Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly.

The tolerance and efficacy of oxaliplatin and irinotecan for metastatic colorectal cancer are unknown in elderly patients. Methods. All consecutive patients over 74 years treated with oxaliplatin or irinotecan for metastatic colorectal cancer were enrolled. The tumour response was assessed every 2-3 months and toxicity was collected at each cycle according to World Health Organisation criteria. A total of 66 patients were enrolled from 12 centres. The median age was 78 years (range, 75-88 years); 39 patients had no severe comorbidity according to the Charlson score. In total, 44 and 22 patients received oxaliplatin or irinotecan, respectively, in combination with 5-fluororuracil+/-folinic acid or raltitrexed in 64 patients. A total of 545 chemotherapy cycles were administered in first (41%), second (51%) or third line (8%). A dose reduction occurred in 190 cycles (35%). Complete response, partial response and stabilisation occurred in 1.5, 20 and 47% of patients, respectively. The median time to progression and overall survival were 6.8 and 11.2 months in first line and 6.3 and 11.6 months in second line, respectively. Grade 3 and 4 toxicity occurred in 42% of patients: neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea and vomiting 8% and thrombopenia 6%. There was no treatment-related death. In selected elderly patients, chemotherapy with oxaliplatin or irinotecan is feasible with manageable toxicity.

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.

[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.

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.

[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.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy.

The association of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is thought to be rare, and its optimal treatment is unknown. Of 130 consecutive patients with a diagnosis of PBC, we identified 12 cases (9.2%) of overlap syndrome (10 females, 2 males; median age, 50 years) strictly defined by the presence of at least two of the three recognized biochemical, serological, and histological criteria of each disease. One patient had initially pure PBC and developed AIH characterized by a flare of alanine transaminase (ALT) (1,330 IU/L; N < 35), elevated immunoglobulin G (IgG) (42 g/L; N < 14.0), and presence of anti-smooth muscle antibodies (ASMA) after 20 months of ursodeoxycholic acid (UDCA) therapy. A complete clinical and biochemical remission was achieved under combination of corticosteroids and UDCA. Eleven patients had features of both diseases at presentation: high serum levels of alkaline phosphatase (AP) (median: 280 IU/L; N < 100), ALT (140 IU/L), and IgG (30.8 g/L), presence of mitochondrial antibodies (n = 9) or ASMA (n = 9), florid bile duct lesions (n = 8), and moderate or severe periportal or periseptal lymphocytic piecemeal necrosis (n = 11). UDCA (13-15 mg/kg/d) given alone in 5 patients induced a significant decrease in biochemical cholestasis but not in ALT levels, and liver fibrosis progressed in 3 patients. Corticosteroids given alone in 6 patients induced a significant decrease in ALT, IgG, and AP levels, but none had a biochemical normalization. The patients with persistently abnormal liver tests under either UDCA or corticosteroids received both UDCA and corticosteroids. A further marked biochemical improvement was observed, and all patients became asymptomatic. We conclude that, in patients with PBC: 1) overlap syndrome with AIH is not rare; 2) flares of AIH may occur either spontaneously or under UDCA; and 3) combination of UDCA and corticosteroids is required in most patients to obtain a complete biochemical response. Overlap syndrome may represent an important and unrecognized cause of resistance to UDCA in patients with PBC.

[Hemorrhagic ascites disclosing massive Fasciola hepatica infection]. / Ascite hémorragique révélant une infection massive à Fasciola hepatica.

Multi-organ infection with Fasciola hepatica is uncommon. We report a case of severe infection with Fasciola hepatica as a cause of liver and peritoneum injuries with hemorrhagic ascites as well as pulmonary, pericardial, splenic and portal system injuries in a 37-year old man who was a native of Green Cape. The patient was in poor general health, had a major inflammatory syndrome, and polyclonal hypergammaglobulinemia (90 g/L). The diagnosis was confirmed by positive distomatosis serology and the presence of eggs of Fasciola hepatica in the histological samples of the liver and peritoneum. After treatment with praziquantel then triclabendazole, the global outcome was favorable.