Maria Squillante - Academia.edu (original) (raw)

Papers by Maria Squillante

Gastroenterology, Jan 6, 1991

Gastroenterology, Jul 1, 1991

Ten patients with fatty liver changes were subjected to liver biopsies. In seven, ultrasonography... more Ten patients with fatty liver changes were subjected to liver biopsies. In seven, ultrasonography showed focal hypoechogenicity within a "bright" liver, generally interpreted as focal sparing. Three patients had hyperechoic areas surrounded by "normal" parenchyma usually felt to represent local fat accumulation without diffuse involvement. Morphometric analysis was used to determine the total area occupied by fat (area density) and the number of lipid droplets (numerical density) per microscopic field in lesional and perilesional specimens. Compared with respective perilesional values, hypoechoic lesional numerical densities were significantly lower in 6 of 7 patients; the three hyperechoic samples had significantly higher values. In most cases, lesional and perilesional area densities were not significantly different. These hypoechoic focal lesions are believed to be merely areas in which a similar quantity of fat is contained in fewer droplets, and focal hyperechogenicity is believed to result from a larger number of fat-filled vacuoles with respect to that of the surrounding parenchyma. Variation in the number of solid-liquid interfaces causes the ultrasonic contrast between these lesions and the similarity fatty liver parenchyma surrounding them.

Liver International, 2016

The current standard-of-care for treatment of HCV genotype 2 (GT-2) patients is the combination o... more The current standard-of-care for treatment of HCV genotype 2 (GT-2) patients is the combination of sofosbuvir (SOF) with weight-based ribavirin (RBV). Patients with HCV GT-2 infection and ribavirin contraindications require the use of SOF plus NS5A inhibitor daclatasvir (DCV) which is not reimbursed everywhere. We conducted an open-label observational, prospective study on a subgroup of GT-2 patients either naïve or treatment experienced (TE) with contraindications to the use of RBV. Patients with cirrhosis of Child-Pugh-Turcotte (CPT) class A and B, or advanced fibrosis with co-morbidities were included. They were assigned to receive 12 or 24 weeks of SOF/DCV. The primary end point of the study was sustained virological response (SVR) defined as HCV RNA levels <12 IU/ml, 12 weeks post-treatment. Out of 106 patients with GT-2 who received treatment at our Unit from July 2014 to June 2015, 20 (18.8%) whose treatment could not be deferred, were ribavirin intolerant; 19 received SOF/DCV combination for 12 or 24 weeks. The majority was male, 58% had cirrhosis, 58% were TE. All treated patients achieved SVR regardless of treatment duration. The most common adverse events (AEs) were fatigue, headache and nausea. No discontinuations due to AEs were observed. Two patients had oesophageal bleeding but continued treatment and achieved SVR; one patient developed HCC 12 weeks post-treatment, but remained HCV RNA undetectable. This study supports the use of SOF/DCV for 12 in non cirrhotics, or 24 weeks in cirrhotic GT-2 patients who cannot tolerate RBV, including those with decompensated disease. This article is protected by copyright. All rights reserved.

Liver, 1993

Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been... more Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been considered a contraindication to needle biopsy of the liver, but there are very limited data on the actual rate of bleeding in patients with such severe alterations and none whatsoever on the bleeding risk associated with newer, fine-gauge needles that produce less trauma to the liver tissue. In addition, there has never been any evidence that platelet count and/or prothrombin time are the most sensitive indices of bleeding risk. This retrospective study of 85 patients, with platelet counts less than 50000/mm3 and/or prothrombin times less than 50% of controls, subjected to ultrasound-guided fine-needle liver punctures for diagnostic or therapeutic (percutaneous ethanol injection) purposes showed no bleeding episodes after any of the 229 punctures performed.

Journal of Hepatology, 1994

One hundred and sixty-five patients with cirrhosis were prospectively investigated, by regular ul... more One hundred and sixty-five patients with cirrhosis were prospectively investigated, by regular ultrasonographic follow up, to assess the incidence of gallstones. The mean length of follow up was 33 months (range 12 to 108). Cholelithiasis was diagnosed in 31 patients (18.8%), with a cumulative incidence over 84 months of 38.3% (4.7% yearly incidence). The risk of gallstones was similar in males (38%) and females (38.3%), although the final cumulative incidence was reached at 72 months in males. The percentage of patients with new stones was higher in alcoholic cirrhosis (28.9%) (with a cumulative incidence of 48.8% at 84 months) and lower in hepatitis-related cirrhosis (1.9%) (only one new case at 96 months of follow up) (p < 0.001). The cumulative incidence of gallstones in the Child's C group reached 49.3% at 48 months versus 24% in Child's B and 6.4% in Child's A (p < 0.0001). At multivariate analysis, Child's C and alcoholic cirrhosis were shown to be the independent variables significantly associated with a high risk of development of cholelithiasis. This study confirms that cirrhosis represents a high risk factor for gallstones. The risk is greater for alcoholic cirrhosis and increases with the severity of the disease.

Journal of Gastroenterology and Hepatology, 1992

The accuracy of ultrasonographic diagnosis of hypoechoic focal fatty change in the 'bright liver'... more The accuracy of ultrasonographic diagnosis of hypoechoic focal fatty change in the 'bright liver' was evaluated in 40 lesions found in 35 patients followed up for a mean period of 37.8 months. Patients with ultrasound and laboratory findings suggesting liver cirrhosis were excluded from the study.

Journal of Gastroenterology and Hepatology, 1994

The protective role of large spontaeous portosystemic shunts in oesophageal varices bleeding due ... more The protective role of large spontaeous portosystemic shunts in oesophageal varices bleeding due to portal hypertension in liver cirrhosis is still debated. A series of 20 consecutive patients with haemodynamically efficient collaterals involving the para-umbilical-epigastric venous route (evaluated by Echo-Doppler flowmetry) is reported. All patients presented absent or mild oesophageal varices at endoscopy. During a mean follow-up period of 23.5 months, no patient developed large varices or experienced variceal bleeding. Hepatic encephalopathy was present in 35% of patients. Haemodynamically efficient spontaneous portosystemic shunts may 'protect cirrhotic patients from the risk of oesophageal varices forming and bleeding. The diversion of large amounts of blood from portal to systemic circulation correlates with the higher trend of hepatic encephalopathy in these patients.

Journal of Clinical Ultrasound, 1993

Journal of Clinical Gastroenterology, 1989

Journal of Clinical Gastroenterology, 1993

Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting ... more Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting needle biopsy. Specimens were obtained from the focal lesions under ultrasound guidance and histologically diagnosed as regenerative nodules. An image analyzer was then used to determine the cytoplasmic area, nuclear area, and nuclear/cytoplasmic ratio for 100 randomly selected cells from each specimen. Data were then compared with data for specimens of normal liver tissue and data from patients with alcoholic or posthepatic cirrhosis or well-differentiated hepatocellular carcinoma (HCC). The morphometric parameters for the group of regenerative nodule specimens fell within an intermediate range between those for HCC and the nondysplastic samples, strongly suggesting a preneoplastic nature. Nine of the 10 regenerative lesions showed liver cell dysplasia, and 3 of these patients developed HCC during follow-up. Ultrasonically discernible focal masses in a cirrhotic liver should be considered preneoplastic, if not neoplastic lesions and treated aggressively to prevent their progression to outright malignancy.

Digestive Diseases and Sciences, 1990

In the period 1985-1988, 62 focal liver lesions in 58 cirrhotic patients were studied by ultrason... more In the period 1985-1988, 62 focal liver lesions in 58 cirrhotic patients were studied by ultrasonography; 12 of these focal lesions were documented to be regenerating lesions by echo-guided fine-needle biopsy. During an average follow-up period of 10.2 months (range 3-22 months), hepatocellular carcinoma was subsequently found in 10 of the cases of regenerating nodules, whereas the initial diagnosis of regenerating nodule was confirmed in the remaining two cases. Based upon this finding, it is suggested that every focal mass visualized by ultrasonography in a cirrhotic liver should either be considered to be a neoplastic lesion or at least a preneoplastic lesion if the possibility of either a metastatic or benign lesion (eg, hemangiomas, focal fatty liver change areas) can be excluded. Therefore either fine-needle aspiration or biopsy of aU ultrasonographically revealed mass lesions within a cirrhotic liver is advised, such that early appropriate treatment for hepatocellular carcinoma can be instituted.

Digestive Diseases and Sciences, 1996

There is still debate over the relative merits of cytology and histology in diagnosing hepatocell... more There is still debate over the relative merits of cytology and histology in diagnosing hepatocellular carcinoma in cirrhotic livers. Previous comparisons of the diagnostic accuracies of these two methods may have been biased by sampling errors due to multiple punctures. We compared the diagnostic accuracies of cytology and microhistology using tissue and cells from the same point in liver nodules subsequently proved to be hepatocellular carcinoma. A single ultrasound-guided liver-nodule biopsy was obtained with a 20- to 21-G cutting needle from 131 cirrhotic patients. The solid portion of samples was used for microhistology; the remainder was subjected to smear cytology. The results of each type of examination were expressed as true positive, nonspecific malignancy, false negative, or inadequate for diagnosis. No false-positive diagnoses were made in 13 benign lesions. In 118 HCC nodules (particularly those <30 mm in diameter), cytology provided a significantly higher percentage of correct diagnoses (85.6%) that was only slightly inferior to that based on results of both studies (89.8%). The single-biopsy technique generally provides adequate tissue for histology and cytology specimens with a high cellularity. It reduces both the cost and the risks of fine-needle biopsy diagnosis of hepatocellular carcinoma.

Digestive and Liver Disease, 2008

Digestion, 1992

Being more evident that primary achalasia is not confined to the esophagus and that it may involv... more Being more evident that primary achalasia is not confined to the esophagus and that it may involve other organs in the digestive tract, gallbladder emptying was ultrasonographically evaluated in 10 patients affected with primary achalasia and in 10 controls. An intravenous cerulein infusion was used to induce gallbladder contraction. Eight out of 10 achalasic patients had a lower gallbladder emptying, and 6 out of 10 had a markedly delayed gallbladder emptying compared with the controls. Achalasic patients, taken as a whole, showed a significantly lower and delayed mean gallbladder emptying when compared with the controls. Such a finding confirms the possible extra-esophageal extension of primary achalasia. In this study, the hypothesis of impaired cholinergic gallbladder innervation in primary achalasia is discussed.

European Journal of Ultrasound, 1995

Objective: To assess the role of pulsed Doppler ultrasound in the differential diagnosis of focal... more Objective: To assess the role of pulsed Doppler ultrasound in the differential diagnosis of focal liver lesion, based upon the presence of a Doppler signal and its waveform. Merhodr: The presence of a Doppler signal was accurately investigated in 267 focal liver lesions which had subsequently a definitive diagnosis. Most representative groups included hepatocellular carcinomas (188 cases), metastases (34 cases) and haemangiomas (42 cases). Remits: Doppler signals were detected with a significantly higher rate in hepatocellular carcinomas than in metastases (P = 0.001) and haemangiomas (P c 0.0001). The detection rate in metastases was significantly higher than in haemangiomas (P = 0.001). Assuming the detection of a Doppler signal allows to classify a liver lesion as malignant, we obtained sensitivity of 84.9%. specificity of 90.5%, diagnostic accuracy of 85.8%, positive predictive value of 97.9% and negative predictive value of 52.8%. Considering only the presence of a pulsatile wave as a diagnostic sign of malignancy, these figures resulted 80.8%, lOO%, 84.2%, 100% and 52.8%, respectively. Conclusions: The detection of Doppler signals from within a liver lesion has a clinical relevance. The finding of a pulsatile waveform makes it possible to differentiate a malignant lesion from haemangioma with high sensitivity and absolute specificity.

Gastroenterology, Jan 6, 1991

Gastroenterology, Jul 1, 1991

Ten patients with fatty liver changes were subjected to liver biopsies. In seven, ultrasonography... more Ten patients with fatty liver changes were subjected to liver biopsies. In seven, ultrasonography showed focal hypoechogenicity within a "bright" liver, generally interpreted as focal sparing. Three patients had hyperechoic areas surrounded by "normal" parenchyma usually felt to represent local fat accumulation without diffuse involvement. Morphometric analysis was used to determine the total area occupied by fat (area density) and the number of lipid droplets (numerical density) per microscopic field in lesional and perilesional specimens. Compared with respective perilesional values, hypoechoic lesional numerical densities were significantly lower in 6 of 7 patients; the three hyperechoic samples had significantly higher values. In most cases, lesional and perilesional area densities were not significantly different. These hypoechoic focal lesions are believed to be merely areas in which a similar quantity of fat is contained in fewer droplets, and focal hyperechogenicity is believed to result from a larger number of fat-filled vacuoles with respect to that of the surrounding parenchyma. Variation in the number of solid-liquid interfaces causes the ultrasonic contrast between these lesions and the similarity fatty liver parenchyma surrounding them.

Liver International, 2016

The current standard-of-care for treatment of HCV genotype 2 (GT-2) patients is the combination o... more The current standard-of-care for treatment of HCV genotype 2 (GT-2) patients is the combination of sofosbuvir (SOF) with weight-based ribavirin (RBV). Patients with HCV GT-2 infection and ribavirin contraindications require the use of SOF plus NS5A inhibitor daclatasvir (DCV) which is not reimbursed everywhere. We conducted an open-label observational, prospective study on a subgroup of GT-2 patients either naïve or treatment experienced (TE) with contraindications to the use of RBV. Patients with cirrhosis of Child-Pugh-Turcotte (CPT) class A and B, or advanced fibrosis with co-morbidities were included. They were assigned to receive 12 or 24 weeks of SOF/DCV. The primary end point of the study was sustained virological response (SVR) defined as HCV RNA levels <12 IU/ml, 12 weeks post-treatment. Out of 106 patients with GT-2 who received treatment at our Unit from July 2014 to June 2015, 20 (18.8%) whose treatment could not be deferred, were ribavirin intolerant; 19 received SOF/DCV combination for 12 or 24 weeks. The majority was male, 58% had cirrhosis, 58% were TE. All treated patients achieved SVR regardless of treatment duration. The most common adverse events (AEs) were fatigue, headache and nausea. No discontinuations due to AEs were observed. Two patients had oesophageal bleeding but continued treatment and achieved SVR; one patient developed HCC 12 weeks post-treatment, but remained HCV RNA undetectable. This study supports the use of SOF/DCV for 12 in non cirrhotics, or 24 weeks in cirrhotic GT-2 patients who cannot tolerate RBV, including those with decompensated disease. This article is protected by copyright. All rights reserved.

Liver, 1993

Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been... more Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been considered a contraindication to needle biopsy of the liver, but there are very limited data on the actual rate of bleeding in patients with such severe alterations and none whatsoever on the bleeding risk associated with newer, fine-gauge needles that produce less trauma to the liver tissue. In addition, there has never been any evidence that platelet count and/or prothrombin time are the most sensitive indices of bleeding risk. This retrospective study of 85 patients, with platelet counts less than 50000/mm3 and/or prothrombin times less than 50% of controls, subjected to ultrasound-guided fine-needle liver punctures for diagnostic or therapeutic (percutaneous ethanol injection) purposes showed no bleeding episodes after any of the 229 punctures performed.

Journal of Hepatology, 1994

One hundred and sixty-five patients with cirrhosis were prospectively investigated, by regular ul... more One hundred and sixty-five patients with cirrhosis were prospectively investigated, by regular ultrasonographic follow up, to assess the incidence of gallstones. The mean length of follow up was 33 months (range 12 to 108). Cholelithiasis was diagnosed in 31 patients (18.8%), with a cumulative incidence over 84 months of 38.3% (4.7% yearly incidence). The risk of gallstones was similar in males (38%) and females (38.3%), although the final cumulative incidence was reached at 72 months in males. The percentage of patients with new stones was higher in alcoholic cirrhosis (28.9%) (with a cumulative incidence of 48.8% at 84 months) and lower in hepatitis-related cirrhosis (1.9%) (only one new case at 96 months of follow up) (p < 0.001). The cumulative incidence of gallstones in the Child's C group reached 49.3% at 48 months versus 24% in Child's B and 6.4% in Child's A (p < 0.0001). At multivariate analysis, Child's C and alcoholic cirrhosis were shown to be the independent variables significantly associated with a high risk of development of cholelithiasis. This study confirms that cirrhosis represents a high risk factor for gallstones. The risk is greater for alcoholic cirrhosis and increases with the severity of the disease.

Journal of Gastroenterology and Hepatology, 1992

The accuracy of ultrasonographic diagnosis of hypoechoic focal fatty change in the 'bright liver'... more The accuracy of ultrasonographic diagnosis of hypoechoic focal fatty change in the 'bright liver' was evaluated in 40 lesions found in 35 patients followed up for a mean period of 37.8 months. Patients with ultrasound and laboratory findings suggesting liver cirrhosis were excluded from the study.

Journal of Gastroenterology and Hepatology, 1994

The protective role of large spontaeous portosystemic shunts in oesophageal varices bleeding due ... more The protective role of large spontaeous portosystemic shunts in oesophageal varices bleeding due to portal hypertension in liver cirrhosis is still debated. A series of 20 consecutive patients with haemodynamically efficient collaterals involving the para-umbilical-epigastric venous route (evaluated by Echo-Doppler flowmetry) is reported. All patients presented absent or mild oesophageal varices at endoscopy. During a mean follow-up period of 23.5 months, no patient developed large varices or experienced variceal bleeding. Hepatic encephalopathy was present in 35% of patients. Haemodynamically efficient spontaneous portosystemic shunts may 'protect cirrhotic patients from the risk of oesophageal varices forming and bleeding. The diversion of large amounts of blood from portal to systemic circulation correlates with the higher trend of hepatic encephalopathy in these patients.

Journal of Clinical Ultrasound, 1993

Journal of Clinical Gastroenterology, 1989

Journal of Clinical Gastroenterology, 1993

Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting ... more Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting needle biopsy. Specimens were obtained from the focal lesions under ultrasound guidance and histologically diagnosed as regenerative nodules. An image analyzer was then used to determine the cytoplasmic area, nuclear area, and nuclear/cytoplasmic ratio for 100 randomly selected cells from each specimen. Data were then compared with data for specimens of normal liver tissue and data from patients with alcoholic or posthepatic cirrhosis or well-differentiated hepatocellular carcinoma (HCC). The morphometric parameters for the group of regenerative nodule specimens fell within an intermediate range between those for HCC and the nondysplastic samples, strongly suggesting a preneoplastic nature. Nine of the 10 regenerative lesions showed liver cell dysplasia, and 3 of these patients developed HCC during follow-up. Ultrasonically discernible focal masses in a cirrhotic liver should be considered preneoplastic, if not neoplastic lesions and treated aggressively to prevent their progression to outright malignancy.

Digestive Diseases and Sciences, 1990

In the period 1985-1988, 62 focal liver lesions in 58 cirrhotic patients were studied by ultrason... more In the period 1985-1988, 62 focal liver lesions in 58 cirrhotic patients were studied by ultrasonography; 12 of these focal lesions were documented to be regenerating lesions by echo-guided fine-needle biopsy. During an average follow-up period of 10.2 months (range 3-22 months), hepatocellular carcinoma was subsequently found in 10 of the cases of regenerating nodules, whereas the initial diagnosis of regenerating nodule was confirmed in the remaining two cases. Based upon this finding, it is suggested that every focal mass visualized by ultrasonography in a cirrhotic liver should either be considered to be a neoplastic lesion or at least a preneoplastic lesion if the possibility of either a metastatic or benign lesion (eg, hemangiomas, focal fatty liver change areas) can be excluded. Therefore either fine-needle aspiration or biopsy of aU ultrasonographically revealed mass lesions within a cirrhotic liver is advised, such that early appropriate treatment for hepatocellular carcinoma can be instituted.

Digestive Diseases and Sciences, 1996

There is still debate over the relative merits of cytology and histology in diagnosing hepatocell... more There is still debate over the relative merits of cytology and histology in diagnosing hepatocellular carcinoma in cirrhotic livers. Previous comparisons of the diagnostic accuracies of these two methods may have been biased by sampling errors due to multiple punctures. We compared the diagnostic accuracies of cytology and microhistology using tissue and cells from the same point in liver nodules subsequently proved to be hepatocellular carcinoma. A single ultrasound-guided liver-nodule biopsy was obtained with a 20- to 21-G cutting needle from 131 cirrhotic patients. The solid portion of samples was used for microhistology; the remainder was subjected to smear cytology. The results of each type of examination were expressed as true positive, nonspecific malignancy, false negative, or inadequate for diagnosis. No false-positive diagnoses were made in 13 benign lesions. In 118 HCC nodules (particularly those <30 mm in diameter), cytology provided a significantly higher percentage of correct diagnoses (85.6%) that was only slightly inferior to that based on results of both studies (89.8%). The single-biopsy technique generally provides adequate tissue for histology and cytology specimens with a high cellularity. It reduces both the cost and the risks of fine-needle biopsy diagnosis of hepatocellular carcinoma.

Digestive and Liver Disease, 2008

Digestion, 1992

Being more evident that primary achalasia is not confined to the esophagus and that it may involv... more Being more evident that primary achalasia is not confined to the esophagus and that it may involve other organs in the digestive tract, gallbladder emptying was ultrasonographically evaluated in 10 patients affected with primary achalasia and in 10 controls. An intravenous cerulein infusion was used to induce gallbladder contraction. Eight out of 10 achalasic patients had a lower gallbladder emptying, and 6 out of 10 had a markedly delayed gallbladder emptying compared with the controls. Achalasic patients, taken as a whole, showed a significantly lower and delayed mean gallbladder emptying when compared with the controls. Such a finding confirms the possible extra-esophageal extension of primary achalasia. In this study, the hypothesis of impaired cholinergic gallbladder innervation in primary achalasia is discussed.

European Journal of Ultrasound, 1995

Objective: To assess the role of pulsed Doppler ultrasound in the differential diagnosis of focal... more Objective: To assess the role of pulsed Doppler ultrasound in the differential diagnosis of focal liver lesion, based upon the presence of a Doppler signal and its waveform. Merhodr: The presence of a Doppler signal was accurately investigated in 267 focal liver lesions which had subsequently a definitive diagnosis. Most representative groups included hepatocellular carcinomas (188 cases), metastases (34 cases) and haemangiomas (42 cases). Remits: Doppler signals were detected with a significantly higher rate in hepatocellular carcinomas than in metastases (P = 0.001) and haemangiomas (P c 0.0001). The detection rate in metastases was significantly higher than in haemangiomas (P = 0.001). Assuming the detection of a Doppler signal allows to classify a liver lesion as malignant, we obtained sensitivity of 84.9%. specificity of 90.5%, diagnostic accuracy of 85.8%, positive predictive value of 97.9% and negative predictive value of 52.8%. Considering only the presence of a pulsatile wave as a diagnostic sign of malignancy, these figures resulted 80.8%, lOO%, 84.2%, 100% and 52.8%, respectively. Conclusions: The detection of Doppler signals from within a liver lesion has a clinical relevance. The finding of a pulsatile waveform makes it possible to differentiate a malignant lesion from haemangioma with high sensitivity and absolute specificity.