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P Tomassetti

Publications and source records attributed to P Tomassetti.

At least 19 recordsLinked to original sources

Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?

Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7-24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.

Adult↗

Diagnostic value of plasma chromogranin A in neuroendocrine tumours.

AIM: The aim of this study was to assess the value of plasma chromogranin A (CgA), a protein produced by neuroendocrine cells, in the diagnosis of neuroendocrine tumours. METHODS: Eighty subjects with neuroendocrine tumours were studied. Thirty-four had carcinoids, 21 nonfunctioning endocrine pancreatic tumours, 17 multiple endocrine neoplasia type 1 (MEN 1) (six of these also had gastrinomas), and eight had functioning pancreatic tumours (four gastrinomas, two glucagonomas, two somatostatinomas). Twenty-eight healthy subjects were studied as controls. A fasting plasma sample was obtained from each subject, and CgA plasma levels were measured by the ELISA method using a kit (Dako A/S, Denmark). RESULTS: In control subjects, plasma CgA values were below 5 U/l. Among the patients, 20 of the 34 with carcinoid tumours, 12 of the 21 with nonfunctioning pancreatic tumours, nine of the 17 with MEN 1 (including the six with gastrinomas), and the four gastrinomas of the eight functioning pancreatic tumours, i.e. overall, 45 of the 80 patients (56.3%) had abnormally high CgA values (22-961 U/l). Most of the patients with elevated CgA values, except nine of the 10 with gastrinomas, had multiple liver metastasis. CONCLUSIONS: The results show that the diagnostic value of plasma CgA in neuroendocrine tumours is relatively low; it may be of some interest only in patients with advanced disease and liver metastasis. Gastrinoma seems to be an exception, because in this tumour high CgA values are generally found even in the absence of liver metastasis.

Adult↗

Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR.

BACKGROUND: Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days. AIM: To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours. METHODS: A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months). RESULTS: In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed. CONCLUSIONS: Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.

Adult↗

Fecal elastase 1 determination in chronic pancreatitis.

This study assessed the diagnostic accuracy of fecal elastase 1 in chronic pancreatitis. Fifty-three healthy subjects, 44 patients with chronic pancreatitis (22 severe, 13 moderate, and 9 mild), and 43 patients with nonpancreatic digestive disease were studied. Elastase 1 concentration was determined on a small sample of feces using a commercially available kit. Fecal chymotrypsin was also measured. With a cutoff level of 190 microg/g, all healthy controls except one (98.1%), and the majority of patients with nonpancreatic digestive diseases (40 of 43; 93.0%) had elastase values above this limit. Among the 44 patients with chronic pancreatitis, 34 (77.3%) had pathological values: all 22 (100%) with severe disease, 10 of 13 (76.9%) with moderate disease and 2 of 9 (22.2%) with mild disease. Chymotrypsin values were pathological in 25 of 44 (56.8%) patients with chronic pancreatitis: 17 of 22 (77.2%) with severe pancreatitis, 7 of 13 (53.8%) with moderate pancreatitis, and 1 of 9 (11.1%) with mild disease. The specificity was 95.8% for elastase 1 and 85.4% for chymotrypsin. The difference both in sensitivity and specificity of the two enzymes was statistically significant (P < 0.05). Fecal elastase 1 has a high sensitivity, superior to that of fecal chymotrypsin, in the diagnosis of chronic pancreatitis. For its simplicity and rapidity, it could represent the tubeless test of choice in chronic pancreatitis.

Adolescent↗

Treatment of metastatic glucagonoma to the liver: case report and literature review.

Glucagonoma, a rare neuroendocrine pancreatic tumour, is frequently malignant and often accompanied by hepatic metastases. Our aim was to consider the different treatments of metastatic glucagonoma to the liver and their results. A case of glucagonoma with metachronous, small, multiple and bilobar liver metastases is reported. Combined treatment with octreotide and hepatic arterial chemoembolization was applied with good results in terms of symptom relief, plasma glucagon levels and regression of hepatic metastases. Survival rates were also improved. Based on our experience, glucagonoma with metachronous, multiple, diffuse and bilobar hepatic metastases should be treated with octreotide plus hepatic arterial chemoembolization with improved outcome and prognosis.

Antineoplastic Agents, Hormonal↗

Clinical aspects of carcinoid tumours.

Carcinoid tumours are the most commonly occurring gut endocrine tumours; they are characterized by relatively slow rate of growth, local spread and distant metastases as compared with other malignant neoplasms. The carcinoid syndrome occurs in less than 10% of patients with carcinoid tumours when liver metastases are present. The combination of symptoms, humoral markers and imaging techniques provide an optimal means for the identification of carcinoid tumours and their metastases.

Carcinoid Tumor↗

Slow-release lanreotide treatment in endocrine gastrointestinal tumors.

OBJECTIVES: Lanreotide is a somatostatin analogue whose activity persists for 10-14 days. In this study, we treated a group of patients with gastrointestinal endocrine tumors with lanreotide to assess its therapeutic efficacy and tolerability. METHODS: Eighteen patients, 12 male and six female, mean age 58 yr (range, 25-80 yr) were studied. Ten had carcinoid tumors, five had nonfunctioning endocrine tumors, two had glucagonomas, and the remaining one had a gastrinoma. All patients had somatostatin receptors, demonstrated by octreoscan scintigraphy. Lanreotide was administered intramuscularly at a dose of 30 mg every 10 days, for a mean of 12 months (range, 5-18 months). Fifteen of the 18 patients had been previously treated with octreotide. RESULTS: In patients with carcinoid tumors, lanreotide markedly reduced daily bowel movements and flushing episodes. A reduction was also observed in urinary serotonin and urinary 5-hydroxyindoleacetic acid, although it was not statistically significant. A marked reduction in symptoms, and in plasma glucagon and serum gastrin levels, was also observed in patients with glucagonoma and gastrinoma. In the five patients with nonfunctioning endocrine tumors, as in all the other 13 patients, no significant effects were noted in the size of the tumor. The administration of lanreotide did not cause side effects, apart from transient abdominal pain and pain at the injection site in two patients. Only in the patient with gastrinoma was lanreotide suspended, because of the appearance of attacks of marked hypoglycemia. In the 15 patients previously treated with octreotide, no differences in the effects were noted with lanreotide. CONCLUSIONS: Lanreotide has a satisfactory therapeutic efficacy and tolerability in the treatment of gastrointestinal endocrine tumors; its effects are similar to those of octreotide. However, unlike octreotide, it can be administered once every 10-14 days, instead of 2 or 3 times daily and for this reason, it is preferable in clinical practice.

Adult↗

Plasma cholecystokinin and neurotensin after an ordinary meal in humans. A prolonged time study.

BACKGROUND/AIM: Ingestion of a meal causes the release of cholecystokinin and neurotensin into the circulation, but little is known about the duration of this release. METHODS: Six healthy volunteers were studied. Blood samples for cholecystokinin, neurotensin and gastrin assessment were drawn before and after consumption of a typical Italian lunch. Postprandial samples were obtained every hour for a total of 10 hours. All peptides were measured using previously validated radioimmunoassays. RESULTS: Ingestion of the meal caused a prompt and significant increase in plasma levels of all three peptides. Cholecystokinin remained elevated for about 7 hours and then tended to return towards basal values, whereas the increase of neurotensin persisted for the entire period of the study (10 hours). Gastrin remained elevated for about 5 hours and then declined. The integrated CCK and gastrin responses during the initial postprandial hours were greater than those in the late hours, whereas the integrated neurotensin response during the initial hours was lower than that in the late hours. CONCLUSIONS: The results indicate that, after an ordinary meal, cholecystokinin is released into the circulation for about 7 hours, much longer than previously reported (3-4 hours). The release of neurotensin begins soon after the meal and persists even longer, for at least 10 hours. Possible physiological implications of these findings are discussed.

Adult↗

Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I.

In recent classifications of gastric endocrine tumors, tumors arising in patients with multiple endocrine neoplasia type 1 (MEN-1) are regarded to be regulated by the concomitant hypergastrinemia resulting from to pancreatic or, most commonly, duodenal gastrinomas and to have a benign behavior. In this article, we report on two cases of MEN-1 gastric neuroendocrine tumors having a fatal course. Case 1 was a young male with hyperparathyroidism and Zollinger-Ellison syndrome and with florid development of multiple gastric carcinoids and multiple duodenal gastrinomas. Metastases occurred in the liver, of exclusive gastric origin, in periduodenal lymph nodes, of exclusive duodenal origin, and in perigastric lymph nodes, of mixed origin. The patient died 48 months after diagnosis. Case 2 was an adult female patient with hyperparathyroidism, adrenocortical disorders, and gastric tumors but no hypergastrinemia. The patient died 3 months after tumor diagnosis. At autopsy, the stomach showed multiple benign carcinoids and two independent neuroendocrine carcinomas not reported before in MEN-1 and massively metastatizing to lymph nodes, liver, and peritoneum. Multiple islet cell tumors mostly producing pancreatic polypeptide were found, whereas gastrinomas were seen in neither the pancreas nor the duodenum. Allelic losses at the MEN-1 gene locus in chromosome 11q13, the mechanism responsible for tumor development in MEN-1 syndrome, were demonstrated in the carcinoid tumors of case 1 and in the neuroendocrine carcinoma of case 2. We conclude that gastric neuroendocrine tumors in patients with MEN-1 may have a poor outcome, they have the same genetic mechanism as MEN-1 tumors in other organs, and they may be independent of the trophic effect of hypergastrinemia.

Adult↗

Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia.

BACKGROUND: The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. AIMS: To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. PATIENTS AND CONTROLS: Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p < 0.001). METHODS: Immunohistochemistry was performed on 3 microns sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine. RESULTS: The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (phi h value) was significantly higher in patients with CAG or ZES compared with controls (p < 0.01 in both patient groups versus controls). CONCLUSIONS: Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Adult↗

Clonal analysis by chromosome 11 microsatellite-PCR of microdissected parathyroid tumors from MEN 1 patients.

Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the majority of larger parathyroid tumors from patients affected by Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the whole parathyroid gland does not permit a clear morpho-genetic correlation, the clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained from single nodules and non-nodular areas within MEN 1 parathyroid lesions. Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci in at least one microdissected area for each familial MEN 1 patient, but not in the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited a polyclonal cell composition of these microdissected samples, indicating the existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a "clonal" pattern for allelic losses.

Adolescent↗

Effects of ischemia on the human pancreas.

BACKGROUND & AIMS: Patients undergoing cardiac surgery frequently have pancreatic damage; several factors, including tissue hypoperfusion, have been implicated. The aim of this study is to better understand the effects of decreased blood supply on human pancreas. METHODS: Twenty-one consecutive patients undergoing surgery for thoracic or thoracoabdominal aortic aneurysm were studied. During surgery, the descending thoracic aorta was cross-clamped for a mean of 44 minutes (range, 15-85 minutes). Effects of the resultant pancreatic ischemia were assessed by examining the patients daily for evidence of acute pancreatitis for at least 20 days after surgery and by determining serum concentrations of amylase, pancreatic isoamylase, and lipase before clamping the aorta and at varying intervals after its release (1, 2, and 6 hours during the first day and once daily for the following 6 days). RESULTS: One patient died of acute necrotizing pancreatitis. None of the others had symptoms of pancreatitis postoperatively, but all showed a significant increase in serum pancreatic enzyme concentrations soon after declamping; this peaked about 24 hours later and persisted for all 7 days of the study. A significant relationship was found between the increase in pancreatic enzyme concentrations and the aortic clamping time. CONCLUSIONS: Acinar cell injury is a constant, rapidly appearing consequence of severe pancreatic ischemia, even that of brief duration; acinar cell injury is usually subclinical but may also present as severe acute pancreatitis.

Aged↗

[The risk factors for pancreatic cancer].

This review summarises the current state of knowledge regarding the risk factors for pancreatic cancer. Of all the factors studied, only smoking is well established. Excessive dietary fat and protein may increase the risk, but this has not been proven conclusively. Fruits and vegetables, on the other hand, may offer a protective effect. The role of coffee remains controversial. There is no concrete evidence that alcohol, tea, occupational exposure, diabetes, gallstones, cholecystectomy or gastrectomy are significantly associated with this tumour. A possible predisposing role for chronic pancreatitis cannot be excluded.

Adult↗

[New etiopathogenic, clinical and therapeutic findings in multiple endocrine neoplasia type 1].

Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome comprises tumors or hyperplasia of different glands, including parathyroid, pituitary, adrenal cortex and the gastroenteropancreatic system. The vast majority of MEN 1 are found in familial clusters, although a few cases are sporadic. Hypercalcemia and/or nephrocalcinosis are the first and most common clinical manifestation in familial MEN 1 syndrome, followed by islet cell tumors (especially those secreting gastrin or insulin) and pituitary dysfunction due to either functioning or non-functioning microadenomas. Genetic studies indicate that familial MEN 1 syndrome is inherited through a dominant gene with incomplete penetrance and variable expression. The diagnosis of MEN 1 syndrome is mainly based on the careful assessment of the clinical history, symptoms physical evaluation along with the assay of serum electrolytes (i.e., calcium, phosphorus, etc.) and hormonal substances (i.e., gastrin, insulin, pancreatic polypeptide, prolactin, adrenocorticotropic hormone, etc.). In addition, several provocative tests have been used to identify endocrine tumors (particularly those of the gastroenteropancreatic system) and imaging techniques play a crucial role for the diagnostic approach in MEN 1 syndrome. Even though in the long term, the prognosis of MEN 1 syndrome is unfavourable. Recently, however, many therapeutic strategies, including both surgical and pharmacological options, have been developed to reduce the size of the neoplasm and control symptoms associated with hormone oversecretion.

Antineoplastic Agents, Hormonal↗

Unusual association of macroamylasemia and hyperlipasemia: report of two cases.

OBJECTIVE: To describe two cases of macroamylasemia associated with hyperlipasemia. METHODS AND RESULTS: The patients were a young male soccer player who had sustained a kick in the groin during a match and a woman with a specific dyspeptic complaints. In both the macroamylasemia had been previously undetected; when admitted with the above complaints, serum pancreatic isoamylase levels, as determined by the inhibitor method, were markedly increased, as were serum lipase levels. In both cases these findings led to the erroneous diagnosis of pancreatitis and consequent multiple diagnostic and therapeutic procedures. The cause of the hyperlipasemia was not clear in either case, although the possibility that it was due to the presence of macrolipase cannot be excluded. CONCLUSION: The possibility of macroamylasemia associated with hyperlipasemia should be kept in mind to avoid unnecessary diagnostic and therapeutic efforts.

Adolescent↗

[The innervation of the digestive tract: its morphofunctional and neurochemical aspects].

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

Animals↗

RFLP analysis of human chromosome 11 region q13 in multiple symmetric lipomatosis and multiple endocrine neoplasia type 1-associated lipomas.

Six lipomas from patients affected by Multiple Symmetric Lipomatosis (MSL) and by Multiple Endocrine Neoplasia Type 1 (MEN 1) were analyzed for loss of heterozygosity on chromosome 11 region q12-13 using four RFLPs. Allelic loss for the D11S146 locus was found only in one visceral MEN 1-associated lipoma. Lipomas that exhibited a lack of allelic lesions were analyzed for an eventual abnormal amount or a defective function of the Gs protein by studying the Gs alpha subunit gene, codons 201 and 207, by PCR and TGGE techniques. All the samples were negative for activating mutations.

Alleles↗