RESUMEN
BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
Asunto(s)
Adenocarcinoma , Neoplasias Duodenales , Humanos , Masculino , Femenino , Quimioterapia Adyuvante , Persona de Mediana Edad , Anciano , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Neoplasias Duodenales/tratamiento farmacológico , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ampolla Hepatopancreática/patología , Pancreaticoduodenectomía , Estudios de Cohortes , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Estudios Retrospectivos , Capecitabina/uso terapéutico , Capecitabina/administración & dosificaciónRESUMEN
OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.
RESUMEN
BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Neoplasias Duodenales , Escisión del Ganglio Linfático , Metástasis Linfática , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Estudios Retrospectivos , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Masculino , Femenino , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma/secundario , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Anciano , Persona de Mediana Edad , Pronóstico , Estudios de Seguimiento , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/secundarioRESUMEN
BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
Asunto(s)
Ampolla Hepatopancreática , Carcinoma Ductal Pancreático , Colangiocarcinoma , Neoplasias del Conducto Colédoco , Neoplasias Duodenales , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Tasa de Supervivencia , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Anciano , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Persona de Mediana Edad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/mortalidad , Estudios de Seguimiento , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Pronóstico , Estudios de Cohortes , Estudios RetrospectivosRESUMEN
BACKGROUND: Popliteal artery aneurysms (PAA) were traditionally treated by open repair (OR). Endovascular repair (ER) has become a new treatment strategy. The aim of this systemic review and meta-analysis was to evaluate and compare the current outcomes of OR and ER in the emergency treatment of PAA. METHODS: A systematic literature search of the PubMed/Medline database was carried out. Outcomes were 30-day mortality, morbidity, major amputation rate (30 days), major amputation rate (1 year), 1-year primary patency rate, 1-year secondary patency rate and 1-year survival. Additionally, we included clinical data of patients with popliteal aneurysms treated between 2009 and 2021 at the Martin-Luther University Halle-Wittenberg. RESULTS: We identified two cohort studies from 2014 and 2015 with a total of 199 patients that underwent emergent surgery (39 ER and 160 OR). We also included 26 patients from our institution. For emergency treatment, 30-day major amputation rates (18% vs 3%, Odds Ratio 5.82, 95% CI [1.75; 19.30], p = .004), 30-day mortality rates (10% vs 1%, Odds Ratio 5.57, 95% CI [1.01; 30.58], p = .05), 1-year major amputation rates (15% vs 6% Odds Ratio 3.61, 95% CI [1.18; 11.09], p = .02), 1-year loss of primary patency (54% vs 23%, Odds Ratio 3.19, 95% CI [0.91; 11.20], p = .07), and 1-year loss of secondary patency (44% vs 12%, Odds Ratio 6.91, 95% CI [3.01; 15.83], p < .05) were higher in the ER group when compared to the OR group. CONCLUSION: Endovascular repair represents an alternative approach for the emergency treatment of PAA. Limited evidence from the available non-randomized studies shows unfavorable outcomes for patients undergoing ER. However, the results are prone to selection bias, and only randomized trials comparing ER to OR might reveal whether a subgroup of patients would benefit from ER as primary treatment of PAA in an emergency setting.
Asunto(s)
Amputación Quirúrgica , Procedimientos Endovasculares , Recuperación del Miembro , Aneurisma de la Arteria Poplítea , Grado de Desobstrucción Vascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Implantación de Prótesis Vascular/instrumentación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Arteria Poplítea/cirugía , Arteria Poplítea/fisiopatología , Arteria Poplítea/diagnóstico por imagen , Aneurisma de la Arteria Poplítea/complicaciones , Aneurisma de la Arteria Poplítea/diagnóstico por imagen , Aneurisma de la Arteria Poplítea/mortalidad , Aneurisma de la Arteria Poplítea/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Exosomes play a crucial role in the progression and spread of pancreatic cancer, serving not only as promoters of tumor growth and organ-specific metastasis but also as promising biomarkers and targets for treatment. These nano vesicles enhance intercellular communication by transferring bioactive molecules, such as proteins and RNAs, between cells. This process significantly affects cancer cell dynamics, including their proliferation, migration, and invasion, while also contributing to drug resistance. Our review focuses on the crucial interactions between cancer cells and fibroblasts mediated by exosomes within the pancreatic cancer microenvironment. We delve into how exosomes from both cancer-associated fibroblasts and the cancer cells themselves drive tumor progression through various mechanisms, such as epithelial-mesenchymal transition and facilitating metastasis to specific organs like the lungs and liver. The potential of leveraging exosomes for therapeutic interventions is also explored, highlighting the importance of understanding their role in cell communication as a step forward in developing more effective pancreatic cancer treatments.
RESUMEN
For solid malignancies of the gastrointestinal tract, surgical removal is a central pillar of treatment and often the only possibility to achieve a long-term cure. While there are additional qualifications for an oncological subspecialization in other surgical disciplines, such as gynecology or urology nothing comparable exists for visceral surgery in Germany, despite the fact that interdisciplinary cancer treatment strategies are becoming increasingly more complex. The Association of Surgical Oncology (ACO) in cooperation with the European Union of Medical Specialists (UEMS) has created the curriculum for surgical oncology, a structured further education concept, which concludes with the European Board of Surgical Qualification (EBSQ) examination. This results in a standardization and improvement in surgical and oncological treatment in Germany. Furthermore, successful graduates receive an ACO as well as a UEMS certificate and are Fellows of the European Board of Surgery (FEBS).
Asunto(s)
Ginecología , Oncología Quirúrgica , Oncología Quirúrgica/educación , Alemania , Unión Europea , Ginecología/educación , CurriculumRESUMEN
Pancreatic stellate cells (PSC) are one source of cancer-associated fibroblasts (CAF) and play, therefore, an essential role in pancreatic ductal adenocarcinoma (PDA). Paracrine signalling between PDA cells and CAF has been widely studied, yet external influences on paracrine crosstalk are poorly understood. This study aimed to gain a deeper insight into the communication of PSC and cancer cells under different co-culture conditions via analysis of PSC gene expression profiles. Two contactless co-culture models with tumor cells from the p48-Cre; lox-stop-lox-KrasG12D/+; lox-stop-lox-Trp53R172H/+ mouse model (KPC) and murine PSC separated through a microporous membrane and grown in different compartments (standard co-culture) or on different sides of the same membrane (inverse co-culture), were established. RNA-Sequencing analysis of PSC mRNA was performed 24 h and 72 h after co-culture with KPC cells. For selected genes, results were confirmed by quantitative RT-PCR and immunocytochemistry. Standard co-culture displayed 19 differentially expressed genes (DEG) at 24 h and 52 DEG at 72 h. In inverse co-culture, 800 DEG at 24 h and 2213 DEG at 72 h were enriched. PSC showed great heterogeneity in their gene expression profiles; however, mutually regulated genes of both co-cultures, such as VCAN and CHST11, could be identified. VCAN-protein-protein interaction-network analysis revealed several shared genes between co-culture models, such as SDC4 and FN1. In conclusion, PSC show a varying susceptibility to cancer cell signals depending on the co-culture method, with intensified transcriptome changes with closer proximity.
Asunto(s)
Carcinoma Ductal Pancreático , Técnicas de Cocultivo , Neoplasias Pancreáticas , Células Estrelladas Pancreáticas , Comunicación Paracrina , Transcriptoma , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Animales , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Pancreatic cancer is one of the most aggressive human malignancies. Previous research has shown that periostin (POSTN) promotes pancreatic cancer cell proliferation, migration, and invasion. Further, POSTN is involved in tumor microenvironment remodeling during tumor progression. However, the relationship between POSTN expression, immune cell infiltration, and the efficacy of immunotherapy in pancreatic cancer is unclear. METHODS: We conducted a comprehensive evaluation of POSTN differential expression, examining mRNA and protein levels. To gather data, we utilized various databases including gene expression profiling interactive analysis 2 (GEPIA2), gene expression omnibus (GEO), and the human protein atlas (HPA). To investigate the correlation between POSTN expression and clinical characteristics, we analyzed data from the Kaplan-Meier plotter database and clinical data sourced from the cancer genome atlas (TCGA). Furthermore, we performed gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). Additionally, we explored the relationship between POSTN expression and immune cell infiltration, as well as the immunophenoscore (IPS), by leveraging the cancer immunome atlas (TCIA) database. Lastly, we examined the tumor mutational burden (TMB) in pancreatic cancer in relation to POSTN expression. RESULTS: When compared with healthy pancreatic tissues, pancreatic cancer tissues displayed significantly higher levels of POSTN, which was indicative of a worse prognosis. POSTN expression was closely associated with extracellular matrix (ECM) organization, ECM-receptor interaction, and focal adhesion by GO, KEGG pathway, and GSEA analyses. Higher expression of POSTN was associated with increased infiltration of M2 macrophages. Additionally, increased IPS was linked to lower POSTN expression. IPS scores for CTLA4, PD-1/PDL1, and CTLA4/PD-1/PDL1 immune checkpoint inhibitors were also higher in the POSTN-low expression group, suggesting that lower expression of POSTN is associated with a better outcome with checkpoint inhibitor treatment. CONCLUSION: POSTN is related to pancreatic cancer prognosis, and may influence immune cell infiltration. High expression of POSTN is predicted to correlate with lower sensitivity to immunotherapy with checkpoint inhibitors in pancreatic cancer.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Antígeno CTLA-4 , Neoplasias Pancreáticas/genética , Periostina , Pronóstico , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: With the continuous advancement of cancer treatments, a comprehensive analysis of the impact of multivisceral oncological pancreatic resections on morbidity, mortality, and long-term survival is currently lacking. OBJECTIVE: This manuscript presents the protocol for a systematic review and meta-analysis designed to summarize the existing evidence concerning the outcomes of multivisceral oncological pancreatic resections across diverse tumor entities. METHODS: We will conduct a systematic search of the PubMed or MEDLINE, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The predefined outcomes encompass postoperative mortality, postoperative morbidity, overall and disease-free survival (1- to 5-year survival rates), the proportion of macroscopically complete (R0) resections (according to the Royal College of Pathologists definition), duration of hospital stay (in days), reoperation rate (%), postoperative complications (covering all complications according to the Clavien-Dindo classification), as well as pancreatic fistula, postpancreatectomy hemorrhage, and delayed gastric emptying (all according to the definitions of the International Study Group of Pancreas Surgery). RESULTS: Systematic database searches will begin in July 2024. The completion of the meta-analysis is anticipated by December 2024. Before completion, the literature search will be checked for new publications that must be considered in the context of the work. CONCLUSIONS: The forthcoming findings will provide an up-to-date overview of the feasibility, safety, and oncological efficacy of multivisceral pancreatic resections across diverse tumor entities. This data will serve as a valuable resource for health care professionals and patients to make well-informed clinical decisions. TRIAL REGISTRATION: PROSPERO CRD42023437858; https://tinyurl.com/bde5xmfw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54089.
Asunto(s)
Metaanálisis como Asunto , Pancreatectomía , Neoplasias Pancreáticas , Revisiones Sistemáticas como Asunto , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Pancreatectomía/métodos , Pancreatectomía/efectos adversos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Necrotizing pancreatitis with superinfection of necrotic tissue is associated with a high rate of complications and mortality. The step-up approach is a well-established treatment strategy for necrotizing pancreatitis, emphasizing minimally invasive and endoscopic interventions before considering surgical options. Minimally invasive strategies often involve percutaneous drainage of collections, which carries the risk of persisting cutaneous pancreatic fistulas. Since there is currently no guidance for managing this scenario, we present a novel treatment approach that utilized tissue glue to occlude a persisting and clinically compromising percutaneous fistula. In addition, we summarize the current knowledge in the treatment of percutaneous pancreatic fistulas and provide a potential therapeutic algorithm for further evaluation.
RESUMEN
Diagnosis of relevant organ injury after blunt abdominal injury (AI) in multiple-injury/polytraumatised patients is challenging. AI can be distinguished between injuries of parenchymatous organs (POI) of the upper abdomen (liver, spleen) and bowel and mesenteric injuries (BMI). Still, such injuries may be associated with delays in diagnosis and treatment. The present study aimed to verify laboratory parameters, imaging diagnostics, physical examination and related injuries to predict intraabdominal injuries. This retrospective, single-centre study includes data from multiple-injury/polytraumatised patients between 2005 and 2017. Two main groups were defined with relevant abdominal injury (AI+) and without abdominal injury (AI-). The AI+ group was divided into three subgroups: BMI+, BMI+/POI+, and POI+. Groups were compared in a univariate analysis for significant differences. Logistic regression analysis was used to determine predictors for AI+, BMI+ and POI+. 26.3% (271 of 1032) of the included patients had an abdominal injury. Subgroups were composed of 4.7% (49 of 1032) BMI+, 4.7% (48 of 1032) BMI+/POI+ and 16.8% (174 of 1032) POI+. Pathological abdominal signs had a sensitivity of 48.7% and a specificity of 92.4% for AI+. Transaminases were significantly higher in cases of AI+. Pathological computed tomography (CT) (free fluid, parenchymal damage, Bowel Injury Prediction Score (BIPS), CT Grade > 4) was summarised and had a sensitivity of 94.8%, a specificity of 98%, positive predictive value (PPV) of 94.5% and, negative predictive value (NPV) of 98.2% for AI+. The detected predictors for AI+ were pathological abdominal findings (odds ratio (OR) 3.93), pathological multi-slice computed tomography (MSCT) (OR 668.9), alanine (ALAT) ≥ 1.23 µmol/ls (OR 2.35) and associated long bone fractures (OR 3.82). Pathological abdominal signs, pathological MSCT and lactate (LAC) levels ≥ 1.94 mmol/l could be calculated as significant risk factors for BMI+. For POI+ pathological abdominal MSCT, ASAT ≥ 1.73 µmol/ls and concomitant thoracic injuries had significant relevance. The study presents reliable risk factors for abdominal injury and its sub-entities. The predictors can be explained by the anatomy of the trunk and existing studies. Elevated transaminases predicted abdominal injury (AI+) and, specifically, the POI+. The pathological MSCT was the most reliable predictive parameter. However, it was essential to include further relevant parameters.
Asunto(s)
Traumatismos Abdominales , Traumatismo Múltiple , Humanos , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Traumatismo Múltiple/diagnóstico por imagen , Traumatismo Múltiple/diagnóstico , Adulto , Persona de Mediana Edad , Diagnóstico Precoz , Tomografía Computarizada por Rayos X/métodos , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/complicaciones , AncianoRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basallike PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if druginduced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Classical and basallike PDAC cell lines PaTuS, Capan1, Capan2, Colo357, PaTuT, PANC1 and MIAPaCa2, were treated for a short (up to 96 h) and long (up to 30 weeks) period with histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. The cells were analyzed using gene expression approaches, immunoblot analysis, and various cell assays to assess cell characteristics, such as proliferation, colony formation, cell migration and sensitivity to chemotherapeutic drugs. Classical and basallike PDAC cell lines showed pronounced epigenetic regulation of subtypespecific genes through acetylation of lysine 27 on Histone H3 (H3K27ac). Moreover, classical cell lines revealed a significantly decreased expression of HDAC2 and increased total levels of H3K27ac in comparison with the basallike cell lines. Following HAT inhibitor treatment, classical cell lines exhibited a loss of epithelial marker gene expression, decreased chemotherapy response gene score and increased cell migration in vitro, indicating a tumorpromoting phenotype. HDAC inhibitor treatment, however, exerted minimal reprogramming effects in both subtypes. Epigenetic reprogramming of classical and basallike tumor cells did not have a major impact on gemcitabine response, although the gemcitabine transporter gene SLC29A1 (solute carrier family 29 member 1) was epigenetically regulated.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Histonas/genética , Histonas/metabolismo , Gemcitabina , Epigénesis Genética , Acetilación , Línea Celular Tumoral , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión GénicaRESUMEN
This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.
RESUMEN
Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.