MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Tumor induced osteomalacia: A single center experience on 17 patients.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces Fibroblast Growth Factor 23 (FGF-23), causing hyperphosphaturia, hypophosphatemia, low 1,25(OH)2D and osteomalacia. Tumor localization is critical, diagnostic delay ranges from 2.5 to 28 years and to date surgical removal is considered effective treatment. We retrospectively evaluated patients with definite diagnosis of TIO referred to a tertiary Rheumatology Center between September 2000 and May 2020, investigating clinical management and disease outcome. We included 17 patients: 10 (58.8%) were females, mean age at diagnosis was 55.3 ± 13.9 years (mean ± standard deviation), with a diagnostic delay from symptoms onset to tumor detection of 6.6 ± 6.25 years. Biochemical data were: serum phosphorus 1.3 ± 0.4 mg/dL (Reference Range: 2.5-4.6), serum 1,25(OH)2D 31.8 ± 22.9 ng/mL (RR: 25-86), intact FGF-23, 358.9 ± 677 pg/mL (RR: 25-45); 24 h-Urine Phosphorus was increased in only 2 patients, while tubular reabsorption of phosphate (TRP) was decreased in all patients confirming a renal phosphate wasting. In 2013 68Ga- DOTA-based PET/CT was introduced in routinely practice and diagnostic delay was consistently reduced (from 8.6 ± 7.9 to 4.3 ± 2.4 years). Thirteen patients underwent surgery, one patient underwent radiofrequency ablation; 3 patients, not eligible for surgery, were treated only with supplements of phosphorus and calcitriol. One was started on Burosumab after several unsuccessful surgical attempts. After surgery or ablation, 8 patients had complete remission, 3 TIO persistence, and 3 had overtime relapse. Relapses were observed only in patients who previously underwent closed biopsy. To our knowledge, this is the widest European cohort of TIO patients in the last two decades. We confirm a usual diagnostic delay and recommend a stepwise diagnostic approach. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is generally considered a definitive treatment, even though other approaches have been successful in curing TIO. Active surveillance on possible recurrence is always needed. Burosumab appears a promising therapy.

The safety of iloprost in systemic sclerosis in a real-life experience.

Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of this study was to evaluate the safety and tolerability of the intravenous treatment with ILO in different phases of SSc. Eighty-one consecutive non-selected SSc patients, all on nifedipine, with moderate RP, treated with ILO infusion, were retrospectively evaluated. Patients were sub classified according to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was infused with a progressive increase of the dosage up to the achievement of patient's tolerance, 1 day/week. In cases of slower infusion regimen due to adverse events (AE) at the beginning of the administration, patients received a lower dose of the drug (not possible to quantify precisely the final cumulative dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9 developed transient hypotension during the infusion at 20 ml/h that ameliorated when the drug was withdrawn. Moreover, 10/16 edematous patients experienced significant and painful digital swelling, unlike patients in the fibrotic group (p < 0.0001); 11/16 patients reported flushing and 7/16 headache, always controlled with dose tapering below 10 ml/h. In the atrophic/fibrotic phase patients (65/81), 10 developed diarrhea and 24 hypotension at infusion rate of 20 ml/h that led to temporary withdrawal of the drug. When ILO was restarted and kept below 10 ml/h, no side effects were experienced. 23/65 patients experienced flushing and 8/65 headache, all controlled with infusion reduction below 10 ml/h. In these patients, adverse events were significantly less frequent than in the edematous group (p = 0.023 and p = 0.008, respectively). Our data suggest that calcium channel blockers should be transitorily stopped while using ILO and that a pre-treatment approach might reduce or control adverse events. In patients with digital edema, ILO infusion should be carefully employed after the evaluation of patient's drug tolerance.

A cross-sectional nationwide survey on esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Our study aims at disclosing epidemiology and most relevant clinical features of esophageal atresia (EA) pointing to a model of multicentre collaboration. METHODS: A detailed questionnaire was sent to all Italian Units of pediatric surgery in order to collect data of patients born with EA between January and December 2012. The results were crosschecked by matching date and place of birth of the patients with those of diagnosis-related group provided by the Italian Ministry of Health (MOH). RESULTS: A total of 146 questionnaires were returned plus a further 32 patients reported in the MOH database. Basing on a total of 178 patients with EA born in Italy in 2012, the incidence of EA was calculated in 3.33 per 10,000 live births. Antenatal diagnosis was suspected in 29.5% patients. 55.5% showed associated anomalies. The most common type of EA was Gross type C (89%). Postoperative complications occurred in 37% of type C EA and 100% of type A EA. A 9.5% mortality rate was reported. CONCLUSIONS: This is the first Italian cross-sectional nationwide survey on EA. We can now develop shared guidelines and provide more reliable prognostic expectations for our patients.

Neonatal laparoscopic inguinal hernia repair: a 3-year experience.

PURPOSE: To retrospectively analyze the feasibility, safety and complication rate of laparoscopic inguinal herniorraphy in babies weighing 5 kg or less. METHODS: Thirty infants weighing 5 kg or less underwent laparoscopic inguinal hernia repair during a 3-year period. Twenty-eight infants were born preterm and the mean body weight at surgery was 3,800 kg. Internal inguinal ring was closed with a non-absorbable purse-string suture. Contralateral processus vaginalis was closed if patent. Feeding was started on the same day and the patient discharged the following day. Follow-up consisted of physical examination at 1 week, 6 and 12 months post-operatively. RESULTS: Of the 30 patients (27 males, 3 females), 11 had bilateral and 19 monolateral hernia (16 right, 3 left). At laparoscopy, 23 infants needed to have bilateral herniorraphies. The mean corrected gestational age at surgery was 49.1 weeks. The mean operative time for repair was 30 min for unilateral and 41 min for bilateral hernia. There were not intra- or post-operative complications as well as conversions or recurrences. CONCLUSIONS: Laparoscopic inguinal hernia repair in newborns and in ex-preterm infants is a safe and effective procedure to perform and, perhaps, even less technically demanding than open herniotomy.

[Focal spontaneous colic perforation in term or near-term neonates: rare and potentially insidious]. / Perforation colique néonatale focale spontanée en dehors de la grande prématurité : rare et potentiellement insidieuse.

Two cases of neonatal focal spontaneous colic perforations are reported. The 1st infant, born at 36 3/7 weeks gestational age, presented on day 3 with crying, abdominal distension, and liquid stools. Clinical examination showed a slightly irritable hypothermic (35.7 °C) infant with a distended abdomen and few bowel sounds. Blood tests were normal apart from an elevated C-reactive protein level (59 mg/l). The abdomen x-ray was erroneously considered normal. The infant's condition remained stable for nearly 3 days. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was started on antibiotics and operated. Macroscopically, the entire gut was normal apart from a focal sigmoid perforation, which was stitched. A transmural colic biopsy revealed focal vascular dilation but was negative for necrotising enterocolitis or Hirschsprung disease. The infant recovered quickly. She is now a healthy, normal 3-year-old. The 2nd infant, born at 38 5/7 weeks gestational age, presented between day 1 and 2 with clinical signs of infection associated with slowly progressive ileus. The chest and abdomen x-ray was mistakenly considered normal. Frank septicemia developed. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was operated. Macroscopically, the small intestine was normal, the ascending and transverse colons were dilated, and the descending and sigmoid colons were narrow. Three cecal perforations were discovered and stitched. An ileostomy and multiple colic biopsies were also performed. The postoperative course was complicated by persistent septic ileus due to descending and sigmoid colon leaks, which led to colic resections with end-to-end anastomosis. Rectal aspiration biopsies were also performed. At 1 month of age, the infant was discharged from the hospital. The ileostomy was closed in two steps at 2 and 5 months of age. A normal sweat test excluded cystic fibrosis. All colic and rectal biopsies revealed nonspecific inflammatory signs and excluded necrotizing enterocolitis and Hirschsprung disease. Nonspecific irregular thinning of muscularis mucosae and muscularis propria were observed in the two resected colic segments. The boy is now a healthy 7-year-old. The incidence of neonatal focal spontaneous colic perforations at term or close to term is unknown but probably very rare. Our department is the neonatal referral center for approximately 14,000 annual births. In the last 10 years (2000-2009), out of 5115 neonatal admissions in our unit, only ten cases have presented a neonatal spontaneous intestinal perforation, seven of ten in very-low-birth-weight infants and three of ten in term or near-term neonates (one with Hirschsprung disease and the two cases reported herein). In the same period, 108 infants suffered from necrotizing enterocolitis, seven of 108 were term infants and 6 out of 7 had a congenital heart disease. The medical literature is poor on the subject of focal spontaneous colic perforations at term; no risk factor is described. The most specific clinical sign seems to be the abdominal distension. The presence of pneumoperitoneum on an abdominal x-ray is the most sensitive paraclinical sign. In case of an intestinal perforation, surgery must be performed quickly. The vital prognosis seems to be good. The objective of this study was to draw pediatricians' attention to focal spontaneous colic perforations in term or close to term newborns. In the cases reported, the diagnostic delays could have been prevented if the entity - with its radiological manifestation - had been well known.

Sjögren's syndrome: correlation between histopathologic result and clinical and serologic parameters.

AIM: Sjögren's syndrome (SS) represents a challenging illness to diagnose properly and, because of the serious complications such as lymphoma, it is important to reach a correct diagnosis in early stages. Aim of this retrospective study was to evaluate the correlation between histopathologic result of minor salivary gland biopsy and clinical and serologic parameters for the diagnosis of SS. METHODS: We evaluated 360 biopsies, taken from the lower lip, of 360 patients (18 males) on suspicion that they were suffering from SS. The Chisolm and Mason classification was used to state the diagnosis of SS. For each patient, the medical history and the symptoms were evaluated, and diagnostic tests were performed. The revised rules of the American-European Consensus Group Criteria were used to diagnose primary and secondary SS. For the statistical analysis we used the Chi(2) test; a difference of P<0.05 was considered significant. RESULTS: Considering the statistical correlation between a focal score > or =1 and the serological data, it was noted that a positive score was significantly correlated to all serological parameters examined (P<0.0001). A significant correlation was also found between a positive biopsy score and Schirmer's test and Rose Bengal test (P<0.0001). However, with regard to the clinical data, a significant correlation was found only for two parameters: xerostomia (P<0.0001) and parotid swelling (P<0.05). CONCLUSION: Minor salivary gland biopsies are of great diagnostic value in detecting SS. However, for the diagnosis of SS both clinical and serologic parameters should be considered. The data obtained from the present survey reveal that the serologic markers are more predictive than clinical parameters for a positive biopsy score.

Xanthogranulomatous pyelonephritis is associated with higher tissue expression of monocyte chemotactic protein-1.

TOPIC: Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammation of the kidney characterized by destruction and replacement of its parenchyma with granulomatous tissue. It is associated with both chronic urinary obstruction and urinary tract infection (UTI). METHODS: We studied two children with chronic ureteropelvic junction obstruction (UPJO) and recurrent UTI nephrectomized for poor kidney function. An intraoperative renal biopsy was taken to relate the presence of infiltrating monocytes plus tubular atrophy to tissue expression of monocyte chemotactic protein-1 (MCP-1) and epidermal growth factor (EGF). XGP was diagnosed by a pathologist in both cases. RESULTS: MCP-1 expression was significantly higher in the two patients compared with the controls or patients with uncomplicated UPJO. It also correlated with the extent of monocyte infiltration, whereas EGF was only significantly downregulated when compared with the controls. CONCLUSIONS: MCP-1 would seem to play a key role in the pathogenesis of XGP by mediating the recruitment of circulating monocytes or by cells resident in the interstitial space.

TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease.

BACKGROUND: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. AIMS: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. PATIENTS AND METHODS: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. RESULTS: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p=0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6mgkg(-1)day(-1) versus 2.0mgkg(-1)day(-1), p=0.043). CONCLUSIONS: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

[Risk factors conditioning the incidence and severity of cyclosporine A-induced gingival overgrowth and methods of prevention]. / Fattori condizionanti l'incidenza e la severità dell'ipertrofia gengivale indotta da ciclosporina A e possibilità di prevenzione.

Cyclosporin A (CsA) induced gingival overgrowth is one of the major side-effects conditioning the quality of life of the patient under immunosuppressive therapy. This adverse effect has been first reported in 1983 and affects almost 30% of treated patients. Several papers have been published concerning the cellular/molecular mechanisms by which CsA may induce, at the same time, an immunosuppressive and proliferative action. In this review various factors concerning the patient and his milieu that account for the different prevalence of the severity of gingival overgrowth in clinical studies are analyzed and briefly discussed. In particular, age, sex, pharmacokinetic properties, pharmaceutical preparation, genetic predisposition, association with other drugs and the parodontal conditions before transplantation are considered. In addition, a unique approach to the patients with gingival overgrowth as well as effective methods of prevention and therapy are suggested.

MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy.

BACKGROUND: Obstructive nephropathy is characterized at the histologic level by tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms underlying these histologic changes are still poorly defined. Epidermal growth factor (EGF) produced by tubular cells seems to play a pivotal role in the modulation of tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful and specific chemotactic and activating factor for monocytes. METHODS: Twenty-four patients with congenital ureteropelvic junction obstruction [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15 healthy children were studied. Diagnosis was made by renal ultrasound, intravenous pielography, and MAG3 scan. Urinary samples were collected before and after surgery. In 10 patients, urine was also collected directly from the affected pelvis at the time of surgery. Urinary EGF and MCP-1 levels were measured by enzyme-linked immunosorbent assay. MCP-1 and EGF gene expression were evaluated by in situ hybridization in 15 biopsies from congenital UPJO and in 10 normal kidneys. RESULTS: In normal kidneys, there was a high expression of EGF mRNA, whereas MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly increased at the tubulointerstitial level in UPJO biopsies compared with controls and was directly correlated with the extent of monocyte infiltration. In addition, UPJO kidney sections showed a marked reduction in EGF gene expression that was directly correlated with the degree of tubular damage. EGF urine concentration was significantly reduced in UPJO when compared with control and directly correlated with its renal gene expression. On the other hand, the MCP-1 urine concentration was strikingly increased in UPJO patients. It is noteworthy that a significant and inverse correlation was observed between the MCP-1 concentration in the urine collected from the obstructed pelvis and the MAG3 clearance of the obstructed kidney (r = -0.76). The presence of recurrent UTI was associated with a significantly higher MCP-1 excretion and a slight reduction in EGF urine concentration. The surgical correction of UPJO was followed by an improvement of renal function together with a significant reduction in MCP-1 excretion and a marked increase in EGF urine concentrations. Interestingly, EGF urine concentration measured before surgery was significantly correlated with the difference between the MAG3 clearance of the obstructed kidney before and after surgery. CONCLUSIONS: MCP-1 and EGF seem to be involved in the pathogenesis of tubulointerstitial damage in congenital obstructive nephropathy, and their urine excretion may represent a powerful prognostic marker in this form of renal disease.

Renal expression of monocyte chemotactic protein-1 and epidermal growth factor in children with obstructive hydronephrosis.

BACKGROUND/PURPOSE: The authors studied the potential role of ureteropelvic junction obstruction (UPJ-O) in causing progressive renal damage in children through the renal expression of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) mRNA. METHODS: Renal tissues were harvested from 11 children with UPJ-O and from 10 normal kidneys to study the renal expression of EGF and MCP-1 detected by means of in situ hybridization. Five of the patients were found to have a history of urinary tract infection (UTI). RESULTS: Children with UPJ-O had marked reduction of EGF gene expression when compared with controls. Interstitial expression of MCP-1 mRNA was present in all UPJ-O cases. Both EGF and MCP-1 expression did not correlate with age, with differential renal function, and with renal thickness measured through MAG3 renal scan. Children with a history of UTI had a more severe reduction of the renal thickness of the affected kidney compared with those without UTI. MCP-1 expression was higher and EGF more reduced in children with a history of UTI. CONCLUSIONS: Our results suggest a potential role of EGF and MCP-1 in the pathogenesis of renal damage and growth failure in UPJ-O, especially in children with UTI. These important functional changes begin early in life, possibly during fetal life.

DNA-based selection and screening of peptide ligands.

Phage display selection strategies rely on the physical link between the displayed heterologous protein ligand and the DNA encoding it. Thus, genes expressing a ligand with a specific binding affinity can be selected rapidly. To improve the specificity and sensitivity of this technology for potential use in identifying ligands to a specific antibody present in a complex mixture, we incorporated a DNA selection step along with the phage display technology. Ligands for hepatitis C virus (HCV) antibodies present in serum were identified by panning a phage-displayed random peptide library against pools of serum HCV antibodies. An additional DNA hybridization screening step using single-stranded DNA isolated from one of the pools increased the specificity and sensitivity, resulting in the selection of an HCV antibody ligand with diagnostic potential.

Expression of biological activity of draculin, the anticoagulant factor from vampire bat saliva, is strictly dependent on the appropriate glycosylation of the native molecule.

Draculin, a glycoprotein isolated from vampire bat (Desmodus rotundus) saliva, is a natural anticoagulant which inhibits activated coagulation factors IX (IXa) and X (Xa). The observation that under captivity conditions, the anticoagulant activity present in vampire bat saliva is dependent upon the salivation protocol, led us to investigate the possible relationship between the expression of biological activity of native draculin and the post-translational glycosylation of the protein backbone. Daily salivation of vampire bats yields a saliva that progressively decreases in anticoagulant activity, without any significant change in overall protein content, or in the amount of protein specifically recognized by a polyclonal anti-draculin antibody. Anticoagulant activity of the saliva is restored after a 4-day period of rest. Besides the marked difference in anticoagulant activity, purified native draculin, obtained from high- and low-activity saliva, shows significant differences in: (a) composition of the carbohydrate moiety, and (b) Glycosylation pattern. Furthermore, controlled chemical deglycosylation of native draculin, under conditions that do not affect the polypeptide backbone, progressively leads to complete loss of the biological activity. Our present results implicate that correct glycosylation of draculin is a seminal event for the expression of the biological activity of this glycoprotein.

[Pancreatic cancer. Analysis of 149 cases in our 17-year experience]. / Il carcinoma del pancreas. Analisi di 149 casi in 17 anni di esperienza.

The Authors analyse a series of 149 consecutive patients with carcinoma of the pancreas or the periampullary region. Curative surgical treatment was achievable in 55 patients, palliative procedures included surgery in 68 patients; biliary decompression with endoscopic or percutaneous procedure in 25 patients and chemotherapy in one patient with lymphoma. Perioperative complications consisted in gastroplegia (33%), pancreatic fistula (22%), biliary fistula (7.3%), abdominal abscess (5.5%) and hemoperitoneum (1.8%). Five patients died within 30 days after surgery (9%). The overall median postoperative survival was 37, 29 and 21 months in papillary, choledochal and pancreatic cancer, respectively.

Selection of biologically active peptides by phage display of random peptide libraries.

Random peptide libraries displayed on phage are used as a source of peptides for epitope mapping, for the identification of critical amino acids responsible for protein-protein interactions and as leads for the discovery of new therapeutics. Efficient and simple procedures have been devised to select peptides binding to purified proteins, to monoclonal and polyclonal antibodies and to cell surfaces in vivo and in vitro.

Transjugular intrahepatic portosystemic shunt in patients with end-stage liver disease: results in 85 patients.

Transjugular intrahepatic portosystemic shunt (TIPS) is becoming an accepted procedure as a bridge to orthotopic liver transplantation (OLT) in patients with end-stage liver disease (ESLD) and bleeding from portal hypertension. It allows the immediate control of acute bleeding and decreases the risk of recurrent acute bleeding while the patient is awaiting OLT. We review in this report, our experience with 85 patients who underwent a TIPS procedure for gastrointestinal variceal bleeding from September 1991 until April 1994. All patients had liver cirrhosis and all had previous sclerotherapy before TIPS. Child-Pugh score was calculated at enrollment, and all patients were evaluated for possible OLT. Thirteen patients were Child A, 49 were Child B, and 23 were Child C. Fifty-three patients were candidates for OLT, and 32 were not. TIPS was performed urgently in 25 patients. At a median follow-up of 582 days (range, 1 to 1,095), 35 patients underwent transplantation, 21 patients died, and 29 patients are still alive and did not undergo transplantation. Technical complications were observed in 7% of patients and new onset of clinical encephalopathy in 37%. The 30-day mortality rate after TIPS was 13%. Actuarial survival was 60% at 1 and 3 years. Child class C and urgent TIPS were shown to be two independent predictor factors for mortality. TIPS was shown to be a valuable procedure, not only as a bridge to OLT but also as palliation for bleeding from portal hypertension in patients who were not candidates for either surgical shunt or OLT. However, its role in bleeding patients with acceptable liver function needs further investigation.

Urothelium damage as the primary cause of ureteropelvic junction obstruction: a new hypothesis.

Ten infants under 6 months old underwent surgery for obstruction of the ureteropelvic junction. Craniocaudal light microscopy showed subdivision of the resected ureteropelvic junction into three portions: prestenotic, stenotic, and poststenotic. The prestenotic portion was characterized by dilatation of the ureteral lumen, flattening of its mucosal folds and thinning of the urothelium; the stenotic tract showed partial or total loss of the epithelium and fibrosis of the mucosal and fibromuscular coats. No modifications were detected in the poststenotic portion. We advance the hypothesis that a primary epithelial break might cause urine to spread inside the ureteral wall and consequently the mastocytes to migrate and degranulate within the mucosal and fibromuscular coats. The histamine and prostaglandins produced by the mastocytes could induce prolonged muscular spasm, in turn responsible for increasing the intrapelvic pressure and so causing enlargement of the epithelial break. A connective tissue reaction of the ureteral wall would thus occur, which should be considered a secondary event leading to fibrotic stenosis of the ureteropelvic junction.

Mixed pleomorphic-osteoclast-like tumor of the pancreas. Light microscopical, immunohistochemical, and molecular biological studies.

The morphological, immunohistochemical, and molecular biological features of a case of giant cell tumor of the pancreas are described. This neoplasm showed mononuclear and multinucleated tumor giant cells as well as numerous osteoclast-like cells with multiple foci of osteoid-osseous metaplasia. The pleomorphic and osteoclastic giant cells displayed extensive homologies in their immunohistochemical profiles. Neither the pleomorphic nor osteoclast-like portion of the tumor showed neither c-Ki-ras nor p53 mutation and did not express the mutated p53 protein. The results suggest that the pleomorphic and osteoclast-like components are histogenetically related and that this rare neoplasm originates from a precursor cell capable of differentiating along divergent cell type.

Further characterization and comparison of inducible nitric oxide synthase in mouse, rat, and human hepatocytes.

Marked differences in induced nitric oxide (NO) synthesis occur between species. We have previously shown that both human and rat hepatocytes express an inducible NO synthase in response to cytokines and lipopolysaccharide. In this study, we compare the expression and regulation of cytokine-induced NO synthase in hepatocytes isolated from three species, human, rat, and mouse. On stimulation with tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS), it was found that hepatocytes from all three species produce high levels of NO with levels of production exhibiting the following hierarchy: rat hepatocytes > mouse hepatocytes > human hepatocytes. Whereas rat and mouse hepatocytes express inducible NO synthase messenger RNA (mRNA) in response to TNF alpha, IL-1 beta, or IFN gamma as a single stimulus, human hepatocytes respond to LPS alone. Inhibition of NO generation through transforming growth factor (TGF-beta 1) was seen in mouse (77% +/- 5.9) and rat hepatocytes (17% +/- 2.6) whereas only about 10% was seen in human hepatocytes. Epidermal growth factor (EGF) was shown to inhibit NO synthesis in human and mouse hepatocytes but not rat. A marked NO-dependent inhibition of total protein synthesis was seen in rat and human hepatocytes, whereas mouse hepatocytes showed almost no inhibition in protein synthesis when stimulated. NO-dependent cyclic guanosine monophosphate (cGMP) release was found in all three species.(ABSTRACT TRUNCATED AT 250 WORDS)