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Donatella Santini

Publications and source records attributed to Donatella Santini.

31 records · Page 2Linked to original sources

Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization.

OBJECTIVE: The objective was to identify the factors, if any, that may predict long-term results of CIN treatment and HPV clearance/persistence after locally excisional therapy. METHODS: A series of 252 women with CIN lesions treated by conization were subjected to sequential HPV detection by repeated PCR during the prospective posttreatment follow-up. Factors predicting viral clearance during the follow-up (10.26 months) were elaborated using univariate and multivariate statistical techniques applied on epidemiological, clinical and biological data of the lesions. RESULTS: Sensitivity of the PAP test in detecting high-grade lesions was 93.9%, and specificity 27.3%. Odds ratio for having CIN 3/Stage IA1 squamous cervical cancer in the cone with HSIL PAP test was 5.69; 77.8 and 22.2% residual disease were found among PCR-positive and -negative cases, respectively. HPV DNA was negative in 74/252 (29.8%) samples at the first PCR. Multivariate logistic regression analysis showed that HPV 16 was an independent explanatory factor for high-grade CIN (P = 0.0001). HPV clearance increased to 63.5% at completion of the follow-up, corresponding to the monthly clearance rate of 5.27%. In Kaplan-Meier analysis, the highly significant (P = 0.0001) predictors of HPV clearance/persistence were age, lesion grade in the biopsy, lesion grade in the cone, volume of the cone, length of active sexual life, and involvement of endocervical margin (P = 0.0013). In chi-square tests, high-risk HPV type (P = 0.001) was such a predictor. In multivariate (Cox) model, the significant independent predictors of HPV clearance were involved endocervical margin (P = 0.001), lesion grade in the cone (P = 0.004), high-grade lesion in the colposcopic biopsy (P = 0.023), age (P = 0.029), and HSIL in PAP smear (P = 0.029). CONCLUSIONS: These data suggest that posttreatment follow-up should include both the PAP test and HPV detection techniques for early detection of any patients at increased risk for disease recurrence and progression, because of persistent oncogenic HPV types.

Adolescent↗

Histopathologic features and risk factors for benignity, hyperplasia, and cancer in endometrial polyps.

OBJECTIVE: The purpose of this study was to determine the rate of benign, hyperplastic, and malignant endometrial polyps and whether clinical data can predict histopathologic outcome. STUDY DESIGN: Five hundred nine patients with endometrial polyps who consecutively underwent hysteroscopic removal of endometrial polyps over 48 months were identified from our gynecologic oncology surgical database. Medical reports provided clinical data. Statistical analysis was performed. RESULTS: Histologically, 358 polyps (70.3%) were benign; 131 polyps (25.7%) had simple or complex endometrial hyperplasia, 16 polyps (3.1%) had hyperplasia with atypia, and 4 polyps (0.8%) were cancerous. Polyps were divided into group A and group B, according to the risk of malignancy (group A, benign; group B, atypical hyperplastic and cancerous). Age, menopause status, and hypertension were associated significantly with group B. CONCLUSION: Endometrial polyps rarely become malignant, but hyperplastic changes are more common. Age, menopause status, and hypertension may increase the risk of premalignant and malignant polyps. To achieve complete removal of the polyp and a reliable histologic analysis, operative hysteroscopy should be offered to symptomatic patients or to patients with risk factors.

Aged↗

Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study.

OBJECTIVES: Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms that have been the object of few studies that have involved only small numbers of patients. This study was carried out to obtain a comprehensive and up-to-date clinical picture of these tumors. METHODS: A total of 184 patients with NFPT admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis of NFPT was confirmed histologically using conventional and immunohistochemical techniques. Data were obtained from the medical charts or directly from the patients. RESULTS: There were 85 men (46.2%) and 99 women (53.8%). The mean age at diagnosis was 55.2 yr (range 17-82 yr). The percentage of smokers and alcohol drinkers was similar to that in the general population. Seven patients (3.9%) had a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the diagnosis was made after workup for pain or other symptoms, in the remaining 64 cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group survival was significantly greater than it was for the symptomatic patients (p=0.0043). Survival was also found to be improved by tumor resection (p<0.0001), absence of metastases (p<0.0001), and small tumor size (< or =3 cm) (p<0.0007). CONCLUSIONS: NFPTs were slightly more frequent in women and were diagnosed most often in middle-aged individuals. No risk factors other than a family history of exocrine pancreatic carcinoma were found. Tumor discovery while patients were still asymptomatic, tumor resection, absence of metastases, and tumor size < or =3 cm significantly prolonged survival.

Adenoma, Islet Cell↗

Genetic pathways in the evolution of breast ductal carcinoma in situ.

The patterns of allelic loss in 28 cases of pure ductal carcinoma in situ (DCIS) and 25 cases of DCIS associated with invasive ductal carcinoma (IDC) were compared, in order to define whether pure DCIS represented an earlier stage than DCIS associated with IDC in the progression of breast carcinoma. To this aim, the polymerase chain reaction (PCR) was performed on microdissected normal and neoplastic breast tissue, formalin-fixed and paraffin-embedded. Fifteen microsatellite markers were examined, on chromosomes 1p, 3p, 7q, 11q, 12p, 13q, 16q and 17q, mostly focused on regions altered in breast cancer. Loss of heterozygosity (LOH) was greater in pure DCIS than in the DCIS component associated with IDC for 11 out of 15 markers. The difference was statistically significant for D13S260 and D17S800 (p=0.008 and p=0.01, respectively). DCIS associated with IDC showed a lesser degree of alteration than the synchronous IDC component for ten out of 15 markers. In contrast, LOH at D11S1816 and D16S318 was lower in pure DCIS than in DCIS associated with IDC and even greater in the IDC component. These results confirm that DCIS is a possible but not an obligate precursor of invasive breast cancer and suggest that pure DCIS and DCIS associated with IDC may be genetically distinct. The evolution from DCIS to IDC may follow multiple pathways and not a linear model.

Breast Neoplasms↗

Disease persistence in patients with cervical intraepithelial neoplasia undergoing electrosurgical conization.

OBJECTIVE: Cone margin status has been reported to be the most important predictor of residual disease in patients with cervical intraepithelial neoplasia (CIN) undergoing electrosurgical excisional treatment. The primary aim of this study of patients treated with electrosurgical conization was to evaluate the association of cone margin status and other clinical and pathologic factors with the probability of residual disease. METHODS: The study population comprised 699 patients with at least one follow-up visit within 12 months of conization. Residual disease was defined as a histology diagnosis of CIN within 3 years of conization. Multivariate associations were evaluated with multiple logistic regression analysis. RESULTS: Attendance to follow-up was 97% for the second visit and 34% for the third visit. Residual disease was detected in a total of 38 patients (5.4%). The detection rate was 3.3% at the first visit, 2.1% at the second visit, and 0.4% at the third visit. An increased probability of residual disease was associated with a referral Pap smear reported as high-grade squamous intraepithelial neoplasia and carcinoma (odds ratio, 2.9; reference category, low-grade squamous intraepithelial neoplasia). A decreased probability was associated with a squamocolumnar junction entirely visible at the first follow-up visit (odds ratio, 0.2; reference category, squamocolumnar junction not visible). Patient age, time period, lesion size, lesion site, grade of CIN, cone width, cone depth, and margin status had no influence. CONCLUSIONS: The determinants of residual disease in this study differed from those generally reported so far. Factors associated with effectiveness of electrosurgical treatment of CIN need further research.

Adult↗

Does microcolposcopy protect patients with CIN and unsatisfactory colposcopy from the risk of incomplete excision of disease at the time of conization?

OBJECTIVE: To evaluate the effectiveness of microcolposcopy in preventing incomplete electrosurgical excision at the endocervical cone margin in patients with CIN and unsatisfactory colposcopy. MATERIALS AND METHODS: Four-hundred and twenty-one patients were studied. Complete excision of disease at the endocervical margin was evaluated using multiple logistic regression analysis. RESULTS: One-hundred and eighty-three patients underwent microcolposcopy. In 160 patients, the cone depth exceeded the endocervical extension of the squamocolumnar junction as predicted by microcolposcopy. In 23 patients, the opposite was observed. Microcolposcopy was not performed in 238 patients. For the three groups, the frequency of endocervical cone margin involvement was 22%, 22%, and 13%, respectively. Multiple logistic regression analysis showed that patients with a cone depth exceeding the endocervical margin of the squamocolumnar junction as predicted by microcolposcopy had no reduction in the risk of incomplete conization. CONCLUSION: The use of microcolposcopy awaits validation for assessment of the transformation zone to predict negative conization margins.

Journal Article↗

Immunocytochemical expression of epidermal growth factor receptor in myoepithelial cells of the breast.

The immunohistochemical expression and distribution of epidermal growth factor receptor (EGFr) in mammary myoepithelial cells (MECs) in normal tissue, benign epithelial proliferative lesions, and in situ carcinoma was performed. Results of the current study demonstrated that MECs stained constantly and strongly for EGFr, creating an outer continuous ring surrounding the epithelium of ducts and acini in healthy, in proliferative epithelial lesions, and in in situ carcinoma, both of ductal and lobular type. Foci of microinvasion were easily appreciated for the complete loss of EGFr immunostaining. Epidermal growth factor receptor expression in normal epithelia ranged from negative to weakly positive; it was positive in hyperplasia, whereas it was not constantly negative in in situ carcinoma. In conclusion, immunohistochemical staining for EGFr is diagnostically useful for MEC identification. The specific EGFr in MECs leads the authors to suggest that its expression may be related to the recently recognized high-specialized paracrine function by which the MECs exert the natural mechanical and functional role in the juxtaposition between epithelium and stoma.

Breast↗

Carcinoid of the pancreas.

Pancreatic carcinoids are very rare and usually have a poor prognosis. We describe a case of a pancreatic carcinoid with liver micrometastases in a female of 54 years of age in whom the tumor was without pronounced symptoms apart from rare episodes of flushing. The patient had been treated since November 1995 with the somatostatin analogue octreotide 200 micrograms twice daily for the first 2 years, with the long-acting analogue lanreotide 30 mg every 10 days for the following year, and then with octreotide LAR 20 mg every 28 days until the present. The flushing episodes disappeared completely, and the patient was well. Moreover, the dimensions of the tumor and the liver micrometastases remained stable during the observation period. As far as we known, this is the first case of a pancreatic carcinoid treated successfully with somatostatin analogues and having a satisfactory prognosis.

Antineoplastic Agents↗

A search for acute necrotic pancreatitis in early stages of alcoholic chronic pancreatitis.

OBJECTIVES: Various investigators believe that alcoholic chronic pancreatitis is the result of recurrent episodes of acute necrotic pancreatitis. The aim of this work is to study pancreatic histology in early stages of the disease to search for evidence of these acute episodes. STUDY: Of about 650 patients with alcoholic pancreatitis seen during the 30-year period from 1972 to 2002, 45 underwent surgery for this disease, all within 2 years of clinical onset. Of these 45, tissue samples adequate for study were obtained from 42, and this was the study material. Tissue samples were prepared for histologic examination by standard procedures. RESULTS: Areas of pancreatic necrosis were seen in tissue samples of only three (7%) of the 42 patients, and in all three cases chronic lesions were also present. No evidence of localized scarring that could be attributed to prior episodes of focal necrotic pancreatitis was found. A typical feature was the patchy distribution of the lesions in largely normal pancreatic tissue. The main lesions observed were perilobular and intralobular fibrosis, dilation of acini and ducts, and protein plugs in dilated ducts surrounded by periductal fibrosis. CONCLUSIONS: This study shows that, in the early stages of alcoholic chronic pancreatitis, signs of acute necrotic pancreatitis are very infrequent and, when present, they are associated with chronic lesions. These findings suggest that alcoholic pancreatitis begins as a chronic disease.

Adult↗

Relationship of up-regulation of 67-kd laminin receptor to grade of cervical intraepithelial neoplasia and to high-risk HPV types and prognosis in cervical cancer.

OBJECTIVE: To evaluate the 67-kd laminin receptor (67LR) in cervical cancer and its molecular links to oncogenic HPV types. STUDY DESIGN: As part of the HPV-PathogenlSS Study, a series of 150 squamous cell carcinomas (SCCs) and 152 carcinoma in situ (CIN) lesions were examined using immunohistochemical staining for LR67 and tested for HPV using polymerase chain reaction (PCR) with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Followup data were available for all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment. RESULTS: 67LR expression increased in parallel with increasing grade of CIN (p = 0. 0001), with the most dramatic up-regulation upon the transition from CIN 2 to CIN 3 and further to SCC. This increased expression was associated with CIN 3/cancer at OR 17.04 (95% CI 7.28-39.87). The seemingly significant association of 67LR with high-risk HPV (HR-HPV) detection (OR 2.20, 95% CI 1.27-3.80) was due to confounding by the histologic grade (Mantel-Haenszel common OR = 1.118, 95% CI 0.576-2.168). Using performance indicators, 67LR expression was of little value as a marker of HR-HPV type, and it did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, 67LR expression was not an independent prognostic factor in cervical cancer. CONCLUSION: In cervical carcinogenesis, both integrin- and nonintegrin-type LRs (67LR) probably have functions complementary to each other, mediating transient early and stable adhesions, respectively. Up-regulated 67LR expression is significantly associated with progression from CIN 2 to CIN 3 as a marker of cell proliferation. 67LR is probably orchestrated by mechanisms independent of HR-HPV oncoproteins, which seem to be more closely associated with integrin-type laminin receptors.

Adolescent↗

p53 expression, DNA ploidy and mitotic index as prognostic factors in patients with epithelial ovarian carcinoma.

AIMS AND BACKGROUND: Biological variables linked to genomic instability were examined and related to survival in 52 patients affected by ovarian carcinoma and nine patients with low malignant potential tumors (LMP). METHODS: DNA ploidy was measured by image cytometry in isolated neoplastic cells; the mitotic index was measured in Feulgen-toluidine blue-stained sections and p53 was investigated by immunohistochemistry. RESULTS: Twenty-five tumors (4 LMP) were peridiploid (ploidy < 2.25c), 22 tumors (4 LMP) were hyperdiploid (2.25c > ploidy < 2.9c) and 14 (1 LMP) had high ploidy (> or = 2.9c). MI ranged from 0.3 to 24.2 with a mean of 1.8 for LMP and 6.8 for carcinomas (P<0.001). Widespread p53 overexpression was detected in 49% of carcinomas and in none of the LMP tumors. CONCLUSIONS: Survival analysis performed in patients with carcinomas indicated that, of the examined biological variables, only MI was moderately associated with survival in a subgroup of early-stage patients.

Adult↗

Inflammatory pseudotumor of the pancreas resembling pancreatic cancer: clinical, diagnostic and therapeutic considerations.

Pancreatic masses could be malignant or benign. Among these latter inflammatory pseudotumor is an uncommon mass rarely located in the pancreas and it must be considered in differential diagnosis with pancreatic cancer. A case report and literature review of inflammatory pseudotumor were recognized to well known this rare pathology regarding its clinical, diagnostic, therapeutic and histopathological feature. Twenty-one cases of inflammatory pseudotumor in the adult were reviewed from the literature; 10 (47.6%) were female, 11 (52.3%) male; mean age 53.3 years (range 23-73). They were solid single mass in 18 cases, with median size of 5.1 cm (range 1.5-13), cystic mass in one case; 18 were located in the head, 1 in the body. In 2 cases it appeared as a volumetric increase of the pancreas. Diagnosis was possible only histologically and surgical treatment was mandatory in 20 cases; only in one patient a corticosteroid treatment was performed. Pancreatic inflammatory pseudotumor is a rare lesion of the pancreas but it must be distinguished from pancreatic cancer. Pancreatic resectioning is mainly due to the preoperative diagnostic difficulties that must be resolved surely only with histopathological examination of the specimen.

Adult↗

Neuromuscolar and vascular hamartoma of the duodenum. A clinical case and review of the literature.

BACKGROUND AND AIMS: The NMVH of the intestine is a rare lesion, typical located in the small bowel. After the first 2 cases, reported in 1982, other 12 cases have been described, ten localized in the jejunual or ileal tract, only 1 in the cecum. SUBJECTS AND METHODS: A case of NMVH of the duodenum, simulating a Crohns disease, is described. The lesion extended about 12 cm. and it caused intestinal stenosis. The microscopic analysis on the operative specimen highlighted the presence of a neuronal hyperplasia at mucous membranae and submucosal levels, associated to muscolaris mucosae hypertrophy and disorganisation. Expanded and ectasic veins, proliferation of nervous fibres and ganglion cells in the submucosal were also observed. RESULTS: NMVH is a non-epithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. In the controversy about the nature of the NMVH, we consider it a separate entity, where the final diagnosis depend on the clinicopathologic setting, as well as on the location and number of the lesions. CONCLUSIONS: The Authors analyse the main characteristics of this rare pathology with regard to clinical, diagnostic and therapeutic aspects.

Biopsy↗