of bone tumors in Lebanon: a retrospective study from 2000 to 2022 at a tertiary center.

Aim: Bone tumors are rare and have an uneven geographic distribution. Methods: 730 patients diagnosed with bone tumors were included in this retrospective analysis. Results: With a 64% rate of malignancy, the most common tumors were metastasis (40%) mostly in the axial skeleton, Osteosarcoma (9%) mostly in the femur, Osteochondroma (8%) mostly in the femur, giant cell tumors (7%) mostly in the knee, and Ewing's sarcoma (6%) mostly in the axial skeleton. Conclusion: Even though a some of the tumors have a predilection for certain localizations in the human body, they may differ in the middle-eastern population. One must also pay attention to the higher rates of malignancies as compared with other cohorts.

With significant morbidity and mortality, bone tumors incidence is low and varies geographically. In our Lebanese population, Seven-hundred-thirty patients with bone tumors were identified with a 64% rate of malignancy with osteosarcoma being the most common primary bone cancer and metastasis being the overall most prevalent bone malignancy. This higher rate of malignancy compared with other populations should be taken into consideration when evaluating Lebanese or Middle eastern patients.

Clinical and pathological features associated with high-risk, multiple, and recurrent basal cell carcinomas: a retrospective cohort analysis from the Levantine coast of the Mediterranean Sea.

Basal cell carcinoma (BCC) data coming from the Levantine coast of the Mediterranean Sea are limited. The study aimed to primarily analyze the demographic, clinical, pathological, and prognostic characteristics of BCC in this region of the world and secondarily identify features associated with high-risk, recurrent, or multiple BCCs. Patients with at least one diagnosis of BCC registered in the pathology department between January 2015 and December 2019 were included in this analytical retrospective single-center cohort study. Patients with basal cell nevus syndrome were excluded. Patients' characteristics and pathological features were collected through file check for a first analysis. Risk factors and evolution were sought through a phone call interview for the second analysis. The first analysis included 506 BCCs corresponding to 365 patients with a mean age of 65 ± 15 years, twenty-two (6%) were less than 40 years old, 180 (49.3%) were women, and 85 (23.3%) had two or more BCCs. The second analysis included 279 BCCs corresponding to 205 patients. Periorificial and infiltrative BCCs were more frequent in men. Periorificial tumors were more frequently nodular or infiltrative and were associated with recurrence. Tumors with perineural involvement were histologically never nodular nor superficial. Recurrence was more frequent in BCCs having periorificial location, a size larger than 2 cm, or an infiltrative subtype. Multiple BCCs were more frequent in patients with light skin type or familial history of skin cancer. High-risk BCCs were more common in patients with low sun exposure.

Osteitis fibrosa cystica mimicking bone tumor, a case report.

BACKGROUND: We report a case of osteitis fibrosa cystica, a rare benign resorptive bone lesion caused by hyperparathyroidism, that presented on imaging as an aggressive bone tumor. CASE PRESENTATION: The patient is a 51-year-old male complaining of severe sustained pain of the right hip region. Imaging studies were suspicious for a malignant tumor of the right iliac bone. Biopsy under CT guidance was performed and showed remodeled bone trabeculae with numerous osteoclasts, excluding bone tumor and raising the possibility of osteitis fibrosa cystica. Complementary tests disclosed elevated blood level of parathyroid hormone and a partially cystic enlarged left inferior parathyroid gland consistent with adenoma. After parathyroidectomy, the clinical symptoms were relieved and the radiological findings were significantly improved, which confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions should always be considered in the differential diagnosis of bone tumors, to avoid unnecessary surgeries and treatments.

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids.

PURPOSE: Several clinical studies suggested that light-to-moderate alcohol intake could alleviate nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism is still poorly understood. METHODS: Mice fed a high-fat diet (HFD) were submitted or not to moderate ethanol intake for 3 months (ca. 10 g/kg/day) via drinking water. Biochemical, analytical and transcriptomic analyses were performed in serum and liver. RESULTS: Serum ethanol concentrations in ethanol-treated HFD mice comprised between 0.5 and 0.7 g/l throughout the experiment. NAFLD improvement was observed in ethanol-treated HFD mice as assessed by reduced serum transaminase activity. This was associated with less microvesicular and more macrovacuolar steatosis, the absence of apoptotic hepatocytes and a trend towards less fibrosis. Liver lipid analysis showed increased amounts of fatty acids incorporated in triglycerides and phospholipids, reduced proportion of palmitic acid in total lipids and higher desaturation index, thus suggesting enhanced stearoyl-coenzyme A desaturase activity. mRNA expression of several glycolytic and lipogenic enzymes was upregulated. Genome-wide expression profiling and gene set enrichment analysis revealed an overall downregulation of the expression of genes involved in collagen fibril organization and leukocyte chemotaxis and an overall upregulation of the expression of genes involved in oxidative phosphorylation and mitochondrial respiratory chain complex assembly. In addition, mRNA expression of several proteasome subunits was upregulated in ethanol-treated HFD mice. CONCLUSIONS: Moderate chronic ethanol consumption may alleviate NAFLD by several mechanisms including the generation of non-toxic lipid species, reduced expression of profibrotic and proinflammatory genes, restoration of mitochondrial function and possible stimulation of proteasome activity.

A Case Report Presenting an Undifferentiated Pancreatic Carcinoma with Osteoclastic-Like Giant Cells with an Unusual Indolent Course.

BACKGROUND Undifferentiated pancreatic carcinoma with osteoclast-like giant cells represents less than 1% of pancreatic cancers. Histogenesis and prognosis are still debated. Three subtypes are defined by the World Health Organization: osteoclastic, pleomorphic, and mixed. The differential diagnosis of a pancreatic tumor with giant cells varies from a benign osteoclastoma to an undifferentiated pancreatic carcinoma with osteoclastic-like cells. The specimen should be carefully examined to rule out conventional pancreatic adenocarcinoma even in the presence of the giant cells. CASE REPORT A 77-year-old male was diagnosed with a pancreatic tail tumor with osteoclastic like cells revealed by a biopsy done by echo-endoscopy; the patient was lost to follow up for 24 months before he was admitted to our institute for severe abdominal pain. A computed tomography showed the same lesion without progression. He was operated on using laparoscopic distal pancreatectomy with splenectomy. Pathology analysis revealed the presence of osteoclast-like giant cells without pleomorphic cells. Mutated KRAS on molecular study confirmed the diagnosis of undifferentiated pancreatic carcinoma with osteoclast-like giant cells. The patient was in good performance status and disease-free 19 months after surgery without any sign of progression. CONCLUSIONS Undifferentiated pancreatic carcinoma with osteoclast-like cells has a challenging pathology diagnosis. Molecular and immunostaining are essential to diagnosis. The absence of pleomorphic cells in the present case has classified it into the osteoclastic subtype. Further cases and studies are needed to confirm the heterogeneity of the malignant course between subtypes.

Corrigendum: Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose-Derived Mesenchymal Stem Cells Through a TNF/NF-κB-Dependent Mechanism.

[This corrects the article DOI: 10.3389/fimmu.2019.01482.].

Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose-Derived Mesenchymal Stem Cells Through a TNF/NF-κB-Dependent Mechanism.

Introduction: Adipose-derived mesenchymal stem cells (ADSC) have been shown to have remarkable immune-modulating effects. However, their efficacy in clinical trials has yet to be fully demonstrated. This could be due to a lack of a proper inflammatory environment in vivo that primes ADSC. Here, we define how the articular microenvironment of rheumatoid arthritis (RA) patients modulates the therapeutic efficiency of ADSC. Methods: Synovial fluids (SF) were collected from 8 RA patients, 2 Spondyloarthritis patients and one control synovial fluid from a patient undergoing traumatic-related surgery. SF inflammatory status was determined by routine analysis and quantification of pro-inflammatory cytokines. ADSC were first treated with SF and ADSC proliferation and gene expression of immunomodulatory factors was evaluated. In order to determine the mechanisms underlying the effect of SF on ADSC, tumor necrosis factor (TNF), interleukin-6 (IL-6), and NF-κB neutralization assays were performed. To evaluate the effect of SF on ADSC functions, ADSC were pre-treated with SF and then co-cultured with either macrophages or T cells. The modulation of their phenotype was assessed by flow cytometry. Results: Pro-inflammatory RASF maintained the proliferative capacity of ADSC and upregulated the gene expression of cyclooxygenase-2 (COX2), indoleamine-1,2-dioxygenase (IDO), interleukin-6 (IL-6), tumor-necrosis factor stimulated gene 6 (TSG6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and programmed death-ligand 1 (PD-L1), all factors involved in ADSC immunomodulatory potential. The RASF-induced gene expression was mainly mediated by TNF alone or in combination with IL-6 and signaled through the NF-κB pathway. Conditioning ADSC with pro-inflammatory RASF enhanced their ability to induce CD4+Foxp3+CD25high regulatory T cells (Tregs) and inhibit pro-inflammatory markers CD40 and CD80 in activated macrophages. Conclusions: Inflammatory synovial fluids from RA patients had the capacity to modulate ADSC response, to induce Tregs and modulate the phenotype of macrophages. The clinical use of ADSC in affected joints should take into account the influence of the local articular environment on their potential. Having a sufficient pro-inflammatory microenvironment will determine whether optimal immunoregulatory response should be expected. Direct ADSC intra-articular delivery to patients could be a potential strategy to properly prime their immunomodulatory potential and enhance their clinical benefits.

Fructose threshold for inducing organ damage in a rat model of nonalcoholic fatty liver disease.

A fructose-enriched diet has been shown to be associated with an increase in fatty infiltration of liver, kidney, and pancreas. Our objective was to determine the concentration threshold at which a fructose-enriched diet induces damage in these organs. We hypothesized that a 20% fructose-enriched diet will induce steatosis or histopathological changes in the kidneys or pancreas. In this study, 40 Wistar male rats were randomly divided into 4 groups of 10, and each group was assigned a diet of equal quantity (15 g/rat) but of varying fructose amount. The first group (control group) was fed a standardized diet. The second and third groups were fed 10% and 20% fructose-enriched diets, respectively, whereas the fourth group was fed a high-fructose diet (30% fructose). At week 16, the 30% fructose group had the highest percentage of fat-enriched cells (10%) and a significant decrease in adiponectin as compared with week 1 (P < .05). Twenty percent of this group developed interstitial fibrosis, but none presented changes in the pancreatic islet structure or fibrosis. The 10% fructose group showed the absence of perisinusoidal and interstitial fibrosis, whereas these were present in the 20% fructose group, but neither group showed significant steatosis (5%) or pancreatic damage. The results suggest that a 20% fructose-enriched diet could be considered as the threshold for inducing kidney and liver damage in the rat. Nutritional interventions to reduce fructose to less than 20% of the total energy intake should be considered to prevent metabolic risks and organ damage.

Chronic and low exposure to a pharmaceutical cocktail induces mitochondrial dysfunction in liver and hyperglycemia: Differential responses between lean and obese mice.

Pharmaceuticals are found in the environment but the impact of this contamination on human and animal health is poorly known. The liver could be particularly targeted since a significant number of these drugs are hepatotoxic, in particular via oxidative stress and mitochondrial dysfunction. Notably, the latter events can also be observed in liver diseases linked to obesity, so that the obese liver might be more sensitive to drug toxicity. In this study, we determined the effects of a chronic exposure to low doses of pharmaceuticals in wild-type and obese mice, with a particular focus on mitochondrial function. To this end, wild-type and ob/ob mice were exposed for 4 months to a cocktail of 11 pharmaceuticals provided in drinking water containing 0.01, 0.1, or 1 mg/L of each drug. At the end of the treatment, liver mitochondria were isolated and different parameters were measured. Chronic exposure to the pharmaceuticals reduced mitochondrial respiration driven by succinate and palmitoyl-l-carnitine in wild-type mice and increased antimycin-induced ROS production in ob/ob mice. Hyperglycemia and hepatic histological abnormalities were also observed in treated ob/ob mice. Investigations were also carried out in isolated liver mitochondria incubated with the mixture, or with each individual drug. The mitochondrial effects of the mixture were different from those observed in treated mice and could not be predicted from the results obtained with each drug. Because some of the 11 drugs included in our cocktail can be found in water at relatively high concentrations, our data could be relevant in environmental toxicology. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1375-1389, 2017.

Characteristics of nonalcoholic fatty liver disease induced in wistar rats following four different diets.

BACKGROUND/OBJECTIVES: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide in parallel with overnutrition characterized by high-fat and high-carbohydrate intake. Our objective was to establish, in 16 weeks, a model of NAFLD in Wistar pathogen-free rats following four dietary types. MATERIALS/METHODS: Forty (6 weeks old) healthy Wistar male rats, weighing an average of 150 g were randomly divided into four groups of ten and assigned a diet with the same quantity (15 g/rat/day), but with different composition. The moderate-fat (MF) group was fed a moderate-fat diet (31.5% fat and 50% carbohydrates), the high-fat (HF) group was fed a fat-rich diet (51% fat), the high-sucrose (HS) group and the high-fructose (HFr) group were fed a carbohydrate-rich diet (61%). The carbohydrate contents of the HS group was composed of 60.3% sucrose while that of the HFr group was composed of 59.3% fructose. RESULTS: At week 16, the HF group had the highest percentage of cells enriched in fat (40%) and the highest weight and liver weight (P < 0.05). The HFr group showed significantly higher levels of serum triglycerides, alanine aminotransferase and adiponectin at week 16 as compared to week 1 (P < 0.05). CONCLUSIONS: The 15 g/rat/day diet composed of 51% fat or 61% carbohydrates enriched mainly in fructose may induce characteristics of NAFLD in rats.

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice.

Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 106 ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 106 ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10²-10³ ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants.

Bilateral ovary adrenal rest tumor in a congenital adrenal hyperplasia following adrenalectomy.

OBJECTIVE: In contrast to the high incidence of testicular adrenal rest tumors in adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal rest tumors (OARTs) in female CAH patients are rare. In this case report, we describe a case of bilateral OART in a female patient with CAH due to 21-hydroxylase deficiency. METHODS: We present a detailed case report with the clinical, imaging, and laboratory findings of the patient. The pertinent literature is also reviewed. RESULTS: A 17-year-old patient was known to have CAH due to 21-hydroxylase deficiency. Since the second month of her gestational age, her mother was treated with cortisone-replacement therapy. The patient was treated with hydrocortisone and fludrocortisone since the neonatal period. Her pertinent history included a bilateral adrenalectomy at the age of 13 years in 2006, and for 3 years she led a normal puberty life with no complaint with hormonal replacement therapy. Nevertheless, in 2009, she developed a virilizing syndrome. Subsequently, she underwent surgery in December 2009 for right adnexectomy. However, the regression of the masculinizing mass was not complete and worsened several months after the surgery. A new pelvic magnetic resonance image showed the activation of a contralateral ovarian mass, necessitating a left adnexectomy in August 2010. CONCLUSION: This case demonstrates some interesting features of OART that pose challenges to its management. If an OART is detected early enough and glucocorticoid therapy is received, it is possible that the OART will decrease in size following suppression of adrenocorticotropic hormone levels.

Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis.

Patients with chronic liver diseases frequently exhibit decreased bone mineral densities (BMD), which is defined as hepatic osteodystrophy (HOD). HOD is a multifactorial disease whose regulatory mechanisms are barely understood. Thus, an early diagnosis and therapy is hardly possible. Therefore, the aim of our study consisted in characterizing a mouse model reflecting the human pathomechanism. Serum samples were collected from patients with chronic liver diseases and 12-week old C57Bl6/N mice after 6-week treatment with carbon tetrachloride (CCl4). Repetitive injections of CCl4 induced liver damage in mice, resembling liver fibrosis in patients, as assessed by serum analysis and histological staining. Although CCl4 did not affect primary osteoblast cultures, µCT analysis revealed significantly decreased BMD, bone volume, trabecular number and thickness in CCl4-treated mice. In both HOD patients and CCl4-treated mice, an altered vitamin D metabolism with decreased CYP27A1, CYP2R1, vitamin D-binding protein GC and increased 7-dehydrocholesterol reductase hepatic gene expression, results in decreased 25-OH vitamin D serum levels. Moreover, both groups exhibit excessively high active transforming growth factor-beta (TGF-ß) serum levels, inhibiting osteoblast function in vitro. Summarizing, our mouse model presents possible mediators of HOD, e.g. altered vitamin D metabolism and increased active TGF-ß. Liver damage and significant changes in bone structure and mineralization are already visible by µCT analysis after 6 weeks of CCl4 treatment. This fast response and easy transferability makes it an ideal model to investigate specific gene functions in HOD.

Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the commonest liver diseases in Western countries. Although leptin deficient ob/ob and db/db mice are frequently used as murine models of NAFLD, an exhaustive characterization of their hepatic lesions has not been reported to date, particularly under calorie overconsumption. Thus, liver lesions were characterized in 78 ob/ob and db/db mice fed either a standard or high-calorie (HC) diet, for one or three months. Steatosis, necroinflammation, apoptosis and fibrosis were assessed and the NAFLD activity score (NAS) was calculated. Steatosis was milder in db/db mice compared to ob/ob mice and was more frequently microvesicular. Although necroinflammation was usually mild in both genotypes, it was aggravated in db/db mice after one month of calorie overconsumption. Apoptosis was observed in db/db mice whereas it was only detected in ob/ob mice after HC feeding. Increased apoptosis was frequently associated with microvesicular steatosis. In db/db mice fed the HC diet for three months, fibrosis was aggravated while steatosis, necroinflammation and apoptosis tended to alleviate. This was associated with increased plasma ß-hydroxybutyrate suggesting an adaptive stimulation of hepatic mitochondrial fatty acid oxidation (FAO). Nevertheless, one-third of these db/db mice had steatohepatitis (NAS ≥ 5), whereas none of the ob/ob mice developed non-alcoholic steatohepatitis under the same conditions. Steatosis, necroinflammation, apoptosis and fibrosis are modulated by calorie overconsumption in the context of leptin deficiency. Association between apoptosis and microvesicular steatosis in obese mice suggests common mitochondrial abnormalities. Enhanced hepatic FAO in db/db mice is associated with fibrosis aggravation.

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study.

OBJECTIVE: We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects. METHODS: In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/male=2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery. RESULTS: OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P<0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (P=0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (r=0.295, r=0.20, P<0.05) and after adjustment for age (r=0.28, r=0.20, P<0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (r=0.30, P<0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (P=0.02, P=0.006, P=0.007, P<0.001, P<0.001, P<0.001 respectively) and a significant increase in adiponectin and HDL values (P<0.001 for both variables). CONCLUSION: Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.

Extraovarian cystadenomas: ultrasound and MR findings in 7 cases.

OBJECTIVE: To describe the ultrasound and MR appearance of paraovarian cystadenomas. METHODS: We reviewed retrospectively the radiologic findings in 7 patients with surgically proven paraovarian cystic neoplasms, including 6 serous cystadenomas and 1 borderline seromucinous cystadenoma. All had ultrasound and 4 had MR preoperatively. RESULTS: On ultrasound, the ipsilateral ovary was visualized in six cases, in contact with the cyst in five and separate from it in one. On MR, the ovary and the cyst were visible in four cases, in contact in three and separate in one. Internal papillary excrescences, present at pathology in all cysts, were seen in five on ultrasound and in four on MR. CONCLUSION: Although the extraovarian location of these neoplasms is difficult to determine preoperatively by ultrasound and MR, these imaging modalities are more reliable in predicting the histology of these rare lesions and differentiating them from simple paraovarian cysts.

Role of replicative senescence in the progression of fibrosis in hepatitis C virus (HCV) recurrence after liver transplantation.

BACKGROUND: Although hepatitis C virus (HCV) recurrence is almost universal after orthotopic liver transplantation (OLT), the impact of viral infection on liver graft is highly variable and difficult to predict. Because of the possible relationship between replicative senescence (RS) and the accelerated development of liver fibrosis, we aimed to assess the potential role of RS in the severity of HCV-related chronic hepatitis recurrence after OLT. METHODS: One hundred three liver biopsies from 56 patients receiving transplants for HCV-related cirrhosis were studied, including 30 revascularization biopsies and 52 and 21 biopsies performed during and beyond the first year of OLT, respectively. The presence of senescent cells in liver grafts was assessed by the senescence-associated beta-galactosidase (SA-beta-Gal) staining method. Chronic hepatitis was defined by fibrosis stage and necrotico-inflammatory activity grade using the METAVIR score. RESULTS: A total of 34 of the 103 (33%) frozen liver biopsies displayed SA-beta-Gal-positive cells, including 6 (20%) of the revascularization biopsies, 14 (34%) of the biopsies performed within the first year, and 10 (46%) of the biopsies performed beyond 1 year of follow-up. The presence of senescent cells in revascularization biopsies was significantly associated with the degree of ischemic necrosis at time of OLT (P = 0.01) and hepatitis C recurrence in the first year after OLT (P = 0.05). Furthermore, the presence of RS in the biopsy performed within the first year was associated with further development of fibrosis (P = 0.05). CONCLUSIONS: These data show that RS has a significant impact upon the course of liver transplantation, especially in the long-term progression of fibrosis observed in HCV-infected patients.