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BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.
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Adenocarcinoma , Neoplasias Pancreáticas , Radiocirurgia , Humanos , Adenocarcinoma/etiologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/etiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Estudos Prospectivos , Qualidade de Vida , Neoplasias PancreáticasRESUMO
BACKGROUND: The treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC. METHODS: Post-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015-December 2017). Patients were divided in three groups according to age (<65, 65-74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders. RESULTS: Overall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65-74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival. CONCLUSION: Elderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.
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Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Tratamento Farmacológico , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Análise de Sobrevida , Adulto JovemRESUMO
Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.
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Técnicas de Ablação/métodos , Eletroporação/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Pancreáticas/cirurgia , Humanos , Fígado/cirurgia , Pâncreas/cirurgiaRESUMO
OBJECTIVES: Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. METHODS: Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). RESULTS: Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens. CONCLUSIONS: This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation. KEY POINTS: ⢠Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. ⢠The ablation zone shows a sharp demarcation between avital and vital tissue. ⢠Apoptosis is involved in cell death of colorectal liver metastases after IRE. ⢠Effects of IRE can be monitored real-time using intraoperative ultrasound. ⢠Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols.
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Técnicas de Ablação/métodos , Neoplasias Colorretais/cirurgia , Eletroporação/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Cirurgia Assistida por Computador/métodos , Idoso , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Humanos , Laparotomia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. DESIGN: A retrospective cohort study. MATERIALS AND METHODS: A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. RESULTS: Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group (p = .01). The median duration of thrombolysis was 67 hours (4-304 hours) in the low-dose and 49 hours (2-171 hours) in the high-dose group (p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group (p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group (p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group (p = .22). CONCLUSIONS: Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis.
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Arteriopatias Oclusivas/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Complicações Pós-Operatórias , Terapia Trombolítica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fibrinolíticos/uso terapêutico , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversosRESUMO
BACKGROUND: Irreversible electroporation (IRE) is a novel tumour ablation technique involving repetitive application of electrical energy around a tumour. The use of pulsed electrical gradients carries a risk of cardiac arrhythmias, severe muscle contractions, and seizures. We aimed to identify IRE-related risks and the appropriate precautions for anaesthetic management. METHODS: All patients who were treated with IRE were prospectively included. Exclusion criteria were arrhythmias, congestive heart failure, active coronary artery disease, and epilepsy. All procedures were performed under general anaesthesia with complete muscle relaxation during ECG-synchronized pulsing. Adverse events, cardiovascular effects, blood samples, cerebral activity, and post-procedural pain were analysed. RESULTS: Twenty-eight patients underwent 30 IRE sessions for tumours in the liver, pancreas, kidney, and lesser pelvis. No major adverse events occurred during IRE. Median systolic and diastolic blood pressure increased by 44 mm Hg (range -7 to 108 mm Hg) and 19 mm Hg (range 1-50 mm Hg), respectively. Two transient minor cardiac arrhythmias without haemodynamic consequences were observed. Muscle contractions were mild and IRE caused no reactive brain activity on a simplified EEG. Pain in the first 24 h after percutaneous IRE was generally mild, but higher pain scores were reported after pancreatic treatment (mean VAS score 3; range 0-9). CONCLUSIONS: Side-effects during IRE on tumours in the liver, pancreas, kidney, and lesser pelvis seem mild and manageable when current recommendations for anaesthesia management, including deep muscle relaxation and ECG synchronized pulsing, are followed. Electrical pulses do not seem to cause reactive cerebral activity and evidence for pre-existing atrial fibrillation as an absolute contra-indication for IRE is questionable.
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Técnicas de Ablação/métodos , Anestesia Geral/métodos , Eletroporação/métodos , Neoplasias/cirurgia , Técnicas de Ablação/efeitos adversos , Idoso , Arritmias Cardíacas/etiologia , Contraindicações , Eletrocardiografia , Eletroencefalografia , Feminino , Humanos , Hipertensão/etiologia , Neoplasias Renais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Monitorização Intraoperatória/métodos , Contração Muscular , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pélvicas/cirurgia , Assistência Perioperatória/métodos , Estudos ProspectivosRESUMO
AIM: To describe initial clinical experience with bipolar radiofrequency ablation (RFA) for symptomatic giant hepatic haemangiomas. MATERIALS AND METHODS: Four consecutive patients with a large-volume, symptomatic hepatic cavernous haemangioma of >10 cm were treated with bipolar RFA during laparotomy with ultrasound guidance. Complications were carefully noted. Clinical and radiological effectiveness were evaluated comparing baseline with 3 and 6 months follow-up of symptom assessments and upper abdominal magnetic resonance imaging (MRI) or computed tomography (CT). RESULTS: RFA was successfully performed for all four giant haemangiomas. No major complications were observed. Peri-procedural shrinking was remarkable and intermediate-term volume reduction ranged from 58-92% after 6 months. Symptom relief after 6 months was complete in two patients and considerable in the other two. CONCLUSION: Preliminary results suggest intra-operative bipolar RFA to be a safe, feasible, and effective technique for treatment of giant symptomatic hepatic cavernous haemangiomas.
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Ablação por Cateter/métodos , Hemangioma Cavernoso/cirurgia , Neoplasias Hepáticas/cirurgia , Dor Abdominal/etiologia , Adulto , Dor nas Costas/etiologia , Ablação por Cateter/instrumentação , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Dor no Flanco/etiologia , Hemangioma Cavernoso/patologia , Humanos , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoRESUMO
Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings.
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BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.
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Neoplasias Pancreáticas , Ablação por Radiofrequência , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Países Baixos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Intervalo Livre de Progressão , Ablação por Radiofrequência/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Because sunitinib can induce extensive necrosis in metastatic renal cell cancer (mRCC), we examined whether criteria defined by Choi might be valuable to predict early sunitinib efficacy. METHODS: Computed tomography was used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield units (HUs). According to Choi criteria partial response (PR) was defined as > or =10% decrease in size or > or =15% decrease in attenuation. RESULTS: A total of 55 mRCC patients treated with sunitinib were included. At first evaluation, according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7 patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour attenuation decreased from 66 to 47 HUs (P< or =0.001). In patients with PR, Choi criteria had a significantly better predictive value for progression-free survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191 respectively). The predictive value for RECIST increased (P=0.001 and <0.001 respectively), when best response during treatment was taken into account. CONCLUSION: Choi criteria could be helpful to define early mRCC patients who benefit from sunitinib, but the use of these criteria will not change the management of these patients.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sunitinibe , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Intraoperative ultrasonography (IOUS) has been the standard in surgical decision making in oncologic liver surgery. Preoperative imaging techniques have improved substantially in recent years; therefore, the importance of IOUS might change. The current results of IOUS were compared with preoperative high-resolution helical CT scanning and the impact of IOUS on surgical decision making was evaluated. METHODS: A total of 100 consecutive patients who underwent open surgery for colorectal liver metastases within 4 weeks after preoperative imaging, performed with high-speed helical CT scanners, were included for this study. During surgery, IOUS was performed by a liver specialized radiologist. The findings on preoperative and intraoperative imaging and surgical exploration were compared regarding number, site, and size of the hepatic lesions. The preoperative surgical plan was compared with the final surgical treatment. RESULTS: One hundred patients with CRLM underwent 117 surgical treatments. In 38 patients IOUS differed from preoperative data. In 23 cases IOUS identified more metastatic lesions. In five patients, intraoperative findings identified smaller or less hepatic lesions. Additional information on the localization of the hepatic lesions was gathered by IOUS and changed the surgical treatment in ten cases. IOUS alone altered the surgical strategy 35 times during 117 procedures. In nearly all cases, discrepancy between the preoperative CT scan and IOUS resulted in a change of surgical treatment. CONCLUSIONS: Despite improvement in preoperative imaging technology, the intraoperative use of ultrasonography remains of crucial importance. The detection of preoperatively unknown lesions remains high with great consequence on surgical therapy.
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Neoplasias Colorretais/patologia , Cuidados Intraoperatórios , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: For patients with colorectal cancer liver metastases (CRLM), local treatment is the only treatment with curative intent. The majority of patients with CRLM are however evaluated in multidisciplinary teams of colorectal cancer specialists often lacking expertise in local treatment of liver tumors. The aim of this study was therefore to assess the value of a dedicated multidisciplinary panel consisting of hepatobiliary surgeons and interventional radiologists for patients suffering from liver-only CRLM. METHODS: Patients diagnosed with liver-only CRLM in 2016 were identified in a tertiary referral hospital, and two of the referring hospitals in the Netherlands. Diagnostic imaging was independently reviewed by a panel of four hepatobiliary surgeons and two interventional radiologists to re-evaluate treatment strategy retrospectively. If two or more panelists assessed all lesions eligible for resection and/or ablation, patients were deemed eligible for local treatment with curative intent. Interrater reliability between hepatobiliary surgeons was assessed through intraclass correlation coefficient (ICC) and weighted Cohen's kappa. RESULTS: Diagnostic imaging of 61 patients with liver-only metastases were reviewed. Local treatment strategies appeared feasible in 40/61 (65.6%) patients. Five out of 25 patients (20.0%) initially assigned to systemic therapy were deemed eligible for upfront local treatment with curative intent (p = 0.015). In this subgroup, interrater reliability between hepatobiliary surgeons was substantial (ICC: 0.704, 95% CI: 0.536-0.838, n = 25). CONCLUSION: Assessment of treatment strategy by a dedicated multidisciplinary panel including liver experts may result in an increased number of patients eligible for potentially curative treatment and reduce undertreatment of patients suffering from liver-only CRLM.
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Neoplasias Colorretais/terapia , Comunicação Interdisciplinar , Neoplasias Hepáticas/terapia , Médicos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Equipe de Assistência ao Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: In patients with colorectal liver metastases (CRLM) preoperative imaging may include contrast-enhanced (ce) MRI and [18 F]fluorodeoxyglucose (18 F-FDG) PET-CT. This study assessed trends and variation between hospitals and oncological networks in the use of preoperative imaging in the Netherlands. METHODS: Data for all patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were retrieved from a nationwide auditing database. Multivariable logistic regression analysis was used to assess use of ceMRI, 18 F-FDG PET-CT and combined ceMRI and 18 F-FDG PET-CT, and trends in preoperative imaging and hospital and oncological network variation. RESULTS: A total of 4510 patients were included, of whom 1562 had ceMRI, 872 had 18 F-FDG PET-CT, and 1293 had combined ceMRI and 18 F-FDG PET-CT. Use of ceMRI increased over time (from 9·6 to 26·2 per cent; P < 0·001), use of 18 F-FDG PET-CT decreased (from 28·6 to 6·0 per cent; P < 0·001), and use of both ceMRI and 18 F-FDG PET-CT 16·9 per cent) remained stable. Unadjusted variation in the use of ceMRI, 18 F-FDG PET-CT, and combined ceMRI and 18 F-FDG PET-CT ranged from 5·6 to 100 per cent between hospitals. After case-mix correction, hospital and oncological network variation was found for all imaging modalities. DISCUSSION: Significant variation exists concerning the use of preoperative imaging for CRLM between hospitals and oncological networks in the Netherlands. The use of MRI is increasing, whereas that of 18 F-FDG PET-CT is decreasing.
ANTECEDENTES: En pacientes con metástasis hepáticas colorrectales (colorrectal liver metastases, CRLM), los estudios de imagen preoperatorios pueden incluir resonancia magnética con contraste (ce)MRI y 18 F-FDG-PET-CT. Este estudio evaluó las tendencias y la variación entre los hospitales y las redes oncológicas en el uso de estudios de imagen preoperatorios en los Países Bajos. MÉTODOS: Todos los pacientes que se sometieron a una resección hepática por CRLM en los Países Bajos entre 2014 y 2018 fueron seleccionados a partir de una base de datos a nivel nacional auditada. El análisis de regresión logística multivariable se utilizó para evaluar el uso de ceMRI, de 18 F-FDG-PET-CT y de ceMRI combinado con 18 F-FDG-PET-CT, así como para determinar las tendencias en los estudios de imagen preoperatorios y las variaciones hospitalarias y de la red oncológica. RESULTADOS: En total, se incluyeron 4.510 pacientes, de los cuales 1.562 se sometieron a ceMRI, 872 a 18 F-FDG-PET-CT y 1.293 a ceMRI combinado con 18 F-FDG-PET-CT. El uso de ceMRI aumentó con el tiempo del 9,6% al 26,2% (P < 0,001), el uso de 18 F-FDG-PET-CT disminuyó (25% a 6,0%, P < 0,001) y el uso de ceMRI y 18 F-FDG-PET- CT (17%) se mantuvo estable. La variación no ajustada entre hospitales en el uso de ceMRI, 18 F-FDG-PET-CT y la combinación de ceMRI y 18 F-FDG-PET-CT oscilaba del 5% al 10%. Después de la corrección por case-mix, la variación hospitalaria y de la red oncológica persistía en todas las pruebas de imagen. CONCLUSIÓN: En los Países Bajos existe una variación significativa entre hospitales y redes oncológicas respecto al uso de pruebas de imagen preoperatorias para el CRLM. El uso de MRI está aumentando, mientras que el uso de 18 F-FDG-PET-CT está disminuyendo.
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Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/estatística & dados numéricos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer/estatística & dados numéricos , Meios de Contraste , Bases de Dados Factuais , Feminino , Hospitais/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Período Pré-OperatórioRESUMO
The human body is exposed to many xenobiotic, potentially harmful compounds. The intestinal immune system is crucial in protecting the human body from these substances. Moreover, many microorganisms, residing in the gastrointestinal tract, play an important role in modulating immune responses. Pre- and probiotics may have beneficial effects on the microbial composition and activity within the human gut, subsequently affecting the immune system. Prebiotics can exert their effects via different mechanisms, like selectively stimulating the growth of bacteria by providing substrates or via direct immune stimulation. Probiotics may have beneficial health effects via competition with pathogens for substrates and binding intestinal sites, bioconversions of for example sugars into fermentation products with inhibitory properties, production of growth substrates like vitamins for the host, direct antagonism of pathogens via antimicrobial peptide production, reduction of inflammation and stimulation of immune cells. This review focuses on the different mechanisms via which the pre- and probiotics exert their beneficial effects on the host, addressing their immunomodulatory properties in particular.
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Imunomodulação , Prebióticos , Probióticos , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Fermentação , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Sistema ImunitárioRESUMO
BACKGROUND & AIMS: Exocrine pancreatic function is affected in patients with locally advanced pancreatic cancer (LAPC), clinically leading to steatorrhea. It is unknown whether maldigestion and malabsorption can also be attributed to impaired intestinal enterocyte function. In this exploratory study enterocyte function was assessed in patients with locally advanced pancreatic cancer, treated with Irreversible Electroporation (IRE). METHODS: Enterocyte function was studied by Citrulline Generation Test (CGT). Intestinal absorption capacity of energy and fat was calculated from the differences between nutritional intake (four-days diary) and quantified fecal losses energy and fat in three-days feces collection. RESULTS: Twelve patients were included before IRE, and 5 patients had follow-up measurements. Fasted citrulline [CIT] and glutamine [GLU] levels were below reference levels of healthy subjects ([CIT] 38 ± 8 µmol/L; [GLU] 561 ± 77 µmol/L) both before ([CIT] 25 ± 9 µmol/L; [GLU] 65 ± 35 µmol/L) and after IRE ([CIT] 19 ± 9 µmol/L; [GLU] 53 ± 26 µmol/L) whereas CGT curves were normal, indicating normal enterocyte function (slope 0.21 ± 0.12 and 0.17 ± 0.07 µmol/L/min; [CIT] increment 63 ± 39 and 80 ± 44% respectively). Severe energy/fat malabsorption was present in 6 out of 12 patients with LAPC (mean loss 349 kcal/d, 13 g fat/d) before and in 4 out of 5 patients (mean loss 509 kcal/d, 32 g fat/d) after IRE respectively. CONCLUSIONS: Enterocyte function was generally within reference limits in patients with advanced pancreatic cancer. Severe malabsorption may be explained by exocrine pancreatic insufficiency.
Assuntos
Enterócitos/metabolismo , Pâncreas , Neoplasias Pancreáticas , Idoso , Citrulina/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Insuficiência Pancreática Exócrina/fisiopatologia , Gorduras/metabolismo , Fezes/química , Feminino , Glutamina/metabolismo , Humanos , Absorção Intestinal/fisiologia , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/fisiopatologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatologia , Estudos ProspectivosRESUMO
OBJECTIVE: To describe the initial experience with irreversible electroporation (IRE) to treat pelvic tumor recurrences. METHODS: A retrospective single-center analysis was performed. Adverse events were recorded using Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Clinical outcome was determined using pain- and general- symptom assessment, including Seddon's peripheral nerve injury (PNI) types. Radiological outcome was evaluated by comparing baseline with three-month 18F-FDG PET-CT follow-up. RESULTS: Eight patients (nine tumors [recurrences of primary rectal (n = 4), anal (n = 1), sigmoid (n = 1), cervical (n = 1), and renal cell carcinoma (n = 1)]) underwent percutaneous IRE as salvage therapy. Median longest tumor diameter was 3.7 cm (range 1.2-7.0). One CTCAE grade III adverse event (hemorrhage) and eight CTCAE grade II complications occurred in 6/8 patients: vagino-tumoral fistula (n = 1), lower limb motor loss (n = 3; PNI type II) with partial recovery in one patient, hypotonic bladder (n = 2; PNI types I and II) with complete recovery in one patient, and upper limb motor loss (n = 2; PNI type II) with partial recovery in both patients. No residual tumor tissue was observed at 3-month follow-up. After a median follow-up of 12 months, local progression was observed in 5/9 lesions (4/5 were >3 cm pre-IRE); one lesion was successfully retreated. Debilitating preprocedural pain (n = 3) remained unchanged (n = 1) or improved (n = 2). CONCLUSION: IRE may represent a suitable technique to treat pelvic tumor recurrences, although permanent neural function loss can occur. Complete ablation seems realistic for smaller lesions; for larger lesions symptom control should be the focus.
Assuntos
Carcinoma de Células Renais/terapia , Eletroporação/métodos , Neoplasias Renais/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Retais/terapia , Neoplasias do Colo Sigmoide/terapia , Neoplasias do Colo do Útero/terapia , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Neoplasias Retais/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/diagnóstico por imagem , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
BACKGROUND AND AIM: To provide a comprehensive quantitative assessment of nutritional status, digestion and absorption, and quality of life (QoL) in patients with locally advanced pancreatic cancer (LAPC). METHODS: Sixteen patients with LAPC were prospectively assessed for weight loss (WL), body mass index (BMI), fat-free mass index (FFMI), handgrip strength (HGS), dietary macronutrient intake, serum vitamin levels, resting and total energy expenditure (REE and TEE, indirect calorimetry), intestinal absorption capacity and fecal losses (bomb calorimetry), exocrine pancreatic function (fecal elastase-1 (FE1)), and gastrointestinal quality of life (GIQLI). RESULTS: Two patients had a low BMI, 10 patients had WL > 10%/6 months, 8 patients had a FFMI < P10, and 8 patients had a HGS < P10. Measured REE was 33% higher (P = 0.002) than predicted REE. TEE was significantly higher than daily energy intake (P = 0.047). Malabsorption (<85%) of energy, fat, protein, and carbohydrates was observed in, respectively, 9, 8, 12, and 10 patients. FE1 levels were low (<200 µg/g) in 13 patients. Total QoL scored 71% (ample satisfactory). CONCLUSION: Patients with LAPC have a severely impaired nutritional status, most likely as a result of an increased REE and malabsorption due to exocrine pancreatic insufficiency. The trial is registered with PANFIRE clinicaltrials.gov NCT01939665.