RESUMO
BACKGROUND: Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. METHODS: 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. RESULTS: Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05). DISCUSSION: Our results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM.
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Sobrevivência Celular , Neoplasias Colorretais , Técnicas de Imagem por Elasticidade , Elasticidade , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Viscosidade , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS: Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS: Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS: Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Recidiva Local de Neoplasia , Reoperação , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Masculino , Feminino , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Hepatectomia/mortalidade , Hepatectomia/métodos , Taxa de Sobrevida , Pessoa de Meia-Idade , Idoso , Reoperação/estatística & dados numéricos , Seguimentos , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. METHODS: All patients that underwent primary LT between 2006 and 2018 at the Charité-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. RESULTS: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). DISCUSSION: CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.
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Infecções por Citomegalovirus , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Citomegalovirus , Imunossupressores/efeitos adversos , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/diagnóstico , Imunoglobulina G/uso terapêutico , Progressão da Doença , Estudos Retrospectivos , Antivirais/uso terapêuticoRESUMO
PURPOSE: Minimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses. METHODS: A prospective observational study comparing surgical approach in patients within an ERAS program compared to standard care from 2018-2022 at the Charité - Universitätsmedizin Berlin. Cost data were provided by the medical controlling office. ERAS items were applied according to the ERAS society recommendations. RESULTS: 537 patients underwent liver surgery (46% laparoscopic, 26% robotic assisted, 28% open surgery) and 487 were managed by the ERAS protocol. Implementation of ERAS reduced overall postoperative complications in the MILS group (18% vs. 32%, p = 0.048). Complications greater than Clavien-Dindo grade II incurred the highest costs ( 31,093) compared to minor ( 17,510) and no complications (13,893; p < 0.001). In the event of major complications, profit margins were reduced by a median of 6,640. CONCLUSIONS: Embracing the ERAS society recommendations in liver surgery leads to a significant reduction of complications. This outcome justifies the higher cost associated with a well-structured ERAS protocol, as it effectively offsets the expenses of complications.
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Análise Custo-Benefício , Recuperação Pós-Cirúrgica Melhorada , Hepatectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Humanos , Estudos Prospectivos , Masculino , Feminino , Hepatectomia/economia , Hepatectomia/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Laparoscopia/economia , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
PURPOSE: With growing knowledge about ovarian cancer over the last decades, diagnosis, evaluation and treatment of ovarian cancer patients have become highly specialized, and an individually adapted approach should be made in each woman by interdisciplinary cooperation. The present study aims to show the variety and extent of medical specialties involved at our institution according to the European Society of Gynecologic Oncology (ESGO) Quality indicators (QI). METHODS: A woman, diagnosed with high-grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) class IVb was selected for a single case observational study. The observation period (total = 22d) comprised preoperative diagnostic procedures, including imaging, the in-patient stay for cytoreductive surgery, and the postoperative course and case discussion at our interdisciplinary tumor board. Data were obtained by self-reporting and by patient file review. RESULTS: Patient tracking demonstrated an interdisciplinary cooperation of 12 medical specialties [62 physicians (63% male, 37% female)], 8 different types of nursing staff [n = 59 (22% male, 78% female)], and 9 different types of perioperative/administrative staff (n = 23; male 17,4%, female n = 19, 82,6%). Contact with the patient was direct (n = 199; 76%) or without face-to-face interaction (n = 63; 24%). CONCLUSION: The present study demonstrates the high diversity of physicians and the affiliated medical staff, as well as interdisciplinary intersections within teams of a specialized hospital. Matching the ESGO QIs, this report underlines the requirement of an adequate infrastructure for the complex management of advanced ovarian cancer patients. Future prospective studies are warranted to evaluate the specific procedures and actions to optimize the interprofessional and interdisciplinary workflows.
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Neoplasias Ovarianas , Equipe de Assistência ao Paciente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos de Citorredução , Comunicação Interdisciplinar , Relações Interprofissionais , Oncologia , Neoplasias Ovarianas/terapia , Indicadores de Qualidade em Assistência à SaúdeRESUMO
OBJECTIVE: The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch. METHODS: In this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers. Following surgical resection, the transection plane was closed according to the standard of care and manually covered with the sealant patch. As primary endpoint the incidence of CR-POPF up to 30-days postoperatively was evaluated. The secondary endpoints included the assessment of complications and device usability. RESULTS: Among 40 patients after distal pancreatectomy, CR-POPF occurred in 7 (17.5%) up to postoperative day 30. No type C POPF was observed. There was no intraoperative bleeding observed after patch application. CONCLUSION: The results of this international phase II study demonstrate promising results of a new sealant patch regarding the rate of CR-POPF. Randomized studies are now needed to confirm the superiority of the current patch as compared to the best current practice.
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Pancreatectomia , Fístula Pancreática , Humanos , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Pancreatectomia/efeitos adversos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Fatores de Tempo , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: To investigate the value of gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5th edition of the WHO Classification of Digestive System Tumors in a western population. METHODS: This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists. Gd-EOB-enhanced MRI datasets were assessed by two radiologists for qualitative and quantitative imaging features, including imaging features defined in LI-RADS v2018 and area of hepatobiliary phase (HBP) iso- to hyperintensity. RESULTS: The combination of non-rim arterial phase hyperenhancement with non-peripheral portal venous washout was more common in "not otherwise specified" (nos-ST) (88/168, 52%) than other subtypes, in particular macrotrabecular massive (mt-ST) (3/15, 20%), chromophobe (ch-ST) (1/8, 13%), and scirrhous subtypes (sc-ST) (2/9, 22%) (p = 0.035). Macrovascular invasion was associated with mt-ST (5/16, p = 0.033) and intralesional steatosis with steatohepatitic subtype (sh-ST) (28/32, p < 0.001). Predominant iso- to hyperintensity in the HBP was only present in nos-ST (16/174), sh-ST (3/33), and clear cell subtypes (cc-ST) (3/13) (p = 0.031). Associations were found for the following non-imaging parameters: age and sex, as patients with fibrolamellar subtype (fib-ST) were younger (median 44 years (19-66), p < 0.001) and female (4/5, p = 0.023); logarithm of alpha-fetoprotein (AFP) was elevated in the mt-ST (median 397 µg/l (74-5370), p < 0.001); type II diabetes mellitus was more frequent in the sh-ST (20/33, p = 0.027). CONCLUSIONS: Gd-EOB-MRI reproduces findings reported in the literature for extracellular contrast-enhanced MRI and CT and may be a valuable tool for noninvasive HCC subtype differentiation. CLINICAL RELEVANCE STATEMENT: Better characterization of the heterogeneous phenotypes of HCC according to the revised WHO classification potentially improves both diagnostic accuracy and the precision of therapeutic stratification for HCC. KEY POINTS: ⢠Previously reported imaging features of common subtypes in CT and MRI enhanced with extracellular contrast agents are reproducible with Gd-EOB-enhanced MRI. ⢠While uncommon, predominant iso- to hyperintensity in the HBP was observed only in NOS, clear cell, and steatohepatitic subtypes. ⢠Gd-EOB-enhanced MRI offers imaging features that are of value for HCC subtype differentiation according to the 5th edition of the WHO Classification of Digestive System Tumors.
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Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Neoplasias Hepáticas , Humanos , Feminino , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Gadolínio DTPA , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Bile leakage (BL) is a challenging complication after hepatobiliary surgery and liver trauma. Gadolinium ethoxybenzyl (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiopancreatography (MRCP) is used to diagnose BL non-invasively. We assessed the value of Gd-EOB-DTPA-MRCP in the detection of postoperative and post-traumatic BL hypothesizing that exact identification of the leakage site is pivotal for treatment planning and outcome. METHODS: We retrospectively enrolled 39 trauma and postoperative patients who underwent Gd-EOB-DTPA-MRCP for suspected BL. Three readers rated the presence of BL and leakage site (intraparenchymal, central, peripheral ± aberrant or disconnected ducts). Imaging findings were compared to subsequent interventional procedures and their complexity and outcome. RESULTS: BL was detected in Gd-EOB-DTPA-MRCP in 25 of patients and was subsequently confirmed. Sites of BL differed significantly between postoperative (central [58%] and peripheral [42%]) and trauma patients (intraparenchymal [100%]; p < 0.001). Aberrant or disconnected ducts were diagnosed in 8%/26% of cases in the postoperative subgroup. Inter-rater agreement for the detection and localization of BL was almost perfect (Κ = 0.85 and 0.88; p < 0.001). Intraparenchymal BL required significantly less complex interventional procedures (p = 0.002), whereas hospitalization and mortality did not differ between the subgroups (p > 0.05). CONCLUSIONS: Gd-EOB-DTPA-MRCP reliably detects and exactly locates BL in postoperative and trauma patients. Exact localization of biliary injuries enables specific treatment planning, as intraparenchymal leakages, which occur more frequently after trauma, require less complex interventions than central or peripheral leaks in the postoperative setting. As a result of specific treatment based on exact BL localization, there was no difference in the duration of hospitalization or mortality. CLINICAL RELEVANCE STATEMENT: Gd-EOB-DTPA-MRCP is a reliable diagnostic tool for exactly localizing iatrogenic and post-traumatic biliary leakage. Its precise localization helps tailor local therapies for different injury patterns, resulting in comparable clinical outcomes despite varying treatments. KEY POINTS: ⢠Gd-EOB-DTPA-MRCP enables adequate detection and localization of bile leakages in both postoperative and post-traumatic patients. ⢠The site of bile leakage significantly impacts the complexity of required additional interventions. ⢠Intraparenchymal bile leakage is commonly seen in patients with a history of liver trauma and requires less complex interventions than postoperative central or peripheral bile leakages, while hospitalization and mortality are similar.
Assuntos
Doenças Biliares , Neoplasias Hepáticas , Humanos , Colangiopancreatografia por Ressonância Magnética/métodos , Meios de Contraste , Estudos Retrospectivos , Bile , Gadolínio DTPA , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/patologia , Resultado do Tratamento , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Extrahepatic transection of the right hepatic artery and right portal vein before parenchymal dissection is a widely used standard for minimal invasive right hepatectomy. Hereby, hilar dissection represents a technical difficulty. We report our results of a simplified approach in which the hilar dissection is omitted and the line of dissection is defined with ultrasound. METHODS: Patients undergoing minimally invasive right hepatectomy were included. Ultrasound-guided hepatectomy (UGH) was defined by the following main steps: (1) ultrasound-guided definition of the transection line, (2) dissection of the liver parenchyma according to the caudal approach, (3) intraparenchymal transection of the right pedicle and (4) of the right liver vein, respectively. Intra- and postoperative outcomes of UGH were compared to the standard technique. Propensity score matching was performed to adjust for parameters of perioperative risk. RESULTS: Median operative time was 310 min in the UGH group compared to 338 min in the control group (p = 0.013). No differences were observed for Pringle maneuver duration (35 min vs. 25 min; p = ns) nor postoperative transaminases levels (p = ns). There was a trend toward a lower major complication rate in the UGH group (13 vs. 25%) and a shorter median hospital stay (8 days vs. 10 days); however, both being short of statistical significance (p = ns). Bile leak was observed in zero cases of UGH compared to 9 out of 32 cases (28%) for the control group (p = 0.020). CONCLUSIONS: UGH appears to be at least comparable to the standard technique in terms of intraoperative and postoperative outcomes. Accordingly, transection of the right hepatic artery and right portal vein prior to the transection phase can be omitted, at least in selected cases. These results need to be confirmed in a prospective and randomized trial.
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Laparoscopia , Neoplasias Hepáticas , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Estudos Prospectivos , Veias Hepáticas/cirurgia , Laparoscopia/métodosRESUMO
PURPOSE: The present study assesses long-term overall survival (OS) and disease-free survival (DFS) after curative resection for intrahepatic cholangiocarcinoma (ICCA) depending on resection margin (RM) status and lymph node (LN) status. METHODS: Clinical data of all consecutively resected patients with ICCA at a single high-volume center between 2005 and 2018 were collected. Minimum follow-up was 36 months. Perioperative and long-term oncological outcome was assessed. RESULTS: One hundred ninety-two cases were included in the analysis. Thirty- and 90-day-mortality was 5.2% (n = 10) and 10.9% (n = 21). OS was 26 months with 1-, 2-, and 5-year-OS rates of 72%, 53%, and 26%. One-, 2-, and 5-year-DFS rates were 54%, 42%, and 35% (N0 vs. N1: 29 vs. 9 months, p = 0.116). R1 was not found to be an independent risk factor for reduced survival in the overall cohort (p = 0.098). When differentiating according to the LN status, clear resection margins were significantly associated with increased DFS for N0 cases (50 months vs. 9 months, p = 0.004). For N1 cases, no significant difference in DFS was calculated for R0 compared to R1 cases (9 months vs. 9 months, p = 0.88). For N0 cases, clear resection margins > 10 mm were associated with prolonged OS (p = 0.048). CONCLUSION: For N1 cases, there was no significant survival benefit when comparing R0 versus R1, while the complication rate remained high for the extended resection types. In view of merging multimodal treatment, the hilar first concept assesses locoregional LN status for optimal surgical therapy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Margens de Excisão , Hepatectomia , Estudos Retrospectivos , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/patologia , Resultado do Tratamento , Taxa de SobrevidaRESUMO
PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 , 1,633 and 1,205 , respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 vs. 14,578 , p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 , p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Hepatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Fígado , Laparoscopia/métodosRESUMO
The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics.
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Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hormônios Tireóideos/metabolismo , Homeostase , Metabolismo Energético , Metabolismo dos Lipídeos/fisiologiaRESUMO
BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18).
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Neoplasias Colorretais , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos ProspectivosRESUMO
INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).
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Artéria Hepática/cirurgia , Transplante de Fígado , Trombose/prevenção & controle , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Procedimentos de Cirurgia Plástica , Fatores de Risco , Taxa de Sobrevida , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. METHODS: Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. RESULTS: Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. CONCLUSIONS: We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.
Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Estudos de Viabilidade , Humanos , Laparoscopia/efeitos adversos , Cirrose Hepática/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
BACKGROUND: While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. METHODS: We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. RESULTS: One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien-Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B-C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. CONCLUSIONS: We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.
Assuntos
Laparoscopia , Fígado , Procedimentos Cirúrgicos Robóticos , Estudos de Viabilidade , Humanos , Laparoscopia/métodos , Fígado/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In times of critical organ shortage, poor organ pool utilization and increased use of extended-criteria donor (ECD) allografts remain a major problem. Hypothermic oxygenated machine perfusion (HOPE) has emerged as a promising and feasible strategy in ECD liver transplantation (LT). However, potential safety limits regarding the duration of perfusion are yet to be explored. Besides marginal allograft quality (steatosis), prolonged cold ischemia time remains the most important factor for a high number of liver allografts being declined for transplantation. PATIENTS AND METHODS: Two ECD-allografts were each allocated to two recipients, who proved to be unsuitable to receive the assigned allograft upon arrival at the transplant center. The organs were reallocated by Eurotransplant and accepted by our center for two different backup patients. During that time, HOPE was commenced and continued until the recipient hepatectomy was completed. Postoperative allograft function was assessed by serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and International Normalized Ratio. Incidence of early allograft dysfunction (EAD), postoperative complications, and length of hospital stay were analyzed. RESULTS: HOPE was applied for 4 h 35 min and 4 h 20 min, resulting in a total cold preservation time of 17 h 29 min and 15 h 20 min, respectively. Both recipients displayed decreasing serum transaminases and bilirubin levels postoperatively. No EAD or major postoperative complications occurred in either patient. Serum ALT and AST levels were within the normal range at discharge. CONCLUSIONS: Extended HOPE enables the safe extension of preservation time for up to 18 h in human LT. End-ischemic HOPE may significantly improve organ pool utilization, while simultaneously facilitating operating room logistics and preventing organ injury.
Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Idoso , Alanina Transaminase/sangue , Aloenxertos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Isquemia Fria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
PURPOSE: The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. METHODS: In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis. Cases with use of IPM (IPM) and those without use of IPM (no IPM) were then compared regarding intraoperative and postoperative outcomes after propensity score matching (PSM) for surgical difficulty. RESULTS: One hundred fifty-one patients underwent liver resection for HCC at our center and met inclusion criteria. Of these, 73 patients (48%) received IPM with a median duration of 18 min (5-78). One hundred patients (66%) had confirmed liver cirrhosis. In multivariate analysis, patients with large tumors (≥ 3 cm) and difficult tumor locations (segments VII or VIII) were more likely to undergo IPM (OR 1.176, p = 0.043, and OR 3.243, p = 0.001, respectively). After PSM, there were no differences in intraoperative blood transfusion or postoperative complication rates between the IPM and no IPM groups. Neither did we observe any differences in the subgroup analysis for cirrhotic patients. Postoperative serum liver function tests were not affected by the use of IPM. CONCLUSIONS: Based on our findings, we conclude that the use of IPM in minimally invasive liver resection is safe and feasible for patients with HCC, including those with compensated liver cirrhosis.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
PURPOSE: The concept of "textbook outcome" (TO) as composite quality measure depicting the ideal surgical has not yet been defined for patients undergoing major hepatectomy (MH) for perihilar cholangiocarcinoma (PHC). This study sought to propose a uniform definition through a systematic literature review as well as to identify patient- or procedure-related factors influencing TO. METHODS: In this retrospective study, we analyzed all patients undergoing MH for PHC at our department between January 2005 and August 2019. After conducting a systematic literature search, we defined TO as the absence of 90-day mortality and major complications, no hospital readmission within 90 days after discharge, and no prolonged hospital stay (<75. percentile). A binary logistic regression analysis was performed to identify factors influencing TO. RESULTS: Of 283 patients, TO was achieved in 67 (24%) patients. Multivariate analysis revealed that preoperative biliary drainage was associated with a decreased (OR= 0.405, 95% CI: 0.194-0.845, p=0.016) and left-sided-resection (OR= 1.899, 95% CI: 1.048-3.440, p=0.035) with increased odds for TO. Overall survival (OS) and DFS (disease-free survival) did not differ significantly between the outcome groups (OS: p=0.280, DFS: p=0.735). However, there was a trend towards better overall survival, especially in the late course with TO. CONCLUSION: Our analysis proposed a uniform definition of TO after MH for PHC. We identified left hepatectomy as an independent factor positively influencing TO. In patients where both right- and left-sided resections are feasible, this underlines the importance of a careful selection of patients who are scheduled for right hepatectomy.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Tumor de Klatskin/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Robotic-assisted pancreatic surgery is limited to specialized high-volume centers and selected patient cohorts. Especially for patients with a history of previous abdominal surgeries, the standard procedure remains open surgery due to the fear of complications caused by abdominal adhesions. METHODS: Clinical data of all consecutive patients undergoing robotic-assisted pancreatic surgery using the daVinci Xi system (Intuitive Surgical) at our center (Department of Surgery, Universitätsmedizin Berlin, Germany) were collected prospectively and further analyzed from October 2017 to October 2020. Prior abdominal surgeries were specified according to the surgical approach and localization. In univariate and multivariate analysis, baseline and perioperative parameters of patients with a history of prior abdominal surgeries (PS) were compared to those of patients with no history of prior abdominal surgeries (NPS). RESULTS: Out of 131 patients undergoing robotic-assisted pancreatic surgery, 62 (47%) had a history of abdominal surgery. Previous procedures included most often appendectomy (32%) followed by gynecological surgery (29%) and cholecystectomy (27%). 24% of PS had received multiple surgeries prior to the robotic-assisted pancreatic resections. Baseline characteristics and comorbidities were comparable between the groups. We did not detect differences in the duration of surgery (262 min), conversion rates (10%), and postoperative complications between NPS and PS. Postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and in-house mortality showed no significant differences between the two groups. Multivariate analysis revealed male sex and high BMI as a potential predictive factor for severe postoperative complications. Other characteristics like the type of pancreatic resection, ASA, and underlying malignancy showed no difference in the multivariable analysis. CONCLUSIONS: We propose robotic-assisted pancreatic surgery to be safe and feasible for patients with a history of minor prior abdominal surgery. Hence, each patient should individually be evaluated for a minimally invasive approach regardless of a history of previous operations.