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BACKGROUND: The contribution of the tumor microenvironment and extracellular matrix to the aggressive biology of Gastric Cancer (GC) has been recently characterized; however, the role of EMILIN-1 in this context is unknown. EMILIN-1 is an essential structural element for the maintenance of lymphatic vessel (LV) integrity and displays anti-proliferative properties as demonstrated in skin and colon cancer. Given the key role of LVs in GC progression, the aim of this study was to investigate the role of EMILIN-1 in GC mouse models. METHODS: We used the syngeneic YTN16 cells which were injected subcutaneously and intraperitoneally in genetically modified EMILIN-1 mice. In alternative, carcinogenesis was induced using N-Methyl-N-nitrosourea (MNU). Mouse-derived samples and human biopsies were analyzed by IHC and IF to the possible correlation between EMILIN-1 expression and LV pattern. RESULTS: Transgenic mice developed tumors earlier compared to WT animals. 20 days post-injection tumors developed in EMILIN-1 mutant mice were larger and displayed a significant increase of lymphangiogenesis. Treatment of transgenic mice with MNU associated with an increased number of tumors, exacerbated aggressive lesions and higher levels of LV abnormalities. A significant correlation between the levels of EMILIN-1 and podoplanin was detected also in human samples, confirming the results obtained with the pre-clinical models. CONCLUSIONS: This study demonstrates for the first time that loss of EMILIN-1 in GC leads to lymphatic dysfunction and proliferative advantages that sustain tumorigenesis, and assess the use of our animal model as a valuable tool to verify the fate of GC upon loss of EMILIN-1.
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Progressão da Doença , Glicoproteínas de Membrana , Camundongos Transgênicos , Neoplasias Gástricas , Microambiente Tumoral , Animais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Camundongos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Linfangiogênese , MetilnitrosoureiaRESUMO
BACKGROUND: The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET). METHODS: IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively. RESULTS: 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached. CONCLUSION: The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.
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Colite Ulcerativa , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Criança , Masculino , Feminino , Adolescente , Estudos Prospectivos , Pré-Escolar , Colite Ulcerativa/complicações , Colite Ulcerativa/microbiologia , Doença de Crohn/complicações , Doença de Crohn/microbiologia , Índice de Gravidade de Doença , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/microbiologia , Gastroscopia , Seguimentos , Antibacterianos/uso terapêuticoRESUMO
Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing-NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations.
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Carcinoma Pulmonar de Células não Pequenas , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Projetos Piloto , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/diagnóstico , Proteínas de Fusão Oncogênica/genética , Fusão Gênica , Adulto , Mutação , Quinase do Linfoma Anaplásico/genética , Idoso de 80 Anos ou mais , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Tirosina Quinases , Proteínas Proto-OncogênicasRESUMO
INTRODUCTION: Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up. METHODS: A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained. RESULTS: Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03). DISCUSSION: Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.
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Anemia Perniciosa , Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Gastrite Atrófica/complicações , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Incidência , Estudos de Coortes , Anemia Perniciosa/epidemiologia , Anemia Perniciosa/complicações , Anemia Perniciosa/patologia , Estudos Prospectivos , Gastrite/complicações , Fatores de Risco , Neoplasias Gástricas/patologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Metaplasia/patologia , Infecções por Helicobacter/complicações , Mucosa Gástrica/patologiaRESUMO
BACKGROUND: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats. Thus, microsatellite instability (MSI) is the epiphenomenon of dMMR. In colorectal cancer (CRC), MMR/MSI status is a biomarker with prognostic and predictive value of resistance to 5-fluorouracil and response to immune checkpoint inhibitor therapy. SUMMARY: In this Review, we describe the challenges the practicing pathologist may face in relation to the assessment of MMR/MSI status and any open issues which still need to be addressed, focusing on pre-analytic issues, pitfalls in the interpretation, and technical aspects of the different assays. KEY MESSAGES: The current methods of detecting dMMR/MSI status have been optimized for CRCs, and whether these techniques can be applied to all tumor and specimen types is still not fully understood. Following the Food and Drug Administration (FDA), tissue/site agnostic drug approval of pembrolizumab for advanced/metastatic MSI tumors, MMR/MSI status in gastrointestinal tract is a common request from the oncologist. In this setting, several issues still need to be addressed, including criteria for sample adequacy.
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Adenocarcinoma , Neoplasias Colorretais , Humanos , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologiaRESUMO
INTRODUCTION: Clear cell gastric cancer (CCGC) represents an extremely rare variant of adenocarcinoma of the stomach. It can be mistaken for a clear cell metastatic lesion arising from other anatomic parts, especially renal cell carcinoma. PATIENTS AND METHODS: We describe the case of a 66-year-old woman who was operated for a pyloric adenocarcinoma which resulted to be a CCGC at definitive histology. Moreover, we offer a systematic review of the current pertinent literature on CCGC. RESULTS: Our case represents the 160th example of CCGC. Clear cell aspect is due to the intracytoplasmic accumulation of glycogen in most cases, followed by mucin, lipid or water; the reason of the underlying biochemical process is still unclear. Paralleling other epithelial clear cell malignancies (as ovarian, bladder, urothelial or pancreatic cancers), also CCGC shows a more aggressive clinical behavior over conventional neoplastic counterparts. CONCLUSIONS: Differently from clear cell carcinomas involving other organs, CCGC has been rarely investigated by the literature. Since, compared to non clear cell cancers, this particular phenotype of gastric cancer appears to be associated with poorer prognosis, further studies are needed in order to corroborate its real adverse prognostic significance and standardize the correct management and treatment.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , PrognósticoRESUMO
Colorectal and glioblastoma cancer stem-like cells (CSCs) are essential for translational research. Cell line authentication by short tandem repeat (STR) profiling ensures reproducibility of results in oncology research. This technique enables to identify mislabeling or cross-contamination of cell lines. In our study, we provide a reference dataset for a panel of colorectal and glioblastoma CSCs that allows authentication. Each cell line was entered into the cell Line Integrated Molecular Authentication database 2.1 to be compared to the STR profiles of 4485 tumor cell lines. This article also provides clinical data of patients from whom CSCs arose and data on the parent tumor stage and mutations. STR profiles and information of our CSCs are also available in the Cellosaurus database (ExPASy) as identified by unique research resource identifier codes.
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Autenticação de Linhagem Celular/métodos , Autenticação de Linhagem Celular/normas , Linhagem Celular Tumoral , Repetições de Microssatélites , Células-Tronco Neoplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/normas , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Corpus atrophic gastritis (CAG) is associated with intestinal metaplasia (IM) and pseudopyloric metaplasia (PPM). Prospective data on corpus mucosa PPM and its link to the development of gastric cancer (GC) are lacking. This study aimed to investigate the relationship between the presence of corpus mucosa PPM at baseline and the development of GC at follow-up in patients with CAG. METHODS: A longitudinal cohort study was conducted on patients with consecutive CAG adhering to endoscopic-histological surveillance. Patients were stratified for the presence/absence of corpus PPM without concomitant corpus IM at baseline, and the occurrence of gastric neoplastic lesions at the longest available follow-up was assessed. RESULTS: A total of 292 patients with CAG with a follow-up of 4.2 (3-17) years were included. At baseline, corpus PPM without corpus IM was diagnosed in 62 patients (21.2%). At the follow-up, GC was detected in 5 patients (1.7%) and gastric dysplasia (GD) in 4 patients (1.4%). In all these 9 patients with GC/GD at the follow-up, corpus IM was present at baseline and follow-up. Age <50 years (odds ratio [OR] 2.5), absence of pernicious anemia (OR 4.3), and absence of severe corpus atrophy (OR 2.3) were associated with corpus PPM without corpus IM. DISCUSSION: At the 4.2-year follow-up, in patients with CAG characterized at baseline with corpus PPM without corpus IM, GC or GD was not observed because these lesions were consistently associated with corpus IM. Corpus PPM without corpus IM was associated with younger age, absence of pernicious anemia, and severe corpus atrophy, suggesting a lower stage of disease progression. Corpus PPM alone seems not to be associated with GC, whose development seems to require the presence of corpus IM as a necessary step.
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Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Metaplasia/complicações , Neoplasias Gástricas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Gastrite Atrófica/patologia , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
INTRODUCTION: Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-dependent pathways in pancreatic neuroendocrine neoplasms (PanNENs) underlies the introduction of the mTORC1 inhibitor everolimus as treatment of advanced progressive PanNENs. Although everolimus significantly increases progression-free survival, most patients acquire secondary resistance to the drug. This study aimed at identifying mechanisms involved in acquisition of resistance to everolimus. METHODS: BON-1 and everolimus-resistant (ER) BON-1 cells were used as in vitro system of sensitivity and acquired resistance. Transcriptome changes occurring in BON-1 and ER-BON-1 were investigated by RNA sequencing and validated by quantitative PCR analysis. RNA extracted from patients' biopsies was used to validate MYC upregulation. Drug screening and functional assays were performed using ER-BON-1 cells. Cell cycle progression was evaluated by FACS analysis. RESULTS: Our results show that MYC overexpression is a key event in the development of secondary resistance to everolimus in PanNEN cell lines and in metastatic lesions from neuroendocrine neoplasm patients. MYC knockdown restored ER-BON-1 sensitivity to everolimus. Pharmacological inhibition of MYC mediated by the cyclin-dependent kinase inhibitor dinaciclib strongly reduced viability of ER-BON-1. Dinaciclib synergized with everolimus and inhibited ER-BON-1 cell cycle progression. DISCUSSION: Our findings suggest that MYC upregulation drives the development of secondary resistance to everolimus in PanNENs and that its inhibition is an exploitable vulnerability. Indeed, our results indicate that combined treatments with cyclin-dependent kinase and mTOR inhibitors may counteract secondary resistance to everolimus in PanNENs and may pave the ground for new therapeutic regimens for these tumors.
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Antineoplásicos/farmacologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Everolimo/farmacologia , Genes myc/efeitos dos fármacos , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , Regulação para CimaRESUMO
BACKGROUND: Laparoscopic resections for rectal cancer are routinely performed in high-volume centres. Despite short-term advantages have been demonstrated, the oncological outcomes are still debated. The aim of this study was to compare the oncological adequateness of the surgical specimen and the long-term outcomes between open (ORR) and laparoscopic (LRR) rectal resections. METHODS: Patients undergoing laparoscopic or open rectal resections from January 1, 2013, to December 31, 2019, were enrolled. A 1:2 propensity score matching was performed according to age, sex, BMI, ASA score, comorbidities, distance from the anal verge, and clinical T and N stage. RESULTS: Ninety-eight ORR were matched to 50 LRR. No differences were observed in terms of operative time (224.9 min. vs. 230.7; p = 0.567) and postoperative morbidity (18.6% vs. 20.8%; p = 0.744). LRR group had a significantly earlier soft oral intake (p < 0.001), first bowel movement (p < 0.001), and shorter hospital stay (p < 0.001). Oncological adequateness was achieved in 85 (86.7%) open and 44 (88.0%) laparoscopic resections (p = 0.772). Clearance of the distal (99.0% vs. 100%; p = 0.474) and radial margins (91.8 vs. 90.0%, p = 0.709), and mesorectal integrity (94.9% vs. 98.0%, p = 0.365) were comparable between groups. No differences in local recurrence (6.1% vs.4.0%, p = 0.589), 3-year overall survival (82.9% vs. 91.4%, p = 0.276), and disease-free survival (73.1% vs. 74.3%, p = 0.817) were observed. CONCLUSIONS: LRR is associated with good postoperative results, safe oncological adequateness of the surgical specimen, and comparable survivals to open surgery.
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Laparoscopia , Protectomia , Neoplasias Retais , Humanos , Recidiva Local de Neoplasia , Protectomia/efeitos adversos , Pontuação de Propensão , Neoplasias Retais/cirurgia , Reto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: BRAF mutations represent the main negative prognostic factor for metastatic colorectal cancer and a supposed negative predictive factor of response to standard chemotherapy. We have explored survival difference in right-sided colon cancer (RCC) patients according to BRAF mutations, with the aim to identify any predictive factors of response to targeted-based therapy. METHODS: A retrospective study of RCC patients, with BRAF known mutation status, treated with chemotherapy (CT) from October 2008 to June 2019 in 5 Italian centers, was conducted. RESULTS: We identified 207 advanced RCC patients: 20.3% BRAF mutant and 79.7% BRAF wild type (wt). BRAF-mutant cancers were more likely to be pT4 (50.0% v 25.7%, p = 0.016), undifferentiated (71.4% v 44.0%, p = 0.004), KRAS wt (90.5% v 38.2%, p < 0.001), and MSI-H (41.7% v 16.2%, p = 0.019) tumors, with synchronous (52.4% v 31.5%, p = 0.018) and peritoneal metastases (38.1% v 22.4%, p = 0.003). Median overall survival (OS) was 16 v 27 months in BRAF mutant and BRAF wt (P = 0.020). In first-line setting, BRAF-mutant showed a 2ys OS of 80% in clinical trials, 32% in anti-VEGF, 14% in epidermial growth factor receptor (EGFR), and 0% in chemotherapy alone regimens (P = 0.009). BRAF-mutant patients demonstrated worse survival, regardless of targeted therapy administered. However, survival difference was statistically significant in the anti-EGFR-treated subgroup (16 v 28 months, P = 0.005 in BRAF mutant v BRAF wt, respectively). CONCLUSIONS: Our study demonstrated that BRAF status makes the difference in treatment's outcome. Therefore, the anti-EGFR should not be excluded in all advanced RCC but considered on a case-by-case basis.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Receptores ErbB , Humanos , Mutação/genética , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos RetrospectivosRESUMO
Gastric biopsies represent one of the most frequent specimens that the pathologist faces in routine activity. In the last decade or so, the landscape of gastric pathology has been changing with a significant and constant decline of H. pylori-related pathologies in Western countries coupled with the expansion of iatrogenic lesions due to the use of next-generation drugs in the oncological setting. This overview will focus on the description of the elementary lesions observed in gastric biopsies and on the most recent published recommendations, guidelines and expert opinions.
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Gastrite , Biópsia , Endoscopia , Mucosa Gástrica/patologia , Gastrite/etiologia , Gastrite/patologia , Helicobacter pylori/patogenicidade , Humanos , Gradação de Tumores , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologiaRESUMO
AIM: In patients affected by atrophic body gastritis (ABG) gastro-oesophageal reflux (GER) related symptoms have been reported, despite the presence of hypochlorhydria. OBJECTIVE: Objectives of this single-centre study was to assess in ABG the occurrence of GER-related symptoms and their relationship with histopathologic oesophageal findings. MATERIALS AND METHODS: Fifty-four consecutive patients (20.4%male, 57.6 ± 14 years) undergoing to follow-up for ABG, underwent assessment of GER-related symptoms and gastroscopy with multiple gastric and oesophageal biopsies to investigate the presence of microscopic esophagitis (ME). RESULTS: At least one typical GER symptoms were reported in 24.1% with 9.2% of patients complaining of heartburn and 18.5% regurgitation. One or more atypical GERD symptoms were reported in 44.4% of patients. Two symptomatic ABG patients presented oesophageal lesions at endoscopy (one with erosive esophagitis (LA-C) and one with Barrett's oesophagus (C2M2)), 49% reported a mild ME and 24.5% a severe ME. No significant differences regarding GERD prevalence were found among patients with or without ME, but cough was the only symptom significantly more frequent in patients with ME (38.95% vs. 7.7%, p = .042). CONCLUSIONS: These data showed that GERD is present in a quarter of ABG patients, suggesting that hypochlorhydria not exclude per se arising of oesophageal symptoms. In ABG we found that ME is a frequent finding but its clinical relevance remains to be investigated with further studies.
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Gastrite Atrófica/fisiopatologia , Refluxo Gastroesofágico/etiologia , Adulto , Idoso , Esôfago de Barrett/etiologia , Estudos de Coortes , Esofagite Péptica/etiologia , Esofagoscopia , Esôfago/patologia , Feminino , Gastrite Atrófica/complicações , Gastroscopia , Azia/etiologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
PURPOSE: Stage II colon cancer (CC) represents a challenging scenario for the choice of adjuvant chemotherapy; here, histologic factors need to be weighed up to establish the risk of recurrence. Tumor budding (TB) has recently been indicated as a confident predictor of clinical outcome in CC. Likewise, the presence of poorly differentiated clusters (PDCs) in a tumor has been pointed out as a leading criterion of a tumor grading system. Our aim was to evaluate in patients with stage II CC the relationship between these features and clinical outcome. PATIENTS AND METHODS: The study included 174 cases of stage II CC; histopathologic parameters such as TB, PDCs, microsatellite instability (MSI), and CDX2 expression were analyzed. RESULTS: There were 107 (70.9%), 32 (21.2%), and 12 (7.9%) TB scored 1, 2, and 3 respectively; 113 (72.9%), 30 (19.4%), and 12 (7.7%) tumors showed grade 1, 2, and 3 PDCs respectively. A high-MSI was detected in 32 cases (18.4%) while CDX2 was negative in 20 (11.5%) tumor samples. In the whole study population, only the TB was found to be associated with disease-specific survival (P = 0.01). No parameter apart from age (P = 0.04) was a significant prognostic factor for overall survival (P < 0.05). Other commonly reported variables, including tumor size, degree of tumor differentiation, lymphovascular invasion, number of lymph nodes harvested ≥ 12, MSI, and PDCs, were not shown to have significant results. CONCLUSIONS: Although confirmatory studies are awaited, our work supports the role of the TB in defining risk groups of the stage II CC.
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Neoplasias do Colo/patologia , Idoso , Diferenciação Celular , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Técnicas de Reprogramação Celular/métodos , Células Epiteliais/citologia , Neoplasias Pulmonares/patologia , Idoso , Animais , Biópsia , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias do Colo/patologia , Células Epiteliais/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Transplante de Neoplasias , Fenótipo , Células-Tronco/citologia , Células-Tronco/patologia , Células Tumorais CultivadasRESUMO
BACKGROUND: Lymphocyte expansion and true lymphocytosis are commonly observed in the everyday clinical practice. The meaning of such phenomenon is often poorly understood so that discrimination between benign and malignant lymphocytosis remains difficult to establish. This is mainly true when lymphocytosis rises in patients affected by immune-mediated chronic inflammatory diseases under immunosuppressive treatment, conditions potentially associated with lymphomagenesis. In this brief report the development of mild T CD4pos lymphocytosis in a group of patients with chronic arthritis under anti-TNF-α treatment is described. METHODS: Two hundred eight rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients have been evaluated longitudinally for at least 1-year before and 2-years after anti-TNF-α therapy introduction for the possible appearance of a lymphocyte expansion. In patients who developed lymphocyte expansion, T, B and NK cells were analysed. RESULTS: Twenty-five out of 208 (12%) subjects developed a mild T CD4pos lymphocytosis, during anti-TNF-α therapy, which reverted after its interruption. Higher lymphocyte count, more frequent use of steroids and shorter disease duration, before biological therapy start, have emerged as risk factors for lymphocytosis development. CONCLUSIONS: This is the first longitudinal cohort study evaluating the onset of lymphocytosis in RA and PsA patients under anti-TNF-α treatment and its possible clinical relevance. A mild T CD4pos lymphocytosis has been observed in 12% of RA and PsA patients probably related to anti-TNF-α treatment as previously reported by anecdotal cases. Patients with higher baseline lymphocyte count, use of steroids and shorter disease duration before the introduction of biologic therapy, seem to be prone to develop this laboratory reversible abnormality.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Antígenos CD4/metabolismo , Linfocitose/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/farmacologia , Artrite Psoriásica/imunologia , Artrite Reumatoide/imunologia , Demografia , Feminino , Humanos , Contagem de Linfócitos , Linfocitose/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: The aim of this study was to correlate computed tomography (CT) findings with pathology in gastrointestinal stromal tumors (GISTs). METHODS: A retrospective evaluation of CT images of 44 patients with GISTs was performed. Computed tomography findings analyzed were location, size, margins, degree and pattern of contrast enhancement, angiogenesis, necrosis, signs of invasion, peritoneal effusion, peritoneal implants, surface ulceration, and calcifications.Associations between CT features and mitotic rate, Miettinen classes of risk, lesions size, and among CT features were investigated. χ Test and Fisher test were performed. RESULTS: Mitotic rate was associated with margins (P = 0.016) and with adjacent organ invasion (P = 0.043). Pattern of contrast enhancement (P = 0.002), angiogenesis (P = 0.006), necrosis (P = 0.006), invasion of adjacent organs (P = 0.011), and margins (P = 0.006) were associated with classes of risk. Several associations (P < 0.05) between lesion size and CT features and among all the investigated CT features were found. CONCLUSIONS: Computed tomography features could reflect GIST biology being associated with the mitotic rate and with classes of risk.
Assuntos
Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Despite different prognostic factors have been already studied, patients undergoing potentially curative resection for gastric cancer, still have a poor outcome. There is therefore the need to identify novel prognostic factors. Recently, Tumor-Stroma Ratio (TSR) was proven to be associated with prognosis in different types of cancers. Aim of this study was to evaluate the prognostic value of TSR in gastric cancer patients. METHODS: 106 patients underwent gastrectomy between January 2004 and December 2015. Demographics and histopathological characteristics were collected. We considered a 50% TSR cutoff value to divide patients in Stroma-Rich (≥50%) and Stroma-Poor (<50%) groups. RESULTS: Forty-one (38.7%) patients were classified as Stroma-Poor while 65 (61.3%) as Stroma-Rich (61.3%). The Stroma-Rich patients had a higher number of positive lymph-nodes, lymph node ratio (LNR), a higher percentage of T3/T4 local invasion and N2/N3, and a more advanced TNM. Moreover, these patients showed a higher percentage of lymphovascular and perineural invasion. With a median FU of 38 months Stroma-Rich patients had a significantly worse 5-years actuarial overall survival (OS) and disease free survival (DFS) compared to Stroma-Poor patients. Moreover, the multivariate analysis showed that Stroma-Rich was the only independent factor associated with OS and DFS together with TNM-Stage. CONCLUSIONS: TSR is an independent marker of poor prognosis in patients with gastric cancer that should be readily incorporated into routine clinical pathology reporting. Identification of sensitive markers for patients who had undergone curative gastrectomy and who are at high risk of recurrence could provide useful information for planning follow-up after surgery or intensive and or/targeting adjuvant chemotherapy.
Assuntos
Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Estômago/patologia , Gastrectomia , Humanos , Metástase Linfática , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estômago/cirurgia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Carga TumoralRESUMO
OBJECTIVE: Atrophic gastritis (AG) is a risk condition for gastric cancer and type I gastric carcinoids. Recent studies assessing the overall risk of gastric cancer and carcinoids in AG at long-term follow up are lacking. This study aimed to investigate in a prospective cohort of AG patients the occurrence of gastric cancer and carcinoids at long-term follow up. METHODS: A total of 200 AG patients from a prospective cohort (67% female, median age 55 years) with a follow up of 7.5 (range: 4-23.4) years were included. Inclusion criteria were presence of AG and at least one follow-up gastroscopy with biopsies at ≥4 years after AG diagnosis. Follow-up gastroscopies at 4-year intervals were performed. RESULTS: Overall, 22 gastric neoplastic lesions were detected (crude incidence 11%). Gastric cancer was diagnosed in four patients at a median follow up of 7.2 years (crude incidence 2%). Eleven type I gastric carcinoids were detected at a median follow up of 5.1 years (crude incidence of 5.5%). In seven patients, six low-grade and one high-grade dysplasia were found. The annual incidence rate person-year were 0.25% (95% confidence interval [CI]: 0.067-0.63%), 0.43% (95% CI: 0.17-0.89%), and 0.68% (95% CI: 0.34-1.21%) for gastric cancer, dysplasia, and type I-gastric carcinoids, respectively. The incidence rates of gastric cancer and carcinoids were not different (p = 0.07). CONCLUSION: This study shows an annual incidence rate of 1.36% person-year for gastric neoplastic lesions in AG patients at long-term follow up. AG patients are similarly exposed to gastric cancer and type I gastric carcinoids.
Assuntos
Tumor Carcinoide/patologia , Gastrite Atrófica/patologia , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Coortes , Feminino , Gastroscopia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Análise de Regressão , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Atrophic body gastritis (ABG) is associated with both type I gastric carcinoids (T1-GCs) and intestinal-type gastric cancer. The occurrence of gastric cancer in ABG patients with type I gastric carcinoids has not yet been described. AIM: To describe the occurrence at follow-up of gastric cancer in ABG patients with type I gastric carcinoid in a retrospective case series in a single tertiary referral center. METHODS: Between 1994 and 2012, 17 new cases of T1-GCs were diagnosed among a cohort of ABG patients in a single tertiary referral center for ABG. The clinical charts of these 17 T1-GC patients were retrospectively evaluated for the occurrence of gastric cancer at follow-up (median 4.2 years, range 0.5-13). RESULTS: In 4 (23.5 %)/17 T1-GCs patients (3 females, age 40-78 years), gastric cancer occurred (median follow-up 5.9 years, range 5.1-13). Three cases were intestinal-type adenocarcinomas and one a signet-ring cell diffuse gastric cancer, localized in three cases in the antrum. In two patients, it was detected on random biopsies during follow-up gastroscopy; in the other two, gastroscopy was performed because of new symptoms. All patients with gastric cancer had associated autoimmune features (pernicious anemia, autoimmune thyroid disease and a spared antrum) compared to 77, 46 and 54 % of those without gastric cancer, although statistical significance was not reached. CONCLUSIONS: This case series shows that in patients with T1-GCs, gastric cancer may frequently occur at long-term follow-up. Thus, these patients should be monitored by a long-term surveillance program, including an accurate bioptic sampling of the antral mucosa.