Home parenteral nutrition improves quality of life and nutritional status in patients with cancer: a French observational multicentre study.

PURPOSE: Malnutrition is a predictor of poor outcomes in patients with cancer. Little is known about the benefit of nutritional support in these patients. The purpose of this study was to assess the impact of home parenteral nutrition (HPN) on quality of life (Qol) in cancer patients. METHODS: We performed an observational prospective study to determine the impact of HPN on Qol in a population of patients with heterogeneous cancer. Physicians, patients and family members had to complete a questionnaire before HPN administration and 28 days after the course of HPN. Qol was evaluated using the self-administered questionnaire FACT-G. RESULTS: We included 767 patients with cancer of whom 437 ended the study. Mean patient age was 63±11.4 years and 60.5% were men. Primary gastrointestinal cancer was reported in 50% of patients and 65.3% were presenting metastases. Malnutrition was reported in 98.3%. After 28 days of HPN intake, significant improvement was observed in the Qol (49.95±5.82 vs. 48.35±5.01 at baseline, p<0.0001). The mean weight, serum albumin and the nutrition risk index had also improved significantly. Most patients (78%) had perceived a positive impact of the HPN. A significant improvement in patient's well-being was perceived also by family members and physicians. CONCLUSIONS: Our data suggest that preventing and correcting malnutrition using HPN in patients with cancer might have a significant benefit on their well-being. Randomized controlled studies are required to confirm this finding.

Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features.

BACKGROUND: Studies using consecutive liver biopsies constitute an attractive approach to gaining insight into the pathogenesis of alcoholic liver disease. AIM: To analyse histological factors at baseline, which are predictive of fibrosis progression and recurrence of alcoholic hepatitis. RESULTS: A total of 193 drinkers underwent consecutive biopsies at an interval of 4 years. At baseline, 20 had normal livers, 135 steatosis, five fibrosis and 33 alcoholic hepatitis. The fibrosis score increased from 1.07 +/- 0.07 to 1.7 +/- 0.94 (P < 0.001). In multivariate analysis, only steatosis (P = 0.04), alcoholic hepatitis (P = 0.0004) and stage of fibrosis (P < 0.0001) were independent predictive factors of the fibrosis score at the second biopsy. Cirrhosis developed more frequently in patients with steatosis (11%) and alcoholic hepatitis (39%) than in others (0%, P < 0.0001). Alcoholic hepatitis recurred more frequently in patients with alcoholic hepatitis at baseline: 58% vs. 15%, P < 0.0001. In multivariate analysis, alcoholic hepatitis at the first biopsy was the only predictive factor of its recurrence (P < 0.0001). CONCLUSIONS: In a large cohort of drinkers with consecutive biopsies, steatosis, fibrosis stage and alcoholic hepatitis at baseline were independent predictive factors of fibrosis progression. In terms of mechanisms, we propose a novel concept of multiple hits of alcoholic hepatitis occurring in the same patient.

Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study.

BACKGROUND AND AIMS: Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma. PATIENTS AND METHODS: Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI). RESULTS: After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)). CONCLUSION: In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer.

[Ulceronecrotic tracheobronchial involvement in Crohn's disease]. / Atteinte trachéo-bronchique ulcéro-nécrotique au cours d'une maladie de Crohn.

We report the case of a young female patient hospitalized for the first episode of a colonic Crohn's disease with specific ulceronecrotic tracheobronchial involvement leading to chronic and invalidant cough. Symptomatic bronchopulmonary manifestations are very rare in the course of inflammatory bowel diseases and usually not mentioned in Gastroenterology textbooks.

Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract.

BACKGROUND & AIMS: Involvement of an abnormal von Willebrand factor in the bleeding expression of gastrointestinal angiodysplasias has been suggested but not assessed by prospective studies. METHODS: To address this issue, 27 patients with either nonbleeding (group A, n = 9) or bleeding (group B, n = 9) digestive angiodysplasias or telangiectasias or diverticular hemorrhage (group C, n = 9) were enrolled. In all patients, an analysis of von Willebrand factor and a screening for the most common disorders associated with an acquired von Willebrand disease were performed. RESULTS: In all patients from groups A and C, von Willebrand factor was normal, and no underlying disease could be found. In contrast, all but 1 patient from group B had a variable selective loss of the largest multimeric forms of von Willebrand factor, associated in 7 cases with a stenosis of the aortic valve. CONCLUSIONS: This study indicates that most patients with bleeding angiodysplasia or telangiectasia have a deficiency of the largest multimers of von Willebrand factor induced by a latent acquired von Willebrand disease. Because these multimers are the most effective in promoting primary hemostasis at the very high shear conditions related to these vascular malformations, we suggest that their deficiency is likely to contribute to the bleeding diathesis.

[Regenerative nodular hyperplasia: variable clinical aspects]. / Hyperplasie nodulaire régénérative: des aspects cliniques très variables.

BACKGROUND: Regenerative nodular hyperplasia can take on very misleading aspects making diagnosis difficult. CASE REPORTS: We report three cases of regenerative nodular hyperplasia (RNH). In the first patient rupture of esophageal varices was associated with myelofibrosis. In the second, extensive portal thrombus formation was associated with consumption coagulopathy and essential thrombocytemia. The third patient had systemic sclerodermia, hepatic macronodules, refractory exsudative ascitis and chronic hepatic encephalopathy following surgery for a porto-cava anastomosis. DISCUSSION: The diagnosis of RNH should be suspected in a variety of clinical situations with search for associated diseases in all cases. The prognosis is related to the consequences of portal hypertension and the severity of the associated diseases.

Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis.

OBJECTIVES: In experimental models, liver injury induced by ethanol, cytotoxic activity of tumor necrosis factor (TNF) -alpha is principally mediated by TNF receptor p55 (TNFRp55). Among the various mechanisms underlying the toxic effects of TNF-alpha, overproduction of reactive oxygen species seems to play a key role in mediating TNF-alpha-induced cytotoxicity. The aim of this study was to evaluate, in patients with alcoholic liver disease, whether alcohol TNFRp55-mediated hepatotoxicity could account for lipid peroxidation expressed by significant increase in serum thiobarbituric reactive acid substances (TBARS) content, and could be amplified by decrease in blood total glutathione content and decrease in plasma antioxidant protective capacity. METHODS: We studied 27 patients with histological alcoholic liver disease (five fibrosis, six acute alcoholic hepatitis (AAH) without cirrhosis, four cirrhosis without AAH, and 12 cirrhosis with AAH. TNFsRp55 and TNFsRp75 plasma levels were measured using ELISA assays. Plasma lipid peroxidation was evaluated by the content of TBARS. Total glutathione (tGSH) content in blood was determined by a kinetic assay. The sensitivity of erythrocytes to an oxidative stress and the plasma antioxidant protective capacity were simultaneously determined by a simple method. RESULTS: In the 18 patients with mild or severe AAH, the plasma levels of TNFsRp55 were negatively correlated with tGSH and were positively correlated with TBARS, with total bilirubin and with discriminant function. tGSH was positively correlated with plasma selenium. The plasma levels of TNFsRp75 were positively correlated with TBARS and with total bilirubin. There was no significant correlation with the mean inhibitory 50% plasma volume or with the percentage of hemolyzed erythrocytes. CONCLUSIONS: Our data support the notions that, in patients with AAH, TNFsRp55 probably mediates cytotoxicity of TNF-alpha, and that cytotoxic effect could be amplified by tGSH depletion in enhancing lipid peroxidation.

Fetal echocardiography at West Virginia University: a seven-year experience.

The last decade has seen tremendous growth and utilization of fetal echocardiography. In order to assess the indications and yield of fetal echocardiography at West Virginia University, all fetal echocardiograms performed during a seven-year period were reviewed. There were 931 fetal echocardiograms performed on 803 women during this time period and there was a large increase in referral rate as has been seen in other regions. The highest yield of abnormalities was seen in fetuses referred secondary to the finding of an abnormal fetal cardiac exam on routine screening ultrasound (55.6%), or fetal anomalies of other organs (8.2%). These two indications alone were responsible for 77.8% of identified cases of congenital heart disease by fetal echocardiography during this time period. The resultant findings highlight the need for thorough obstetrical screening ultrasound, including the four chamber view of the heart.

Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d'Etude de la Maladie de von Hippel-Lindau.

BACKGROUND & AIMS: Pancreatic involvement in von Hippel-Lindau (VHL) disease, a genetic disorder with a dominant mode of inheritance affecting various organs, has rarely been studied. We assessed the prevalence, type of lesions, natural history, and impact of pancreatic involvement in patients with VHL. METHODS: A total of 158 consecutive patients from 94 families with VHL disease were studied in a prospective French collaborative study. All patients underwent systematic screening for VHL lesions, including computerized tomography (CT) scanning of the pancreas reviewed by an experienced radiologist. Clinical data, investigations, and treatments performed were also reviewed. RESULTS: Pancreatic involvement was observed in 122 patients (77.2%) and included true cysts (91.1%), serous cystadenomas (12.3%), neuroendocrine tumors (12.3%), or combined lesions (11.5%). The pancreas was the only organ affected in 7.6% of patients. Patients with pancreatic lesions had fewer pheochromocytomas than those without (14/122 vs. 16/36; P<0.0001), and patients with neuroendocrine pancreatic tumors had renal involvement less often than those without (8/99 vs. 6/20; P = 0.013). None of the patients with neuroendocrine tumors had symptoms of hormonal hypersecretion. Pancreatic lesions evolved in half of patients but required specific treatment in only 10 (8.2%) when they were symptomatic or for the resection of large neuroendocrine tumors. CONCLUSIONS: Pancreatic involvement is seen in most patients with VHL disease. Although symptoms are rare, specific treatment of pancreatic lesions is required in selected patients, mainly those with neuroendocrine tumors.

Pretreatment expression of the perforin gene by circulating CD8(+) T lymphocytes predicts biochemical response to interferon-alpha in patients with chronic hepatitis C.

It would be of great value to be able to predict, before the initiation of treatment, which patients with hepatitis C virus-induced chronic hepatitis will be cured by interferon-alpha (IFN-alpha). Competitive RT-PCR was used to evaluate spontaneous expression of the perforin gene, a marker of cytotoxic cell activation, by circulating mononuclear cells in 17 patients undergoing IFN-alpha treatment. IFN-alpha increased perforin gene expression (p < 0.003), but this was not correlated with outcome. In contrast, pretreatment perforin gene expression levels were higher in the 8 patients with a sustained biochemical response after treatment than in the 9 non-responsive patients (p = 0.01). This factor predicted favorable clinical outcome with a sensitivity of 75% and a specificity of 89%. Thus, pretreatment immunological status has a major influence on the ability of IFN-alpha to cure chronic hepatitis C, and the evaluation of perforin gene expression may help to select patients that will benefit from IFN-alpha treatment.

[Abdominal tuberculosis: deceptive and still encountered]. / La tuberculose abdominale: trompeuse et toujours d'actualité.

BACKGROUND: Extrapulmonary manifestations of tuberculosis are increasing in incidence. Abdominal tuberculosis may mimic a variety of gastrointestinal disorders. The diagnosis of abdominal tuberculosis is still difficult to establish before surgery. CASE REPORTS: We report 3 cases of abdominal tuberculosis in immunocompetent individuals. One patient presented with an ileocecal mass mimicking cancer. The second one presented with fever, ileocecal mass and ascites leading to the diagnosis of appendiceal peritonitis. The last patient was admitted for ascites, ovarian mass and high CA 125 serum level simulating ovarian cancer with peritoneal carcinomatosis. COMMENTS: In cases of abdominal tuberculosis when standard investigations are unhelpful, a PCR should be performed. Estimation of adenosine deaminase in ascitic fluid is an easy and reliable method for diagnosing tuberculous ascites. With these non invasive diagnostic procedures, surgery should be reserved only to patients with complications.

Increased susceptibility to gingival colonization by specific HACEK microbes in children with congenital heart disease.

It is well established that infective endocarditis (IE) involving the HACEK (Hemophilus, Actinobacillus, Cardiobacter, Eikenella, Kingella) group of microbes occurs in patients with congenital heart defects (CHD) and in those with prosthetic grafts. Dental caries and gingival disease have been presumed to be the focus of microbial shedding. The purpose of this study was to determine if children with CHD had a more severe gingival inflammatory condition and harbored the HACEK group of microbes to a greater extent than normal children. Two groups of 12 age and sex matched children were selected for this study. The experimental group consisted of twelve children with CHD, 1-1/2 to 8 years of age. The control group consisted of 12 healthy children 2 to 8 years of age. Each child had a gingival index score recorded as described by Massler. Subgingival cultures were obtained. Gingival samples were cultured for HACEK microbes and total Streptococcus (spp) using standard techniques. Fisher's exact test was performed with significance defined at P < 0.05. Children with CHD had more severe gingival inflammatory index than the control group (P < 0.05). 8/12 CHD patient had Actinobacillus actinomycetemcomitans (A.a.) as compared with 2/12 controls (P < 0.05). Furthermore, all cyanotic CHD patients (4/4) had A.a. whereas, only 2/12 controls did (P < 0.05). 4/12 CHD patients harbored Eikenella corrodens (E.c.) compared to 1/12 controls (N.S.). There was no significant difference in colonization with E.c. or A.a. between cyanotic and acyanotic patients. No significant difference in total Streptococcus (spp) was found between the two groups. This study suggests that children with CHD have a more severe gingival inflammatory index and are colonized with specific HACEK microbes more so than normal children.

Fractalkine receptor expression by T lymphocyte subpopulations and in vivo production of fractalkine in human.

Expression and function of the fractalkine receptor CX3CR1 by T lymphocyte subpopulations was evaluated in healthy individuals. In CD8(+) T lymphocytes, CX3CR1 was expressed by and functional in both CD45RO(-) and CD45RO(+) cells. In CD4(+) T lymphocytes, CX3CR1 was expressed mainly by CD45RO(+) cells, and almost exclusively by activated HLA-DR(+) T lymphocytes. This receptor was functional in CD45RO(+) cells, but not in CD45RO(-) cells. Expression of fractalkine was detected by in situ hybridization and immunohistochemistry in endothelial cells of normal lung and thymus. In hyperplastic lymph nodes, fractalkine was expressed by endothelial cells of high endothelial venules and of subcapsular vessels, by follicular dendritic cells (FDC) and by some follicle lymphocytes. Fractalkine mRNA was constitutively present in the HK FDC-like cell line, and it was induced in vitro in B lymphocytes stimulated by an anti-micro or by a CD40 mAb. These findings indicate that fractalkine may contribute to the recruitment of effector T helper lymphocytes, either in peripheral tissues or in lymphoid organs. In these tissues, fractalkine and its receptor may favor contact within follicles between activated T helper lymphocytes, activated B lymphocytes and FDC, thus contributing to the maturation of the B lymphocyte response.

Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa. Multicenter GER-CYT 04 Group.

BACKGROUND/AIMS: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-alpha and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. METHODS: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon alpha. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). RESULTS: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791+/-210 pg/ml versus 956+/-88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308+/-206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (delta s IL-2R) was smaller in the SVR than in the NR (142+/-219 pg/ml versus 704+/-107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86-98) and a specificity of 60% (95% confidence interval 49-71), delta sIL-2R had a sensitivity of 42% (95% confidence interval 31-53) and a specificity of 81% (95% confidence interval 79-90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. CONCLUSIONS: At week 4, delta sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.

Prothrombin 20210G/A mutation in two patients with mesenteric ischemia.

Primary cases of splanchnic vein thrombosis are now less common since a systematic screening for hypercoagulability is performed. In 1996, a sequence variation in the 3'-untranslated region of the prothrombin gene (F.II 20210G/A mutation) has been linked to a threefold increased risk for venous thrombosis. The role of this thrombophilic disorder is not documented in patients with thrombosis of the splanchnic veins. This report presents two patients with a mesenteric ischemia associated with a heterozygous state for the F.II 20210G/A mutation. The first patient developed an ischemic colitis and the second one an ischemic necrosis of the terminal ileum related to a thrombosis of the superior mesenteric vein. In both cases, another thrombotic risk factor was associated: either a general prothrombic state (primary antiphospholipid syndrome) or a focal factor (abnormal hemodynamic conditions related to a liver cirrhosis). It has recently been proposed that several conditions need to be combined for deep vein thrombosis to develop. Screening for the combination of multiple underlying prothrombotic conditions thus appears justified in patients with splanchnic thrombosis. The role of the F.II 20210G/A mutation as a predisposing factor for thrombosis of the digestive vessels should be considered and needs further investigation.

Comparative study of clinical evaluation of heart murmurs by general pediatricians and pediatric cardiologists.

In a study to compare the clinical diagnostic skills of academic general pediatricians and academic pediatric cardiologists in the evaluation of heart murmurs, a total of 128 patients (aged 1 month to 18 years) newly referred to a university pediatric cardiology clinic were evaluated by one of three general pediatricians and one of four pediatric cardiologists. The murmurs were clinically classified as innocent, pathologic, or possibly pathologic. The classification was revised after the review of electrocardiogram (EKG) and chest radiograph (CXR), if indicated. The definitive diagnosis was ascertained by echocardiography (94 normal, 34 abnormal). The general pediatricians identified as many pathologic heart murmurs as the pediatric cardiologists (27/34 vs. 29/34), with no difference in sensitivity, 79% vs. 85% (p = 0.53). The similarity in sensitivity could be because the general pediatricians were more cautious in the classification of heart murmurs and had classified more innocent heart murmurs as pathologic than the pediatric cardiologists (13/39 vs. 3/23), 41% vs. 13% (p = 0.02). The pediatric cardiologists correctly identified more innocent murmurs than general pediatricians (52/94 vs. 72/94), with a better specificity, 55% vs. 76% (p = 0.001); however, the accuracy of prediction of innocence was similar for both groups (52/59 vs. 72/77), 88% vs. 93% (p = 0.36). The revision of diagnosis with review of EKG and CXR was more often misleading than helpful for either group. Academic general pediatricians would identify most of the pathologic murmurs and are no more likely than an academic pediatric cardiologist to misclassify a pathologic heart murmur as innocent.

[Biological diagnosis of the type of liver disease in alcoholic patients with abnormal liver function tests]. / Diagnostic biologique du type d'hépatopathie chez des malades alcooliques ayant des tests biologiques hépatiques anormaux.

OBJECTIVES: The histological diagnosis of the different stages of alcoholic liver disease is not systematic. The aim of this study was to assess whether common biological features were useful in identifying the different stages. METHODS: One thousand twenty six alcoholic patients with liver histology and without any associated diseases or infections likely to alter serum liver tests were studied. Diagnostic analyses were performed using stepwise discriminant analysis in the entire population and in asymptomatic patients. RESULTS: a) Serum ASAT activity levels were only normal in 39% of the patients with normal histological liver and in 14% of the patients with steatosis; b) liver failure was already present in patients with fibrosis without cirrhosis; c) betagamma block was the only biochemical parameter which confirmed the diagnosis of cirrhosis without biopsy; d) the diagnostic accuracy of common tests was weak for the diagnosis of alcoholic liver disease without cirrhosis but prothrombin time could be useful in excluding the diagnosis of cirrhosis with and without acute alcoholic hepatitis when liver biopsy is not available. CONCLUSION: Only a prothrombin time of 80% with a negative predictive value of 94% and the presence of beta-gamma [corrected] block with a positive predictive value of 98% were useful for assessing the diagnosis of cirrhosis in all patients with alcoholic liver disease.

A particularly aggressive combined glucagonoma and gastrinoma syndrome.

Duodeno-pancreatic biochemically polyfunctional endocrine tumour is a well known entity. Usually, only one hormone is responsible for the clinical features. We report a case of aggressive combined glucagonoma and gastrinoma tumour without metastases, causing respectively diabetic ketoacidosis and fulminant peptic ulcer, and death. Occasional patients can present with clinical features of both glucagonoma and gastrinoma. Diabetic patients exhibiting migratory skin lesions should be suspected of glucagonoma. In addition, a multidisciplinary approach to such patients including dermatologists, surgeons, radiologists and endoscopists is mandatory.