Gabriella Carnevale Maffè

Image-Aided Estimate of Tumor Burden in Hodgkin’s Disease: Evidence of Its Primary Prognostic Importance

PURPOSE To explore a more direct method for evaluating tumor burden (TB) in Hodgkins disease (HD) and to verify its prognostic importance. PATIENTS AND METHODS The volume of TB at diagnosis was directly and retrospectively measured in 121 HD patients through images of the lesions recorded by computed tomographic (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement and many superficial ones, and by ultrasonography (US) for the remaining superficial lesions. RESULTS The TB, which was obtained from the sum of the volumes of all the lesions measured on CT scans and US and normalized to body-surface area (relative TB [rTB]), showed a median value of 102.6 cm(3)/m(2) (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the parameter that statistically correlated best with time to treatment failure (P = 2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone proved to be clearly superior to that obtained with the score of the International Prognostic Factor Project. The rTB was found to be correlated with many clinical staging parameters (bulky disease, number of involved lymph node regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its predictability from these variables was low (R(2) =.668). CONCLUSION Relative TB is emerging as a strong prognostic factor in HD, more powerful than and largely independent of those hitherto known and used. Further studies are needed to confirm these results and exploit their clinical value, particularly the relationship among rTB, drug doses, and response.

Is it worth investigating splenic function in patients with celiac disease

Celiac disease, an immune-mediated enteropathy induced in genetically susceptible individuals by the ingestion of gluten, is the most frequent disorder associated with splenic hypofunction or atrophy. Defective splenic function affects more than one-third of adult patients with celiac disease, and it may predispose to a higher risk of infections by encapsulated bacteria and thromboembolic and autoimmune complications, particularly when celiac patients have concomitant pre-malignant and malignant complications (refractory celiac disease, ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma). However, the clinical management of patients with celiac disease does not take into account the evaluation of splenic function, and in patients with high degree of hyposplenism or splenic atrophy the prophylactic immunization with specific vaccines against the polysaccharide antigens of encapsulated bacteria is not currently recommended. We critically re-evaluate clinical and diagnostic aspects of spleen dysfunction in celiac disease, and highlight new perspectives in the prophylactic management of infections in this condition.

The effect of gluten on intestinal fermentation, gastric and gallbladder emptying in healthy volunteers.

BACKGROUND The relationship between gluten ingestion and gastrointestinal tract function is a matter of debate. AIM We analysed the effect of gluten on gastric and gallbladder emptying and intestinal fermentation in healthy volunteers. METHODS Ultrasound measurement of gastric and gallbladder emptying after both gluten-containing and gluten-free meals was performed in 18 volunteers (8 women, age 25.0±2.5 years; BMI 22±1.9). Breath hydrogen excretion after a gluten-containing meal, a gluten-free meal and a gluten-free meal with added gluten powder was measured in 16 volunteers (10 women, age 25.2±2.7 years; BMI 22±1.8). The severity of symptoms was monitored. RESULTS Gluten presence in the meals was not recognised. Gastric emptying time was 81.6±13.8min after gluten-containing and 73.9±21.6min after gluten-free meals (p=0.11). Percentage ejection fraction after gluten-containing meals was 60±9% and 60.6±6% after gluten-free meals (p=0.68). Peak and cumulative hydrogen excretion were significantly higher after gluten-containing than after gluten-free meals (peak: 12.5±7.3 vs 6.5±5.1 parts-per-million, p<0.01; and cumulative: 2319±1720 vs 989±680 parts-per-million/minute, respectively; p<0.01). Adding gluten powder to the gluten-free meal did not modify fermentation. Symptoms were mild and not different after the meals. CONCLUSIONS In healthy volunteers, gluten may induce gastrointestinal alterations. Further studies are needed to clarify which patients could benefit from dietary modification.

Usefulness of abdominal ultrasonography with studies of the intestinal loops in Turner syndrome patients

Turner syndrome, a chromosomal disorder caused by partial or complete absence of one of the two X chromosomes, is characterized by an increased incidence (compared with that in the normal population) of either autoimmune disorders, including chronic inflammatory bowel diseases, or angiodysplasia of the small intestine. Because ultrasonography and color Doppler ultrasound are widely used to investigate gastrointestinal disorders, we decided to carry out an ultrasound-based screening study in patients with Turner syndrome to determine whether this method might be useful in the follow-up of this population.RiassuntoLa sindrome di Turner, patologia cromosomica dovuta a parziale o totale assenza di uno dei due cromosomi X, è caratterizzata da un’aumentata incidenza rispetto alla popolazione normale di malattie autoimmuni, tra cui le malattie infiammatorie croniche intestinali, e di angiodisplasie del tenue. In considerazione dell’attuale ampio utilizzo dell’ecografia e dell’ eco-color-Doppler nello studio diagnostico delle patologie gastrointestinali si è pensato di effettuare uno screening ecografico in una popolazione di pazienti affetti da sindrome di Turner per valutare l’utilità dell’inserimento di questa metodica nel loro follow up.

Splenic hypofunction in patients with an incidental finding of small-sized spleen at abdominal ultrasound.

Splenic hypofunction is an acquired condition, ranging from a reversible mild hyposplenism to severe splenic atrophy, and may be accompanied by a reduction in spleen size. It is potentially associated with a number of different diseases, including hematological, immunological, gastroenterological and iatrogenic disorders. Functional hyposplenism, as well as asplenia, has been shown to predispose to thromboembolic events, autoimmunity and infectious complications, the latter of which are the most widely recognized risk of these states [1]. In particular, a significantly higher relative risk of pneumococcal sepsis has been demonstrated in patients affected by splenic hypofunction or atrophy [2] due to reduced levels of circulating IgM memory B cells, a unique B cell population that needs the spleen for their survival and generation [3]. Nevertheless, the relationship between splenic function and size in hyposplenic individuals is unknown. Since a small-sized spleen can be easily detected in the course of an abdominal ultrasound examination, we aimed at evaluating splenic function through pitted erythrocyte counting in patients with an incidental finding of atrophic spleen at abdominal ultrasound. Between October 2009 and January 2011, 4,585 patients were referred to the Ultrasound Unit of our Department of Internal Medicine to undergo an abdominal ultrasound evaluation. The most frequent indications were abdominal pain (49 %), malignancy (37 %), liver and biliary disorders (10 %), bowel disorders (7 %), and nephrolithiasis (5 %). All images were obtained by an expert sonographer, using an Esaote model MyLab 70 XVG, with a 1–8 MHz convex probe and an ATL model HDI 3500, a 5.2 MHz convex probe (Philips Medical Systems, Bothel, Washington). The length of the spleen, defined as the maximum distance between the dome and the tip of the spleen, was measured on a longitudinal section with the patient in the supine or right lateral decubitus position and on deep inspiration. Patients, who were diagnosed as having a small spleen: defined as a spleen length B8 cm in men and B7.5 cm in women [4], underwent peripheral blood collection for the evaluation of spleen function. Splenic function was assessed by counting the number of pitted red cells—that is, erythrocytes bearing membrane abnormalities visible under interference phase microscopy as a so-called ‘pit’. Briefly, one drop of fresh venous blood was taken and mixed with 0.5 ml 3 % buffered glutaraldehyde solution, pH 7.4, in a plastic tube. One thousand erythrocytes were examined in a wet preparation (magnification, 1,0009) with a directinterference phase microscope Leica DMLB (Leica Microsystems Wetzlar GmbH, Wetzlar, Germany) equipped with Nomarsky optics by the same experienced observer unaware of the study. The percentage of pitted erythrocytes was calculated and taken as a measure of splenic function (upper limit of normal = 4 %) [5]. A peripheral blood sample was also collected from 52 splenectomized patients, who were used as positive controls. Data were analyzed in the GraphPad Prism statistical PC program (GraphPad Software, San Diego, CA) using the paired t test and the Mann–Whitney U test. Correlations were studied by Spearman’s rank correlation test. A level of p \ 0.05 was considered statistically significant. A small spleen was found in 203 out of 4,585 patients. Only 128 (mean age 61.5 years; 90 females and 38 males) A. Di Sabatino (&) G. Carnevale Maffe L. Brunetti M. Guerci G. R. Corazza First Department of Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Piazzale Golgi 19, 27100 Pavia, Italy e-mail: a.disabatino@smatteo.pv.it

Ruolo dell’ecografia addominale nella diagnosi di amiloidosi AL: un caso clinico emblematico

L’amiloidosi da catene leggere immunoglobuliniche (AL) e la forma di amiloidosi sistemica di piu frequente riscontro. Essa e causata da un clone plasmacellulare secernente una catena leggera strutturalmente anomala che si deposita nei tessuti sotto forma di fibrille insolubili. L’estrema variabilita e la frequente aspecificita dei sintomi rendono spesso difficile la diagnosi e la completa stadiazione di malattia. La diagnosi di certezza richiede la dimostrazione istologica di amiloide nei tessuti. Una precoce ed accurata diagnosi costituisce condizione fondamentale per una terapia efficace e per il miglioramento della prognosi. In tal senso riteniamo l’ecografia di estrema utilita sia nella diagnosi il piu precoce possibile sia nella completa stadiazione di malattia. In questo articolo descriviamo un caso emblematico nel quale il primo esame che ha suggerito la diagnosi di amiloidosi AL e stata l’ecografia addominale che altri esami strumentali quali la TC non avevano identificato e sospettato.

Aspetti ecografici dell’amiloidosi AL: revisione di un’ampia casistica

Le amiloidosi sistemiche sono un gruppo complesso di patologie caratterizzate dal deposito interstiziale di materiale proteico che comporta un progressivo danno d’organo. La forma piu frequente risulta essere l’amiloidosi da catene leggere immunoglobuliniche (AL), causata da un clone plasmacellulare che produce una catena leggera strutturalmente anomala. Una precoce ed accurata diagnosi, confermata dalla dimostrazione istologica di amiloide nei tessuti, costituisce condizione fondamentale per una terapia efficace e per il miglioramento della prognosi. Tuttavia l’estrema variabilita e la frequente aspecificita dei sintomi rendono spesso difficile la diagnosi e la completa stadiazione di malattia. Lo scopo di questa revisione e quello di definire i principali quadri ecografici che riteniamo, in accordo all’ampia casistica disponibile, se non patognomonici, fortemente suggestivi di interessamento amiloidotico d’organo.

Un caso di ileo biliare

Gallstone ileus is a rare complication of cholelithiasis caused by the impaction of one or more stones in the lumen of the gastrointestinal tract; pathophysiological prerequisite is the presence of a bilio-digestive fistula. The clinical signs and symptoms of intestinal obstruction, such as constipation, abdominal pain, nausea, vomiting and abdominal distension predominate, usually preceded by symptoms of acute cholecystitis. Plain abdominal X-ray, ultrasound and TC (gold standard) are cardinal for the diagnosis. Early diagnosis is a crucial point for the improvement of the prognosis, since this pathological condition is still characterized by an high morbidity and mortality burden. Treatment is surgical; currently most of the authors prefer a two-stage strategy. The case described below shows how diagnosis of gallstone ileus can be laborious and complex, requiring integration of more instrumental examination to reach the diagnosis as early as possible.

Un caso di epatopatia rapidamente ingravescente

Acute liver failure is a clinical syndrome characterized by the sudden onset of coagulopathy and encephalopathy. The most common aetiology are drug-induced liver failure, hepatitis, acute Wilson’s disease, acute Budd-Chiari syndrome, autoimmune hepatitis and miscellaneous. Wilson Disease is a rare inherited autosomal disorder of copper balance leading to hepatic damage and neurological disturbance of variable degree. The gene involved is ATP7B, which encodes a hepatic copper-transporting protein that plays a key role in human copper metabolism. Clinical manifestations are due to copper accumulation in particular in the liver and brain and include hepatic disease ranging from mild hepatitis to acute liver failure. Early diagnosis and therapy are essential for favorable outcome. In this article we describe a paradigmatic case of Wilson disease in a patient of 47 years marked by an acute onset which has led to acute liver failure for which she underwent orthotopic liver transplantation.

Lesioni nodulari epatiche come inusuale manifestazione di mieloma multiplo in progressione: descrizione di un caso clinico

Extramedullary localizations during the course of multiple myeloma (MM) are rare. They can arise in any tissue and their presence has been associated with more aggressive disease. Particularly atypical appear liver involvement in living patient. Here we describe a case in whom investigation of liver nodules by biopsy revealed hepatic localization during advanced MM. Pathological hepatic involvements found in MM reported in post-mortem studies are more prevalent compared with those on living patients; therefore a critical evaluation of these circumstances is required in order to understand if those associations are actually unusual as reported previously.