Publications by authors named "Antonio Ciardi"

66 Publications

Zero-ischemia testis-sparing surgery for probably benign pediatric testicular tumors.

Pediatr Surg Int 2021 May 2;37(5):673-676. Epub 2021 Mar 2.

Pediatric Surgery Unit, Sapienza University of Rome, AOU Policlinico Umberto I, Viale Regina Elena, 324, 00161, Rome, Italy.

Permanent ischemia-induced testicular damage may occur as early as 30 min in prepupertal rats. With the goal of potentially enhancing testicular function and fertility preservation, we performed testis-sparing surgery (TSS) without ischemia for testicular lesions in select children with negative markers and high likelihood of benignity on ultrasonography. Preliminary experience suggests that off-clamp TSS should be more liberally encouraged, especially in infants and prepubertal children, given their particularly vulnerable spermatic cord elements.
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http://dx.doi.org/10.1007/s00383-021-04865-7DOI Listing
May 2021

Impact of uni- or multifocal perineural invasion in prostate cancer at radical prostatectomy.

Transl Androl Urol 2021 Jan;10(1):66-76

Department of Maternal-Infant and Urological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.

Background: Aim of this study was to correlate perineural invasion (PNI) with other clinical-pathological parameters in terms of prognostic indicators in prostate cancer (PC) cases at the time of radical prostatectomy (RP).

Methods: Prospective study of 288 consecutive PC cases undergoing RP. PNI determination was performed either in biopsy or in RP specimens classifying as uni- and multifocal PNI. The median follow-up time was 22 (range, 6-36) months.

Results: At biopsy PNI was found in 34 (11.8%) cases and in 202 (70.1%) cases at the time of surgery. Among those identified at RP 133 (46.1%) and 69 (23.9%) cases had uni- and multi-PNI, respectively. Presence of PNI was significantly (P<0.05) correlated with unfavorable pathological parameters such higher stage and grade. The percentage of extracapsular extension in PNI negative RP specimens was 18.6% 60.4% of PNI positive specimens. However, the distribution of pathological staging and International Society of Urological Pathology (ISUP) grading did not vary according to whether PNI was uni- or multifocal. The risk of biochemical progression increased 2.3 times in PNI positive cases was significantly associated with the risk of biochemical progression (r=0.136; P=0.04). However, at multivariate analysis PNI was not significantly associated with biochemical progression [hazard ratio (HR): 1.87, 95% confidence interval (CI): 0.68-3.12; P=0.089]. Within patients with intermediate risk disease, multifocal PNI was able to predict cases with lower mean time to biochemical and progression free survival (chi-square 5.95; P=0.04).

Conclusions: PNI at biopsy is not a good predictor of the PNI incidence at the time of RP. PNI detection in surgical specimens may help stratify intermediate risk cases for the risk of biochemical progression.
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http://dx.doi.org/10.21037/tau-20-850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844528PMC
January 2021

Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis.

World J Surg Oncol 2021 Jan 12;19(1):10. Epub 2021 Jan 12.

Department of Surgical Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Purpose: The differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma.

Methods: One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered.

Results: CRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin < 35 g/L (p = 0.05), CA 19-9 > 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1.

Conclusion: This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreatic cancer histologic origin and to improve target therapeutic strategy.
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http://dx.doi.org/10.1186/s12957-021-02120-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802249PMC
January 2021

A Prognostic Score for Predicting Survival in Patients With Pancreatic Head Adenocarcinoma and Distal Cholangiocarcinoma.

In Vivo 2021 Jan-Feb;35(1):507-515

Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy;

Background/aim: Survival of patients with pancreatic cancer remains poor despite improvements in therapeutic strategies. This study aims to create a novel preoperative score to predict prognosis in patients with tumors of the pancreaticobiliary head.

Patients And Methods: Data on 190 patients who underwent to pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2018 were retrospectively analyzed. After exclusion criteria, 101 patients were considered eligible for retrospective study. Preoperative biological, clinical and radiological parameters were considered.

Results: Pancreatic ductal adenocarcinoma [hazard ratio (HR)=1.995, 95% confidence intervaI (CI)=1.1-3.3; p=0.01], carbohydrate antigen 19.9 (CA 19.9) >230 U/ml (HR=2.414, 95% CI=2.4-1.5, p<0.0001) and Wirsung duct diameter >3 mm (HR=1.592, 95% CI=1.5-0.9; p=0.08) were the only parameters associated with poor prognosis. Through these parameters, a prognostic score (PHT score) was developed which predicted worst survival when exceeding 2 and better survival when ≤2.

Conclusion: The PHT score may have a potential impact on predicting overall survival and consequently modulate the timing and type of treatment (up-front surgery vs. neoadjuvant therapy) patients are offered.
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http://dx.doi.org/10.21873/invivo.12285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880773PMC
October 2020

Cribriform pattern does not have a significant impact in Gleason Score ≥7/ISUP Grade ≥2 prostate cancers submitted to radical prostatectomy.

Medicine (Baltimore) 2020 Sep;99(38):e22156

Department of Maternal-Infant and Urological Sciences.

Introduction: The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP).

Methods: This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients.

Results: At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = -0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ 0.906; P = .341; Rp = χ 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ = 3.617; P = .057) in cases without CP.

Conclusions: In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.
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http://dx.doi.org/10.1097/MD.0000000000022156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505347PMC
September 2020

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

Ann Surg Oncol 2021 Feb 5;28(2):1167-1177. Epub 2020 Aug 5.

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer.

Patients And Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability.

Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status.

Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.
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http://dx.doi.org/10.1245/s10434-020-08926-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801310PMC
February 2021

Elective procedures for prostate cancer in the time of Covid-19: a multidisciplinary team experience.

Prostate Cancer Prostatic Dis 2020 May 18:1-3. Epub 2020 May 18.

3Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.

On March 29th 2020, 97,689 cases of COVID-19 have been diagnosed only in Italy, with 73,880 actually positive cases, a daily increase of 3815 cases, 27,386 hospitalized and 3906 patients in intensive care units, causing a total of 10,779 known deaths. In all urological departments, quickly inpatient and outpatient services have been significantly reduced. Even in this COVID-19 situation, urological neoplasm care must go on, but significant changes need to be made in the way some care is delivered. We compared diagnostic and therapeutic elective procedures requested and performed for PC management from our multidisciplinary team (MDT) during 1 month activity in the highest national level of COVID-19 infection (March 2020) and under restrictions for all the population, with the management performed in a no-COVID-19 month (March 2019) 1 year ago. The only management that did not received a significant reduction are medical therapies for advanced hormone sensitive (HS) or castration resistant (CR) PC. We describe our MDT identifications of elective undeferrable PC management in this COVID-19 time. These suggestions have been considered for a country (ITALY) under a rapid increase of COVID-19 cases and complications, but in a region with an actual lower impact (2914 actual positive and 1079 hospitalized cases) from the infection and in an hospital not completely converted to COVID-19 management. Indications should be different and restricted only to emergencies on the basis of COVID-19 pandemic situation and hospital involvement.
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http://dx.doi.org/10.1038/s41391-020-0240-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233331PMC
May 2020

Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Mod Pathol 2020 07;33(7):1453

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41379-020-0512-5DOI Listing
July 2020

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Mod Pathol 2020 07 17;33(7):1398-1409. Epub 2020 Feb 17.

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
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http://dx.doi.org/10.1038/s41379-020-0497-0DOI Listing
July 2020

A pre-existing population of ZEB2 quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer.

J Exp Clin Cancer Res 2020 Jan 8;39(1). Epub 2020 Jan 8.

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

Background: Quiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown.

Methods: A population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses. Factors expressed by the quiescent/slow cycling population were analyzed through lentiviral overexpression approaches for their ability to induce a dormant chemoresistant state both in vitro and in mouse xenografts. The correlation between quiescence-associated factors, CRC consensus molecular subtype and cancer prognosis was analyzed in large patient datasets.

Results: Untreated colorectal tumors contain a population of quiescent/slow cycling cells with stem cell features (quiescent cancer stem cells, QCSCs) characterized by a predetermined mesenchymal-like chemoresistant phenotype. QCSCs expressed increased levels of ZEB2, a transcription factor involved in stem cell plasticity and epithelial-mesenchymal transition (EMT), and of antiapototic factors pCRAF and pASK1. ZEB2 overexpression upregulated pCRAF/pASK1 levels resulting in increased chemoresistance, enrichment of cells with stemness/EMT traits and proliferative slowdown of tumor xenografts. In parallel, chemotherapy treatment of tumor xenografts induced the prevalence of QCSCs with a stemness/EMT phenotype and activation of the ZEB2/pCRAF/pASK1 axis, resulting in a chemotherapy-unresponsive state. In CRC patients, increased ZEB2 levels correlated with worse relapse-free survival and were strongly associated to the consensus molecular subtype 4 (CMS4) characterized by dismal prognosis, decreased proliferative rates and upregulation of EMT genes.

Conclusions: These results show that chemotherapy-naive tumors contain a cell population characterized by a coordinated program of chemoresistance, quiescence, stemness and EMT. Such population becomes prevalent upon drug treatment and is responsible for chemotherapy resistance, thus representing a key target for more effective therapeutic approaches.
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http://dx.doi.org/10.1186/s13046-019-1505-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947904PMC
January 2020

Upfront debulking surgery versus interval debulking surgery for advanced tubo-ovarian high-grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC.

J Surg Oncol 2019 Dec 17;120(7):1208-1219. Epub 2019 Sep 17.

Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy.

Background: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial.

Methods: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up.

Results: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients.

Conclusion: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.
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http://dx.doi.org/10.1002/jso.25703DOI Listing
December 2019

Separation of Low- Versus High-grade Crohn's Disease-associated Small Bowel Carcinomas is Improved by Invasive Front Prognostic Marker Analysis.

J Crohns Colitis 2020 Mar;14(3):295-302

Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Background And Aims: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis.

Methods: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium.

Results: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months.

Conclusions: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.
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http://dx.doi.org/10.1093/ecco-jcc/jjz140DOI Listing
March 2020

Intrapancreatic accessory spleen false positive to 68Ga-Dotatoc: case report and literature review.

World J Surg Oncol 2019 Jul 9;17(1):117. Epub 2019 Jul 9.

Department of Surgical Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Background: Intrapancreatic accessory spleen (IPAS) is an uncommon finding of pancreatic mass. Differential diagnosis with pancreatic tumor, especially with non-functional neuroendocrine tumor (NF-NET), may be very hard and sometimes it entails unnecessary surgery. A combination of CT scan, MRI, and nuclear medicine can confirm the diagnosis of IPAS. 68-Ga-Dotatoc PET/CT is the gold standard in NET diagnosis and it can allow to distinguish between IPAS and NET.

Case Presentation: A 69-year-old man was admitted to our hospital for an incidental nodule in the tail of the pancreas with focal uptake of 68-Ga-dotatate at PET/CT. NET was suspected and open distal splenopancreatectomy was performed. Pathologic examination revealed an IPAS.

Conclusion: This is the second IPAS case in which a positive 68Ga-Dotatoc uptake led to a false diagnosis of pancreatic NET. Here is a proposal of a literature review.
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http://dx.doi.org/10.1186/s12957-019-1660-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617599PMC
July 2019

Analysis of Short-term Blood Pressure Variability in Pheochromocytoma/Paraganglioma Patients.

Cancers (Basel) 2019 May 12;11(5). Epub 2019 May 12.

Department of Translational and Precision Medicine, Unit of Secondary Arterial Hypertension, "Sapienza" University of Rome, Viale del Policlinico 155, 00165 Rome, Italy.

Data on short-term blood pressure variability (BPV), which is a well-established cardiovascular prognostic tool, in pheochromocytoma and paraganglioma (PPGL) patients is still lack and conflicting. We retrospectively evaluated 23 PPGL patients referred to our unit from 2010 to 2019 to analyze 24 h ambulatory blood pressure monitoring (24-h ABPM)-derived markers of short-term BPV, before and after surgical treatment. PPGL diagnosis was assessed according to guidelines and confirmed by histologic examination. The 24-h ABPM-derived markers of short-term BPV included: circadian pressure rhythm; standard deviation (SD) and weighted SD (wSD) of 24-h, daytime, and night-time systolic and diastolic blood pressure (BP); average real variability (ARV) of 24-h, daytime, and night-time systolic and diastolic BP. 7 males and 16 females of 53 ± 18 years old were evaluated. After surgical resection of PPGL we found a significant decrease in 24-h systolic BP ARV (8.8 ± 1.6 vs. 7.6 ± 1.3 mmHg, < 0.001), in 24-h diastolic BP ARV (7.5 ± 1.6 vs. 6.9 ± 1.4 mmHg, = 0.031), and in wSD of 24-h diastolic BP (9.7 ± 2.0 vs 8.8 ± 2.1 mmHg, = 0.050) comparing to baseline measurements. Moreover, baseline 24-h urinary metanephrines significantly correlated with wSD of both 24-h systolic and diastolic BP. Our study highlights as PPGL patients, after proper treatment, show a significant decrease in some short-term BPV markers, which might represent a further cardiovascular risk factor.
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http://dx.doi.org/10.3390/cancers11050658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562701PMC
May 2019

Dynamic contrast-enhanced magnetic resonance imaging in locally advanced rectal cancer: role of perfusion parameters in the assessment of response to treatment.

Radiol Med 2019 May 17;124(5):331-338. Epub 2018 Dec 17.

Department of Surgical and Medical Sciences and Translational Medicine, "Sapienza" University of Rome, Radiology Unit - Sant'Andrea University Hospital, Via di Grottarossa, 1035-1039, 00189, Rome, Italy.

Purpose: To correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to tumor grading and to assess their reliability in predicting pathological complete response (pCR) before neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC).

Materials And Methods: Forty patients (24 male; mean age, 67.3 ± 8.1 years) with histologically proven LARC who had undergone 3-Tesla DCE-MRI before (MRI_1) and after CRT (MRI_2) between August 2015 and February 2016 were included in this retrospective study. DCE-MRI parameters at MRI_1 and MRI_2 were extracted by two board certified radiologists in consensus reading with Olea Sphere 2.3 software using the extended Tofts model. Based on DCE-MRI results, patients were divided in complete responders (CR) and non-complete responders (nCR) and the perfusion parameters were correlated to tumor grading and pCR.

Results: Wash-out and K at MRI_1 showed significant correlation with LARC grading (P = 0.004 and 0.01, respectively). V showed a significant increase between MRI_1 (0.47 ± 0.27) and MRI_2 (0.63 ± 0.23; P = 0.007). K measured at MRI_1 was significantly higher in CR (0.66 ± 0.48) compared to nCR (0.53 ± 0.34, P = 0.02).

Conclusion: Wash-out and K measured before CRT correlate with LARC grading. V changes during CRT, while K measured before CRT may predict the response to therapy. Therefore, DCE-MRI parameters can predict tumor aggressiveness and CRT efficacy, playing a role as imaging biomarkers in patients with LARC.
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http://dx.doi.org/10.1007/s11547-018-0978-0DOI Listing
May 2019

A rare case report of hypertrophic cardiomyopathy induced by catecholamine-producing tumor.

Medicine (Baltimore) 2018 Dec;97(50):e13369

Secondary Hypertension Unit, Department of Internal Medicine and Medical Specialties, University of Rome.

Rationale: Catecholamine-producing tumors are rare, occurring in less than 0.2% of patients with hypertension, but can have relevant cardiovascular morbidity and mortality.

Patient Concerns: A 37-year-old woman presented with a history of dyspnea, chest pain, palpitations, and paroxysmal hypertension. Electrocardiogram, echocardiogram, and cardiac magnetic resonance showed severe LVH with a prevalent involvement of the anterior portion of interventricular septum. Endomyocardial biopsy found severe hypertrophy with disarray of cardiomyocytes and ultrastructural evidence of contraction and necrosis of myocytes. Hormone investigations revealed high values of 24-hours urinary metanephrines. Abdominal computed tomography (CT) showed an enlarged left adrenal gland with a strong uptake of I-metaiodobenzylguanidine at scintigraphy scan.

Interventions: Thus, the adrenal tumor was surgically removed.

Outcomes: At follow-up examination, the patient's metanephrines levels were normalized and the transthoracic echocardiogram showed a reduction of LVH.

Diagnosis And Lessons: We report a rare case of catecholamine-induced cardiomyopathy due to an adrenal adenoma mixed with nodules enriched in epinephrine-types secreting granules.
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http://dx.doi.org/10.1097/MD.0000000000013369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319915PMC
December 2018

Improvement of prostate cancer detection combining a computer-aided diagnostic system with TRUS-MRI targeted biopsy.

Abdom Radiol (NY) 2019 01;44(1):264-271

Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, V.le Regina Elena, 324, 00161, Rome, Italy.

Purpose: To validate a novel consensus method, called target-in-target, combining human analysis of mpMRI with automated CAD system analysis, with the aim to increasing the prostate cancer detection rate of targeted biopsies.

Methods: A cohort of 420 patients was enrolled and 253 patients were rolled out, due to exclusion criteria. 167 patients, underwent diagnostic 3T MpMRI. Two expert radiologists evaluated the exams adopting PI-RADSv2 and CAD system. When a CAD target overlapped with a radiologic one, we performed the biopsy in the overlapping area which we defined as target-in-target. Targeted TRUS-MRI fusion biopsy was performed in 63 patients with a total of 212 targets. The MRI data of all targets were quantitatively analyzed, and diagnostic findings were compared to pathologist's biopsy reports.

Results: CAD system diagnostic performance exhibited sensitivity and specificity scores of 55.2% and 74.1% [AUC = 0.63 (0.54 ÷ 0.71)] , respectively. Human readers achieved an AUC value, in ROC analysis, of 0.71 (0.63 ÷ 0.79). The target-in-target method provided a detection rate per targeted biopsy core of 81.8 % vs. a detection rate per targeted biopsy core of 68.6 % for pure PI-RADS based on target definitions. The higher per-core detection rate of the target-in-target approach was achieved irrespective of the presence of technical flaws and artifacts.

Conclusions: A novel consensus method combining human reader evaluation with automated CAD system analysis of mpMRI to define prostate biopsy targets was shown to improve the detection rate per biopsy core of TRUS-MRI fusion biopsies. Results suggest that the combination of CAD system analysis and human reader evaluation is a winning strategy to improve targeted biopsy efficiency.
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http://dx.doi.org/10.1007/s00261-018-1712-zDOI Listing
January 2019

Relationship and Predictive Role of the Dual Expression of FGFR and IL-8 in Metastatic Renal Cell Carcinoma Treated with Targeted Agents.

Anticancer Res 2018 05;38(5):3105-3110

Department of Radiology, Oncology and Human Pathology, Oncology Unit, Sapienza University of Rome, Rome, Italy.

Background/aim: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients.

Materials And Methods: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry.

Results: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047).

Conclusion: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents.
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http://dx.doi.org/10.21873/anticanres.12569DOI Listing
May 2018

Clearance of human papillomavirus related anal condylomas after oral and endorectal multistrain probiotic supplementation in an HIV positive male: A case report.

Medicine (Baltimore) 2018 Apr;97(16):e0329

Department of Public Health and Infectious Diseases Department of Molecular Medicine, Laboratory of Virology Department of Radiological, Oncological and Pathology Sciences, "Sapienza" University of Rome, Italy.

Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity.

Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.
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http://dx.doi.org/10.1097/MD.0000000000010329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916677PMC
April 2018

Negative Multiparametric Magnetic Resonance Imaging for Prostate Cancer: What's Next?

Eur Urol 2018 07 19;74(1):48-54. Epub 2018 Mar 19.

Sapienza University of Rome, Rome, Italy.

Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csPCa). Nevertheless, the clinical utility of negative mpMRI (nMRI) is less clear.

Objective: To assess outcomes of men with nMRI and clinical follow-up after 7 yr of activity at a reference center.

Design, Setting, And Participants: All mpMRI performed from January 2010 to May 2015 were reviewed. We selected all patients with nMRI and divided them in group A (naïve patients) and group B (previous negative biopsy). All patients without a diagnosis of PCa had a minimum follow-up of 2 yr and at least two consecutive nMRI. Patients with positive mpMRI were also identified to assess their biopsy outcomes.

Outcome Measurements And Statistical Analysis: A Kaplan-Meier analysis was performed to assess both any-grade PCa and csPCa diagnosis-free survival probabilities. Univariable and multivariable Cox regression models were fitted to identify predictors of csPCa diagnosis.

Results And Limitations: We identified 1545 men with nMRI, and 1255 of them satisfied the inclusion criteria; 659 belonged to group A and 596 to group B. Any-grade PCa and csPCa diagnosis-free survival probabilities after 2 yr of follow-up were 94% and 95%, respectively, in group A; in group B, they were 96%. After 48 mo of follow-up, any-grade PCa diagnosis-free survival probability was 84% in group A and 96% in group B (log rank p<0.001). Diagnosis-free survival probability for csPCa was unchanged after 48 mo of follow-up. On multivariable Cox regression analysis, increasing age (p=0.005) was an independent predictor of lower csPCa diagnosis probability, while increasing prostate-specific antigen (PSA) and PSA density (<0.001) independently predicted higher csPCa diagnosis probability. The prevalence of and positive predictive value for csPCa were 31.6% and 45.5%, respectively. Limitations include limited follow-up and the inability to calculate true csPCa prevalence in the study population.

Conclusions: mpMRI is highly reliable to exclude csPCa. Nevertheless, systematic biopsy should be recommended even after nMRI, especially in younger patients with high or raising PSA levels.

Patient Summary: It is a matter of debate whether patients with negative multiparametric magnetic resonance imaging (mpMRI) of the prostate could obviate the need to perform a systematic biopsy. In this report, we looked at the outcomes of patients with negative mpMRI and midterm clinical follow-up at a reference center. We found mpMRI to be highly reliable to exclude significant prostate cancer; nonetheless, systematic biopsy must still be recommended after negative mpMRI in patients with high clinical suspicion of prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2018.03.007DOI Listing
July 2018

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.

Ann Surg Oncol 2018 Mar 27;25(3):679-687. Epub 2017 Dec 27.

First Department of Surgical Oncology, Metaxa Cancer Hospital, Pireaus, Greece.

Background: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome.

Results: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor.

Conclusions: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.
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http://dx.doi.org/10.1245/s10434-017-6307-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814516PMC
March 2018

An update of pitfalls in prostate mpMRI: a practical approach through the lens of PI-RADS v. 2 guidelines.

Insights Imaging 2018 Feb 23;9(1):87-101. Epub 2017 Oct 23.

Department of Radiology, Ghent University Hospital, Ghent, Belgium.

Objectives: The aim of the current report is to provide an update in the imaging interpretation of prostate cancer on multiparametric magnetic resonance imaging (mpMRI), with a special focus on how to discriminate pathological tissue from the most common pitfalls that may be encountered during daily clinical practice using the Prostate Imaging Reporting and Data System (PI-RADS) version 2 guidelines.

Methods: All the cases that are shown in this pictorial review comply with the European Society of Urogenital Radiology (ESUR) guidelines for technical mpMRI requirements.

Results: Despite the standardised manner to report mpMRI (PI-RADS v. 2), some para-physiologic appearances of the prostate can mimic cancer. As such, it is crucial to be aware of these pitfalls, in order to avoid the under/overestimation of prostate cancer.

Conclusions: A detailed knowledge of normal and abnormal findings in mpMRI of the prostate is pivotal for an accurate management of the wide spectrum of clinical scenarios that radiologists may encounter during their daily practice.

Teaching Points: • Some para-physiologic appearances of the prostate may mimic cancer. • Knowledge of normal and abnormal findings in prostate mpMRI is pivotal. • Any radiologist involved in prostate mpMRI reporting should be aware of pitfalls.
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http://dx.doi.org/10.1007/s13244-017-0578-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825307PMC
February 2018

Silent Adrenal Pheochromocytoma Coexistent with Corticomedullary Hyperplasia: A Case Incidentally Discovered.

Eur J Case Rep Intern Med 2017 6;4(10):000714. Epub 2017 Oct 6.

Specialized Center of Secondary Hypertension, Department of Internal Medicine and Medical Specialties, University "Sapienza", Rome, Italy.

Introduction: Pheochromocytoma (PHEO) is a rare catecholamine-producing tumour arising from chromaffin cells in the sympatho-adrenal system, and can present as asymptomatic adrenal incidentaloma (AI).

Patient: We describe the case of a 61-year-old woman with a right adrenal mass incidentally discovered, who was biochemically characterized with subclinical hypercortisolism (SH). The patient was scheduled for adrenalectomy because of increasing seizure of the right adrenal gland with a haemorrhagic and focal pseudocystic appearance macroscopically, incidental histological and immunohistochemical PHEO, and micronodular cortico-adrenal hyperplasia.

Discussion: This report describes a rare case of incidental non-functioning PHEO coexisting with corticomedullary hyperplasia and SH.

Learning Points: Rare presentation of coexisting common (adrenal incidentaloma and subclinical Cushing's syndrome) and uncommon (pheochromocytoma) endocrinological conditions.
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http://dx.doi.org/10.12890/2017_000714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346797PMC
October 2017

tsRNA signatures in cancer.

Proc Natl Acad Sci U S A 2017 07 10;114(30):8071-8076. Epub 2017 Jul 10.

Department of Cancer Biology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;

Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the cluster (now called "" and "," respectively), , and are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that and can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knocked-out cell model for and in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressed and in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival.
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http://dx.doi.org/10.1073/pnas.1706908114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544330PMC
July 2017

Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.

J Crohns Colitis 2017 Aug;11(8):942-953

Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.

Background And Aims: An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC].

Methods: A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations.

Results: CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications.

Conclusions: In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy.
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http://dx.doi.org/10.1093/ecco-jcc/jjx031DOI Listing
August 2017

Archetype and Rearranged Non-coding Control Regions in Urothelial Bladder Carcinoma of Immunocompetent Individuals.

Cancer Genomics Proteomics 2016 11-12;13(6):499-509

Department of Health Sciences and Infectious Diseases, Sapienza University of Rome, Rome, Italy

Background: Polyomaviruses (PyVs) are potential transforming viruses. Despite their involvement in human tumours still being debated, there is evidence to suggest a role for PyVs in bladder carcinoma (BC). Therefore, a possible association between PyVs and BC was investigated.

Materials And Methods: Urine, blood and fresh bladder tissue specimens were collected from 29 patients with BC. PyV prevalence, non-coding control region (NCCR) organization and genotypic analysis were assessed.

Results: Data showed a significant prevalence of John Cunningham (JC) PyV in BC tissues and in urine with respect to BKPyV, while simian virus 40 was not revealed. A BKPyV rearranged NCCR sequence was isolated, whereas a JCPyV archetypal structure was consistently retained. A prevalence of European genotypes was observed.

Conclusion: Our data would suggest a JCPyV involvement in cancer progression and a BKPyV association with BC pathogenesis in immunocompetent patients. However, further work is necessary to better understand the exact role of PyVs in urothelial carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219924PMC
http://dx.doi.org/10.21873/cgp.20013DOI Listing
January 2017

A case report of subclinical hypercortisolism due to adrenal incidentaloma complicated by myasthenia gravis after adrenalectomy.

Tumori 2016 Nov 11;102(Suppl. 2). Epub 2016 Nov 11.

Department of Internal Medicine and Medical Specialties, La Sapienza University, Rome - Italy.

A 62-year-old woman was admitted for evaluation of an incidentally discovered adrenal mass and hypertension. CT scan revealed a 7 cm mass in the right adrenal gland. After careful examination, the patient was diagnosed with subclinical hypercortisolism (SH). Adrenalectomy was performed. Histopathological examination showed an adrenocortical adenoma. Symptoms and signs of myasthenia gravis appeared 5 months later. CT of the chest showed a solid tissue mass in the mediastinum. The patient underwent a sternotomy with excision of the tumor, which histologically proved to be a type 2B thymoma. We describe a rare case of SH due to an incidentally discovered adrenocortical adenoma in a patient who manifested myasthenia gravis after surgical remission of the cortisol excess.
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http://dx.doi.org/10.5301/tj.5000503DOI Listing
November 2016

Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer.

Oncoimmunology 2016 Jul 25;5(7):e1175800. Epub 2016 Apr 25.

Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helios(high) and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression.
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http://dx.doi.org/10.1080/2162402X.2016.1175800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006916PMC
July 2016

A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer.

Medicine (Baltimore) 2016 Jul;95(27):e3845

Department of Urological Sciences, University Sapienza, Rome Statistics Institute, Rome Department of Radiological Sciences, Oncology & Pathology, University Sapienza, Rome Department of Experimental Medicine, University Sapienza, Rome.

Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78-1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26-1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix.
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http://dx.doi.org/10.1097/MD.0000000000003845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058791PMC
July 2016

Subclinical Atherosclerosis in Patients with Cushing Syndrome: Evaluation with Carotid Intima-Media Thickness and Ankle-Brachial Index.

Endocrinol Metab (Seoul) 2015 Dec 10;30(4):488-93. Epub 2015 Sep 10.

Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Rome, Italy.

Background: Cushing syndrome (CS) has been described as a killing disease due its cardiovascular complications. In fact, chronic cortisol excess leads to a constellation of complications, including hypertension, hyperglycemia, adiposity, and thromboembolism. The main vascular alteration associated with CS is atherosclerosis.

Methods: Aim of this study was to analyze carotid intima-media thickness (cIMT) and ankle-brachial index (ABI), two surrogate markers of subclinical atherosclerosis in a consecutive series of CS patients, compared to patients with essential hypertension (EH) and health subjects (HS).

Results: Patients with CS showed a significant increase (P<0.05) of cIMT (0.89±0.17 mm) compared to EH (0.81±0.16 mm) and HS (0.75±0.4 mm), with a high prevalence of plaque (23%; P<0.03). Moreover, CS patients showed a mean ABI values (1.07±0.02) significantly lower respect to HS (1.12±0.11; P<0.05), and a higher percentage (20%) of pathological values of ABI (≤0.9; P<0.03).

Conclusion: In conclusion, we confirmed and extended the data of cIMT in CS, and showed that the ABI represent another surrogate marker of subclinical atherosclerosis in this disease.
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http://dx.doi.org/10.3803/EnM.2015.30.4.488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722403PMC
December 2015