Prognostic factors for progression-free and overall survival in advanced biliary tract cancer.

BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.

Simultaneous acute pulmonary embolism and isolated septal myocardial infarction in a young patient

While the overall incidence of myocardial infarction (MI) has been decreasing since 2000 [1], there is an increasing number of younger patients presenting with MI [2]. Few studies have focused on MI in very young patients, aged 35 years or less, as they only account for a minority of all patients with myocardial infarction [3]. According to the age category, MI differs in presentation, treatment and outcome, as illustrated in table 1. Echocardiography is considered mandatory according to scientific guidelines in the management and diagnosis of MI [4,5,6]. However, new imaging techniques such as cardiac magnetic resonance (CMR) and computed tomography (CT) are increasingly performed and enable further refinement of the diagnosis of MI. These techniques allow, in particular, precise location and quantification of MI. In this case, MI was located to the septum, which is an unusual presentation of MI. The incidence of pulmonary embolism (PE) has also increased in young patients over the past years [7]. Since symptoms and signs of PE may be non-specific, establishing its diagnosis remains a challenge [8]. Therefore, PE is one of the most frequently missed diagnosis in clinical medicine. Because of the widespread use of CT and its improved visualization of pulmonary arteries, PE may be discovered incidentally [9]. In the absence of a congenital disorder, multiple and/or simultaneous disease presentation is uncommon in the young. We report the rare case of a 35 year old male with isolated septal MI and simultaneous PE. The diagnosis of this rare clinical entity was only possible by means of newer imaging techniques.

Perfuração espontânea de colédoco em adolescente

Spontaneous perforation of the common bile duct is rare. It happens predominantly in children and it is related to obstructive disease of the biliary tract. We present a case of an 18 year-old male patient, with ulcerative rectocolitis associated with malignant tumor of the head of pancreas. The patient developed an acute abdomen syndrome and laparotomy, a spontaneous perforation of common bile duct was evidenced. The authors make a revision of the clinical aspects of that pathology.

Úlcera gástrica terebrante e pancreatite aguda provocadas por tricobezoar

Bezoar is a foreing body whitin the digestive tract originated from ingestion of varied substances, mainly vegetal fiber or hair. We present a case of a 14-year-old girl with trichotillomania, gastric trichobezoar, gastric ulcer and acute pancreatitis. The patient was operated on for anterior gastrotomy and removal of trichobezoar, with good postoperative follow-up. We illustrate this case to emphasize the need for recognition of gastric ulcer with acute pancreatitis and surgical management.

Complicated diverticular disease: the changing paradigm for treatment

The term "complicated" diverticulitis is reserved for inflamed diverticular disease complicated by bleeding, abscess, peritonitis, fistula or bowel obstruction. Hemorrhage is best treated by angioembolization (interventional radiology). Treatment of infected diverticulitis has evolved enormously thanks to: 1) laparoscopic colonic resection followed or not (Hartmann's procedure) by restoration of intestinal continuity, 2) simple laparoscopic lavage (for peritonitis +/- resection). Diverticulitis (inflammation) may be treated with antibiotics alone, anti-inflammatory drugs, combined with bed rest and hygienic measures. Diverticular abscesses (Hinchey Grades I, II) may be initially treated by antibiotics alone and/or percutaneous drainage, depending on the size of the abscess. Generalized purulent peritonitis (Hinchey III) may be treated by the classic Hartmann procedure, or exteriorization of the perforation as a stoma, primary resection with or without anastomosis, with or without diversion, and last, simple laparoscopic lavage, usually even without drainage. Feculent peritonitis (Hinchey IV), a traditional indication for Hartmann's procedure, may also benefit from primary resection followed by anastomosis, with or without diversion, and even laparoscopic lavage. Acute obstruction (nearby inflammation, or adhesions, pseudotumoral formation, chronic strictures) and fistula are most often treated by resection, ideally laparoscopic. Minimal invasive therapeutic algorithms that, combined with less strict indications for radical surgery before a definite recurrence pattern is established, has definitely lead to fewer resections and/or stomas, reducing their attendant morbidity and mortality, improved post-interventional quality of life, and less costly therapeutic policies.

Severity assessment of acute pancreatitis: applying Marshall scoring system

Objective: To analyze the effectiveness of the Marshall scoring system to evaluate the severity of acute pancreatitis (AP). Methods : We performed a prospective, observational study in 39 patients with AP evaluated by the Marshall scoring system and the Ranson criteria (admission and 48 hours). We assessed the progression of the disease for seven days and compared the data of the two criteria. Results : Seven patients died during the observation period and one died afterwards. All deaths had shown failure of at least one system by the Marshall method. Conclusion : The Marshall scoring system may be used as an effective and simplified application method to assess the severity of acute pancreatitis.

Effects of Socioeconomic Status and Sociodemographic Features on Cardiovascular Disease. Mortality and Morbidity in Finland

Despite declining trends in morbidity and mortality, cardiovascular diseases have a considerable impact on Finnish public health. A goal in Finnish health policy is to reduce inequalities in health and mortality among population groups. The aim of this study was to assess inequalities in cardiovascular diseases according to socioeconomic status (SES), language groups and other sociodemographic characteristics. The main data source was generated from events in 35-99 year-old men and women registered in the population-based FINMONICA and FINAMI myocardial infarction registers during the years ranging from 1988-2002. Information on population group characteristics was obtained from Statistics Finland. Additional data were derived from the FINMONICA and FINSTROKE stroke registers and the FINRISK Study. SES, measured by income level, was a major determinant of acute coronary syndrome (ACS) mortality. Among middle-aged men, the 28-day mortality rate of the lowest group of six income groups was 5.2 times and incidence 2.7 times as high when compared to the highest income group. Among women, the differences were even larger. Among the unmarried, the incidence of ACS was approximately 1.6 times as high and their prognosis was significantly worse than among married persons - both in men and women and independent of age. Higher age-standardized attack rates of ACS and stroke were found among Finnish-speaking compared to Swedish-speaking men in Turku and these differences could not be completely explained by SES. In these language groups, modest differences were found in traditional risk factor levels possibly explaining part of the found morbidity and mortality inequality. In conclusion, there are considerable differences in the morbidity and mortality of ACS and stroke between socioeconomic and sociodemographic groups, in Finland. Focusing measures to reduce the excess morbidity and mortality, in groups at high risk, could decrease the economic burden of cardiovascular diseases and thus be an important public health goal in Finland.

Acute fasciolosis in cattle in southern Brazil

This study describes the epidemiological and pathological aspects of an outbreak of acute fasciolosis in cattle in southern Brazil. Fifteen out of 70 three-year-old pregnant cows lost weight in the 30-40 days prior to calving. Clinical signs included diarrhea, weakness, mild anemia and jaundice. Dark yellow fluid in the abdominal cavity was observed at necropsy. Fibrin and clotted blood were adhered to the pericardium and lung, primarily in the diaphragmatic lobes. The liver was enlarged, and the capsular surface was irregular with clear areas and petechiae. At the cut surface, the liver was irregular, firm and edematous, and several hemorrhagic channels could be observed. Areas of fibrosis through the parenchyma and whitish thrombi occluding the great vessels were also observed. The livers of 10 cows that not died were condemned at slaughter for lesions of fasciolosis similar to those observed at necropsy. Microscopically, the liver showed areas of coagulation necrosis, extensive hemorrhages in the streaks or foci and disruption of the parenchyma with neutrophil and eosinophil infiltration. Fibrosis and bile duct proliferation were also observed. Immature Fasciola hepatica flukes were observed in the parenchyma surrounded by degenerated hepatocytes, neutrophils, eosinophils, and hemorrhages. The outbreak occurred on a farm located in an area endemic for fasciolosis, although the acute form of the disease is not common in cattle in this region. It is likely that the cows were infected by F. hepatica metacercariae released in the late fall or early spring in the rice stubble where the herd was grazing prior to calving. Although mortality due to fasciolosis in cattle is infrequent, outbreaks can occur and treatments that are effective in both the immature and adult forms of the parasite should be administered to prevent economic losses.

Molecular characteristics of Machado-Joseph disease mutation in 25 newly described Brazilian families

Machado-Joseph disease (MJD) is a form of autosomal dominant spinocerebellar ataxia first described in North-American patients originating from the Portuguese islands of the Azores. Clinically this disorder is characterized by late onset progressive ataxia with associated features, such as: ophthalmoplegia, pyramidal and extrapyramidal signs and distal muscular atrophies. The causative mutation is an expansion of a CAG repeat in the coding region of the MJD1 gene. We have identified 25 unrelated families segregating the MJD mutation during a large collaborative study of spinocerebellar ataxias in Brazil. In the present study a total of 62 family members were genotyped for the CAG repeat in the MJD1 gene, as well as 63 non-MJD individuals (126 normal chromosomes), used as normal controls. We observed a wide gap between the size range of the normal and expanded CAG repeats: the normal allele had from 12 to 33 CAGs (mean = 23 CAGs), whereas the expanded alleles ranged from 66 to 78 CAGs (mean = 71.5 CAGs). There were no differences in CAG tract length according to gender of affected individuals or transmitting parent. We observed a significant negative correlation between age at onset of the disease and length of the CAG tract in the expended allele (r = -0.6, P = 0.00006); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2 = 0.4). There was instability of the expanded CAG tract during transmission from parent to offspring, both expansions and contractions were observed; however, there was an overall tendency for expansion, with a mean increase of +2.4 CAGs. The tendency for expansion appeared to the greater in paternal (mean increase of +3.5 CAGs) than in maternal transmissions (mean increase of +1.3 CAGs). Anticipation was observed in all transmissions in which ages at onset for parent and offspring were known; however, anticipation was not always associated with an increase in the expanded CAG repeat length. Our results indicate that the molecular diagnosis of MJD can be confirmed or excluded in all suspected individuals, since alleles of intermediary size were not observed.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using balloon desendothelization without dietary intervention

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1% cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80%) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P<0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches

Cytokine profiles during experimental Chagas' disease

People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-g in both mouse strains. However, the amount of IFN-g in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

IFN-g in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

Acute promyelocytic leukemia: the study of t(15;17) translocation by fluorescent in situ hybridization, reverse transcriptase-polymerase chain reaction and cytogenetic techniques

Acute promyelocytic leukemia (AML M3) is a well-defined subtype of leukemia with specific and peculiar characteristics. Immediate identification of t(15;17) or the PML/RARA gene rearrangement is fundamental for treatment. The objective of the present study was to compare fluorescent in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and karyotyping in 18 samples (12 at diagnosis and 6 after treatment) from 13 AML M3 patients. Bone marrow samples were submitted to karyotype G-banding, FISH and RT-PCR. At diagnosis, cytogenetics was successful in 10 of 12 samples, 8 with t(15;17) and 2 without. FISH was positive in 11/12 cases (one had no cells for analysis) and positivity varied from 25 to 93% (mean: 56%). RT-PCR was done in 6/12 cases and all were positive. Four of 8 patients with t(15;17) presented positive RT-PCR as well as 2 without metaphases. The lack of RT-PCR results in the other samples was due to poor quality RNA. When the three tests were compared at diagnosis, karyotyping presented the translocation in 80% of the tested samples while FISH and RT-PCR showed the PML/RARA rearrangement in 100% of them. Of 6 samples evaluated after treatment, 3 showed a normal karyotype, 1 persistence of an abnormal clone and 2 no metaphases. FISH was negative in 4 samples studied and 2 had no material for analysis. RT-PCR was positive in 4 (2 of which showed negative FISH, indicating residual disease) and negative in 2. When the three tests were compared after treatment, they showed concordance in 2 of 6 samples or, when there were not enough cells for all tests, concordance between karyotype and RT-PCR in one. At remission, RT-PCR was the most sensitive test in detecting residual disease, as expected (positive in 4/6 samples). An incidence of about 40% of 5' breaks and 60% of 3' breaks, i.e., bcr3 and bcr1/bcr2, respectively, was observed.

von Willebrand factor antigen levels in plasma of patients with malignant breast disease

von Willebrand factor (vWF) is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag) by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 ± 78 U/dl in patients with cancer, 148.4 ± 59 U/dl in patients with benign disease and 130.6 ± 45 U/dl in controls (P<0.005). We also detected a significant increase in the levels of vWF:Ag (P<0.0001) in patients with advanced stages of the disease (stage IV = 263.3 ± 113 U/dl, stage IIIB = 194.0 ± 44 U/dl) as compared to those with earlier stages of the disease (stage I = 155.3 ± 65 U/dl, stage IIA = 146.9 ± 75 U/dl). In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression.

Early prediction of poor outcome in patients with acute asthma in the emergency room

Early identification of patients who need hospitalization or patients who should be discharged would be helpful for the management of acute asthma in the emergency room. The objective of the present study was to examine the clinical and pulmonary functional measures used during the first hour of assessment of acute asthma in the emergency room in order to predict the outcome. We evaluated 88 patients. The inclusion criteria were age between 12 and 55 years, forced expiratory volume in the first second below 50% of predicted value, and no history of chronic disease or pregnancy. After baseline evaluation, all patients were treated with 2.5 mg albuterol delivered by nebulization every 20 min in the first hour and 60 mg of intravenous methylprednisolone. Patients were reevaluated after 60 min of treatment. Sixty-five patients (73.9%) were successfully treated and discharged from the emergency room (good responders), and 23 (26.1%) were hospitalized or were treated and discharged with relapse within 10 days (poor responders). A predictive index was developed: peak expiratory flow rates after 1 h <=0% of predicted values and accessory muscle use after 1 h. The index ranged from 0 to 2. An index of 1 or higher presented a sensitivity of 74.0, a specificity of 69.0, a positive predictive value of 46.0, and a negative predictive value of 88.0. It was possible to predict outcome in the first hour of management of acute asthma in the emergency room when the index score was 0 or 2.