COMPOSITE POLYMER-COATED MINERAL SCAFFOLDS FOR BONE REGENERATION: FROM MATERIAL CHARACTERIZATION TO HUMAN STUDIES.

Bovine bone xenografts, made of hydroxyapatite (HA), were coated with poly(L-lactide-co-ε- caprolactone) (PLCL) and RGD-containing collagen fragments in order to increase mechanical properties, hydrophilicity, cell adhesion and osteogenicity. In vitro the scaffold microstructure was investigated with Environmental Scanning Electronic Microscopy (ESEM) analysis and micro tomography, while mechanical properties were investigated by means compression tests. In addition, cell attachment and growth within the three-dimensional scaffold inner structure were validated using human osteosarcoma cell lines (SAOS-2 and MG-63). Standard ISO in vivo biocompatibility studies were carried out on model animals, while bone regenerations in humans were performed to assess the efficacy of the product. All results from in vitro to in vivo investigations are here reported, underlining that this scaffold promotes bone regeneration and has good clinical outcome.

Parotid metastasis of renal cell carcinoma, mimicking primary clear cell oncocytoma: report of a case and brief review of the literature.

Malignancies of the parotid gland are relatively uncommon, accounting for only 3-6% of all head and neck cancers. Most of them are primary neoplasms, metastases are uncommon. Renal cell carcinoma (RCC) represents 3% of adult malignancies, the clear cell type comprises up to 70% of all RCC. RCC has an unpredictable behavior and the unique potential to metastasize to nearly every organ in the body. Though not as frequent, metastatic RCC to the head and neck has been identified in the thyroid, salivary glands, skull base, sinuses, pharynx, tonsils, tongue, lip and skin. Metastasis to the parotid gland is very rare. Here, we report the case of a clear cell type RCC metastatic to the parotid gland and mimicking a primary clear cell oncocytoma. Differential diagnoses and a brief review of the literature are added.

Gastric metastasis from cervix carcer: a case report.

Gastric metastasis by solid tumor cancer is a rare event. Concomitant metastases to other organs are frequent, so that this condition is often associated to a poor prognosis. Upper gastrointestinal bleeding and anemia are the most common presenting symptoms. We present the case of a 81 years old women previously treated for cervix carcinoma showing later a stomach metastasis. The patient is alive and disease free 39 months after salvage gastrectomy. A radical surgery in selected patients could be useful for symptom palliation and prolonged survival.

Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study.

Among 843 cases of breast cancer, p53 oncoprotein was detected by the monoclonal antibody (MoAb) Pab-1801 in only 13%. Low-grade carcinomas (tubular, mucinous, papillary, and invasive cribriform types) did not express p53 protein, but it was observed in 4.2% of infiltrating lobular carcinomas (6 of 140 cases) and 50% of pure medullary carcinomas (5 of 10 cases). In intermediate-grade neoplasms, no correlation was seen between p53 status and other putative determinants of a poor prognosis. The latter included high tumor stage, lymph nodal involvement, high growth fraction (as determined by labeling with the MoAb Ki-67), negative results for estrogen receptor (ER) and progesterone receptor (PR) proteins, and amplification of the c-erbB-2 oncogene product in the neoplastic cells. Ninety-nine of 640 (15.5%) cases of high-grade, invasive, ductal breast carcinoma, however, showed an inverse relationship between expression of p53 protein and positive results for ER/PR proteins and a direct correlation with large tumor size, Ki-67-determined growth fraction, and amplification of c-erbB-2 oncopeptide. All of the latter associations were highly significant statistically. The authors conclude that mutant p53 protein may serve a prognostic role in a subset of cases of invasive ductal mammary carcinoma.

Epidermal growth factor receptor immunohistochemistry in different histological types of infiltrating breast carcinoma.

AIMS: To determine the immunohistochemical expression of epidermal growth factor receptor (EGF-R) in high grade, intermediate, and low grade tumours. METHODS: Specimens from 931 breast carcinomas were partly formalin fixed and paraffin wax embedded, to classify cases, and partly frozen in liquid nitrogen, cryostat sectioned, and immunostained using two monoclonal antibodies from clone 455 and 528 to demonstrate EGF-R positive cells. An avidin-biotin complex and peroxidase method was used after incubation with biotinylated anti-mouse antibody; colour was developed using a diaiminobenzidine solution. RESULTS: Low grade carcinomas seldom expressed EGF-R (n = 3) compared with 106 high grade infiltrating ductal carcinomas: EGF-R positive cases were much less common in infiltrating lobular than in infiltrating ductal carcinoma. Medullary carcinomas did not differ from infiltrating ductal carcinomas. CONCLUSIONS: The very low incidence of EGF-R positive cases in the "special type" group of breast carcinomas with a good prognosis is in line with the absence of the homologous c-erbB-2 and p53 oncoproteins, and the rarity of highly proliferating and oestrogen/progesterone negative cases. EGF-R expression in infiltrating lobular carcinoma was in keeping with the intermediate behaviour of this kind of tumour. EGF-R expression in cases of pure medullary carcinoma is the same as that of high grade tumours.

Scarff-bloom-richardson histoprognostic grading correlates with the immunohistochemical expressions of genomic alterations in infiltrating ductal carcinomas (nos) of the breast.

The Scarff-Bloom-Richardson (SBR) multiparametric histological grading has been correlated with the immunohistochemical expression of EGF-R, c-erbB-2 and p53 oncoproteins, with the growth fraction (Ki67 antibody) and with the receptor status (ER, PgR) in 365 infiltrating ductal carcinomas of the breast (IDC-NOS). Specimens of carcinomas after surgery were sectioned and a section of each lesion was formalin-fixed and paraffin-embedded, and stained by hematoxylin-eosin in order to classify and grade cases. Another section was liquid nitrogen frozen, cryostatcut and immunostained using monoclonal antibodies against EGF-R (455 and 528 clones), c-erbB-2 (3B5 clone), p53 (Pab 1801 clone) and Ki67 antigen. An ABC-peroxidase was used after incubation with biotinylated antimouse antibody. Colour was developed using a DAB solution. ER-ICA and PgR-ICA Kits (Abbott) served to detect the hormonal receptor status. A significant direct correlation between SBR and the immuno-histochemical markers (EGF-R, c-erbB-2, p53, Ki67 growth fraction) was found. An inverse relationship of grade to ER and a weaker one to PgR was evident. An increasing histological grade was found parallel with the progressive appearance of one, two or three immunohistochemical markers in the same tumour.

Immunohistochemical distribution of mucinous-like carcinoma associated antigen (MCA) in breast and non-breast cancer: comparison with other biological parameters.

The present study reports the immunohistochemical reactivity of the monoclonal antibody b-12 (MAb b-12) with malignant human tissues. 173 neoplastic tissues were tested: MAb b-12 stained all breast carcinomas independently of their histology, with different patterns within the various type of cancer. Some other carcinomas (stomach, bowel, ovary, lung, endometrium), were also reactive even if the fraction of positive cells was lower. A comparison between the histological localization of MCA and that of CEA was performed; anti-CEA antibodies stained the cancer tissues with different reactivity and showed different percentages of positivity. MCA expression was also compared with other biological parameters such as the presence of estrogen receptors (ER), progesterone receptors (PgR), epithelial growth factor receptors (EGF-R), and oncoprotein p-53 which is encoded by the oncogene N-myc. The proliferative activity was also evaluated by measuring the growth fraction (GF) using the antibody Ki67. Any correlation was demonstrated between MCA and these parameters except for growth fraction as revealed by Ki67 antibody.

[Angioimmunoblastic lymphadenopathy. 2 case reports]. / Linfoadenopatia angioimmunoblastica. Osservazioni su due casi.

Of the two cases of angioimmunoblastic lymphadenopathy described, one had arisen after infection by a non-A non-B hepatitis virus and HIV. The possible cause of the immunological changes that triggered the disease are discussed as are its clinical picture, course and treatment. In the first case a 6 month remission period was obtained after a short cycle of cortisone treatment, a second remission followed treatment with CVP. Unfortunately the bronchial pneumonia that followed the second cycle proved fatal. The second case featured recurring infections of the middle ear and respiratory tract causing the patient's death about a year after the onset of the disease.

Spontaneous expulsion of decidualized pseudopolyps in pregnant women with uterine malformation.

Two cases concerning expulsion of decidualized polyps in early pregnancy associated with uterine malformation are described. The authors discuss the differential diagnosis between the expulsion of cervical polyps during pregnancy and the ectopic pregnancy associated with polyposis. They suggest that a spontaneous expulsion of polyps or pseudopolyps during early pregnancy may be a sign of the presence of uterine malformation.

[Multiple jejuno-ileal metastasis of malignant schwannoma from the leg. Report of a case presenting anemia symptoms and review of the literature]. / Metastasi multiple digiuno-ileali da schwannoma maligno dell'arto inferiore. Descrizione di un caso presentante sintomatologia da anemizzazione e revisione della letteratura.

A case of jejunal-ileal metastasis from a left leg malignant schwannoma in a 73 year old woman is described. The patient was affected by progressive anemization without signs of bleeding. A colonoscopy performed during hospitalization revealed an ulcerative lesion at the ileo-colonic junction which at histologic examination was suspected for sarcomatous proliferation arising in peripheral nerve tissue. At operation multiple ileal resections of numerous polypoid formations were performed. Histological examination of polypoid masses revealed the presence of malignant proliferation of spindle cells consistent with a malignant schwannoma. Differential diagnoses are discussed with a review of the literature.

[Malignant schwannoma of the mesentery. Presentation of a clinical case and clinical and histopathological considerations]. / Schwannoma maligno del mesentere. Presentazione di un caso clinico e considerazioni cliniche ed istopatologiche.

A case of malignant schwannoma of the mesentery is described which was treated with radical surgery. The natural history, diagnosis and therapy of neoplasias of the mesentery are discussed.

[Tumor markers in colorectal neoplasm pathology: our experience of the diagnostic and prognostic importance of CEA antigen]. / I markers tumorali nella patologia neoplastica del colon-retto: nostra esperienza sul significato diagnostico e prognostico dell'antigene CEA.

It is well known that the presence of a tumour may be accompanied by production and release into the serum of a substantial number of protein and/or hormonal substances. Only relatively recently, however, have investigators begun to identify which of these supposed markers may actually be clinically useful. A picture is thus gradually emerging of a number of markers (in actual fact only very few) which are already clinically useful, as well as others which are clinically promising and numerous markers which require more thorough clinical evaluation. Prominent among those already in clinical use is undoubtedly CEA. Carcinoembryonic antigen (CEA) is a glycoprotein isolated for the first time by Gold and Friedman in 1965. Very recently, sensitive radioimmune and immuno-enzymatic assays have made it possible to determine serum levels lower than 3 ng/ml. Though high plasma levels of CEA do not indicate the presence of a tumour with certainty, very high levels are, however, to some extent indicative of its existence. In view of the fact that CEA possesses neither the sensitivity nor the specificity to be able to diagnose the presence or otherwise of a tumour, its use is generally recommended when formulating a prognosis or for monitoring surgical and/or medical therapy (chemotherapy and radiotherapy) in asymptomatic patients. We therefore carried out tests in 357 patients on file as having undergone surgery for neoplasms of the colon-rectum-anus, monitored in our colostomy outpatients' department, which was started up in 1980. 188 of these patients had already been submitted to CEA assay prior to surgery. The data are analyzed in relation to the site, stage and grade of differentiation of the neoplasm, the supposed radicality of the operation and the period of follow-up in these patients.

Different behaviour of 19S thyroglobulin extracted from normal thyroid, simple goitre and toxic goitre in polyacrylamide slab gel isoelectric focusing.

19S thyroglobulin (19S TG) was isolated from normal thyroids, simple goitres and one case of toxic goitre (Graves' disease). With isoelectric focusing on polyacrylamide gel slabs (pH 4--6) several bands for each specimen were detected. The migration patterns of the toxic goitre 19S TG were clearly different from the patterns of normal 19S TG and simple goitre 19S TG.

Immunohistochemical study of hepatic and enteric structures in testicular endodermal sinus tumors.

Features of hepatic and enteric tissue have been detected in serial sections of 2 out of 6 endodermal sinus tumors (EST) and embryonal carcinomas of the testis showing endodermal sinus areas. Hepatic nests, which appeared as tubules, cords and giant multinucleated cells, were PAS-positive as well as immunoreactive for alphafetoprotein (AFP) and cytokeratin (CK). Enteric tubules were found within EST areas and were characterized by their lack of cell atypism. The presence of diffuse PAS-, AFP- and CK-reactivity in cytoplasm, together with a brush border or an apical staining for CEA, were quite distinctive. EST showed a potential for both intra- and extraembryonal endodermic development and may be interpreted as a monophyletic teratoma.

Bioequivalence of endogenous substances facing homeostatic equilibria: an example with potassium.

Oral administration of endogenous substances in most cases results in negligible net increases in baseline plasma concentrations, associated with high variability. This poses the problem of their bioequivalence. Using the data obtained from a bioequivalence investigation of potassium aspartate (test vs reference formulation), the authors demonstrate the inconsistency of bioequivalence based on plasma concentrations and standard methods. Potassium aspartate was given orally at a dose of 15.8 mmoles to 12 healthy volunteers as test and reference values according to a two-period, two-formulation, two-sequence design. The individual net values of the area under the curve of plasma concentration (AUC) and cumulative urinary excretion (CUE), both obtained with the test formulation as post-dose minus baseline, were multiplied by 2, 3, 4, 5 and 6 and added to the baseline in order to simulate the administration of increasing single doses of the test, assuming dose-linear kinetics. Data generated with the test formulation were compared with original data of the reference according to 90% confidence intervals. With AUC, bioequivalence of test and reference formulations was demonstrated with 1 : 1, 2 : 1 and 3 : 1 test to reference dose ratios. With CUE only the 1 : 1 dose ratio comparison produced bioequivalence. The authors conclude that bioequivalence of endogenous substances conducted with standard procedures in most cases is a useless exercise. With potassium and more generally with drugs cleared via urine, urinary excretion would reflect the extent of absorption more faithfully than AUC.

Relationships between epidermal growth factor receptor (EGF-R) and other predictors of prognosis in breast carcinomas. An immunohistochemical study.

The importance of epidermal growth factor receptor (EGF-R) as an immunohistochemical factor of prognosis has been investigated in 820 cases of breast carcinoma irrespective of subtyping. An immunohistochemical membrane positivity for EGF-R (Ab1, clone 455 and Ab2, clone 528, Oncogene Science Manhasset NY, USA, ABC-peroxidase method) has been observed in neoplastic cells of 131/820 breast carcinomas (15.9%); the percentage is lower than those of the majority of reported series, but the total number of cases is higher. A significant inverse relationship between EGF-R and estrogen/progesterone receptors has been found (ER-ICA, PgR-ICA, Abbott, PAP-method). Highly proliferating Ki67 positive (> = 20% stained nuclei-Dakopatts Denmark) and oncoprotein p53 (Pab 1801 clone, Oncogene Science) positive carcinomas are more frequently EGF-R positive (p < 0.001). No relationship exists between EGF-R expression, c-erbB-2 (3B5 clone, Oncogene Science) expression, tumor size and lymph node status. The detection of EGF-R may be a useful addition to other immunohistochemical prognosticators, but it must be related with clinical outcome in further studies.

Low, intermediate and high grade breast carcinomas as determined by histotyping, immunohistochemical prognosticators and histological grading.

Low grade breast cancers i.e. mucinous (17 cases--3.2%), tubular (7 cases--1.3%) and invasive cribriform carcinomas (3 cases--0.5%) have been identified within a series of 524 breast cancers only by histotyping in hematoxylin-eosin stained sections: the reactivities of immunohistochemical prognosticators as estrogen/progesterone receptors (ER, PgR), growth fraction (GF: Ki67), p53 and c-erbB-2 oncoproteins are in agreement with clinical behaviours. Invasive papillary carcinomas (9 cases--1.6%) are not to be considered low grade carcinomas. Intermediate grade cancers are also determined by histotyping. Medullary carcinoma (13 cases--3.4%) has a paradoxical behaviour displaying a favourable clinical prognosis together with high grading and GF, absence of ER, PgR, high p53 and c-erbB-2 values, as compared with invasive ductal carcinomas: an extensive tissue immune response as suggested by a heavy lymphocyte infiltration may explain this behaviour. Invasive lobular carcinoma (62--11.6%) shows an intermediate immunohistochemical pattern, paralleling an intermediate prognosis, when compared with low and high grade carcinomas: ER, PgR and GF positivities are nearly the same as in ductal carcinomas whereas grading, p53 and c-erbB-2 are less expressed. These data are confirmed both for lobular carcinomas as a whole and for all variants of this kind of tumors. Invasive ductal carcinomas (413 cases--79%) may be stratified on three prognostic classes corresponding to histological grading (G1, G2, G3). Significant relationships of grading with all the immunohistochemical prognosticators studied has been observed. It may be concluded that grading is a parameter of paramount importance in this group of tumors.

[The workload in Pathological Anatomy measured on the basis of categories of services]. / I carichi di lavoro in Anatomia Patologica misurati sulla base del nomenclatore di prestazioni.

Workload measurement is one of the most reliable tools in perspective payment systems, to evaluate clerk and technical personnel needs in a Surgical Pathology Department. In 1992 Italian Government began a full-comprehensive modification of financial support in National Health Care System, and during the last four years Public Hospitals and Local Health Units modified their financial organization with the introduction of workload measurement for the personnel needs. We propose a synthetic method for the workload measurement in Surgical Pathology Departments, similar to that proposed for perspective payment of surgical pathology services. The method is reliable and simple representing the full performance to obtain pathological report.

[Biomorphological features of "minimal" carcinomas selected from a series of 2077 breast cancer cases]. / Caratteri biomorfologici dei carcinomi "minimi" selezionati da una serie di 2077 casi di carcinoma mammario.

Two hundred eighty nine pT1a/pT1b (less than < or = 1 cm in diameter) mammary carcinomas were selected from a series of 2077 consecutive cases of breast carcinoma. When compared with carcinomas of a larger size, they were significantly associated with a lower histological grade (SBR), a lower growth fraction (Ki-67 antigen in less than 20% of neoplastic cells) and a lower number of positive cases (more than 10% of neoplastic cells) as far as p53, c-erbB-2 oncoproteins and EGF-R, as detected by immunohistochemical methods, are concerned. Moreover, a significantly higher number of estrogen and progesterone receptors positive cases (more than 10% of positive cells), and a higher frequency of "other" histotypes with a favourable prognosis, was detected. No difference between pT1a and pT1b cases was noted so that "1 cm size" only stratifies a class with a better prognosis. It is possible that small cases, although invasive, did not undergone sufficient mytotic cycles to produce the sequence of genetic changes that characterize the "no return" phase of breast cancer. A 17% of pT1a and pT1b cases displayed lymph node metastases (mean 26 lymph node/case examined): the number is so high that cautions about simple lumpectomies and about sentinel lymphadenectomy, even in cases of small cancers, are necessary, until a larger number of studies will become available.

[Proliferative activity of stage I testicular neoplasms: evaluation by image analysis of immunoreactive MIB-1]. / L'attività proliferativa delle neoplasie del testicolo in stadio I: valutazione mediante analisi di immagine dell'immunoreattività MIB-1.

The proliferative activity has been evaluated in 55 cases of seminoma and 36 cases of non-seminomatous germ cell tumors of the testis (NSGCT) in clinical stage I from patients alive and well within 5 years, by a semi-quantitative image analysis method of determination of the percent MIB-1 positive nuclear areas, using a Leica Quantimet 500+ analyzer. Significant differences of growth fraction have been detected between classical seminomas and seminomas showing more than 3 mitoses/1HPF (anaplastic seminoma)-mean of MIB-1 positivity in classic seminoma 23.8%, versus 43.9% in anaplastic seminoma; confirming this value of cut-off in distinguishing two classes of cases with different growth fractions, but without any difference as far as prognosis is concerned. The non seminoma- germ cell tumours (NSGCT) in toto display a growth fraction significantly higher than that of seminomas (mean value of MIB-1 positivity: 26.3% in seminoma versus 40.4% in NSGCT), but absolute values of positivity as high as those obtained by others by subjective evaluation have not been observed. A higher growth fraction in NSGCT is positively correlated with an embryonal carcinoma component as high as 80% of the tumor mass and/or with vascular invasion, but not with different histotypes. The proliferative activity doesn't stratify subgroups with different prognosis within the two groups of germinal tumours of the testis (seminomas and NSGCT) in our cases of clinical stage I testicular tumours.