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1.
J Exp Clin Cancer Res ; 43(1): 189, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978141

RESUMEN

BACKGROUND: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. METHODS: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). RESULTS: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. CONCLUSIONS: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence.


Asunto(s)
Carcinoma Ductal Pancreático , Vesículas Extracelulares , MicroARNs , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroARNs/sangre , MicroARNs/genética , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Anciano , Biomarcadores de Tumor/sangre , Estudios Prospectivos
2.
Surgery ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39013674

RESUMEN

OBJECTIVE: For patients with T1b gallbladder cancer or greater, an adequate lymphadenectomy should include at least 6 nodes. Studies comparing short- and long-term outcomes of the open approach with those of laparoscopy and robotic approaches are limited, with small sample sizes, and there are none comparing laparoscopic and robotic approaches. This study compared patients who underwent robotic, laparoscopic, and open resection of gallbladder cancer, evaluating short- and long-term outcomes. METHODS: We conducted a multicenter retrospective study of patients with T1b gallbladder cancer or greater (excluding combined organ resection and T4) who underwent open, laparoscopic, and robotic liver resection and lymphadenectomy between January 2012 and December 2022. The 3 groups were matched in terms of patient baseline and disease characteristics based on propensity score matching, comparing robotic with open and robotic with laparoscopic groups. RESULTS: We enrolled 575 patients from 37 institutions. After propensity score matching, the median number of harvested nodes was higher in the robotic group than in the open (7 vs 5; P = .0150) and laparoscopic groups (7 vs 4; P < .001). The Pringle maneuver time was shorter with robotic resection than with laparoscopy (38 vs 59 minutes; P = .0034), and the robotic group also had a lower conversion rate (3% vs 14%, respectively; P = .005) and less estimated blood loss than open and laparoscopic resections. The perioperative morbidity and mortality rates did not differ. The robotic and laparoscopic approaches were associated with faster functional recovery than the open group. In the multivariate analysis, the factors related to the retrieval of at least 6 nodes were the robotic approach over open (odds ratio, 5.1529) and over laparoscopy (odds ratio, 6.7289) and the center experience (≥20 minimally invasive liver resections/year) (odds ratio, 4.962). After a mean follow-up of 42.6 months, overall survival and disease-free survival were not different between groups. CONCLUSION: Compared with open and laparoscopic surgeries, the robotic approach for gallbladder cancer performed in a center with appropriate experience in minimally invasive surgery can provide adequate node retrieval.

3.
Int J Biol Sci ; 20(8): 3173-3184, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904016

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome. The research involved a transcriptome-wide analysis, comparing profiles of splicing profiles in PDAC primary cells with normal ductal cells. This revealed more than 400 significant differential splicing events in genes involved in regulation of gene expression, primarily related to mRNA splicing, and metabolism of nucleic acids. PDAC cultures were highly sensitive to the SF3B1 modulators, E7107 and Pladienolide-B, showing IC50s in the low nanomolar range. These compounds induced apoptosis, associated to induction of the MCL-1/S splice variant. and reduced cell migration, associated to RON mis-splicing. In an orthotopic mouse model, E7107 showed promising results. Furthermore, we evaluated SF3B1 expression in specimens from 87 patients and found a significant association of SF3B1 expression with progression-free and overall survival. In conclusion, SF3B1 emerges as both a potential prognostic factor and therapeutic target in PDAC, impacting cell proliferation, migration, and apoptosis. These findings warrant future studies on this new therapeutic strategy against PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Factores de Empalme de ARN , Humanos , Factores de Empalme de ARN/metabolismo , Factores de Empalme de ARN/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Ratones , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Compuestos Epoxi/farmacología , Compuestos Epoxi/uso terapéutico , Pronóstico , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Macrólidos/uso terapéutico , Macrólidos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Empalme del ARN , Empalme Alternativo , Femenino , Movimiento Celular/genética
4.
World J Emerg Surg ; 19(1): 20, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38835071

RESUMEN

BACKGROUND: Robotic surgery has gained widespread acceptance in elective interventions, yet its role in emergency procedures remains underexplored. While the 2021 WSES position paper discussed limited studies on the application of robotics in emergency general surgery, it recommended strict patient selection, adequate training, and improved platform accessibility. This prospective study aims to define the role of robotic surgery in emergency settings, evaluating intraoperative and postoperative outcomes and assessing its feasibility and safety. METHODS: The ROEM study is an observational, prospective, multicentre, international analysis of clinically stable adult patients undergoing robotic surgery for emergency treatment of acute pathologies including diverticulitis, cholecystitis, and obstructed hernias. Data collection includes patient demographics and intervention details. Furthermore, data relating to the operating theatre team and the surgical instruments used will be collected in order to conduct a cost analysis. The study plans to enrol at least 500 patients from 50 participating centres, with each centre having a local lead and collaborators. All data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. Ethical considerations and data governance will be paramount, requiring local ethical committee approvals from participating centres. DISCUSSION: Current literature and expert consensus suggest the feasibility of robotic surgery in emergencies with proper support. However, challenges include staff training, scheduling conflicts with elective surgeries, and increased costs. The ROEM study seeks to contribute valuable data on the safety, feasibility, and cost-effectiveness of robotic surgery in emergency settings, focusing on specific pathologies. Previous studies on cholecystitis, abdominal hernias, and diverticulitis provide insights into the benefits and challenges of robotic approaches. It is necessary to identify patient populations that benefit most from robotic emergency surgery to optimize outcomes and justify costs.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Prospectivos , Urgencias Médicas , Estudios Observacionales como Asunto , Colecistitis/cirugía , Diverticulitis/cirugía
5.
HPB (Oxford) ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38853075

RESUMEN

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

6.
Int J Cancer ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924078

RESUMEN

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

7.
BJS Open ; 8(3)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38805357

RESUMEN

BACKGROUND: Total mesorectal excision (TME) is the standard surgery for low/mid locally advanced rectal cancer. The aim of this study was to compare three minimally invasive surgical approaches for TME with primary anastomosis (laparoscopic TME, robotic TME, and transanal TME). METHODS: Records of patients undergoing laparoscopic TME, robotic TME, or transanal TME between 2013 and 2022 according to standardized techniques in expert centres contributing to the European MRI and Rectal Cancer Surgery III (EuMaRCS-III) database were analysed. Propensity score matching was applied to compare the three groups with respect to the complication rate (primary outcome), conversion rate, postoperative recovery, and survival. RESULTS: A total of 468 patients (mean(s.d.) age of 64.1(11) years) were included; 190 (40.6%) patients underwent laparoscopic TME, 141 (30.1%) patients underwent robotic TME, and 137 (29.3%) patients underwent transanal TME. Comparative analyses after propensity score matching demonstrated a higher rate of postoperative complications for laparoscopic TME compared with both robotic TME (OR 1.80, 95% c.i. 1.11-2.91) and transanal TME (OR 2.87, 95% c.i. 1.72-4.80). Robotic TME was associated with a lower rate of grade A anastomotic leakage (2%) compared with both laparoscopic TME (8.8%) and transanal TME (8.1%) (P = 0.031). Robotic TME (1.4%) and transanal TME (0.7%) were both associated with a lower conversion rate to open surgery compared with laparoscopic TME (8.8%) (P < 0.001). Time to flatus and duration of hospital stay were shorter for patients treated with transanal TME (P = 0.003 and 0.001 respectively). There were no differences in operating time, intraoperative complications, blood loss, mortality, readmission, R0 resection, or survival. CONCLUSION: In this multicentre, retrospective, propensity score-matched, cohort study of patients with locally advanced rectal cancer, newer minimally invasive approaches (robotic TME and transanal TME) demonstrated improved outcomes compared with laparoscopic TME.


Asunto(s)
Laparoscopía , Complicaciones Posoperatorias , Puntaje de Propensión , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Femenino , Persona de Mediana Edad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Europa (Continente) , Estudios Retrospectivos , Resultado del Tratamiento , Cirugía Endoscópica Transanal/métodos , Cirugía Endoscópica Transanal/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Recto/cirugía , Proctectomía/métodos , Proctectomía/efectos adversos
8.
Surg Oncol ; 54: 102081, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729088

RESUMEN

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.


Asunto(s)
COVID-19 , Pancreatectomía , Neoplasias Pancreáticas , SARS-CoV-2 , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/epidemiología , COVID-19/epidemiología , Italia/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Terapia Neoadyuvante , Complicaciones Posoperatorias/epidemiología , Estudios de Seguimiento , Pronóstico , Pandemias
9.
Physiol Plant ; 176(2): e14273, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566156

RESUMEN

Sacoglossa sea slugs have garnered attention due to their ability to retain intracellular functional chloroplasts from algae, while degrading other algal cell components. While protective mechanisms that limit oxidative damage under excessive light are well documented in plants and algae, the photoprotective strategies employed by these photosynthetic sea slugs remain unresolved. Species within the genus Elysia are known to retain chloroplasts from various algal sources, but the extent to which the metabolic processes from the donor algae can be sustained by the sea slugs is unclear. By comparing responses to high-light conditions through kinetic analyses, molecular techniques, and biochemical assays, this study shows significant differences between two photosynthetic Elysia species with chloroplasts derived from the green alga Acetabularia acetabulum. Notably, Elysia timida displayed remarkable tolerance to high-light stress and sophisticated photoprotective mechanisms such as an active xanthophyll cycle, efficient D1 protein recycling, accumulation of heat-shock proteins and α-tocopherol. In contrast, Elysia crispata exhibited absence or limitations in these photoprotective strategies. Our findings emphasize the intricate relationship between the host animal and the stolen chloroplasts, highlighting different capacities to protect the photosynthetic organelle from oxidative damage.


Asunto(s)
Acetabularia , Gastrópodos , Animales , Plastidios/metabolismo , Cloroplastos/metabolismo , Fotosíntesis , Gastrópodos/metabolismo
11.
Langenbecks Arch Surg ; 409(1): 103, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517543

RESUMEN

BACKGROUND: The aim of the present study is to compare outcomes of the robotic hand-sewn, linear- and circular-stapled techniques performed to create an intrathoracic esophagogastric anastomosis in patients who underwent Ivor-Lewis esophagectomy. METHODS: Patients who underwent a planned Ivor-Lewis esophagectomy were retrospectively analysed from prospectively maintained databases. Only patients who underwent a robotic thoracic approach with the creation of an intrathoracic esophagogastric anastomosis were included in the study. Patients were divided into three groups: hand-sewn-, circular stapled-, and linear-stapled anastomosis group. Demographic information and surgery-related data were extracted. The primary outcome was the rate of anastomotic leakages (AL) in the three groups. Moreover, the rate of grade A, B and C anastomotic leakage were evaluated. In addition, patients of each group were divided in subgroups according to the characteristics of anastomotic fashioning technique. RESULTS: Two hundred and thirty patients were enrolled in the study. No significant differences were found between the three groups about AL rate (p = 0.137). Considering the management of the AL for each of the three groups, no significant differences were found. Evaluating the correlation between AL rate and the characteristics of anastomotic fashioning technique, no significant differences were found. CONCLUSIONS: No standardized anastomotic fashioning technique has yet been generally accepted. This study could be considered a call to perform ad hoc high-quality studies involving high-volume centers for upper gastrointestinal surgery to evaluate what is the most advantageous anastomotic technique.


Asunto(s)
Neoplasias Esofágicas , Procedimientos Quirúrgicos Robotizados , Humanos , Esofagectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Neoplasias Esofágicas/cirugía , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/cirugía , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento
13.
Plant Physiol ; 194(3): 1662-1673, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-37966976

RESUMEN

Carotenoids are health-promoting plastidial isoprenoids with essential functions in plants as photoprotectants and photosynthetic pigments in chloroplasts. They also accumulate in specialized plastids named chromoplasts, providing color to non-photosynthetic tissues such as flower petals and ripe fruit. Carotenoid accumulation in chromoplasts requires specialized structures and proteins such as fibrillins (FBNs). The FBN family includes structural components of carotenoid sequestering structures in chromoplasts and members with metabolic roles in chloroplasts and other plastid types. However, the association of FBNs with carotenoids in plastids other than chromoplasts has remained unexplored. Here, we show that Arabidopsis (Arabidopsis thaliana) FBN6 interacts with phytoene synthase (PSY), the first enzyme of the carotenoid pathway. FBN6, but not FBN4 (a FBN that does not interact with PSY), enhances the activity of plant PSY (but not of the bacterial PSY crtB) in Escherichia coli cells. Overexpression of FBN6 in Nicotiana benthamiana leaves results in a higher production of phytoene, the product of PSY activity, whereas loss of FBN6 activity in Arabidopsis mutants dramatically reduces the production of carotenoids during seedling de-etiolation and after exposure to high light. Our work hence demonstrates that FBNs promote not only the accumulation of carotenoids in chromoplasts but also their biosynthesis in chloroplasts.


Asunto(s)
Arabidopsis , Arabidopsis/genética , Carotenoides , Cloroplastos , Escherichia coli , Plastidios , Fibrilinas
15.
Semin Cancer Biol ; 97: 50-67, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37956937

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.


Asunto(s)
Carcinoma Ductal Pancreático , Exosomas , Vesículas Extracelulares , Neoplasias Pancreáticas , Humanos , Reproducibilidad de los Resultados , Vesículas Extracelulares/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Biomarcadores , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Microambiente Tumoral
16.
Int J Med Robot ; : e2596, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37937476

RESUMEN

BACKGROUND: Robotic distal pancreatectomy (RDP) is associated with a lower conversion rate and less blood loss than laparoscopic distal pancreatectomy (LDP). LDP has similar oncological outcomes as open surgery in PDAC. The aim of this study was to compare perioperative and oncological outcomes in obese patients with RDP versus LDP for PDAC. MATERIALS AND METHODS: Retrospectively, all obese patients who underwent RDP or LDP for PDAC between 2012 and 2022 at 12 international expert centres were included. RESULTS: out of 372, 81 patients were included. All baseline features were comparable between the two groups. RDP was associated with decreased blood loss (495mlLDP vs. 188mlRDP; p = 0.003), lower conversion rate (13.5%RDP vs. 36.4%LDP; p = 0.019) and lower rate of Clavien-Dindo ≥3 complications (13.5%RDP vs. 36.4%LDP; p = 0.019). Overall and disease-free survival were comparable. CONCLUSIONS: In obese patients with left-sided PDAC, the robotic approach was associated with improved intraoperative outcomes and fewer severe complications.

17.
Trials ; 24(1): 665, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37828593

RESUMEN

BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. METHODS/DESIGN: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-ß), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. DISCUSSION: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. TRIAL REGISTRATION: ISRCTN27483786. Registered on August 2, 2023.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Calidad de Vida , Complicaciones Posoperatorias/epidemiología , Páncreas/cirugía , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Estudios Retrospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
18.
Int J Med Robot ; : e2571, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37655499

RESUMEN

INTRODUCTION: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy, especially after pylorus preservation (Pp). We evaluated the effect of a fully robotic approach with da Vinci Xi on DGE after PpPD. METHODS: Open and robotic PDs were performed in 353 and 50 cases, respectively, from January 2009 to March 2022. We compared the clinical outcomes and incidence of clinically relevant DGE between robotic PpPD (R-PpPD) and open PpPD after one-to-one case-control matching. RESULTS: Each group consisted of 30 patients. Clinically relevant DGE was less common after R-PpPD (3/30 [10%] vs. 10/30 cases [33.3%], p = 0.028). The median length of hospital stay (LoS) was significantly lower in the R-PpPD group (10 vs. 15 days, p = 0.013). CONCLUSION: The reduced tissue trauma by the minimally invasive robotic approach is associated with a lower incidence of DGE, reducing the LoS and encouraging PpPD performed using the fully robotic approach.

19.
Carcinogenesis ; 44(8-9): 642-649, 2023 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-37670727

RESUMEN

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudios de Casos y Controles , Genoma Humano , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , ADN , Polimorfismo de Nucleótido Simple/genética
20.
Surg Endosc ; 37(11): 8384-8393, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37715084

RESUMEN

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/efectos adversos , Neoplasias Pancreáticas/cirugía , Pancreatectomía , Resultado del Tratamiento , Laparoscopía/efectos adversos , Tempo Operativo , Tiempo de Internación , Estudios Retrospectivos
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