Perforated Gallbladder into the Abdominal Wall.

Objective: Perforation of the gallbladder (PG) is a dreaded complication of an acute cholecystitis and is associated with increased morbidity and mortality. Cholecystocutaneous abscess (CCA) is an extremely rare complication. There is usually a history of cholecystolithiasis or neglected chronic gallbladder disease. We report a case of perforated gallbladder into the abdominal wall. Methods: A 65-year-old female, obese, was admitted to our department complaining of right upper quadrant abdominal pain. The diagnosis of acute cholecystitis was based on the clinical picture, laboratory test, and ultrasound findings. She was treated with oral antibiotics for 10 days and readmitted due to a painful, erythematous mass on the right subcostal region. An abdominal computed tomography showed the presence of a subparietal formation in communication with the gallbladder, and a gallbladder perforation was postulated. The treatment consisted of percutaneous drainage of the abdominal wall abscess followed by laparoscopic cholecystectomy in a two-stage protocol. Anatomical pathology analysis found chronic inflammation and excluded malignancy. The postoperative follow-up was uneventful. Discussion. This case demonstrates a very rare presentation of PG that created an abscess into the muscles of the abdominal wall. This kind of PG is rarely seen due to medicine improvements. When the conditions of the patient are good, rather than perform immediate surgery that could lead to serious complications, we propose a two-stage approach. Conclusion: CCA is a possible complication of gallbladder's pathology that all surgeons have to know. There is no standard baseline management for this pathology, due to the few numbers of cases and to the differences in the quality of the patients' illness. We suggest a two-stage approach with drainage of the abscess followed by laparoscopic cholecystectomy with abscess debridement.

Fluorescence-guided selective arterial clamping during RAPN provides better early functional outcomes based on renal scan compared to standard clamping.

To compare the functional and operative outcomes of robot-assisted partial nephrectomy with selective arterial clamping guided by near infrared fluorescence imaging (NIRF-RAPN) versus a cohort of patients who underwent standard RAPN without selective arterial clamping (S-RAPN). 62 consecutive patients underwent RAPN from January 2016 to May 2017: the last 20 patients underwent NIRF-RAPN. Preoperative and postoperative renal scan at 1 month were performed to evaluate the glomerular filtration rate (GFR) of the operated renal unit and total function. Functional and operative outcomes of cases were compared with a cohort of 42 patients undergoing S-RAPN. Selective clamping was performed in 15 patients (75%), whereas five (25%) cases were converted to S-RAPN, due to incomplete ischemic appearance of the tumor after selective clamping. Median tumor diameter was 40 mm in both groups. Median selective clamping was 24 min in both groups. Operative time (206' vs 190') and blood loss (200 vs 170 cc) were comparable. No major complications have been reported in the NIRF-RAPN group, whereas three acute hemorrhages with embolization were found in the S-RAPN group. The analysis of renal scan data revealed that a greater loss of GFR in the operated renal unit was observed after S-RAPN compared to NIRF-RAPN [21.5% vs. 5.5%; p = 0.046], as well as total GFR loss [8% vs 0%; p = 0.007]. The use of NIRF imaging was associated with improved short-term renal functional outcomes compared to RAPN without selective arterial clamping. To our knowledge, this is the first comparative study analyzing the GFR obtained from renal scan.

First case of robotic laparoendoscopic single-site radical prostatectomy with single-site VesPa platform.

This study aimed at reporting our first experience with robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with single-site VesPa platform (Intuitive Surgical Inc.). A 68-year-old-man presenting with a cT1c adenocarcinoma Gleason Score 3 + 4 = 7 in 4/12 bilateral cores underwent a transperitoneal robotic LESS-RP with a single-site Vespa platform. Initial PSA, prostate weight, and body mass index (BMI) were 4.4 ng/ml, 45 g, and 25, respectively. Instruments and camera cross within the Single-Site port; the da Vinci System software detects and reassigns the user's hands with the instruments position. The single-site port is inserted through a 2-cm intraumbilical incision. The robotic 8.5 mm scope and two surgical curved instruments (fenestrated bipolar forceps and cautery hook) are introduced through the ports and used for most of the procedure, whereas a wristed needle driver on the right hand is used for the reconstructive steps. An additional 12 mm port (Air Seal, SurgiQuest) is placed in a midline between the umbilicus and the right iliac spine in order to facilitate table assistance during surgery and to place a drain at the end of the procedure.Operative time and blood loss were 300 min and 400 mL, respectively. The postoperative course was uneventful. The drain and the catheter were removed on days 1 and 6, respectively. The patient experienced a temporary mild stress incontinence (one pad at sixth month) and erectile dysfunction.Our first robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with the single-site VesPa platform was associated with acceptable operative times and perioperative outcome. This procedure is feasible without complications, provided that a proper patient selection has occurred. Limited movements together with the lack of the fourth robotic arm require a considerable expertise in robotic surgery. Some tricks can help overcome technical limitations. The Robotic LESS-RP reduces in some measure the limitations of conventional LESS RP, although further refinement of the robotic instruments is necessary.

AKT inhibition synergistically enhances growth-inhibitory effects of gefitinib and increases apoptosis in non-small cell lung cancer cell lines.

OBJECTIVES: EGFR inhibitors are ineffective against most EGFR wild-type non-small cell lung cancer, for which novel treatment strategies are needed. AKT signalling is essential for mediating EGFR survival signals in NSCLC. We evaluated the combination of gefitinib and two different AKT inhibitors, the allosteric inhibitor AKTi-1/2 and the ATP-competitive pan-AKT inhibitor AZD5363, in EGFR-mutant (HCC-827 and PC-9) and -wild-type (NCI-H522, NCI-H1651), non-small cell lung cancer cell lines. MATERIALS AND METHODS: Drug interaction was studied in two EGFR mutant and two EGFR wild-type non-small cell lung cancer cell lines by calculating combination index (CI) using median effect analysis. The effects on p-EGFR, p-ERK, p-AKT, p-S6 and apoptosis were studied by Western blot analysis. RESULTS: The combination of gefitinib and AKTi-1/2 or AZD5363 showed synergistic growth inhibition in all cell lines. CI values for the combination of gefitinib and AKTi-1/2 were 0.35 (p=0.0048), 0.56 (p=0.036), 0.75 (p=0.13) and 0.64 (p=0.0003) in NCI-H522, NCI-H1651, HCC-827 and PC-9 cell lines, respectively; CI values of 0.45 (p=0.0087) and 0.22 (p<0.0001) were observed in NCI-H522 and PC-9 cells, respectively, when gefitinib was combined with AZD5363. Additive inhibition of signalling output through AKT and key downstream proteins (S6) and increased apoptosis were demonstrated. CONCLUSION: Dual inhibition of EGFR and AKT may be a useful up-front strategy for patients with EGFR-mutant and -wild-type non-small cell lung cancer.

An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity.

BACKGROUND: Vitamin B12 and folic acid (referred to as vitamin supplementation) improves the toxicity profile of pemetrexed containing regimens. Low baseline vitamin B12 and folate levels are reflected in a raised total homocysteine level (HC). Studies have suggested that pretreatment HC levels predict neutropenia toxicity. We have tested supplementation with vitamin B12 and folate in non-pemetrexed platinum-based regimens to decrease treatment-related toxicity and looked for a correlation between toxicity and change in homocysteine levels. PATIENT AND METHOD: Eighty-three patients with advanced lung cancer and malignant mesothelioma were randomly assigned to receive platinum-based chemotherapy with (arm A) or without (arm B) vitamin B12 and folic acid supplementation. The primary end point was grade 3/4 neutropenia and death within 30 days of treatment. Secondary end points included quality of life, overall survival (OS) and the relationship between baseline and post supplementation HC levels and toxicity. RESULTS: In the intention-to-treat population, no significant difference was seen between the two groups with respect to chemotherapy-induced grade 3/4 neutropenia and death within 30 days of chemotherapy (36% vs 37%; p=0.966, emesis (2% vs 6%; p=0.9) or OS (12.3 months vs 7 months; p=0.41). There was no significant difference in survival rates by baseline HC level (p=0.9). Decrease in HC with vitamin supplementation was less frequent than expected. High baseline HC levels decreased with vitamin supplementation in only 9/36 (25%) patients (successful supplementation). Post hoc analysis showed that patients in arm A who were successfully supplemented (9/36=25%) had less neutropenic toxicity (0% vs 69%; p=0.02) compared to unsupplemented patients. CONCLUSIONS: The addition of vitamin B12 and folic acid to platinum-containing regimens did not overall improve the toxicity, quality of life or OS. Rates of grade 3/4 neutropenia at 36/37% was as predicted. Further studies to increase the rate of successful supplementation and to further test the biomarker potential of post supplementation HC levels in predicting chemotherapy-induced neutropenia in platinum-based chemotherapy are warranted. TRIAL REGISTRATION NUMBER: EudracCT 2005-002736-10 ISRCTN8734355.

Association of creatine kinase and skin toxicity in phase I trials of anticancer agents.

BACKGROUND: We investigated the association between skin rash and plasma creatine kinase (CK) levels in oncology phase I trials. METHODS: We analysed data from 295 patients treated at our institution within 25 phase I trials which included CK measurements in the protocol. Trials involved drugs targeting EGFR/HER2, m-TOR, VEGFR, SRC/ABL, aurora kinase, BRAF/MEK, PARP, CDK, A5B1 integrin, as well as oncolytic viruses and vascular disrupting agents. RESULTS: Creatine kinase measurements were available for 278 patients. The highest levels of plasma CK during the trial were seen among patients with Grade (G) 2/3 rash (median 249 U l(-1)) compared with G1 (median 81 U l(-1)) and no rash (median 55 U l(-1)) (P<0.001). There was a significant reduction in CK after the rash resolved (mean 264.2 vs 100.1; P=0.012) in 25 patients, where serial CK values were available. In vitro exposure of human keratinocytes to EGFR, MEK and a PI3Kinase/m-TOR inhibitor led to the increased expression of CK-brain and not CK-muscle or mitochondrial-CK. CONCLUSION: Plasma CK elevation is associated with development of skin rash caused by novel anticancer agents. This should be studied further to characterise different isoforms as this will change the way we report adverse events in oncology phase I clinical trials.

Creatinine clearance is associated with toxicity from molecularly targeted agents in phase I trials.

OBJECTIVES: This study aimed to evaluate any correlations between baseline creatinine clearance and the development of grade 3/4 toxicities during treatment within oncology phase I trials of molecularly targeted agents where entry criteria mandate a serum creatinine of ≤ 1.5 × the upper limit of normal. METHODS: Documented toxicity and creatinine clearance (calculated by the Cockcroft-Gault formula) from all patients treated with molecularly targeted agents in the context of phase I trials within our centre over a 5-year period were analyzed. RESULTS: Data from 722 patients were analyzed; 116 (16%) developed at least one episode of grade 3/4 toxicity. Patients who developed a late-onset (>1 cycle) grade 3/4 toxicity had a lower creatinine clearance than those who did not (82.69 ml/min vs. 98.97 ml/min; p = < 0.001). CONCLUSION: Creatinine clearance (even when within normal limits) should be studied as a potential factor influencing late toxicities in the clinical trials of molecularly targeted anti-cancer drugs.

Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience.

BACKGROUND: This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA). PATIENTS AND METHODS: A retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity. RESULTS: Data from 687 patients [median age, 59.1 years (range 12.5-85.5)] treated in 36 trials were analysed. Two hundred and eleven patients were of Eastern Cooperative Oncology Group performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate of grade 3 and 4 events was 14.1% (n=97) and 1.9% (n=13), respectively. Twenty-four percent of events were gastrointestinal, 22% constitutional and 20% metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1-6.1; P=0.032] as was receiving >100% of maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6-3.9; P<0.001). Mortality rate was 0.43% (n=3). CONCLUSIONS: Therapy with novel MTAs in phase I trials is associated with a moderate risk of significant toxicity. This appears less than in phase I studies involving cytotoxic agents, particularly in relation to grade 4 toxicity. The risk of death is low.

A phase II study of ¹8F-fluorodeoxyglucose PET-CT in non-small cell lung cancer patients receiving erlotinib (Tarceva); objective and symptomatic responses at 6 and 12 weeks.

BACKGROUND: The aim of this study was to assess if (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva). METHODS: Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points. RESULTS: Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point. CONCLUSIONS: The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks.

Adipose tissue-derived mesenchymal stem cells and hepatic differentiation: old concepts and future perspectives.

Mesenchymal stem cells (MSCs) are multipotent cells, able to differentiate into elements of the mesodermal lineage. Bone marrow and adipose tissue represent the main sources for MSC isolation. In the last decade, several studies have reported the plasticity of MSCs toward a hepatocyte-like phenotype. The use of MSCs to generate hepatocyte-like cells holds great promises to overcome the scarcity of available organs for transplantation. However, little is known about the molecular pathways involved in lineage cross-differentiation and several issues remain to be answered before MSC application in clinical settings. Aim of this review is to critically analyze the possible sources of MSCs suitable for liver repopulation and the molecular mechanisms underlying MSC hepatic differentiation.

[Lymphadenectomy in differentiated thyroid carcinoma]. / La linfectomia nel carcinoma differenziato della tiroide.

Differentiated thyroid carcinoma accounts for 90% of all thyroid cancers and occurs as papillary carcinoma in 90% of cases. It was shown as this is characterized by an excellent long-term prognosis, although in follow-up long series, were described recurrence rates up to 35%. Although in the past has not been attributed prognostic significance to the lymph nodes, in the last decade has shown how these can affect the rate of locoregional recurrence of differentiated thyroid carcinoma. This renewed interest in lymph node metastatic disease has prompted a shift in surgical treatments more aggressive, with a view to achieving a low incidence of locoregional recurrence. Analyzing the more recent guidelines formulated at the international level, we can highlight how we gradually consolidated the role of prophylactic central compartment lymphadenectomy in the surgical treatment of patients with differentiated thyroid carcinoma. The aim of this treatment, in fact, is not only to reduce the mortality of patients, but to obtain an adequate staging, facilitate radiotherapy treatment, obtain undetectable thyroglobulin levels, avoiding the need for repeated reiterventi, made more simple follow-up. All these objectives can be achieved by careful surgery. Total thyroidectomy associated with prophylactic lymphadenectomy of the central compartment was found to achieve these objectives, although in the absence of data from randomized trials, its role remains controversial.

Post-translational modulation of CD133 expression during sodium butyrate-induced differentiation of HT29 human colon cancer cells: implications for its detection.

The CD133 molecule has been proposed as a surface marker of cancer stem cells in several human malignancies, including colon cancers. The function and the mechanisms regulating CD133 expression remain unknown. The HT29 human colon cancer cells undergo differentiation following treatment with various agents and represent a useful in vitro model of colon differentiation. This study evaluated the behavior of CD133 during sodium butyrate-induced differentiation of HT29 cells. Treatment with sodium butyrate induced a progressive decrease of CD133 expression, as assessed by flow cytometry using the AC133 monoclonal antibody. Indeed, expression of CD133, which was about 47% in untreated control cells, gradually decreased down to about 3% after 72 h in a time- and dose-dependent manner. No relationship was observed between CD133 protein evaluated by flow cytometry and mRNA expression level, and no changes were detected in the methylation status of the CD133 gene promoter during HT29 differentiation. Moreover, the expression of the CD133 protein, evaluated by Western blot analysis using a specific anti-CD133 antibody directed against the C-terminal intracytoplasmic region of human CD133 protein, did not correlate with flow cytometry results. Different results were also obtained using the two antibodies to analyze the expression of the CD133 molecule in human colon cancers. These findings demonstrate that membrane expression of the CD133 stem cell marker might undergo a complex regulation during differentiation of colon cells and suggest that HT29 cells are a useful in vitro model to study the mechanisms involved in this regulation which likely occurs at a post-transcriptional level.

Histology classification is not a predictor of clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with vinorelbine or gemcitabine combinations.

BACKGROUND: Until recently, histology has not been clearly or consistently described in the literature as a prognostic or predictive variable in advanced NSCLC studies. We have categorised patients treated with vinorelbine and gemcitabine based first line chemotherapy regimes for advanced NSCLC as either squamous or non-squamous, and also as either adenocarcinoma and non-adenocarcinoma, and compared outcome. MATERIAL AND METHODS: 420 patients treated with platinum/gemcitabine, platinum/vinorelbine or single agent gemcitabine or vinorelbine as first line chemotherapy for advanced NSCLC were identified. The influence of pathology on progression free survival (PFS) and overall survival (OS) has been investigated by means of a Cox regression analysis. Hazard ratios with 95% CIs have been given for each pathological type after adjusting for the effects of age, gender, stage (III vs. IV), PS (0/1 vs. 2/3) and treatment type (platinum doublet vs. single agent). RESULTS: Neither univariate nor multivariate analysis suggested that there was a significant difference in the response rates for adenocarcinoma vs. non-adenocarcinoma or between squamous and non-squamous pathology. There was no difference in PFS between adenocarcinoma and non-adenocarcinoma pathologies until 8 months (p = 0.98), and there was a statistically significant advantage in PFS for squamous vs. non-squamous pathologies (p = 0.04). Using multivariate Cox regression analysis to adjust for the effects of age, gender, stage, PS, and treatment type, the pathology subtype was not significant. There was no difference in OS in any group. CONCLUSIONS: These results suggest that histology may not be considered as a predictor of clinical outcome using these drugs.

Treatment options for small cell lung cancer - do we have more choice?

Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.

Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer.

BACKGROUND: "Cancer stem cells" (CSC) have been identified as a minority of cancer cells responsible for tumor initiation, maintenance and spreading. Although a universal marker for CSC has not yet been identified, CD133 has been proposed as the hallmark of CSC in colon cancer. The aim of our study was to assess the presence of a CD133+ cell fraction in samples of colon cancer and liver metastasis from colon cancer and evaluate their potential as tumor-initiating cells. METHODS: Tissue samples from 17 colon cancers and 8 liver metastasis were fragmented and digested using collagenase. Cell suspensions were characterized by flow cytometry using anti-CD133, CD45 and CD31 antibodies. CD133+ cells were also isolated by magnetic cell sorting and their tumor-initiating potential was assessed versus the remaining CD133- fraction by soft-agar assay. RESULTS: Our results confirmed the existence of a subset of CD133+ tumor cells within human colon cancers. Interestingly, CD133+ cells were detectable in liver metastasis at a higher percentage when compared to primary tumors. Soft-agar assay showed that CD133+ cell fraction was able to induce larger and more numerous colonies than CD133-cells. CONCLUSION: Our findings data that the CD133+ colon cancer cells might play an important role in both primary tumors as well as in metastatic lesions thus warranting further studies on the role(s) of this subset of cells in the metastatic process.

Mesenchymal stromal cells multipotency and plasticity: induction toward the hepatic lineage.

BACKGROUND: Human mesenchymal stromal cells (MSCs) can be isolated from a variety of adult and perinatal tissues and exert multipotency and self renewal properties which make them suitable for cell-based therapy. Their potential plasticity extended to non-mesodermal-derived tissues has been indicated, although it is still a debated issue. In this study we have isolated MSCs from both adult and fetal tissues. Their growth, immunophenotype and multi-lineage differentiation potentials have been analyzed, focusing, in particular, on the hepatic differentiation. METHODS: Cells were isolated from bone marrow (BMSC), adipose tissue (ATSC) and second trimester amniotic fluid (AFSC), upon a written informed consent obtained from donor patients. Cells were expanded and growth kinetics was assessed by means of proliferation assay. Their immunophenotype was analyzed using cytometry and multi-lineage differentiation potential was evaluated by means of in vitro differentiation assays. Finally, the expression of tissue-specific markers was also assessed by mean of semi-quantitative PCR. RESULTS: Bipolar spindle-shaped cells were successfully isolated from all these tissues. Interestingly, ATSCs and AFSCs showed a higher proliferation potential than BMSCs. Mesodermal differentiation capacity was verified in all MSC populations, even if AFSCs were not able to undergo adipogenesis in our culture conditions. Furthermore, we showed that MSC cultured in appropriate conditions were able to induce hepatic-associated genes, such as ALB and TDO2. CONCLUSION: Taken together the data here reported suggest that MSCs from both adult and fetal tissues are capable of tissue-specific commitment along mesodermal and non-mesodermal lineages. In particular we have demonstrated that a specific hepatogenic commitment can be efficiently induced, proposing these cells as suitable tool for cell-based applications aimed at liver regeneration.

Impact of macrophage toll-like receptor 4 deficiency on macrophage infiltration into adipose tissue and the artery wall in mice.

AIMS/HYPOTHESIS: Toll-like receptor 4 (TLR4) is a receptor for saturated fatty acids (SFAs), global deficiency of which has been shown to protect against inflammation, insulin resistance and atherosclerotic lesion formation. Because macrophages express Tlr4 and are important in insulin resistance and atherosclerotic lesion formation due to their infiltration of white adipose tissue (WAT) and the artery wall, respectively, we hypothesised that deficiency of macrophage TLR4 could protect against these disorders. METHODS: Bone marrow transplantation of agouti, LDL-receptor deficient (A(y)/a; Ldlr (-/-)) mice with marrow from either C57BL/6 or Tlr4 (-/-) mice was performed. Recipient mice with Tlr4 (+/+) marrow (MthetaTLR4(+/+)) or with Tlr4 (-/-) marrow (MthetaTLR4(-/-)) were then placed on one of four diets: (1) low fat; (2) high fat; (3) high fat rich in SFAs (HF(SFA)); and (4) HF(SFA) supplemented with fish oil. RESULTS: There were no differences in body composition or plasma lipids between MthetaTLR4(+/+) and MthetaTLR4(-/-) mice on any of the diets. However, we observed a decrease in some macrophage and inflammatory markers in WAT of female low fat-fed MthetaTLR4(-/-) mice compared with MthetaTLR4(+/+) mice. MthetaTLR4(-/-) mice fed low-fat diet also displayed decreased atherosclerotic lesion area. There were no differences in macrophage accrual in WAT or atherosclerosis between MthetaTLR4(+/+) and MthetaTLR4(-/-) mice fed any of the high-fat diets. Finally, no difference was seen in insulin sensitivity between MthetaTLR4(+/+) and MthetaTLR4(-/-) mice fed the HF(SFA) diet. CONCLUSIONS/INTERPRETATION: These data suggest that under certain dietary conditions, macrophage expression of Tlr4 can be an important mediator of macrophage accumulation in WAT and the artery wall.

Identification and characterization of a novel expandable adult stem/progenitor cell population in the human exocrine pancreas.

It is a general opinion that tissue-specific stem cells are present in adult tissues but their specific properties remain elusive. They are rare in tissues and heterogeneous; in addition, their identification and the characterization of their progeny has encountered technical difficulties. In particular, the existence of pancreatic stem cells remains elusive because specific markers for their identification are not available. We established a method for the isolation of a population of stem/progenitor cells from the human exocrine pancreas, and propose it as a model for other human compact organs. We also used markers that identified and finally characterized these cells. Spheroids with self-replicative potential were obtained from all specimens. The isolated population contained a subset of CD34+ CD45- cells and was able to generate, in appropriate conditions, colonies that produce insulin. We obtained evidence that most freshly isolated spheroids, when co-cultured with the c-kit positive neuroblastoma cell line LAN 5, produced a c-kit positive progeny of cells larger in their cytoplasmic content than the original spheroid population, with elongated morphology resembling the neuronal phenotype. We identified a novel predominant functional type of stem/progenitor cell within the human exocrine pancreas, able to generate insulin-producing cells and potentially non-pancreatic cells.

Role of Helicobacter pylori in patients with portal hypertensive gastropathy by liver cirrhosis hepatitis C virus-related.

AIM: Portal hypertensive gastropathy (PHG) defines a pathological endoscopic picture characterized by the presence of alterations of the gastric mucosa found in patients with hepatopathy associated to an initial or evident portal hypertension. Gastropathy appears with two forms of different seriousness: the mild form, characterized by diffused congestion, petechiae of gastric mucosa (scarlatina type rash) and by the presence of typical hyperemic and edematous polygonal areas, delimited by a thin snake skin reticulation. In the severe form, together with such aspects, mucosal erosion, red spots, or a diffused hemorrhagic gastropathy are added. The pre-eminent pathogenetic element of such lesions seems to be the pathological increase of the portal pressure. The role of the Helicobacter pylori (H. pylori) in the development of these alterations, in terms of prevalence of infection in hepatopathic subjects, is still controversial. The authors have performed a research to verify if the H. pylori infection is correlated to the presence and/or to the gravity of PHG. METHODS: One-hundred and nine patients, all suffering from hepatitis C virus (HCV)-correlated liver cirrhosis, with clinical and/or instrumental signs of portal hypertension have been analysed. RESULTS: The histological prevalence of the infection from H. pylori in our statistical analysis was of 23.8% (26/109 patients). CONCLUSIONS: The H. pylori infection appears to be not significant for the determination and the preservation of PHG.