Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma.

BACKGROUND: Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long-term efficacy and safety are not conclusive. AIM: This study reports a prospective survey on radiofrequency thermal ablation in north-east Italy. METHODS: Data were collected on 401 patients with hepatocellular carcinoma (males 301, mean age: 68 years) treated by radiofrequency thermal ablation in 13 centres. Indication to treatment was: single nodule not eligible for surgery in 77% of patients, 2-3 nodes in 18% and multiple lesions in 5%. Mean size was 3 cm (1-8 cm). Treatment response was assessed at 1 month by spiral computerized tomography and then with ultrasound examination and new spiral computerized tomography. RESULTS: Complete response was obtained in 67% of patients and in 27% response was 75-99%. Complete response raised to 77% in lesions smaller than 3 cm. The morbidity rate was 34%; the mortality was 0.5%, seeding was observed in four patients. Ten patients presented an unexpected rapid disease progression. CONCLUSION: The above data show that by radiofrequency thermal ablation, complete response can be achieved only in about two-third of the cases, clearly less than expected, and that, beyond seeding, unexpected progression can be observed.

Serum carcinoembryonic antigen in the differential diagnosis of pancreatic cancer: influence of tumour spread, liver impairment, and age.

In order to verify the role of CEA in the differential diagnosis of pancreatic cancer and to evaluate some influencing factors like age, tumor spread and liver dysfunction, this antigen was measured in the sera of 60 control subjects, 45 patients with pancreatic cancer, 37 with chronic pancreatitis, 67 with benign, and 28 with malignant extra-pancreatic diseases. CEA was found to be elevated in 23/45 pancreatic cancers, in 8/37 chronic pancreatitis, in 17/67 benign and in 9/28 malignant extra-pancreatic diseases. Significant correlations were documented between CEA and age in all the subjects; between CEA and immunoglobulins G in liver cirrhosis and between CEA and alkaline phosphatase in gastrointestinal extra-pancreatic malignancies. In pancreatic cancer higher CEA levels were detected in patients with metastases. We can conclude that CEA is of limited value in the differential diagnosis of pancreatic cancer; it does not seem to be able to detect early pancreatic tumors. Age and liver dysfunction may contribute towards elevating this marker in serum.

Alpha-fetoprotein, tissue polypeptide antigen and ferritin in diagnosing primary hepatocellular carcinoma in patients with liver cirrhosis.

This study was undertaken in order to compare the usefulness of three indices of tumour proliferation in detecting primary hepatocellular carcinoma (HCC) and in differentiating this neoplasm from liver cirrhosis. In 10 patients with HCC and in 63 with liver cirrhosis serum alpha-fetoprotein (AFP), tissue polypeptide antigen (TPA) and ferritin were assayed. Increased levels of AFP but not of TPA and ferritin were observed in HCC as compared to liver/cirrhosis. The receiver-operating characteristic curves demonstrated that AFP is more discriminating between HCC and liver cirrhosis than the other two markers. Correlations between liver function tests and serum markers were observed in liver cirrhosis but no in HCC. We can conclude that AFP is more useful than TPA and ferritin in detecting HCC in patients with liver cirrhosis, owing to the high frequency of false positive results of the latter two indices in liver cirrhosis. Liver dysfunction is probably involved in increasing all these markers of malignancy, thus reducing the specificity of these tests.

Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis.

Pancreatic tissue obtained from 26 patients with alcoholic chronic pancreatitis (ACP), nine patients with nonalcoholic idiopathic chronic pancreatitis (NAICP), and seven patients with obstructive chronic pancreatitis (OCP) was studied in an attempt to determine whether clinical or etiologic differences have a morphologic counterpart. Histologically it was easy to distinguish ACP from OCP occurring distal to an obstruction of the pancreatic duct. Nine patients with NAICP showed histological features similar to those found in ACP. Plugs and calcifications were found as frequently in NAICP as in ACP, suggesting that NAICP, whatever the etiology, is truly pancreatolithiasis, which leads to slowly progressive fibrosis and acinar atrophy in the obstructed pancreatic lobule. Nerve fibers were found to be more numerous in all disease categories. Inflammatory foci of lymphocytes associated with nerves were observed in 57 and 35% of cases with OCP and ACP, respectively, but only in one patient with NAICP. These findings may constitute a pathological basis for the existing clinical data showing that NAICP frequently runs a pain-free course.

[Ca 19-9 in the diagnosis of pancreatic carcinoma]. / Il CA-19-9 nella diagnosi di carcinoma pancreatico.

This study was undertaken in order to ascertain the role of CA 19-9 in pancreatic cancer diagnosis. Therefore CA 19-9 was determined in the sera of 83 control subjects, 108 patients with pancreatic cancer, 112 with chronic pancreatitis and 126 with extrapancreatic diseases. Sensitivity, specificity and accuracy in detecting pancreatic cancer were: 75%, 86% and 61% respectively. The receiver-operating characteristic curves showed that CA 19-9 is able to well discriminate pancreatic cancer from controls; satisfactorily it differentiated pancreatic malignancy from chronic pancreatitis and other benign extrapancreatic diseases. Extrapancreatic neoplasms were not accurately separated. No difference was detected in CA 19-9 levels between pancreatic cancer patients with or without hepatic metastases. We can conclude that CA 19-9 is a test for pancreatic malignancy with a satisfactory sensitivity and specificity in respect of other pancreatic and extrapancreatic benign pathologies; the presence of hepatic metastases is only one of the factors which may increase its serum levels.

[Role of serum markers and or various clinical parameters in the diagnosis of pancreatic carcinoma]. / Ruolo dei marcatori sierici e di alcuni parametri clinici nella diagnosi di carcinoma pancreatico.

This study was performed to ascertain the role of serum markers and simple clinical data in detecting pancreatic cancer and in distinguishing this malignancy from chronic pancreatitis and other gastrointestinal diseases. Serum CA 19-9, tissue polypeptide antigen and carcinoembryonic antigen were measured in 38 control subjects, 37 patients with pancreatic cancer, 39 with chronic pancreatitis and 44 with extra-pancreatic diseases mainly of gastrointestinal origin. Clinical data recorded included age, sex, presence of pancreatic calcifications, weight loss, pain, jaundice, alcohol abuse, diabetes mellitus. Serum markers gave a correct allocation of the subjects in 48.1% of the cases with pancreatic cancer patients correctly predicted in 62.2%. Clinical data correctly diagnosed 74.2% of subjects. Chronic pancreatitis was identified in 84.6% of the cases and pancreatic cancer in 64.9%. The first clinical variables selected were pain and age. The addition of serum markers to clinical data did not enhance accuracy of the results. We conclude that the diagnosis of chronic pancreatic diseases should first be suspected on the basis of accurately recorded simple clinical data; serum markers seem to be only occasionally useful. Since indicative clinical data and serum markers become positive in the advanced phases of pancreatic cancer, early diagnosis of this malignancy still remains an objective to reach.

Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis.

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.

Pancreolauryl test in chronic pancreatitis.

The pancreolauryl test was performed in 30 subjects with chronic pancreatitis, in order to evaluate its behavior in relation to the duration of the clinical history and the presence of pancreatic calcifications, diabetes mellitus, jaundice, and pancreatic pseudocysts. A significant inverse linear correlation was found between the onset of symptoms and FDL test values. While calcifications and diabetes were present in patients with both normal and abnormal test results, those with pseudocysts or jaundice always had pathological results.

Renal handling of amylase and immunoreactive trypsin in pancreatic cancer and chronic pancreatitis.

In order to evaluate the renal metabolism of amylase and immunoreactive trypsin (IRT) in chronic pancreatic disease, we assayed amylase, IRT and creatinine in serum and urine and gamma-glutamyl transferase (GGT) in dialyzed urine as well as alpha-glucosidase (AGL) and ribonuclease (RNase) in 24 control subjects, 34 patients with pancreatic cancer, 52 with chronic pancreatitis and 32 with extra-pancreatic diseases. Urinary amylase and IRT outputs were found to be more elevated in chronic pancreatitis than in control subjects. The levels of serum amylase, its renal inputs and outputs were correlated with the corresponding IRT values. Multiple regression analyses (dependent on amylase or IRT urinary outputs, circulating levels of the two enzymes, creatinine clearance and the excretion of GGT, AGL and RNase predictor variables) showed significant correlations. The standardized partial regression coefficients found to be significant were: GGT, RNase and serum amylase for amylase, and GGT and RNase for IRT. No difference was found between amylase and IRT outputs in patients with chronic pancreatitis, taking the presence or the absence of alcohol abuse, exocrine insufficiency and pancreatic pseudocysts into consideration. Urinary GGT excretion correlated with serum amylase and IRT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

C reactive protein in pancreatic cancer and chronic pancreatitis.

Serum C reactive protein was determined in 30 control subjects, 32 patients with pancreatic cancer, 28 with chronic pancreatitis and 23 with extra-pancreatic diseases of the upper gastrointestinal tract. The aim was to ascertain possible alterations of this index in chronic pancreatic disease and to speculate on some influencing factors. Higher C reactive protein levels were found in pancreatic cancer as compared to controls. Pancreatic cancer patients with systemic metastases had higher levels of this index compared to those with non-metastatic disease. Raised concentrations of C reactive protein were detected in 7/28 subjects with chronic pancreatitis. In this group these higher levels were found in patients in a relapsing phase of the disease; no association was observed with pancreatic pseudocysts. Among all subjects a correlation was found, between C reactive protein and age; patients with abnormal fasting blood glucose levels or increased white blood cell count had higher levels of this protein as compared to the remaining patients. We may conclude that C reactive protein increases in pancreatic cancer, specially in relation to tumour extent; in chronic pancreatitis it reflects the inflammatory status of the gland. While acting in the context of the acute phase response, this test may provide an adjunct in evaluating patients with a chronic pancreatic disease.

Ribonucleases and deoxyribonucleases in pancreatic cancer: clinical value and pathophysiological interrelationships.

In this study we evaluated some pathophysiological aspects of pancreatic and liver ribonucleases and alkaline deoxyribonuclease and their clinical usefulness in diagnosing pancreatic cancer. Pancreatic RNase was found to be a sensitive index of pancreatic malignancy; however it was not specific in distinguishing pancreatic malignancy from chronic pancreatitis or other pathologies. Liver RNase and alkaline DNase did not provide better results than pancreatic RNase. These three enzymes were found to be age-dependent and related to each other. Therefore serum nucleases are not useful for clinical purposes since they are influenced, at least in part, by different non-specific factors.

Limits of CEA and ferritin in the diagnosis of pancreatic cancer.

In this paper the clinical usefulness of CEA and ferritin in the diagnosis of pancreatic cancer was pointed out. CEA was found to be increased in 51% of patients with pancreatic cancer; it was also abnormal in 22% of chronic pancreatitis and 31% of extra-pancreatic diseases. In patients with metastatic pancreatic cancer CEA was found to be more elevated than in those with localized tumor. CEA correlated with the age of the subjects in all material; in liver cirrhosis with IgG and in extra-pancreatic gastro-intestinal malignancies with alkaline-phosphatase. Ferritin was found to be increased in 73% of pancreatic cancer patients; it was also abnormal in 40% of chronic pancreatitis and in 38% of extra-pancreatic diseases. Patients with chronic pancreatitis studied during a relapsing phase all had elevated serum ferritin. We can conclude that neither CEA nor ferritin are useful indices of pancreatic malignancy, due to the lack of sensitivity or specificity. Both are influenced by several factors: CEA mainly by age and liver dysfunction, ferritin by the presence of an acute inflammation with cell necrosis.

Cytology in the diagnosis of pancreatic cancer.

The study of cytology in duodenal and/or pure pancreatic juice has been proposed in the differential diagnosis of pancreatic cancer. In our experience the sensitivity of cytology in duodenal juice, collected during Secretin-Cholecystokinin test, in diagnosing pancreatic cancer was 66.6%. False positive results were obtained only rarely (1.4%) in patients with chronic pancreatitis and benign diseases of the gastrointestinal tract. The cytological evaluation of pure pancreatic juice, obtained by ERCP, increases sensitivity up to 80-90%, especially when the combination of the results of ERCP and cytology is performed. Cytological examination of duodenal and/or pure pancreatic juice is a useful tool in detecting pancreatic malignancy and in differential diagnosis with chronic pancreatitis.

Tissue polypeptide antigen, galactosyltransferase isoenzyme II and pancreatic oncofetal antigen serum determination: role in pancreatic cancer diagnosis.

The clinical usefulness of tissue polypeptide antigen, galactosyltransferase II and pancreatic oncofetal antigen was evaluated in detecting pancreatic cancer and in differentiating this malignancy from chronic pancreatitis and other diseases (mainly of the liver and biliary tract) which may enter in differential diagnosis. TPA seems to be the most sensitive among these indices in detecting pancreatic cancer and appears to discriminate this malignancy quite satisfactorily from chronic pancreatitis. It is also frequently pathological in a number of other diseases and is influenced by the presence of liver dysfunction. GT II and POA do not grossly differ from TPA in specificity, but they appear to be less sensitive. Both are frequently pathological in hepato-biliary diseases. All these markers seem, therefore, to be of limited value in the diagnosis of pancreatic cancer.

Tumor-associated trypsin inhibitor in patients with chronic pancreatic diseases.

Serum TATI (tumor-associated trypsin inhibitor) was measured in 41 control subjects, 30 patients with pancreatic cancer, 53 with chronic pancreatitis, and 47 with extrapancreatic diseases, mainly of gastrointestinal origin. TATI was found to be elevated in some subjects in all groups of patients; patients with chronic pancreatitis studied during an acute exacerbation of the disease had the highest percentage (68%) of pathological values. TATI was found to be correlated with elastase 1, tissue polypeptide antigen, and total and pancreatic isoamylase. A significant relationship was also found between TATI and serum creatinine levels.

Urinary elastase 1 in chronic pancreatic disease.

Serum and urine elastase 1, its renal output and clearance and urinary gamma-glutamyltransferase and ribonuclease excretions were measured in 16 patients with pancreatic cancer, 23 with chronic pancreatitis and in 22 healthy controls in order to evaluate elastase 1 plasma-urine transfer in chronic pancreatic disease and to investigate any factors that might influence the clearance of this enzyme. In an additional group of 17 patients with different pancreatic diseases the serum molecular size distribution of elastase 1 after chromatography was ascertained. An increased urinary elastase 1 output was found in 4/16 patients with pancreatic cancer and in 6/23 with chronic pancreatitis. No correlation was found between circulating elastase 1 and its urinary output; a negative correlation was detected between the serum levels of this enzyme and its clearance. The excretion of ribonuclease and gamma-glutamyltransferase was correlated with elastase 1 output and clearance. While the majority of elastase 1 in serum was accounted for by high molecular forms, probably the expression of complexes with serum inhibitors, free circulating enzyme was present in all patients with high serum elastase 1. Our findings suggest that elastase 1 urinary excretion increases in some patients with chronic pancreatic disease regardless of the neoplastic or inflammatory nature of the illness. Although the availability of different amounts of ultrafiltrable enzyme may play a role in influencing elastase 1 plasma-urine transfer, renal tubular damage appears to be the most important factor influencing the increase in the urinary output of elastase 1.

[Changes in the pattern of serum biliary acids and lipoprotein picture during therapy with biliary acids in cholesterol lithiasis]. / Modificazioni del "pattern" degli acidi biliari sierici e del quadro lipoproteico in corso di terapia con acidi biliari nella litiasi colesterolica.

Several studies are present in the literature about the efficacy of medical treatment with biliary acid, orally administered, on the symptomatic gallstone patients. Both this drugs act, with different mechanisms, on the same pathophysiological pathway, represented by the supersaturated bile in cholesterol. Aim of the present investigation was to study the possible modifications of serum bile acids pattern and of lipoproteins in a large sample of gallstone patients under long-term treatment with biliary acids. One hundred and twelve patients with radiolucent gallstones entered the study; 54 received chenodeoxycholic acid (CDCA) and 58 ursodeoxycholic (UDCA) at dosage of 15 mg/kg/daily. Blood samples for determination of serum cholesterol, triglycerides, phospholipids, lipoproteins, total and fractionated biliary acids were collected from each subjects every three months for a mean "follow-up" of 24 months. The levels of serum cholesterol, triglycerides and phospholipids showed a mild decrease only in the patients under therapy with CDCA, while no modifications were detected using UDCA. The same was found for two other parameters, HDL-cholesterol and lipoproteins, with both treatments during the overall period of follow-up. The biliary acids levels showed a significant increase only in the patients treated with CDCA, but no differences were found between "responders" and "non responders" to the therapy.

How does liver dysfunction influence serum CA 19-9 in pancreatic cancer?

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.

Renal involvement in chronic pancreatic disease: effects on trypsin and amylase plasma-urine transfer.

This study was undertaken in order to ascertain the behaviour of amylase and trypsin fractional clearances in chronic pancreatic disease and to speculate on the factors involved. Renal tubular function was also assessed in these patients. An increase of both clearances was found in a number of patients with pancreatic cancer and chronic pancreatitis. Amylase urinary output seems to be mainly related to the circulating enzyme levels; urinary IRT is principally accounted for by a functional tubular impairment. Tubular damage was observed in a number of patients with chronic pancreatic disease. This was related to pancreatic inflammation in chronic pancreatitis and to several factors, among which jaundice and pancreatic damage, in pancreatic cancer.