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

Vauthey, Jean Nicolas; Pawlik, Timothy M.; Ribero, Dario; Wu, Tsung Teh; Zorzi, Daria; Hoff, Paulo M.; Xiong, Henry Q.; Eng, Cathy; Lauwers, Gregory Y.; Mino‐Kenudson, Mari; Risio, Mauro; Muratore, Andrea; Capussotti, Lorenzo; Curley, Steven A.; Abdalla, Eddie K.

doi:10.1200/jco.2005.05.3074

Cited by 1,163 publications

(886 citation statements)

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“…A study by Allen et al [14] showed that patients whose disease remained stable without progression while receiving chemotherapy experienced significantly improved survival as compared to patients who did not receive chemotherapy prior to surgery (85% vs. 35%, P ¼ 0.03). However, patients receiving neoadjuvant chemotherapy face increased morbidity and mortality following major hepatic resection for metastases [15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Response to chemotherapy predicts survival following resection of hepatic colo‐rectal metastases in patients treated with neoadjuvant therapy

Small¹,

Lubezky²,

Shmueli³

et al. 2008

Journal of Surgical Oncology

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Background: Prognosis of patients following resection of CRC metastases to the liver has traditionally been predicted by clinical risk factors. In the era of neoadjuvant chemotherapy, determination of new prognostic indicators of outcome are necessary. Methods: This retrospective study includes patients with CRC liver metastases, who received oxaliplatin or irinotecan based neoadjuvant chemotherapy and underwent R0 resection. Patients were followed by CT and PET-CT, before, during and after chemotherapy and surgery. The predictive value of the Memorial Sloan-Kettering Cancer Center Clinical Score (MSKCC-CS) and degree of response to chemotherapy (measured by CT and PET-CT), were analyzed by univariate and multivariate COX regression. Results: Included are 54 patients. Overall 1-, 2-, 3-year survival rates 88%, 70%, and 39%. Response to chemotherapy on CT was a significant predictor of survival on univariate (P ¼ 0.03) and multivariate analysis (P ¼ 0.03), whereas MSKCC-CS and response to chemotherapy on PET-CT were not. Multivariate analysis demonstrated response to chemotherapy as a predictor of time to recurrence on CT (P ¼ 0.02) and PET-CT (P ¼ 0.03), while the MSKCC-CS (P ¼ 0.64) was not. Conclusions: In this cohort of patients treated by neoadjuvant chemotherapy, the outcome was not predicted by the traditional clinical scoring system, but rather by response to chemotherapy as evaluated by CT and PET-CT.

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Section: Discussionmentioning

confidence: 99%

Response to chemotherapy predicts survival following resection of hepatic colo‐rectal metastases in patients treated with neoadjuvant therapy

Small¹,

Lubezky²,

Shmueli³

et al. 2008

Journal of Surgical Oncology

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“…This has been attributed to the aspect of post-chemotherapy metastases that often have reduced contrast in respect to the liver and ill-defined borders [9]. Although these morphological characteristics might simply be the consequence of a decrease in tumour size to sub-centimetre diameters, frequently they are determined by a drug-induced steatosis [10], which modifies the imaging aspect of the liver parenchyma.…”

Section: Introductionmentioning

confidence: 99%

Staging of colorectal liver metastases after preoperative chemotherapy. Diffusion-weighted imaging in combination with Gd-EOB-DTPA MRI sequences increases sensitivity and diagnostic accuracy

et al. 2012

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Objectives To compare the diagnostic accuracy and sensitivity of Gd-EOB-DTPA MRI and diffusion-weighted (DWI) imaging alone and in combination for detecting colorectal liver metastases in patients who had undergone preoperative chemotherapy. Methods Thirty-two consecutive patients with a total of 166 liver lesions were retrospectively enrolled. Of the lesions, 144 (86.8 %) were metastatic at pathology. Three image sets (1, Gd-EOB-DTPA; 2, DWI; 3, combined Gd-EOB-DTPA and DWI) were independently reviewed by two observers. Statistical analysis was performed on a per-lesion basis. Results Evaluation of image set 1 correctly identified 127/ 166 lesions (accuracy 76.5 %; 95 % CI 69.3-82.7) and 106/ 144 metastases (sensitivity 73.6 %, 95 % CI 65.6-80.6). Evaluation of image set 2 correctly identified 108/166 (accuracy 65.1 %, 95 % CI 57.3-72.3) and 87/144 metastases (sensitivity of 60.4 %, 95 % CI 51.9-68.5). Evaluation of image set 3 correctly identified 148/166 (accuracy 89.2 %, 95 % CI 83.4-93.4) and 131/144 metastases (sensitivity 91 %, 95 % CI 85.1-95.1). Differences were statistically significant (P<0.001). Notably, similar results were obtained analysing only small lesions (<1 cm). Conclusions The combination of DWI with Gd-EOB-DTPAenhanced MRI imaging significantly increases the diagnostic accuracy and sensitivity in patients with colorectal liver metastases treated with preoperative chemotherapy, and it is particularly effective in the detection of small lesions. Key Points • Accurate detection of colorectal liver metastases is essential to determine resectability.• Almost 80 % of patients are candidates for neoadjuvant chemotherapic treatment at diagnosis. After chemotherapy, metastases usually decrease, and drug-induced liver steatosis may be present.• The sensitivity of imaging is significantly inferior to that in chemotherapy-naïve patients.• DWI combined with Gd-EOB-DTPA increases sensitivity in detecting small metastases after chemotherapy.

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“…In fact, since our initial report (1), several groups have confirmed the existence of oxaliplatin-related SOS in 25% to 36% of treated patients. This has led to concerns that oxaliplatin-associated hepatotoxicity may decrease the chances of curative liver surgery by increasing morbidity through preoperative hemorrhage, postoperative liver failure, delayed regeneration, and portal hypertension (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Rare fatal cases have been reported, inducing a group of experts to publish a cautionary note on the use of chemotherapy before surgical liver resection (14).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Rubbia‐Brandt

Tauzin

Brézault

et al. 2011

Molecular Cancer Therapeutics

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Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

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

Abstract: 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.

Cited by 1,163 publications

References 44 publications

Response to chemotherapy predicts survival following resection of hepatic colo‐rectal metastases in patients treated with neoadjuvant therapy

Response to chemotherapy predicts survival following resection of hepatic colo‐rectal metastases in patients treated with neoadjuvant therapy

Staging of colorectal liver metastases after preoperative chemotherapy. Diffusion-weighted imaging in combination with Gd-EOB-DTPA MRI sequences increases sensitivity and diagnostic accuracy

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

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