Publications by authors named "Giuseppe Neri"

8 Publications

  • Page 1 of 1

Poorly Cohesive Carcinoma of the Nonampullary Small Intestine: A Distinct Histologic Subtype With Prognostic Significance.

Am J Surg Pathol 2021 Oct 11. Epub 2021 Oct 11.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia Anatomic Pathology, Fondazione IRCCS San Matteo Hospital Clinical Epidemiology & Biometry Unit, Fondazione IRCCS San Matteo Hospital Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, Pavia Pathology Unit, Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua Veneto Institute of Oncology, IOV-IRCCS, Padua Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese Gatroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital Department of Biochemical and Clinical Sciences, University of Milan, Milan Division of General and HPB Surgery, ASST Rhodense, Rho Gatroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for >50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixed-poorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of <10% of signet-ring cells, and all but 1 SB-PCCs exhibited loss of membranous expression of E-cadherin. Compared with SBAs-NOS, SB-PCCs showed a significantly younger patient age at diagnosis, and a stronger association with Crohn disease, and both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs featured a higher rate of lymphovascular and perineural invasion and a lower percentage of mismatch repair-deficient cases. Importantly, the cancer-specific survival of SB-PCC (hazard ratio: 3.81; 95% confidence interval: 1.90-7.64; P<0.001) and mixed-poorly-cohesive-glandular-SBA (4.12; 2.20-7.71; P<0.001) patients was significantly worse compared with SBAs-NOS cases. This study provides objective evidence to the World Health Organization (WHO) 2019 introduction of SB-PCC as a distinctive subtype of nonampullary SBA, by virtue of its unique clinical and histologic features, and suggests that both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs should be separated from SBAs-NOS.
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http://dx.doi.org/10.1097/PAS.0000000000001821DOI Listing
October 2021

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall.

Cancers (Basel) 2020 Nov 19;12(11). Epub 2020 Nov 19.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy.

Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers ( = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.
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http://dx.doi.org/10.3390/cancers12113441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699330PMC
November 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.

Unit of Pathology, Cervello Hospital, Palermo, 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

Long Survival and Prolonged Remission after Surgery and Chemotherapy in a Metastatic Mismatch Repair Deficient Pancreatic Neuroendocrine Carcinoma with MLH1/PMS2 Immunodeficiency and Minimal Microsatellite Shift.

Endocr Pathol 2020 Dec;31(4):411-417

Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Pancreatic neuroendocrine carcinomas (NECs) are rare and very aggressive neoplasms with dismal prognosis, especially when metastatic or with negative prognostic factors, such as vascular invasion. To the best of our knowledge, no case of pancreatic NEC with mismatch repair deficiency has been reported to date. We describe a 62-year-old patient who underwent pancreaticoduodenectomy for a NEC located in the pancreatic head, with peripancreatic lymph node metastases. Tumor necrosis was prominent and the Ki67 proliferative index was 60%. One year after the diagnosis, the patient experienced recurrence with a left supraclavicular lymph node metastasis, which was surgically removed, followed by standard cisplatin-etoposide chemotherapy. Neoplastic cells showed combined loss of expression of MLH1 and PMS2 in both primary tumor and lymph node metastasis. Microsatellite instability (MSI) test using a mononucleotide repeats pentaplex PCR (BAT-25, BAT-26, NR-21, NR-22, and NR-24) revealed minimal mononucleotide shifts showing deletion of less than 3 bp at NR-21, BAT-26, NR-24, and NR-22 loci. MLH1 methylation analysis revealed absence of the gene promoter methylation. BRAF and KRAS mutations were not detected. In gut, NECs' mismatch repair deficiency phenotype has been reported in about 10% of cases, and it represents an independent factor of more favorable outcome. Likewise, our patient is currently alive with a follow-up of more than 12 years after pancreaticoduodenectomy, by itself an unexpected finding for such an aggressive neoplasm.
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http://dx.doi.org/10.1007/s12022-020-09622-5DOI Listing
December 2020

The influence of previous infections and antichlamydia pneumoniae seropositivity on functional outcome in ischemic stroke patients: results from the IN2 study.

J Neurol 2015 May 26;262(5):1310-6. Epub 2015 Mar 26.

Department of Neurology, "G. Jazzolino" Hospital, Via P. Fleming, 89900, Vibo Valentia, Italy,

Although a growing attention is being paid to acute ischemic stroke patients, the correlation between clinical outcome and infectious events in this population has been poorly investigated. 749 ischemic stroke (mean age 71 years old, males 56%) patients were enrolled in this prospective case-control study by 11 Italian Stroke Units. Demographic data, vascular risk factors, previous infections and post-stroke infections (PSIs) were recorded. Blood samples were collected and the enzyme-linked immunoassay was chosen to measure Chlamydia pneumoniae IgG and IgA plasma antibodies (antibody titers were classified with specific cut-off levels: IgA > 1:16 and IgG > 1:64). Early poor outcome was defined as mRS score >2 at discharge, while poor outcome at 6-month follow-up. Univariate and multivariate analyses were performed. Median NIHSS was 7, IgA and IgG antichlamydia pneumoniae seropositivities were observed in 308 (37.1%) and 207 (23.6%) patients, respectively. Multivariate analyses showed significant correlations between PSIs and NIHSS (RR: 1.06; 95% CI 1.02-1.09; p < 0.001) and PSIs and IgA antichlamydia pneumoniae seropositivity (RR: 3.84; 95% CI 2.53-5.84; p < 0.001). Significant disability was associated with baseline NIHSS (RR: 1.32; 95% CI 1.16-1.50; p < 0.001), IgA (RR: 2.67; 95% CI 1.06-6.70; p = 0.035) and IgG antichlamydia (RR: 5.75; 95% CI 1.83-18.03; p = 0.003) seropositivity and atrial fibrillation (RR: 2.58; 95% CI 1.81-3.67; p < 0.001). While previous infections were not associated with functional outcome, antichlamydia antibodies play a negative role in ischemic stroke patients. Preventive strategies may reduce the stroke burden and improve the clinical outcome.
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http://dx.doi.org/10.1007/s00415-015-7712-9DOI Listing
May 2015

[Multidisciplinary position paper on the management of patent foramen ovale in the presence of cryptogenic cerebral ischemia - Italian version 2013].

G Ital Cardiol (Rome) 2013 Oct;14(10):699-712

There is no generally accepted consensus on the management of patent foramen ovale (PFO) in the presence of cryptogenic cerebral ischemia, because of the lack of conclusive evidence. The aim of this position paper was to develop and promote a joint approach based on available data that may be shared by different specialists, while waiting for definite results from randomized controlled trials. A position statement was produced involving the major national scientific societies. The task force members were nominated by the presidents and/or executive boards of each society or working group, as appropriate, based on their previous work in relevant topic areas. Specific task force working groups prepared the drafts. In order to achieve maximum agreement, these drafts were merged and distributed to the scientific societies for local evaluation. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by all scientific societies. The following issues were addressed: definitions of transient ischemic attack (TIA) and both symptomatic and asymptomatic cryptogenic stroke; formulation of a diagnostic workup for patients with clinical event(s) and PFO; recommendations regarding medical and interventional treatment options considering individual risk factors based on the three available randomized trials and other observational studies; recommendations regarding requirements for operators and centers in Italy; definition of a follow-up evaluation protocol. In conclusion, available data provided the basis for the first multi-society position paper on the management of cryptogenic stroke/TIA and PFO.
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http://dx.doi.org/10.1714/1335.14838DOI Listing
October 2013

Management of patients with patent foramen ovale and cryptogenic stroke: a collaborative, multidisciplinary, position paper: executive summary.

Catheter Cardiovasc Interv 2013 Jul;82(1):122-9

Clinical Research Centre and Cardiovascular Department, San Filippo Neri Hospital, Roma, Italy.

Objectives: To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists.

Background: The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures.

Methods: A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies.

Results: Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow-up evaluation was appraised.

Conclusions: Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited.
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http://dx.doi.org/10.1002/ccd.24693DOI Listing
July 2013

Management of patients with patent foramen ovale and cryptogenic stroke: a collaborative, multidisciplinary, position paper.

Catheter Cardiovasc Interv 2013 Jul 8;82(1):E38-51. Epub 2013 Apr 8.

Clinical Research Centre and Cardiovascular Department, San Filippo Neri Hospital, Roma, Italy.

Objectives: To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists.

Background: The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures.

Methods: A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies.

Results: Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow-up evaluation was appraised.

Conclusions: Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited.
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http://dx.doi.org/10.1002/ccd.24637DOI Listing
July 2013
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