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Chemotherapy Associated Liver Injury

Aiman Obed, Anwar Jarrad, Abdalla Bashir
BACKGROUND Associated Liver Partition and Portal vein ligation with Staged hepatectomy (ALPPS) leads to rapid hepatic hypertrophy and decreases incidence of post-hepatectomy liver failure in patients with a marginal future liver remnant. Various procedural ALPPS modifications were previously described. Here, we present the first case of a new ALPPS modification, carrying out a left hepatic trisectionectomy with segment 1. CASE REPORT We present the case of a 36-year-old woman with locally advanced sigmoid adeno-carcinoma and extensive left liver metastases extending to segment V and VIII, who received state-of-the-art systemic conversion chemotherapy...
October 19, 2016: American Journal of Case Reports
Norio Kubo, Kenichiro Araki, Hiroyuki Kuwano, Ken Shirabe
The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines...
August 14, 2016: World Journal of Gastroenterology: WJG
Arnaud Monier, Boris Guiu, Rafael Duran, Serge Aho, Pierre Bize, Pierre Deltenre, Vincent Dunet, Alban Denys
OBJECTIVES: To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. METHODS: In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups...
July 19, 2016: European Radiology
Sébastien Héritier, Jean-François Emile, Mohamed-Aziz Barkaoui, Caroline Thomas, Sylvie Fraitag, Sabah Boudjemaa, Florence Renaud, Anne Moreau, Michel Peuchmaur, Catherine Chassagne-Clément, Frédérique Dijoud, Valérie Rigau, Despina Moshous, Anne Lambilliotte, Françoise Mazingue, Kamila Kebaili, Jean Miron, Eric Jeziorski, Geneviève Plat, Nathalie Aladjidi, Alina Ferster, Hélène Pacquement, Claire Galambrun, Laurence Brugières, Guy Leverger, Ludovic Mansuy, Catherine Paillard, Anne Deville, Corinne Armari-Alla, Anne Lutun, Marion Gillibert-Yvert, Jean-Louis Stephan, Fleur Cohen-Aubart, Julien Haroche, Isabelle Pellier, Frédéric Millot, Brigitte Lescoeur, Virginie Gandemer, Christine Bodemer, Roger Lacave, Zofia Hélias-Rodzewicz, Valérie Taly, Frédéric Geissmann, Jean Donadieu
PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Fernando A Alvarez, Rodrigo Sanchez Claria, Sebastian Oggero, Eduardo de Santibañes
Liver resection is the treatment of choice for patients with colorectal liver metastases (CLM). However, major resections are often required to achieve R0 resection, which are associated with substantial rates of morbidity and mortality. Maximizing the amount of residual liver gained increasing significance in modern liver surgery due to the high incidence of chemotherapy-associated parenchymal injury. This fact, along with the progressive expansion of resectability criteria, has led to the development of a surgical philosophy known as "parenchymal-sparing liver surgery" (PSLS)...
June 27, 2016: World Journal of Gastrointestinal Surgery
Nadia Russolillo, Serena Langella, Serena Perotti, Roberto Lo Tesoriere, Fabio Forchino, Alessandro Ferrero
BACKGROUND: The aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI). METHODS: Patients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered. RESULTS: 166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria...
July 2016: International Journal of Surgery
Fernando Bessone, Marcelo Gabriel Roma
Ursodeoxycholic acid (UDCA) is the first choice medication for most cholestatic hepatopathies, due to its capability to counteract inflammation and bile-acid-induced liver damage, two common features in cholestasis. However, UDCA is usually contraindicated in obstructive cholestasis, due to the alleged risk of biliary integrity disruption due to its choleretic effect. We report on an 83-year-old man with an unsuspected malignant biliary obstruction who received moderate doses of UDCA (8-12 mg/kg/day) for 5 weeks, because the preliminary evidence suggested he had chemotherapy-induced cholestasis...
May 2016: Annals of Hepatology
Dominique-Charles Valla, Dominique Cazals-Hatem
Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be associated with a partial or complete occlusion of small hepatic veins, hence the previous denomination of hepatic veno-occlusive disease (VOD). Exposure to certain exogenous toxins appears to be specific to this condition and is frequently included in its definition. Typical histopathological features of SOS in a liver biopsy specimen are presented in the text...
September 2016: Clinics and Research in Hepatology and Gastroenterology
Michael A White, Yuman Fong, Gagandeep Singh
Chemotherapy can cause liver injury, which should be considered when planning for safe surgical hepatic resections. This article reviews the pertinent clinical findings and applications for surgeons to take into account in evaluating patients for hepatic resection with liver injury secondary to chemotherapy. A selection of the pertinent literature discussing types of chemotherapy-associated hepatotoxicities, mechanisms of injury, methods for identification of liver injury, and impact on surgical outcomes is discussed...
April 2016: Surgical Clinics of North America
J Martins, H Alexandrino, R Oliveira, M A Cipriano, D Falcão, L Ferreira, R Martins, M Serôdio, M Martins, J G Tralhão, L Prado e Castro, F Castro E Sousa
INTRODUCTION: Advances in neoadjuvant chemotherapy (NCT) have allowed surgical treatment in otherwise unresectable patients with colorectal liver metastases (CRLM). It is well known that NCT induces liver lesions such as sinusoidal obstruction syndrome (SOS) and steatohepatitis (SH). However, whether it affects postoperative morbidity remains controversial. The aim of this study was both to evaluate the impact of NCT on liver parenchyma and postoperative morbidity, and to identify preoperative predictive markers for liver injury...
May 2016: European Journal of Surgical Oncology
Qin Sun, Qing Zhang, Jin Gu, Wen-Wen Sun, Peng Wang, Chong Bai, He-Ping Xiao, Wei Sha
PURPOSE: Antituberculosis drug-induced liver injury (ATDILI) is one of the most deleterious side effects associated with chemotherapy against tuberculosis (TB). In this study, our objective was to determine the incidence, risk factors, and management of ATDILI and analyze its impact on the treatment outcome in patients receiving standard anti-TB chemotherapy. METHODS: A prospective cohort study of ATDILI prevalence was conducted in 938 enrolled patients of the 1426 TB cases in Shanghai from March 2011 to September 2012...
August 2016: Pharmacoepidemiology and Drug Safety
Andrea Janz Moreira, Raquel Ordoñez, Carlos Thadeu Cerski, Jaqueline Nascimento Picada, Andrés García-Palomo, Norma Possa Marroni, Jose L Mauriz, Javier González-Gallego
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide because of its high incidence, its metastatic potential and the low efficacy of conventional treatment. Inactivation of apoptosis is implicated in tumour progression and chemotherapy resistance, and has been linked to the presence of endoplasmic reticulum stress. Melatonin, the main product of the pineal gland, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects in HCC cells, but these effects still need to be confirmed in animal models...
2015: PloS One
Naoto Nishigori, Masanori Matsumoto, Fumikazu Koyama, Masaki Hayakawa, Kinta Hatakeyayama, Saiho Ko, Yoshihiro Fujimura, Yoshiyuki Nakajima
Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients...
2015: PloS One
Maximilian Jara, Jan Bednarsch, Maciej Malinowski, Johann Pratschke, Martin Stockmann
PURPOSE: Chemotherapy-associated liver injury of patients undergoing therapy for colorectal liver metastases stimulates concerns on surgical safety. No common guidelines for the optimal timing of liver surgery after the application of systemic chemotherapy (chemotherapy-free interval) have been established and effects on individual liver function remain unexplored. METHODS: Maximum liver function capacity (LiMAx) and indocyanine green plasma disappearance rate (ICG-PDR) were measured in 20 patients with colorectal cancer receiving adjuvant oxaliplatin-based chemotherapy (OBC) prior to the first and after the last treatment course as well as 4 and 8 weeks thereafter...
February 2016: Langenbeck's Archives of Surgery
Justin D Schumacher, Grace L Guo
Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A...
November 15, 2015: Toxicology and Applied Pharmacology
Wei Geng, Chung-Mau Lo, Kevin T P Ng, Chang-Chun Ling, Xiang Qi, Chang-Xian Li, Yuan Zhai, Xiao-Bing Liu, Yuen-Yuen Ma, Kwan Man
Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort...
September 29, 2015: Oncotarget
Eman Kandil, Nahed Abdel Aziz
Combining chemotherapy with radiotherapy represents a key oncology strategy for a more comprehensive attack toward cancers and improves treatment outcome for various solid tumor malignancies. The present study aims to evaluate the synergistic antitumor effect of γ-radiation together with gallium trichloride (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg b...
February 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Anne-Clémence Vion, Pierre-Emmanuel Rautou, François Durand, Chantal M Boulanger, Dominique C Valla
Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients...
September 2015: Seminars in Thrombosis and Hemostasis
Daisuke Hokuto, Takeo Nomi, Ichiro Yamato, Satoshi Yasuda, Shinsaku Obara, Takatsugu Yamada, Hiromichi Kanehiro, Yoshiyuki Nakajima
Portal vein arterialization (PVA) has been applied as a salvage procedure in hepatopancreatobiliary surgeries, including transplantation and liver resection, with revascularization for malignancies. Here we describe the use PVA as a salvage procedure following accidental injury of the hepatic artery to the remnant liver occurred during left hepatic trisectionectomy for colorectal liver metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and initially unresectable CRLM received 11 cycles of hepatic arterial infusion chemotherapy with 5-fluorouracil (1500mg/week), after which CRLM was downstaged to resectable...
2015: International Journal of Surgery Case Reports
Hidehiro Tajima, Tetsuo Ohta, Tomoharu Miyashita, Shinichi Nakanuma, Miki Matoba, Takashi Miyata, Seisho Sakai, Koichi Okamoto, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Keishi Nakamura, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Hiroyuki Takamura, Hirohisa Kitagawa, Sachio Fushida, Hiroko Ikeda
Oxaliplatin-based chemotherapy plays a central role in the treatment of patients with colorectal liver metastasis (CRLM). This treatment, however, has been associated with hepatic sinusoidal obstruction syndrome (SOS), a clinically important adverse effect characterized by a bluish hue of the liver, splenomegaly and thrombocytopenia, resulting in liver dysfunction. The significant association between the sinusoidal endothelium and platelets has suggested that oxaliplatin-based chemotherapy affects platelets in the liver...
May 2015: Molecular and Clinical Oncology
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