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Biomedical subjects

G Zamboni

Publications and source records attributed to G Zamboni.

At least 73 records · Page 4Linked to original sources

Surgical treatment of pancreatic metastases from renal cell carcinomas.

Pancreatic metastases from a renal cell carcinoma are rare and may occur long after manifestation of the primary disease. Resection of the metastases should be regarded as the best treatment. In our center, owing to the slow evolution of these secondaries, we perform resections capable of limiting the destruction of the pancreatic parenchyma as far as possible. The use of 'atypical' resections of the pancreas is characterized by a higher incidence of postoperative complications, particularly fistulas. Despite this, we believe that adjusted resection is to be advocated because of the possibility of additional remote secondaries, the shorter duration of surgery, the preservation of the glandular parenchyma and intact adjacent organs, such as duodenum, stomach, and spleen, and the fact that there have been no reports on local recurrences.

Aged↗

High-affinity monomeric 67-kD laminin receptors and prognosis in pancreatic endocrine tumours.

Cell-surface high-affinity monomeric 67-kD laminin receptors have been proposed to promote the invasion and metastasis of a variety of tumours, but there are, as yet, no data regarding the expression of these molecules in pancreatic endocrine tumours (PETs). The prognosis of these very rare tumours is problematic and the only irrefutable evidence of their malignancy still continues to be the occurrence of local invasion and metastases. In this retrospective investigation, 34 functioning and 48 non-functioning sporadic PETs were evaluated for the expression of the MLuC5 monoclonal antibody, which specifically recognizes the 67-kD laminin receptors. Laminin receptors were found in 42/82 cases (51 per cent) and their expression was associated with metastatic disease (P < 0.001), high proliferative activity expressed by a Ki-67 index above 5.0 per cent (P < 0.001), absence of progesterone receptors (P = 0.013), immunoreactivity for hormones other than insulin (P < 0.001), a tumour diameter more than 3.0 cm (P = 0.001), and a fatal clinical outcome (P < 0.001). Laminin receptors were also expressed by most metastatic foci and all intravascular emboli of tumour cells. Positivity for laminin receptors was associated with shorter survival in functioning (P = 0.026) and non-functioning (P = 0.042) tumours, as well as in the whole series of pancreatic endocrine tumours (P < 0.001). On multivariate analysis, laminin receptor expression was not an independent prognostic factor, while a Ki-67 index above 5.0 per cent was the most powerful predictor of survival. However, the association of laminin receptor expression and Ki-67 index could identify a group of malignant PETs with low proliferative activity characterized by an intermediate prognosis. In conclusion, these data suggest that monomeric laminin receptors may play a role in the invasion and metastasis of PETs and that their expression may be an additional prognostic factor, along with proliferative activity.

Biomarkers, Tumor↗

[Malignant non-epithelial tumors of the pancreas].

Nonepithelial malignant tumors of the pancreas are extremely rare neoplasms with a frequency of approximately 0.6%. They are always explored because of a suspected diagnosis of pancreatic carcinoma. Amongst the more than 600 primary pancreatic neoplasms in our pancreatic tumor archive only 5 neoplasms were of nonepithelial origin (one was a malignant peripheral nerve sheath tumor [MPNST], one a leiomyosarcoma, one a malignant mesothelioma, and two were peripheral neuroectodermal tumors [PNET]. The differential diagnosis includes secondary infiltration of the pancreas by mesenchymal tumors of the retroperitoneum, undifferentiated pancreatic carcinoma and, especially in the case of PNET, malignant lymphoma. Preoperative chemotherapy and down-staging can improve the operability and prognosis, especially in PNET.

Adolescent↗

Cystic dystrophy of the duodenal wall: radiologic findings.

PURPOSE: To determine the radiologic characteristics of cystic dystrophy of the duodenal wall. MATERIALS AND METHODS: Ten patients with cystic dystrophy of the duodenal wall and chronic pancreatitis underwent ultrasonography (US) (n = 10), computed tomography (CT) (n = 10), endoscopic US (n = 5), and endoscopic retrograde cholangiopancreatography (ERCP) (n = 9). Cystic dystrophy of the duodenal wall was classified as either cystic or solid. The imaging findings were retrospectively analyzed and compared with findings at pancreatoduodenectomy (n = 10). RESULTS: The more frequent cystic type (n = 7) of cystic dystrophy of the duodenal wall was characterized by the presence of easily recognizable cystic lesions (diameter, more than 1 cm), located within the thickened wall of the second portion of the duodenum. The solid type (n = 3) of cystic dystrophy of the duodenal wall demonstrated fibrous thickening of the duodenal wall within which small cysts (diameter, less than 1 cm) were present. The intraduodenal cysts were usually elongated or bilobate with a thick wall. The thickening of the duodenal wall appeared as a solid layer between the duodenal lumen and the pancreas, hypoechoic at US, isoattenuating at unenhanced CT, and hypoattenuating in the early phase (after initiation of infusion of contrast material) and isoattenuating in the late phase (after completion of infusion) at contrast material-enhanced CT. Findings at retrospective analysis of CT and endoscopic US images were characteristic. CONCLUSION: Imaging modalities, notably CT and endoscopic US, helped establish the diagnosis of cystic dystrophy of the duodenal wall.

Adult↗

Antral mucosal Helicobacter pylori infection density as a risk factor of duodenal ulcer.

OBJECTIVE: Duodenal ulcer is regarded as the end result of alterations in which Helicobacter pylori (HP) plays a major role as a pathogenetic agent. The aim of this prospective study was to evaluate duodenal ulcer risk factors such as alcohol intake, smoking, use of non-steroidal anti-inflammatory drugs, age and sex in relation to HP colonization density. PATIENTS AND METHODS: 495 patients consecutively examined by diagnostic upper digestive endoscopy were assessed; none of them had had previous upper digestive endoscopy or peptic ulcer, recent anticulcer-antibiotic treatment, upper gastrointestinal surgery, or cancer. The HP colonization on antral bioptic specimens was graded semi-quantitatively as follows: HP--- (absence of HP); HP+--(focal presence of small amounts of HP); HP++- (intermediate situation between HP+-- and HP+++), and HP+++ (diffuse presence of large amounts of HP). RESULTS: Logistic regression analysis identified only male sex (odds ratio 1.88, p < 0.02), smoking more than 10 cigarettes/day (odds ratio 2.53, p < 0.01), and HP grade (HP +-- odds ratio 0.79, p = NS; HP++- odds ratio 2.42, p < 0.02; HP+++ odds ratio 3.66, p < 0.001) as independent risk factors of duodenal ulcer. CONCLUSION: The duodenal ulcer risk was found to correlate with HP density, male sex, and smoking, but not with non-steroidal anti-inflammatory drug use.

Alcohol Drinking↗

Human neoplastic Schwann cells: changes in the expression of neurotrophins and their low-affinity receptor p75.

Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In neoplastic conditions. Schwann cells from experimentally-induced schwannomas appear to retain their responsiveness to nerve growth factor (NGF), although the role of neurotrophins in the neoplastic process in poorly understood. In this study, human neoplastic Schwann cells (five cases of acoustic schwannoma and two cases of malignant peripheral nerve sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied the 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be the present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RNA for NGF and NT-3 was detected by reverse transcriptase in situ polymerase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of either ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred during the neoplastic transformation of Schwann cells. In benign schwannomas, such changes are likely to reflect the loss of axonal contact, while in MPNST they may be related to a complete derangement of cell machinery in the tumour cells.

Adult↗

Cancers of the papilla of vater: mutator phenotype is associated with good prognosis.

Cancer of the papilla (ampulla) of Vater is an uncommon disease that kills 60% of affected patients. There is general agreement that local spread of the tumor (T stage) is the only significant and independent prognostic factor for this cancer, whereas the predictive value of tumor grade and lymph node metastases is controversial. The genetic anomalies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurrence of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (RER-positive) cancers. Ten microsatellites from five different chromosomes were amplified by PCR from both normal and cancer tissue DNA of the same patients. A tumor was defined as RER-positive when microsatellite instability was found in the majority (>/=6) of the loci analyzed. Five cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas RER-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (12%) patients belonged to cancer-prone families and four (16%) were cancer-prone individuals.

Actuarial Analysis↗

APC gene mutations and allelic losses in sporadic ampullary tumours: evidence of genetic difference from tumours associated with familial adenomatous polyposis.

We explored APC gene mutations and chromosome 5q21 allelic losses (5qLOH) in 18 neoplasms of the papilla of Vater, including 6 early-stage tumours (3 adenomas, 3 carcinomas) and 12 advanced-stage cancers. Eleven PCR-amplified polymorphic sequences were used to analyse 5qLOH. APC mutations were investigated both by an in vitro APC-protein truncation test and by single-strand conformation polymorphism analysis. Mutations in the Ki-ras, N-ras and p53 genes were also assessed. We found: 5qLOH in 8 of 16 cases (50%), including 1 adenoma, 3 early- and 4 advanced-stage cancers; APC mutations in 2 adenomas and 1 advanced-stage carcinoma; Ki- or N-ras mutations in 3 adenomas and 3 advanced-stage cancers; p53 mutations in 2 early-stage and 7 advanced-stage adenocarcinomas. Our results suggest that 5qLOH, APC mutations and ras mutations are present at early stages, whereas p53 inactivation is associated with progression of malignancy in a large proportion of cases. These data indicate that sporadic ampullary tumours differ from those occurring in familial adenomatous polyposis in the frequency (17% vs. 64%) as well as in the site of APC somatic mutations, suggesting a different molecular pathogenesis in the 2 conditions.

Adenomatous Polyposis Coli↗

Chromosome 7q allelic losses in pancreatic carcinoma.

During our DNA fingerprinting studies of paired normal and pancreatic cancer tissues using arbitrarily primed PCR, we noticed a band showing an apparent homozygous deletion in a pancreatic cancer cell line and a decreased intensity in a number of primary cancers. That band was assigned to chromosome 7. Such information led us to analyze chromosome 7 loss of heterozygosity (LOH) in a panel of 12 cryostat-enriched primary pancreatic cancers and 2 pancreatic cancer cell lines, despite the reportedly low frequency of chromosome 7 LOH in xenograft-enriched pancreatic cancers. Seventeen PCR-amplified CA-microsatellite polymorphic sites were analyzed. One of the two cell lines and eight common-type cancers (including all five poorly differentiated and three of five moderately differentiated cancers) showed chromosome 7q LOH, whereas the two uncommon types of ductal cancer (one adenosquamous and one mucinous noncystic) scored negative. Our data suggest that chromosome 7q LOH is a frequent event (80%) in cryostat-enrichable common pancreatic ductal carcinomas, that is, those primarily of high cellularity. The chromosome 7q smallest common deleted region described by our cases was between 7q31.1 and 7q32.

Adult↗

Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both?

The differential diagnosis between Helicobacter pylori (H pylori-associated chronic gastritis and low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) and the assessment of endoscopic biopsy specimens after treatment of lymphoma can be problematic. Although immunocytochemistry can be used to identify clonal B-cell populations, which are characteristic of MALT lymphoma, its application to small biopsy specimens and the subsequent interpretation can be difficult. The polymerase chain reaction (PCR) can detect clonal B-cell populations by analysis of the Ig heavy chain gene in routinely fixed paraffin-embedded material and might provide a useful tool in the assessment of these specimens. We have investigated the value of histology and PCR in the diagnosis of lymphoma and its followup in formalin-fixed paraffin-embedded gastric endoscopy biopsy specimens from 69 sequential patients selected on the basis of a dense mucosal lymphoid infiltrate associated with H pylori infection. Histologic evidence of MALT lymphoma was identified in 13 cases, 9 of which showed PCR-detected monoclonality. In 12 of 13 cases, H pylori was eradicated, and in 11 of 12 cases, histologic regression of the lymphoma followed. PCR evidence of monoclonality disappeared in 6 of 9 originally monoclonal cases. This was synchronous with histologic remission in 1 case, but lagged in the remaining 5 cases by up to 28 months. Two of the 3 of the 9 cases originally monoclonal by PCR that have not shown molecular regression have monoclonal-amplified products 17 and 24 months after negative histology. In 3 cases, the histology of the biopsies was considered indeterminate or discordant. In 1 of these cases, the histologic features were obscured by crush artefact. In a second case, there was molecular evidence of monoclonality in the absence of histologic features suggestive of lymphoma; this persisted after H pylori eradication. An additional single case originally diagnosed as reactive developed a PCR detectable clonal population 29 months after original evaluation in the absence of histologic features of lymphoma but in the presence of persistent H pylori infection. These findings suggest that the histologic assessment of gastric biopsies remains the method of choice for the diagnosis of lymphoma in gastric endoscopic biopsies with a dense mucosal lymphoid infiltrate. PCR provides a useful technique to support the diagnosis if clonal amplification products are found. The significance of PCR detected clonality in the absence of histologic evidence of lymphoma in uncertain but may represent a stage of tumor progression/regression when the clonal population is insufficient to be detected by conventional histology. This is supported by the evidence that PCR-detectable monoclonality can persist after treatment and the disappearance of histologically detectable lymphoma.

Adolescent↗

The capacity to accumulate cyclic AMP in the preoptic-anterior hypothalamic area of the rat is affected by the exposition to low ambient temperature and the subsequent recovery.

The accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) was measured in the preopticanterior hypothalamic area, the cerebral cortex, and the hippocampus of rats exposed to different ambient temperatures: (1) 23 +/- 0.5 degrees C, for 53 h +/- 20 min (control); (2) -10 +/- 1 degrees C, for 53 h +/- 20 min (exposure to low ambient temperature); (3) -10 degrees C for 48 h and 23 degrees C for the following 5 h +/- 20 min (recovery). The capacity to accumulate cAMP was tested by subjecting animals to acute hypoxia, a stimulus which is known to induce a large increase in brain cAMP concentration. In the control condition, hypoxic stimulation increases cAMP concentration in all the brain regions studied. In contrast, during the exposure to low ambient temperature, whilst both the cerebral cortex and the hippocampus show the same levels of accumulation found in the control condition, cAMP accumulation is reduced in the preoptic-anterior hypothalamic area. However, during the first few hours of the recovery period, the preoptic-anterior hypothalamic area is able to reattain the capacity for cAMP accumulation observed in the control condition.

Animals↗

Lymphoepithelial cyst of the pancreas. Report of two cases and review of the literature.

CONCLUSION: Lymphoepithelial cyst of the pancreas (LC) is a very rare benign lesion and preoperative diagnosis is difficult. Conservative surgery seems to be the appropriate therapy in symptomatic patients or when a precise preoperative diagnosis is not achieved. The benign behavior of all reported cases suggests that the asymptomatic patients with a certain morphological preoperative diagnosis might be clinically followed up. The histogenesis of LC remains to be elucidated. BACKGROUND: LC of the pancreas is a cyst that is histologically characterized by a fibrous tissue, a lymphoid component and a lining squamous epithelium. METHODS: Clinical and pathological findings of two personal cases are reported with review of the literature. RESULTS: A 56-yr-old man, complaining of epigastric pain, and a 47-yr-old man, with a history of alcohol abuse, were admitted to hospital. In both cases the lesion was detected with abdominal ultrasound but a certain diagnosis was obtained only after histological examination of the resected cysts.

Follow-Up Studies↗

Gonadal function and response to growth hormone (GH) in boys with isolated GH deficiency and to GH and gonadotropins in boys with multiple pituitary hormone deficiencies.

OBJECTIVE: [corrected] To evaluate spermatogenesis in patients with isolated GH deficiency and multiple pituitary hormone deficiencies. DESIGN: Treatment of isolated GH-deficient patients with recombinant human GH (weekly dose of 0.7 IU/kg) for 5.3 +/- 0.4 (mean +/- SD) years and cotreatment of multiple pituitary deficient patients with GH at the same dosage for 8.0 +/- 0.4 years and hCG (2,000 IU, three times per week) and hMG (500 IU, two times per week) for 13.7 +/- 1.1 months. SETTING: Endocrine Pediatric Unit. PATIENTS: Eight patients affected by isolated GH deficiency and seven by multiple pituitary hormone deficiencies. MAIN OUTCOME MEASURES: Serum LH, FSH, and T, testicular volume, semen volume, density, count, and motility. RESULTS: Patients with isolated GH deficiency completed their pubertal development in 19.0 +/- 3.5 months and patients with multiple pituitary hormone deficiencies in 13.7 +/- 1.1 months. At the end of puberty, the two groups of patients had similar testicular volume, penis size, sperm concentration, motility, and morphology, although T levels and seminal volume were lower in isolated GH-deficient patients than in multiple pituitary deficient patients. CONCLUSIONS: The two groups of patients, treated specifically for their identified hormonal deficiencies, in the end had similar satisfactory reproductive results.

Adolescent↗

Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis.

OBJECTIVES: We studied growth rate, bone density, and bone metabolism in patients affected by type I osteogenesis imperfecta (OI) with quantitative defect in type I collagen synthesis during treatment with human growth hormone (hGH), being aware of its collagen-stimulating synthesis activity in vitro. STUDY DESIGN: Fourteen patients (6 boys; ages 4.8 to 10.8 years) were studied. Any structural alteration in the collagen chains was excluded, and reduced production of structurally normal type I collagen (increase in type III/type I collagen; reduction in the messenger ribonucleic acid alpha 1 (I)/ alpha 2 (I) ratio) was demonstrated. The patients were divided into two groups comparable in sex, age, height, and clinical severity of OI; seven patients (three boys) were treated for 12 months with hGH at a dosage of 0.2 mg/kg per week (0.6 IU/kg per week), in six injections subcutaneously, and seven were followed as control subjects. Auxologic data were measured every 3 months, and bone age was determined at the start, after 1 year of treatment, and 1 year after its completion. Every 3 months, serum insulin-like growth factor type I, osteocalcin, carboxyterminal propeptide of type I procollagen, alkaline phosphatase, calcium, and phosphorus levels and urinary hydroxyproline and calcium levels were determined. Bone mass measurements were carried out at the start of the study in all patients and repeated after 12 months in treated patients at the lumbar spine by dual-energy x-ray absorptiometry and by anteroposterior (second, third, and fourth lumbar vertebrae) and lateral (third lumbar vertebra) scan. Results were expressed as areal (anteroposterior and lateral) bone density (in milligrams per square centimeter) and as calculated true density (in milligrams per cubic centimeter). RESULTS: After 12 months, linear growth velocity in treated patients increased significantly in comparison with the pretreatment period (from 3.57 +/- 0.55 to 6.04 +/- 0.69 cm/yr; p < 0.05) and with the untreated group (p < 0.05). Bone age did not advance faster than chronologic age. The fracture index per year was low before treatment, and during therapy no patient had any fractures. Serum osteocalcin levels were statistically lower than in control subjects before treatment and increased significantly after 12 months (3.3 +/- 1.0 vs 2.1 +/- 0.9 nmol/L; p < 0.05). Serum levels of carboxyterminal propeptide of type I procollagen were significantly lower than normal values before treatment (164.6 +/- 46.7 vs 310.3 +/- 97.6 ng/ml; p < 0.05) and rose, but not significantly, during and after treatment. Before therapy, patients with OI had significantly lower lumbar anteroposterior, lateral, and calculated true bone density than the normal population of the same sex compared for both age and height. After hGH treatment, bone density increased significantly in the lumbar spine, in anteroposterior and lateral scans (+2.6 +/- 2.5% and +9.8% +/- 14.0%, respectively; p < 0.05). CONCLUSIONS: From our results, we conclude that hGH treatment in moderate OI does not increase the fracture risk in treated patients in the short term, significantly increases the rate of linear growth velocity, and increases bone turnover and mineral content in trabecular bone at the lumber spine.

Alkaline Phosphatase↗

Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables.

Prediction for malignancy of pancreatic endocrine tumors (PET) is often a formidable challenge for the pathologist. The authors evaluated the role of the proliferative activity and progesterone receptor protein (PgRP) in predicting prognosis and survival of PET. Twenty-three functioning (FT) and 31 nonfunctioning tumors (NFT) were evaluated for mitotic activity and immunostaining for Ki-67 antigen, proliferating cell nuclear antigen (PCNA), and progesterone receptor protein (PgRP) on paraffin sections. The results were expressed as a percentage (index) of immunoreactive or mitosing cells. All 54 cases showed immunostaining for Ki-67 and PCNA, and valuable mitotic index, whereas only a fraction of tumors (25 of 54 cases) exhibited PgRP expression. Ki-67 and PCNA indexes correlated strongly between themselves and to mitotic index, whereas an inverse relationship was observed between cell proliferation and PgRP status in both FT and NFT. Although univariate analysis showed that Ki-67, PCNA, mitotic and PgRP indexes, stage, immunoreactivity for hormones other than insulin, diameter, and nonfunctioning type of tumor were statistically correlated to survival, Cox's regression method let only Ki-67 index emerge as an independent predictor of survival using a cutoff value of 5% in both FT and NFT.

Adenoma, Islet Cell↗

Carcinoma-like signet-ring cells in gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

We noticed the presence of epithelial signet-ring cells (SRCs) in a proportion of primary gastric B-cell lymphomas, and in some endoscopic biopsies we found it difficult to decide whether they represented an associated carcinoma. To evaluate the frequency and nature of this phenomenon, we reviewed 108 stomachs resected for primary lymphoma, including 70 mucosa-associated lymphoid tissue (MALT) and 38 non-MALT lymphomas. We found SRCs, either isolated or grouped in clusters, in 26 of 70 MALT lymphomas. The SRCs were always localized in the superficial portion of the lamina propria and associated exclusively with lymphomatous areas. Isolated and scarce SRCs were also found in four of 22 cases of polyclonal atypical lymphoid hyperplasia. Our data suggests that SRCs occurring in gastric MALT lymphomas represent a particular type of LEL in which the foveolar cells disaggregated by the lymphomatous infiltration acquire a globoid, signet-ring appearance. These "foveolar" LELs are found in 37% of MALT lymphomas and are usually associated with the more classic and constant "neck" LELs, which are localized between the foveolae and mucopeptic glands. An awareness of the existence of the foveolar LEL may help avoid overdiagnosis of SRC carcinoma on gastric endoscopic biopsies.

Adult↗