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Biomedical subjects

L Rubbia-Brandt

Publications and source records attributed to L Rubbia-Brandt.

At least 19 recordsLinked to original sources
PubMed2006

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Adult↗
PubMed2006

Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection.

BACKGROUND: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. AIM: To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. METHODS: We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. RESULTS: PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. CONCLUSIONS: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.

Adult↗
PubMed2006

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary.

BACKGROUND: In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high-impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors. METHODS: Twenty consecutive patients with non-obstructive colonic (nine patients) or rectal (11 patients) cancer and advanced synchronous liver metastases were treated according to this strategy. Median age was 56 years. Patients received between two and six cycles of 5-fluorouracil, oxaliplatin and irinotecan-based chemotherapy. Data were collected prospectively. RESULTS: Overall survival rates at 1, 2, 3 and 4 years after the start of treatment were 85, 79, 71 and 56 per cent respectively, with a median survival of 46 months. Sixteen of the 20 patients had complete removal of liver metastases and colorectal tumours (resectability rate 80 per cent). CONCLUSION: This new strategy produced resectability and survival rates better than those expected from the published data on patients with disease of similar severity. It allows initial control and downstaging of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure.

Adult↗
PubMed2006

In vivo microscopic examination of the esophagus for the detection of cancer before liver transplantation in patients with alcoholic cirrhosis.

Esophageal squamous-cell carcinoma is relatively common in alcohol and tobacco abusers, and it can develop rapidly after liver transplantation. We report the early detection of an esophageal squamous-cell carcinoma in a patient with alcoholic cirrhosis, diagnosed during the pre-enlistment work-up that he was undergoing before liver transplantation. This lesion had not been detected at standard endoscopy, but was well characterized using in vivo staining and microscopic examination with an "endocytoscopy" system.

Carcinoma, Squamous Cell↗
PubMed2006

Steatosis in chronic hepatitis C: why does it really matter?

Hepatic steatosis is a common histological feature of chronic hepatitis C. Various factors are associated with hepatic steatosis, including obesity, high alcohol consumption, diabetes type II, and hyperlipidaemia. These factors may contribute to steatosis in patients with chronic hepatitis C. In humans, hepatitis C virus (HCV) genotype 3 is more commonly associated with steatosis. In vitro studies and the transgenic mouse model have suggested that the HCV core protein (genotype 1) can induce lipid accumulation within hepatocytes. However, what is the relevance of steatosis in chronic hepatitis C? It seems that in certain populations, steatosis may be associated with fibrosis progression and this may be genotype specific. The mechanisms underlying this association are unknown; neither is it clear whether this holds true for all patients or only a subgroup. Indeed, after antiviral treatment, virus related steatosis disappears whereas the host associated steatosis remains unaffected. This review describes and discusses the basic and clinical aspects of the relationship between steatosis and progression of fibrosis, and response to treatment in patients with chronic hepatitis C.

Animals↗
PubMed2005

[Alcoholic and nonalcoholic steatohepatitis: the same disease! I. Diagnosis and mechanisms].

Alcoholic steatohepatitis includes steatosis, inflammatory changes and hepatocellular damage. In severe form, jaundice and hepatic failure persist for several weeks, while non severe alcoholic steatohepatitis may follow an insidious course towards cirrhosis. Except for alcohol consumption, nonalcoholic steatohepatitis shares histological features and pathogenic mechanisms with alcoholic steatohepatitis, and is associated to the development of cirrhosis over time. Thus, given the increasing epidemics of the metabolic syndrome in industrialized countries, it is likely that alcoholic cirrhosis has been overdiagnosed in the past years. Obesity, insulin resistance and the oxidative stress including iron-mediated oxidative stress are involved both in alcoholic and non-alcoholic steatohepatitis.

Alcohol Drinking↗
PubMed2005

Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease.

Reactive oxygen species (ROS) are at the centre of many physiological and pathological processes. NOX1, a ROS-producing NADPH oxidase, is highly expressed in the colon but its function in colonic physiology or pathology is still poorly understood. It has been suggested to play a role in host defence, but also in cell growth and possibly malignant transformation. In this study we characterized NOX1 expression in human colon samples derived from healthy control subjects and patients with colon cancer or inflammatory bowel disease (IBD). NOX1 mRNA expression was assessed by dot-blot hybridization, real-time PCR and in situ hybridization, using samples derived from surgical specimens from patients undergoing colon resection. In normal tissues, NOX1 expression was low in the ileum, intermediate in the right colon, and high in the left colon (p = 0.0056 right vs. left colon). NOX1 mRNA levels were not influenced by factors linked to colon tumourigenesis, such as age or sex. Moreover, there was no statistical difference in NOX1 expression between samples derived from adenomas, well differentiated or poorly differentiated colon adenocarcinomas. At a cellular level, NOX1 was highly expressed in colon epithelial cells, both within the crypts and on the luminal surface. In addition, a population of lymphocytes, particularly in the appendix, showed NOX1 expression. Lymphocytes in lesions of Crohn's disease and ulcerative colitis were also strongly positive for NOX1. In conclusion, NOX1 is an enzyme that is constitutively expressed in colon epithelium and is not associated with tumourigenesis. Its distribution in crypts and on the luminal surface, as well as its left-to-right gradient in the colon, suggests a role in host defence function. In addition to the known epithelial localization, we define lymphocytes as a novel site of NOX1 expression, where it may potentially be involved in the pathogenesis of inflammatory bowel diseases.

Adenocarcinoma↗
PubMed2004

Ganciclovir for severe cytomegalovirus primary infection in an immunocompetent child.

Described here is the unusual case of a previously healthy 17-month-old girl who developed severe cytomegalovirus (CMV) disease with prolonged fever and hepatitis. The severity of her illness required hospitalization and prompted antiviral treatment. Short-term intravenous ganciclovir treatment was associated with immediate and sustained resolution of the symptoms as well as a sharp decrease of CMV viremia. This observation suggests that antiviral therapy might be considered in select cases of severe primary CMV infection in immunocompetent children.

Cytomegalovirus↗
PubMed2004

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. PATIENTS AND METHODS: A large series of surgically resected liver metastases (n=153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (alpha-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. RESULTS: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. CONCLUSIONS: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.

Adenocarcinoma↗
PubMed2004

Steatosis affects chronic hepatitis C progression in a genotype specific way.

BACKGROUND AND AIMS: Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype. METHODS: A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m(2); 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated). RESULTS: Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients. CONCLUSIONS: Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.

Adult↗
PubMed2003

Formaldehyde application for haemorrhagic radiation-induced proctitis: a clinical and histological study.

OBJECTIVES: Haemorrhagic radiation-induced proctitis is a serious complication of radiotherapy of pelvic organs. In severe cases, massive haemorrhage may necessitate hospitalization and repeated transfusions. Application of formaldehyde under direct vision is one of the most efficient treatments. The aim of this study was to evaluate the results of this treatment as well as the histological changes induced by formaldehyde on the rectal mucosa. MATERIAL AND METHODS: From January 1991 to September 2001, 13 patients who presented a haemorrhagic radiation-induced proctitis have been treated in our outpatient clinic with 4% formaldehyde cotton soaked applications. They were followed up to one year after the treatment. Endoscopic biopsies were performed before, immediately after the application, 1 month later, as well as at the one-year follow-up. RESULTS: In eight cases bleeding stopped after the first application. In two patients a second application was necessary to control the haemorrhage and in two other patients bleeding ceased definitively after the fourth application. Follow-up evaluation at 12 months showed no sign of acute proctitis or rebleeding. One asymptomatic patient had a mild stenosis of the rectum. Baseline biopsies showed signs of acute inflammation. Those performed after the application of formaldehyde showed fresh thromboses of the vessels of the mucosa. Biopsies at 1 month and 1 year showed only chronic changes secondary to the radiotherapy. CONCLUSION: Local application of 4% formaldehyde for the treatment of haemorrhagic radiation-induced proctitis gives good results, is well tolerated and easy to perform. Formaldehyde applied selectively causes thromboses of the bleeding vessels, without deep lesions or extended necrosis.

Aged↗
PubMed2001

Detection of the negative-strand hepatitis C virus RNA in tissues: implications for pathogenesis.

The replication of hepatitis C virus (HCV) RNA is believed to occur via its transcription into a complementary, genomic-length RNA, the so-called negative-strand HCV RNA. This is based on the comparison with the replication of other members of the Flaviviridae family. Detection of the negative-strand HCV RNA in human tissues by semi-quantitative, strand-specific RT-PCR has contributed to the understanding of the HCV cell tropism and of the pathogenesis of HCV-associated disease manifestations. In particular, it was shown that the levels of intrahepatic HCV RNA are not correlated to the extent of the necroinflammation, but that a significant correlation was found with the liver steatosis. These results suggest that most liver disease associated with HCV infection is mediated by the host immune response. However, in some patients, most notably those infected with HCV genotype 3, HCV may cause a cytopathic effect, consisting in the lipid accumulation within hepatocytes.

Carcinoma, Hepatocellular↗
PubMed2001

Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood.

BACKGROUND/AIMS: In alcoholic hepatitis (AH), enhanced expression of intercellular adhesion molecule-1 (ICAM-1) correlates to neutrophil infiltration and histology. In severe AH under steroids, the evolution of the hepatocyte membranous ICAM-1 expression and its soluble form (sICAM-1) is not known. METHODS: Twenty-six consecutive patients with biopsy-proven severe AH had liver tissue studies for hepatocyte membranous ICAM-1 expression by immunostaining. Lobular neutrophils (mean per high power field) were counted after chloracetate esterase staining. Histological damage was assessed semiquantitatively. Circulating levels of sICAM-1 and TNFalpha in peripheral and hepatic vein were measured using immunoassays. After 8 days on steroids, 19 patients had repeat biopsy. RESULTS: At baseline, hepatocyte membranous ICAM-1 correlated both to histology (r=0.55, P<0.01) and to lobular neutrophils (r=0.56, P<0.01). On steroids, sICAM-1 in hepatic vein and TNFalpha in both vascular beds decreased. Hepatocyte membranous ICAM-1 and hepatocellular damage decreased, but lobular neutrophils increased. Changes in sICAM-1 in hepatic vein correlated to histological changes (r=0.68, P<0.01). CONCLUSIONS: In severe AH under steroids, the short term histological improvement was associated with a decrease in circulating TNFalpha, a decrease in ICAM-1 expression, and correlated to hepatic vein sICAM-1 changes.

Adult↗
PubMed2001

Acute valproate-associated microvesicular steatosis: could the [13C]methionine breath test be useful to assess liver mitochondrial function?

Microvesicular steatosis is a potentially severe manifestation of valproic acid hepatotoxicity due to an acquired impairment of mitochondrial function. Tests currently used to investigate mitochondrial fonction are cumbersome and cannot be used routinely. We report on a noninvasive breath test using [13C]methionine for estimation of mitochondrial function in a case of pure severe valproic acid overdose-induced microvesicular changes. The initially abnormal breath test improved together with the recovery of liver failure. In conclusion, this observation suggests that the [13C]methionine breath test may provide a noninvasive estimate of hepatic mitochondrial function in vivo.

Adult↗
PubMed2001

Absence of leukocyte microchimerism in oral lichen planus (OLP): an in situ hybridisation study.

Oral lichen planus (OLP) is a relatively common chronic inflammatory disease. The majority of patients are between 30 and 50 years of age with a higher incidence in females. The aetiology is unknown and various hypotheses on the pathogenic mechanisms, including autoimmunity, have been proposed over the years. In the present study, we investigated whether leukocyte microchimerism, a biological situation implicated in the aetiology of some autoimmune diseases, might play a role in the pathogenesis of OLP. We used in situ hybridisation to identify Y chromosome DNA in a series of formalin-fixed paraffin-embedded oral mucosa biopsies of women with established clinical and histological disease who had given birth to a male child. The positive control, two mucosal specimens from a man with OLP, showed over 90% of keratinocytes and cells within the inflammatory infiltrate, a positive nuclear signal. The negative control, biopsies from three women having carried only female foetuses and one nulliparous woman, all with OLP, did not show any nuclear signal. In the fifteen selected cases of OLP biopsies from women who had only male offspring, nucleated cells containing the Y chromosome were not detected within the chronic inflammatory infiltrate. These results suggest that unlike some other immunologically mediated diseases, leukocyte microchimerism does not seems to be involved in the pathogenesis of OLP.

Adult↗