RESUMO
Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA.
Assuntos
Neoplasias dos Ductos Biliares , Proliferação de Células , Colangiocarcinoma , Transição Epitelial-Mesenquimal , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Humanos , Transição Epitelial-Mesenquimal/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Linhagem Celular Tumoral , Sulfotransferases/metabolismo , Sulfotransferases/genética , Sulfotransferases/deficiência , Sulfoglicoesfingolipídeos/metabolismo , Sistemas CRISPR-Cas , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologiaRESUMO
BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.
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Ácidos e Sais Biliares , Neoplasias dos Ductos Biliares , Fatores de Crescimento de Fibroblastos , Hepatectomia , Tumor de Klatskin , Regeneração Hepática , Humanos , Masculino , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Fatores de Crescimento de Fibroblastos/sangue , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/sangue , Feminino , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/sangue , Pessoa de Meia-Idade , Regeneração Hepática/fisiologia , Idoso , Estudos de Casos e Controles , Fígado/metabolismo , Fígado/cirurgiaRESUMO
BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia. METHODS: Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma (n = 10 without cachexia, n = 20 cachectic without inflammation (CRP < 10 mg/L), n = 10 cachectic with inflammation (CRP ≥ 10 mg/L). L3-CT scans were analysed to assess body composition based on validated thresholds in Hounsfield units (HU). Muscle sections were stained with Oil-Red O and H&E to assess general lipid accumulation and atrophy. Untargeted lipidomic analyses were performed on laser-microdissected myotubes using LC-MS/MS. The spatial distribution of intramyocellular lipids with differential abundance between groups was visualized by mass-spectrometry imaging. Genes coding for inflammation markers and enzymes involved in de novo ceramide synthesis were studied by qPCR. RESULTS: Muscle radiation attenuation was lower in cachectic patients with inflammation (median 24.3 [18.6-30.8] HU) as compared with those without inflammation (34.2 [29.3-38.7] HU, P = 0.033) or no cachexia (37.4 [33.9-42.9] HU, P = 0.012). Accordingly, intramyocellular lipid content was lower in non-cachectic patients (1.9 [1.6-2.1]%) as compared with those with cachexia with inflammation (5.5 [4.5-7.3]%, P = 0.002) or without inflammation (4.8 [2.6-6.0]%, P = 0.017). Intramyocellular lipid accumulation was associated with both local IL-6 mRNA levels (rs = 0.57, P = 0.015) and systemic CRP levels (rs = 0.49, P = 0.024). Compared with non-cachectic subjects, cachectic patients had a higher relative abundance of intramyocellular glycerophospholipids and a lower relative abundance of glycerolipids. Furthermore, increases in several intramyocellular lipids such as SM(d36:1), PC(34:1), and TG(48:1) were found in cachectic patients with inflammation and correlated with specific cachexia features. Altered intramyocellular lipid species such as PC(34:1), LPC(18:2), and TG(48:1) showed an uneven distribution in muscle sections of cachectic and non-cachectic patients, with areas featuring abundance of these lipids next to areas almost devoid of them. CONCLUSIONS: Intramyocellular lipid accumulation in patients with cachexia is associated with both local and systemic inflammation, and characterized by changes in defined lipid species such as glycerolipids and glycerophospholipids.
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Caquexia , Inflamação , Metabolismo dos Lipídeos , Neoplasias Pancreáticas , Humanos , Caquexia/etiologia , Caquexia/metabolismo , Inflamação/metabolismo , Masculino , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/metabolismo , Feminino , Idoso , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Lipídeos/análise , Composição CorporalRESUMO
BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.
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Embolização Terapêutica , Hepatectomia , Veias Hepáticas , Neoplasias Hepáticas , Regeneração Hepática , Veia Porta , Humanos , Masculino , Feminino , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Regeneração Hepática/fisiologia , Idoso , Hepatectomia/métodos , Taxa de Sobrevida , Análise de Sobrevida , AdultoRESUMO
PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.
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Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Qualidade de Vida , Humanos , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Idoso , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Resultado do TratamentoRESUMO
Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians', students', and patients' assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients' HRQoL. Correlation was assessed through Pearson's and Kendall's τb coefficients. Physicians' and patients' assessments correlated for one out of six of the functional and a third of the symptom scores. Students' and patients' assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients' symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients' symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL.
Assuntos
Neoplasias Gastrointestinais , Médicos , Qualidade de Vida , Estudantes de Medicina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Médicos/psicologia , Inquéritos e Questionários , Estudantes de Medicina/psicologia , Adulto , Neoplasias Gastrointestinais/psicologia , Trato Gastrointestinal Superior/patologia , Idoso , PercepçãoRESUMO
(1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients.
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BACKGROUND: Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation. METHODS: N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized. Receptor activation was studied in cell-free and cell-based assays. MBSCs were quantified in mesenteric and portal blood and bile of patients undergoing pancreatic surgery. RESULTS: MBSCs were activating ligands of TGR5 as evidenced by recruitment of Gsα protein, activation of a cAMP-driven reporter, and diminution of lipopolysaccharide-induced cytokine release from macrophages. Intestine-enriched and liver-enriched FXR isoforms were both activated by MBSCs, provided that a bile salt importer was present. The affinity of MBSCs for TGR5 and FXR was not superior to host-derived bile salt conjugates. Individual MBSCs were generally not detected (ie, < 2.5 nmol/L) in human mesenteric or portal blood, but Leu-variant and Phe-variant were readily measurable in bile, where MBSCs comprised up to 213 ppm of biliary bile salts. CONCLUSIONS: MBSCs activate the cell surface receptor TGR5 and the transcription factor FXR and are substrates for intestinal (apical sodium-dependent bile acid transporter) and hepatic (Na+ taurocholate co-transporting protein) transporters. Their entry into the human circulation is, however, nonsubstantial. Given low systemic levels and a surplus of other equipotent bile salt species, the studied MBSCs are unlikely to have an impact on enterohepatic TGR5/FXR signaling in humans. The origin and function of biliary MBSCs remain to be determined.
Assuntos
Ácidos e Sais Biliares , Receptores Citoplasmáticos e Nucleares , Receptores Acoplados a Proteínas G , Humanos , Bile/química , Ácidos e Sais Biliares/farmacologia , Ácidos e Sais Biliares/metabolismo , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.
Assuntos
Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Seguimentos , Morte Encefálica , Sobrevivência de Enxerto , Perfusão/métodosRESUMO
BACKGROUND: Differentiation between adenomas and carcinomas of the ampulla of Vater is crucial for therapy and prognosis. This was a systematic review of the literature on the accuracy of diagnostic modalities used to differentiate between benign and malignant ampullary tumours. METHODS: A literature search was conducted in PubMed, Embase, CINAHL, and the Cochrane Library. Studies were included if they reported diagnostic test accuracy information among benign and malignant ampullary tumours, and used pathological diagnosis as the reference standard. Risk of bias was assessed using Quality Assessment on Diagnostic Accuracy Studies (QUADAS) 2 and QUADAS-C. RESULTS: Ten studies comprising 397 patients were included. Frequently studied modalities were (CT; 2 studies), endoscopic ultrasonography (EUS; 3 studies), intraductal ultrasonography (IDUS; 2 studies), and endoscopic forceps biopsy (3 studies). For CT, the reported sensitivity for detecting ampullary carcinoma was 44 and 95%, and the specificity 58 and 60%. For EUS, the sensitivity ranged from 63 to 89% and the specificity between 50 and 100%. A sensitivity of 88 and 100% was reported for IDUS, with a specificity of 75 and 93%. For forceps biopsy, the sensitivity ranged from 20 to 91%, and the specificity from 75 to 86%. The overall risk of bias was scored as moderate to poor. Data were insufficient for meta-analysis. CONCLUSION: To differentiate benign from malignant ampullary tumours, EUS and IDUS seem to be the best diagnostic modalities. Sufficient high-quality evidence, however, is lacking.
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Carcinoma , Humanos , Biópsia , Estudos Transversais , Endoscopia , EndossonografiaRESUMO
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor and usually associated with a poor oncological prognosis. The current gold standard is the surgical resection of the tumor with subsequent adjuvant therapy. However, in case of irresectability e.g. in case of liver cirrhosis, a palliative treatment regime is conducted.This report demonstrates the case of an irresectable iCCA in liver cirrhosis due to primary sclerosing cholangitis (PSC) treated by living-donor liver transplantation (LDLT) facilitated by minimal invasive donor hepatectomy. No postoperative complications were observed in the donor and the donor was released on the 6th postoperative day. Further, after a follow-up of 1.5 years, no disease recurrence was detected in the recipient.According to the recent international literature, liver transplantation can be evaluated in case of small solitary iCCA (< 3 cm) in cirrhosis. Less evidence is provided for transplantation in advanced tumors which are surgically not resectable due to advanced liver disease or infiltration of major vessels, however some reports display adequate long-term survival after strict patient selection. The selection criteria comprise the absence of distant metastases and locoregional lymph node metastases as well as partial remission or stable disease after neoadjuvant chemotherapy. Due to no established graft allocation for iCCA in Germany, LDLT is currently the best option to realize transplantation in these patients. Developments in the last decade indicate that LDLT should preferentially be performed in minimal invasive manner (laparoscopic or robotic) as this approach is associated with less overall complications and a shorter hospitalization. The presented case illustrates the possibilities of modern surgery and the introduction of transplant oncology in the modern therapy of patients combining systemic therapy, surgical resection and transplantation to achieve optimal long-term results in patients which were initially indicated for palliative treatment.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite Esclerosante , Laparoscopia , Transplante de Fígado , Humanos , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/cirurgia , Doadores Vivos , Recidiva Local de NeoplasiaRESUMO
Minimal-invasive resection of the esophagus for esophageal cancer has led to a relevant decrease in postoperative morbidity. Postoperatively, patients still suffer from surgical and adjuvant therapy-related symptoms impairing nutrition and quality of life. The aim of this study was to evaluate the nutritional status and associated symptoms six months after esophagectomy. Patients who attended follow-up examination six months after minimal-invasive esophagectomy were included. Blood and fecal tests, quality of life surveys (QLQ-C30 and QLQ-OG25) and nutritional risk screening (NRS) were performed. Twenty-four patients participated. The mean weight loss was 11 kg. A significant decrease in vitamin B12 (737 to 467 pg/mL; p = 0.033), ferritin (302 to 126 ng/mL; p = 0.012) and haptoglobin (227 to 152 mg/dL; p = 0.025) was found. In total, 47% of the patients had an impaired pancreatic function (fecal elastase < 500 µg/g). Physical (72 to 58; p = 0.034) and social functioning (67 to 40; p = 0.022) was significantly diminished, while self-reported global health status remained stable (52 to 54). The number of patients screened and found to be in need of nutritional support according to NRS score decreased slightly (59% to 52%). After MIE, patients should be meticulously monitored for nutritional status after surgery.
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BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA. METHODS: All patients with pCCA who underwent curative-intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan-Meier analysis to evaluate oncological risk factors in the study cohort. RESULTS: BC was frequently altered in patients undergoing curative-intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien-Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no-sarcopenia, 21 months vs. 32 months, p = 0.048 log rank). CONCLUSIONS: BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.
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Neoplasias dos Ductos Biliares , Composição Corporal , Tumor de Klatskin , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tumor de Klatskin/cirurgia , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Tumor de Klatskin/complicações , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Idoso , Fatores de Risco , Sarcopenia/complicações , Hepatectomia/efeitos adversos , Índice de Massa Corporal , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS: Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS: Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION: In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.
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Neoplasias dos Ductos Biliares , Colangite , Fígado Gorduroso , Tumor de Klatskin , Cirrose Hepática Biliar , Falência Hepática , Neoplasias Hepáticas , Humanos , Idoso , Tumor de Klatskin/cirurgia , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/cirurgia , Complicações Pós-Operatórias , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Colangite/complicações , Colangite/cirurgia , Neoplasias dos Ductos Biliares/complicações , Estudos RetrospectivosRESUMO
Intrahepatic cholangiocarcinoma is a common primary liver tumor with limited treatment options and poor prognosis. Changes in body composition (BC) have been shown to affect the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC and clinical and oncological outcomes in patients with iCCA. All patients with iCCA who had surgery from 2010 to 2022 at our institution were included. We used CT scans and 3D Slicer software to assess BC and conducted logistic regressions as well as Cox regressions and Kaplan-Meier analyses to investigate associations between BC and clinical variables with focus on postoperative complications and oncological outcomes. BC was frequently altered in iCCA (n = 162), with 53.1% of the patients showing obesity, 63.2% sarcopenia, 52.8% myosteatosis, 10.1% visceral obesity, and 15.3% sarcopenic obesity. The multivariate analysis showed no meaningful association between BC and perioperative complications. Myosteatosis was associated with reduced overall survival (OS) in iCCA patients (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016 log rank). Further, the subgroup analysis revealed a notable effect in the subset of R0-resected patients (myosteatosis vs. non-myosteatosis, 18 vs. 32 months, p = 0.025) and patients with nodal metastases (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016). While altered BC is not associated with perioperative outcomes in iCCA, myosteatosis emerges as a prognostic factor for reduced OS in the overall and sub-populations of resected patients.