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1.
Medicine (Baltimore) ; 103(18): e37880, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701302

RESUMO

INTRODUCTION: Incidental gallbladder carcinoma refers to a discovery of gallbladder cancer during or after cholecystectomy. Late port-site metastasis (PSM) following Laparoscopic cholecystectomy (LC) is rare with an incidence rate of 10.3%. PATIENT CONCERNS: We report a case of a 58-year-old man who presented with a painful abdominal wall mass for 6 weeks. He had a history of LC for symptomatic cholelithiasis, 8 years prior. DIAGNOSIS: Histopathological examination revealed a positive result for metastatic adenocarcinoma from the abdominal wall mass. Moreover, Positron emission tomography (PET) showed a small focus of intense fluorodeoxyglucose (FDG) uptake in the gallbladder bed, which was highly suspicious for malignancy. INTERVENTION: Decision was to proceed with surgery owing to uptake in the gallbladder bed with single-site metastasis to the previous port site. In addition, in the board meeting, an agreement was reached for performing distal pancreatectomy with splenectomy owing to uncertainty of malignancy based on what was discovered during the full metastatic workup. Diagnostic laparoscopy followed by midline laparotomy performed. Radical completion cholecystectomy with lymphadenectomy was done. Followed by complete resection of the anterior abdominal wall. Distal pancreatectomy and splenectomy were then performed. OUTCOME: Pathological diagnosis showed metastatic/invasive, moderately differentiated adenocarcinoma with positive margins on the posterior surface of excised port-site mass. The positive margins necessitated further chemoradiotherapy, followed by adjuvant chemotherapy until lung metastasis was identified. After this, the patient was scheduled for palliative chemotherapy. CONCLUSION: Presence of PSM is often associated with peritoneal metastasis. For this reason, it is advised to evaluate the patient for possible metastasis.


Assuntos
Adenocarcinoma , Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/secundário , Neoplasias da Vesícula Biliar/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/secundário , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Inoculação de Neoplasia , Parede Abdominal/patologia , Achados Incidentais
3.
J Cell Mol Med ; 28(9): e18328, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683130

RESUMO

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.


Assuntos
Adenosina/análogos & derivados , Proliferação de Células , Progressão da Doença , Neoplasias da Vesícula Biliar , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a RNA , Ubiquitina-Proteína Ligases , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/metabolismo , Humanos , Animais , Proliferação de Células/genética , Camundongos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Linhagem Celular Tumoral , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Movimento Celular/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Camundongos Nus , Masculino , Feminino , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
4.
Hum Pathol ; 146: 86-94, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38615999

RESUMO

AIMS: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. MATERIALS AND METHODS: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. RESULTS: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). CONCLUSION: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.


Assuntos
Capilares , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Capilares/patologia , Idoso , Adenoma/patologia , Adulto , Vesícula Biliar/patologia , Vesícula Biliar/irrigação sanguínea , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Carcinoma in Situ/patologia , Invasividade Neoplásica , Diagnóstico Diferencial
5.
BMC Gastroenterol ; 24(1): 146, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689244

RESUMO

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.


Assuntos
Neoplasias da Vesícula Biliar , Pólipos , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores Etários , Idoso , Fatores de Risco , Colecistectomia , China/epidemiologia , Período Pré-Operatório , Adulto Jovem , Cuidados Pré-Operatórios
6.
Comput Assist Surg (Abingdon) ; 29(1): 2331774, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38520294

RESUMO

The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the gallbladder are considered precancerous and have a high likelihood of progressing into malignancy. Preoperatively, distinguishing between benign gallbladder polyps, adenomatous polyps, and malignant polyps is challenging. Therefore, the objective is to develop a neural network model that utilizes these risk factors to accurately predict the nature of polyps. This predictive model can be employed to differentiate the nature of polyps before surgery, enhancing diagnostic accuracy. A retrospective study was done on patients who had cholecystectomy surgeries at the Department of Hepatobiliary Surgery of the Second People's Hospital of Shenzhen between January 2017 and December 2022. The patients' clinical characteristics, lab results, and ultrasonographic indices were examined. Using risk variables for the growth of adenomatous and malignant polyps in the gallbladder, a neural network model for predicting the kind of polyps will be created. A normalized confusion matrix, PR, and ROC curve were used to evaluate the performance of the model. In this comprehensive study, we meticulously analyzed a total of 287 cases of benign gallbladder polyps, 15 cases of adenomatous polyps, and 27 cases of malignant polyps. The data analysis revealed several significant findings. Specifically, hepatitis B core antibody (95% CI -0.237 to 0.061, p < 0.001), number of polyps (95% CI -0.214 to -0.052, p = 0.001), polyp size (95% CI 0.038 to 0.051, p < 0.001), wall thickness (95% CI 0.042 to 0.081, p < 0.001), and gallbladder size (95% CI 0.185 to 0.367, p < 0.001) emerged as independent predictors for gallbladder adenomatous polyps and malignant polyps. Based on these significant findings, we developed a predictive classification model for gallbladder polyps, represented as follows, Predictive classification model for GBPs = -0.149 * core antibody - 0.033 * number of polyps + 0.045 * polyp size + 0.061 * wall thickness + 0.276 * gallbladder size - 4.313. To assess the predictive efficiency of the model, we employed precision-recall (PR) and receiver operating characteristic (ROC) curves. The area under the curve (AUC) for the prediction model was 0.945 and 0.930, respectively, indicating excellent predictive capability. We determined that a polyp size of 10 mm served as the optimal cutoff value for diagnosing gallbladder adenoma, with a sensitivity of 81.5% and specificity of 60.0%. For the diagnosis of gallbladder cancer, the sensitivity and specificity were 81.5% and 92.5%, respectively. These findings highlight the potential of our predictive model and provide valuable insights into accurate diagnosis and risk assessment for gallbladder polyps. We identified several risk factors associated with the development of adenomatous and malignant polyps in the gallbladder, including hepatitis B core antibodies, polyp number, polyp size, wall thickness, and gallbladder size. To address the need for accurate prediction, we introduced a novel neural network learning algorithm. This algorithm utilizes the aforementioned risk factors to predict the nature of gallbladder polyps. By accurately identifying the nature of these polyps, our model can assist patients in making informed decisions regarding their treatment and management strategies. This innovative approach aims to improve patient outcomes and enhance the overall effectiveness of care.


Assuntos
Adenoma , Pólipos Adenomatosos , Neoplasias da Vesícula Biliar , Hepatite B , Pólipos , Humanos , Estudos Retrospectivos , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Fatores de Risco , Pólipos/diagnóstico por imagem , Pólipos/patologia , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Redes Neurais de Computação
7.
Int J Biol Macromol ; 264(Pt 1): 130426, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428766

RESUMO

Gallbladder cancer (GBC) is one of the most aggressive types of biliary tree cancers and the commonest despite its rarity. It is infrequently diagnosed at an early stage, further contributing to its poor prognosis and low survival rate. The lethal nature of the disease has underlined a crucial need to discern the underlying mechanisms of GBC carcinogenesis which are still largely unknown. However, with the continual evolution in the research of cancer biology and molecular genetics, studies have found that non-coding RNAs (ncRNAs) play an active role in the molecular pathophysiology of GBC development. Dysregulated long non-coding RNAs (lncRNAs) and their interaction with intracellular signaling pathways contribute to malignancy and disease development. LncRNAs, a subclass of ncRNAs with over 200 nucleotides, regulate gene expression at transcriptional, translational, and post-translational levels and especially as epigenetic modulators. Thus, their expression abnormalities have been linked to malignancy and therapeutic resistance. lnsRNAs have also been found in GBC patients' serum and tumor tissue biopsies, highlighting their potential as novel biomarkers and for targeted therapy. This review will examine the growing involvement of lncRNAs in GBC pathophysiology, including related signaling pathways and their wider clinical use.


Assuntos
Neoplasias da Vesícula Biliar , RNA Longo não Codificante , Humanos , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Transdução de Sinais/genética , RNA não Traduzido
8.
Zhonghua Wai Ke Za Zhi ; 62(4): 273-277, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432667

RESUMO

Gallbladder cancer, notoriously known for its high malignancy, predominantly requires radical surgery as the treatment of choice. Although laparoscopic techniques have become increasingly prevalent in abdominal surgeries in recent years, the progress of laparoscopic techniques in gallbladder cancer is relatively slow. Due to the anatomical complexity, technical difficulty, and biological features of gallbladder cancer that is prone to metastasis and dissemination, traditional open surgery is still the main surgical approach. This study aims to reappraisal the current state of laparoscopic surgery for gallbladder cancer by appraising clinical practice and research evidence. Laparoscopic surgery for various stages of gallbladder cancer, including early, advanced, incidental, and unresectable gallbladder cancer were discussed. The promise and limitations of laparoscopic techniques are systematically explored.


Assuntos
Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar , Laparoscopia , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Colecistectomia Laparoscópica/métodos , Achados Incidentais , Colecistectomia/métodos
9.
Zhonghua Wai Ke Za Zhi ; 62(4): 278-283, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432668

RESUMO

Surgical treatment is one of the most important forms of treatment in patients with gallbladder cancer. With the development of minimally invasive technology, the feasibility, safety and efficacy of minimally invasive approaches such as laparoscopic or robotic-assisted radical cholecystectomy for gallbladder cancer have received continuous attention.For patients with an early T-stage (Tis or T1a), laparoscopic simple cholecystectomy is safe and economical, with a good prognosis for postoperative patients, and it has been widely accepted and performed. Radical resection of advanced gallbladder cancer requires resection of the gallbladder, its liver bed, and other neighboring invaded organs, as well as clearance of regional lymph nodes, which requires experienced gallbladder cancer treatment teams to strictly grasp the indications, select appropriate patients, and formulate a good surgical strategy to ensure the therapeutic effect. Meanwhile, robot-assisted radical resection for gallbladder cancer has been performed in a few centers and shows good clinical potential, but more high-quality studies are needed to further evaluate its value in gallbladder cancer treatment.


Assuntos
Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar , Laparoscopia , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Colecistectomia , Fígado/patologia , Excisão de Linfonodo , Estadiamento de Neoplasias , Estudos Retrospectivos
10.
Sci Bull (Beijing) ; 69(9): 1286-1301, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38519399

RESUMO

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.


Assuntos
Antineoplásicos , Neoplasias da Vesícula Biliar , Estruturas Metalorgânicas , Proteínas Tirosina Quinases , Pirimidinonas , Proteína Supressora de Tumor p53 , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Proteínas Tirosina Quinases/antagonistas & inibidores , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Mutações Sintéticas Letais , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Mutação , Camundongos Nus , Dano ao DNA/efeitos dos fármacos , Feminino
12.
J Surg Oncol ; 129(6): 1121-1130, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348696

RESUMO

INTRODUCTION: Neuroendocrine neoplasms (NENs) are classified as neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) according to World Health Organization classification. We present our experience of NENs of the gallbladder (GB) from a high-volume cancer hospital. MATERIALS AND METHODS: The present study is a retrospective analysis of all patients with GB NENs who presented between January 2015 and June 2023. The patient details and treatment received with follow-up were noted. The primary endpoint was overall survival (OS). RESULTS: A total of 147 patients were included in the study. The median age was 52 (27-81) years. There was a female predominance (70.7%). NEC was the most common subtype (84.4%) followed by MiNEN (12.9%) and NET (2.7%). The most common stage at presentation was metastatic (70.7%) followed by locally advanced (21.8%), and early disease (7.5%). The median follow-up was 9.92 (1.77-76.06) months. Median OS was 6.14 (3.93-8.35) months. Median OS in patients who received multimodality treatment was 20.20 (17.99-22.41) months versus 4.00 (2.91-5.10) months in those who did not receive it. CONCLUSION: GB NENs are rare, but aggressive tumors with NEC being the most common type. Multimodality treatment yields favorable outcomes. However, the development of better systemic therapy is needed to help improve survival further.


Assuntos
Neoplasias da Vesícula Biliar , Tumores Neuroendócrinos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Neoplasias da Vesícula Biliar/mortalidade , Idoso , Estudos Retrospectivos , Adulto , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/mortalidade , Idoso de 80 Anos ou mais , Prognóstico , Taxa de Sobrevida , Seguimentos , Terapia Combinada
13.
Cancer Lett ; 586: 216677, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301910

RESUMO

Gallbladder cancer (GBC) is a common solid tumor of the biliary tract with a high mortality rate and limited curative benefits from surgical resection. Here, we aimed to elucidate the pathogenesis of GBC from the perspective of molecular mechanisms and determined that protein phosphatase 4 regulator subunit 1 (PP4R1) is overexpressed in GBC tissues and contributes to poor prognosis. Through a series of in vitro and in vivo experiments, we demonstrated that PP4R1 overexpression improved tumorigenesis in GBC cells. Further mechanistic exploration revealed that PP4R1 directly interacts with pyruvate kinase-M2 (PKM2), a key regulator of glycolysis. PP4R1 promotes the extracellular signal-related kinase 1 and 2 (ERK1/2)-mediated PKM2 nuclear translocation, thereby participating in the regulation of tumor glycolysis. Interestingly, we determined that PP4R1 strengthens the interaction between ERK1/2 and PKM2. Furthermore, PP4R1 enhanced the suppressive effects of the ERK inhibitor SCH772984 on GBC. In conclusion, our data showed that PP4R1 is a promising biomarker associated with GBC and confirmed that PP4R1 regulates PKM2-mediated tumor glycolysis, which provides a metabolic growth advantage to GBC cells, thereby promoting GBC tumor growth and metastasis1.


Assuntos
Neoplasias da Vesícula Biliar , Humanos , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica , Glicólise , Sistema de Sinalização das MAP Quinases , Monoéster Fosfórico Hidrolases/metabolismo
14.
World J Surg Oncol ; 22(1): 63, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389074

RESUMO

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.


Assuntos
Neoplasias do Sistema Biliar , Sistema Biliar , Carcinoma , Neoplasias da Vesícula Biliar , Má Junção Pancreaticobiliar , Humanos , Feminino , Idoso , Hiperplasia/cirurgia , Hiperplasia/patologia , Ductos Pancreáticos/patologia , Sistema Biliar/patologia , Ductos Biliares/cirurgia , Ductos Biliares/patologia , Carcinoma/patologia , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia
15.
Medicine (Baltimore) ; 103(8): e37302, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394528

RESUMO

RATIONALE: Melanoma is one of a common cutaneous malignancy. Currently, metastatic malignant melanoma is difficult to be diagnosed through imaging examinations. Furthermore, the incidence of metastatic melanoma affecting the gallbladder and ureter is exceptionally rare. PATIENT CONCERNS: A 54-year-old female was admitted to the hospital with a half-month history of left lower back pain. Correlative examination revealed an occupying lesion in the mid-left ureter and the neck of the gallbladder. DIAGNOSES: The patient was initially diagnosed with gallbladder cancer and left ureteral carcinoma based on imaging. Following 2 operations, immunohistochemical staining confirmed the presence of metastatic melanoma involving both the gallbladder and ureter. INTERVENTION: After multidisciplinary consultation and obtaining consent from the patient and her family, the patient underwent left radical nephroureterectomy, radical cholecystectomy, laparoscopic partial hepatectomy (Hep IV, Hep V), and lymph node dissection of hepatoduodenal ligament. OUTCOMES: One month after treatment, the patient imaging showed no disease progression, and at 6 months of follow-up, the patient was still alive. LESSONS: It is difficult to distinguish metastatic melanoma from carcinoma in situ by imaging. In addition, metastatic malignant melanoma lacks specific clinical manifestations and is prone to misdiagnosis, which emphasizes the highly aggressive nature of malignant melanoma.


Assuntos
Neoplasias da Vesícula Biliar , Melanoma , Neoplasias Cutâneas , Ureter , Humanos , Feminino , Pessoa de Meia-Idade , Melanoma/diagnóstico , Melanoma/cirurgia , Melanoma/patologia , Ureter/patologia , Neoplasias Cutâneas/patologia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia
16.
HPB (Oxford) ; 26(4): 594-602, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38336604

RESUMO

BACKGROUND: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer. METHODS: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018. Patients were stratified by surgical management. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Altogether, 950 patients were identified with pathologic T1B gallbladder cancer: 187 (19.7 %) receiving simple and 763 (80.3 %) radical cholecystectomy. Median OS was 89.5 (95 % CI 62.5-137) and 91.4 (95 % CI 75.9-112) months for simple and radical cholecystectomy, respectively (log-rank p = 0.55). Receipt of simple cholecystectomy was not associated with greater hazard of mortality compared to radical cholecystectomy (HR 1.23, 95 % CI 0.95-1.59, p = 0.12). DISCUSSION: In this analysis, we report comparable outcomes with simple cholecystectomy among patients with pathologic T1B gallbladder cancer. These findings suggest that highly selected patients, such as those with R0 resection and imaging at low risk for residual disease and/or nodal metastasis, may not benefit from extended resection; however, radical cholecystectomy remains standard of care until prospective validation can be achieved.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Colecistectomia , Excisão de Linfonodo , Carcinoma in Situ/patologia
17.
JNMA J Nepal Med Assoc ; 62(270): 152-154, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38409975

RESUMO

Large cell neuroendocrine carcinoma of the gallbladder is an extremely rare tumour with aggressive behaviour and a bad prognosis. Here, we report a case of a 65-year-old lady suspected of carcinoma of the gallbladder and underwent extended cholecystectomy. The histopathology report revealed neuroendocrine carcinoma of a large cell type of gall bladder infiltrating the liver and three periportal and pericholedochal lymph nodes. She had an uneventful perioperative period and was doing good till 6 months of follow-up. The only potentially curative treatment for large cell neuroendocrine carcinoma of the gallbladder is aggressive surgical resection, owing to its aggressive behaviour and bad prognosis. Keywords: carcinoma; case reports; cholecystectomy; gallbladder.


Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Feminino , Humanos , Idoso , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia , Colecistectomia , Prognóstico , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Grandes/patologia
18.
Adv Sci (Weinh) ; 11(16): e2308531, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38380551

RESUMO

Gallbladder cancer (GBC) is an extremely lethal malignancy with aggressive behaviors, including liver or distant metastasis; however, the underlying mechanisms driving the metastasis of GBC remain poorly understood. In this study, it is found that DNA methyltransferase DNMT3A is highly expressed in GBC tumor tissues compared to matched adjacent normal tissues. Clinicopathological analysis shows that DNMT3A is positively correlated with liver metastasis and poor overall survival outcomes in patients with GBC. Functional analysis confirms that DNMT3A promotes the metastasis of GBC cells in a manner dependent on its DNA methyltransferase activity. Mechanistically, DNMT3A interacts with and is recruited by YAP/TAZ to recognize and access the CpG island within the CDH1 promoter and generates hypermethylation of the CDH1 promoter, which leads to transcriptional silencing of CDH1 and accelerated epithelial-to-mesenchymal transition. Using tissue microarrays, the association between the expression of DNMT3A, YAP/TAZ, and CDH1 is confirmed, which affects the metastatic ability of GBC. These results reveal a novel mechanism through which DNMT3A recruitment by YAP/TAZ guides DNA methylation to drive GBC metastasis and provide insights into the treatment of GBC metastasis by targeting the functional connection between DNMT3A and YAP/TAZ.


Assuntos
DNA Metiltransferase 3A , Neoplasias da Vesícula Biliar , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos CD , Caderinas , Linhagem Celular Tumoral , Modelos Animais de Doenças , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/genética , DNA Metiltransferase 3A/metabolismo , DNA Metiltransferase 3A/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica/genética , Metástase Neoplásica/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética
19.
Eur J Cancer ; 199: 113564, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38266541

RESUMO

Biliary tract cancers (BTCs) encompass a heterogeneous group of rare tumors, including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC) and ampullary cancer (AC). The present first-line palliative treatment regimen comprises gemcitabine and cisplatin in combination with immunotherapy based on two randomized controlled studies. Despite the thorough investigation of these palliative treatments, long-term survival remains low. Moving beyond conventional chemotherapies and immunotherapies, the realm of precision medicine has demonstrated remarkable efficacy in malignancies such as breast and gastric cancers, characterized by notable HER2 overexpression rates. In the context of biliary tract cancer, significant HER2 alterations are observed, particularly within eCCA and GBC, heightening the interest in precision medicine. Various anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab-deruxtecan, zanidatamab and neratinib, have undergone investigation. The objective of this review is to summarize the current evidence and outline future directions of targeted HER2 treatment therapy in patients with biliary tract tumors, specially extrahepatic cholangiocarcinoma and gallbladder cancer.


Assuntos
Ampola Hepatopancreática , Anticorpos Biespecíficos , Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Colangiocarcinoma , Neoplasias do Ducto Colédoco , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Colangiocarcinoma/patologia , Neoplasias do Sistema Biliar/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Trastuzumab/uso terapêutico
20.
BMC Gastroenterol ; 24(1): 7, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166603

RESUMO

Gallbladder polyps are a common biliary tract disease whose treatment options have yet to be fully established. The indication of "polyps ≥ 10 mm in diameter" for cholecystectomy increases the possibility of gallbladder excision due to benign polyps. Compared to enumeration of risk factors in clinical guidelines, predictive models based on statistical methods and artificial intelligence provide a more intuitive representation of the malignancy degree of gallbladder polyps. Minimally invasive gallbladder-preserving polypectomy procedures, as a combination of checking and therapeutic approaches that allow for eradication of lesions and preservation of a functional gallbladder at the same time, have been shown to maximize the benefits to patients with benign polyps. Despite the reported good outcomes of predictive models and gallbladder-preserving polypectomy procedures, the studies were associated with various limitations, including small sample sizes, insufficient data types, and unknown long-term efficacy, thereby enhancing the need for multicenter and large-scale clinical studies. In conclusion, the emergence of predictive models and minimally invasive gallbladder-preserving polypectomy procedures has signaled an ever increasing attention to the role of the gallbladder and clinical management of gallbladder polyps.


Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Inteligência Artificial , Doenças da Vesícula Biliar/cirurgia , Colecistectomia , Pólipos/cirurgia , Pólipos/patologia , Estudos Retrospectivos , Estudos Multicêntricos como Assunto
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