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Annals of Surgical Oncology

, Volume 26, Issue 12, pp 4100–4107 | Cite as

Dynamic Changes in Normal Liver Parenchymal Volume During Chemotherapy for Colorectal Cancer: Liver Atrophy as an Alternate Marker of Chemotherapy-Associated Liver Injury

  • Junichi ShindohEmail author
  • Yuta Kobayashi
  • Keiichi Kinowaki
  • Yoshihiro Mise
  • Wataru Gonoi
  • Shuntaro Yoshida
  • Keigo Tani
  • Shuichiro Matoba
  • Hiroya Kuroyanagi
  • Masaji Hashimoto
Hepatobiliary Tumors

Abstract

Background

The purpose of this study was to investigate the incidence, origin, and clinical significance of liver atrophy during chemotherapy for colorectal cancer.

Methods

This study included 103 patients who underwent chemotherapy before resection for colorectal liver metastases (training set) and 171 patients who underwent adjuvant or first-line chemotherapy without liver resection (validation set). A greater than 10% decrease (atrophy) or increase (hypertrophy) of the liver volume from the baseline was defined as a significant change.

Results

In the training set, the numbers of patients who developed atrophy, no change of volume, and hypertrophy of the liver after chemotherapy were 15 (14.6%), 73 (70.9%), and 15 (14.6%), respectively. Liver atrophy was associated with impaired hepatic function, and the postoperative morbidity rate and refractory ascites/pleural effusion were higher in the patients with liver atrophy than those without (60.0% vs. 31.8%, P = 0.045 and 46.7% vs. 8.0%, P < 0.001, respectively). Histopathological examination revealed a strong association between sinusoidal injury and liver atrophy (P < 0.001). The cumulative incidence of liver atrophy increased with increasing duration of chemotherapy, whereas the incidence of liver atrophy was less frequent in patients who had received bevacizumab than those who had not in both the training set (odds ratio [OR], 0.13; P = 0.001) and the validation set (OR, 0.31; P = 0.007).

Conclusions

Liver atrophy is associated with impaired hepatic functional reserve and observed at an increasing frequency as the duration of chemotherapy increases with frequent histopathological evidence of sinusoidal injury in the liver. Bevacizumab may protect against the development of liver atrophy.

Notes

Funding

This study was supported by JSPS KAKENHI Grant No. 26861063 and a study grant from Okinaka Memorial Institute for Medical Disease 2018–2019.

Disclosure

Junichi Shindoh reports receiving honoraria from Chugai and Takeda. No other authors reported disclosures.

Supplementary material

10434_2019_7740_MOESM1_ESM.pptx (950 kb)
Supplemental Fig. 1 Study population. Supplemental Fig. 2: Correlation of 3D volumetry results between two independent examiners. Volumetric measurement results: examiner 1, 1198.7 ± 272.6 mL; examiner 2, 1199.9 ± 260.4 mL (r = 0.992, p < 0.0001). Supplemental Fig. 3: Various clinical manifestations with dynamic changes of the liver volume during/after chemotherapy for colorectal cancer. A Significant shrinkage of the liver (− 24.4%) with elevated serum transaminase and bilirubin levels. B Significant shrinkage of the liver (− 16.7%) associated with massive ascites. C Significant hypertrophy of the liver (+ 71.2%) with marked steatosis. Supplemental Fig. 4: Correlation between the degree of atrophy and changes in CT numbers. Supplemental Fig. 5: Correlation between the degree of atrophy and ICG retention rate at 15 min (PPTX 949 kb)

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Junichi Shindoh
    • 1
    • 2
    Email author
  • Yuta Kobayashi
    • 1
  • Keiichi Kinowaki
    • 3
  • Yoshihiro Mise
    • 4
  • Wataru Gonoi
    • 5
  • Shuntaro Yoshida
    • 6
  • Keigo Tani
    • 7
  • Shuichiro Matoba
    • 1
  • Hiroya Kuroyanagi
    • 1
  • Masaji Hashimoto
    • 1
  1. 1.Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological SurgeryToranomon HospitalTokyoJapan
  2. 2.Okinaka Memorial Institute for Medical DiseaseTokyoJapan
  3. 3.Department of PathologyToranomon HospitalTokyoJapan
  4. 4.Department of Gastroenterological Surgery, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
  5. 5.Department of Radiology, Graduate School of MedicineThe University of TokyoTokyoJapan
  6. 6.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
  7. 7.Department of SurgeryTokyo Takanawa HospitalTokyoJapan

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