Chemotherapy Regimen Predicts Steatohepatitis and an Increase in 90-Day Mortality After Surgery for Hepatic Colorectal Metastases

2006 ◽  
Vol 24 (13) ◽  
pp. 2065-2072 ◽  
Author(s):  
Jean-Nicolas Vauthey ◽  
Timothy M. Pawlik ◽  
Dario Ribero ◽  
Tsung-Teh Wu ◽  
Daria Zorzi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Resection ◽  
Odds Ratio ◽  
Hepatic Injury ◽  
Chemotherapy Regimen ◽  
Postoperative Outcome ◽  
Colorectal Metastases ◽  
Hepatic Surgery ◽  
Perioperative Outcome ◽  
Pathologic Analysis

Purpose Chemotherapy before resection of hepatic colorectal metastases (CRM) may cause hepatic injury and affect postoperative outcome. Patients and Methods Four hundred six patients underwent hepatic resection of CRM between 1992 and 2005. Pathologic review of the nontumorous liver was performed using established criteria for steatosis, steatohepatitis, and sinusoidal injury. The effect of chemotherapy and liver injury on perioperative outcome was analyzed. Results One hundred fifty-eight patients (38.9%) received no preoperative chemotherapy, whereas 248 patients (61.1%) did. The median duration of chemotherapy was 16 weeks (range, 2 to 70 weeks). Chemotherapy consisted of fluoropyrimidine-based regimens (fluorouracil [FU] alone, 15.5%; irinotecan plus FU, 23.1%; and oxaliplatin plus FU, 19.5%) and other therapy (3.0%). On pathologic analysis, 36 patients (8.9%) had steatosis, 34 (8.4%) had steatohepatitis, and 22 (5.4%) had sinusoidal dilation. Oxaliplatin was associated with sinusoidal dilation compared with no chemotherapy (18.9% v 1.9%, respectively; P < .001; odds ratio [OR] = 8.3; 95% CI, 2.9 to 23.6). In contrast, irinotecan was associated with steatohepatitis compared with no chemotherapy (20.2% v 4.4%, respectively; P < .001; OR = 5.4; 95% CI, 2.2 to 13.5). Patients with steatohepatitis had an increased 90-day mortality compared with patients who did not have steatohepatitis (14.7% v 1.6%, respectively; P = .001; OR = 10.5; 95% CI, 2.0 to 36.4). Conclusion Steatohepatitis is associated with an increased 90-day mortality after hepatic surgery. In patients with hepatic CRM, the chemotherapy regimen should be carefully considered because the risk of hepatotoxicity is significant.

Preoperative transcatheter arterial chemoembolization (TACE) and chemotherapy for hepatic colorectal metastases: Impact on hepatic histology and postoperative outcome

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15090-e15090
Author(s):  
Q. Lu ◽  
A. Zhao ◽  
L. Shen
Keyword(s):  
Preoperative Chemotherapy ◽  
Median Duration ◽  
Chemotherapy Regimen ◽  
Postoperative Outcome ◽  
Colorectal Metastases ◽  
Preoperative Treatment ◽  
Chemotherapy Group ◽  
Tace Group ◽  
Pathologic Analysis ◽  
Hepatic Histology

e15090 Background: The objective was to evaluate the effect of preoperative administration of TACE and chemotherapy on hepatic injury and on postoperative outcome in patients with colorectal liver metastases (CRM) Methods: Seventy seven patients underwent hepatic resection for CRM between January 1999 and December 2007 were evaluated. Pathologic review of the non-tumorous liver was performed using established criteria for steatosis, steatohepatitis, and sinusoidal dilation. The effect of two different treatment and hepatotoxicity on postoperative outcome was analyzed. Results: 40 patients (51.9%) received no preoperative treatment, where 27 patients (35.0%) received preoperative chemotherapy, 10 patients (12.9%) performed TACE before resection. The median duration of TACE group was 4.5 months (range, 1–6 months), where the median duration of chemotherapy group was 5 cycles (range, 2–9 cycles). Chemotherapy regimen consisted of oxalipaltin plus FU (29.9%), or irinotecan plus FU (5.2%). On pathologic analysis, 36 patients (46.7%) had steatosis, 24 (31.1%) had sinusoidal dilation, and 8 (10.3%) had steatohepatitis. TACE was associated with steatosis, steatohepatosis and postoperative complication, when compared with no chemotherapy (all p<0.05).Among chemotherapy group,Oxaliplatin was associated with steatohepatitis compared with no preoperative treatment (13.0% v 0%, respectively; p<0.05). Irinotecan was associated with steatohepatitis compared with no preoperative treatment (50% v 0%, respectively; p=0.0006). Patients with preoperative chemotherapy had increased steatohepatitis compared with no treatment group (18.5% v 0%, respectively, p=0.0008), the postoperative morbility rate in preoperative chemotherapy (25.9%) was double that of the no-chemotherapy (12.5%), but this difference was not statistically significant (p=0.20). Preoperative chemotherapy was also not associated with 90-day mortality. Conclusions: Preoperative TACE treatment may cause pathological liver injury, and increase postoperative morbility after hepatic surgery. The standard preoperative chemotherapy regimen with Oxaliplatin or Irinotecan may increase steatohepatis. No significant financial relationships to disclose.

Impact of obesity on postoperative outcome of hepatic resection for colorectal metastases

Surgery ◽  
2015 ◽  
Vol 158 (6) ◽  
pp. 1521-1529 ◽  
Author(s):  
Serena Langella ◽  
Nadia Russolillo ◽  
Fabio Forchino ◽  
Roberto Lo Tesoriere ◽  
Marco D'Eletto ◽  
...  
Keyword(s):  
Hepatic Resection ◽  
Postoperative Outcome ◽  
Colorectal Metastases

scholarly journals Optimal Morphologic Response to Preoperative Chemotherapy: An Alternate Outcome End Point Before Resection of Hepatic Colorectal Metastases

2012 ◽  
Vol 30 (36) ◽  
pp. 4566-4572 ◽  
Author(s):  
Junichi Shindoh ◽  
Evelyne M. Loyer ◽  
Scott Kopetz ◽  
Piyaporn Boonsirikamchai ◽  
Dipen M. Maru ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Preoperative Chemotherapy ◽  
Odds Ratio ◽  
Chemotherapy Regimen ◽  
Independent Predictor ◽  
Colorectal Metastases ◽  
Optimal Response ◽  
End Point ◽  
Morphologic Response ◽  
Response Group

Purpose The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response. Patients and Methods The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis. Results An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response. Conclusion Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM.

scholarly journals Acute liver injury associated with Oxyfluorfen toxicity

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110004
Author(s):  
Selladurai Pirasath ◽  
Ayshanie Gayanthika Samasundara Mudiyanselage ◽  
Manosha Harshani Seneviratne
Keyword(s):  
Sri Lanka ◽  
Liver Injury ◽  
Young Woman ◽  
Broad Spectrum ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Toxic Dose ◽  
Acute Hepatic Injury ◽  
Haem Biosynthesis ◽  
Spectrum Control

Oxyfluorfen is a phenoxyphenyl-type herbicide which is used for broad-spectrum control of broadleaf and grassy weeds. Ingestion of toxic dose of oxyfluorfen can be fatal among animals. However, toxicity to humans are rare in literature. The alterations in haem biosynthesis (anaemia) and in liver are the primary toxic effects. There are no specific antidotes and none of the current treatments have proven efficacious till date. Therefore, prevention needs to be the utmost priority, and on exposure, aggressive decontamination should be initiated. Herein, we described an oxyfluorfen toxicity with acute hepatic injury in a young woman who presented with a deliberate self-harming with an oxyfluorfen poisoning in Sri Lanka.

Lipopolysaccharide andd-galactosamine-induced hepatic injury is mediated by TNF-α and not by Fas ligand

2000 ◽  
Vol 278 (5) ◽  
pp. R1196-R1201 ◽  
Author(s):  
Michael D. Josephs ◽  
F. Rena Bahjat ◽  
Kunitaro Fukuzuka ◽  
Riadh Ksontini ◽  
Carmen C. Solorzano ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Injury ◽  
Fas Ligand ◽  
Nuclear Dna ◽  
Spontaneous Mutation ◽  
Hepatic Expression ◽  
Soluble Fas ◽  
Tnf Α ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-α and Fas ligand (FasL) are trimeric proteins that induce apoptosis through similar caspase-dependent pathways. Hepatocytes are particularly sensitive to inflammation-induced programmed cell death, although the contribution of TNF-α and/or FasL to this injury response is still unclear. Here, we report that d-galactosamine and lipopolysaccharide-induced liver injury in C57BL/6 mice is associated with increased hepatic expression of both TNF-α and FasL mRNA. Pretreatment of mice with a TNF-binding protein improved survival, reduced plasma aspartate aminotransferase concentrations, and attenuated the apoptotic liver injury, as determined histologically and by in situ 3′ OH end labeling of fragmented nuclear DNA. In contrast, pretreatment of mice with a murine-soluble Fas fusion protein (Fasfp) had only minimal effect on survival, and apoptotic liver injury was either unaffected or exacerbated depending on the dose of Fasfp employed. Similarly, mice with a spontaneous mutation in FasL (B6Smn.C3H- Faslgldderived from C57BL/6) were equally sensitive tod-galactosamine/lipopolysaccharide-induced shock. We conclude that the shock and apoptotic liver injury afterd-galactosamine/lipopolysaccharide treatment are due primarily to TNF-α release, whereas increased FasL expression appears to contribute little to the mortality and hepatic injury.

scholarly journals Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China

2021 ◽  
Author(s):  
Ling Ye ◽  
Chengxian Guo ◽  
Zeying Feng ◽  
Longjian Huang ◽  
Chengjun Guo ◽  
...  
Keyword(s):  
Intensive Care ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Sodium Succinate ◽  
Drug Combinations ◽  
Fat Emulsion ◽  
Drug Induced ◽  
Multiple Drugs ◽  
Enzyme Metabolism ◽  
Long Chain

Abstract Purpose Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). We also collated drug combinations that may affect CYP enzyme metabolism, which may be one of the mechanisms that lead to DILI. Results A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while children’s hepatic injury types were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the assessment by the RUCAM, in newborns, the drugs that were most considered to cause or associated with hepatic injury comprised medium and long chain fat emulsion (17%), sodium glycerophosphate (12%) and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%) and meropenem (8%) are the primary culprit of DILI in children. Drug combinations that may affect CYP enzyme metabolism frequently seen in neonates are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%) and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%) and diazepam + omeprazole (15.3%). Conclusions The drugs that have been found to have hepatotoxicity (meropenem, medium and long chain fat emulsion, ibuprofen.etc.) are also related to DILI in newborns and children. When giving these drugs to newborns and children, physicians need to be more cautious. Also, pay attention to the effect on CYP 450 enzymes when using multiple drugs at the same time.

scholarly journals Long-Term Outcomes of Hepatic Resection versus Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Propensity Score-Matching Study

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Toshimi Kaido ◽  
Satoshi Morita ◽  
Sachiko Tanaka ◽  
Kohei Ogawa ◽  
Akira Mori ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Propensity Score ◽  
Hepatic Resection ◽  
Propensity Score Matching ◽  
Odds Ratio ◽  
Living Donor ◽  
Survival Rates ◽  
Controlled Study ◽  
Recurrence Rates

Hepatic resection (HR) and liver transplantation (LT) are surgical treatment options for hepatocellular carcinoma (HCC). However, it is clinically impossible to perform a randomized, controlled study to determine the usefulness of these treatments. The present study compared survival rates and recurrence rates of HR versus living donor LT (LDLT) for HCC by using the propensity score method. Between January 1999 and August 2012, 936 patients (732 HR, 204 LDLT) underwent surgical therapy for HCC in our center. Using the propensity score matching, 80 well-balanced patients were defined. The 1- and 5-year overall survival rates were 90% and 53% in the HR group and 82% and 63% in the LT group, respectively. They were not significantly different between the two groups. The odds ratio estimated using the propensity score matching analysis was 0.842 (P=0.613). The 1- and 5-year recurrence rates were significantly lower in the LT group (9% and 21%) than in the HR group (43% and 74%) (P<0.001), and the odds ratio was 0.214 (P=0.001). In conclusion, HR should be considered a valid alternative to LDLT taking into consideration the risk for the living donor based on the results of this propensity score-matching study.

Chemotherapy Near the End of Life in Onco–Hematological Adult Patients

2020 ◽  
Vol 37 (8) ◽  
pp. 641-647
Author(s):  
Marina Sánchez-Cuervo ◽  
Lorena García-Basas ◽  
Esther Gómez de Salazar-López de Silanes ◽  
Cristina Pueyo-López ◽  
Teresa Bermejo-Vicedo
Keyword(s):  
Observational Study ◽  
End Of Life ◽  
End Of Life Care ◽  
Odds Ratio ◽  
Chemotherapy Regimen ◽  
Female Gender ◽  
Tertiary Hospital ◽  
Life Care ◽  
Oncological Patients ◽  
Scarce Data

Objective: The use of chemotherapy near the end of life is not advisable. There are scarce data in Europe but shows signs of aggressiveness. We designed this study to analyze the proportion of onco–hematological patients receiving chemotherapy within their last 2 weeks of life as well as starting a new chemotherapy regimen in the 30 days prior to death. Methods: A retrospective observational study was conducted in a tertiary hospital. Adults who died of an onco-hematological neoplasia while hospitalized between April 2017 and March 2018 were included. We assessed the use of chemotherapy over the course of the last 14 days of life, defined as the administration of at least one dose of chemotherapy. We also examined the proportion of patients starting a new chemotherapy regimen in the last 30 days of life. Results: A total of 298 inpatients died in the Hematology and Oncology units. During the last 14 days, 28.2% (n = 11) of hematological and 26.3% (n = 68) of oncological patients received chemotherapy; the overall rate was 26.5% (n = 79). Furthermore, the proportion of patients starting a new chemotherapy regimen in the last 30 days of life was high (20.5% and 20.8%, respectively). Female gender (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.18-3.35) and age <45 (OR = 2.68, 95% CI = 1.05-6.88) were associated with higher rates of chemotherapy. Conclusion: The proportion of patients receiving chemotherapy in the last 14 days of life was high, as well as the proportion of patients starting a new regimen in their last 30 days. This was indicative of excessive aggressiveness at the end-of-life care.

Sign in / Sign up

Export Citation Format

Share Document