RESUMO
Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis characterized by systemic features, due to histiocytic infiltration along with haemophagocytosis, which may also appear in bone marrow, spleen, lymph nodes, and liver. Haemophagocytic lymphohistiocytosis (HLH) is a group of autoinflammatory disorders, which include macrophage activation syndrome, sometimes observed in the course of systemic autoimmune diseases, such as juvenile chronic polyarthritis, systemic lupus erythematosus or vasculitis, and infection-associated haemophagocytic syndrome; if not promptly recognised and treated, HLH can be fatal. Visceral leishmaniasis (VL) is a systemic disease caused by different forms of Leishmania spp., an intracellular protozoa. VL is endemic in tropical countries such as in the Middle East and the Mediterranean. The typical clinical and laboratory features are fever, hepato-splenomegaly, hypergammaglobulinaemia and pancytopenia. The features of VL may mimic some haematologic diseases. We report a case of cytophagic histiocytic panniculitis and HLH, triggered by a previous visceral leishmania infection. Cyclosporine was quickly effective in this case, after failure of high-dose glucocorticoids, anakinra and etoposide.
Assuntos
Ciclosporina , Histiocitose , Leishmania , Leishmaniose Visceral , Linfo-Histiocitose Hemofagocítica , Paniculite , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Medula Óssea/parasitologia , Exame de Medula Óssea/métodos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Monitoramento de Medicamentos , Substituição de Medicamentos/métodos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Histiocitose/diagnóstico , Histiocitose/etiologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Leishmania/efeitos dos fármacos , Leishmania/isolamento & purificação , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/fisiopatologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Masculino , Paniculite/diagnóstico , Paniculite/etiologia , Resultado do TratamentoRESUMO
Abdominal vasculitis represents a rare, but life-threatening manifestation in mixed cryoglobulinemic syndrome (MCsn), despite aggressive immunosuppressive treatments. Anti-CD20 monoclonal antibody, rituximab (RTX) has already been used with good results in MC in preliminary studies. No data have been provided, however, on the efficacy of RTX in gastrointestinal involvement of MCsn. Herein, we report the favourable outcomes of the gastrointestinal manifestations in five patients treated with RTX, where the diagnosis of abdominal vasculitis was confirmed by histopathological findings in 2 out of 5 patients, while in the other three patients the diagnosis was made on the basis of positive endoscopy or by integrating clinical and laboratory data.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Crioglobulinemia/complicações , Fatores Imunológicos/administração & dosagem , Vasculite/complicações , Vasculite/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Murinos , Biópsia , Feminino , Trato Gastrointestinal/irrigação sanguínea , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab , Índice de Gravidade de Doença , Resultado do Tratamento , Vasculite/patologiaRESUMO
Pseudo-aneurysms (PAs) of the hepatic artery are rare complications of liver transplantation, which are characterized by a high mortality rate. The majority occur within the first 2 months after orthotopic liver transplantation. They become clinically manifest with sudden hypotension, gastrointestinal bleeding, and abnormal liver function test results. Early diagnosis and treatment are essential to prevent life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction, but a feasible treatment option involves an angiographic approach with the positioning of a stent or transarterial coil embolization followed by revascularization. We report a case of posttransplantation hepatic artery PA (HA-PA) with bleeding into the duodenum, diagnosed using abdominal computed tomography (CT). Arterial kinking prevented a covered stent graft from being inserted successfully using X-ray angiography, so the patient underwent emergency surgery in an attempt to exclude the PA and revascularize the organ via an aorto-hepatic bypass with an iliac vascular graft obtained from the donor. The surgical procedure failed due to progressive macroscopic dissection of the HA wall up to the bifurcation. The patient underwent retransplantation but died 25 days later due to multiple-organ failure. Histopathology of the first liver graft confirmed arterial graft dissection and pathological changes in the donor HA wall.
Assuntos
Falso Aneurisma/patologia , Carcinoma Hepatocelular/cirurgia , Artéria Hepática/patologia , Cirrose Hepática Alcoólica/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/patologia , Anastomose Cirúrgica , Anemia/etiologia , Duodenopatias/diagnóstico , Evolução Fatal , Veias Hepáticas/cirurgia , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Veia Cava Inferior/cirurgiaRESUMO
Early cholestatic graft dysfunction is a frequent cause of morbidity after orthotopic liver transplantation (OLT). We analyze the role of selective bilirubin plasma absorption (PAP) using Plasorba BR-350 in 4 OLT patients who had experienced early severe cholestatic graft dysfunction within 15 days after transplantation. Patients were treated with 3 consecutive cycles of PAP with Plasorba BR-350. The median amount of plasma treated was 7500 mL. Median treatment duration was 231 minutes. The average plasma bilirubin level was 37 +/- 1 mg/dL before PAP and decreased to 15 +/- 0.2 mg/dL at the end of the third cycle of PAP; 3 of 4 cases had progressive bilirubin normalization after PAP. The average amount of bilirubin removed from the plasma of the patients during each PAP treatment was 143 +/- 24 mg. At the beginning of each cycle of PAP, the Plasorba BR-350 was able to remove >90% of the total plasma bilirubin, a percentage that decreased to 60%, 50%, and 40% after 2 L, 4 L, and 7 L of plasma were treated, respectively. Liver biopsies performed after the third treatment showed reduced cholestasis when compared with the pretreatment biopsy specimen. The preliminary data suggested that PAP selective for bilirubin removal may not only reduce the bilirubin level, but may also improve the histological pattern of the graft in terms of reduced cholestatic signs.
Assuntos
Absorção , Bilirrubina/sangue , Bilirrubina/isolamento & purificação , Colestase/sangue , Colestase/terapia , Transplante de Fígado/fisiologia , Humanos , Valores de ReferênciaRESUMO
Oxidative stress is a condition occurring in liver disorders and causing liver damage due to ischemia-reperfusion (I/R) during liver transplantation. Several markers of chronic oxidative stress are well known; however, early protein targets of oxidative injury are not well defined. To identify them, we used a differential proteomics approach to HepG2 human liver cells that has been treated for 10 minutes with 500 micromol/L H(2)O(2). By differential proteomic analysis, using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, we identified four proteins sensitive to H(2)O(2) treatment that underwent posttranslational modification of native polypeptides. Three of the proteins belong to the Peroxiredoxin family of hydroperoxide scavengers, PrxI, PrxII, and Prx VI, that showed changes in their pI as result of hyperoxidation. Mass mapping experiments demonstrated specific modification of the peroxiredoxins active site thiol into sulphinic and/or sulphonic acid, thus explaining an increased negative charge. The oxidation kinetics of all peroxiredoxins were extremely rapid and sensitive, occurring at H(2)O(2) doses unable to affect common markers of cellular oxidative stress. A differential proteomics approach was also applied to liver needle biopsies after cold (T(1)) and warm (T(2)) ischemia. Proteomic analysis of this material was related to histological changes and immunophenotypic expression of APE1/Ref-1. Hyperoxidation of PrxI occurring during I/R upon liver transplantation is dependent on the time of warm ischemia. Histological changes and APE1/Ref-1 expression parallel Peroxiredoxin changes. Our present data may be relevant to better graft preservation and evaluation for transplantation.
Assuntos
Proteoma , Traumatismo por Reperfusão/genética , Humanos , Fígado/patologia , Circulação Hepática , Oxirredução , Traumatismo por Reperfusão/patologiaRESUMO
The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Hepatite B/complicações , Hepatite B/cirurgia , Hepatite C/complicações , Hepatite C/cirurgia , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate histological variables correlated with pathological response to chemo-radiotherapy protocols for rectal cancer and with local recurrence and survival. METHODS: From 1994 to 2003, 58 patients with rectal cancer were enrolled in a non-randomised study based on standardised treatment with radiotherapy, 5-fluorouracil, and surgical resection, followed by histological examination, including tumour regression grading and depth of neoplastic infiltration within the perirectal fat. All patients were followed up. Mean (SD) length of follow up was 55.3 (28.1) months, range 5 to 108. RESULTS: No case was found with no regression (grade 0). Tumour regression was defined as grade 1 in 24.5% of cases, grade 2 in 58.5%, grade 3 in 7.5%, and grade 4 (complete regression) in 9.5%. Neoplastic infiltration of >4 mm within the perirectal fat was found in 25.6% of cases in grade 1, 55.8% in grade, 2.7% in grade 3, and 11.6% in grade 4. In 80% cases of pT4 depth of neoplastic infiltration within the perirectal fat was >4 mm (100% were pN+), and the same spread was also found in 53.4% of pT2 and 86.2% of pT3. Pathological response was associated with regression grade (p = 0.006) and depth of neoplastic infiltration within the perirectal fat (p = 0.04). Tumour regression grading was an independent variable for pT (p = 0.0002), pN status (p = 0.00004), pathological staging (p = 0.000001), and local recurrence (p = 0.003). CONCLUSIONS: Involvement of the lateral resection margins correlates with a poor prognosis and indicates the likelihood of local recurrence of rectal cancer. Tumour regression grading and the depth of neoplastic infiltration within the perirectal fat are important prognostic factors that need to be evaluated routinely.
Assuntos
Adenocarcinoma/patologia , Tecido Adiposo/patologia , Neoplasias Retais/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Radioterapia Adjuvante , Neoplasias Retais/cirurgia , Neoplasias Retais/terapia , Taxa de SobrevidaRESUMO
Liver transplantation (OLT) is a treatment for hepatocellular carcinoma (HCC) superimposed on cirrhosis provided that the disease meets defined criteria. The aim of the study was to evaluate our experience with respect to clinical and pathological staging and long-term results. From 1996 to 2005, 50 patients underwent OLT for HCC including 43 men (86%) and seven women (14%) of median age 57 years (range 37 to 67). All patients fulfilled the Milan criteria. The HCC diagnosis was based on preoperative imaging and alpha-fetoprotein levels; no tumor biopsy was performed. Upon histological examination of the resected specimens, we discovered 6 (12%) incidentalomas and 8 (16%) cases of no HCC. Finally we had 42 "true" HCC. Twenty-six patients (52%) have been downstaged and 10 (20%) upstaged by preoperative imaging; 15% were pT1, 45% were pT2, 27% pT3, and 13% pT4a. Twenty-six percent of cases exceeded the Milan criteria. One patient (pT4a) with microvascular invasion died of pulmonary metastases at 14 months after transplantation. No HCC recurrences within the liver have been encountered at a median follow-up of 20 months (range 0 to 80 months). Overall the estimated 1-, 3-, and 5-year survival rates were 83%, 77%, and 72%, respectively. One-, 3-, and 5-year estimated survival rates were 87%, 75%, and 75% for pT1, and pT2, and 75%, 67%, and 67% for pT3 and pT4a, respectively (P = .99). Based on our experience OLT for HCC has long-term results comparable to those without HCC despite the presence of a significant number of cases exceeding the Milan criteria upon pathological staging.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/fisiologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Transplante de Fígado/mortalidade , Transplante de Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The ability to predict graft function before transplantation has proven to be a difficult task, especially for macrovacuolar steatosis that is considered a major cause of posttransplant dysfunction. It is well known that macrovacuolar steatosis greater than 25% influences the short- and long-term outcomes of liver transplantation. We retrospectively analyzed frozen sections from 43 donor livers comparing preoperative laboratory/clinical values, and liver ultrasound of a cohort of donors without (group A, n=21) versus with steatosis of 25% to 35% (group B, n=22) upon liver biopsy performed during harvesting. We analyzed the possible correlations between preoperative donor data and the degree of macrovacuolar steatosis. None of the biochemical and clinical parameters were related to the degree of hepatic steatosis. The only difference between the two groups was the echographic pattern, with evidence of 27% fatty liver by ultrasound in group B and 5% in group A (p=.04). The specificity of hepatic ultrasound for macrovacuolar steatosis was 95% and the sensitivity was only 27%, while the positive and negative predictive value were 86% and 55%, respectively. In conclusion, liver biopsy during donor harvesting remains the gold standard to identify macrovacuolar steatosis greater than 25%. Hepatic ultrasound has a role to exclude the presence of steatosis in normal livers due to its high specificity, but it is not useful to make the diagnosis of a fatty liver since it has a low sensitivity and negative predictive value. Thereafter a liver ultrasound positive for hepatic steatosis alone should not be considered a valuable tool to discard an organ from transplantation.
Assuntos
Fígado Gorduroso/patologia , Fígado/patologia , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Fígado Gorduroso/diagnóstico por imagem , Feminino , Hepatectomia , Humanos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Retrospectivos , UltrassonografiaRESUMO
De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.
Assuntos
Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Neoplasias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Cadáver , Seguimentos , Humanos , Incidência , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Transplante de Fígado/mortalidade , Neoplasias/classificação , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Doadores de TecidosRESUMO
High temperature requirement A1 (HtrA1) is a secreted protease involved in placental development. Fibronectin (FN) is involved in important process such as wound healing, cell adhesion and spreading, growth, migration, and differentiation. The purpose of this study was to analyse the expression patterns of HtrA1 in relationship to FN and to the key growth zones of placenta such as mesenchymal villi as well as cell islands and cell columns. We demonstrated that FN and HtrA1 are localized in the placental key growth zones suggesting a pivotal role in maintaining the balance among the molecules involved in the placental development and differentiation.
Assuntos
Vilosidades Coriônicas/metabolismo , Fibronectinas/biossíntese , Regulação da Expressão Gênica/fisiologia , Serina Endopeptidases/biossíntese , Feminino , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , GravidezRESUMO
Increasing evidence supports the hypothesis that TGFb1 signalling may be mediated by high temperature requirement A1 (HtrA1) serine protease, acting on important regulatory mechanisms such as cell proliferation and mobility. Evidence is now accumulating to suggest that HtrA1 is involved in the development and progression of several pathologies. The aim of this study was to evaluate: i) if HtrA1 and TGFb1 expressions differ in eutopic and ectopic endometrium in women with endometriosis; ii) if HtrA1 correlates to TGFb1, pSmad and Ki67. This study was carried out including 10 women with ovarian endometriosis (cases) and 10 women with non endometriotic diseases (controls). Endometrial tissue underwent immunohistochemical H-score analysis for HtrA1, TGFb1, pSmad and Ki67 molecules. Data evaluation was performed by a nonparametric Kruskal-Wallis test and Spearman correlation was applied to evaluate the relationship among the molecules investigated in the epithelial and in the stromal compartment. The HtrA1 was significant decreased in ectopic and eutopic endometrium of women with endometriosis when compared with control endometrium in epithelial compartment. TGFb1was significantly increased in eutopic endometrium and decreased in ectopic endometrium in epithelial and stromal compartment. In addition, Ki67 was significant increased and an increase, but not significant, was detected for pSMAd2 in eutopic and ectopic endometrium compared to control one. In summary, the significant direct correlation between TGFb1 and pSmad2 as well as between HtrA1 and TGFb1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis.
Assuntos
Endometriose , Endométrio , Antígeno Ki-67/metabolismo , Serina Endopeptidases/metabolismo , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Endometriose/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Feminino , Serina Peptidase 1 de Requerimento de Alta Temperatura A , HumanosRESUMO
In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy at different risks for gastric cancer (GC), plasma levels of pepsinogens (PGI and PGII) and fat-soluble vitamins were assayed. Pepsinogen levels were used to identify individuals with chronic atrophic gastritis (CAG). Severe CAG (PGI < or = 20 pg/liter) affected 5.8% of the population, but the prevalence rose with increasing age and declining social class. Severe CAG was 5 times more common in areas with high compared to low rates of GC. Risk also rose with increasing consumption of salted/dried fish but was inversely related to dietary intake of beta-carotene and to plasma retinol and cholesterol levels. The prevalence of moderate CAG (PGI > 20 pg/liter, but PGI/PGII < or = 2.9) was 6.3%. Moderate CAG was also related to age and social class and increased 1.8-fold in areas where GC rates were high, but was not strongly associated with diet or plasma nutrients. The authors discuss these findings in relation to those from a previous case-control study of GC in the same areas.
Assuntos
Gastrite Atrófica/epidemiologia , Pepsinogênios/sangue , Vitaminas/sangue , Adulto , Fatores Etários , Idoso , Animais , Colesterol/sangue , Feminino , Peixes , Gastrite Atrófica/sangue , Gastrite Atrófica/complicações , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Classe Social , Sódio na Dieta/efeitos adversos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaRESUMO
In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy, two at low and two at high risk for gastric cancer, plasma levels of Helicobacter pylori IgG antibodies were assayed in order to investigate associations with the geographical distribution of gastric cancer and other dietary and life-style factors, as assessed by personal interview. H. pylori positivity (antibody titer above or equal to 10 micrograms/ml), 45% overall, increased with age and was inversely associated with social class but showed little geographical variation or association with dietary variables and blood nutrients. H. pylori positivity was also associated with increased blood levels of pepsinogens, particularly pepsinogen II. The authors discuss these findings in relation to those from a previous case-control study of gastric cancer in the same areas.
Assuntos
Anticorpos Antibacterianos/sangue , Helicobacter pylori/imunologia , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Anticorpos Anti-Idiotípicos/sangue , Biomarcadores Tumorais/sangue , Dieta , Feminino , Humanos , Itália/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Pepsinogênios/sangue , Prevalência , Distribuição Aleatória , Fatores de Risco , Classe Social , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologiaRESUMO
A stillborn female with a "de novo" deletion of band 12p13 is described. Her main clinical manifestations are intrauterine growth retardation, unilateral cleft lip, protruding tongue, and small, low set, and posteriorly angulated ears. Comparison of this case with 4 previous reported patients with an isolated distal del(12p) fails to show significant common phenotypic characteristics.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 12 , Morte Fetal/genética , Anormalidades Múltiplas/genética , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , SíndromeRESUMO
DNA index (DI) values seen in 86 sporadic colorectal adenocarcinomas were related to clinical, morphological, and disease progression features. DI, whose overall distribution was bimodal with peaks in the diploid and from hypotriploid to tetraploid ranges, was related to pathological lymph node staging (pN), staging, lymphoid reaction, and tubular configuration. With increasing severity in pathological features, an irregular shift in DI class prevalence was seen, with no steady increase from diploidy to higher degrees of aneuploidy. All UICC stage I tumors (13% of total) were aneuploid, 50% being hypertriploid; diploidy (35%) and hypertriploidy (22%) prevailed in stage II carcinomas (41% of total), diploidy (35%) and hypotriploidy (30%) in stage III (30% of total), and triploidy (33%) in stage IV (15% of total). Amongst features related to stage (lymphoid reaction, depth of neoplastic embolization, grading, tubular configuration, and polymorphism), few were associated with DI, and none influenced DI shift and class prevalence through the stages. The biological capabilities of colorectal adenocarcinoma in relation to stage are expressed by certain aneuploid DI classes (hypertriploidy: absence of extracolonic spread; hypotriploidy: lymph node metastases; triploidy: distant metastases). Diploidy is unrelated to criteria defining stage above I and predicts 50% of cases with development of metachronous metastases. Irregular DI class shift through the stages may be attributable to different pathways of cancerogenesis and disease progression in diploid versus aneuploid carcinomas. Alternatively, assuming that the diploid fraction in aneuploid tumors contains neoplastic cells, pure diploid carcinomas represent the selection of a vital clone that may give rise to a further mixed population whose aneuploid DI is different and best fitted to express the biological capabilities of that given stage.
Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , DNA de Neoplasias/genética , Índice Mitótico/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ploidias , Taxa de SobrevidaRESUMO
The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 +/- 5.9 versus 63.2 +/- 6.9 years, P = 0.024) and younger in men (58.8 +/- 8.9 versus 66.0 +/- 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected.
Assuntos
Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Veia Porta/patologia , Tromboflebite/complicações , Fatores Etários , Idoso , Autopsia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Tromboflebite/mortalidade , Tromboflebite/patologiaRESUMO
Histologically detectable iron (HDI) and HFE mutations were searched for in liver biopsy specimens from 58 Italian patients with chronic hepatitis C, and morphologic features were compared to examine their reciprocal relation and their contribution to disease progression. HDI was evident in 48% of cases with features of nonhemochromatosis iron overload. Total, sinusoidal, and portal HDI increased with stage; grade was related to all iron scores because of the contribution of portal inflammation and interface hepatitis. HFE mutations were seen in 47% of patients with chronic hepatitis C and in 28% of control subjects; they were related to stage and the His63Asp mutation to portal HDI. On multivariate analysis, grade but not stage or HFE mutations was associated with HDI in all sites. Interface hepatitis with its sequelae (sinusoidal capillarization and microshunting) represents a major factor in iron deposition in chronic hepatitis C and justifies the features of HDI. HFE mutations are not responsible for HDI deposition but could favor the progression of virus-induced damage independently from interference with iron metabolism.
Assuntos
Antígenos HLA/genética , Hemocromatose/genética , Hepatite C Crônica/genética , Antígenos de Histocompatibilidade Classe I/genética , Ferro/metabolismo , Proteínas de Membrana , Mutação de Sentido Incorreto , Adolescente , Adulto , Idoso , Anticorpos Antivirais/análise , Progressão da Doença , Feminino , Hemocromatose/metabolismo , Hemocromatose/patologia , Proteína da Hemocromatose , Hepacivirus/genética , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIMS: To investigate the immunohistochemical expression of p53 and bcl-2 proteins in squamous cell carcinoma (SCC) of the oesophagus and to assess whether expression of these oncoproteins can be used to stratify patients into groups with a favourable or unfavourable response to preoperative chemo/radiotherapy. METHODS: The initial diagnostic biopsy and the corresponding resected samples were obtained from 22 consecutive patients with SCC. All patients underwent preoperative chemo/radiotherapy. Tumour sections were incubated with a monoclonal antibody directed against p53 (DO-7). Twenty four non-neoplastic oesophageal biopsy specimens immunostained for p53 served as controls. Twelve randomly chosen sections from the 22 SCC samples were immunostained to test for bcl-2 protein expression. RESULTS: After chemo/radiotherapy, 12 (55%) of the 22 patients had no evidence of tumour in the resected oesophagus. Before chemoradiotherapy, however, 17 (77%) patients were p53 positive. After treatment, residual carcinoma was detected in seven (41%) of the 17 p53 positive patients. All non-responsive cases had the same p53 immunopattern as before treatment. Bcl-2 immunoexpression was detected in six (50%) of 12 patients. Residual tumour was detected in the residual oesophagus in two (33%) of the six bcl-2 positive patients. After treatment, bcl-2 expression was no longer detected in the residual neoplastic cells of a previously bcl-2 positive tumour. Using Fisher's exact test no significant association was found between oncoprotein expression and response to preoperative treatment. CONCLUSION: This study confirms the observation that p53 protein is frequently expressed in SCCs of the oesophagus, probably as a result of a mutation of the TP53 gene. However, no significant association was found between oncoprotein expression and response to chemo/radiotherapy. Anticancer agents do not seem to modify the expression of p53 and bcl-2 proteins.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Feminino , Proteínas de Ligação ao GTP/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-bcl-2 , Resultado do Tratamento , Proteína Supressora de Tumor p53/análiseRESUMO
Serum iron indices are believed to be elevated in patients with hepatitis C virus (HCV) infection in connection to the presence of hepatic inflammation, though this hypothesis has never been formally tested. We studied 69 consecutive, unselected anti HCV antibody positive patients, aged 14 to 70 years. Iron, transferrin saturation and ferritin were measured in fasting serum samples. Histologically detectable iron (HDI) as well as histologic grading and staging were estimated semiquantitatively in liver biopsy samples. The median values for serum iron, transferrin saturation and serum ferritin were 24 micromol/l (range, 8-61), 29 percent (range, 6-77) and 170 microg/l (range, 1-954), respectively. At univariate analysis, all three serum iron indices were positively correlated with grading and staging scores, as well as with HDI in the liver; only serum iron was positively correlated with transaminases. At multivariate analysis, independent associations were found between serum iron and the grading score; ferritin and sinusoidal and portal HDI; transferrin saturation and total hepatic HDI. In conclusion, in hepatitis C, serum iron reflects the degree of current hepatic inflammation and necrosis, whereas the extent of progressive deposition of iron in sites of fibrosis is best reflected by serum ferritin. Transferrin saturation is the best predictor of the status of hepatic iron deposits.