Histological findings of the internal inguinal ring in patients having indirect inguinal hernia.

BACKGROUND: Aiming to deepen the understanding of the factors involved in the genesis of groin hernia, this study is focused on identifying the histological changes within the muscle fibers of the internal inguinal ring in patients having indirect inguinal hernia. METHODS: In eight patients with primary or recurrent bilateral indirect inguinal hernia who underwent a Stoppa open posterior inguinal hernia repair, a tissue specimen from the edge of the internal inguinal ring was biopsied and histologically examined. RESULTS: In all of the tissue samples, remarkable degenerative changes such as fibrohyaline degeneration of the muscle fibers, vascular congestion, and phlogistic infiltration through lymphohistiocytary elements was constantly detected. Also, in the patients with recurrent hernia, the key characteristic of the muscular change was that of fibrohyaline and, occasionally, myxoid degeneration of the myocytes. Nerve endings were frequently detected within the muscular structures of the internal inguinal ring. CONCLUSION: The degenerative fibrohyaline alteration, as well as the evidence of phlogistic elements within the examined structures, could represent a reason for a contractile incompetence of the internal inguinal ring. Consequently, the described findings lead the authors to depict this inflammatory degenerative structural weakness of the internal inguinal ring as a possible culprit of indirect inguinal hernia formation.

[Breast cancer less than 1 cm: bio-morphologic characterization with ER, PgR, Ki67, Her-2/Neu, MDV, MAGS, p53, EGF-R]. / Carcinoma della mammella con diametro inferiore ad 1 cm. Caratterizzazione bio-morfologica: ER, PgR, Ki67, Her-2/Neu, MDV, MAGS, p53, EGF-R.

Breast carcinoma is the most common malignant tumour and the main cause of carcinoma death in women. There has been a sharp increase in the detection of breast carcinoma, although mortality is still unvaried. In the last ten years the incidence of breast cancer measuring less than 1 cm, corresponding to pT1a, pT1b in TNM stadiation, has greatly increased. The present study describes the biologic characterisation of small breast carcinomas. The Nottingham/Tenovus Primary Breast Cancer Study stated that tumour size is a significant, independent factor for breast cancer prognosis. Cases were selected among formalin-fixed, paraffin-embedded tissues from 360 ductal breast cancers. In one-half of cases, the tumour was less than 1 cm in diameter, pT1a- pT1b; in the other half the tumour size was greater than 1 cm, but less than 2 cm, pT1c. Histological grading was assessed with the Scarff-Bloom-Richardson method, without Nottingham grade. Immunohistochemical determinations for ER, PgR, Ki-67, Her-2/Neu, CD34, p53, EGFR were done with an automated method. From the above analyses, it was demonstrated that the tumour size is indeed an important prognostic factor, particularly in cases without lymph node metastasis (N0). In particular, we observed significant differences between pT1a-b and pT1c cases, confirming that tumour size is an important criterion for prognostic valuation in ductal breast cancer without lymph node metastasis.

Collagen IV, laminin, fibronectin, vitronectin. Comparative study in basal cell carcinoma. Correlation between basement membrane molecules expression and invasive potential.

AIM: Basal cell carcinoma (BCC) is a malignant carcinoma arising by cells of epidermal basal layer and adnexal epithelium. It appears intimately connected with a stromale component that holds a relevant role for tumour's evolution. It occurs frequently on sun-exposed regions, and is considered as low potential for metastasis, whereas its local invasion, destruction and recurrence are well known. METHODS: Particularly formalin-fixed, paraffin-embedded tissue from 40 cases of BCC, 20 recurring and 20 not recurring, had been studied, with immunohistochemical techniques to value the distribution of intrinsic and extrinsic components of basal membrane. RESULTS: The immunohistochemical examination showed collagen IV and laminin continuous positivity in peripheral cells, seating around neoplastic nests of 62.5% not recurring BCC. The same antigens exhibited discontinuous positivity in cells with non distinguished borders, seating around nests of 85% micronodular recurring BCC. The valuation of fibronectin and vitronectin could have a more significant prognostic value. Fibronectin in fact appeared hyper-expressed in peritumoral stroma of 80% recurring BCC, vitronectin appeared less expressed than normally in peritumoral stroma of 95% recurring BCC. CONCLUSION: A correlation between basal membrane's break and carcinoma's recurrence has been noticed. This shows the utility of other prognostic factors helping the valuation of malignant progression.

CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome.

AIMS: CD1a is a molecule belonging to the highly conserved group of CD1 proteins. Its expression in dendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently, the development of a successful antitumour response. The aim was to investigate the presence of CD1a+ cells in both primary tumours and lymph nodes (LN) of a series of 35 invasive ductal carcinomas by both immunohistochemistry and reverse transcription-polymerase chain reaction. METHODS AND RESULTS: CD1a antigen was more expressed in N0 than N1 breast cancer (P < 0.0001) in both primary lesions and LN metastases and correlated positively and significantly with oestrogen (ER) (P = 0.0025) and progesterone (P = 0.0226) receptor (PR) status, as well as CD4+ and CD8+ T-lymphocyte infiltration. CONCLUSIONS: This is the first report to show a link between CD1a+ mononuclear cells in breast cancer and in paired LN metastases. The positive and significant correlations between the number of CD1a+ cells and positivity of the primary tumour for ER and PR suggest a possible role for CD1a as a prognostic marker for breast cancer, raising the possibility that hormone receptor-positive breast cancer patients may have a better prognosis in the presence of greater dendritic cell infiltration.

Atrial natriuretic peptide and CD34 overexpression in human idiopathic dilated cardiomyopathies.

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause characterized by ventricular chamber enlargement with impaired contractile function. In familial forms of IDCM, mutations of genes coding for cytoskeletal proteins related to force transmission, such as dystrophin, cardiac actin, desmin, and delta-sarcoglycan, have been identified. Here, we report the data of a retrospective investigation carried out to evaluate the expression of atrial natriuretic peptide (ANP), CD34, troponin T and nestin in the myocardium of patients affected with IDCM. Formalin-fixed and paraffin-embedded consecutive tissue sections from the ventricular wall of 10 human normal hearts (NH) following forensic autopsy and 22 IDCM (living explanted hearts) were studied using primary monoclonal antibodies against ANP, CD34, troponin T and nestin by immunohistochemistry. Myocardial fibers were counted independently by three pathologists. Statistics included analysis of variance, log-rank test for Kaplan-Meier analysis, and kappa assessment for intra- and inter-observer variability. ANP and CD34 were significantly overexpressed in IDCM compared to NH (p<0.05). Conversely, troponin T and nestin expression levels did not show significant variation. Inter-observer kappa statistics showed a value of 0.87 and intra-observer kappa statistics a value of 0.98. Evaluation of the marker distribution in the myocardium of patients with IDCM CD34 expression curve was similar to that of troponin T (p<0.0001), although two groups could be identified. Patients with a difference of more than 20 myocardial fibers in expression of CD34 and troponin T had a somewhat less favorable survival although the difference was not significant. The analysis of cells positive for troponin T resulted in a similar number of cardiac fibers between NH and IDCM. This is in agreement with cardiac enlargement present in IDCM, which is due to ventricular dilatation rather than increased number of myocytes. Moreover, the expression of nestin, a marker of activation of myocardial precursors, did not change either, and this may confirm that there are no hyperplastic phenomena in the IDCM pathogenesis. The increase in ANP-positive cells in IDCM could be a consequence of neurohormonal activation due to a decline in the impaired myocyte contractility. Furthermore, since it was already shown that ANP could be important in the control of vascular remodeling, we postulated that the increase in CD34-positive cells might be functionally correlated with the increase in ANP production. Differential expression of CD34 and troponin T might be used in future studies to evaluate their prognostic value.

[The reevaluation of neoangiogenesis indices in cutaneous melanoma]. / La rivalutazione degli indici di neoangiogenesi nel melanoma cutaneo.

The melanoma today represents one of more diffuse malignant neoplasm and known, object of numerous studies and you debate yourself, topic more and more puts into effect them, observed and estimated under more it varies aspects to you. Our study has been lead taking in consideration the process of neoangiogenesis, fundamental stage in the progression graduates them of the malignant melanoma, than it comes true through the release of VEGF and many other angiogenic molecules from part of the same neoplastic cells. The evolution of such process represents a critical moment for the development of whichever neoplasm, but in particular way in the melanoma it is in charge of the transition from the phase of horizontal increase to that one of vertical increase. We have therefore place the attention on the appraisal of objective indices of the vascularization as factor I prognosticate of the melanoma; particularly way we have correlated the indices of vascularisation in 54 cases of melanomas, all to III the level of Clark, and have obtained of turns out to you that confirm the possibility to insert between the prognostic factors determinants also those.

[Urinary schistosomiasis: remarks on a case]. / Considerazioni su un caso di schistosomiasi urinaria.

Urinary tract schistosomiasis is a parasitic disease caused by S. haematobium with a wide range of clinical manifestations related to the mucosal and submucosal granulomatous lesions of the bladder. It affects about 80 million people in Africa, Middle-East and India, while in Italy it is rarely seen among immigrants from endemic areas and returning travellers. The authors describe a case occurred in a 26 years old man, recently emigrated from a rural area of Ghana. He had the symptoms of a haemorrhagic cystitis. Cystoscopy and biopsy showed granulomatous lesions of bladder with calcified eggs. Microscopic examination of urine was positive for Schistosoma haematobium eggs. The therapy with Praziquantel (40 mg/Kg una tantum) was effective. The authors emphasized the risk of introduction of schistosomiasis in some regions of our country, in consideration of the presence of the intermediate host as well as of an appropriate climate.

Ligand binding and cytochemical analysis of estrogen and progesterone receptors in relation to follow-up in patients with breast cancer.

Soluble and nuclear estrogen receptor (ER) content was measured by ligand binding assay, and estrogen and progesterone receptors by immunohistochemical assays (ER-ICA and PR-ICA) in 214 patients with breast cancer recruited at the "M. Ascoli" Cancer Hospital Centre in Palermo, Sicily, to assess the discriminant and predictive value of these parameters. On follow-up, data from both ER-ICA and PR-ICA showed a statistically significant difference, PR-positive patients having longer disease-free (DSF) and overall (OS) survival than PR-negative ones. Conversely, ER status did not correlate significantly with both DFS (P = 0.6) and OS (P = 0.2). In particular, PR-positive patients had 59 +/- 18 months DFS and 67 +/- 12 months OS, compared to 51 +/- 22 months DFS and 57 +/- 17 months OS of PR-negative cases. The present evidence implies that a PR-negative status identifies breast cancer patients with early relapse, as also suggested by previous studies. It also agrees with the results of ligand binding assay of ER, where ER status is a good discriminant and predictor of response to endocrine treatment, but is unable to anticipate early relapse in breast cancer patients. Evidence that PR status is a statistically significant prognostic indicator deserves further study to ascertain whether or not PR should be regarded as an ER-dependent parameter or be related to other biological variables such as growth factor (e.g., EGF), oncogene (e.g., Her2/Neu), or tumor suppressor gene (e.g., p53) products.

[The correlations between color Doppler using a contrast medium and the neoangiogenesis of small prostatic carcinomas]. / Correlazioni tra color Doppler con uso di mezzo di contrasto e neoangiogenesi dei piccoli carcinomi prostatici.

PURPOSE: To investigate if the use of a contrast agent (Levovist) improves the specificity of US in the diagnosis of prostate carcinoma, having the results of prostate biopsy as the gold standard. MATERIAL AND METHODS: Thirty patients with physical findings suspicious for prostate carcinoma and PSA ranging 5 ng/mL to 15 ng/mL were examined with transrectal US (TRUS) integrated with the color Doppler mode and contrast agent administration (4 g injected at 4 mL/min: 300 mL concentration). RESULTS: Based on bioptic and surgical results, 14 prostate carcinomas were found, all of them < 1.2 cm. Conventional US recognized the suspected nodule in 11 cases, with 78% sensitivity and 93% specificity. Color Doppler showed color signals in 8/14 cases, which were peripheral to the lesion or intranodular, but did not add any important finding to those of gray-scale US. In contrast, contrast enhanced studies showed 13/14 carcinomas, which improved sensitivity significantly (92%). Particularly, 11/14 lesions had a typical avascular pattern within the strongly enhanced peripheral gland, while 2 small lesions only exhibited intranodular vessels. DISCUSSION AND CONCLUSIONS: We compared our results with the Microscopic Angiogenesis Grading System (MAGS) index and found it exceeded 30 in the 11 avascular lesions value indicates microneoangiogenesis. In the other two cases a value < 30 was correlated with a different type of tumor vascularization typical of macroangiogenesis.

Serum concentration of E-selectin in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.

OBJECTIVES: High levels of soluble E-selectin have been reported in acute and chronic inflammatory disorders. Moreover, in some types of tumor elevated values have been found while in other types reduced levels have been reported. Our aims were to determine whether soluble E-selectin levels might be useful in monitoring the progression of chronic liver disease, including hepatocellular carcinoma. METHODS: Circulating soluble E-selectin was measured by an enzyme-linked immunosorbent assay in the sera of 18 patients with chronic hepatitis, 44 with liver cirrhosis, and 38 with hepatocellular-carcinoma-associated liver cirrhosis. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. RESULTS: Serum levels of soluble E-selectin were higher in the chronic hepatitis and liver cirrhosis patients than in the hepatocellular carcinoma patients and healthy controls. Levels in the hepatocellular carcinoma patients and controls were not significantly different. In the liver cirrhosis group, divided according to the Child-Pugh classification, soluble E-selectin decreased with disease severity. Similarly, in patients with liver cirrhosis who developed hepatocellular carcinoma, soluble E-selectin decreased as the disease progressed. Immunohistochemical localization showed strong membrane staining on endothelial cells in areas rich in inflammatory cells in severe chronic hepatitis. In some hepatocellular carcinoma tissues a marked E-selectin staining was observed on endothelial cells of tumor-associated small vessels. CONCLUSIONS: The results obtained suggest that high serum levels of soluble E-selectin are associated with chronic hepatitis and liver cirrhosis, and that levels decrease in liver cirrhosis patients as the disease progresses. Patients with hepatocellular carcinoma have different types of soluble E-selectin behaviour the significance of which requires further investigation.

Thyroid carcinosarcoma, a rare and aggressive histotype: a case report.

Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histological examination of a tumor showed the characteristic of epithelial carcinoma and mesenchymal differentiation. We retrospectively analyzed the course of the patient and reviewed the literature in which only 19 other cases are described. Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. Survival is very short despite aggressive multimodal treatment.

pap, reg Ialpha and reg Ibeta mRNAs are concomitantly up-regulated during human colorectal carcinogenesis.

We have established the phenotype of a colorectal tumor by partial sequencing of 2166 transcripts that were eventually arrayed on high-density filters. These filters were used for differential screening with mRNAs of colorectal cancer and normal adjacent mucosa to characterize genes whose expression is altered in colorectal carcinoma. Three genes encoding related proteins, PAP, reg Ialpha and reg Ibeta, were over-expressed in cancer. Northern-blot analysis confirmed that their expression was very low in normal colonic epithelial cells, but elevated in 75% of tumors. Western blotting with specific antibodies to pap and reg Ialpha revealed in tumors a single band of the expected size ( 15-16 kDa), demonstrating synthesis of the proteins. Pap was localized by immunohistochemistry to the cytoplasm of epithelial cells. In cancerous tissue, many cells showed a strong staining signal, but the proportion of stained cells was variable among patients. In normal mucosa, staining was light and restricted to a few cells scattered in the epithelium. Similar results were obtained with antibodies against reg Ialpha. No significant relationship was found between concentrations of pap, reg Ialpha or reg Ibeta and clinical outcome. We looked at potential effectors of pap/reg gene over-expression by testing, in 2 adenocarcinoma cell lines, the efficacy of the pap promoter at driving a reporter gene; strong induction was observed upon exposure to IFNgamma and IL-6. By analogy with observations in hepatocellular carcinoma, our results suggest that prevention of PAP/reg expression in normal colon cells by silencing their gene promoters is relieved during colon carcinogenesis, allowing their up-regulation by mediators such as cytokines.

Quantitative image analysis of estrogen and progesterone receptors as a prognostic tool for selecting breast cancer patients for therapy.

OBJECTIVE: To assess estrogen and progesterone receptor presence in human breast tumors using immunocytochemical analysis. STUDY DESIGN: For both estrogen (ER) and progesterone (PR) receptor assay, percent of stained cells and intensity of staining were estimated on a series of 251 consecutive breast cancer cases from the M. Ascoli Cancer Hospital Center in Palermo using the CAS 200 image analysis system. RESULTS: Cytochemical assay revealed a differential distribution of both ER and PR, by menopausal status of the patients; premenopause (PreM) was mostly ER negative (63%), and postmenopause (PostM) > 10 years was mostly ER and PR positive (64%). The percent of cells stained for ER was significantly different between PreM and PostM patients when they were considered as a whole. By contrast, no difference emerged for PR staining among menopausal groups. Overall, patients whose tumors were PR positive showed a significantly (P < .03) longer interval free of relapse. CONCLUSION: The present results suggest that PRs behave as better indicators than ERs of early relapse in breast cancer patients. Further studies, with longer follow-up, are needed, however, to validate this concept.

Circulating intercellular adhesion molecule-1 in patients with hepatocellular carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.

Pancreatitis-associated protein in patients with celiac disease: serum levels and immunocytochemical localization in small intestine.

Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (127.3 +/- 56.8) than in the other groups (B: 47.2 +/- 20.5; C: 51.5 +/- 32.2; D: 47 +/- 22.8; E: 27.6 +/- 9.0), which were not different from each other. In group A, a positive correlation was observed between serum PAP values and antigluten antibody levels (vs. AGA IgG r = 0.58, p < 0.001; vs. AGA IgA r = 0.66, p < 0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months of gluten-free diet and in all of them PAP serum concentration had decreased (mean +/- SE before the diet 122.5 +/- 36.4, after the diet 48.7 +/- 13.7, p < 0.0001). In addition, we performed an immunocytochemical study to localize PAP in the intestinal mucosa of patients from all groups except E. PAP was localized to the Paneth cells and to some globet cells, in patients with mucosal atrophy as well as in those with normal mucosa with no obvious quantitative difference. We concluded that in patients with celiac disease the active phase of the disease was accompanied by an increased serum concentration of PAP. Further studies are necessary to understand the mechanism leading to PAP elevation in the serum of patients with celiac disease.

[Angiogenetic capacity of breast neoplasms and correlation with color-Doppler semiology]. / Capacità angiogenetica delle neoplasie mammarie e correlazione con la semeiotica color Doppler.

The authors correlated the presence/absence of color signal-as shown by color-Doppler ultrasonography (CDUS) in 22 cases of breast carcinoma-with lesion angiogenesis potentials, as evaluated in the histologic sections with the determination of the microscopic angiogenesis grading system (MAGS) index. In all 4 cases in which CDUS showed no color signal, MAGS index value exceeded 30, which is suggestive of high neoplastic neoangiogenesis potentials. In contrast, in 17 of 18 cases positive to CDUS, MAGS index value remained below 30 and the microscopic analysis showed the presence of many fresh vessels more than 1 mm in caliber. Consequently, the presence of color signals at CDUS exams may be related to the features of tumor feeding vessels and therefore a negative CDUS exam cannot be considered as a reliable sign to exclude a malignant lesion.

Ovarian cortex surrounding benign neoplasms: a histologic study.

OBJECTIVE: Our purpose was to assess the functional morphologic features of the ovarian cortex surrounding benign cysts. STUDY DESIGN: Fifty-four specimens (13 mature teratomas, nine benign cystadenomas, and 32 endometriomas) were obtained from the area of maximum distention of the ovarian cortex overlying benign cysts from 48 patients. The type and number of follicles were scored on a semiquantitative scale (0 to 4). Alterations of the cortical stroma that were related to the primary tumor were investigated. The vascular network was assessed by means of monoclonal antibodies directed against endothelial cells (anti-VW, QBEND/10) and scored on a scale from 0 to 2. The chi 2 and Mann-Whitney U test were used for statistical analysis. RESULTS: Morphologic patterns similar to those of the normal ovarian cortex were observed in the cortical tissue surrounding mature teratomas, benign cystomas, and endometriomas in 92%, 77%, and 19% (p < 0.01) of specimens, respectively, and a regular vascular network was observed in 84%, 78%, and 22% (p < 0.01). Although microscopic endometriosis was observed surrounding the endometrioma in the stroma of 82% of specimens, stromal alterations related to the ovarian tumor were absent in the cortex surrounding mature teratomas and cystadenomas. CONCLUSIONS: The study shows that the ovarian cortex, which is stretched and thinned by the growth of a benign tumor, is not morphologically altered in the presence of teratomas or benign cystadenomas. Endometriomas are associated with microscopic stromal implants and reduced follicular number and activity.