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D Pacchioni

Publications and source records attributed to D Pacchioni.

At least 19 recordsLinked to original sources
PubMed2004

Prostatic duct carcinoma with combined prostatic duct adenocarcinoma and urothelial carcinoma features: report of a case.

We report a unique case of prostatic duct carcinoma (PDC) featuring both prostatic duct adenocarcinoma (PDA) and high-grade urothelial carcinoma (HG-UC). An 84-year-old man presenting with hematuria showed at ultrasonography and cystoscopy a papillary neoplasia located near to the verumontanum. Histopathologic examination of specimens from transurethral resection revealed a tumor originating from large prostatic ducts showing 2 different components: PDA with endometrioid features (main pattern) and HG-UC (minor part). Immunohistochemically, the areas of PDA were positive for prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and androgen receptors (AR), while negative for estrogen (ER) and progesterone receptors (PGR). Prognostic factors evaluation pointed out a low proliferation index (10%) and focal expression of p53 (6%); c-erb-B2 was not overexpressed. The HG-UC areas were negative for all previous markers, while positive for thromobomodulin. The proliferation index was high (60%), and p53 was diffusely expressed (55%). The incidence and significance of PDC with combined features is discussed with reference to literature data.

Adenocarcinoma↗
PubMed2001

Progression from superficial to invasive carcinoma of the bladder: genetic evidence of either clonal heterogeneous events.

Until now, no definitive molecular evidence proving or disproving a true progression from superficial to invasive bladder tumors has been reported. A total of 36 lesions from 6 patients affected by invasive bladder cancer after multiple superficial recurrences were analyzed for loss of heterozygosity on 8 loci of chromosome 9 and 2 loci of chromosome 17. In addition, the clonal composition of the tumors from two female patients was examined using the human androgen receptor assay. Our data suggest that papillary bladder lesions can and sometimes do make a true progression into invasive life-threatening tumors; however, this progression is not an invariable sequence because it was definitely proven in 2 but not confirmed in 3 of the cases we examined.

Aged↗
PubMed2000

Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder.

OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer. METHODS: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1, mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence-free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS: Recurrence-free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence-free survival could not be predicted either by p53 status or MI. A 20% cut-off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta-T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups. CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well-differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of treatment.

Aged↗
PubMed1999

Immunohistochemical evaluation of the safety of transurethral electrovaporization of the prostate and its clinical results.

Short term follow up studies on transurethral electrovaporization (TUEVP) have shown a relative low morbidity over TURP. The use of high power current has been claimed as a source of possible damage on the neuronal structures surrounding the prostate. The aims of our study were to assess longer follow up results as well as the safety of this technique. Over an 18 month mean follow up period symptom relief remained relatively stable. Postoperative dysuria was detected in a higher percentage of patients and was seen for a longer period in comparison with previous reports. Immunohistochemical staining performed using S-100 and NF monoclonal antibodies showed anatomical integrity of the prostatic neuronal fibres surrounding the vaporization edge. In conclusion, although the effectiveness and safety of TUEVP are confirmed by the present study, the occurrence of a significant rate of long-lasting postoperative irritative symptoms must be taken into account.

Journal Article↗
PubMed1998

[Actinomycosis of the tongue. Report of two cases and review of the literature].

Actinomycosis of the tongue is a rare form of infection whose initial clinical manifestation is a submucosal swelling that may mimic both benign and malignant neoplasias. Two cases are, presented and their clinical features and diagnostic criteria are discussed in the light of twelve cases drawn from the literature. Infection in the tongue is rare, though perhaps underestimated. It is generally located on the anterior two thirds laterally to the median sulcus, and presents as a moderately painful nodule set deep in the extrinsic and intrinsic muscles and poorly mobile on the adjacent planes. In a few weeks the lesion increases in size and painfulness with consequent loss of function in the absence of diagnosis and appropriate antibiotic management. Both our patients, in fact, presented with deep lesions and no apparent involvement of the mucosa, and were investigated by means of fine-needle aspiration biopsy (FNAB). The aspirated material was used to prepare both routine smears and cell blocks embedded in paraffin. The pathological material provided by this combination of methods proved quantitatively and qualitatively sufficient for the definitive diagnosis of actinomycosis in both cases.

Actinomycosis↗
PubMed1997

Antitumoral activity of liposomes and immunoliposomes containing 5-fluorouridine prodrugs.

Liposomes and immunoliposomes containing cytotoxic agents may be highly efficacious in intracavity therapy of malignancies confined principally to the peritoneal cavity. To assess the feasibility of this locoregional treatment, we prepared two derivatives of 5-fluorouridine (5-FUR), a highly cytotoxic metabolite of 5-fluorouracile, and incorporated them into REV liposomes, prepared with the reverse phase evaporation method. Encapsulation efficiency, drug leakage, and stability were determined, and size analysis and differential scanning calorimetry were carried out to evaluate the drug delivery potential of liposomes containing 5'-palmitoyl-5-FUR, 5'-succinyl-5-FUR, or the parent drug 5-FUR. The most suitable drug for encapsulation, in terms of minimum leakage and encapsulation efficiency, was 5'-palmitoyl-5-FUR, which differential scanning calorimetry indicated as being firmly anchored to the lipid bilayer. Thus, 5'-palmitoyl-5-FUR was chosen to prepare a chemotherapeutic liposome-monoclonal antibody conjugate (immunoliposome). The covalent linkage between antibody and liposome was realized by coupling the thiolated monoclonal antibody AR-3 with REV liposomes, containing N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine. The cytotoxic activity of drug-bearing liposomes and immunoliposomes was evaluated on the HT-29 human colon adenocarcinoma cell line; the immunoliposomes had higher cytotoxicity than liposomes or 5-FUR. To explore the potential of these drug formulations in anticancer therapy, we ip injected liposomes or immunoliposomes into athymic mice ip grafted with human HT-29 cell line. In this mouse model, the immunoliposome containing 5'-palmitoyl-5-FUR displayed the best antitumoral activity, since on day 27 postgraft only 5% of residual tumor mass was present, compared to control mice; there was a close relationship between exposure time of tumor tissue to the drug and antitumor potency.

Animals↗
PubMed1997

Tobacco smoke, recurrences, and p53/bcl-2 expression in bladder cancer.

Overexpression of p53 is considered to be predictive of mutations of the p53 gene. Exposure-specific mutations of the p53 gene have been described for cancers at different sites. An association between p53 mutation/overexpression and smoking has been described in early stage bladder cancer, but results were conflicting. We have conducted a study on 131 bladder cancer cases, considering p53 expression and smoking habits in an area where the use of air-cured tobacco, rich in carcinogenic arylamines, is common. The study suggests that the use of air-cured tobacco induces p53 overexpression (possibly via mutation) in early stage-low grade bladder cancer, more frequently than flue-cured tobacco (odds ratios = 3.4, 95% confidence intervals 0.9-13 in stage 1; odds ratios = 24, 95% confidence intervals 1.1-519 in stage 1, grade 1). However, all the excess associated with air-cured tobacco was concentrated in recurrences. When available, the biopsies of recurrent cases with early-stage disease were re-examined and all showed p53 expression at first diagnosis (with 10-50% of cells positive) (n = 5). It is hypothesized that exposure to tobacco-related chemicals increases the risk of recurrences via p53 overexpression/mutation. Expression of the bcl-2 gene was detected in only 2 out of 13 p53-positive smokers.

Adult↗
PubMed1997

Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues.

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.

Carcinoma, Hepatocellular↗
PubMed1997

In vitro and in vivo antitumor activity of immunoconjugates prepared by linking 5-fluorouridine to antiadenocarcinoma monoclonal antibody.

5-Fluorouridine (5-FUr), a cytotoxic antitumoral agent not in clinical use because of its systemic toxicity, and AR-3, a monoclonal antibody specific to a human colorectal adenocarcinoma, were covalently linked via two different strategies. 5-FUr was 5' succinilated after protection of the secondary hydroxyl groups and the carboxylate derivative was then activated as N-hydroxysuccinimidyl ester in order to react with the amino groups present in the monoclonal antibody, giving an amide linkage. Alternatively, a 5-FUr immunoconjugate containing an acid-cleavable hydrazone bond was formed from the reaction between an acyl hydrazide derivative of 5-FUr and a periodate oxydized antibody with approximately 12 aldehyde groups in its carbohydrate region. An average of 9 to 12 drug molecules were attached to the antibody. In a cytotoxic assay on the human colorectal carcinoma cell line HT-29, the hydrazone containing drug conjugate was equally active as the succinylamido conjugate and the free drug. However, ELISA showed that while in the case of the succinylamido conjugate the Mab immunoreactivity was not affected after conjugation, there was a significant loss of reactivity in the acid cleavable conjugate. In a model of a disseminated intraabdominal carcinomatosis by HT-29 intraperitoneal graft in nude mice, the 5-FUr immunoconjugate selected was more effective than the unconjugated drug in medium-term therapy (21 days after the graft and 16 days after drug treatment), albeit in the longer period the efficacy of the two formulations was similar. The toxic effect of the drug-conjugate in vivo was much weaker, demonstrating its clear advantage over the drug, in terms of pharmacological efficacy.

Adenocarcinoma↗
PubMed1997

[Perirenal immunoblastic lymphoma. Description of a case].

The primary perirenal localization of non-Hodgkin lymphomas is rare and normal methods of image diagnosis do not enable a reliable preoperative diagnosis. In the majority of cases renal function is not affected and this pathology is often presented as an occasional finding. The pathologies included in the differential diagnosis are renal neoplasias, abscess and inflammatory processes in a perirenal site. Echotomography shows the lesion as an hypoanechoic zone surrounding the kidney. Computed tomography show it as isodense with the renal parenchyma. Histological tests together with immunohistochemical tests identified a malignant large B cell immunoblastic-type lymphoma in the case described here, with plasmoblastic-plasmocytic differentiation and high malignancy according to the Working Formulation. The pathogenesis of this rare localisation is controversial. We maintain that lymphomatous proliferation may be triggered off by lymphatic follicles present in the perirenal space. The concomitant presence of other clinical signs, such as splenomegalia and adenopathies, may contribute to the diagnosis. On the contrary, monolateral involvement in the absence of other signs, as in this case, raises considerable problems of differential diagnosis. Perirenal lymphoma must therefore always be borne in mind in the diagnosis of renal or perirenal masses.

Humans↗
PubMed1997

p53 expression compared with other prognostic factors in OMS grade-I stage-Ta transitional cell carcinoma of the bladder.

OBJECTIVE: Recent studies have investigated the possibility that p53 protein and some macroscopic tumoral features, such as diameter and focality of the lesion, play a significant prognostic role in bladder cancer progression. A retrospective study was conducted on papillary grade-I stage-Ta transitional cell carcinoma (TCC) of the bladder. METHODS: p53 expression was evaluated using the immunohistochemical method. A group of 31 patients with papillary grade-I and stage-Ta TCC of the bladder with no recurrence or who recurred with no histological grading and staging variation in a 4-year mean follow-up period was compared with 28 grade-I and stage-Ta papillary TCC patients who underwent recurrences and a worsening in histological grading (grade II or grade III) or staging (T1) within the same period of time. The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein products of the mutated p53 tumor-suppressor gene, when independently evaluated in comparison with other tumoral prognostic factors, are associated with tumor recurrence and progression in patients with Ta papillary grade-I TCC of the bladder. RESULTS: Our data show that when a p53 threshold of > 0% was considered, 53.6% of patients with tumor progression in the follow-up period were p53-positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p = 0.02). On the contrary, p53 failed to show any value in predicting progression when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of the tumoral lesion and recurrent tumor was highly predictive of tumor progression for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006, respectively). Multivariate analysis revealed p53 nuclear overexpression (at a threshold of > 0%) to be a single valuable prognostic factor of progression (OR = 10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01). CONCLUSIONS: Our results lead to the conclusion that p53 immunohistochemical detection has no prognostic value in predicting tumoral relapse or progression of TaGI TCC of the bladder when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear labelling of > 0% is considered as positive staining, this tumor marker becomes highly predictive of tumor recurrence and progression. These findings seem therefore to suggest the use of a slight p53 positivity (> 0%) as a valid tool in predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a multifocal lesion and a recurrent tumor as markers of progression is also confirmed by these results.

Aged↗
PubMed1997

DNA flow cytometry and 67Ki proliferating index as prognostic factors of early recurrence and progression in G1-G2/Ta-T1 and G3/Ta-T1 transitional cell carcinoma of the bladder.

Using flow cytometry, gross genomic alterations, defined as DNA ploidy, and the fraction of S-phase cells, can be calculated in bladder cancer cells. In aneuploid superficial bladder cancer the recurrence rate has been reported to be three times higher than in diploid forms. A correlation between the S-phase fraction and progression has been reported for G1-G2/Ta-T1 tumours, but not for G3/Ta-T1. The aim of our study is to evaluate whether the traditional cytometric parameters can be used as valid predictors of early recurrences and progression in G1-G2/Ta-T1 and G3/Ta-T1 bladder cancer patients and to compare the proliferation indexes as defined by S-phase fraction and 67Ki monoclonal antibody in the two groups of patients.

Aneuploidy↗
PubMed1996

In situ hybridization study of messenger RNA for estrogen receptor and immunohistochemical detection of estrogen and progesterone receptors in the human ovary.

The expression of estrogen and progesterone receptors (ER and PR), as well as the presence of messenger RNA for estrogen receptor (ER-mRNA), were analyzed by immunohistochemistry and in situ hybridization, respectively, in the ovary of 25 healthy eumenorrheic women. Ovarian biopsies were taken in different phases of the menstrual cycle during laparotomy or operative laparoscopy performed for extraovarian benign diseases. A total of 126 follicles (105 primordial, 13 preantral and eight antral) and 50 corpora lutea (eight active and 42 atretic) was analyzed. Granulosa cells stained positively for ER, PR and ER-mRNA in 13.3, 9.5 and 17.1% of primordial follicles, respectively. The proportions of preantral and antral follicles with ER-positive granulosa cells were 23.1 and 37.5%, respectively; these follicles were positive for PR in 23.1 and 37.5% of cases, and for ER-mRNA in 30.7 and 37.5% of cases, respectively. For thecal cells, 38.5% of preantral and 37.5% of antral follicles were PR-positive, but no more than 25% stained positive for ER and ER-mRNA. Active corpora lutea stained positive for ER, PR and ER-mRNA in 50, 62.5 and 50% of cases, respectively. Corpora albicantes always stained negative. In all subjects the stroma surrounding both follicles and corpora lutea contained several fibroblast-like cells which stained positive for ER, PR and ER-mRNA. Oocytes and blood vessels stained negative in all cases. This study supports the hypothesis that estrogens and progesterone play a role in the intraovarian regulation of follicle growth from the first steps of follicle development, and participate in the regulation of corpus luteum.

Adult↗
PubMed1994

Pharmacokinetics of an antibody-ricin conjugate administered intraperitoneally to mice.

Immunotoxins have been extensively studied for the treatment of neoplasias; their intracavitary administration could be useful for the therapy of tumors confined to the pleural or peritoneum spaces. To study the feasibility of this "locoregional" treatment, a pharmacokinetic study of immunotoxins delivery is necessary. Ricin, a plant toxin extracted from the seeds of Ricinus communis, has often been used in immunoconjugates for its high activity; nevertheless, appropriate strategies have been necessary to limit the aspecific toxicity. We previously prepared a AR-3-ricin immunotoxin lacking the ability to bind galactosidic cell surface residues, a so-called sterically blocked immunotoxin. The monoclonal antibody AR-3, an IgG1 specific to the CAR-3 antigen, was able to recognize human colorectal adenocarcinomas. Preclinical trials in nude mice, intraperitoneally grafted with the target neoplasia, showed that this immunotoxin suppressed tumor growth without showing any undesirable ricin toxicity. In the present work we report the pharmacokinetic properties of this immunotoxin, showing the in vivo stability and a relatively long blood survival. With a biodistribution study in tumor-bearing mice, we demonstrate that in tumor-invaded tissues, the concentration of the specific AR-3-ricin immunotoxin was higher and progressively increased in a multiple-dose regimen. In contrast, an irrelevant immunotoxin behaved differently because it did not show specific tumor uptake. Moreover the pharmacokinetic data reported in this work improve the potential for "locoregional" treatment of malignancy with blocked immunotoxins.

Animals↗
PubMed1994

Epstein-Barr virus detection by in situ hybridization in fine-needle aspiration biopsies.

Metastasis to neck lymph nodes is often the presenting symptom of occult head and neck tumors, including undifferentiated nasopharyngeal carcinoma (UNPC). The diagnosis of the primary site of the tumor by conventional cytological analysis of tissue obtained by fine-needle aspiration (FNA) may be difficult. As Epstein-Barr virus (EBV) infection is consistently associated with UNPC, we evaluated the diagnostic significance of EBV detection using a nonradioisotopic in situ hybridization assay. The data obtained by FNA from metastatic head and neck tumors was correlated with the histology of the corresponding surgical specimens. In a series of 25 FNA specimens of cervical lymph node metastases of tumors of unknown origin, EBV was found expressed in all seven metastases of UNPC but in none of 18 metastases of tumors of different types. Therefore, detection of EBV in cervical metastatic adenopathy may be successfully used to identify the presence of occult UNPC.

Adult↗
PubMed1994

Infection by Epstein-Barr virus in Hodgkin's disease is not restricted to the Reed-Sternberg cells.

The presence of Epstein-Barr virus (EBV) DNA was analysed by a non-radioisotopic in situ hybridization procedure within eight Hodgkin's disease tissues. Seven specimens contained EBV DNA, that was found not only within the Reed-Sternberg tumour cells, but also, to a varying degree, within the surrounding lymphocytes. The staining was more diffuse in the nodular sclerosis and interfollicular types, whereas it involved only a minority of lymphocytes in cases with mixed cellularity. Appropriate controls established the specificity of these findings. The widespread expression of EBV DNA within Hodgkin's disease tissue heavily underscores the involvement of EBV in the pathogenesis of this illness.

DNA, Viral↗
PubMed1994

Detection of human androgen receptor mRNA in hepatocellular carcinoma by in situ hybridisation.

Recent evidence suggests that anti-androgen therapy may be useful in patients with androgen receptor (AR)-positive hepatocellular carcinomas (HCC), as determined by a steroid binding assay. To evaluate the AR expression of HCC, in both histological and cytological material, we developed a non-radioisotopic in situ hybridisation (NISH) assay specific for the human AR mRNA. A synthetic oligonucleotide complementary to positions 661-695 of the human AR coding sequence was end-labelled with digoxigenin-dUTP and revealed by an alkaline phosphatase-conjugated anti-digoxigenin antibody. We analysed 22 formalin-fixed, paraffin-embedded HCC, obtained at surgery, together with the corresponding non-neoplastic liver tissues (19 cases). In six cases, cell blocks obtained by fine-needle aspiration (FNA) prior to surgery were also available. Positive controls included seminal vesicles and prostate tissues. Sixteen HCCs (73%) expressed a variable amount of AR mRNA, with the proportion of positive cells ranging from very few to more than 90%. Normal hepatocytes were stained weakly and focally in eight cases (42%). Appropriate controls, inclusive of immunohistochemical detection of the AR protein in selected cases, established the specificity of the assay. Data obtained on FNA specimens were predictive of the results on histologic material. However, in two cases the NISH assay was negative on the cytological specimen but stained rare hepatocytes within the surgically resected tumor. In conclusion, NISH is a novel procedure for rapid and specific assessment of the expression of AR in HCC tissue. Its clinical significance, in terms of predictivity of response to anti-androgen treatment, needs to be assessed in large correlative studies.

Adult↗