Letizia Gnetti - Academia.edu (original) (raw)

Papers by Letizia Gnetti

PubMed, 2003

Pathological examination in the spleen of an 81-year old female with hemoperitoneum, hypovolemic ... more Pathological examination in the spleen of an 81-year old female with hemoperitoneum, hypovolemic shock, anemia, thrombocytopenia and hyperglicemia revealed the presence of an angiosarcoma. On histological examination, characteristically the neoplasm was formed by vascular lumina and cystic spaces into which papillary fronds projected and solid nests. Neoplastic cells had scant cytoplasm, hyperchromatic, oval or reniform nuclei, with prominent nucleoli. The necrosis was evident and mitoses were frequent. Immunohistochemical analysis revealed positivity for endothelial (CD31, CD34) and histiocytic markers (CD68 and lysozyme) and negativity for CD21. Ultrastructural examination also disclosed a biphasic differentiation, showing the presence of organelles associated with histiocytic and endothelial differentiation. These findings suggest that this lesion can be considered a conventional splenic angiosarcoma with focal histocytic differentiation.

Frontiers in Oncology, 2021

Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance t... more Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments.Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum–etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum–etoposide compared with control (p < 0.05). A review...

Cancer Drug Resistance, 2021

Pancreatic cancer is one of the most aggressive diseases among solid tumors. Most patients are di... more Pancreatic cancer is one of the most aggressive diseases among solid tumors. Most patients are diagnosed with advanced or metastatic disease and are characterized by poor chemosensitivity. Therefore, earlier diagnosis and novel therapeutic possibilities for pancreatic cancer patients are urgently needed. Liquid biopsy is an emerging technology that allows the noninvasive sampling of tumor material. Nowadays, liquid biopsy has shown promising results as diagnostic, prognostic and predictive biomarkers, but it has not yet been universally adopted into regular use by clinicians. In this review, we describe different components of liquid biopsy, especially circulating tumor cells, circulating tumor DNA and exosomes and their potential clinical utility for pancreatic cancer patients.

Interactive CardioVascular and Thoracic Surgery, 2017

The aim of this study is to analyse the preoperative comorbidity and the survival time of lung ca... more The aim of this study is to analyse the preoperative comorbidity and the survival time of lung cancer for octogenarians and investigate reasonable prognostic factors from multicentre retrospective analysis. Methods: We performed a retrospective multicentre analysis and clinical data was collected from medical files. All patients, who were 80-years-old or older, underwent radical surgery for primary lung cancer from January 1998 to December 2015 in 7 hospitals. Preoperative clinical date, surgical results and survival time were evaluated. As prognostic factors, Charlson Comorbidity Index (CCI) and Glasgow Prognostic Score (GPS) were used. Results: Three hundred and thirty-seven cases were included and analysed in this study. Median age was 82 (range 80-92), and male predominance was 68.1% (216 cases). Preoperative comorbidity was complicated in 61.4% (207 cases). CCI 0/1/2/3 were 130/67/85/55, and GPS 0/1/2 were 240/60/20, respectively. GPS and CCI did not have any significant relationship by Pearson's correlation analysis (P=0.16). Operations included 237 (70.3%) lobectomies, 66 (19.6%) partial resections, 28 (8.3%) segmentectomies, 5 (1.5%) bilobectomies, and 1 (0.3%) pneumonectomy. Postoperative complications and mortality rates were 119 (35.3%) and 7 (2.1%), respectively. Pathological staging I/II/III were 239/60/38. Death due to cancer and death due to non-cancerous causes were 52 and 50, respectively. On univariative and multivariative analyses, pathological staging (P < 0.01, hazard ratio 2.28), CCI over 2 (P=0.01, hazard ratio 2.25), and GPS 1 and 2 (P=0.04, hazard ratio 2.12) were significant prognostic factors for overall survival. The 5-year overall survival rate combined with CCI and GPS revealed that 77.8%, 57.1% and 36.6% with CCI (0, 1) and GPS (0), CCI (2-) or GPS (1, 2), and CCI (2-) and GPS (1, 2), respectively (P < 0.01). Conclusions: Both CCI and GPS as well as pathological staging were useful prognostic factors for an octogenarian with lung cancer who underwent radical surgery in this Japanese cohort study. Disclosure: No significant relationships.

Immunotherapy, 2019

The knowledge of the immune context of renal cell carcinoma (RCC) is useful to predict benefit fr... more The knowledge of the immune context of renal cell carcinoma (RCC) is useful to predict benefit from immunotherapy. We retrospectively characterized the immune context of RCC patients underwent primary nephrectomy and pulmonary metastasectomy. Materials & methods: Intratumoral infiltrating lymphocytes and peritumoral renal infiltrating lymphocytes, lymphocyte subpopulations (CD4 + , CD8 +), PD-1, PD-L1 were explored in paired samples of primary RCC (T) and respective pulmonary metastases (M). Results: The immune variables demonstrated intralesional and intratumoral heterogeneity. Intralesional lymphocyte heterogeneity reached 76% of cases in T, 28% in M. The heterogeneity rate for PD-L1 expression was from 44% (T) to 56% (M); it correlated with better survival. Conclusion: The immune context of RCC is highly variable both within a given tumor and among primary and metastases.

Vascular Pharmacology, Oct 1, 2022

Urolithiasis, Jul 17, 2014

Renal bone metaplasia (RBM) is a uncommon condition and is often an incidental finding. The patho... more Renal bone metaplasia (RBM) is a uncommon condition and is often an incidental finding. The pathogenesis of this phenomenon is not clearly understood. The radiological signs described are not always present and the diagnosis is challenging. In the literature, there is no any conclusion about the optimal management of this condition due to the absence of some conclusions regarding its etiology. In our opinion, no treatment should be applied to prevent its possible evolution into urolithiasis. Surgical removal of the RBM is an overtreatment for a phenomenon not understood and potentially insignificant. We report our experience with a watchful waiting approach in a case of incidental diagnosis of RBM. After 3 years, the patient is asymptomatic, with no evidence of malignancies evolution, new renal stones or growth of the residual RBM.

Journal of Onco-Nephrology, 2021

Objective:To identify histopathological and immunophenotypical features with potential predictive... more Objective:To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC).Methods:We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry.Results:A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with ...

Clinical Lung Cancer, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

$Research paper thumbnail of 39PLOH as “the missing instability” potentially underlying the tumor immunogenicity: On the trails of a correlation between fractional allelic loss and response to nivolumab in renal cancer$

Journal of Maternal-fetal & Neonatal Medicine, May 1, 2005

In this paper we report a case of early onset fetal akinesia, with unusual pathological findings.... more In this paper we report a case of early onset fetal akinesia, with unusual pathological findings. This is a product of medical abortion of young, healthy, unrelated parents. The mother&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s obstetrical history revealed two previous early miscarriages and a suspicion of FADS in the second previous gestation. At 17 weeks of gestation, an ultrasound examination disclosed absence of fetal movements, fixed extended knees and deformation of the feet. Amniocentesis showed a normal 46, XX karyotype. Hydrops fetalis and multiple skin webs (pterygia), which are usually present in cases of early fetal akinesia, were absent. A diagnosis of arthrogryposis was made and the pregnancy was terminated at 17 weeks of gestation. Postmortem examination was performed according to the necropsy technique suggested by Langley. Thus, body weight and external measurement, including crown-rump, crown-heel, foot lengths, head, thorax and abdominal circumferences were estimated and compared with standard values for assessment of fetal growth. External dysmorphic features were evaluated prior to the evisceration. On internal examination the location and shape of every organ was evaluated. Every organ, skin, muscles from different parts of the body, the brain and spinal cord were sampled and histologically examined. External examination revealed a female fetus with marked muscular hypoplasia of upper and lower extremities with thin arms and legs and multiple joint contractures of lower extremities. The face showed a flattened nose, micrognatia, hypertelorism, cleft palate and low-set ears. There was also a small nuchal fold. The abdomen was distended with a very thin and almost transparent wall. Histologically, muscles were characterized by severe fibrosis with fatty infiltration and by moderate variability in diameter of muscle fibers. The spinal cord disclosed a paucity of anterior horn motor neurons. We suggest multiple pterygium as a diagnosis. Lethal multiple pterygium syndrome (LMPS) is only a symptom and the precise diagnosis is more likely to be spinal atrophy. We, moreover believe that the paucity of spinal motoneurons could be due to the anomalies of programmed death during fetal development and the consequence of genetic defects.

Data in Brief, 2020

Anti-Cancer Drugs

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGF... more Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) used both as the first-line treatment of EGFR-mutated non–small cell lung cancer patients and in second-line after T790M-positive disease progression to first- or second-generation TKIs. Unfortunately, patients unavoidably experience disease progression to osimertinib and the current research is focused on resistance mechanisms and the relative therapeutic strategy. We report the case of a patient with advanced EGFR-mutated (exon 19 deletion and T790M-positive) non–small cell lung cancer who developed disease progression to osimertinib characterized by the loss of T790M concurrently with the emergence of G724S EGFR mutation, which was tackled by subsequent afatinib treatment. Next-generation sequencing molecular study of rebiopsy at time of progression to osimertinib revealed the persistence of EGFR exon 19 deletion, loss of T790M with a new G724S EGFR mutation; other concomitant mechanisms were excluded. Retrospective analysis of cell-free DNA revealed the emergence of G724S EGFR mutation four months before the radiologically-proven disease progression. The patient, after chemotherapy, was treated with afatinib with clinical and radiological benefit. Our case report contributes to increase the knowledge on acquired resistance mechanisms to osimertinib treatment, and it shows, for the first time, the efficacy of afatinib in the case of T790M loss and emergence of G724S EGFR mutation.

Tumori Journal

Objective: To evaluate the influence of lung adenocarcinoma second predominant pattern on the max... more Objective: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. Methods: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. Results: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern ( p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort ( p = 0.002) and in low- and intermediate-grade predominant pattern groups ( p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVm...

Frontiers in Oncology

IntroductionThe Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like liga... more IntroductionThe Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab.MethodsImmunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 rat...

Medicine, 2017

Background: The identification of pancreatic carcinoma (PC) patients with poor prognosis is a pri... more Background: The identification of pancreatic carcinoma (PC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. However, the prognostic value of pretreatment 18 F-fluorodeoxyglucose (18 F-FDG)-positron emission tomography (PET)/computed tomography (CT) parameters in PC patients is controversial and no consensus exists as to its predictive capability. This meta-analysis was performed to comprehensively explore the prognostic significance of 18 F-FDG-PET/CT parameters in patients with pancreatic carcinoma. Methods: Extensive literature searches of the PubMed, Embase, Web of Science, and Cochrane Library databases were conducted to identify literature published until March 5, 2017. Comparative analyses of the pooled hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS) were performed to assess their correlations with pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Either the fixedor the random-effects model was adopted, depending on the heterogeneity observed across studies. Subgroup and sensitivity analyses were performed to assess the robustness of the results. Results: Sixteen studies including 1146 patients were identified. The pooled HRs for the probability of EFS were 1.90 (95% confidential interval (CI): 1.48-2.45) for SUVmax, 1.76 (95% CI: 1.20-2.58) for MTV, and 1.81 (95% CI: 1.27-2.58) for TLG. The pooled HRs for the probability of OS were 1.21 (95% CI: 1.12-1.31) for SUVmax, 1.56 (95% CI: 1.13-2.16) for MTV, and 1.70 (95% CI: 1.25-2.30) for TLG. A slight publication bias was detected using Begg test. After adjustment using the trim and fill procedure, the corrected HRs were not significantly different. The results of the subgroup analyses by SUVmax, MTV, and TLG showed that these factors may have similar prognostic significance. Conclusion: 18 F-FDG-PET/CT parameters, such as SUVmax, MTV, and TLG, may be significant prognostic factors in patients with pancreatic carcinoma. 18 F-FDG-PET/CT imaging could be a promising tool to provide prognostic information for these patients. Abbreviations: CI = confidence interval, DFS = disease-free survival, DMFS = disease metastasis-free survival, EFS = event-free survival, HR = hazard ratio, LAPC = locally advanced pancreatic cancer, MTV = metabolic tumor volume, OS = overall survival, PC = pancreatic carcinoma, PFS = progress-free survival, ROC = receiver operating characteristic curve, SUVmax = maximum standardized uptake value, TLG = total lesion glycolysis, VOI = volume of interest.

PURPOSE: This study aimed to evaluate a potential relationship between the diffusing capacity of ... more PURPOSE: This study aimed to evaluate a potential relationship between the diffusing capacity of the lung for carbon monoxide(DLCO) and the aggressiveness of lung adenocarcinoma(ADC).METHODS: Patients who underwent radical surgery for lung ADC between 2001 and 2018 were retrospectively reviewed. DLCO values were dichotomized into DLCOlow(<80% of predicted) and DLCOnormal(≥80%).Relationships between DLCO and ADC histopathological features, clinical features, as well as with overall survival (OS), were evaluated. RESULTS: Four hundred and sixty patients were enrolled, of which 193(42%) were included in the DLCOlow group. DLCOlow was associated with smoking status, low FEV1, micropapillary and solid ADC, tumour grade 3,high tumour lymphoid infiltrate and presence of tumour desmoplasia. In addition, DLCO values were higher in low-grade ADC and progressively decreased in intermediate and high-grade ADC(p=0.024). After adjusting for clinical variables, at multivariable logistic regress...

Cancers

Introduction: BRAF mutation involved 2–4% of lung adenocarcinoma. Differences in clinicopathologi... more Introduction: BRAF mutation involved 2–4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. Materials and Methods: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. Results: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly...