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1.
S Afr J Surg ; 62(2): 33-38, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38838117

RESUMO

BACKGROUND: The value of the textbook outcome in pancreatic surgery (TOPS) score, a composite measure of surgical performance for quality assurance, was evaluated in a South African tertiary hospital cohort of pancreaticoduodenectomies (PD) performed for adenocarcinoma of the ampulla of Vater (AAV). METHODS: A review of all patients undergoing a PD for AAV at a single centre between January 1999 and December 2023 was performed. Demographic, operative, pathological and postoperative variables were recorded. Ten clinical and histological variables were used to construct a TOPS score. These included an R0 resection, no postoperative pancreatic fistula (POPF), no bile leak, no post-pancreatectomy haemorrhage, no delayed gastric emptying, no major postoperative complications (< Gr 3 Clavien-Dindo), no readmission to ICU, length of stay ≤ 10 days, no 30-day readmission or intervention and no 30-day mortality. A textbook outcome (TO) was defined as the fulfilment of all 10 variables. In patients in whom TO was not achieved, the reasons for failure were identified. In addition, the number of patients who had major complications and died were categorised as failure to rescue (FTR). RESULTS: A positive TOPS score was achieved in 27 of 79 (34.2%) patients undergoing a PD. Overall five-year survival after PD was 33.9%. TOPS conferred a significant 1-year survival benefit, 88.9% vs 66.7% (OR 4.12, 95% CI 1.08-15.67, p = 0.038). There was no significant difference in 5-year survival between TOPS and non-TOPS patients, 40.0% vs 32.4% (OR 1.39, 95% CI 0.48-3.99, p = 0.54). A POPF occurred in 31.6% patients, resulting in a significantly longer hospital admission, 17 vs 10 days (95% CI 2.66-11.34, p = 0.0019). Twenty-one (26.6%) patients developed a major complication, five of whom died (FTR = 6.3%). CONCLUSION: This study confirmed the value of TOPS as a useful measurement to assess hospital quality metrics and short-term survival after PD for AAV. One quarter of patients developed a major complication with a 6.3% FTR.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Pancreaticoduodenectomia , Humanos , Ampola Hepatopancreática/cirurgia , Masculino , Feminino , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/patologia , Pessoa de Meia-Idade , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Estudos Retrospectivos , Prognóstico , Complicações Pós-Operatórias , África do Sul , Adulto , Resultado do Tratamento
3.
Pan Afr Med J ; 47: 116, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828424

RESUMO

Non-small cell lung cancer (NSCLC) is a significant global health issue with diverse molecular profiles affecting treatment responses. Yet, NSCLC's molecular epidemiology in Morocco is largely unexplored. This study focuses on NSCLC genetic mutations, specifically in adenocarcinoma, among Moroccan patients to contribute to understanding NSCLC in this population. Ninety-four patients diagnosed with lung adenocarcinoma were analyzed. Formalin-fixed paraffin-embedded tissue samples were processed, and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) was extracted using standardized protocols. Mutations were detected using the AmoyDx Pan Lung Cancer Polymerase Chain Reaction (PCR) Panel kit, and their frequencies were assessed through statistical analysis. Epidermal Growth Factor Receptor (EGFR) mutations were detected in 22.34% of patients, predominantly exon 19 deletions (66.66%) and exon 21 L858R mutations (23.80%). Anaplastic lymphoma kinase (ALK) gene fusion was observed in 3.19% of patients, and KRAS mutations in 1.06%. No mutations were found in other tested genes. A slightly higher mutation rate was noted in females (54.16%) compared to males (45.84%). The study reveals a distinct mutation profile in Moroccan NSCLC patients, with a notable prevalence of EGFR mutations, albeit lower than in some Asian populations. The significance of EGFR mutations in treatment response aligns with global findings, highlighting the importance of understanding regional molecular variations for personalized therapy. Despite limitations in sample size and clinical data, this study sheds light on the genetic landscape of NSCLC in Morocco. The observed mutation rates, particularly in EGFR, underscore the potential for targeted therapies in Moroccan NSCLC patients, emphasizing the need for further research to refine treatment strategies tailored to this population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Marrocos , Masculino , Feminino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Receptores ErbB/genética , Idoso , Adulto , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Quinase do Linfoma Anaplásico/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Reação em Cadeia da Polimerase , Idoso de 80 Anos ou mais , Taxa de Mutação , Fatores Sexuais
4.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824512

RESUMO

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.


Assuntos
Neoplasias Gastrointestinais , Humanos , Espanha/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Adulto , Idade de Início , Estilo de Vida , Adenocarcinoma/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Microambiente Tumoral , Qualidade de Vida , Incidência , Biomarcadores Tumorais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia
5.
PLoS One ; 19(6): e0304701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870120

RESUMO

This paper presents the initial exploration of the free radical scavenging capabilities of peptides derived from protein hydrolysates (PPH) obtained from Zingiber cassumunar rhizomes (Phlai). To replicate the conditions of gastrointestinal digestion, a combination of pepsin and pancreatin proteolysis was employed to generate these hydrolysates. Subsequently, the hydrolysate underwent fractionation using molecular weight cut-off membranes at 10, 5, 3, and 0.65 kDa. The fraction with a molecular weight less than 0.65 kDa exhibited the highest levels ABTS, DPPH, FRAP, and NO radical scavenging activity. Following this, RP-HPLC was used to further separate the fraction with a molecular weight less than 0.65 kDa into three sub-fractions. Among these, the F5 sub-fraction displayed the most prominent radical-scavenging properties. De novo peptide sequencing via quadrupole-time-of-flight-electron spin induction-mass spectrometry identified a pair of novel peptides: Asp-Gly-Ile-Phe-Val-Leu-Asn-Tyr (DGIFVLNY or DY-8) and Ile-Pro-Thr-Asp-Glu-Lys (IPTDEK or IK-6). Database analysis confirmed various properties, including biological activity, toxicity, hydrophilicity, solubility, and potential allergy concerns. Furthermore, when tested on the human adenocarcinoma colon (Caco-2) cell line, two synthetic peptides demonstrated cellular antioxidant activity in a concentration-dependent manner. These peptides were also assessed using the FITC Annexin V apoptosis detection kit with PI, confirming the induction of apoptosis. Notably, the DY-8 peptide induced apoptosis, upregulated mRNA levels of caspase-3, -8, and -9, and downregulated Bcl-2, as confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot analysis indicated increased pro-apoptotic Bax expression and decreased anti-apoptotic Bcl-2 expression in Caco-2 cells exposed to the DY-8 peptide. Molecular docking analysis revealed that the DY-8 peptide exhibited binding affinity with Bcl-2, Bcl-xL, and Mcl-1, suggesting potential utility in combating colon cancer as functional food ingredients.


Assuntos
Apoptose , Neoplasias do Colo , Peptídeos , Rizoma , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , Rizoma/química , Células CACO-2 , Transdução de Sinais/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Zingiberaceae/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
6.
Pathol Oncol Res ; 30: 1611734, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873175

RESUMO

Background: Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the cause, classification, and clinicopathological features of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods: 37 cases diagnosed with GEN-FGMLs were included in this study. H&E-stained slides were reviewed and clinicopathological parameters were recorded. Immunohistochemical staining was conducted for MUC2, MUC5AC, MUC6, CD10, CD56, synaptophysin, chromograninA, p53, Ki67, pepsinogen-I, H+/K+-ATPase and Desmin. Results: The patients' ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between OGA, GA-FG, and GA-FGM. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. These cells resembled fundic gland cells. None of the OGA invaded the submucosal layer. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Non-atrophic gastritis was observed in more than half of the background mucosa. All cases were diffusely positive for MUC6 and pepsinogen-I on immunohistochemistry. H+/K+-ATPase staining was negative or showed a scattered pattern in most cases. MUC5AC was expressed on the surface of GA-FGMs. p53 was focally expressed and the Ki67 index was low (1%-20%). Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p < 0.05) and had larger sizes (p < 0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p < 0.0001). Specimens with Ki-67 proliferation indices >2.5% and size >4.5 mm are more likely to be diagnosed with GA-FG and GA-FGM than OGA. Conclusion: GEN-FGMLs are group of well-differentiated gastric tumors with favourable biological behaviours, low cellular atypia, and low proliferation. Immunohistochemistry is critical for confirming diagnosis. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. Pathologists and endoscopists should be cautious to prevent misdiagnosis and overtreatment, especially in biopsy specimens.


Assuntos
Biomarcadores Tumorais , Mucosa Gástrica , Antígeno Ki-67 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Antígeno Ki-67/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Fundo Gástrico/patologia , Fundo Gástrico/metabolismo , Adenoma/patologia , Adenoma/metabolismo , Prognóstico
7.
Int J Gynecol Pathol ; 43(4): 362-372, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38870078

RESUMO

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/diagnóstico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/classificação , Pessoa de Meia-Idade , Adulto , Idoso , Imuno-Histoquímica , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/classificação , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição PAX8/análise , Fator de Transcrição PAX8/metabolismo , Diferenciação Celular , Endometriose/patologia
8.
Mol Biol Rep ; 51(1): 756, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874783

RESUMO

AIM: Dedifferentiated endometrial adenocarcinoma (DEAC) is a rare, aggressive subtype, accounting for 2% of all endometrial cancers. Poor survival in DEAC prompts the need for effective treatment modalities through better prognostic classification. MicroRNAs (miRNA) have essential roles in tumor angiogenesis, which might enable their use as novel biomarkers. In this study, we aimed to reveal the relationship between the expression of miRNA-21 and miRNA-143, which are associated with angiogenesis, and the prognosis of DEAC. METHOD: The study included six cases diagnosed with DEAC. The expression levels of miRNA-21 and miRNA-143 were detected by quantitative real-time PCR. Microvascular density (MVD) was measured by CD34 staining. All data and effects on survival were compared for statistical significance. RESULTS: Six cases diagnosed with DEAC were included in the study. The percentage of undifferentiated components ranged from 50 to 90%. The second component of differentiated carcinoma was detected as endometrioid (3/5 grade I, 1/5 grade II, 1/5 grade III) in five cases and serous in one case. The mean MVD was 27 (range 17-44, SD 9.4). In three cases, miRNA-21 expression was down-regulated in neoplastic areas compared to non-neoplastic areas. On the contrary, it was found to be up-regulated in the remaining three cases. MiRNA-143 expression decreased in four cases and increased in two cases. CONCLUSIONS: Based on these findings, we found a significant irregular expression of miRNA-21 in DEACs. As in other cancers, angiogenesis is significantly associated with survival in DEACs. This study provides initial data for revealing possible implications of miRNAs as prognostic indicators in DEAC.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Endométrio , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Prognóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Idoso , Regulação Neoplásica da Expressão Gênica/genética , Neovascularização Patológica/genética , Adulto
9.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 552-556, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825899

RESUMO

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Endométrio , Imuno-Histoquímica , Sensibilidade e Especificidade , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Pessoa de Meia-Idade , Diagnóstico Diferencial , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Antígenos de Neoplasias/metabolismo , Idoso de 80 Anos ou mais
10.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 578-584, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825903

RESUMO

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Receptores ErbB , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Receptor ErbB-2 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Feminino , Estudos Retrospectivos , Quinase do Linfoma Anaplásico/genética , Receptores ErbB/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-ret/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Pessoa de Meia-Idade
11.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 605-609, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825907

RESUMO

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.


Assuntos
Hepatoblastoma , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Primárias Múltiplas , Tumor Rabdoide , Neoplasias Gástricas , Humanos , Masculino , Criança , Feminino , Pré-Escolar , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Renais/patologia , Neoplasias Renais/genética , Lactente , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Hepatoblastoma/genética , Hepatoblastoma/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/diagnóstico , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/genética , Teratoma/patologia , Teratoma/genética , Teratoma/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteína SMARCB1/genética , Proteína 1 Homóloga a MutL/genética , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/genética , Sequenciamento de Nucleotídeos em Larga Escala , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia
12.
Cancer Lett ; 595: 217025, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38844063

RESUMO

Despite the confirmed role of LKB1 in suppressing lung cancer progression, its precise effect on cellular senescence is unknown. The aim of this research was to clarify the role and mechanism of LKB1 in restraining telomerase activity in lung adenocarcinoma. The results showed that LKB1 induced cellular senescence and apoptosis either in vitro or in vivo. Overexpression of LKB1 in LKB1-deficient A549 cells led to the inhibition of telomerase activity and the induction of telomere dysfunction by regulating telomerase reverse transcriptase (TERT) expression in terms of transcription. As a transcription factor, Sp1 mediated TERT inhibition after LKB1 overexpression. LKB1 induced lactate production and inhibited histone H4 (Lys8) and H4 (Lys16) lactylation, which further altered Sp1-related transcriptional activity. The telomerase inhibitor BIBR1532 was beneficial for achieving the optimum curative effect of traditional chemotherapeutic drugs accompanied by the glycolysis inhibitor 2DG. These data reveal a new mechanism by which LKB1 regulates telomerase activity through lactylation-dependent transcriptional inhibition, and therefore, provide new insights into the effects of LKB1-mediated senescence in lung adenocarcinoma. Our research has opened up new possibilities for the creation of new cancer treatments.


Assuntos
Quinases Proteína-Quinases Ativadas por AMP , Adenocarcinoma de Pulmão , Senescência Celular , Histonas , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Fator de Transcrição Sp1 , Telomerase , Humanos , Telomerase/metabolismo , Telomerase/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Senescência Celular/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Histonas/metabolismo , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Animais , Células A549 , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Apoptose/efeitos dos fármacos , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Camundongos , Linhagem Celular Tumoral
13.
Nat Cell Biol ; 26(6): 975-990, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38862786

RESUMO

Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours. This distinct Gstt1high population is highly metastatic and retains slow-cycling phenotypes, epithelial-mesenchymal transition features and DTC characteristics compared to the Gstt1low population. Mechanistic studies indicate that in this subset of cancer cells, Gstt1 maintains metastases by binding and glutathione-modifying intracellular fibronectin, in turn promoting its secretion and deposition into the metastatic microenvironment. We identified Gstt1 as a mediator of metastasis, highlighting the importance of heterogeneity and its influence on the metastatic tumour microenvironment.


Assuntos
Glutationa Transferase , Neoplasias Pancreáticas , Microambiente Tumoral , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/metabolismo , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Fibronectinas/metabolismo , Metástase Neoplásica , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/enzimologia , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Camundongos , Feminino , Camundongos Endogâmicos C57BL
14.
Sci Rep ; 14(1): 13555, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867070

RESUMO

In order to construct a prognostic evaluation model of TLS features in COAD and better realize personalized precision medicine in COAD. Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive system. At present, there is no effective prognostic marker to predict the prognosis of patients. Tertiary lymphoid structure (TLS) affects cancer progression by regulating immune microenvironment. Mining COAD biomarkers based on TLS-related genes helps to improve the prognosis of patients. In order to construct a prognostic evaluation model of TLS features in COAD and better realize personalized precision medicine in COAD. The mRNA expression data and clinical information of COAD and adjacent tissues were downloaded from the Cancer Genome Atlas database. The differentially expressed TLS-related genes of COAD relative to adjacent tissues were obtained by differential analysis. TLS gene co-expression analysis was used to mine genes highly related to TLS, and the intersection of the two was used to obtain candidate genes. Univariate, LASSO, and multivariate Cox regression analysis were performed on candidate genes to screen prognostic markers to construct a risk assessment model. The differences of immune characteristics were evaluated by ESTIMATE, ssGSEA and CIBERSORT in high and low risk groups of prognostic model. The difference of genomic mutation between groups was evaluated by tumor mutation burden score. Screening small molecule drugs through the GDSC library. Finally, a nomogram was drawn to evaluate the clinical value of the prognostic model. Seven TLS-related genes ADAM8, SLC6A1, PAXX, RIMKLB, PTH1R, CD1B, and MMP10 were screened to construct a prognostic model. Survival analysis showed that patients in the high-risk group had significantly lower overall survival rates. Immune microenvironment analysis showed that patients in the high-risk group had higher immune indicators, indicating higher immunity. The genomic mutation patterns of the high-risk and low-risk groups were significantly different, especially the KRAS mutation frequency was significantly higher in the high-risk group. Drug sensitivity analysis showed that the low-risk group was more sensitive to Erlotinib, Savolitinib and VE _ 822, which may be used as a potential drug for COAD treatment. Finally, the nomogram constructed by pathological features combined with RiskScore can accurately evaluate the prognosis of COAD patients. This study constructed and verified a TLS model that can predict COAD. More importantly, it provides a reference standard for guiding the prognosis and immunotherapy of COAD patients.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo , Estruturas Linfoides Terciárias , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Neoplasias do Colo/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Estruturas Linfoides Terciárias/genética , Estruturas Linfoides Terciárias/patologia , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Mutação , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Antineoplásicos/uso terapêutico
15.
Cancer Rep (Hoboken) ; 7(6): e2108, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837874

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. AIMS: In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. METHODS AND RESULTS: We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K-AKT-mTOR signaling pathway in PAAD. CONCLUSION: After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Proliferação de Células , Neoplasias Pancreáticas , Canais de Cátion TRPM , Humanos , Canais de Cátion TRPM/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/imunologia , Proliferação de Células/genética , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Idoso , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Metilação de DNA
16.
Am J Case Rep ; 25: e943466, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822519

RESUMO

BACKGROUND Various resistance mechanisms of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have been reported, and approximately half of the cases show a T790M point mutation as resistance to EGFR-TKI. In addition, 3-14% of cases of non-small cell lung cancer transform into small cell lung carcinoma (SCLC) during treatment. However, there are few reported cases in which 2 mechanisms of resistance have been observed simultaneously. This report describes a 66-year-old man with initial presentation of stage IIA right-sided lung adenocarcinoma with EGFR gene exon 21 L858R mutation and 3 years of stable disease. During treatment with erlotinib, the patient developed SCLC and adenocarcinoma with EGFR exon 21 L858R and exon 20 T790M mutation. CASE REPORT A 66-year-old man underwent right pneumonectomy plus nodal dissection 2a for right hilar lung cancer and was diagnosed with an EGFR exon21 L858R mutated lung adenocarcinoma. Three years later, pleural dissemination was observed in the right chest wall. Although erlotinib was continued for 52 months, new metastases to the right ribs were detected. Chest wall tumor resection was performed. Based on the World Health Organization classification, the patient was diagnosed with combined SCLC, with EGFR exon21 L858R and exon20 T790M mutation. The patient received 4 cycles of carboplatin plus etoposide, 14 cycles of amrubicin, and 2 cycles of irinotecan. Chemotherapy continued for 25 months. CONCLUSIONS Long-term survival was achieved by chemotherapy after transformation. Since EGFR mutation-positive lung cancer shows a variety of acquired resistances, it is important to consider the treatment strategy of performing re-biopsy.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Receptores ErbB , Cloridrato de Erlotinib , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Idoso , Humanos , Masculino , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , /uso terapêutico
19.
Technol Cancer Res Treat ; 23: 15330338241258570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832431

RESUMO

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Camundongos , Animais , Biomarcadores Tumorais/genética , Nomogramas , Biologia Computacional/métodos , Genes Mitocondriais , Modelos Animais de Doenças , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Perfilação da Expressão Gênica , Estadiamento de Neoplasias , Masculino , Bases de Dados Genéticas , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Feminino
20.
Cancer Immunol Immunother ; 73(8): 144, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832979

RESUMO

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Antígeno B7-H1 , Biomarcadores Tumorais , Neoplasias Esofágicas , Junção Esofagogástrica , Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Feminino , Pessoa de Meia-Idade , Junção Esofagogástrica/patologia , Junção Esofagogástrica/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Idoso , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso de 80 Anos ou mais , Prognóstico
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