Multiple non-metastatic gastrointestinal stromal tumors. Differential features.

INTRODUCTION: gastrointestinal stromal tumors (GISTs) are specific, generally KIT (CD117)-positive, mesenchymal tumors of the digestive tract displaying KIT or PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the intestinal wall; more rarely, multiple tumors may occur in one or more organs. OBJECTIVE: to review the morphological, immunohistochemical and molecular features of multiple, non-metastatic forms of GIST. SOURCES: review of the literature on Medline, and authors own experience. CONCLUSIONS: multiples GISTs may occur in three different contexts: as spontaneous lesions (in both adults and children); due to familial GIST syndrome (autosomal dominant inheritance); or in association with specific syndromes (e.g. Carney s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside these contexts, the existence of multiple GISTs is deemed to be the result of tumor metastasis, and therefore indicative of advanced-stage disease. Clinicians need to be aware of these variants, whose prognosis and treatment differ.

[Splanchnic hemodynamic effects of somatostatin and octreotide in cirrhotic patients. A Doppler ultrasonographic study]. / Efecto hemodinámico esplácnico de somatostatina y octreótido en cirróticos. Estudio con ultrasonografía Doppler.

AIM: Doppler-ultrasound assessment of the splanchnic hemodynamic effects of intravenous somatostatin and octreotide administration. MATERIAL AND METHOD: Forty-five cirrhotic patients with esophageal varices were randomized to receive 1-hour intravenous somatostatin (SOM, 250 mg), octreotide (OCT, 50 mg), or placebo (PLA). In baseline and at 15, 30, 45 and 60 minutes of infusion, mean velocity, congestion index, flow volume and diameter of the portal vein, as well as the superior mesenteric artery resistivity index, were measured. Plasma bradykinine and vasoactive intestinal peptide (VIP) concentrations were also measured at baseline and at 30 and 60 minutes. RESULTS: While placebo caused no changes in any of the venous and arterial parameters, SOM and OCT caused a sustained decrease in portal vein velocity (-19.41 vs. -11.19%) and flow (-22.79 vs. -12.33%), and an increase in the congestion index (+17.5 vs. +7.5%) and resistivity index of the superior mesenteric artery (+7.18 vs. +6.16%) with respect to baseline (p < 0.05). These changes were already evident at 15 minutes and remained unchanged during the time of the study period. With respect to OCT, SOM caused a higher reduction in mean velocity and flow of the portal vein, with no significant differences for congestion index and mesenteric artery resistivity index, both increased by SOM and OCT. Plasma bradykinine and VIP concentrations remained unchanged in the three groups. CONCLUSIONS: At therapeutic doses, intravenous somatostatin and octreotide reduce portal vein velocity and flow, and increase portal vein congestion index and superior mesenteric artery resistivity index. Somatostatin causes a higher portal flow reduction than octreotide in spite of a similar splanchnic arterial effect.

A strategy to improve the detection of drug-induced hepatotoxicity.

AIMS: To report a new strategy for the detection of hepatotoxic adverse drug reactions (ADRs) in hospitalized patients improving the results obtained with other methods. DESIGN: The model is based on the identification of a single alert signal in various target clinical departments over a 12-month period. Each patient was later interviewed following a set protocol. The main results analyzed were the drugs suspected of ADR; causal relationship between suspected drugs and ADRs; ADR severity, and incidence of hepatotoxic ADR/100,000 inhabitants. SUBJECTS: Population served by a university-affiliated urban teaching hospital (519,381 inhabitants). RESULTS: The overall ratio of confirmed/suspected ADRs was high (35/80). The most commonly reported drug was amoxicillin-clavulanic acid (4 cases). With regard to causality, 2 suspected cases were classified as definite and 14 as probable. The distribution according to the severity of hepatotoxicity was 6 severe and 29 mild cases. The incidence of hepatotoxic ADRs/100,000 inhabitants as revealed by our method was much higher versus voluntary report (6.74 and 1.79, respectively). CONCLUSIONS: Our method has proven effective for improving the detection of hepatotoxic ADRs, and may be extended to other types of adverse reactions.

Refractory bleeding after endoscopic sphincterotomy: a new indication for recombinant factor VII therapy?

The therapeutic approach in post-ERCP bleeding depends on the severity of the episode. In most instances early bleeding is self-limited, but when it is severe enough endoscopic injection of epinephrine (EP) is the usual treatment. Nevertheless, in some cases bleeding relapses, whereas in between 5% and 10% of patients the refractoriness to endoscopic management may even be fatal and other therapeutic alternatives would be needed. Otherwise, in a small subgroup of cases the bleeding becomes massive, the vision is obscured, and the injection may be very difficult in a situation of hemodynamic instability. We here report a case of refractory post-endoscopic sphincterotomy (ES) bleeding in a patient without preexisting coagulopathy, successfully treated with a single injection of rFVII. This novel experience suggests that rFVIIa, besides its actual high costs, might be useful and safe as a second-line, noninvasive, therapeutic tool in selected cases of massive, or refractory, post-ES bleeding.

Hepatic encephalopathy: nomenclature, pathogenesis and treatment.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome in patients with liver failure and/or a portal-systemic bypass. Since 2002 a new nomenclature of HE exists, that classifies HE in encephalopathy type A (associated with acute liver failure), type B (associated with portal-systemic bypass), and type C (associated with liver cirrhosis). HE type A is characterized by a rapid development to coma, cerebral edema, and a poor short-term prognosis. Therefore, these patients should be referred to a liver transplantation center. Standard treatment of HE consists of non absorbable disaccharides, non absorbable antibiotics, and a diet with an appropriate amount of proteins. In addition, the possibility of performing a liver transplantation should be evaluated. In patients with intractable HE other alternative treatments adjunct to standard treatment, like zinc, sodium benzoate, ornithine aspartate, branched chain amino acids, flumazenil, and bromocriptine should be considered.

Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?

Minimal hepatic encephalopathy (MHE) refers to subtle neurocognitive and neurophysiological defects in patients with liver cirrhosis without clinical signs of hepatic encephalopathy. Using appropriate diagnostic methods the prevalence of MHE is approximately 25-30%. MHE has clinical significance as it results in a diminished daily functioning, precedes overt hepatic encephalopathy and is associated with a poor prognosis. Treatment with non-absorbable disaccharides can reverse the neurocognitive and neurophysiological defects found in MHE. The failure to diagnose MHE in apparently normal cirrhotic patients could, therefore, be considered a medical error. However, whether treatment also improves patients' quality of life and prognosis remains to be determined.