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1.
Br J Dermatol ; 186(4): 694-704, 2022 04.
Article in English | MEDLINE | ID: mdl-34773645

ABSTRACT

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.


Subject(s)
Melanoma , Skin Neoplasms , Transforming Growth Factor beta2/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Epidermis/metabolism , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Transforming Growth Factor beta/metabolism , Transforming Growth Factors/metabolism
2.
Eur Rev Med Pharmacol Sci ; 25(20): 6300-6310, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34730210

ABSTRACT

OBJECTIVE: Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. PATIENTS AND METHODS: Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspid regurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. RESULTS: Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. CONCLUSIONS:  Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.


Subject(s)
Arrhythmias, Cardiac/epidemiology , Tetralogy of Fallot/surgery , Ventricular Dysfunction, Right/epidemiology , Ventricular Function, Right/physiology , Adolescent , Adult , Age Factors , Child , Disease Progression , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Risk Factors , Stroke Volume/physiology , Ventricular Dysfunction, Right/diagnostic imaging , Young Adult
4.
Surg Neurol Int ; 9: 38, 2018.
Article in English | MEDLINE | ID: mdl-29527396

ABSTRACT

BACKGROUND: The paraspinal, posterolateral, or Wiltse approach is an old technique that observes the principles of an MIS procedure. The aim of this study was to provide a step-by-step description from the literature of the Wiltse paraspinal approach and analyze its main advantages and limitations. METHODS: Here, we provide a step-by-step description of the Wiltse approach. Utilizing PubMed and Lilacs and the Mesh terms "Wiltse approach," "paraspinal approach," "muscle sparing approach," and "lumbar spine," we identified 10 papers. We then put together, based on these publications, a step-by-step analysis of the preparation, patient positioning, skin incision, fascial opening, dissection, bone identification, retractors, deperiostization, decompression, discectomy, instrumentation, arthrodesis, and closure for the Wiltse technique. RESULTS: Most papers underscored the minimally invasive aspects of the typical Wiltse approach. Advantages included minimal intraoperative bleeding, a shorter hospital length of stay, and a low infection rate. CONCLUSION: The classical approach described by Wiltse is essentially minimally invasive, sparing both the muscle planes and soft tissues, allowing for ample far lateral lumbar decompression, including discectomy and fusion, with a low complication rate.

5.
Nutr Metab Cardiovasc Dis ; 28(4): 418-424, 2018 04.
Article in English | MEDLINE | ID: mdl-29499851

ABSTRACT

BACKGROUND AND AIM: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes. METHODS AND RESULTS: We performed these studies in mouse hepatoma cells, that were grown in standard medium, or in media containing low glucose concentration, or no glucose, or no amino acids. We applied quantitative real-time PCR to cDNA, methylation-enriched DNA and nuclease-treated DNA in order to evaluate gene expression, DNA methylation, and chromatin condensation, respectively. This study shows that the expression of sirtuin genes varies following nutrient deprivation. Moreover, we observed that changes of DNA methylation and chromatin condensation occur at the transcription start site of sirtuin genes following nutrient deprivation. CONCLUSIONS: Epigenetic mechanisms may have a role in the sirtuin response to nutrient deprivations in cultured hepatoma cells. Replicating these results in vivo to achieve a comprehensive understanding of the epigenetic control of sirtuin expression following nutrient deprivations might open up novel therapeutic possibilities to cure metabolic diseases and promote human health.


Subject(s)
Amino Acids/deficiency , DNA Methylation , Epigenesis, Genetic , Glucose/deficiency , Hepatocytes/enzymology , Sirtuins/genetics , Sirtuins/metabolism , Animals , Caloric Restriction , Cell Line, Tumor , Chromatin Assembly and Disassembly , Gene Expression Regulation, Enzymologic , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription, Genetic , Transcriptome
6.
Pediatr Cardiol ; 38(8): 1613-1619, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28831530

ABSTRACT

Hyperplastic left heart syndrome (HLHS) patients are palliated by creating a Fontan-type circulation passing from different surgical stages. The aim of this work is to describe the evolution of ventricular energetics parameters in HLHS patients during the different stages of palliation including the hybrid, the Norwood, the bidirectional Glenn (BDG), and the Fontan procedures. We conducted a retrospective clinical study enrolling all HLHS patients surgically treated with hybrid procedure and/or Norwood and/or BDG and/or Fontan operation from 2011 to 2016 collecting echocardiographic and hemodynamic data. Measured data were used to calculate energetic variables such as ventricular elastances, external and internal work, ventriculo-arterial coupling and cardiac mechanical efficiency. From 2010 to 2016, a total of 29 HLHS patients undergoing cardiac catheterization after hybrid (n = 7) or Norwood (n = 6) or Glenn (n = 8) or Fontan (n = 8) procedure were retrospectively enrolled. Ventricular volumes were significantly higher in the Norwood circulation than in the hybrid circulation (p = 0.03) with a progressive decrement from the first stage to the Fontan completion. Ventricular elastances were lower in the Norwood circulation than in the hybrid circulation and progressively increased passing from the first stage to the Fontan completion. The arterial elastance and Rtot increased in the Fontan circulation. The ventricular work progressively increased. Finally, the ventricular efficiency improves passing from the first to the last stage of palliation. The use of ventricular energetic parameters could lead to a more complete evaluation of such complex patients to better understand their adaptation to different pathophysiological conditions.


Subject(s)
Heart Ventricles/physiopathology , Hypoplastic Left Heart Syndrome/surgery , Norwood Procedures/methods , Cardiac Catheterization/methods , Child, Preschool , Echocardiography , Female , Hemodynamics/physiology , Humans , Infant , Infant, Newborn , Male , Palliative Care/methods , Retrospective Studies , Treatment Outcome
7.
Eye (Lond) ; 31(12): 1740-1743, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28731055

ABSTRACT

PurposeTo describe multimodal imaging features of choroidal osteoma (CO) complicated by choroidal neovascularization (CNV) and focal choroidal excavation (FCE).MethodsPatients presenting with CO and CNV between January and October 2016 were considered for this study. Diagnosis of CO was confirmed by ultrasound examination. All patients underwent multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (DRI OCT Triton, Topcon, Inc., Tokyo, Japan) and fluorescein angiography (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).ResultsTwo patients (one with bilateral CO) were included in the study. OCT showed a FCE in two eyes of two patients (one in correspondence of the CNV and the other adjacent to the CNV). OCT-A demonstrated presence of microvascular flow within neovascular network of the CNVs. Decalcification of the tumor was noted in correspondence of one eye with FCE.ConclusionsFCE may be found in eyes with choroidal osteoma and CNV. OCT-A was a valuable tool for detection of CNV complicating choroidal osteoma. Decalcification of choroidal osteoma may represent a common pathogenic pathway for development of FCE and CNV in choroidal osteoma.


Subject(s)
Choroid Neoplasms/diagnosis , Choroid/pathology , Choroidal Neovascularization/etiology , Osteoma/diagnosis , Adult , Choroid Neoplasms/complications , Choroidal Neovascularization/diagnosis , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Male , Osteoma/complications , Retrospective Studies , Tomography, Optical Coherence
8.
Mater Sci Eng C Mater Biol Appl ; 59: 488-499, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26652400

ABSTRACT

This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs.


Subject(s)
Drug Carriers , Lactic Acid , Materials Testing , Nanoparticles/chemistry , Polyglycolic Acid , Rhodamines , Adsorption , Animals , Blood Proteins/chemistry , Cell Line, Transformed , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Lactic Acid/chemistry , Lactic Acid/pharmacokinetics , Lactic Acid/pharmacology , Mice , Polyglycolic Acid/chemistry , Polyglycolic Acid/pharmacokinetics , Polyglycolic Acid/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer , Rhodamines/chemistry , Rhodamines/pharmacokinetics , Rhodamines/pharmacology
9.
Med Eng Phys ; 37(9): 898-904, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26215925

ABSTRACT

The results of Hybrid procedure (HP) for the hypoplastic left heart syndrome (HLHS) depend on several variables: pulmonary artery banding tightness (PAB), atrial septal defect size (ASD) and patent ductus arteriosus stent size (PDA). A HP complication could be the aortic coarctaction (CoAo). The reverse Blalock-Taussig shunt (RevBT) placement was proposed to avoid CoAo effects. This work aims at developing a lumped parameter model (LPM) to investigate the effects of the different variables on HP haemodynamics. A preliminary verification was performed collecting measurements on a newborn HLHS patient to calculate LPM input parameters to reproduce patient's baseline. Results suggest that haemodynamics is affected by ASD (ASD: 0.15-0.55 cm, pulmonary to systemic flow ratio Qp/Qs: 0.73-1, cardiac output (CO): 1-1.5 l/min and ventricular stroke work SW: 336-577 ml mmHg) and by the PAB diameter (PAB: 0.07-0.2 cm, Qp/Qs: 0.46-2.1, CO: 1.3-1.6 l/min and SW: 591-535 ml mmHg). Haemodynamics was neither affected by RevBT diameter nor by PDA diameter higher than 0.2 cm. RevBT implantation does not change the HP haemodynamics, but it can make the CoAo effect negligible. LPM could be useful to support clinical decision in complex physiopathology and to calibrate and personalise the parameters that play a role on flow distribution.


Subject(s)
Hypoplastic Left Heart Syndrome/physiopathology , Models, Cardiovascular , Blalock-Taussig Procedure , Blood Pressure , Computer Simulation , Decision Support Systems, Clinical , Hemodynamics , Humans , Hypoplastic Left Heart Syndrome/diagnosis , Hypoplastic Left Heart Syndrome/pathology , Hypoplastic Left Heart Syndrome/surgery , Infant, Newborn
10.
PLoS One ; 10(7): e0132517, 2015.
Article in English | MEDLINE | ID: mdl-26161907

ABSTRACT

INTRODUCTION AND RESULTS: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. CONCLUSIONS: In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients.


Subject(s)
Centromere/genetics , DNA Methylation/genetics , Genome, Human , Immunologic Deficiency Syndromes/genetics , Case-Control Studies , Cell Line , Chromosomes, Human/genetics , CpG Islands/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Female , Gene Expression Regulation , Genetic Variation , Humans , Male , Promoter Regions, Genetic/genetics , Reproducibility of Results , Sequence Analysis, DNA , DNA Methyltransferase 3B
11.
Eur J Surg Oncol ; 39(9): 1025-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23827381

ABSTRACT

BACKGROUND: To evaluate the feasibility and the predictive value of cone biopsy before performing radical hysterectomy in locally advanced cervical cancer patients showing complete clinical response to neo-adjuvant chemoradiation. METHODS: Between March 2010 to March 2012 74 consecutive FIGO stage IIA2-IIB patients were submitted to neo-adjuvant chemoradiation. All complete clinical responder patients were enrolled in this pilot trial. RESULTS: Fifty-seven out of 74 patients (77%) showed complete clinical response and were enrolled in the study. Forty-two out of 57 patients (74%) underwent successful pre-completion surgery cone biopsy with a median cone's tissue diameter of 24 mm (range 18-35). In 33 out of 42 patients (58%) a complete pathological response was found. In the remaining 5 (9%) and 4 (7%) a microscopic partial and partial response was found, respectively. All 33 cases (58%) with negative cone showed complete pathological response in the radical hysterectomy specimens. Patients with microscopic residual tumor foci in the cone showed negative residual cervical and paracervical tissue at definitive diagnosis, whereas in patients with partial response macroscopic residual disease in the surgical specimens was found. The negative predictive value of cone biopsy, MRI and PET/CT in the prediction of pathological status of the cervical and paracervical tissue was 100%, 79% and 79%, respectively (Table 2). CONCLUSIONS: In this study we observed that, in locally advanced cervical patients showing complete clinical response to neo-adjuvant chemoradiation, the cone biopsy feasibility was almost 75%, and that there is a complete pathological correspondence between cone and definitive pathology.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy, Adjuvant , Conization , Neoadjuvant Therapy , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/therapy , Carcinoma, Squamous Cell/therapy , Cohort Studies , Combined Modality Therapy , Feasibility Studies , Female , Humans , Hysterectomy , Middle Aged , Pilot Projects , Remission Induction , Treatment Outcome , Uterine Cervical Neoplasms/therapy , Young Adult
12.
Pediatr Cardiol ; 34(8): 2080-5, 2013.
Article in English | MEDLINE | ID: mdl-23515761

ABSTRACT

Coarctation of the abdominal aorta is extremely rare. It generally involves a long segment of the descending aorta and causes uncontrolled and unexplainable hypertension in children. The therapeutic choice is very challenging because acute and chronic complications are reported for both the surgical and the percutaneous approaches. The two reported cases of abdominal coarctation were treated primarily and successfully through the use of covered stents. Three covered stents were implanted in two children. No complication occurred with either procedure. At this writing, an 18-month follow-up assessment has found the patients in good health with no restenosis at the coarctation site. Covered stent implantation in children with abdominal coarctation is a feasible, safe, and effective procedure. It provides adequate relief of symptoms and reduces the risk of aneurysm formation. To avoid covering important side branches with polytetrafluoroethylene, this type of procedure must be preceded by precise study of the aorta and its branches.


Subject(s)
Aorta, Abdominal/surgery , Aortic Coarctation/surgery , Blood Vessel Prosthesis , Coated Materials, Biocompatible , Polytetrafluoroethylene , Stents , Adolescent , Aorta, Abdominal/diagnostic imaging , Aortic Coarctation/diagnostic imaging , Aortography , Child , Female , Humans , Prosthesis Design
13.
Clin Genet ; 84(4): 362-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23210894

ABSTRACT

Non-compaction of the left ventricle (NCLV) is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intertrabecular recesses. Associated extracardiac anomalies occur in 14-66% of patients of different series, while chromosomal anomalies were reported in sporadic cases. We investigated the prevalence of chromosomal imbalances in 25 syndromic patients with NCLV, using standard cytogenetic, subtelomeric fluorescent in situ hybridization, and array-comparative genomic hybridization (CGH) analyses. Standard chromosome analysis disclosed an abnormality in three (12%) patients, including a 45,X/46,XX mosaic, a 45,X/46,X,i(Y)(p11) mosaic, and a de novo Robertsonian 13;14 translocation in a child affected by hypomelanosis of Ito. Cryptic chromosome anomalies were found in six (24%) cases, including 1p36 deletion in two patients, 7p14.3p14.1 deletion, 18p subtelomeric deletion, 22q11.2 deletion associated with velo-cardio-facial syndrome, and distal 22q11.2 deletion, each in one case. These results recommend accurate clinical evaluation of patients with NCLV, and suggest that chromosome anomalies occur in about one third of syndromic NCLV individuals, without metabolic/neuromuscular disorder. Array-CGH analysis should be included in the diagnostic protocol of these patients, because different submicroscopic imbalances are causally associated with this disorder and can pinpoint candidate genes for this cardiomyopathy.


Subject(s)
Cardiomyopathies/genetics , Chromosome Aberrations , Heart Ventricles/pathology , Adolescent , Adult , Cardiomyopathies/diagnosis , Child , Child, Preschool , Comparative Genomic Hybridization , Echocardiography, Doppler , Electrocardiography , Female , Heart Ventricles/diagnostic imaging , Humans , In Situ Hybridization, Fluorescence , Infant , Infant, Newborn , Karyotype , Male , Syndrome , Young Adult
14.
Eur J Surg Oncol ; 38(12): 1204-10, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22939013

ABSTRACT

BACKGROUND: To examine the surgical treatment and clinical outcome of elderly and very elderly advanced epithelial ovarian cancer patients. METHODS: We retrospectively analyzed FIGO stage IIIC-IV ovarian cancer patients, divided in elderly (Group A, >65 and <75 years) and very elderly patients (Group B, ≥ 75 years) treated by primary debulking surgery (PDS) or by interval debulking surgery (IDS) at the Catholic University at Rome and Campobasso, Italy. RESULTS: 164 patients were included: 123 (Group A) and 41 (Group B). Complete cytoreduction was achieved in 60 patients (60.6%) in Group A and in 20 patients (62.5%) in Group B (p = 0.75). In the remaining cases, optimal cytoreduction was performed (39 cases (39.4%) in Group A and 12 (37.5%) in Group B; p = 0.75). In Group A complete/optimal debulking was achieved in 53 patients (53.5%) at PDS and in 46 patients (46.5%) at IDS (p = 0.55). In the Group B a higher rate of patients was debulked at IDS with respect to PDS (10 (31.3%) vs. 22 patients (68.7%); p = 0.02). In Group A patients debulked at PDS showed better DFS (p = 0.007) and OS (p = 0.003) with respect to patients submitted to successful IDS, whereas in group B we did not observed any survival difference according to time of cytoreduction. CONCLUSIONS: Our data suggest that elderly and very elderly patients may tolerate radical and ultra-radical surgery. These patients should be managed in a gynecologic oncology unit, with prudent but complete approach.


Subject(s)
Neoplasm Staging/methods , Neoplasms, Glandular and Epithelial/epidemiology , Ovarian Neoplasms/epidemiology , Ovariectomy/methods , Age Factors , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Female , Follow-Up Studies , Humans , Incidence , Italy/epidemiology , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Retrospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome
15.
Eur J Surg Oncol ; 37(12): 1085-92, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21945640

ABSTRACT

BACKGROUND: Rectosigmoidectomy (RR) with primary anastomosis or pelvic peritonectomy (PP) are often part of an optimal en bloc tumor resection in advanced ovarian cancer (AOC) patients with contiguous extension to or encasement of the reproductive organs, peritoneum of the cul-de-sac and sigmoid colon. We report our experience with two different surgical approaches in optimally cytoreduced AOC patients evaluating oncologic outcome and surgically associated morbidities METHODS: Data from all consecutive AOC patients undergoing PP or RR as part of the surgical procedure during primary cytoreduction from 2004 through 2009 were extrapolated and analyzed using the chi-squared test, Cox proportional hazard model and Kaplan-Meier method including log-rank test. RESULTS: During the study period, we identified 187 AOC patients, fitting the inclusion criteria: 71 (38%) were submitted to RR and 116 (62%) were managed with PP. The estimated mean disease-free survival (DFS) was 30.7 months (95% CI 24.6-36.8) in the RR arm vs. 25.9 months in the PP arm (95% CI 21.9-29.9) (p 0.299); similarly, the estimated mean overall survival (OS) was 38.8 months (95% CI 33.4-44.2) in the RR arm and 48.2 months in the PP arm (95% CI 43.1-53.3) (p = 0.122). No statistically significant differences were found in terms of DFS and OS according to the mesocolic lymphnode status (p = 0.65 and p = 0.81, respectively). CONCLUSIONS: In conclusion, the current study clearly supports evidence that survival rates are similar for patients who achieved optimal residual tumor (RT), independent to whether they had RR or PP.


Subject(s)
Colon, Sigmoid/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Peritoneum/surgery , Rectum/surgery , Adult , Aged , Aged, 80 and over , Analysis of Variance , Digestive System Surgical Procedures/adverse effects , Digestive System Surgical Procedures/methods , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Ovarian Neoplasms/mortality , Prognosis , Proportional Hazards Models , Risk Assessment , Risk Factors , Treatment Outcome
16.
J Minim Invasive Gynecol ; 18(2): 184-8, 2011.
Article in English | MEDLINE | ID: mdl-21269890

ABSTRACT

STUDY OBJECTIVE: To evaluate whether the systematic use of an intrauterine manipulator influences the accuracy of frozen section analysis in early-stage endometrial cancer. DESIGN: Case-control study (Canadian Task Force classification II-1). PATIENTS: Three hundred fourteen consecutive women with early-stage endometrial cancer. INTERVENTIONS: Between January 2004 and December 2009, 314 women with early-stage endometrial cancer underwent staging at laparoscopy (case group) or laparotomy (control group). All women in the case group underwent total laparoscopic hysterectomy using an intrauterine manipulator. MEASUREMENTS AND MAIN RESULTS: The positive predictive value of frozen section analysis for myometrial infiltration, histotype, and grade of differentiation was 97.2%, 100%, and 97.2%, respectively. The correct diagnosis rate was of 85.7%. The accuracy of frozen section analysis, rate of correct diagnosis, and rate of tumor vascular invasion did not seem to be significantly modified by systematic use of an intrauterine manipulator for total laparoscopic hysterectomy compared with total abdominal hysterectomy in early-stage endometrial cancer staging. CONCLUSIONS: Frozen section analysis of early-stage endometrial cancer is highly accurate, and systematic use of an intrauterine manipulator does not represent a bias for correct evaluation of the specimen.


Subject(s)
Carcinoma, Endometrioid/surgery , Endometrial Neoplasms/surgery , Hysterectomy/methods , Myometrium/surgery , Adult , Aged , Carcinoma, Endometrioid/pathology , Case-Control Studies , Endometrial Neoplasms/pathology , Female , Frozen Sections , Humans , Laparoscopy , Middle Aged , Myometrium/pathology , Neoplasm Staging
17.
Drug Deliv ; 17(6): 452-65, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20504107

ABSTRACT

Drug delivery systems based on synthetic polymers are widely employed in the treatment of several pathologies. In particular, the use of implantable devices able to release one or more active principles in a topic site with a controlled delivery kinetic represents an important improvement in this field. However, the release kinetic, that could be affected by different parameters, like polymer composition or chemical nature and initial drug loading, represents one of the problems related to the implantation of delivery systems. In this study, acrylic membranes with different macromolecular composition were prepared and studied analyzing delivery kinetic properties. Drug delivery systems were prepared using as matrix the copolymer poly(methylmethacrylate-co-butylmethacrylate) in three different compositions and folic acid (less hydrophobic) or Paclitaxel (more hydrophobic) as drugs, to evaluate the effect of macromolecular composition and hydrophilicity degree on the release properties. In addition, the effect of the initial drug loading was considered, loading drug delivery systems with four different initial drug percentages. Results showed a direct dependence of kinetics from macromolecular composition, hydrophilicity degree of solutes, and initial drug loading, allowing one to conclude that it is possible to design and to develop drug delivery systems starting from poly(methylmethacrylate-co-butylmethacrylate) matrices with specific properties by varying these three parameters.


Subject(s)
Acrylic Resins/chemistry , Antineoplastic Agents/administration & dosage , Drug Carriers/administration & dosage , Folic Acid/administration & dosage , Hematinics/administration & dosage , Paclitaxel/administration & dosage , Antineoplastic Agents/analysis , Antineoplastic Agents/chemistry , Chemical Phenomena , Diffusion , Drug Carriers/analysis , Drug Carriers/chemistry , Drug Compounding , Drug Delivery Systems , Folic Acid/analysis , Folic Acid/chemistry , Hematinics/analysis , Hematinics/chemistry , Hydrophobic and Hydrophilic Interactions , Kinetics , Membranes, Artificial , Models, Chemical , Osmolar Concentration , Paclitaxel/analysis , Paclitaxel/chemistry , Polymethacrylic Acids/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , Water/analysis
18.
J Biomed Mater Res B Appl Biomater ; 93(2): 375-85, 2010 May.
Article in English | MEDLINE | ID: mdl-20119946

ABSTRACT

In this work, the characterization of a biodegradable bilayer system, used as controlled and combined drug delivery platform, is reported. For this aim, a bilayer system, composed of poly(lactic-co-glycolic acid) and poly(3-hydroxybutyric-co-3-hydroxyvaleric acid), was investigated under physicochemical and functional aspects by evaluating polymer/polymer and polymer/stent material interactions, the kinetic of in vitro degradation, and drug release properties, comparing results with the monolayer reference systems. Obtained results showed that the bilayer system allowed increasing the total amount of eluted Tacrolimus and Paclitaxel drugs with respect to the monolayer systems in the considered testing period and conditions. This evidence was associated to a faster degradation of the tested copolymers in the bilayered configuration, excluding a synergic effect of two drugs on delivery performance. In addition, a macromolecular relaxation process was identified to govern the PLX release from poly(lactic-co-glycolic acid), whereas a pure Fickian diffusion occurred in the delivery of Tacrolimus from poly(3-hydroxybutyric-co-3-hydroxyvaleric acid).


Subject(s)
Coated Materials, Biocompatible , Drug-Eluting Stents , Immunosuppressive Agents/chemistry , Paclitaxel/chemistry , Polyesters , Polyglactin 910 , Tacrolimus/chemistry , Tubulin Modulators/chemistry , Immunosuppressive Agents/pharmacology , Kinetics , Materials Testing , Paclitaxel/pharmacology , Tacrolimus/pharmacology , Tubulin Modulators/pharmacology
19.
J Biomater Appl ; 24(4): 353-83, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19033328

ABSTRACT

The aim of the present work is the synthesis and characterization of polymer materials showing good adhesion, drug loading, and delivery properties, for potential cardiovascular application. In particular, poly(methylmethacrylate-co-acrylic acid) copolymers are prepared in different compositions by a radical polymerization and investigated as potential materials to coat metallic stents and to carry out a local drug release. Films obtained by dissolving the copolymer in an appropriate organic solvent (also loaded with an anti-restenosis drug, such as tacrolimus) are investigated: physicochemical properties, adhesiveness to metallic stent material, and kinetics of drug release in physiological environment are studied.


Subject(s)
Acrylates/chemistry , Drug-Eluting Stents , Polymers/chemistry , Polymethacrylic Acids/chemistry , Stents , Adhesiveness , Animals , Chemistry, Physical/methods , Drug Delivery Systems , Drug Design , Humans , Kinetics , Materials Testing , Microscopy, Atomic Force , Tacrolimus/therapeutic use
20.
Int J Gynecol Cancer ; 17(5): 1034-9, 2007.
Article in English | MEDLINE | ID: mdl-17388916

ABSTRACT

The aim of the present study was to examine the impact of a specialized pathologist on the accuracy of frozen section analysis for adnexal masses. We included women who underwent frozen section diagnosis for adnexal mass surgery. A specialized and a general pathologist read the sections. We calculated sensitivity, specificity, positive and negative predictive values, and accuracy for the whole series, as well as for the specialized and general pathologist groups. We included 325 patients; in 103 patients (31.7%), frozen section diagnosis was performed by the specialized and in 222 (68.3%), by the general pathologist. There was a significant difference in terms of correspondence between the specialized and the general pathologist groups (P= 0.024). We registered four overdiagnoses (both performed by the general pathologist [1.8% vs 0%]) and 56 underdiagnoses of which 14 (13.6%) were made by the specialized pathologist and 46 (20.7%) by the general pathologist. In 14 cases (4.3%), diagnosis could not be made on frozen section and was postponed to final histology for definitive diagnosis (1/103 [0.9%] for the specialized pathologist and 13/222 [5.8%] for the general pathologist). Our data confirm previous reports on the accuracy of frozen section analysis of adnexal masses and show a significant positive impact of the specialized pathologist as opposed to the general pathologist.


Subject(s)
Adnexa Uteri/pathology , Adnexal Diseases/pathology , Frozen Sections/standards , Adnexal Diseases/diagnosis , Adult , Female , Humans , Middle Aged , Sensitivity and Specificity
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