RESUMEN
The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.
Asunto(s)
Arteria Hepática , Verde de Indocianina , Trasplante de Hígado , Imagen Óptica , Trombosis , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Verde de Indocianina/administración & dosificación , Arteria Hepática/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Imagen Óptica/métodos , Trombosis/etiología , Trombosis/diagnóstico por imagen , Anciano , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Ultrasonografía Doppler/métodos , Valor Predictivo de las Pruebas , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/cirugía , Hígado/diagnóstico por imagen , Hígado/irrigación sanguínea , Hígado/cirugía , Colorantes/administración & dosificación , Constricción Patológica/etiología , Monitoreo Intraoperatorio/métodos , Estudios Retrospectivos , Cuidados Intraoperatorios/métodosRESUMEN
BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Leucovorina/administración & dosificación , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Neoplasias PancreáticasRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the third leading cause of cancer-related mortality within the next decade. Management of PDAC remains challenging with limited effective treatment options and a dismal long-term prognosis. Liquid biopsy and circulating biomarkers seem to be promising to improve the multidisciplinary approach in PDAC treatment. Circulating tumour DNA (ctDNA) is the most studied blood liquid biopsy analyte and can provide insight into the molecular profile and individual characteristics of the tumour in real-time and in advance of standard imaging modalities. This could pave the way for identifying new therapeutic targets and markers of tumour response to supplement diagnostic and provide enhanced stratified treatment. Although its specificity seems excellent, the current sensitivity of ctDNA remains a limitation for clinical use, especially in patients with a low tumour burden. Increasing evidence suggests that ctDNA is a pertinent candidate biomarker to assess minimal residual disease after surgery but also a strong independent prognostic biomarker. This review explores the current knowledge and recent developments in ctDNA as a screening, diagnostic, prognostic and predictive biomarker in the management of resectable PDAC but also technical and analytical challenges that must be overcome to move toward "precision onco-surgery."
Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , ADN Tumoral Circulante , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirugía , ADN Tumoral Circulante/genética , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Pronóstico , Neoplasias PancreáticasRESUMEN
OBJECTIVE: The prognostication of metastatic pancreatic adenocarcinoma (mPDAC) patients remains uncertain, mainly based on carbohydrate antigen 19-9 (CA19-9), with limited utility. Circulating tumour DNA (ctDNA) has been suggested as a prognostic factor, but its added value has been poorly explored. The objective was to determine whether ctDNA is an independent factor for the prognostication of mPDAC. DESIGN: Translational study based on two prospective collections of plasma samples of mPDAC patients naïve for chemotherapy. One used as a test series and the other as validation series coming from two randomised trials (Prodige 35 and Prodige 37). CtDNA was assessed by digital droplet PCR targeting two methylated markers (HOXD8 and POU4F1) according to a newly developed and validated method. Univariate and multivariate analyses were performed according to ctDNA status. RESULTS: Of 372 plasma samples available, 354 patients were analyzed for survival. In the validation series, 145 of 255 patients were found ctDNA positive (56.8%), Median PFS and OS were 5.3 and 8.2 months in ctDNA-positive and 6.2 and 12.6 months in ctDNA-negative patients, respectively. ctDNA positivity was more often associated with young age, high CA19-9 level and neutrophils lymphocytes ratio. In multivariate analysis including these previous markers, ctDNA was confirmed as an independent prognostic marker for PFS (adjusted hazard ratio (HR) 1.5, CI 95% [1.03-2.18], p = 0.034) and OS (HR 1.62, CI 95% [1.05-2.5], p = 0.029). CONCLUSIONS: In this first ctDNA assessment in a large series of mPDAC derived from clinical trials, ctDNA was detectable in 56.8% of patients and confirmed as an independent prognostic marker.
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Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Metilación de ADN , Mutación , Neoplasias Pancreáticas/patología , Anciano , Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/genética , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
The predictive value of a subjective difficulty scale (DS) after surgical procedures is unknown. The objective of this study was to evaluate the prognostic value of a DS after liver transplantation (LT) and to identify predictors of difficulty. Surgeons prospectively evaluated the difficulty of 441 consecutive liver transplantations from donation after brain death at the end of the surgery by using a DS from 0 to 10 ("the easiest to the hardest you can imagine"). DS was associated with severe morbidity. The risk of graft loss at 1 year remained unchanged from 0 to 6 but increased beyond 6. Graft survival and patient survival of group with DS 7-10 was significantly impaired compared to groups with DS: 0-3 or DS: 4-6 but were significantly impaired for the group with DS: 7-10. Independent predictors of difficult LT (DS ≥ 7) were annular segment 1, transjugular intrahepatic portosystemic shunt, retransplantation beyond 30 days, portal vein thrombosis, and ascites. Of them, ascites was a borderline non-significant covariate (p = .04). Vascular complications occurred more often after difficult LT (20.5% vs. 5.9%), whereas there was no difference in the other types of complications. DS can be used to tailor monitoring and anticipate early complications. External validation is needed.
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Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular , Ascitis/complicaciones , Humanos , Cirrosis Hepática/cirugía , Trasplante de Hígado/efectos adversos , Vena Porta/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Derivación Portosistémica Intrahepática Transyugular/métodos , Resultado del TratamientoRESUMEN
In metastatic colorectal cancer (mCRC), circulating tumor DNA (ctDNA) monitoring can be used to genotype tumors and track clonal evolution. We investigated the clearance of RAS mutated clones under chemotherapy pressure by ctDNA analysis in patients with a RAS mutated mCRC. Patients with a RAS mutated tumor included in the prospective PLACOL study were monitored for ctDNA. Analyses were based on optimized targeted next-generation sequencing and/or droplet-based digital polymerase chain reaction (ddPCR). For plasma samples without detectable mutations at progression disease, we tested the methylation status of WIF1 and NPY genes using methylation-ddPCR (met-ddPCR) to validate the presence of ctDNA. Among the 36 patients with positive plasma samples for RAS mutations at inclusion, 28 (77.8%) remained RAS positive at disease progression and 8 (22.2%) became negative. Subsequent met-ddPCR for methylated markers showed that only two out of the eight patients with RAS negative plasma had detectable ctDNA at progression. Therefore, only 2 samples among 36 were confirmed for clearance of RAS mutation in our series. In conclusion, this study suggests that the clearance of RAS mutations in patients treated by chemotherapy for a RAS mutated mCRC is a rare event. Monitoring tumor mutations in plasma samples should be combined with a strict control of the presence of ctDNA. The therapeutic impacts of RAS clearance need to be further explored.
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Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/genética , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/análisis , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Metilación de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , Estudios ProspectivosRESUMEN
BACKGROUND & AIMS: Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS: We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MSâ¯≤60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS: Our algorithm achieved a coefficient of determination R2â¯=â¯0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS ≥30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (<30%)/presence (≥30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION: We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY: Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft.
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Hígado Graso , Trasplante de Hígado/efectos adversos , Hígado/patología , Sistemas de Atención de Punto , Espectroscopía Infrarroja Corta , Biopsia/métodos , Calibración , Reglas de Decisión Clínica , Precisión de la Medición Dimensional , Hígado Graso/diagnóstico , Hígado Graso/etiología , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Espectroscopía Infrarroja Corta/instrumentación , Espectroscopía Infrarroja Corta/métodosRESUMEN
BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/mortalidad , Terapia Neoadyuvante/mortalidad , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although laparoscopic major hepatectomy (LMH) is becoming increasingly common in specialized centers, data regarding laparoscopic extended major hepatectomies (LEMH) and their outcomes are limited. The aim of this study was to compare the perioperative characteristics and postoperative outcomes of LEMH to standard LMH. METHODS: All patients who underwent purely laparoscopic anatomical right or left hepatectomy and right or left trisectionectomy between February 1998 and January 2016 are enrolled. Demographic, clinicopathological, and perioperative factors were collected prospectively and analyzed retrospectively. Perioperative characteristics and postoperative outcomes in LEMH were compared to those of standard LMH. RESULTS: Among 195 patients with LMH, 47 (24.1%) underwent LEMH, colorectal liver metastases representing 66.7% of all indications. Preoperative portal vein embolization was undertaken in 31 (15.9%) patients. Despite more frequent vascular clamping, blood loss was higher in LEMH group (400 vs. 214 ml; p = 0.006). However, there was no difference in intraoperative transfusion requirements. Thirty-one patients experienced liver failure with no differences between LMH and LEMH groups. Postoperative mortality was comparable in the two groups [3 (2.5%) LMH patients vs. 2 (5%) LEMH patients (p = 0.388)]. Overall morbidity was higher in the LEMH group [49 LMH patients (41.5%) vs. 24 LEMH patients (60%) (p = 0.052)]. Patients treated with left LEMH experienced more biliary leakage (p = 0.011) and more major pulmonary complications (p = 0.015) than left LMH. CONCLUSION: LEMH is feasible at the price of important morbidity, with manageable and acceptable outcomes. These exigent procedures require high-volume centers with experienced surgeons.
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Hepatectomía/métodos , Laparoscopía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer. First, we demonstrated that, in PDA, PAP/REG3A is produced by inflamed acinar cells from the peritumoral microenvironment and then enhances the migratory and invasive abilities of cancer cells. More specifically, using perineural ex vivo assays we revealed that PAP/REG3A favors PNI through activation of the JAK/STAT signaling pathway in cancer cells. Finally, we analyzed the level of PAP/REG3A in blood from healthy donors or patients with PDA from three independent cohorts. Patients with high levels of PAP/REG3A had overall shorter survival as well as poor surgical outcomes with reduced disease-free survival. Our study provides a rationale for using the PAP/REG3A level as a biomarker to improve pancreatic cancer prognosis. It also suggests that therapeutic targeting of PAP/REG3A activity in PDA could limit tumor cell aggressiveness and PNI.
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Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/diagnóstico , Lectinas Tipo C/sangre , Neoplasias Pancreáticas/diagnóstico , Perineo/patología , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidad , Línea Celular , Movimiento Celular/efectos de los fármacos , Técnicas de Cocultivo , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Ratones , Microscopía Fluorescente , Invasividad Neoplásica , Fibras Nerviosas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Proteínas Asociadas a Pancreatitis , Pronóstico , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Tirfostinos/farmacologíaRESUMEN
AIM: To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. METHODS: Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included. Two radiologists reviewed baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer Network) classification, largest axis, product of the three axes (P3A), and arterial/venous involvement were studied and compared to pathological response and resection status and to disease-free survival (DFS). RESULTS: Thirty-one patients had R0 resection, including only six exhibiting a downstaging according to the NCCN classification. After treatment, the largest axis and P3A decreased (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0 resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in case of complete pathological response (P = 0.011/P = 0.016). A decrease of the arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05). Progression of the vascular involvement was seen in two (5 %) patients and led to a shorter DFS. CONCLUSION: In BR/LA pancreatic adenocarcinoma after the neoadjuvant FOLFIRINOX regimen (± chemoradiotherapy), significant tumour size decreases were observed on CT. However, CT staging was not predictive of resectability and pathological response. KEY POINTS: ⢠Significant tumour size decreases were observed on CT after FOLFIRINOX (± chemoradiotherapy). ⢠CT is not able to predict R0 resection accurately after FOLFIRINOX (± chemoradiotherapy). ⢠CT is not able to predict complete response accurately after FOLFIRINOX (± chemoradiotherapy). ⢠Even with a stable NCCN classification, BR/LA pancreatic adenocarcinoma could have R0 resection.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Fluorouracilo/administración & dosificación , Leucovorina/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Neoplasias Pancreáticas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Antineoplásicos/administración & dosificación , Camptotecina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Irinotecán , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Oxaliplatino , Pancreatectomía , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirugía , Fármacos Sensibilizantes a Radiaciones/farmacología , Estudios Retrospectivos , Resultado del Tratamiento , Complejo Vitamínico B/administración & dosificación , Neoplasias PancreáticasRESUMEN
BACKGROUND: Detecting single-nucleotide variations and insertions/deletions in circulating tumor DNA is challenging because of their low allele frequency. The clinical use of circulating tumor DNA to characterize tumor genetic alterations requires new methods based on next-generation sequencing. METHODS: We developed a method based on quantification of error rate of each base position [position error rate (PER)]. To identify mutations, a binomial test was used to compare the minor-allele frequency to the measured PER at each base position. This process was validated in control samples and in 373 plasma samples from patients with lung or pancreatic cancer. RESULTS: Minimal mutated allele frequencies were 0.003 for single-nucleotide variations and 0.001 for insertions/deletions. Independent testing performed by droplet digital PCR (n = 231 plasma samples) showed strong agreement with the base-PER method (κ = 0.90). CONCLUSIONS: Targeted next-generation sequencing analyzed with the base-PER method represents a robust and low cost method to detect circulating tumor DNA in patients with cancer.
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ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares/genética , Mutación , Neoplasias Pancreáticas/genética , Análisis de Secuencia de ADN , Alelos , Humanos , Neoplasias Pulmonares/diagnóstico , Mutagénesis Insercional , Neoplasias Pancreáticas/diagnóstico , Polimorfismo de Nucleótido Simple/genética , Eliminación de SecuenciaRESUMEN
OBJECTIVE: To evaluate the prevalence of sarcopenia among European patients with resectable hepatocellular carcinoma (HCC) and to assess its prognostic impact on overall and disease-free survival. BACKGROUND: Identification of preoperative prognostic factors in liver surgery for HCC is required to better select patients and improve survival. Recent studies have shown that preoperative discrimination of patients with low skeletal muscle mass (sarcopenic patients) using computed tomography was associated with morbidity and mortality after liver and colorectal surgery. Assessment of sarcopenia could be used to evaluate patients before hepatectomy for HCC. METHODS: All consecutive patients who underwent hepatectomy for HCC in our institution, between February 2006 and September 2012, were included. Univariate and multivariate analyses evaluating prognostic factors of postoperative mortality and cancer recurrence were performed, including preoperative, surgical, and histopathological factors. RESULTS: Among 198 patients who underwent hepatectomy for HCC, 109 patients had an available computed tomographic scan and represent the study cohort. After a median follow-up of 21.23 months, 27 patients (24.8%) died. There were 20 deaths among the 59 patients who had sarcopenia and only 7 deaths in the nonsarcopenic group. Sarcopenic patients had significantly shorter median overall survival than nonsarcopenic patients (52.3 months vs 70.3 months; P = 0.015). On multivariate analysis, sarcopenia was found to be an independent predictor of poor overall survival (hazard ratio = 3.19; P = 0.013) and disease-free survival (hazard ratio = 2.60; P = 0.001). CONCLUSIONS: Sarcopenia was found to be a strong and independent prognostic factor for mortality after hepatectomy for HCC in European patients and could be used to evaluate eligibility of patients with HCC before surgery.
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Carcinoma Hepatocelular/epidemiología , Hepatectomía/mortalidad , Neoplasias Hepáticas/epidemiología , Sarcopenia/diagnóstico por imagen , Sarcopenia/epidemiología , Anciano , Carcinoma Hepatocelular/cirugía , Comorbilidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Selección de Paciente , Prevalencia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. METHODS: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. RESULTS: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). CONCLUSIONS: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.
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Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/patología , Quimioradioterapia , Neoplasias Pancreáticas/patología , Adenocarcinoma/terapia , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carcinoma Ductal Pancreático/terapia , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Pancreáticas/terapia , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from "ideal" donors under 40 years old. METHODS: Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient's gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death. RESULTS: A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group (p = 0.002). After PSM, the 5-year overall survival was 63% and 73% (p = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85. CONCLUSIONS: In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods.
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Highlight Laparoscopic hepatectomy has become commonly used worldwide and laparoscopic right hepatic mobilization is an important step for right sided liver resection. While the technique has been refined, it remains technically challenging. Ielpo and colleagues present a standardized and reproducible technique for safe mobilization including technical steps and video.
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Laparoscopía , Neoplasias Hepáticas , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Neoplasias Hepáticas/cirugíaRESUMEN
BACKGROUND: prognostic biomarkers could be useful to better select patients with borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma (PA) for chemoradiotherapy (CRT) and/or secondary resection. AIMS: The main objective of this work was to study characteristics, received treatments and prognostic of patients with BR or LA PA according to their baseline circulating tumor DNA status and, for secondary objective, neutrophil-to-lymphocyte Ratio (NLR). METHODS: ctDNA status at baseline was determined using Next Generation Sequencing in a consecutive monocentric cohort of patients with a BR or LA PA. RESULTS: 69 patients were included, 31 with BR PA and 38 with LA PA. 14 (20.3%) patients had baseline positive ctDNA. Five (7.8%) patients had NLR> 5. Patients with positive ctDNA had 3.7 months shorter progression free survival (p = 0.006). Patients with positive ctDNA had earlier progression after the beginning of CRT (4.4 vs 7.1 months; p = 0.068) and shorter relapse free survival after secondary resection (9.2 vs 22.9 months; p = 0.016). CONCLUSIONS: positive ctDNA at baseline was associated with a worse prognosis in patients with BR or LA PA. These data are exploratory and must be confirmed in further prospective trials.
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Adenocarcinoma , ADN Tumoral Circulante , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Biomarcadores , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Humanos , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/terapia , Pronóstico , Neoplasias PancreáticasRESUMEN
BACKGROUND: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed. METHODS: All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching. RESULTS: Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002). CONCLUSIONS: ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Sistema del Grupo Sanguíneo ABO , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Our team previously defined six quantitative transcriptomic components, and a classification in five subtypes by association of these components. In this study, we compared the robustness of quantitative components and qualitative classifications from different transcriptomic profiling techniques, investigated their clinical relevance, and proposed a new prognostic model. EXPERIMENTAL DESIGN: A total of 210 patients from a multicentric cohort and 149 patients from a monocentric cohort were included in this study. RNA microarray profiles were obtained from 165 patients of the multicentric cohort. RNA sequencing (RNA-seq) profiles were obtained from all the patients. RESULTS: For the patients with both RNA microarray and RNA-seq profiles, the concordance in subtype assignment was partial with an 82.4% coherence rate. The correlation between the two technique projections of the six components ranged from 0.85 to 0.95, demonstrating an advantage of robustness. On the basis of the Akaike information criterion, the RNA components showed more prognostic value in univariate or multivariate models than the subtypes. Using the monocentric cohort for training, we developed a multivariate Cox regression model using all six components and clinicopathologic characteristics (node invasion and resection margins) on disease-free survival (DFS). This prognostic model was highly associated with DFS (P < 0.001). The evaluation of the model in the multicentric cohort showed significant association with DFS and overall survival (P < 0.001). CONCLUSIONS: We described the advantage of the prognostic value and robustness of the whole-tumor transcriptomic components than subtypes. We created and validated a new DFS-based multivariate Cox regression prognostic model, including six pancreatic adenocarcinoma transcriptomic component levels and pathologic characteristics.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patología , Supervivencia sin Enfermedad , Humanos , Neoplasias Pancreáticas/genética , Pronóstico , TranscriptomaRESUMEN
In metastatic pancreatic adenocarcinoma, a high neutrophil-to-lymphocyte ratio (NLR) at diagnosis is a marker of poor prognosis. The prognostic role of baseline NLR and NLR change during first-line chemotherapy were determined. We conducted a retrospective study by using data from a single-center prospective cohort and a randomized open-label, multicenter, randomized trial. Two hundred and twelve patients were analyzed. Baseline NLR>5 was an independent marker of poor prognosis for overall survival (HR=2.01, 95% CI 1.33-3.05; P=0.001) and progression-free survival (PFS; HR=1.80, 95% CI 1.23-2.65; P=0.0026). According to NLR dynamics (n=172), patients with NLR≤5 on days 1 and 15 had a significantly better prognosis than those with NLR≤5 on day 1 and NLR>5 on day 15 (HR=2.23, 95% CI 1.18-4.21; P=0.013), NLR >5 on day 1 and NLR ≤5 on day 15 (HR=3.25, 95% CI 1.86-5.68; P<0.001), and NLR>5 on days 1 and 15 (HR=3.37, 95% CI 1.93-5.90; P<0.001). Over time, bad responders (PFS <6 months) had significantly higher mean NLR than good responders (PFS>6 months; group effect: P<0.0001). Seven out of eight patients with baseline NLR>5 had circulating tumor DNA. This study confirmed the independent prognostic value of baseline NLR >5 in metastatic pancreatic cancer. The change in NLR early during chemotherapy was also a prognostic indicator in patients with NLR ≤5.