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R Miceli

Publications and source records attributed to R Miceli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group.

OBJECTIVE: To evaluate the impact of subtotal (SG) versus total (TG) gastrectomy on the oncologic outcome of patients with cancer of the distal stomach from 28 Italian institutions. SUMMARY BACKGROUND DATA: There is controversy over whether SG and TG have a different impact on the 5-year survival probability of patients with cancer of the distal half of the stomach. METHODS: The present analysis involved 618 patients randomized during surgery to SG (315) or TG (303), provided there was at least 6 cm from the proximal edge of the tumor to the cardia, there was no intrapertoneal or distant spread, and it was possible to remove the tumor entirely. Both surgical treatments included regional lymphadenectomy. RESULTS: Four patients died after SG and seven after TG. Median follow-up was 72 months after SG (range 2 to 125) and 75 months after TG (range 7 to 113). Five-year survival probability as computed by the Kaplan-Meier method was 65.3% for SG and 62.4% for TG. The test of equivalence led to the conclusion that the two procedures may be considered equivalent in terms of 5-year survival probability. The analysis of survival using a multivariate Cox regression model showed a statistically significant impact on survival of tumor site, tumor spread within the gastric wall, extent of resection to the spleen plus or minus neighboring organs or structures, and relative frequency of metastasis in resected lymph nodes. CONCLUSIONS: Both procedures have a similar survival probability. The authors believe that SG, which has been reported to be associated with a better nutritional status and quality of life, should be the procedure of choice, provided that the proximal margin of the resection falls in healthy tissue.

Aged↗
PubMed1999

Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-induced murine colitis.

The purpose of this study was to determine the efficacy of a novel human protein, keratinocyte growth factor-2 (KGF-2), in a model of murine colitis induced by ad libitum exposure to a 4% solution of dextran sulfate sodium (DSS) in the drinking water. Initial evaluation of KGF-2 was based on its ability to reduce weight loss, stool score, and histological score in mice exposed to DSS for 7 days. When KGF-2 (0.1-10.0 mg/kg i.p. or s.c.) was injected daily into DSS-treated mice from day 0 to 7, it significantly reduced all three parameters in a dose-response fashion, with a minimum effective dose of between 1 and 3 mg/kg. When KGF-2 was given therapeutically, starting 4 days after initiation of the 7-day DSS treatment, the 3- but not the 0.5-mg/kg dose significantly enhanced weight recovery after discontinuation of DSS treatment. When DSS treatment was prolonged beyond the normal 7 days, therapeutic intervention on day 2 or 4 also significantly reduced mortality, weight loss, and stool score at the 1- and 3-mg/kg dose. Therapeutic treatment also resulted in reduction of colon myloperoxidase levels by more than 50%. These experiments suggest that KGF-2 may be clinically useful in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.

Animals↗
PubMed1999

Course and cost of treatment for depression with fluoxetine, paroxetine, and sertraline.

OBJECTIVE: To compare depression-related treatment costs and total healthcare costs for patients diagnosed with depression and treated with either sertraline, paroxetine, or fluoxetine. PATIENTS AND METHODS: Claims records from a national database of patients diagnosed with depression who began treatment with an SSRI in 1995, following an antidepressant medication-free period of at least 6 months, were included. Treatment course and associated depression-related treatment and total healthcare costs during the subsequent 12-month treatment period were examined using univariate and multivariate methods. RESULTS: Nine-hundred five (905) patients taking sertraline, 492 on paroxetine, and 945 on fluoxetine met inclusion criteria. The groups were similar and representative with respect to gender and age. Mean dose over the 12-month treatment period increased 24%, indicating significant titration in all cohorts. Patients treated with paroxetine had shorter treatment duration (157.0 days) than did patients treated with fluoxetine (192.6 days) or sertraline (166.9 days, P < 0.001). Patients receiving index treatment with paroxetine were most likely to switch to another SSRI (21.3%); those taking sertraline were second most likely to switch (16.1%); and those on fluoxetine were least likely (12.4%, P = 0.001). Mean costs for depression-related outpatient visits and hospitalizations were similar. Mean antidepressant prescription costs differed, being $586, $419, and $446 for fluoxetine, paroxetine and sertraline cohorts, respectively (P < 0.001). In this sample, the fluoxetine cohort did not have lower nonpharmaceutical healthcare costs to offset higher pharmaceutical acquisition costs. Conclusions from median and multivariate analyses were robust to these findings. CONCLUSIONS: During this study period when fluoxetine, paroxetine, and sertraline were all well-established agents, similar depression-related treatment courses and cost characteristics among all 3 drugs were observed.

Adolescent↗
PubMed1998

Is steroid receptor profile in contralateral breast cancer a marker of independence of the corresponding primary tumour?

We compared oestrogen receptor (ER) and progesterone receptor (PgR) profiles between primary and corresponding contralateral breast cancer (CBC) to investigate whether CBC should be considered relapse of a primary or as a feature of the multicentric origin of breast cancer. We adjusted for patient age, menopausal status, histology and adjuvant therapy. In spite of the general application of a cut-off value to dichotomise ER and PgR, we considered them as continuous variables. Moreover, we considered as synchronous cancers only simultaneously occurring lesions. For 399 patients, ER and PgR receptor levels in primary and CBC did not differ significantly, but were significantly correlated within the same patient. The correlation was higher for synchronous than for metachronous lesions when considering ER, but not PgR. The correlation between ER and PgR levels in the same tumour (primary or CBC) appeared stronger than the correlation of either receptor type (ER or PgR) between primary and CBC. Age, histology and adjuvant treatment affected ER concentration, whereas age, menopausal status and histology affected PgR concentration. The analysis indicated that primary and CBC tend to be characterised by a similar steroid receptor profile. The finding may support the hypothesis of CBC as a second primary arising in a common predisposing milieu, rather than a primary-dependent contralateral lesion. In this light, the clinical management of patients with a bilateral breast cancer should be similar to that of a unilateral breast cancer.

Adult↗
PubMed1998

Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer.

Blood vessel density is a prognostic indicator of multiple tumor types. Recently, it has been established that tumor-associated blood vessels express elevated levels of integrin alpha(v)beta3. In fact, there is evidence that integrin alpha(v)beta3 identifies the most proliferative endothelial cells within human breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density and alpha(v)beta3 expression. We found that the antibody LM609 to integrin alpha(v)beta3 preferentially stains the blood vessels of small caliber. Furthermore, comparative studies between LM609 and anti-CD31 antibodies on normal breast indicate that very low and weak expression of integrin alpha(v)beta3 was found on vessels within normal tissue, whereas CD31 antigen was expressed in almost all vasculature. Indeed, expression of integrin alpha(v)beta3 was significantly higher in tumors of patients with metastasis than in those without metastasis. In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha(v)beta3 in tumor vascular "hot spots" was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients. These findings support the contention that angiogenesis plays a critical role in breast cancer progression and suggest that integrin alpha(v)beta3 is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic therapy.

Adult↗
PubMed1997

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases.

Adult↗
PubMed1997

Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: prognostic implications.

Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2-843.1), 0.22 ng/mg (range 0.0-41.65) and 33.80nmol/mg (range 4.20-216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p<0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p<0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.

Journal Article↗
PubMed1997

Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

Abdominal Neoplasms↗
PubMed1997

Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group.

OBJECTIVE: The purpose of this study was to analyze postoperative morbidity and mortality of patients included in a randomized trial comparing total versus subtotal gastrectomy for gastric cancer. SUMMARY BACKGROUND DATA: There is controversy as to whether the optimal surgery for gastric cancer in the distal half of the stomach is subtotal or total gastrectomy. Although only a randomized trial can resolve this oncologic dilemma, the first step is to demonstrate whether the two procedures are penalized by different postoperative morbidity and mortality rates. METHODS: A total of 624 patients with cancer in the distal half of the stomach were randomized to subtotal gastrectomy (320) or total gastrectomy (304), both associated with a second-level lymphadenectomy, in a multicenter trial aimed at assessing the oncologic outcome after the two procedures. The end points considered were the occurrence of a postoperative event, complication, or death and length of postoperative stay. RESULTS: Nonfatal complications and death occurred in 9% and 1% of subtotal gastrectomy patients and in 13% and 2% of total gastrectomy patients, respectively. Multivariate analysis of postoperative events showed that splenectomy or resection of adjacent organs was associated with a twofold risk of postoperative complications. Random surgery and extension of surgery influenced the length of stay. The mean length of stay, adjusted for extension of surgery, was 13.8 days for subtotal gastrectomy and 15.4 days for total gastrectomy. CONCLUSIONS: Our data show that subtotal and total gastrectomies, with second-level lymphadenectomy, performed as an elective procedure have a similar postoperative complication rate and surgical outcome. A conclusive long-term evaluation of the two operations and an accurate estimate of the oncologic impact of surgery on long-term survival, not penalized by excess surgical risk of one of the two operations, are consequently feasible.

Aged↗
PubMed1996

Cancer of the low and middle rectum: local and distant recurrences, and survival in 350 radically resected patients.

The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.

Adult↗
PubMed1996

Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy.

PURPOSE: To gather information on metastatic growth from the time-distribution of first treatment failure in breast cancer patients undergoing mastectomy alone. METHODS: The risk of recurrence at a given time after surgery was studied utilizing the cause-specific hazard function. Recurrence was categorized as first treatment failure at any site, local-regional recurrence, distant metastases, and contralateral tumor. The risk distribution was assessed relative to tumor size, axillary lymph node involvement, and menopausal status. RESULTS: A total of 1173 patients treated between 1964 and 1980 with mastectomy alone and no adjuvant therapy were studied. The hazard function for first failure presented an early peak at about 18 months after surgery, a second peak at about 60 months and then a tapered plateau-like tail extending up to 15 years. A similar risk pattern was detectable for both local recurrence and distant metastases, while the curve of contralateral breast tumors showed a near flat plateau. The risk of early local-regional and distant recurrences was much lower for tumors less than 2 cm in diameter than for larger tumors; the risk of late recurrence was similar for small and large primaries. Node-positive patients showed peaks four to five times higher than node-negative patients. Sub-dividing node-positive patients into 1-3 and > 3 node-positive subsets did not substantially change the general picture of tumor recurrence. The hazard functions for premenopausal and postmenopausal patients were virtually superimposable. CONCLUSIONS: The multipeak hazard curve suggests that the process resulting in overt clinical metastases may have discrete features. Primary tumor size could affect in different ways early and late metastases, while axillary node status should be related to the risk level, not to the risk pattern, and menopausal status does not seem to significantly affect the hazard distribution. Moreover, contralateral breast tumors, occurring at constant risk throughout the time, should be considered as second primary cancers. These findings could be reasonably explained by a tumor dormancy hypothesis, which assumes that micrometastases may be in different biological steady states, most of which do not imply tumor growth. Tumor or microenvironment changes could induce metastatic growth after given mean transition times from surgery and originate a discrete pattern of the hazard function.

Adult↗
PubMed1996

The coiled coil stem loop miniprotein as a presentation scaffold.

The coiled coil helical dimer found in naturally occurring proteins is conformationally stable and can tolerate significant sequence variation on the solvent-exposed surfaces of the helices. We are interested in exploring the use of a de novo designed coiled coil stem loop miniprotein (CCSL) as a template for presenting (1) helical and loop sequences from heterologous proteins and (2) constrained libraries of peptides. Towards this end, we synthesized a 56 residue prototype CCSL and verified its structure by extensive biophysical characterization. CCSL variants with altered sequences in the solvent-exposed helical positions were found to fold similarly to the prototype design. Based on the results with the CCSL produced by peptide synthesis, we assembled a synthetic cDNA for the CCSL prototype and expressed the CCSL miniprotein on filamentous phage. This genetic construction can be used to introduce random peptide libraries into regions within the scaffold loop and helices in order to identify key side chains of native proteins involved in binding, to establish structural models for their pharmacophores and to identify novel peptide recognition mimics of macromolecular ligands and their receptors.

Amino Acid Sequence↗
PubMed1995

Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. A pilot study by the I.T.M.O. Group. Italian Trials in Medical Oncology.

Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.

Adult↗
PubMed1989

Mapping of antibody specificities to VH gene families.

VH gene segments represent the products of the repeated duplication and subsequent diversification of a primordial V gene element. It is widely assumed that natural selection, operating via pathogens, has played the dominant role in this process. Here, we screen some 3.7 x 10(4) C mu+ colonies of mitogen-activated B cells for the production of antibodies specific for phosphorylcholine or hen egg lysozyme and expression of the VH X-24, S107, Q52, or J558 gene families. These gene families were expressed at frequencies proportional to their genomic complexity among both unselected and antigen-specific C mu+ colonies. Thus, the capacity to encode equivalent antibody-combining sites is dispersed uniformly among VH families. This result suggests that individual VH genes have not evolved to address specific antigens.

Animals↗
PubMed1989

[Experiences with coronarography using digital technics].

The authors report their experience with the application of digital techniques to coronary angiography, over the past 2 years. One hundred and fifty coronary angiographies were performed, with excellent results. Indications for surgical by-pass arose for 64 patients, 35 of whom have already undergone surgery. Coronary angioplasty procedures (PTCA) were needed in 13 cases; on 12 the procedure has already been carried out. The difficulty to provide the cardiac surgeon with images in movement has been overcome by recording the images passing on the TV monitor directly on a professional magnetic tape. On the basis of our initial experience, we may affirm that the application of digital techniques to coronary angiography does not modify the technical approach to the exam and, therefore, does not reduce its invasiveness. On the other hand, the examination can be performed using the software commonly found in many units used for digital angiography. From a morphological point of view, the images seem to be superimposable to the conventional ones, especially since sequences of 25 images/second can be acquired with a 512 matrix. The potentials of digital techniques to provide functional data and information on anatomic lesions are very interesting, even though they are still to be fully demonstrated.

Angiography, Digital Subtraction↗