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Biomedical subjects

M Ciocca

Publications and source records attributed to M Ciocca.

At least 19 recordsLinked to original sources
PubMed2006

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis.

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). METHODS: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

CD4-Positive T-Lymphocytes↗
PubMed2006

Neutron production from a mobile linear accelerator operating in electron mode for intraoperative radiation therapy.

Intraoperative electron beam radiotherapy is increasingly performed using mobile linac delivering therapeutic radiation doses in unshielded operating rooms. While no special neutron-shielding problem should arise for operation at 10 MeV or less, it is not clear whether this holds true for operation at higher energies. This paper reports the measured neutron production from a Mobetron mobile electron linac, operated at 12 MeV, and compares the results with those from a conventional linac, also operated at 12 MeV in electron mode. Neutron leakage measurements were performed by means of passive bubble detectors in the scattering foil, patient and floor planes. Neutron dose equivalent rates per unit of electron dose delivered by the Mobetron at its normal treatment distance (50 cm SSD) were 0.33 microSv Gy(-1) at the accelerator head, 0.18 microSv Gy(-1) in the patient plane at 15 cm from the beam axis and 0.31 microSv Gy(-1) at the floor plane, on the beam axis and under the beam stopper. For a weekly workload of 250 Gy, the weekly neutron dose equivalents at 12 MeV for the Mobetron at a distance of 300 cm from the scattering foil were 14.3 and 1.7 microSv/week for floor below and adjoining areas on the same floor, respectively. Neutron dose equivalent rates generated from Mobetron are at least one order of magnitude lower than ones produced by a conventional linac operated at the same energy in electron mode. Mobetron can be used at 12 MeV in an unshielded operating room for a weekly workload of up to 250 Gy if the bremsstrahlung x-rays are shielded to negligible levels.

Combined Modality Therapy↗
PubMed2005

Intraoperative electron beam radiotherapy (ELIOT) to the breast: a need for a quality assurance programme.

Intraoperative radiotherapy (IORT) is a technique in which a high, single-fraction radiation dose is delivered directly to the tumour bed during a surgical intervention, after the removal of a neoplastic mass. IORT has been recently used in early stage cancer as an exclusive radiation modality, rather than as a boost, especially for breast tumours, in particular at the European Institute of Oncology in Milan, where the technique has been called electron intraoperative therapy (ELIOT). Our studies on more than 1000 patients have demonstrated the feasibility of the technique and it is expected that its application will become more widespread in the immediate future. It is important to emphasise that ELIOT relies not only on new technological developments, but also on a multidisciplinary team with clear roles and responsibilities, the establishment of a programme of quality assurance with appropriate guidelines and a comprehensive staff development programme.

Breast Neoplasms↗
PubMed2005

Hypertrophic osteoarthropathy in two children with cholestatic hepatic disease.

AIM: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant. CONCLUSION: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention.

Adolescent↗
PubMed2003

Laparoscopic transduodenal papillosphincteroplasty.

In the past 20 years, the approach to biliary lithiasis has changed tremendously as a result of advances in endoscopic and laparoscopic techniques. The two most important open surgical techniques involve extraction of the stones from the common bile duct combined with choledochoenterostomy and papillotomy followed by transduodenal papillosphinteroplasty. Ideally, the choledochotomy is followed by the insertion of a T-tube in the common bile duct. The transcystic approach has never been considered. The first endoscopic papillotomy was performed in 1973. Subsequently, it became the most widely used method for removal of common bile duct stones. In this report we explore the possibility of performing a laparoscopic transduodenal papillosphincteroplasty, following the strict rules commonly used in surgery. After cholecystectomy, a Fogarty catheter, is introduced through the cystic duct. This is followed by a minimal duodenotomy, then incision of the papillar sphincter. In this surgical proposal, we do not intend to substitute technique, but this method should be considered the ultimate solution in the laparoscopic approach to cholecystic choledocholithiasis.

Ampulla of Vater↗
PubMed2003

Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer.

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

Breast Neoplasms↗
PubMed2001

Cholestasis in juvenile dermatomyositis: report of three cases.

This report describes 3 cases of juvenile dermatomyositis (juvenile DM) complicated by cholestasis. All 3 patients had typical features of juvenile DM, and all developed a cholestatic syndrome within the initial months of their disease. Liver biopsy revealed mixed (cytoplasmic and ductal) cholestasis with no abnormalities in the intrahepatic ducts in all 3 cases. Cholestasis improved or was completely reversible upon treatment with prednisone. In the 2 patients who could be followed up long term, no sequelae remained. The possible role of inflammation in the pathogenesis of cholestasis in juvenile DM is discussed.

Adolescent↗
PubMed2001

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated.

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17-19-21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.

Adult↗
PubMed2001

Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis.

HLA alleles are known to be associated with susceptibility to develop autoimmune hepatitis (AH), and hepatitis A virus (HAV) infection is postulated as a putative trigger for AH. We investigated whether HLA may influence the outcome of the HAV infection by studying 67 children with self-limited and 39 children with protracted forms of this infection. HLA typing of the uncomplicated forms showed no significant increase of any HLA class I or II alleles. In contrast, DRB1*1301 was present in 46.1% of the children with protracted forms (vs. 9.8% in healthy controls; relative risk [RR]: 7.6; chi(2) = 33.3; P = 2 x 10(-9)). In uncomplicated hepatitis, 45% developed anti-smooth muscle antibody (SMA)/actin antibodies, but only 1 child had detectable antibodies after 3 months of infection onset. In contrast, after 1 year, 69% of the patients suffering protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40 and 1:160. Within their follow-up, 2 patients developed a Hashimoto's thyroiditis, but the remaining patients showed no signs of developing autoimmune hepatitis. We conclude that the DRB1*1301 haplotype is strongly associated with the protracted forms of HAV infection and suggest that the infection allows a sustained release of liver self-antigens. However, other still-unknown susceptibility genes are required for the full development of pediatric AH.

Acute Disease↗
PubMed2000

Clinical course and consequences of hepatitis A infection.

Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecal-oral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV IgG appears at the same time but persists lifelong. Unusual clinical manifestations of hepatitis A include cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of cases of acute hepatitis in Argentina, including 7% of atypical clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and has been reported to account for 10% of liver transplants in children in France and 20% in Argentina. One-year survival after liver transplantation is 64%. Prevention must be considered as the main means of averting this severe illness.

Adolescent↗
PubMed2000

[Autoimmune hepatitis in children. Initial presentation as fulminant hepatic failure].

UNLABELLED: There are few cases reported of autoimmune hepatitis (AIH) type 2 presenting as fulminant hepatic failure (FHF) in children. The purpose of this study was to report three girls with AIH type 2 that presented as FHF. METHODS: Over a period of 12 years, 123 patients with AIH diagnosed based on international criteria, 9 (7%) were type 2.3 of them presented as FHF. Other etiologies (viral, metabolic and toxic) were ruled out. The treatment was started with prednisone (2 mg-kg-day) and azathioprine (2 mg-kg-day). EVOLUTION: Patients 1 and 3 died while waiting for liver transplant (LT) at 72 and 48 hours after initiating medical treatment. Patient 2 underwent LT3 days after starting treatment, with excellent evolution at 3 years and 7 months of follow up. CONCLUSIONS: 1--AIH type 2 was very infrequent in our group. 2--33% of cases had initial presentation as FHF. 3--The course of the disease was aggressive, not responding to immunosuppressive therapy. The evolution was unfavorable in all patients. 4--LT is an alternative treatment for this severe disease.

Adolescent↗
PubMed1999

Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition.

The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.

Adult↗
PubMed1999

Patterns of radiotherapy for early breast cancer in Northern Italy compared with European and national standards.

PURPOSE: To assess the current practice of early breast cancer (EBC) post-operative irradiation in Northern Italy and to evaluate its conformance with European standards and recently defined national guidelines. MATERIALS AND METHODS: Fifty Radiotherapy departments in Northern Italy received a questionnaire assessing parameters on pre-treatment evaluation of patients, on preparation, prescription and execution phases of irradiation (XRT), on surgery-XRT-chemotherapy integration and on follow-up. The analysis of collected information was compared with both the 1991 EORTC-EUSOMA guidelines and the 1997 AIRO (Italian Association for Radiation Oncology) minimal requirements on EBC post-operative irradiation. RESULTS: Thirty-nine out of 50 (78%) departments answered the questionnaire. All treat T1-T2 tumours, after tumourectomy or, mostly, quadrantectomy. The mean interval between surgery and XRT is 45 +/- 14 days. Chemotherapy is delivered concurrently in 70% of departments, CTV is represented by residual mammary gland in 100% of cases, while 38% and 52% of departments occasionally treat internal mammary and axillary or supra-clavicular nodes, respectively. Total dose delivered to the whole breast is 46-50 Gy in 98% (1.8-2 Gy/fraction). The tumour bed is boosted in 79% of cases. An immobilization device is used in 28% of cases CTV is clinically localized in 62% of patients. Tangential fields are simulated in 85% of centres, with film storage in 78% of cases. Co-60 units are used in 58% and/or 4-6 MV X-rays in 70% of centres, mostly utilizing beam modifiers. Computerized treatment planning is performed in 95% of cases. Fifty-five percent of departments prescribe the dose at the ICRU point. Portal films are routinely taken in 50% of cases. Boost irradiation is mainly performed using external XRT. Lastly, acute and late side effects and cosmesis are respectively evaluated in 100%, 98% and 90% of centres. CONCLUSIONS: Results on current practice in Northern Italy generally show a good conformance with European standards. However, some variables related to treatment prescription, simulation and treatment planning need to be standardized. This set of information was largely utilized by the AIRO to define national guidelines adapted to the Italian resources and situation.

Breast Neoplasms↗
PubMed1999

Short-term cyclosporine induces a remission of autoimmune hepatitis in children.

BACKGROUND/AIMS: The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. METHODS: This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded. RESULTS: Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. CONCLUSIONS: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.

Adolescent↗
PubMed1998

[Anti-actin antibodies in acute viral hepatitis A in children].

UNLABELLED: Hepatitis A Virus (HAV) infection has been proposed as a possible trigger of autoimmune hepatitis type I. We have previously reported the presence of anti-actin antibodies en protracted hepatitis A. At present the presence of anti-actin antibodies in acute uncomplicated hepatitis A is unknown. The aim of this study was to evaluate the incidence and persistence of anti-actin antibodies un children with acute hepatitis A. MATERIALS AND METHODS: 38 patients, 21 female and 17 male, with mean age of 6.5 years (range 2-13 years) were included. All patients were anti HAV IgM positive. The patients were clinically controlled and laboratory determinations such as ALT/AST, gammaglobulin, gamma GT, nuclear, smooth muscle (anti-actin specificity) and liver-kidney-microsome type I (anti-LKM) antibodies, were evaluated at admission and at the first, third and fifth month. Anti-actin antibodies were determined by indirect immunofluorescense (IIF) on rat kidney, stomach and liver sections and also on monolayers of cultured fibroblasts. Titers higher than 1/40 were considered positive. RESULTS: 18 patients (47.3%) were anti-actin positive in the first determination (titers 1/40 and 1/80). In 4 patients (12.9%) these antibodies remained positive up to one month. All patients were negative 5 months after the onset of illness. ANA and anti-LKM were negative in all cases. CONCLUSIONS: 1) This data demonstrate the presence of anti-actin antibodies in children with uncomplicated HAV hepatitis. 2) The antibodies remained positive for a short period of time. 3) Titers were lower than in autoimmune hepatitis type I. 4) Taken together these results suggest that anti-actin antibodies would be an expression of non specific stimulation of lymphocyte B.

Actins↗
PubMed1997

Clinical target volume localization using conventional methods (anatomy and palpation) and ultrasonography in early breast cancer post-operative external irradiation.

PURPOSE: To evaluate the accuracy of three methods, anatomy (A), palpation (P) and ultrasounds (US) in localizing the clinical target volume (CTV) in patients (pts) with early breast cancer (EBC) undergoing breast external irradiation as part of conservation therapy. MATERIAL AND METHODS: One hundred consecutive pts with EBC (T(is) 1%, T1 78%, T2 21%, N- 68%, N+ 32%), treated with conservation surgery and breast irradiation with opposed tangential portals, were prospectively analyzed. Anatomically, palpatory or ultrasound defined field borders for CTV localizations were determined in the same position thanks to the utilization of a vacuum-formed cellulose acetate immobilization cast, removed during CTV definitions. RESULTS: P and US CTV localizations have been found to coincide on the four margins (superior, inferior, medial, lateral) in only 1/100 pts, while no pt showed identical A and US CTV localizations. Only 31/397 (8%) field measurements with A, and 98/395 (25%) with P corresponded to US border definition. If mean and median values of each field border were considered, the CTV was generally overestimated with P appearing more accurate than A in a gross definition of the target (P < 0.01). However, a geographical miss of at least one field border of CTV occurred in 55% of pts with A and in 36% of pts with P. The most critical margin to be defined with conventional methods was the superior one: an underestimation of the cranial border of CTV with A was observed in 51% and with P in 22% of pts (22% and 8%, respectively, when an underestimation by more than 1.5 cm was considered). When pre-menopausal and peri/post-menopausal groups of pts were separately analyzed, conventional methods were highly inaccurate to define the superior border in younger pts, in which a geographical miss was noted with A in 62% and with P in 35% of cases (P < 0.05). When an underestimation of more than 1.5 cm was evaluated, these values were reduced to 33% and 12%, respectively (P = 0.02). Also, in the subgroup of pre-menopausal patients the CTV defined by palpatory reference lines appeared to be more accurate than A-method (P < 0.01). CONCLUSIONS: Conventional methods frequently appear inadequate to localize residual mammary gland in EBC post-operative external irradiation. This analysis evidentiates the inaccuracy of empirical CTV definition, and suggests that palpation or anatomical reference borders should be critically used and that state of art imaging methods should be included in treatment planning, particularly in pre-menopausal pts. If economical or individual variables have to be taken into account, palpation might be considered in post-menopausal women.

Adult↗