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1.
Cancers (Basel) ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39001409

RESUMO

The influencing role of resection margin (R) status on long-term outcomes, namely overall (OS) and disease-free survival (DFS), after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is not still clear. The aim of this study is to evaluate the prognostic impact of R status after PD and to define tumor characteristics associated with a positive resection margin (R1). All PDs for PDAC performed between 2012 and 2023 were retrospectively enrolled. The effect of R status, patient clinico-demographic features, and tumor features on OS and DFS were assessed. One-hundred and sixty-seven patients who underwent PD for PDAC were included in the study. R0 was achieved in 105 cases (62.8%), while R1 was evidenced in 62 patients (37.1%). R1 was associated with a decreased OS (23 (13-38) months) as compared to R0 (36 (21-53) months) (p = 0.003). Similarly, DFS was shorter in R1 patients (10 (6-25) months) as compared to the R0 cohort (18 (9-70) months) (p = 0.004), with a consequent higher recurrence rate in cases of R1 (74.2% vs. 64.8% in the R0 group; p = 0.04). In the multivariate analysis, R1 and positive lymph nodes (N+) were the only independent influencing factors for OS (OR: 1.6; 95% CI: 1-2.5; p = 0.03 and OR: 1.7; 95% CI: 1-2.8; p = 0.04) and DFS (OR: 1.5; 95% CI: 1-2.1; p = 0.04 and OR: 1.8; 95% CI: 1.1-2.7; p = 0.009). Among 111 patients with N+ disease, R1 was associated with a significantly decreased DFS (10 (8-11) months) as compared to R0N+ patients (16 (11-21) months) (p = 0.05). In conclusion, the achievement of a negative resection margin is associated with survival benefits, particularly in cases of N1 disease. In addition, R0 was recognized as an independent prognostic feature for both OS and DFS. This further outlines the relevant role of radical surgery on long-term outcomes.

2.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39062863

RESUMO

Pancreatic cancer (PC) is an increasing cause of cancer-related death, with a dismal prognosis caused by its aggressive biology, the lack of clinical symptoms in the early phases of the disease, and the inefficacy of treatments. PC is characterized by a complex tumor microenvironment. The interaction of its cellular components plays a crucial role in tumor development and progression, contributing to the alteration of metabolism and cellular hyperproliferation, as well as to metastatic evolution and abnormal tumor-associated immunity. Furthermore, in response to intrinsic oncogenic alterations and the influence of the tumor microenvironment, cancer cells undergo a complex oncogene-directed metabolic reprogramming that includes changes in glucose utilization, lipid and amino acid metabolism, redox balance, and activation of recycling and scavenging pathways. The advent of omics sciences is revolutionizing the comprehension of the pathogenetic conundrum of pancreatic carcinogenesis. In particular, metabolomics and genomics has led to a more precise classification of PC into subtypes that show different biological behaviors and responses to treatments. The identification of molecular targets through the pharmacogenomic approach may help to personalize treatments. Novel specific biomarkers have been discovered using proteomics and metabolomics analyses. Radiomics allows for an earlier diagnosis through the computational analysis of imaging. However, the complexity, high expertise required, and costs of the omics approach are the main limitations for its use in clinical practice at present. In addition, the studies of extracellular vesicles (EVs), the use of organoids, the understanding of host-microbiota interactions, and more recently the advent of artificial intelligence are helping to make further steps towards precision and personalized medicine. This present review summarizes the main evidence for the application of omics sciences to the study of PC and the identification of future perspectives.


Assuntos
Genômica , Metabolômica , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Metabolômica/métodos , Genômica/métodos , Microambiente Tumoral/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Proteômica/métodos , Animais
3.
Colorectal Dis ; 26(8): 1569-1583, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38978153

RESUMO

AIM: Minimally invasive surgery has been increasingly adopted for locally advanced colon cancer. However, evidence comparing robotic (RRC) versus laparoscopic right colectomy (LRC) for nonmetastatic pT4 cancers is lacking. METHODS: This was a multicentre propensity score-matched (PSM) study of a cohort of consecutive patients with pT4 right colon cancer treated with RRC or LRC. The two surgical approaches were compared in terms of R0, number of lymph nodes harvested, intra- and postoperative complication rates, overall (OS), and disease-free survival (DFS). RESULTS: Among a total of 200 patients, 39 RRC were compared with 78 PS-matched LRC patients. The R0 rate was similar between RRC and LRC (92.3% vs. 96.2%, respectively; p = 0.399), as was the odds of retrieving 12 or more lymph nodes (97.4% vs. 96.2%; p = 1). No significant difference was noted for the mean operating time (192.9 min vs. 198.3 min; p = 0.750). However, RRC was associated with fewer conversions to laparotomy (5.1% vs. 20.5%; p = 0.032), less blood loss (36.9 vs. 95.2 mL; p < 0.0001), fewer postoperative complications (17.9% vs. 41%; p = 0.013), a shorter time to flatus (2 vs. 2.8 days; p = 0.009), and a shorter hospital stay (6.4 vs. 9.5 days; p < 0.0001) compared with LRC. These results were confirmed even when converted procedures were excluded from the analysis. The 1-, 3- and 5-year OS (p = 0.757) and DFS (p = 0.321) did not significantly differ between RRC and LRC. CONCLUSION: Adequate oncological outcomes are observed for RRC and LRC performed for pT4 right colon cancer. However, RRC is associated with lower conversion rates and improved short-term postoperative outcomes.


Assuntos
Colectomia , Neoplasias do Colo , Laparoscopia , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Colectomia/métodos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Masculino , Feminino , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Intervalo Livre de Doença , Duração da Cirurgia , Estadiamento de Neoplasias , Excisão de Linfonodo/métodos , Estudos Retrospectivos , Europa (Continente)
4.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892122

RESUMO

Pancreatic islet isolation is critical for type 2 diabetes research. Although -omics approaches have shed light on islet molecular profiles, inconsistencies persist; on the other hand, functional studies are essential, but they require reliable and standardized isolation methods. Here, we propose a simplified protocol applied to very small-sized samples collected from partially pancreatectomized living donors. Islet isolation was performed by digesting tissue specimens collected during surgery within a collagenase P solution, followed by a Lympholyte density gradient separation; finally, functional assays and staining with dithizone were carried out. Isolated pancreatic islets exhibited functional responses to glucose and arginine stimulation mirroring donors' metabolic profiles, with insulin secretion significantly decreasing in diabetic islets compared to non-diabetic islets; conversely, proinsulin secretion showed an increasing trend from non-diabetic to diabetic islets. This novel islet isolation method from living patients undergoing partial pancreatectomy offers a valuable opportunity for targeted study of islet physiology, with the primary advantage of being time-effective and successfully preserving islet viability and functionality. It enables the generation of islet preparations that closely reflect donors' clinical profiles, simplifying the isolation process and eliminating the need for a Ricordi chamber. Thus, this method holds promises for advancing our understanding of diabetes and for new personalized pharmacological approaches.


Assuntos
Separação Celular , Ilhotas Pancreáticas , Humanos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/citologia , Separação Celular/métodos , Doadores Vivos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Insulina/metabolismo , Glucose/metabolismo , Secreção de Insulina
5.
Eur J Intern Med ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871564

RESUMO

AIMS: Chronic pancreatitis (CP) is - along with acute pancreatitis - the most frequent cause of diabetes of the exocrine pancreas (DEP). Although insulin deficiency is widely accepted as the major feature of DEP, it is still unclear whether diabetes associated with CP is characterized by additional or different functional defects of the insulin secretory machinery. To identify possible functional defects specifically induced by CP, we performed a cross-sectional study in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) comparing patients with and without CP (CP vs. NCP). METHODS: We administered an oral glucose tolerance test (OGTT) to all participants and, according to their glucose tolerance, classified them as NGT, IGT and DM. Insulin sensitivity and beta-cell functional parameters were derived from OGTT, hyperglycemic clamp and hyperinsulinemic euglycemic clamp. RESULTS: Studying 146 subjects, we found that beta-cell function and insulin secretion were significantly lower in CP compared to NCP patients. However, when we classified the subjects according to OGTT-derived glucose tolerance, we found no differences in beta-cell function or in insulin sensitivity between CP and NCP with the same glucose tolerance status. Of note, we found that arginine-stimulated insulin secretion is reduced only in subjects with CP and DM compared to NCP subjects with DM. CONCLUSIONS: Patients with CP had no specific alterations in insulin secretion and beta-cell function. However, in patients diagnosed with diabetes, we found a lower arginine-stimulated insulin secretion, a marker of reduced functional mass.

6.
Langenbecks Arch Surg ; 409(1): 184, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862717

RESUMO

PURPOSE: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. METHODS: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. RESULTS: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). CONCLUSION: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland.


Assuntos
Pancreatectomia , Fístula Pancreática , Complicações Pós-Operatórias , Grampeamento Cirúrgico , Humanos , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Grampeamento Cirúrgico/métodos , Grampeadores Cirúrgicos , Adulto , Fatores de Tempo , Neoplasias Pancreáticas/cirurgia
7.
Cancers (Basel) ; 16(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38792007

RESUMO

BACKGROUND: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. METHODS: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. RESULTS: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8-28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9-8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (-1.8954 (95% CI: -2.5761 to -1.2146; p < 0.001). CONCLUSIONS: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.

8.
Cancers (Basel) ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730610

RESUMO

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are currently recommended for the pathologic diagnosis of pancreatic solid lesions (PSLs). The application of contrast-enhanced endoscopic ultrasound (ECEUS) could aid the endoscopist during an FNA and/or FNB procedure. CEUS is indeed able to better differentiate the pathologic tissue from the surrounding healthy pancreatic parenchyma and to detect necrotic areas and vessels. OBJECTIVES: Our objective was to evaluate if ECEUS could reduce the number of needle passes and side effects and increase the diagnostic efficacy of FNA and/or FNB. METHODS: A comprehensive literature search of clinical studies was performed to explore if ECEUS-FNA or FNB could increase diagnostic accuracy and reduce the number of needle passes and adverse effects compared to standard EUS-FNA or FNB. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: The proportion of established diagnoses of ECEUS was 90.9% compared to 88.3% of EUS, with no statistically significant difference (p = 0.14). The diagnosis was made through a single step in 70.9% of ECEUS patients and in 65.3% of EUS patients, without statistical significance (p = 0.24). The incidence of adverse reactions was substantially comparable across both groups (p = 0.89). CONCLUSION: ECEUS-FNA and FNB do not appear superior to standard EUS-FNA and FNB for the diagnosis of pancreatic lesions.

9.
Cir Esp (Engl Ed) ; 102 Suppl 1: S66-S71, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704146

RESUMO

Artificial intelligence (AI) will power many of the tools in the armamentarium of digital surgeons. AI methods and surgical proof-of-concept flourish, but we have yet to witness clinical translation and value. Here we exemplify the potential of AI in the care pathway of colorectal cancer patients and discuss clinical, technical, and governance considerations of major importance for the safe translation of surgical AI for the benefit of our patients and practices.


Assuntos
Inteligência Artificial , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/cirurgia
10.
Updates Surg ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662309

RESUMO

Pancreas units represent new organizational models of care that are now at the center of the European debate. The PUECOF study, endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), aims to reach an expert consensus by enquiring surgical leaders about the Pancreas Units' most relevant organizational factors, with 30 surgical leaders from 14 countries participating in the Delphi survey. Results underline that surgeons believe in the need to organize multidisciplinary meetings, nurture team leadership, and create metrics. Clinical professionals and patients are considered the most relevant stakeholders, while the debate is open when considering different subjects like industry leaders and patient associations. Non-technical skills such as ethics, teamwork, professionalism, and leadership are highly considered, with mentoring, clinical cases, and training as the most appreciated facilitating factors. Surgeons show trust in functional leaders, key performance indicators, and the facilitating role played by nurse navigators and case managers. Pancreas units have a high potential to improve patients' outcomes. While the pancreas unit model of care will not change the technical content of pancreatic surgery, it may bring surgeons several benefits, including more cases, professional development, easier coordination, less stress, and opportunities to create fruitful connections with research institutions and industry leaders.

11.
Surgery ; 176(1): 162-171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38594101

RESUMO

BACKGROUND: Imaging-based classifications do not always reflect the clinical severity and prognosis of acute left-sided colonic diverticulitis. This study aims to investigate the role of an early procalcitonin assessment in the emergency department as a risk stratification tool for severity, prognosis, and need for surgery in patients with acute left-sided colonic diverticulitis. METHODS: In this retrospective cohort study, all adult patients consecutively admitted from January 2015 to September 2020 for acute left-sided colonic diverticulitis and having a procalcitonin determination at admission were enrolled. The following data were collected: age, sex, comorbidities, laboratory parameters, level of urgency, clinical presentation, type of treatment, complications, and post-management outcomes. The association between the procalcitonin value at admission and the following endpoints was analyzed: type of treatment, classification of acute left-sided colonic diverticulitis, mortality, and type of surgery. RESULTS: A total of 503 consecutive patients were enrolled. Procalcitonin >0.5 ng/mL emerged as an independent risk factor for complicated acute left-sided colonic diverticulitis (P = .007). Procalcitonin >0.5 ng/mL (P = .033), together with a history of complicated acute left-sided colonic diverticulitis (P < .001), abdominal pain (P = .04), bowel perforation (P < .001), and peritonitis (P < .001), was a significant risk factor for surgery. Procalcitonin >0.5 ng/mL (P = .007) and peritonitis (P = .03) emerged as independent risk factors for sigmoidectomy without colorectal anastomosis. Procalcitonin >0.5 ng/mL (P = .004), a higher level of urgency at admission (P = .005), Hartmann's procedure (P = .002), and the necessity of mechanical ventilation (P = .004) emerged as independent risk factors for mortality. CONCLUSION: Procalcitonin >0.05 ng/mL at emergency department admission is a useful risk stratification tool for severity, prognosis, and need for surgical treatment in patients with acute left-sided colonic diverticulitis.


Assuntos
Doença Diverticular do Colo , Pró-Calcitonina , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Doença Diverticular do Colo/cirurgia , Doença Diverticular do Colo/sangue , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/complicações , Pró-Calcitonina/sangue , Estudos Retrospectivos , Pessoa de Meia-Idade , Medição de Risco/métodos , Prognóstico , Idoso , Biomarcadores/sangue , Adulto , Doença Aguda , Fatores de Risco , Serviço Hospitalar de Emergência/estatística & dados numéricos
12.
Life (Basel) ; 14(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38541624

RESUMO

The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.

13.
Nat Commun ; 15(1): 2764, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553466

RESUMO

The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Intraductais Pancreáticas/genética , Adenocarcinoma Mucinoso/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Hiperplasia , Proteínas de Homeodomínio/genética
17.
Ann Surg ; 280(1): 56-65, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407228

RESUMO

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Assistência Perioperatória , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Assistência Perioperatória/normas , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Técnica Delphi , Guias de Prática Clínica como Assunto , Estadiamento de Neoplasias , Seleção de Pacientes
18.
Langenbecks Arch Surg ; 409(1): 71, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393349

RESUMO

PURPOSE: Anomalies of the right hepatic artery (RHA) may represent an additional challenge in pancreatoduodenectomy (PD). The aim of this study is to assess the potential impact of variations in hepatic arterial anatomy on perioperative outcomes. METHODS: PDs performed for periampullary malignancies between 2017 and 2022 were retrospectively enrolled and subdivided in two groups: modal pattern of vascularization (MPV) and anomalous pattern of vascularization (APV). A propensity score matching (PSM) analysis was conducted to homogenize the two study populations. The two groups were then compared in terms of perioperative outcomes and pathological findings. RESULTS: Thirty-eight patients (16.3%) out of 232 presented a vascular anomaly: an accessory RHA in 7 cases (3%), a replaced RHA in 26 cases (11.2%), and a replaced HA in 5 cases (2.1%). After PSM, 76 MPV patients were compared to the 38 APV patients. The incidence rate of postoperative complications was comparable between the two study populations (p=0.2). Similarly, no difference was detected in terms of histopathological data, including margin status. No difference was noted in terms of intraoperative hemorrhage and vascular resection. CONCLUSION: When PDs are performed in high-volume centers, the presence of an APV of the RHA does not relate to a significant impact on perioperative complications. Moreover, no influence was noted on histopathological findings.


Assuntos
Neoplasias Duodenais , Artéria Hepática , Humanos , Artéria Hepática/cirurgia , Estudos Retrospectivos , Centros de Atenção Terciária , Pancreaticoduodenectomia , Neoplasias Duodenais/cirurgia
19.
Cell Rep Med ; 5(2): 101411, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38325381

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. PDAC presents with molecularly distinct subtypes, with the basal-like one being associated with enhanced chemoresistance. Splicing dysregulation contributes to PDAC; however, its involvement in subtype specification remains elusive. Herein, we uncover a subtype-specific splicing signature associated with prognosis in PDAC and the splicing factor Quaking (QKI) as a determinant of the basal-like signature. Single-cell sequencing analyses highlight QKI as a marker of the basal-like phenotype. QKI represses splicing events associated with the classical subtype while promoting basal-like events associated with shorter survival. QKI favors a plastic, quasi-mesenchymal phenotype that supports migration and chemoresistance in PDAC organoids and cell lines, and its expression is elevated in high-grade primary tumors and metastatic lesions. These studies identify a splicing signature that defines PDAC subtypes and indicate that QKI promotes an undifferentiated, plastic phenotype, which renders PDAC cells chemoresistant and adaptable to environmental changes.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Processamento Alternativo/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Linhagem Celular , Fenótipo
20.
HPB (Oxford) ; 26(1): 44-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37775352

RESUMO

BACKGROUND: The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) METHODS: Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS. RESULTS: O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins. CONCLUSION: In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Laparoscopia , Neoplasias Pancreáticas , Humanos , Entropia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Esplenectomia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Adenocarcinoma/cirurgia
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