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Biomedical subjects

Stefano M M Basso

Publications and source records attributed to Stefano M M Basso.

12 recordsLinked to original sources

Isolated hepatocytes versus hepatocyte spheroids: in vitro culture of rat hepatocytes.

The use of hepatocytes that express liver-specific functions to develop an artificial liver is promising. Unfortunately, the loss of specialized liver functions (dedifferentiation) is still a major problem. Different techniques, such as collagen entrapment, spherical multicellular aggregates (spheroids), and coculture of hepatocytes with extracellular matrix, have been used to improve the performance of hepatocytes in culture. The aim of this study was to compare two different models of hepatocyte isolation in culture: isolated hepatocytes (G1) and hepatocyte spheroids (60% hepatocytes, 40% nonparenchymal cells, and extracellular matrix) (G2). To test functional activity of hepatocytes, both synthetic and metabolic, production of albumin and benzodiazepine transformation into metabolites was tested. G2 showed a high albumin secretion, while a decrease after 15 days of culture in G1 was noted. Diazepam metabolites were higher in G2 than in G1 in all samples, but had statistical significance at days 14 and 21 (p < 0.01). The glycogen content, after 30 days of culture, was very low in G1 (14.2 +/- 4.4%), while in G2 it was 72.1 +/- 2.6% (p < 0.01). Our study confirms the effectiveness of a culture technique with extracellular matrix and nonparenchymal cells. Maintenance of a prolonged functional activity has been related to restoration of cell polarity and close cell-to-cell contact. We showed that isolated hepatocytes maintain their functional activity for a period significantly reduced, when compared to the hepatocyte spheroids. We confirmed the role of extracellular matrix as a crucial component to promote hepatocyte homeostasis, and the close link between cellular architecture and tissue-specific functions.

Animals↗

Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature.

The long-term surgical cure rate of patients with primary aldosteronism varies widely, and causes of persistent hypertension are not completely established. We reviewed retrospectively charts from 98 patients (range, 19-70 years old) with aldosterone-producing adenomas who underwent unilateral adrenalectomy. At a median follow-up of 81 months (range, 18-186 months), the mean blood pressure values improved in 95 out of 98 (96.9%) patients, although hypertension was cured only in 71 out of 98 (72.4%) patients. Multivariate analysis using a logistic regression model adjusted for duration of follow-up showed that only age of the patients and duration of the disease independently correlated with unresolved hypertension. The cumulative odds ratio (OR), obtained using the logistic regression function, was 5.38 (95% CI 1.78-16.22), and the OR of single variables were 1.32 (95% CI 0.36-19.83) and 4.56 (95% CI 1.41-14.78), respectively. By using discriminant analysis to derive a classification function for the prediction of unresolved hypertension, a maximum predictive power of 75 per cent was achieved. In conclusion, in patients with an aldosterone-producing adenoma undergoing surgery, the combination of age and duration of hypertension gave the best predictive power of a linear classification function and represented the main independent risk factors affecting hypertension cure rate.

Adrenal Cortex Neoplasms↗

Serum tumor markers in patients with breast cancer.

Several serum tumor markers have been investigated in patients with breast cancer for assessing outcome, predicting recurrence and monitoring the therapeutic response. There is a general consensus concerning their limited application in diagnosing malignancy; however, serum tumor markers can be considered for the early detection of recurrence. The most effective markers for this indication are cancer antigens (CA)15-3 and 27.29, and c-erbB-2, although their efficacy in establishing disease progression has not been determined to date. In terms of evaluating prognosis and predicting response to therapy, only the expression of c-erbB-2 has clinical evidence. To conclude, at present, no serum tumor marker is cost effective, and none can be used with confidence in the decision making regarding breast cancer patients.

Antigens, Tumor-Associated, Carbohydrate↗

Usefulness of ultrasound scissors in reducing serous drainage after axillary dissection for breast cancer: a prospective randomized clinical study.

Axillary dissection is usually associated with prolonged serous drainage that may result in several complications. We analyzed whether the use of ultrasound scissors may decrease the total amount of drainage from the axilla (AD) in patients requiring curative surgery for breast cancer. Seventy-six women (median age, 56 years; range, 32-73 years) with confirmed pT1-3, N0-1 breast cancer were prospectively randomly assigned to undergo mastectomy or breast-conserving surgery with axillary dissection by either using (group A) or not using (group B) ultrasound scissors. Overall, there was a linear relationship (P < 0.05) between AD and both total number of the removed nodes and body mass index, whereas no correlation (P = NS) was found with age and size of the tumor. Total AD was higher (492 +/- 153 vs. 408 +/- 136 mL, P = 0.013) in group B, whereas the postoperative hospital stay was shorter (2.4 +/- 0.6 vs. 2.7 +/- 0.7 days, P = NS) in group A. The three-way analysis of covariance using the number of total removed nodes as covariate showed that lymph node status, type of operation, and technique for axillary dissection significantly (P < 0.05) correlated with AD. In conclusion, our initial study shows that the use of ultrasound scissors significantly reduced total AD in patients requiring axillary dissection and may shorten hospital stay.

Adult↗

Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix.

A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.

Animals↗

Prevalence of breast cancer in women with breast complaints. Retrospective analysis in a population of symptomatic patients.

BACKGROUND: The aim of the present study was to analyze whether any correlation exists between breast complaints and the risk of having or developing breast cancer (BC) in a population of self-selected women. PATIENTS AND METHODS: A series of 2,561 patients was reviewed. Three age-groups were sorted out: Group A (40 years old or younger, 45.9%), Group B (41-55 years, 27.8%), and Group C (> 55 years, 26.3%). Breast pain was most common (61.0%) in Group A, and breast lump in Group C (87.8%). RESULTS: BC was found in 271 (10.6%) patients. Breast pain was more frequent in patients without cancer with respect to patients with BC, both in Group B (45.8% vs. 27.9%; p = 0.039) and in Group C (9.2% vs. 1.7%; p = 0.003), but no correlation (p = NS) between BC and breast lump or nipple discharge was found in any Group. Over a median follow-up of 74 months (range 23-146 months). BC arose in 10 (0.44%) patients. CONCLUSION: The majority of the women with breast complaints did not have BC, and their risk of cancer onset was not dissimilar to that reported for the general population.

Adult↗

Relationship between tumor markers CEA and CA 15-3, TNM staging, estrogen receptor rate and MIB-1 index in patients with pT1-2 breast cancer.

BACKGROUND: The aim of this study was to analyze whether a correlation exists between preoperative serum tumor markers (STM) CEA and CA 15-3, age of the patients, TNM staging, hormone receptor (ER, PgR) status, and MIB-1 proliferation index in patients who underwent surgery for primary breast cancer (BC). PATIENTS AND METHODS: Data regarding a series of 255 consecutive women (median age 60 years, range 30-85) with pT1-2 BC were reviewed, while patients with confirmed pT3-4 BC were excluded. All patients underwent preoperative CEA and CA 15-3 serum levels measurement, and the removed tissue was routinely processed for the detection of ER, PgR, and MIB1 index. RESULTS: Serum CEA and CA 15-3 measurements were above the cut-off in 44 (17.2%) and 75 (29.0%) patients, respectively, and the overall sensitivity of STM was 37.6%. A strong correlation between ER and PgR rate (R=0.77) was found. There was no relationship (p=NS) between age of the patients, size (R=0.08), MIB-1 index (R=0.11), and both ER (R=0.01) and PgR (R=0.03) rate. No linear correlation was found between both CEA and CA15-3 and the other variables, except for CA 15-3 vs. tumor size, which showed a mild (R=0.57) linear relationship. Tumor size, ER rate, and the number of positive nodes were significantly (p <0.01) different between patients with CA 15-3 values normal and above the cut-off. Comparing the subgroup of patients with CA 15-3 above the cut-off and CEA within normal values (Group 1) versus patients with CA 15-3 within normal values and CEA above the cut-off (Group 2), a significant difference was found in the tumor size (Group 1: 28.3+/-9 mm; Group 2: 17.9+/-7.5 mm; p<0.0001) and in the number of positive nodes (Group 1: 2.2+/-3.3; Group 2: 0.5+/-1.5; p<0.01). Finally, CA 15-3, but not CEA, showed a significant correlation with the tumor grading (p<0.0001). CONCLUSION: In patients with BC, STM correlate exclusively with the size of the tumor. Both have low sensitivity and no significant relationship with other prognostic factors. Thus, preoperative serum tumor markers measurements are of little value, especially in patients with early-stage BC, and are not useful in the therapeutic decision-making of patients with BC.

Adult↗

Role and cost-effectiveness of adrenal imaging and image-guided FNA cytology in the management of incidentally discovered adrenal tumours.

Incidentally discovered adrenal masses (incidentalomas) are relatively frequent and unsuspected incidentalomas (AI) of more than 1 cm in size may be found in 1-5% of patients who have undergone abdominal or chest computed tomography (CT)-scan for unrelated reasons. Once an AI is detected, the two major questions are whether the patient has biochemical evidence of adrenal hyperfunction, and whether the mass is an adrenal metastasis or a malignant adrenal tumour. In most cases (>90%) AI are non-functioning, with a low (<10%) risk of being malignant, and an estimated cumulative risk of malignant transformation of less than 1:1000. However, all patients with non-functioning AI usually undergo several imaging studies, but the impact of imaging techniques and image-guided fine-needle aspiration cytology (FNAC) on the cost-effectiveness in the management of patients is not well established. A single test for disease probabilities is not always more cost-effective than two-test approaches and it has been shown that the cumulative sensitivity and accuracy of both FNAC + magnetic resonance imaging (MRI) and FNAC + norcholesterol adrenal scintigraphy reach 100%, at a similar cost-to-accuracy ratio (7.5 vs. 7.0), whilst the strategy CT-scan + MRI together is less sensitive at a lower cost-to-accuracy ratio. In conclusion, the significance of AI, as well as the optimal management approach to treatment, is still under discussion. However, image-guided FNAC in conjunction with MRI as the exclusive imaging test has the major role and cost-effectiveness in the management of patients with AL, and should be considered the strategy of choice in distinguishing between benign and malignant non-functioning adrenal masses of more than 2 cm in diameter.

Adrenal Gland Neoplasms↗

Immunomodulation techniques in a pig-to-rat model of xenoislet transplantation to prolong graft survival.

Pancreas allotransplantation can restore full metabolic control in patients with type I diabetes, but has several limitations. Pancreatic islet xenotransplantation (XiTx) is considered a reliable alternative. The aim of this study was to evaluate the effect of gamma-irradiation and a highly selective inducible nitric oxide synthase inhibitor (AE-ITU) in a model of pig-to-rat XiTx. Thirty-five female rats were made diabetic by intraperitoneal injection of streptozocin. Pig pancreatic islets were obtained by enzymatic digestion followed by purification on Ficoll gradients. Approximately 4000 purified pig islet equivalents were placed under the left kidney capsule of the recipient rats. The rats were observed for 15 days and divided into five Groups (G): GI: controls, diabetic rats with no treatment; G2: XiTx; G3: XiTx after gamma-irradiation (20 Gy); G4: XiTx and administration of AE-ITU; G5: XiTx after gamma-irradiation and AE-ITU. Graft survival was defined as the maintenance of the glucose levels at less than 11 mmol/l and a normal response to i.v. glucose challenge. The graft survivals in Groups 2, 3, 4 and 5 were 4.1 +/- 1.8, 7.6 +/- 2.1, 7.6 +/- 2.4, and 10.9 +/- 2.3 days, respectively. The graft survival of G2 was significantly (p < 0.05) lower than the other groups, and the graft survival of G5 was significantly higher in respect of both G3 and G4 (log-rank test: p = 0.007). In conclusion, the combination of AE-ITU (to reduce the early inflammatory damage) and gamma-irradiation (to reduce the immunogenicity of the islets) may be considered an interesting option to prolong the euglycaemic period after XiTx.

Animals↗

Parathyroid cancer: etiology, clinical presentation and treatment.

Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of patients with primary hyperparathyroidism (HPT), but a relatively higher incidence has been reported in Italy and Japan. The etiology of the tumour remains unclear, but molecular analysis studies have hypothesised the involvement of mutations of several genes in the pathogenesis of PC, including the oncogene cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53 tumour suppressor gene. The clinical presentation of patients with PC is mainly related to the increased secretion of PTH rather than to the tumour burden. The pre-operative diagnosis of malignancy is very difficult to obtain, and, thus, intra-operative recognition of PC is mandatory. However, reliable signs of malignancy are rarely detectable. Probably, only vascular invasion, that correlates with tumour recurrence and metastases, should be considered useful in confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used to aid in the definitive diagnosis. The en bloc resection of the tumour, together with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding any capsular rupture of the mass, represents the gold standard of surgical treatment of patients. Although the PC has traditionally been considered as a radioresistant tumour, there are some retrospective data holding a possible benefit from post-operative irradiation. No cytotoxic regimen with proven efficacy is currently available for patients with PC, but since hypercalcemia is ultimately the most frequent cause of death, several studies have suggested the usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate), calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey reports an overall five- and ten-year survival rate of 85% and 49%, respectively. However, it is very difficult to predict the clinical behaviour of patients with PC and probably the ultimate prognosis depends on successful resection of the tumour at the initial surgery.

Humans↗