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Roberta Ruggeri, Tiziana Camerini,
Roberto Patuzzo,
Andrea Maurichi,
Riccardo Pirovano,
Ilaria Mattavelli,
Federica Crippa,
Elena Tolomio,
Daniele Moglia,
Annabella Di Florio,
Mario Santinami
[show abstract]
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ABSTRACT: INTRODUCTION: Melanoma with recurrent loco-regional metastases to limbs often makes difficult a second surgical approach because of the adhesions affecting the vascular access. Our aim was to evaluate whether the placement of a polytetrafluoroethylene (PTFE) membrane around vessels might facilitate a surgical re-approach. PRESENTATION OF CASE: We reported a case of a 64-year-old male with a melanoma on the left foot who developed in transit metastases after LND. While performing the inguinopelvic LND we coated the iliac vessels with PTFE patch to facilitate the vascular access in case of re-intervention for a ILP. In the second surgical approach we made a cutaneous incision in the left iliac region and we proceeded through the subcutaneous tissue until detection of iliac vessels, more clearly visible because of the PTFE patch fixed around vascular walls to minimize adhesions. We removed the PTFE coating and easily performed arteriotomy and venotomy for the completion of the ILP. DISCUSSION: This case report seems to demonstrate the efficacy of a PTFE membrane applied in a patient around iliac vessels during inguinopelvic dissection, to reduce adhesion density. In fact this membrane provided a barrier to adhesions of the iliac vessels, decreasing the risk of vascular injury thereby facilitating a subsequent vascular access. Re-coating of the iliac vessels with PTFE could be preparatory to a better identification of the vascular structures in cases of a surgical re-approach. CONCLUSION: The use of PTFE effectively simplifies the second approach to vessels in event of a melanoma metastasizing to limbs.
International journal of surgery case reports. 09/2012; 4(1):40-43.
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Vincenzo Mazzaferro,
Carlo Sposito,
Sherrie Bhoori,
Raffaele Romito,
Carlo Chiesa,
Carlo Morosi,
Marco Maccauro,
Alfonso Marchianò,
Marco Bongini,
Rodolfo Lanocita,
Enrico Civelli,
Emilio Bombardieri, Tiziana Camerini,
Carlo Spreafico
[show abstract]
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ABSTRACT: BACKGROUND AND RATIONALE: yttrium-90 microspheres radioembolization (Y90RE) is a novel approach to radiation therapy for hepatocellular carcinoma (HCC), never tested in phase II studies. Fifty-two patients with intermediate (n.17) - advanced (n.35) HCC were prospectively recruited to assess, as primary endpoint, efficacy of Y90RE on time-to-progression (TTP). Secondary endpoints were tumor response, safety and overall survival (OS). All patients were ECOG 0-1, Child-Pugh A-B7. Y90RE treatments aimed at lobar delivery of 120 Gy. Retrospective dosimetric correlations were conducted and related to response. MAIN RESULTS: Fifty-eight treatments were performed on 52 patients. Median follow-up was 36 months. Median TTP was 11 months with no significant difference between portal vein thrombosis (PVT) vs. no-PVT (7 vs. 13 mo). Median OS was 15 mo (95%CI: 12-18) with a non-significant trend in favor of non-PVT vs. PVT patients (18 vs. 13 mo). Five complete responses occurred (9.6%) and the 2yr-progression rate was 62%. Objective response was 40.4% whilst disease control rate (DCR: 78.8%) significantly affected survival (responders vs. non-responders: 18.4% vs. 9.1%; P = 0.009). Tumor response significantly correlated with absorbed dose in target lesions (r=0.60, 95%CI: 0.41-0.74, P <0.001) and a threshold of 500 Gy predicted response (AUC= 0.78). Mortality at 30-90 days was 0%-3.8%. Various grades of reduction in liver function occurred within 6 mo in 36.5% of patients with no differences among stages. At the multivariate analysis tumor response was the sole variable affecting TTP (P <0.001) and the second, after Child-Pugh stage, affecting survival. CONCLUSIONS: Y90RE is an effective treatment in intermediate-advanced HCC, particularly in case of PVT. Further prospective evaluations comparing Y90RE with conventional treatments are warranted. (ClinicalTrials.gov NCT00910572) (HEPATOLOGY 2012.).
Hepatology 08/2012; · 11.66 Impact Factor
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James F Reid,
Viktorija Sokolova,
Eugenio Zoni,
Andrea Lampis,
Sara Pizzamiglio,
Claudia Bertan,
Susanna Zanutto,
Federica Perrone, Tiziana Camerini,
Gianfrancesco Gallino,
Paolo Verderio,
Ermanno Leo,
Silvana Pilotti,
Manuela Gariboldi,
Marco A Pierotti
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ABSTRACT: Altered expression of miRNAs is associated with development and progression of various human cancers by regulating the translation of oncogenes and tumor suppressor genes. In colorectal cancer, these regulators complement the Vogelstein multistep model of pathogenesis and have the potential of becoming a novel class of tumor biomarkers and therapeutic targets. Using quantitative real-time PCR, we measured the expression of 621 mature miRNAs in 40 colorectal cancers and their paired normal tissues and identified 23 significantly deregulated miRNAs. We subsequently evaluated their association with clinical characteristics of the samples and presence of alterations in the molecular markers of colorectal cancer progression. Expression levels of miR-31 were correlated with CA19-9 and miR-18a, miR-21, and miR-31 were associated with mutations in APC gene. To investigate the downstream regulation of the differentially expressed miRNAs identified, we integrated putative mRNA target predictions with the results of a meta-analysis of seven public gene expression datasets of normal and tumor samples of colorectal cancer patients. Many of the colorectal cancer deregulated miRNAs computationally mapped to targets involved in pathways related to progression. Here one promising candidate pair (miR-1 and MET) was studied and functionally validated. We show that miR-1 can have a tumor suppressor function in colorectal cancer by directly downregulating MET oncogene both at RNA and protein level and that reexpression of miR-1 leads to MET-driven reduction of cell proliferation and motility, identifying the miR-1 downmodulation as one of the events that could enhance colorectal cancer progression.
Molecular Cancer Research 02/2012; 10(4):504-15. · 4.29 Impact Factor
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International Journal of Cancer 02/2011; 130(2):488-9. · 5.44 Impact Factor
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Andrea Maurichi,
Rosalba Miceli, Tiziana Camerini,
Paolo Contiero,
Roberto Patuzzo,
Gabrina Tragni,
Federica Crippa,
Konstantinos Romanidis,
Roberta Ruggeri,
Antonino Carbone,
Mario Santinami
[show abstract]
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ABSTRACT: The purpose of the study was to evaluate the excision margin necessary for desmoplastic melanoma (DM).
DM consists of 2 histologic subtypes, pure DM (PDM) and mixed DM (MDM), differing in extent of fibrotic component. We investigated clinical and therapeutic determinants of prognosis in these DM entities.
We reviewed 118 PDM and 124 MDM treated at our Institute over 25 years. Local relapse, distant metastasis, and survival were studied.
Most (91.7%) distant metastases in PDM developed after 1 or more local recurrences; whereas distant metastasis usually (79.6%) occurred as first event in MDM. Overall mortality trends in relation to lesion-thickness-plus-excision-width differed for PDM (P = 0.014) but not MDM (P = 0.185). For PDM, 5-year crude cumulative incidence (CCI) of mortality was higher (40.0%) for thin tumors (≤ 2 mm thick) excised with 1 cm margin than those excised with 2 cm (14.8%); CCI of mortality for PDM > 2 mm thick excised with 2 cm margins (13.4%) was similar to that for thin PDM lesions excised with 2 cm (14.8%). CCI of local recurrence was also greater in PDM excised with 1 cm margins. In MDM, mortality increased with stage but was independent of excision width (CCI: 29.4% for ≤ 2 mm/2 cm, 31.3% for ≤ 2 mm/1 cm, and 48.3% for > 2 mm/2 cm); a similar trend was found for MDM distant metastases.
In PDM, limited excision width is associated with significantly greater local recurrence and mortality; treatment should be excision with 2 cm margins even for thin lesions. MDM behaves similarly to other melanomas; treatment should follow guidelines on melanoma management.
Annals of surgery 12/2010; 252(6):1052-7. · 7.90 Impact Factor
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Giulia Bertolini,
Luca Roz,
Paola Perego,
Monica Tortoreto,
Enrico Fontanella,
Laura Gatti,
Graziella Pratesi,
Alessandra Fabbri,
Francesca Andriani,
Stella Tinelli,
Elena Roz,
Roberto Caserini,
Salvatore Lo Vullo, Tiziana Camerini,
Luigi Mariani,
Domenico Delia,
Elisa Calabrò,
Ugo Pastorino,
Gabriella Sozzi
[show abstract]
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ABSTRACT: The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and for predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells, was described as a marker of cancer-initiating cells in different tumor types. Here, we report that a CD133+, epithelial-specific antigen-positive (CD133+ESA+) population is increased in primary nonsmall cell lung cancer (NSCLC) compared with normal lung tissue and has higher tumorigenic potential in SCID mice and expression of genes involved in stemness, adhesion, motility, and drug efflux than the CD133(-) counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction both after acute cytotoxic exposure and in cells with stable cisplatin-resistant phenotype. Subpopulations of CD133+ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts established from primary tumors. A tendency toward shorter progression-free survival was observed in CD133+ NSCLC patients treated with platinum-containing regimens. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and the definition of predictive factors in clinical management of this lethal disease.
Proceedings of the National Academy of Sciences 09/2009; 106(38):16281-6. · 9.68 Impact Factor
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Alfonso Marchianò,
Elisa Calabrò,
Enrico Civelli,
Giuseppe Di Tolla,
Laura Francesca Frigerio,
Carlo Morosi,
Francesco Tafaro,
Elena Ferri,
Nicola Sverzellati, Tiziana Camerini,
Luigi Mariani,
Salvatore Lo Vullo,
Ugo Pastorino
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ABSTRACT: To assess in vivo volumetric repeatability of an automated software algorithm in pulmonary nodules detected during a lung cancer screening trial.
This study was approved by an institutional review board. Written informed consent was obtained from all participants. Data were collected from the Multicentric Italian Lung Detection project, a randomized controlled lung cancer screening trial. The first 1236 consecutive baseline computed tomographic (CT) studies performed at the Istituto Nazionale Tumori of Milan were evaluated. Among the enrolled participants, those who underwent repeat low-dose CT after 3 months and had at least one indeterminate nodule with a volume of more than 60 mm(3) (diameter of 4.8 mm or greater) were considered. Nonsolid, part-solid, and pleural-based nodules were excluded from this study. A descriptive analysis was performed by calculating means and standard deviations of nodule volumes at three assessment times (at baseline and 3 and 12 months later). The volume measurement repeatability was determined by using the approach described by Bland and Altman.
One hundred one subjects (70 men, 31 women; mean age, 58 years) with 233 eligible nodules (mean volume, 98.3 mm(3); range, 5-869 mm(3)) were identified. The 95% confidence interval for difference in measured volumes was in the range of +/-27%. About 70% of measurements had a relative difference in nodule volume of less than 10%. No malignant lesions were registered during the follow-up of these subjects.
Semiautomatic volumetry is sufficiently accurate and repeatable and may be useful in assisting with lung nodule management in a lung cancer screening program.
Radiology 05/2009; 251(3):919-25. · 5.73 Impact Factor
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Vincenzo Mazzaferro,
Josep M Llovet,
Rosalba Miceli,
Sherrie Bhoori,
Marcello Schiavo,
Luigi Mariani, Tiziana Camerini,
Sasan Roayaie,
Myron E Schwartz,
Gian Luca Grazi, [......],
Roberto Troisi,
Massimo Rossi,
Giorgio E Gerunda,
Jan Lerut,
Jacques Belghiti,
Ilka Boin,
Jean Gugenheim,
Fedja Rochling,
Bart Van Hoek,
Pietro Majno
[show abstract]
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ABSTRACT: Patients undergoing liver transplantation for hepatocellular carcinoma within the Milan criteria (single tumour </=5 cm in size or </=3 tumours each </=3 cm in size, and no macrovascular invasion) have an excellent outcome. However, survival for patients with cancers that exceed these criteria remains unpredictable and access to transplantation is a balance of maximising patients' chances of cure and organ availability. The aim of this study was to explore the survival of patients with tumours that exceed the Milan criteria, to assess whether the criteria could be less restrictive, enabling more patients to qualify as transplant candidates, and to derive a prognostic model based on objective tumour characteristics, to see whether the Milan criteria could be expanded.
Data on patients who underwent transplantation for hepatocellular carcinoma despite exceeding Milan criteria at different centres were recorded via a web-based survey completed by specialists from each centre. The survival of these patients was correlated retrospectively with the size of the largest tumour nodule, number of nodules, and presence or absence of microvascular invasion detected at pathology. Contoured multivariable regression Cox models produced survival estimates by means of different combinations of the covariates. The primary aim of this study was to derive a prognostic model of overall survival based on tumour characteristics, according to the main parameters used in the Tumour Node Metastasis classification. The secondary aim was the identification of a subgroup of patients with hepatocellular carcinoma exceeding the Milan criteria, who achieved a 5-year overall survival of at least 70%-ie, similar to the outcome expected for patients who meet the Milan criteria.
Over a 10-month period, between June 25, 2006, and April 3, 2007, data for 1556 patients who underwent transplantation for hepatocellular carcinoma were entered on the database by 36 centres. 1112 patients had hepatocellular carcinoma exceeding Milan criteria and 444 patients had hepatocellular carcinoma shown not to exceed Milan criteria at post-transplant pathology review. In the group of patients with hepatocellular carcinomas exceeding the criteria, the median size of the largest nodule was 40 mm (range 4-200) and the median number of nodules was four (1-20). 454 of 1112 patients (41%) had microvascular invasion and, for those transplanted outside the Milan criteria, 5-year overall survival was 53.6% (95% CI 50.1-57.0), compared with 73.3% (68.2-77.7) for those that met the criteria. Hazard ratios (HR) associated with increasing values of size and number were 1.34 (1.25-1.44) and 1.51 (1.21-1.88), respectively. The effect was linear for size, whereas for number of tumours, the effect tended to plateau above three tumours. The effect of tumour size and number on survival was mediated by recurrence (b=0.08, SE=0.12, p=0.476). The presence of microvascular invasion doubled HRs in all scenarios. The 283 patients without microvascular invasion, but who fell within the Up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumour [in cm] and the number of tumours) achieved a 5-year overall survival of 71.2% (64.3-77.0).
More patients with hepatocellular carcinoma could be candidates for transplantation if the current dual (yes/no) approach to candidacy, based on the strict Milan criteria, were replaced with a more precise estimation of survival contouring individual tumour characteristics and use of the up-to-seven criteria.
The lancet oncology 01/2009; 10(1):35-43. · 14.47 Impact Factor
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[show abstract]
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ABSTRACT: The role of retinol (vitamin A) in breast cancer prognosis has never been investigated in postmenopausal women. We prospectively assessed the long-term prognostic role of retinol plasma levels in a cohort of postmenopausal breast cancer patients. Patients and
We investigated 208 women self-reported as postmenopausal operated on for T(1-2)N(0)M(0) breast cancer who participated in a chemoprevention trial as controls and never received chemotherapy or hormone therapy. Plasma samples were collected 3 months (median) after surgery and assayed within 3 weeks for retinol. Minimum and median potential follow-up were 12 and 15 years, respectively. The main analyses were on all women and on a subgroup ages >or=55 years, assumed too old to be in perimenopause. The main end point was breast cancer death. Breast cancer survival was estimated by the Kaplan-Meier method. The hazard ratios of breast cancer death by retinol level were estimated by Cox models stratified for age, where relevant, and recruitment period, and adjusted for tumor size and histology.
At 12 years, patients with low retinol (<2.08 micromol/L, median of distribution) had lower breast cancer survival than those with high retinol (log-rank P = 0.052); the difference was significant for women >or=55 years (log-rank P = 0.006). The adjusted hazard ratios for low versus high retinol were 2.11 (95% confidence interval, 1.08-4.14) for all women and 3.58 (95% confidence interval, 1.50-8.57) for those >or=55 years.
Low plasma retinol strongly predicts poorer prognosis in postmenopausal breast cancer patients. Retinol levels should be determined as part of the prognostic workup.
Cancer Epidemiology Biomarkers & Prevention 01/2009; 18(1):42-8. · 4.12 Impact Factor
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Andrea Micheli,
Elisabetta Meneghini,
Giorgio Secreto,
Franco Berrino,
Elisabetta Venturelli,
Adalberto Cavalleri, Tiziana Camerini,
Maria G Di Mauro,
Elena Cavadini,
Giuseppe De Palo,
Umberto Veronesi,
Franca Formelli
[show abstract]
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ABSTRACT: High endogenous testosterone is associated with increased breast cancer (BC) risk. We designed this study specifically to assess the long-term prognostic role of testosterone in a cohort of postmenopausal BC patients.
We considered 194 postmenopausal women, operated on for early BC (T1-2N0M0), who never received chemotherapy or hormonal therapy, and who participated in a fenretinide BC prevention trial as untreated controls. Blood samples were collected 3 months (median) after surgery; plasma samples, stored at -80 degrees C, were radioimmunoassayed for testosterone. Median follow-up was 14 years. The main end point was any cancer event. Event-free survival was estimated by the Kaplan-Meier method. Hazard ratios (HRs) of events by testosterone level were estimated by the Cox model, adjusting for age, tumor size, and histology.
Patients with high testosterone (> or = 0.40 ng/mL, median of distribution) had significantly lower event-free survival than those with low testosterone (log-rank P = .004). The adjusted HR of patients with high versus low testosterone was 2.05 (95% CI, 1.28 to 3.27). High testosterone was also associated with a significantly higher risk of BC events (relapse and second primary) with an adjusted HR of 1.77 (95% CI, 1.06 to 2.96). Eleven second primaries (non-BC) occurred in the high-testosterone group, four in the low-testosterone group.
High plasma testosterone strongly predicts poorer prognosis in postmenopausal BC patients not administered adjuvant therapy. Testosterone levels should be determined as part of the prognostic work-up.
Journal of Clinical Oncology 08/2007; 25(19):2685-90. · 18.37 Impact Factor
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Fabio Castiglioni,
Monica Terenziani,
Maria Luisa Carcangiu,
Raffaella Miliano,
Piera Aiello,
Lorenzo Bertola,
Tiziana Triulzi,
Patrizia Gasparini, Tiziana Camerini,
Gabriella Sozzi,
Franca Fossati-Bellani,
Sylvie Ménard,
Elda Tagliabue
[show abstract]
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ABSTRACT: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas.
Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas.
Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset.
Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.
Clinical Cancer Research 02/2007; 13(1):46-51. · 7.74 Impact Factor
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Vincenzo Mazzaferro,
Raffaele Romito,
Marcello Schiavo,
Luigi Mariani, Tiziana Camerini,
Sherrie Bhoori,
Lorenzo Capussotti,
Fulvio Calise,
Riccardo Pellicci,
Giulio Belli,
Alessandro Tagger,
Massimo Colombo,
Ferruccio Bonino,
Pietro Majno,
Josep M Llovet
[show abstract]
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ABSTRACT: Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA-positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09-0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.
Hepatology 01/2007; 44(6):1543-54. · 11.66 Impact Factor
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Natale Cascinelli,
Emilio Bombardieri,
Rosaria Bufalino, Tiziana Camerini,
Antonino Carbone,
Claudio Clemente,
Leonardo Lenisa,
Luigi Mascheroni,
Andrea Maurichi,
Elisabetta Pennacchioli,
Roberto Patuzzo,
Mario Santinami,
Gabrina Tragni
[show abstract]
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ABSTRACT: To evaluate the prognostic significance of sentinel node biopsy in the management of stage IB and II melanoma patients, and to evaluate the status of nonsentinel nodes as a "second step key factor" to assess the prognosis of these patients.
We conducted an analysis of data collected in a prospective database.
From February 1994 to June 2005, 1,108 consecutive patients with stage IB and II melanoma were submitted to sentinel node biopsy; 176 patients (15.9%) had occult node metastases. The frequency of positive nodes increased with increasing Breslow's thickness. The largest diameter of metastatic foci and their localization within the lymph node were associated with the risk of nonsentinel node metastases only. The 5-year survival of patients with positive sentinel nodes was 81.4% in patients with one positive node and 39.6% in patients with two positive nodes (P = .056). Multivariate analysis indicated that status of sentinel nodes is a key factor and that sex and Breslow's thickness maintain statistically significant relevance. Ulceration, which was associated with survival when considered as single factor (P < .001) had no impact on survival in the multivariate analysis (P = .10). To evaluate the relevance of metastases to nonsentinel nodes, we identified four groups of patients.
Evaluation of the sentinel node is a useful procedure to identify patients to be submitted for complete lymph node dissection. The procedure makes it possible to assess the best prognosis of patients.
Journal of Clinical Oncology 10/2006; 24(27):4464-71. · 18.37 Impact Factor
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ABSTRACT: We designed and assessed a new TNM staging system (herein called the INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to overcome the perceived drawbacks of Masaoka's system, which represents the current standard.
In all, 123 cases were evaluated. The histologic types according to the World Health Organization (WHO) classification were as follows: subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were 45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total of 11 INT definitions were grouped into three stages: locally restricted disease (75 cases), which included Masaoka's stage I and selected stage II cases (no pleural invasion); locally advanced disease (37 cases), which included Masaoka's stage III cases plus those staged II owing to pleural invasion and those staged IV owing to intrathoracic nodal or limited pleuropericardial involvement; and systemic disease (11 cases), which included the remaining Masaoka's stage IV cases.
Completeness of resection, WHO types, and both staging systems were significant prognostic factors (p < 0.0001) on univariate analysis. The 95-month progression-free survival rates according to Masaoka's system were stage I: 100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures were as follows: locally restricted disease: 98.6%; locally advanced disease: 46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p = 0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386).
The INT system allows finer disease descriptions than Masaoka's system, resulting in a stage grouping with higher prognostic distinctiveness.
The Annals of thoracic surgery 12/2005; 80(6):1994-2000. · 3.74 Impact Factor
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Vincenzo Mazzaferro,
Carlo Battiston,
Stefano Perrone,
Andrea Pulvirenti,
Enrico Regalia,
Raffaele Romito,
Dario Sarli,
Marcello Schiavo,
Francesco Garbagnati,
Alfonso Marchianò,
Carlo Spreafico, Tiziana Camerini,
Luigi Mariani,
Rosalba Miceli,
Salvatore Andreola
[show abstract]
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ABSTRACT: Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT).
RFA has become the elective treatment of local control of HCC, although histologic data supporting radiologic assessment of response are rare and prospective studies are lacking. Prognostic impact of repeated RFA for HCC persistence is also undetermined.
Percentage of RFA-induced necrosis and tumor persistence-rate at various intervals from treatment was studied in 60 HCC (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic patients undergoing OLT. Single-session RFA was the only treatment planned before OLT. Histologic response determined on explanted livers was related to 28 variables and to pre-OLT CT scan.
Mean interval RFA-->OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC </=3 cm. Tumor size was the only prognostic factor significantly related to response (P = 0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA and significantly correlated with HCC >3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%.
RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.
Annals of Surgery 12/2004; 240(5):900-9. · 7.49 Impact Factor
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Dermatology online journal 02/2004; 10(2):5.
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Andrea Decensi,
Umberto Veronesi,
Rosalba Miceli,
Harriet Johansson,
Luigi Mariani, Tiziana Camerini,
Maria Gaetana Di Mauro,
Elena Cavadini,
Giuseppe De Palo,
Alberto Costa,
Marjorie Perloff,
Winfred F Malone,
Franca Formelli
[show abstract]
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ABSTRACT: High circulating insulin-like growth factor (IGF) -I and/or low IGF-binding protein (IGFBP) -3 levels are associated with increased breast cancer risk in unaffected premenopausal women. We determined whether IGF-I and IGFBP-3 predict second breast cancer risk, and whether their changes during fenretinide explain observed reductions in second breast cancer in women </=50 years of age.
Within a Phase III trial, we measured baseline and 1-year levels of IGF-I, IGFBP-3, and their ratio in 302 subjects on fenretinide and 220 controls who provided plasma samples. The prognostic effect of IGF-I and IGFBP-3, and the surrogate effect of IGF-I during fenretinide were assessed by Cox models after 9.4 years.
Among controls, high IGF-I and low IGFBP-3 were associated with elevated second breast cancer risk [top versus bottom tertile, IGF-I, hazard ratio (HR) = 1.94, 95% confidence interval (CI), 0.87-4.31, P = 0.105; and IGFBP-3, HR = 0.40, 95% CI, 0.18-0.93, P = 0.033]. Fenretinide induced reductions of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 of 8% (95% CI, 2-12%; P = 0.004), 3% (95% CI, 1-5%; P = 0.002), and 5% (95% CI, 0-10%; P = 0.050), respectively. Second breast cancer risk was reduced by 39% (HR = 0.61; 95% CI, 0.40-0.94; P = 0.026). The percentage of treatment effect explained by IGF-I and IGF-I:IGFBP-3 reductions were 4.8% (95% CI, 0.8-28.9%) and 3.1% (95% CI, 0.5-20.8%), respectively.
Fenretinide induced a moderate reduction of IGF-I, which marginally explains observed cancer risk reductions in women </=50 years of age. In this age group high IGF-I and particularly low IGFBP-3 levels predict second breast cancer risk.
Clinical Cancer Research 10/2003; 9(13):4722-9. · 7.74 Impact Factor
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Vincenzo Mazzaferro,
Jorgelina Coppa,
Matteo G Carrabba,
Licia Rivoltini,
Marcello Schiavo,
Enrico Regalia,
Luigi Mariani, Tiziana Camerini,
Alfonso Marchianò,
Salvatore Andreola,
Roberto Camerini,
Marco Corsi,
Jonathan J Lewis,
Pramod K Srivastava,
Giorgio Parmiani
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ABSTRACT: Heat shock proteins (HSP) from tumor cells contain the gp96 polypeptide associated with cancer-specific antigenic peptides. Mice that are immunized with HSP/peptide-complex (HSPPC) derived from cancer tissue reject tumor from which HSPs are purified. We tested in humans whether vaccination with HSPPC-gp96 (Oncophage) from autologous liver metastases of colorectal carcinoma induces cancer-specific T-cell responses in patients rendered disease free by surgery. Experimental Design: Twenty-nine consecutive patients underwent radical resection of liver metastases [Memorial Sloan-Kettering Cancer Center (MSKCC) score 1-3 (good prognosis), 18 patients; score 4-5 (bad prognosis), 11 patients] and received autologous tumor-derived HSPPC-96. Two vaccine cycles were administered (four weekly injections followed by four biweekly injections after 8 weeks). Class-I HLA-restricted, anti-colon cancer lines T-cell response was measured by ELISPOT assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Feasibility, safety, and possible clinical benefits were also evaluated.
Either a de novo induced or a significant increase of preexisting class I HLA-restricted T-cell-mediated anti-colon cancer response was observed in 15 (52%) of 29 patients. Frequency of CD3+, CD45RA+, and CCR7- T lymphocytes increased in immune responders. No relevant toxicity was observed. As expected, patients with good prognosis had a significantly better clinical outcome than those with poor prognosis [2-year overall survival (OS), 89 versus 64%, P = 0.001; disease-free survival (DFS), 46 versus 18%, P = 0.001]. Patients with immune response had a statistically significant clinical advantage over nonresponding subjects (2-year OS, 100% versus 50%, P = 0.001; DFS, 51% versus 8%, P = 0.0001). Occurrence of immune response led to better tumor-free survival, whatever the predicted prognosis was (hazard ratio, 0.11-0.12 with/without stratification; P = 0.0012-0.0003).
HSPPC-96 vaccination after resection of colorectal liver metastases is safe and elicits a significant increase in CD8+ T-cell response against colon cancer. In this limited number of patients, two-year OS and DFS were significantly improved in subjects with postvaccination antitumor immune response, independently from other clinical prognostic factors.
Clinical Cancer Research 09/2003; 9(9):3235-45. · 7.74 Impact Factor
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ABSTRACT: To assess, in women participating in a breast cancer prevention trialon fenretinide (4-HPR), the relationship of drug and retinol levels with the risk of second breast malignancy, taking into account age and menopausal status.
In a multicenter prevention trial, women with early breast cancer were randomly assigned to receive no treatment or 200 mg of 4-HPR/day for 5 years. Blood was collected at baseline and on a yearly basis during intervention from women recruited at the Istituto Tumori (Milan, Italy; 818 and 756 in the 4-HPR and control arm, respectively, who accounted for 53% of the participants in the trial). The plasma concentrations of 4-HPR, its main metabolite N-(4-methoxyphenyl) retinamide, and retinol were assayed by high-performance liquid chromatography. Three age ranges (<or=45, 46-55, and >or=56 years), menopausal status at baseline, and disease outcome at a median follow-up of 97 months were taken into account in the analysis.
Baseline retinol levels were significantly lower (P <or= 0.05) in subjects <or= 45 years than in older subjects, and among subjects in the age range 46-55 years, they were significantly higher (P <or= 0.001) in those in postmenopause than in those in premenopause. Baseline retinol levels were not related to the risk of a second breast malignancy. 4-HPR and N-(4-methoxyphenyl)retinamide levels were not affected by menopausal status. They slightly, but significantly (P <or= 0.05), increased with age (>or=46 years versus <or=45 years) but only in disease-free subjects. Among subjects < 45 years, they were slightly, but significantly (P <or= 0.05), higher in those subjects in which breast cancer recurred. 4-HPR treatment caused a retinol level reduction, which was strongly (r >or= 0.71; P <or= 0.001) related to pretreatment retinol levels.
Retinol plasma levels increased with age and after menopause and were not related to breast cancer recurrence. 4-HPR levels were lower in subjects < 45 years than in older subjects. The inverse relationship between drug plasma levels and 4-HPR preventive effects observed in young women suggests a role for 4-HPR plasma sequestration in 4-HPR biological activity.
Cancer Epidemiology Biomarkers & Prevention 01/2003; 12(1):34-41. · 4.12 Impact Factor
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ABSTRACT: The aim of this study was to update the effect of fenretinide, a synthetic vitamin A analogue proposed for chemoprevention, on the occurrence of ovarian carcinoma.
Data were obtained from a randomized clinical trial for the prevention of second breast cancer. For the present investigation, events of interest were new primary carcinomas of the ovary arising in the fenretinide or the no-treatment (control) arm. The probability of carrying a BRCA germ-line mutation was assessed in women with ovarian carcinoma according to G. Parmigiani et al. (1998, Am J Hum Genet 62, 145-58).
Fenretinide reduced ovarian carcinoma occurrence during the 5-year intervention period (0 versus 6 cases in the fenretinide and control arm, P = 0.0327). This effect was no longer evident after the 5-year intervention period (6 versus 4 cases, P = 0.7563). Therefore with median observation time of 121 months, a total of 6 carcinomas of the ovary occurred in the fenretinide group and 10 in the control group. The probability of carrying a BRCA mutation was lower for women with ovarian carcinoma in the treatment arm.
Fenretinide treatment was associated with a lower incidence of ovarian carcinoma during the intervention period but such a protective effect seems to disappear after treatment. Furthermore, a possible protective effect of fenretinide in BRCA-mutated women was suggested. Further studies on fenretinide for the prevention of ovarian carcinoma particularly in women with genetic susceptibility appear necessary.
Gynecologic Oncology 08/2002; 86(1):24-7. · 3.89 Impact Factor
