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1.
Cancers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893202

RESUMO

BACKGROUND: the role of minimally invasive liver surgery has been progressively developed, with the practice increasing in safety and feasibility also with respect to major liver resections. The aim of this study was to analyze the feasibility and safety of major liver resection in elderly patients. METHODS: data from a multicentric retrospective database including 1070 consecutive robotic liver resections in nine European hospital centers were analyzed. Among these, 131 were major liver resections. Patients were also divided in two groups (<65 years old and ≥65 years old) and perioperative data were compared between the two groups. RESULTS: a total of 131 patients were included in the study. Operative time was 332 ± 125 min. Postoperative overall complications occurred in 27.1% of patients. Severe complications (Clavien Dindo ≥ 3) were 9.9%. Hospital stay was 6.6 ± 5.3 days. Patients were divided into two groups based on their age: 75 patients < 65 years old and 56 patients ≥ 65 years old. Prolonged pain, lung infection, intensive care stay, and 90-day readmission were worse in the elderly group. The two groups were matched for ASA and Charlson comorbidity score and, after statistical adjustment, postoperative data were similar between two groups. CONCLUSIONS: robotic major liver resection in elderly patients was associated with satisfying short-term outcomes.

2.
Ann Surg Oncol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879668

RESUMO

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

3.
Surg Endosc ; 38(6): 3448-3454, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698258

RESUMO

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Veia Porta , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Feminino , Veia Porta/cirurgia , Ligadura/métodos , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Duração da Cirurgia , Estudos Retrospectivos
4.
Updates Surg ; 76(3): 725-741, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713396

RESUMO

Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.


Assuntos
Terapia de Imunossupressão , Imunossupressores , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Neoplasias Hepáticas/cirurgia , Terapia de Imunossupressão/métodos , Itália , Imunossupressores/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Recidiva Local de Neoplasia
5.
Updates Surg ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704462

RESUMO

Hepatocellular carcinoma (HCC) poses a significant global health challenge, and liver transplantation (LT) remains the best curative option. Living donor liver transplantation (LDLT) emerged as a potential solution to organ scarcity, reducing waitlist times. This comprehensive review explores LDLT practices, focusing on patient selection criteria and oncologic outcomes. A systematic review following PRISMA guidelines included 50 studies (2004-2023) with 8062 patients. Data encompassed baseline characteristics, HCC features, and oncologic outcomes. Further analysis categorized results by geography and publication year. Heterogeneity in patient demographics, tumor burden, and transplant characteristics was observed. Recent LDLT series demonstrated a shift towards refined selection criteria, increased neoadjuvant treatment, and improved oncologic outcomes. Geographic disparities revealed unique challenges in Eastern and Western practices. LDLT proves effective for HCC, addressing donor shortages. Evolving practices highlight the importance of refining inclusion criteria and optimizing tumor management. While geographic differences exist, LDLT, when judiciously applied, offers promising outcomes.

6.
Ann Surg ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787528

RESUMO

OBJECTIVE: To establish the first consensus guidelines on the safety and indications of robotics in Hepato-Pancreatic-Biliary (HPB) surgery. The secondary aim was to identify priorities for future research. SUMMARY BACKGROUND DATA: HPB robotic surgery is reaching the IDEAL 2b exploration phase for innovative technology. An objective assessment endorsed by the HPB community is timely and needed. METHODS: The ROBOT4HPB conference developed consensus guidelines using the Zurich-Danish model. An impartial and multidisciplinary jury produced unbiased guidelines based on the work of ten expert panels answering predefined key questions and considering the best-quality evidence retrieved after a systematic review. The recommendations conformed with the GRADE and SIGN50 methodologies. RESULTS: Fifty-four experts from 20 countries considered 285 studies, and the conference included an audience of 220 attendees. The jury (n=10) produced recommendations or statements covering five sections of robotic HPB surgery: technology, training and expertise, outcome assessment, and liver and pancreatic procedures. The recommendations supported the feasibility of robotics for most HPB procedures and its potential value in extending minimally invasive indications, emphasizing however the importance of expertise to ensure safety. The concept of expertise was defined broadly, encompassing requirements for credentialing HPB robotics at a given center. The jury prioritized relevant questions for future trials and emphasized the need for prospective registries, including validated outcome metrics for the forthcoming assessment of HPB robotics. CONCLUSION: The ROBOT4HPB consensus represents a collaborative and multidisciplinary initiative, defining state-of-the-art expertise in HPB robotics procedures. It produced the first guidelines to encourage their safe use and promotion.

7.
Surg Oncol ; 54: 102081, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729088

RESUMO

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.


Assuntos
COVID-19 , Pancreatectomia , Neoplasias Pancreáticas , SARS-CoV-2 , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/epidemiologia , COVID-19/epidemiologia , Itália/epidemiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Terapia Neoadjuvante , Complicações Pós-Operatórias/epidemiologia , Seguimentos , Prognóstico , Pandemias
8.
Eur J Surg Oncol ; 50(6): 108309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626588

RESUMO

BACKGROUND: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. METHODS: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. RESULTS: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. CONCLUSION: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Terapia Neoadjuvante , Pontuação de Propensão , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos
9.
Int J Surg ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608195

RESUMO

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

10.
Updates Surg ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38589746

RESUMO

Liver transplantation (LT) revolutionized the outlook for cirrhotic patients, offering a potential cure with over 80% life expectancy after 5 years. Cirrhosis, with or without hepatocellular carcinoma (HCC), is the primary LT indication. Living donor LT (LDLT) initially explored as an alternative, declined due to poorer outcomes. Studies on LDLT improved outcomes through precise recipient selection, emphasizing the importance of careful donor/recipient matching. Emerging concepts like left lobe preference and minimally invasive donor approaches enhance LDLT outcomes. The RAPID technique shows promise in both cirrhotic and non-cirrhotic livers. LDLT gains significance in transplant oncology, particularly for liver tumors like colorectal liver metastases (CLM), offering better survival than alternatives. Optimal timing integrates chemotherapy with the transplant. As LT indications evolve, LDLT finds a growing role in oncology, surpassing deceased donor transplants in certain scenarios. The decreasing prevalence of virus-related uncompensated cirrhosis highlights the expanding space for LDLT in liver transplantation.

11.
Int J Surg ; 110(5): 2874-2882, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38445440

RESUMO

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT ( P <0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.


Assuntos
Transplante de Fígado , Veia Porta , Trombose Venosa , Humanos , Transplante de Fígado/efeitos adversos , Veia Porta/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Trombose Venosa/cirurgia , Adulto , Itália/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Seleção de Pacientes , Resultado do Tratamento
12.
Ann Surg ; 280(1): 108-117, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38482665

RESUMO

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.


Assuntos
Hepatectomia , Laparoscopia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/métodos , Feminino , Masculino , Laparoscopia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Hepatopatias/cirurgia
13.
Updates Surg ; 76(2): 435-445, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38326663

RESUMO

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is one of the strategies available for patients initially unresectable. High risk of peri-operative morbidity and mortality limited its application and diffusion. We aimed to analyse short-term outcomes of robotic ALPPS versus open approach, to assess safety and reproducibility of this technique. A retrospective analysis of prospectively maintained databases at University of Modena and Reggio Emilia on patients that underwent ALPPS between January 2015 and September 2022 was conducted. The main aim of the study was to evaluate safety and feasibility of robotic approach, either full robotic or only first-stage robotic, compared to a control group of patients who underwent open ALPPS in the same Institution. 23 patients were included. Nine patients received a full open ALPPS (O-ALPPS), 7 received a full robotic ALPPS (R-ALPPS), and 7 underwent a robotic approach for stage 1, followed by an open approach for stage 2 (R + O-ALPPS). PHLF grade B-C after stage 1 was 0% in all groups, rising to 58% in the R + O-ALPPS group after stage 2 and remaining 0% in the R-ALPPS group. 86% of R-ALPPS cases were discharged from the hospital between stages 1 and 2, and median total in-hospital stay and ICU stay favoured full robotic approach as well. This contemporary study represents the largest series of robotic ALPPS, showing potential advantages from full robotic ALPPS over open approach, resulting in reduced hospital stay and complications and lower incidence of 90-day mortality.


Assuntos
Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Reprodutibilidade dos Testes , Fígado/cirurgia , Hepatectomia/métodos , Veia Porta/cirurgia , Veia Porta/patologia , Ligadura , Resultado do Tratamento
14.
Signal Transduct Target Ther ; 9(1): 31, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342897

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies. PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment. Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC. Here, we identified the transcription factor Fos-related antigen-2 (Fra-2) as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation. We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients. Mechanistically, we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting. In miR-15a-low context, IGF1R hyperactivated mTOR, modulated the autophagic flux and sustained PDAC growth in nutrient deprivation. In a genetic mouse model, Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction. Consistently, nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner. Overall, our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Antígeno 2 Relacionado a Fos , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Serina-Treonina Quinases TOR , Microambiente Tumoral , Receptor IGF Tipo 1/genética
15.
Cancers (Basel) ; 16(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38254809

RESUMO

(1) Background: With ageing, the number of pancreaticoduodenectomies (PD) for benign or malignant disease is expected to increase in elderly patients. However, whether minimally invasive pancreaticoduodenectomy (MIPD) should be performed in the elderly is not clear yet and it is still debated. (2) Materials and Methods: A systematic review and meta-analysis was conducted including seven published articles comparing the technical and post-operative outcomes of MIPD in elderly versus younger patients up to December 2022. (3) Results: In total, 1378 patients were included in the meta-analysis. In term of overall and Clavien-Dindo I/II complication rates, post-operative pancreatic fistula (POPF) grade > A rates and biliary leakage, abdominal collection, post-operative bleeding and delayed gastric emptying rates, no differences emerged between the two groups. However, this study showed slightly higher intraoperative blood loss [MD 43.41, (95%CI 14.45, 72.38) p = 0.003], Clavien-Dindo ≥ III complication rates [OR 1.87, (95%CI 1.13, 3.11) p = 0.02] and mortality rates [OR 2.61, (95%CI 1.20, 5.68) p = 0.02] in the elderly compared with the younger group. Interestingly, as a minor endpoint, no differences in terms of the mean number of harvested lymphnode and of R0 resection rates were found. (4) Conclusion: MIPD seems to be relatively safe; however, there are slightly higher major morbidity, lung complication and mortality rates in elderly patients, who potentially represent the individuals that may benefit the most from the minimally invasive approach.

16.
Ann Surg ; 279(2): 297-305, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37485989

RESUMO

OBJECTIVE: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments. BACKGROUND: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature. METHODS: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias. RESULTS: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset. CONCLUSIONS: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Estudos Retrospectivos , Cirrose Hepática/cirurgia , Hepatectomia , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
17.
Eur J Surg Oncol ; 50(1): 107252, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984243

RESUMO

INTRODUCTION: We performed this study in order to investigate the impact of liver cirrhosis (LC) on the difficulty of minimally invasive liver resection (MILR), focusing on minor resections in anterolateral (AL) segments for primary liver malignancies. METHODS: This was an international multicenter retrospective study of 3675 patients who underwent MILR across 60 centers from 2004 to 2021. RESULTS: 1312 (35.7%) patients had no cirrhosis, 2118 (57.9%) had Child A cirrhosis and 245 (6.7%) had Child B cirrhosis. After propensity score matching (PSM), patients in Child A cirrhosis group had higher rates of open conversion (p = 0.024), blood loss >500 mls (p = 0.001), blood transfusion (p < 0.001), postoperative morbidity (p = 0.004), and in-hospital mortality (p = 0.041). After coarsened exact matching (CEM), Child A cirrhotic patients had higher open conversion rate (p = 0.05), greater median blood loss (p = 0.014) and increased postoperative morbidity (p = 0.001). Compared to Child A cirrhosis, Child B cirrhosis group had longer postoperative stay (p = 0.001) and greater major morbidity (p = 0.012) after PSM, and higher blood transfusion rates (p = 0.002), longer postoperative stay (p < 0.001), and greater major morbidity (p = 0.006) after CEM. After PSM, patients with portal hypertension experienced higher rates of blood loss >500 mls (p = 0.003) and intraoperative blood transfusion (p = 0.025). CONCLUSION: The presence and severity of LC affect and compound the difficulty of MILR for minor resections in the AL segments. These factors should be considered for inclusion into future difficulty scoring systems for MILR.


Assuntos
Hipertensão Portal , Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Criança , Humanos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Tempo de Internação , Cirrose Hepática/complicações , Hepatectomia , Hipertensão Portal/cirurgia , Pontuação de Propensão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
18.
Intern Emerg Med ; 19(2): 343-352, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37985618

RESUMO

AIM: Healthy lifestyle and appropriate diet are of critical importance after liver transplant (LT). We provided an analysis of the main patterns of physical activity and found factors associated with physical activity itself. METHODS: Clinically stable LT recipients were enrolled between June and September 2021. Patients completed a composite questionnaire about physical activity, adherence to Mediterranean Diet (MD), quality of life (QoL), and employment. Correlations were analysed using the Pearson coefficients while different subgroups were compared by t-test for independent samples or ANOVAs. Multivariable logistic regression analysis was conducted to find predictors of inactivity. RESULTS: We enrolled 511 subjects (71% males, mean age 63 ± 10.8 years). One hundred and ninety-three patients reported high level of physical activity, 197 a minimal activity and 121 declared insufficient activity. Among these latter, 29 subjects were totally inactive. Considering the 482 LT recipients performing some kind of physical activity, almost all reported a low-quality, non-structured activity. At multivariate analysis, time from LT (odds ratio 0.94, 95% CI 0.89-0.99, p = 0.017), sedentary lifestyle (odds ratio 0.99, 95% CI 0.19-0.81, p = 0.012), low adherence to MD (odds ratio 1.22, 95% CI 1.01-1.48, p = 0.049), and low level of QoL (physical dimension) (odds ratio 1.13, 95% CI 1.08-1.17, p < 0.001), were independently associated with total inactivity. CONCLUSION: A large portion of LT recipients report an insufficient level of physical activity or are wholly inactive. Inactivity increases with time from LT and was strongly associated with suboptimal diet and low QoL.


Assuntos
Dieta Mediterrânea , Transplante de Fígado , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Qualidade de Vida , Exercício Físico , Inquéritos e Questionários
20.
HPB (Oxford) ; 26(1): 83-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37838501

RESUMO

INTRODUCTION: Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images. METHODS: Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters' agreement was explored. RESULTS: The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7-3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0-2.5; p = 0.0004). The inter-raters' agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44). CONCLUSION: 3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures.


Assuntos
Imageamento Tridimensional , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Tecnologia , Inquéritos e Questionários
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