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1.
Pathol Oncol Res ; 30: 1611376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572338

RESUMO

Mammary-like vulvar adenocarcinoma (MLVA) is an exceedingly rare subtype of vulvar adenocarcinoma that shares features with mammary gland tissue. Due to its rarity and lack of consensus, MLVA presents diagnostic challenges to pathologists. We present the case of a 59-year-old female with an ulcerated mass on the right side of the external genitalia, diagnosed as MLVA. Comprehensive immunohistochemistry (IHC) and gene sequencing studies were performed to characterize the tumor. IHC analysis revealed triple expression of hormonal receptors (estrogen receptor, progesterone receptor, and HER2), supporting the mammary gland origin of the tumor. Gene sequencing identified unique genetic mutations associated with the expression of hormonal markers. One fusion gene (ERBB2-NAGLU) has not been reported in any tumors, and other mutations with unique mutation types have not been previously reported in MLVA. Our findings shed light on the molecular characteristics of MLV and may help improve the diagnosis and treatment of this rare type of vulvar adenocarcinoma.


Assuntos
Adenocarcinoma , Glândulas Mamárias Humanas , Neoplasias Vulvares , Feminino , Humanos , Pessoa de Meia-Idade , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Adenocarcinoma/patologia , Neoplasias Vulvares/genética , Neoplasias Vulvares/metabolismo , Neoplasias Vulvares/patologia , Mama/patologia , Sequenciamento de Nucleotídeos em Larga Escala
2.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 331-336, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556815

RESUMO

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/patologia , Adenocarcinoma/patologia , Biópsia , Diagnóstico Diferencial , Proteínas Repressoras
3.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 370-376, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556821

RESUMO

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 µg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Gástricas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , alfa-Fetoproteínas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Gástricas/patologia , China , Adenocarcinoma/patologia , Diferenciação Celular , Biomarcadores Tumorais/metabolismo
5.
Arkh Patol ; 86(2): 30-36, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38591904

RESUMO

BACKGROUND: Pyloric gland adenomas (PGA) are rare neoplasms of the gastrointestinal tract. According to the literature, these lesions may be underdiagnosed, and their true frequency of occurrence is underestimated. OBJECTIVE: Clinical and morphological analysis of eight PGA cases of the upper gastrointestinal tract. MATERIAL AND METHODS: The study included 8 cases of detection of PGA. In 7 out of 8 cases, the tumor was diagnosed by examining endoscopic biopsies, in 1 case, PGA was an accidental finding in the surgical material after proximal gastric resection. RESULTS: 6 out of 8 patients were female, the median age was 65 years (minimum 36 years and maximum 78 years). In 6 cases, PDA was localized in the stomach, in 1 - in the esophagus and in 1 - in the duodenum The size of the tumors ranged from 0.6 cm to 7.5 cm. 4 out of 6 stomach tumors appeared on the background of confirmed autoimmune gastritis, 1 - on the background of lymphocytic gastritis. 4 tumors were found in the body of the stomach, 1 - in the cardia, 1 - in the bottom of the stomach. In 2 out of 8 cases, there were signs of malignancy of the tumor with the transition to a highly differentiated adenocarcinoma. According to the results of the IHC study, the absence of a p53 mutation was noted in these cases. CONCLUSION: PGA should be considered as neoplasms with a high risk of transformation into invasive adenocarcinoma. Increasing the recognition of PGA among pathologists and further understanding of the molecular mechanisms involved in their neoplastic transformation will improve the diagnosis and treatment of this pathology.


Assuntos
Adenocarcinoma , Adenoma , Gastrite , Neoplasias Gástricas , Humanos , Feminino , Idoso , Masculino , Mucosa Gástrica/patologia , Adenoma/diagnóstico , Adenoma/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Adenocarcinoma/patologia , Gastrite/patologia
6.
Arkh Patol ; 86(2): 6-13, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38591901

RESUMO

OBJECTIVE: Study of the features of expression of immune checkpoint proteins PD-L1, CTLA4 and LAG3 in the microenvironment of colon adenocarcinoma depending on MMR status. MATERIAL AND METHODS: The study group consisted of 32 patients with a morphologically confirmed diagnosis of colon cancer; all of them underwent surgical treatment in the form of hemicolonectomy or resection. The work assessed samples of tumor tissue obtained as a result of surgery, the study was carried out in 3 stages: morphological examination of histological slides of colon tumors at the light-optical level, immunohistochemistry examination of tumor samples to determine the dMMR/pMMR status of carcinoma using a panel of antibodies to proteins of the unpaired nucleotide repair system MLH1, MSH2, MSH6 and PMS2, multiplex analysis of PD-L1, CTLA4, LAG3, CD3+, CD8+, CD163+ markers using the Vectra 3.0.3 tissue scanning system (Perkin Elmer, USA). RESULTS: Significant differences in the expression of PD-L1, CTLA4, LAG3 in the area of the invasive tumor margin were revealed between the dMMR and pMMR groups of colon adenocarcinomas in patients comparable in clinical and morphological characteristics and treatment. In the group of tumors with dMMR status, an increase in the expression of all studied markers was noted. The number of CD3+ TILs was also significantly higher in the invasive margin of tumors with dMMR status. Similarly, in this group of colon carcinomas, a large number of CD163+ macrophages were noted both in the center and in the invasive margin zone. No statistically significant differences were found in the expression of immune checkpoints and the composition of TILs in the central zone of tumors with different MMR status. CONCLUSION: A study using multiplex immunohistochemical analysis showed that MMR-deficient colon adenocarcinomas are characterized by more pronounced immune infiltration and increased expression of immune checkpoints in microenvironmental cells, mainly in the area of invasive tumor growth. The data obtained may be important for understanding the mechanisms of immune-mediated control of tumor growth and the choice of immunotherapy tactics depending on MMR status.


Assuntos
Adenocarcinoma , Neoplasias Encefálicas , Neoplasias do Colo , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Antígeno B7-H1/genética , Antígeno CTLA-4/genética , Microambiente Tumoral/genética
7.
Am J Surg ; 227: 208-212, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38587050

RESUMO

BACKGROUND: Asian gastric cancer patients have higher long-term survival rates post-gastrectomy. This study compares 30-day post-gastrectomy outcomes between Asians and non-Asians. METHODS: Gastric cancer patients undergoing elective gastrectomies were identified in 2014-2019 NSQIP datasets (n â€‹= â€‹1,438). Demographics, comorbidities, and postoperative outcomes were analyzed. RESULTS: Asians had lower odds of total gastrectomy (AOR â€‹= â€‹0.52, p â€‹= â€‹0.003), age ≥65 (AOR â€‹= â€‹0.60, p â€‹= â€‹0.006), smoking history (AOR â€‹= â€‹0.35, p â€‹< â€‹0.001), dyspnea (AOR â€‹= â€‹0.25, p â€‹= â€‹0.01), and hypoalbuminemia (AOR â€‹= â€‹0.62, p â€‹= â€‹0.025); they also had lower BMI (p â€‹< â€‹0.001). Postoperative outcomes were not significantly different aside from a shorter median length of hospital stay in days (LOS) (Asians: 7 (6, 11); non-Asians: 8 (6, 11); p â€‹< â€‹0.001). CONCLUSIONS: Asian gastric cancer patients have significantly lower odds of having select preoperative comorbidities and have shorter hospital LOS.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Adenocarcinoma/patologia , Tempo de Internação , Comorbidade , Complicações Pós-Operatórias/etiologia , Gastrectomia/efeitos adversos , Estudos Retrospectivos
8.
BMC Cancer ; 24(1): 441, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594604

RESUMO

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Transição Epitelial-Mesenquimal/genética , Prognóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
9.
Rev Esp Patol ; 57(2): 151-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599738

RESUMO

Adenocarcinoma with enteroblastic differentiation is a rare histologic subtype of adenocarcinoma of the gastrointestinal tract that shows unique histologic and immunohistochemical features that resemble fetal intestinal epithelium. This histological subtype has been widely described in the stomach, where it most frequently appears, but, in other locations, it is misdiagnosed because of the poor experience in routine diagnostic setting. Here we present a case of an 87-year-old male with an adenocarcinoma of the ampulla of Vater with enteroblastic differentiation with a literature review of the cases described of this subtype in this location to date. The anatomical peculiarity of the ampulla, joined with the infrequent nature of this histological subtype, makes this case of great interest to aid to better characterize the biological behavior of these tumors.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Masculino , Humanos , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Adenocarcinoma/patologia
10.
Rev Esp Patol ; 57(2): 120-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599731

RESUMO

Some non-small cell carcinomas of the lung can express TTF1 and p40 in the same tumor cells. This event has been described in only six cases prior to this one, and only in one other female. It is an extraordinary event that appears as a new entity yet to be defined. The case presented is a woman with a non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same cells.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Feminino , Neoplasias Pulmonares/patologia , Fatores de Transcrição/genética , Adenocarcinoma/patologia , Glândula Tireoide/patologia , Carcinoma de Células Escamosas/patologia , Pulmão/patologia
11.
Rev Esp Patol ; 57(2): 141-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599736

RESUMO

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature.


Assuntos
Adenocarcinoma , Condrossarcoma , Divertículo Ileal , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Feminino , Humanos , Pessoa de Meia-Idade , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Íleo/patologia , Adenocarcinoma/patologia , Progressão da Doença , Condrossarcoma/complicações
12.
Sci Rep ; 14(1): 8988, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637560

RESUMO

Esophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational signatures. Group 1 is associated with age and NTHL1 deficiency-related signatures. Group 2 occurs primarily in Black patients and is associated with signatures related to DNA damage from oxidative stress and NTHL1 deficiency-related signatures. Group 3 is associated with defective homologous recombination-based DNA often caused by BRCA mutation in White patients. We observed significantly mutated race related genes (LCE2B in Black, SDR39U1 in White) were (q-value < 0.1). Our findings underscore the possibility of distinct molecular mutation patterns in EAC among different races. Further studies are needed to validate our findings, which could contribute to precision medicine in EAC.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Feminino , Humanos , Masculino , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Mutação , Negro ou Afro-Americano , Brancos , Sequenciamento do Exoma
13.
World J Surg Oncol ; 22(1): 102, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637826

RESUMO

BACKGROUND: Basal cell adenoma (BCA) is a rare benign tumor within the salivary glands. Basal cell adenocarcinoma (BCAC), the malignant counterpart of BCA, is also an exceedingly rare tumor with very limited clinical studies conducted. This study aims to investigate the clinical characteristics, demographics, and surgical outcomes of patients diagnosed with BCA and BCAC within the parotid gland. METHODS: A retrospective analysis from May 2003 to August 2023 was performed for all patients undergoing parotidectomy for masses. Retrospective data on gender, age, tumor characteristics, and outcomes were collected. Surgical approaches, including negative margin attainment, capsule removal, and histological diagnosis, were also detailed. RESULTS: The study included 1268 patients who underwent parotidectomy, resulting in 81 cases of BCA and 7 cases of BCAC. BCA patients, with a mean age of 55.1 years, showed diverse age distribution and predominantly presented in the 50s. In BCAC cases, seven female patients exhibited a predominant location in the deep lobes. FNA revealed BCAC in three out of seven cases, and subsequent parotidectomy was performed, resulting in no observed recurrences or metastases. CONCLUSION: This study reports the largest number of BCA cases from a single institution and provides comprehensive insights into the demographics, tumor characteristics, and clinical outcomes of both BCA and BCAC. Although further research should be conducted, based on clinical follow-up results, appropriately including the capsule in the tumor excision indicates favorable outcomes, especially when the tumor size is not large.


Assuntos
Adenocarcinoma , Adenoma , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Humanos , Feminino , Pessoa de Meia-Idade , Glândula Parótida/cirurgia , Glândula Parótida/patologia , Estudos Retrospectivos , Adenocarcinoma/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Adenoma/cirurgia , Adenoma/patologia , Resultado do Tratamento , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia
14.
BMC Pulm Med ; 24(1): 181, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627639

RESUMO

BACKGROUND: Endobronchial ultrasound-guided transbronchial cryobiopsy (EBUS-cryobiopsy) is advantageous for collecting larger specimens with minimal crushing; however, it has not been widely used for mediastinal tumors. CASE PRESENTATION: A 73-year-old woman with a history of left breast cancer underwent surgery followed by radiotherapy. Computed tomography showed a mass in the anterior mediastinum that was in extensive contact with the sternum on the ventral side and partly with the trachea on the dorsal side. Two computed tomography-guided needle biopsies (CTNBs) were performed on the mass; however, a definitive diagnosis was not made because of severe crush artifacts. Subsequently, we performed EBUS-cryobiopsy and safely obtained sufficient specimen volume with minimal crushing. The histopathological diagnosis was adenocarcinoma, with immunobiological features distinct from those of previous breast cancers. Her overall diagnosis was a rare tumor originating in the anterior mediastinum. CONCLUSIONS: EBUS-cryobiopsy can be safely performed in narrow areas surrounded by major blood vessels, and the obtained specimens may be superior to CTNBs for histopathological diagnosis.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Mediastino/patologia , Neoplasias Pulmonares/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Endossonografia , Broncoscopia/métodos , Linfonodos/patologia
16.
J Gastrointest Surg ; 28(4): 519-527, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583905

RESUMO

BACKGROUND: Anal adenocarcinoma is rare with no standardized treatment regimen or staging system. Therefore, different combinations of chemotherapy, radiation, and surgery are used in management. Within the staging system, tumor stage can be based on the depth of invasion, as for rectal adenocarcinoma, or size, as in anal squamous cell carcinoma. This study aimed to analyze patterns of care and clinically available staging systems for anal adenocarcinoma using a national database. METHODS: Adults diagnosed with anal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (2004-2019). In addition, 6 different treatment regimens were identified. Stages were categorized according to the American Joint Committee on Cancer classifications of rectal adenocarcinoma and anal squamous cell carcinoma. RESULTS: Of 1040 patients, 48% were female, the median age was 67 years, and 18% had distant metastases. Chemoradiotherapy + abdominoperineal resection was the most common treatment regimen (22%). Moreover, 5-year overall survival (OS) and disease-specific survival (DSS) were the highest for local excision only (67% and 85%) and the lowest in the alternative group (34% and 48%). After adjustment, the treatment groups that did not include surgery were associated with worse 5-year OS. In multivariable analysis, the T stage based on depth of invasion showed incrementally lower OS for T2 and T3 anal adenocarcinomas. CONCLUSION: Omission of surgical resection in combination with chemoradiotherapy was associated with worse OS and DSS, suggesting the relevance of surgery in anal adenocarcinoma management. Prognostically, rectal staging based on depth of invasion better discriminated between T stages, indicating that providers should consider using this system in practice.


Assuntos
Adenocarcinoma , Neoplasias do Ânus , Carcinoma de Células Escamosas , Neoplasias Retais , Adulto , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Masculino , Estadiamento de Neoplasias , Neoplasias do Ânus/terapia , Adenocarcinoma/patologia , Neoplasias Retais/patologia , Estudos Retrospectivos
17.
Cell Commun Signal ; 22(1): 224, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600588

RESUMO

BACKGROUND: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. METHODS: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. RESULTS: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. CONCLUSION: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.


Assuntos
Adenocarcinoma , Quimiocina CCL20 , Neoplasias Pancreáticas , Receptores de Calcitriol , Animais , Humanos , Camundongos , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Quimiocina CCL20/metabolismo , Macrófagos/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fenótipo , Receptores de Calcitriol/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor
18.
Arq Bras Cir Dig ; 37: e1796, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511813

RESUMO

BACKGROUND: Duodenal adenocarcinoma is a small percentage of gastrointestinal neoplasms, around 0.5%, and its treatment is based on resection of the tumor, classically by pancreaticoduodenectomy. In recent years, however, segmental resections of duodenal lesions, that do not involve the second portion or the periampullary region, have gained relevance with good surgical and oncological outcomes as well as the benefit of avoiding surgeries that can result in high morbidity and mortality. AIMS: To report a case of an elderly female patient with malignant neoplastic lesion in the third and fourth duodenal portion, non-obstructive, submitted to surgical treatment. METHODS: The technical option was the resection of the distal duodenum and proximal jejunum with preservation of the pancreas and reconstruction with side-to-side duodenojejunal anastomosis. RESULTS: The evolution was satisfactory and the surgical margins were free of neoplasia. CONCLUSIONS: Segmental resections of the duodenum are feasible and safe, offering the benefit of preventing complications of pancreaticoduodenectomies.


Assuntos
Adenocarcinoma , Duodeno , Humanos , Feminino , Idoso , Duodeno/cirurgia , Biópsia , Pancreaticoduodenectomia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Anastomose Cirúrgica , Resultado do Tratamento
19.
World J Gastroenterol ; 30(7): 714-727, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515951

RESUMO

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity of the epidermal growth factor receptor (EGFR) is often observed in pancreatic cancer, and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration. Nevertheless, erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm), facilitate tumor cell uptake of Δψm-sensitive agents, disrupt mitochondrial homeostasis, and subsequently trigger tumor cell death. Erlotinib has not been tested for this effect. AIM: To determine whether erlotinib can elevate Δψm and increase tumor cell uptake of Δψm-sensitive agents, subsequently triggering tumor cell death. METHODS: Δψm-sensitive fluorescent dye was used to determine how erlotinib affects Δψm in pancreatic adenocarcinoma (PDAC) cell lines. The viability of conventional and patient-derived primary PDAC cell lines in 2D- and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone (MitoQ), a Δψm-sensitive MitoQ. The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0. The preclinical efficacy of the two-drug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts. RESULTS: Erlotinib elevated Δψm in PDAC cells, facilitating tumor cell uptake and mitochondrial enrichment of Δψm-sensitive agents. MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses, while erlotinib pretreatment potentiated low doses of MitoQ. SynergyFinder suggested that these drugs synergistically induced tumor cell lethality. Consistent with in vitro data, erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent. CONCLUSION: Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pancreáticas/patologia , Sobrevivência Celular , Adenocarcinoma/patologia , Camundongos Nus , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Quinazolinas , Linhagem Celular Tumoral , Receptores ErbB , Mitocôndrias/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proliferação de Células
20.
Ann Ital Chir ; 95(1): 91-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469603

RESUMO

BACKGROUND: In the context of gastric cancer, surgical resection stands as the sole curative treatment. Central to influencing overall survival are the resection margins. This research aims to identify the factors influential in determining microscopically positive resection margins (R1) and to evaluate overall survival. METHODS: Our study encompassed 549 patients diagnosed with adenocarcinoma of the stomach who underwent curative-intent surgery between January 2011 and December 2021 in our Surgery Department. We investigated the incidence of positive margins (R1) and their impact on survival rates, as well as the determinants of R1. The standardization of R1 involved ensuring a margin distance of less than 1 mm from the tumor line to the margin. RESULTS: The incidence of R1 margins was 13.29% (73 patients). Among these, proximal R1 margins were observed in 29 patients (39.72%), while 49 cases (67.12%) presented circumferentially positive margins, with 20 cases (27.39%) exhibiting distally positive margins. Nineteen patients (26.02%) had two R1 margins, and 3 patients had all resection margins microscopically positive (4.10%). Factors such as tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading demonstrated significance (p < 0.01) in the occurrence of positive R1 margins. CONCLUSION: Tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading could be regarded as factors for predicting microscopically positive margins. Moreover, positive resection margins have a detrimental impact on overall survival.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Prognóstico , Margens de Excisão , Gastrectomia/métodos , Adenocarcinoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida
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