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2.
Scand J Gastroenterol ; 56(8): 929-939, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34224306

RESUMO

INTRODUCTION: Gallbladder cancer (GBC) is a rare malignancy in Western population with poor prognosis. This study aimed to investigate the trends in GBC incidence, treatment pattern, and survival in Finland. METHODS: Patients diagnosed with primary GBC in a geographically defined area (Southern Finland Regional Cancer Center) during 2006-2017 were identified. RESULTS: Final cohort included 270 patients with GBC. The incidence was 1.32/100,000 persons, and it decreased 6.8 cases per million personyears during the study period. One hundred fifty-one (56%) patients were diagnosed at Stage IV. Fifty-one patients (19%) underwent curative-intent resection with 96% R0-resection rate. The median overall survival was 7.1 months and 5-year overall survival 11.6% for all patients, and 67.7 months and 56.8% after curative-intent resection, respectively. No improvement was noted over time in overall survival in patients with GBC, or in subgroups of different stages of GBC. CONCLUSIONS: The incidence of GBC is slightly decreasing in Southern Finland, but survival has not improved over time.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Finlândia/epidemiologia , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Incidência , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
3.
J Surg Oncol ; 124(4): 572-580, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34106475

RESUMO

BACKGROUND: Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. METHODS: Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. CONCLUSION: Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colecistectomia/normas , Neoplasias da Vesícula Biliar/terapia , Icterícia Obstrutiva/complicações , Adulto , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
4.
J Surg Oncol ; 124(4): 581-588, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34115368

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is often incidentally diagnosed after cholecystectomy. Intra-operative biliary tract violations (BTV) have been recently associated with development of peritoneal disease (PD). The degree of BTV may be associated with PD risk, but has not been previously investigated. METHODS: We reviewed patients with initially non-metastatic GBC treated at our institution from 2003 to 2018. Patients were grouped based on degree of BTV during their treatment: major (e.g., cholecystotomy with bile spillage, n = 27, 29%), minor (e.g., intra-operative cholangiogram, n = 18, 19%), and no violations (n = 48, 55%). Overall survival (OS) and peritoneal disease-free survival (PDFS) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Ninety-three patients were identified; the median age was 64 years (range 31-87 years). Seventy-six (82%) were incidentally diagnosed. The median follow-up was 23 months; 20 (22%) patients developed PD. The 3-year PDFS for patients with major, minor, and no BTV was 52%, 83%, and 98%, respectively (major vs. none: p < 0.001; minor vs. none: p < 0.01). BTV was not associated with 5-year OS (HR 1.53, p = 0.16). CONCLUSION: Increasing degree of BTV is associated with higher risk of peritoneal carcinomatosis in patients with GBC and should be considered during preoperative risk stratification. Reporting biliary tract violations during cholecystectomy is encouraged.


Assuntos
Adenocarcinoma/cirurgia , Sistema Biliar/patologia , Colecistectomia/efeitos adversos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias Peritoneais/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
Expert Opin Investig Drugs ; 30(7): 759-772, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33966562

RESUMO

Introduction: Gallbladder cancer (GC) is a rare malignancy with a dismal prognosis. When diagnosed early enough, it can be cured by surgical removal. Unfortunately, only few GC patients can be amenable to surgery, though, with a high relapse rate. Conventional chemotherapy remains the golden standard for unresectable or metastatic GC, both in the first and second-line settings, even if leading to a fair outcome improvement.Areas covered: In recent years, according to the concept of 'precision medicine', new potential molecular targets have been examined. We provided a general outline of the current first- and second-line chemotherapies. New therapeutic possibilities are also reviewed, particularly HER2, EGFR, VEGF, TKI, MEK and BRAF inhibitors, and immunotherapy. Furthermore, published clinical trials are utilized to analyze the principal drug effectiveness in GC.Expert opinion: GC is characterized by vast cancer heterogeneity and individual's efficacy to different drugs. The ongoing trials have the potentiality of reshaping the landscape of systemic treatments for GC in the very next years. Nowadays, amongst therapeutic combinations, the addition of ICIs to chemotherapy has yielded encouraging results needing confirmation. In the next future, systematic implementation of gene profiling and further explorations of combination therapies will likely change the treatment scenario.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Vesícula Biliar/tratamento farmacológico , Terapia de Alvo Molecular , Desenvolvimento de Medicamentos , Neoplasias da Vesícula Biliar/patologia , Humanos , Imunoterapia/métodos , Medicina de Precisão , Prognóstico , Inibidores de Proteínas Quinases/farmacologia
7.
Bratisl Lek Listy ; 122(5): 341-346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33848185

RESUMO

AIM: To assess how laparoscopy has altered the presentation of patients with gallbladder cancer and determine whether radical resection in patients with gallbladder cancer is beneficial. METHOD: 47 patients underwent surgery because of suspected gallbladder cancer. Cancer was found incidentally in 29 patients (61.7 %) during routine laparoscopic cholecystectomy using frozen biopsy. Gallbladder cancer had been diagnosed preoperatively in the other 18 patients (38.3 %). RESULTS: Patients in whom carcinoma was found incidentally at laparoscopic cholecystectomy had a significant increase in survival when compared with those who were admitted electively with a known diagnosis. All patients who presented with a known diagnosis had stage II or higher, and 38.3 % of these were in stage IV. However, 58.6 % of those patients who were found incidentally were in stage I or II. The overall 2-year survival for all patients was 45 %; those discovered incidentally at laparoscopic cholecystectomy (Tis-T2) had a 2-year survival of 87 %. CONCLUSION: Laparoscopic cholecystectomy resulted in an earlier discovery of gallbladder cancer in some patients, resulting in increased probability of survival. Adjunctive radical surgical resection, either at the time of cholecystectomy or subsequently, increases survival significantly in early stage disease (Tab.2, Fig. 2, Ref. 24). Text in PDF www.elis.sk Keywords: gallbladder carcinoma, laparoscopic approach.


Assuntos
Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar , Laparoscopia , Colecistectomia , Colecistectomia Laparoscópica/efeitos adversos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Achados Incidentais , Estadiamento de Neoplasias , Estudos Retrospectivos
8.
Pan Afr Med J ; 38: 144, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33912314

RESUMO

Congenital cystic disease of the biliary tree is a known risk factor for gallbladder cancer. We here report a case of squamous cell carcinoma of the bile duct (BD) complicating a cystic dilatation of the bile ducts in a 54-year-old woman hospitalized for biliary pancreatitis. Abdominal scanner showed nodular thickening of the fundus of the gallbladder and fusiform dilation of the cystic duct and the main bile duct (VBP) with lesion of the tail of the pancreas, initially suggesting mucinous cystadenoma. Extended cholecystectomy involving the gallbladder fossa with resection of the distal biliary tract, choledocoduodenal anastomosis with caudal splenopancreatectomy + drainage were performed. Histopathological examination of the gallbladder mass revealed moderately differentiated invasive squamous cell carcinoma without infiltration of the hepatic parenchyma. The patient underwent adjuvant chemotherapy. The patient did not have the common symptoms of gallbladder cancer. Then radiology was necessary to make a diagnosis. Surgery is the best therapeutic option for early-stage gallbladder cancer, but adjuvant chemo-radiation may also be useful in treating these patients. Cholecystectomy with resection of cystic dilatation of the bile duct in high-risk patients are the most effective means of prevention.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Colecistectomia/métodos , Ducto Colédoco/patologia , Ducto Colédoco/cirurgia , Ducto Cístico/patologia , Ducto Cístico/cirurgia , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreatectomia/métodos , Esplenectomia/métodos
9.
J Environ Pathol Toxicol Oncol ; 40(2): 23-33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822514

RESUMO

Aberrant expression of ß-tubulin-III (TUBB3) is known that related to aggressive tumor features and poor clinical outcomes. However, there is limited research about TUBB3 expression and its role in the outcomes and the progression of gallbladder cancer. We have measured TUBB3 level in gallbladder cancer samples and cell lines from 2012 to 2016, and tested the effects of TUBB3 in cancer cell growth, apoptosis and cell cycle arrest by using appropriate methods. The results revealed that TUBB3 was significantly over-expressed in gallbladder cancer samples and cell lines, and high TUBB3 level contributed to shorter overall survival in patients. The knockdown of TUBB3 with sh-TUBB3 inhibited the proliferation, migration and invasion of cancer cells. Meanwhile, it promotes apoptosis and changes the cell cycle distribution. Suppression of TUBB3 expression could increase p21 and cyclin B1 expression, and decrease cyclin D1. Xenograft mouse model also showed that low expression of TUBB3 reduced the growth of established gallbladder cancer xenograft in vivo. Furthermore, TUBB3 knockdown significantly decreased phosphorylation of Akt and mTOR in vitro and in vivo. TUBB3 can induce the development of gallbladder cancer by Akt/mTOR signal pathway and we point out a potential therapeutic target for gallbladder cancer treatment.


Assuntos
Neoplasias da Vesícula Biliar/metabolismo , Tubulina (Proteína)/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Tubulina (Proteína)/genética
10.
Theranostics ; 11(10): 4585-4598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754015

RESUMO

Background: The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. Methods: This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included TP53 (53%), KRAS (26%), ARID1A (18%), LRP1B (14%) and CDKN2A (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. TP53 and KRAS mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Conclusions: Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.


Assuntos
Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Carcinoma/genética , Colangiocarcinoma/genética , Neoplasias da Vesícula Biliar/genética , Idoso , Neoplasias dos Ductos Biliares/patologia , Carcinoma/patologia , Colangiocarcinoma/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/genética , Feminino , Neoplasias da Vesícula Biliar/patologia , Genômica , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Medicina de Precisão , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores de LDL/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Sequenciamento Completo do Exoma
11.
Genes (Basel) ; 12(2)2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671809

RESUMO

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (ATM) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline ATM large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with ATM-deficient cancers.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Genótipo , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade
12.
BMC Cancer ; 21(1): 288, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731052

RESUMO

BACKGROUND: If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion. METHODS: Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the "shallow group", and 34 patients whose tumors invaded the ss were classified as the "deep group". The EUS findings were compared between the two groups. RESULTS: An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners. CONCLUSIONS: The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.


Assuntos
Endossonografia , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Colecistectomia , Feminino , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
Med Sci Monit ; 27: e929106, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784268

RESUMO

BACKGROUND Gallbladder adenocarcinoma (GBAC) is globally acknowledged as one of the most common malignancies among all gastrointestinal cancers. Despite prognosis of GBAC patients remains poor, patients with early-stage disease can be observed with long-term survival. MATERIAL AND METHODS In this study, 2556 patients with pathological GBAC between 2010 and 2015 were derived from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic nomograms containing all independent prognostic factors for predicting overall survival (OS) and cancer-specific survival (CSS) were constructed to achieve superior prognostic discriminatory ability. RESULTS Based on the AJCC 7th TNM staging system, we found the TNM substaging was not accurate enough to predict the survival and stratify the risk. Based on the results of univariate and multivariate analyses, a more precise prognostic nomogram was constructed containing all significant independent prognostic factors (age, grade, TNM stage, bone metastasis, and chemotherapy) for OS, while age, grade, TNM stage, bone metastasis and radiotherapy significant independent prognostic factors for CSS. The C-index of the constructed nomogram for predicting OS and CSS was 0.740 and 0.737 higher than that of TNM staging alone (0.667 for OS and 0.689 for CSS), respectively. In addition, the calibration curves and decision curve analysis further showed its robust power in survival prediction. CONCLUSIONS The constructed nomograms showed better discrimination abilities to predict OS and CSS rates at 1, 3, and 5 years. In the future, these constructed models for this disease will assist in risk stratification to guide GBAC treatment.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias da Vesícula Biliar/epidemiologia , Nomogramas , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Risco , Análise de Sobrevida
14.
J Surg Oncol ; 124(1): 59-66, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33765331

RESUMO

BACKGROUND: Growing evidence indicates that systemic immune inflammation index (SII) can predict the prognosis of various solid tumors. The objective of this study aimed to investigate the efficacy of SII in predicting the prognosis of gallbladder carcinoma (GBC) patients after radical surgery. METHODS: A consecutive series of 93 patients with GBC who underwent radical resection were enrolled in the retrospective study. The cutoff value for the SII was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the SII and the clinicopathologic characteristics were analyzed using Pearson's χ2 test and Fisher's exact test. Survival curves were calculated using the Kaplan-Meier method. Univariate analysis was performed to evaluate the prognostic relevance of preoperative parameters. The multivariate Cox regression proportional hazard model was used to assess variables significant on univariate analysis. RESULTS: The Kaplan-Meier survival analysis and the multivariate analysis of patients with GBC who received radical resection showed SII independently predicted OS. The univariate analysis showed that the TNM stage, SII, CA19-9, ALP, prealbumin, NLR, MLR, lymph node metastasis, and histopathological type were all associated with overall survival. In time-dependent ROC analysis, the area of the SII-CA19-9 under the ROC curve (AUC) was higher than that of the preoperative SII or CA19-9 levels for the prediction of OS. CONCLUSION: Our results demonstrate that high SII was a predictor of poor long-term outcomes among patients with GBC undergoing curative surgery. SII-CA19-9 classification may be more effective in predicting the postoperative prognosis of GBC patients.


Assuntos
Biomarcadores Tumorais/análise , Plaquetas/patologia , Colecistectomia/mortalidade , Neoplasias da Vesícula Biliar/mortalidade , Mediadores da Inflamação/análise , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Ann Surg Oncol ; 28(5): 2675-2682, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33666814

RESUMO

BACKGROUND: Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. PATIENTS AND METHODS: Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000-2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. RESULTS: Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3-T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49-3.13, P < 0.001], 12-month recurrence-free (HR 3.42, 95% CI 1.88-6.23, P < 0.001), and 24-month recurrence-free (HR 2.71, 95% CI 1.11-6.62, P = 0.029). Of the 125 patients without these risk factors, only 2 had recurrence after 36 months. CONCLUSION: C-RFS improves over time, and only T3-T4 disease remains a risk factor for recurrence at 24 months after OER for GBC. For all recurrence-free survivors after 36 months, the probability of recurrence is similar regardless of T category or disease stage.


Assuntos
Neoplasias da Vesícula Biliar , Colecistectomia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Ann R Coll Surg Engl ; 103(4): e116-e119, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33682446

RESUMO

We report a 48-year-old fit and healthy woman who was incidentally diagnosed to have adenocarcinoma of gallbladder after laparoscopic cholecystectomy. Subsequent imaging showed no evidence of regional or distant spread. She was scheduled for elective laparotomy and resection of gallbladder bed, but during laparotomy frozen section analysis of an incidentally discovered peritoneal deposit confirmed metastasis, so the procedure was abandoned. Thereafter, she received cisplatin and gemcitabine chemotherapy. However, surveillance computed tomography incidentally noted a urinary bladder mass which had not been present before. Transurethral resection of the bladder lesion revealed moderately differentiated adenocarcinoma of urinary bladder. The appearance and immunoprofile of the lesion confirmed metastasis from the primary gallbladder cancer, which has not been documented in the literature to the best of our knowledge. Her disease progressed and she is being challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after the initial diagnosis.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Bexiga Urinária/secundário , Adenocarcinoma/diagnóstico , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Achados Incidentais , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico
17.
Clin Hemorheol Microcirc ; 78(2): 209-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33579828

RESUMO

Gallbladder cancer is a malignant tumor with high mortality. Early diagnosis is significance to improve the prognosis of patients. Gallbladder adenoma is recognized as a kind of precancerous disease, for the past few years, contrast-enhanced ultrasound was used in the diagnosis of biliary tumors. This case is about gallbladder papillary adenoma with carcinogenesis. There is rare literature on the contrast-enhanced ultrasound manifestations of this type of disease. We hope that this report can help improve the recognition of contrast-enhanced ultrasound features and improve the accuracy of early diagnosis of gallbladder cancer.


Assuntos
Adenoma/patologia , Carcinogênese/patologia , Carcinoma Papilar/patologia , Meios de Contraste/química , Neoplasias da Vesícula Biliar/patologia , Ultrassonografia/métodos , Adenoma/diagnóstico por imagem , Idoso , Carcinoma Papilar/diagnóstico por imagem , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Humanos , Prognóstico
18.
Eur Rev Med Pharmacol Sci ; 25(3): 1311-1321, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33629301

RESUMO

OBJECTIVE: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear. MATERIALS AND METHODS: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro. RESULTS: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo. CONCLUSIONS: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclina D1/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Neoplasias da Vesícula Biliar/tratamento farmacológico , Quempferóis/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Quempferóis/química , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células Tumorais Cultivadas
19.
Ann Surg Oncol ; 28(6): 2949-2957, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33566241

RESUMO

BACKGROUND: Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer. METHODS: Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004-2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan-Meier and Cox proportional hazard methods. RESULTS: The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p < 0.0001), private insurance (41.6% vs 27.1%; p < 0.0001), academic centers (50.4% vs 29.7%; p < 0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p = 0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p = 0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p < 0.0001), negative margins on final pathology (90.1% vs 72.6%; p < 0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p < 0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p < 0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p = 0.0004). CONCLUSIONS: Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.


Assuntos
Adenocarcinoma , Neoplasias da Vesícula Biliar , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estadiamento de Neoplasias , Pontuação de Propensão , Análise de Sobrevida
20.
Surgery ; 169(6): 1304-1311, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33551070

RESUMO

BACKGROUND: Liver resection is recommended for T2 gallbladder cancer, but the optimal hepatectomy strategy remains controversial. We aimed to assess the safety and effectiveness of segment IVb and V resection versus wedge resection in patients with T2 gallbladder cancer. METHODS: This is a retrospective multicenter propensity score-matched study in China. Overall survival, disease-free survival, perioperative complications, and hospital length of stay were used to evaluate safety and effectiveness. RESULTS: There are a total of 512 patients. 112 of 117 patients undergoing segment IVb and V resection were matched to 112 patients undergoing wedge resection. After matching, segment IVb and V resection demonstrated no statistical difference in overall survival (hazard ratio, 0.970 [0.639-1.474]; P = .886), but significance in disease-free survival (hazard ratio, 0.708 [0.506-0.991]; P = .040). Patients with incidental gallbladder cancer (hazard ratio, 0.390 [0.180-0.846]; P = .019), stage T2b (hazard ratio, 0.515 [0.302-0.878]; P = .016), and negative lymph nodes status (hazard ratio, 0.627 [0.406-0.991]; P = .043) were associated with improved disease-free survival after segment IVb and V resection, but not in wedge resection. However, perioperative complications occurred more frequently after segment IVb and V resection (28.5% vs 9.1%, P < .001) along with the longer hospital length of stay (17.3 vs 10.2 days, P < .001). Notably, patients with jaundice (odds ratio, 4.053 [1.361-12.23]; P = .013), undergoing laparoscopic resection (odds ratio, 2.387 [1.059-4.484]; P = .028) or surgeon performing per the first 10 segment IVb and V resections (odds ratio, 2.697 [1.035-6.998]; P = .041), were the independent risk factors for perioperative complications in the segment IVb and V resection group. CONCLUSION: T2 gallbladder cancer patients undergoing segment IVb and V resection rather than wedge resection have an improved disease-free survival, especially for incidental gallbladder cancer or hepatic-sided (T2b) gallbladder cancer. However, high rates of perioperative complications and longer hospital length of stay after segment IVb and V resection indicated that surgeons must rely on their own surgical skills and the patient profile to decide the optimal hepatectomy strategy.


Assuntos
Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia/métodos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/patologia , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Complicações Intraoperatórias , Tempo de Internação , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
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