Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 224
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
BMC Cancer ; 24(1): 436, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589856

RESUMO

BACKGROUND: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4-6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8). METHODS: PURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study. Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis. DISCUSSION: Considering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients' outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery. TRIAL REGISTRATION: PURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023-503295-25-00).


Assuntos
Neoplasias do Sistema Biliar , Gencitabina , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Cisplatino , Desoxicitidina , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos
2.
Pathobiology ; : 1-7, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763129

RESUMO

INTRODUCTION: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree. METHODS: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®. RESULTS: ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p < 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed >5% positive cells (p = 0.002; odds ratio 14.7). CONCLUSIONS: The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.

3.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892368

RESUMO

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16). One hour before sacrifice, all mice were intraperitoneally inoculated with 5-bromodeoxyuridine (BrdU), and the number of BrdU-positive cells/total cells (labelling index, LI), both in the jejunum and the colon, was evaluated by immunohistochemistry. Samples were also observed by scanning electron microscopy (SEM). Moreover, the microbiota composition in the large bowel of the HFA mice was compared to that of of human donor's fecal sample. No differences in LI were found in the small bowels of the HFA, holoxenic, and germ-free mice. Conversely, the LI in the large bowel of the HFA mice was significantly higher than that in the germ-free and holoxenic counterparts (p = 0.017 and p = 0.048, respectively). In the holoxenic and HFA mice, the SEM analysis disclosed different types of bacteria in close contact with the intestinal epithelium. Finally, the colonic microbiota composition of the HFA mice widely overlapped with that of the human donor in terms of dominant populations, although Bifidobacteria and Lactobacilli disappeared. Despite the small sample size analyzed in this study, these preliminary findings suggest that human intestinal microbiota may promote a high proliferation rate of colonic mucosa. In light of the well-known role of uncontrolled proliferation in colorectal carcinogenesis, these results may deserve further investigation in a larger population study.


Assuntos
Proliferação de Células , Colo , Microbioma Gastrointestinal , Mucosa Intestinal , Animais , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Camundongos , Colo/microbiologia , Colo/metabolismo , Masculino , Vida Livre de Germes , Feminino , Camundongos Endogâmicos C3H , Fezes/microbiologia
4.
Med Lav ; 115(2): e2024016, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38686579

RESUMO

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.


Assuntos
Amianto , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Doenças Profissionais , Exposição Ocupacional , Humanos , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/etiologia , Exposição Ocupacional/efeitos adversos , Itália/epidemiologia , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/etiologia , Masculino , Amianto/efeitos adversos , Estudos de Coortes , Feminino , Pessoa de Meia-Idade , Idoso , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Sistema de Registros
5.
Semin Cancer Biol ; 86(Pt 3): 1058-1065, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536504

RESUMO

Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still representing one of the main causes of cancer-related death worldwide. Evidence is mounting that suggests the putative role of microbiota in the carcinogenesis as well as in modulating the efficacy and activity of anticancer treatments (e.g., chemotherapy, immune checkpoint inhibitors, targeted therapies) in a large number of hematological and solid tumors. However, few data are available regarding the interactions between prostate cancer and microbiome so far, in particular in terms of the impact of microbiota on disease development, pathogenesis, and response to medical treatments in this genitourinary malignancy. Herein, we provide an overview of current knowledge, novel insights and emerging therapeutic approaches related to gastrointestinal and genitourinary microbiome in prostate cancer patients, especially focusing on available evidence and published trials on this topic.


Assuntos
Microbiota , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/etiologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Carcinogênese
6.
Langenbecks Arch Surg ; 408(1): 102, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36826620

RESUMO

INTRODUCTION: The incidence of cholangiocarinoma (CCA), as well as the related mortality rate, has progressively increased over the last decades. Nevertheless improvement in patient management, diagnosis and therapies, recurrence rate remains high (50-70%) with a low 5-year survival (7-20%). Palliative chemotherapy and best supportive care are the treatment of choice in case of recurrence. In recent years, some reports have been published on repeated resection suggesting a survival benefit. The aim of this study was to evaluate the long-term outcome of all repeated resections for recurrent CCA in our institution. MATERIALS AND METHODS: We performed a retrospective analysis of all data recorded in our prospective maintained database of all patients who underwent repeated resection for recurrence of any type of CCA (intrahepatic, perihilar, distal, and gallbladder) with curative intent in our institution. RESULTS: Between 1997 and 2017, twenty-six patients underwent repeated surgical resection for recurrent CCA. Median time to first recurrence was 20 months. Site of recurrence was liver in 18 patients (70%), lymph nodes in 6 (23%), and lungs in 2 (7%). Twenty-five patients (96%) underwent upfront surgical resection of the recurrence, while one received preoperative chemotherapy. Median overall and disease-free survival from repeated surgical resection was 21 and 18 months with a 1-, 3-, and 5-year survival of 87, 41, 29% and 75%, 27%, and 17% respectively. Five patients (21%) did not experience recurrence after repeated surgical resection after a median follow-up of 73 months. CONCLUSIONS: Repeated surgical resection of recurrent CCAs is feasible with good postoperative results and can lead to an increase in survival.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
7.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445594

RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Imunoterapia/métodos
8.
Anticancer Drugs ; 33(1): e781-e783, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407053

RESUMO

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient's conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.


Assuntos
Administração Metronômica , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Hepatite B/complicações , Hepatite D/complicações , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Gravidade do Paciente , alfa-Fetoproteínas/efeitos dos fármacos
9.
Future Oncol ; 18(8): 1023-1034, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35109664

RESUMO

Hepatocellular carcinoma (HCC) represents the fourth most common cause of cancer-related death. Surgery, local ablative therapies and liver transplantation are the only potentially curative strategies, but the majority of patients present with advanced disease at diagnosis or develop recurrence after surgery. In recent years, immunotherapy for HCC has received growing interest, and one of the most promising strategies is the association of two immune checkpoint inhibitors (ICIs), which has already demonstrated its potential in other solid tumors such as melanoma and renal cell carcinoma. Herein, we discuss the role and the biologic rationale of dual immune checkpoint blockade in HCC patients, focusing on the two ICI combinations: nivolumab plus ipilimumab and durvalumab plus tremelimumab.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Imunoterapia
10.
Int J Mol Sci ; 23(18)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36142781

RESUMO

Systemic treatments have traditionally reported limited efficacy for biliary tract cancer (BTC), and although targeted therapies and immune checkpoint inhibitors have been found to play an increasingly important role in treatment, several questions remain unanswered, including the identification of biomarkers of response. The tumor microenvironment (TME) has recently attracted the attention of the BTC medical community, and is currently being studied due to its potential role in modulating response and resistance to systemic therapies, including immunotherapy. In this perspective article, we discuss available evidence regarding the interplay between TME, IDH inhibitors, and immunotherapy, providing rationale for the design of future clinical trials.


Assuntos
Neoplasias do Sistema Biliar , Inibidores de Checkpoint Imunológico , Neoplasias do Sistema Biliar/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Microambiente Tumoral
11.
Medicina (Kaunas) ; 58(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36363500

RESUMO

Objectives: The ABC-06 and the NIFTY trials recently established the role of second-line chemotherapy (2L) in patients with advanced biliary tract cancer (BTC). Our real-world study aimed to explore 2L in BTC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. The Kaplan−Meier methods were used to estimate survival, and the log-rank test was used to make comparisons. Results: A total of 190 BTC patients treated with 2L were identified and included in the analysis. Among them, 52 (27.3%) were aged ≥ 70 years (range 70−87 years). No statistically significant differences in both median overall survival (mOS) and median progression-free survival (mPFS) were recorded between the elderly and younger patients. Absolute lymphocyte count < 1000/mmc (p < 0.001) and albumin level < 3 g/dL (p < 0.001) were independently associated with worse prognoses. Conclusions: The results of this real-world study suggest that for patients aged ≥ 70 years, 2L could be equally effective for younger patients with survival outcomes aligned to those from the ABC-06 and NIFTY trials. The delivery of 2L should be carefully evaluated and monitored in this patient subset.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Idoso , Humanos , Neoplasias do Sistema Biliar/tratamento farmacológico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Prognóstico , Resultado do Tratamento
12.
Br J Cancer ; 124(8): 1388-1397, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33531690

RESUMO

BACKGROUND: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). METHODS: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. RESULTS: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6-12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354-0.574; p < 0.0001). CONCLUSIONS: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , alfa-Fetoproteínas/metabolismo , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Regulação para Cima , Ramucirumab
13.
Am J Transplant ; 21(2): 870-875, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32715576

RESUMO

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.


Assuntos
Transplante de Fígado , Adulto , Criança , Hepatectomia , Humanos , Fígado/cirurgia , Regeneração Hepática , Recidiva Local de Neoplasia , Baço/cirurgia , Esplenectomia , Transplante Heterotópico
14.
Acta Oncol ; 60(10): 1317-1324, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34282710

RESUMO

BACKGROUND: Standard treatment of advanced biliary tract cancer (aBTC) is represented by first-line chemotherapy (CT1). However, some patients do not gain any benefit from CT1, contributing to the overall dismal prognosis of aBTC. The present study aimed to devise a prognostic model in aBTC patients receiving CT1. METHODS: A large panel of clinical, laboratory, and pathology variables, available before the start of CT1, were retrospectively assessed in a multi-centric cohort to determine their prognostic value on univariate and multivariate regression analysis. The variables that showed a significant correlation with overall survival (OS) were computed in a three-tier prognostic score. External validation of the prognostication performance was carried out. RESULTS: Clinical histories of 935 patients (median OS 10.3 months), with diagnosis dates ranging from 2001 to 2017, were retrieved from 14 institutions. According to multivariate analysis, Eastern Cooperative Oncology Group performance status, carbohydrate antigen 19.9, albumin levels, and neutrophil/lymphocyte ratio were strongly associated with OS (p <0.01). The prognostic score could generate a highly significant stratification (all between-group p values ≤0.001) into groups of favorable (comprising 51.5% of the sample), intermediate (39.2%), and poor prognosis (9.3%): median OS was 12.7 (CI95% 11.0-14.4), 7.1 (CI95% 5.8-8.4), and 3.2 months (CI95% 1.7-4.7), respectively. This OS gradient was replicated in the validation set (129 patients), with median OS of 12.7 (CI95% 11.0-14.3), 7.5 (CI95% 6.1-8.9), and 1.4 months (CI95% 0.1-2.7), respectively (all between-group p values ≤0.05). CONCLUSION: A prognostic score, derived from a limited set of easily-retrievable variables, efficiently stratified a large population of unselected aBTC patients undergoing CT1. This tool could be useful to clinicians, to ascertain the potential benefit from CT1 at the start of treatment.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar/tratamento farmacológico , Humanos , Linfócitos , Prognóstico , Estudos Retrospectivos
15.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576078

RESUMO

Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic "hub" interfaced between the gut and the host.


Assuntos
Microbiota , Neoplasias Pancreáticas/microbiologia , Dieta , Microbioma Gastrointestinal , Homeostase , Humanos , Probióticos/uso terapêutico
16.
Medicina (Kaunas) ; 57(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652960

RESUMO

Cholangiocarcinoma (CCA) includes a group of rare and aggressive hepatobiliary malignancies, including extrahepatic cholangiocarcinoma (eCCA) and intrahepatic cholangiocarcinoma (iCCA), with the former further subdivided into distal (dCCA) and perihilar cholangiocarcinoma (pCCA) [...].


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Humanos
17.
HPB (Oxford) ; 23(4): 618-624, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32958386

RESUMO

BACKGROUND: The Clavien-Dindo classification (CDC) system and Comprehensive Complication Index (CCI®) are both widely used methods for reporting the burden of postoperative complications. This study aimed to compare the accuracy of the CDC and CCI® in predicting outcomes associated with pancreatic surgery. METHODS: The CCI® and CDC were applied to 668 patients who underwent pancreatic resection. Length of postoperative stay (LOS) was chosen as the primary outcome variable. The comparison between CCI® and CDC was made with the Spearman test, reporting þs with standard error (SE) and logistic regression, reporting the Odds Ratio (OR) and Area Under the Curve with SE. RESULTS: The median value with the interquartile range (IQR) of CCI® was 20.9 (0-29.6). Both CCI® (þs = 0.609) and CDC (0.590) were significantly (P < 0.001) correlated to LOS. CCI (OR 1.056 and OR 1.052) and CDC (OR 1.978, and OR 1.994) predicted (P < 0.001) LOS over the median and 75th percentile. The accuracy of CCI® was superior to CDC for LOS over 50th (0.785 vs. 0.740; P = 0.004) and over 75th (0.835 vs. 0.761; P < 0.001) percentile. CONCLUSION: The accuracy of CCI® in measuring the complicated postoperative course was superior to CDC, correctly classifying eight patients every ten tested.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Tempo de Internação , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença
18.
Int J Cancer ; 147(11): 3177-3188, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525595

RESUMO

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Irinotecano/administração & dosagem , Platina/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , França , Humanos , Irinotecano/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Platina/uso terapêutico , Estudos Prospectivos , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
Br J Cancer ; 123(7): 1047-1059, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32694694

RESUMO

Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.


Assuntos
Neoplasias do Sistema Biliar/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Imunoterapia , Biópsia Líquida , Terapia de Alvo Molecular , Medicina de Precisão , Microambiente Tumoral
20.
BMC Med Genet ; 21(1): 225, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208122

RESUMO

BACKGROUND: Polymorphisms in genes modulating xenobiotics metabolism, in particular the ABCC2 c.3972C > T single nucleotide polymorphism (SNP) at exon 28, have been suggested to increase primary liver cancer (PLC) risk. Conversely, the occurrence of PLCs in Wilson disease patients is a rare event, in contrast with the occurrence observed in other chronic liver diseases. Here we report the clinical case of five siblings carrying the ABCC2 c.3972C > T SNP; three of them were affected by Wilson disease and two brothers with Wilson disease also developed PLCs. METHODS: The presence of the ABCC2 c.3972C > T SNP was assessed by Sanger sequencing and the exposure of PLC risk factors by standardized questionnaires. RESULTS: Notably, PLCs occurred only in the two brothers with the ABCC2 c.3972C > T SNP and Wilson disease who resulted exposed to asbestos and cigarette smoking, but not in the other siblings with the ABCC2 c.3972C > T SNP, alone or in association with Wilson disease, not exposed to these carcinogens and/or to other known risk factors for PLCs. CONCLUSIONS: These findings suggest that ABCC2 c.3972C > T SNP and WD, also in association, may not represent a sufficient condition for PLC development, but that co-occurrence of further host/exogenous risk factors are needed to drive this process, reinforcing the notion that liver carcinogenesis is the result of a complex interplay between environmental and host genetic determinants. Due to the sporadic cases of this study and the paucity of data currently available in literature on this issue, future investigations in a larger population are needed to confirm our findings.


Assuntos
Carcinoma Hepatocelular/genética , Colangiocarcinoma/genética , Degeneração Hepatolenticular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Amianto/efeitos adversos , Sequência de Bases , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/patologia , Fumar Cigarros/efeitos adversos , Éxons , Feminino , Expressão Gênica , Interação Gene-Ambiente , Haplótipos , Degeneração Hepatolenticular/etiologia , Degeneração Hepatolenticular/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Linhagem , Fatores de Risco , Irmãos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA