Relationship between Doubling Time of Liver Metastases from Colorectal Carcinoma and Residual Primary Cancer

Nomura, Kazutoshi; Miyagawa, Shinichi; Harada, Haruhisa; Kitamura, Hiroshi; Seki, Hitoshi; Shimada, Ryou; Kobayashi, Akira; Noike, Terumasa; Kawasaki, Seiji

doi:10.1159/000018581

Cited by 19 publications

(14 citation statements)

References 6 publications

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“…In our case, the growth is faster than this reported range. It is close to the TDT range reported for liver metastases, which are known as more aggressive (Nomura et al, 1998). In summary, the notable aggressiveness of metastases in this case, after two surgeries, supports the assumption that each event of surgery leads to faster of metastases.…”

Section: Discussionsupporting

confidence: 87%

Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

et al. 2020

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Most cases of deaths from colorectal cancer (CRC) result from metastases, which are often still undetectable at disease detection time. Even so, in many cases, shedding is assumed to have taken place before that time. The dynamics of metastasis formation and growth are not well-established. This work aims to explore CRC lung metastasis growth rate and dynamics. We analyzed a test case of a metastatic CRC patient with four lung metastases, with data of four serial computed tomography (CT) scans measuring metastasis sizes while untreated. We fitted three mathematical growth models—exponential, logistic, and Gompertzian—to the CT measurements. For each metastasis, a best-fitted model was determined, tumor doubling time (TDT) was assessed, and metastasis inception time was extrapolated. Three of the metastases showed exponential growth, while the fourth showed logistic restraint of the growth. TDT was around 93 days. Predicted metastasis inception time was at least 4–5 years before the primary tumor diagnosis date, though they did not reach detectable sizes until at least 1 year after primary tumor resection. Our results support the exponential growth approximation for most of the metastases, at least for the clinically observed time period. Our analysis shows that metastases can be initiated before the primary tumor is detectable and implies that surgeries accelerate metastasis growth.

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Section: Discussionsupporting

confidence: 87%

Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

et al. 2020

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“…This value is slightly less than the reported average doubling time of 92.4 days for resectable liver metastases from colorectal carcinoma. 18 The significantly increased tumor Ki-67 labeling index in the PVE group (Fig. 4) also provides indirect evidence of increased tumor growth after PVE.…”

Section: Discussionmentioning

confidence: 84%

Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization

et al. 2001

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Although hemihepatic portal vein embolization (PVE) has been used preoperatively to extend indications for hepatectomy in patients with colorectal metastases, the effects of this procedure on tumor growth and outcome remain controversial. To address this issue, we assessed the proliferative activity of intrahepatic metastases after PVE and the long-term outcome of this procedure. Eighteen patients with colorectal metastases underwent preoperative PVE between 1996 and 2000 (PVE group). Twenty-nine patients who underwent major hepatic resection without PVE served as control (non-PVE group). The hepatic parenchymal fraction of the left lobe had significantly increased from 38.1 ؎ 3.2% to 45.9 ؎ 2.9% 3 weeks after PVE (؉20.5%, P < .0001). Tumor volume and percent tumor volume had also significantly increased from 223 ؎ 89 mL to 270 ؎ 97 mL (؉20.8%, P ‫؍‬ .016) and from 13.7 ؎ 4.3% to 16.2 ؎ 4.9% (؉18.5%, P ‫؍‬ .014), respectively. There was no apparent correlation between the increase in parenchymal volume and that in tumor volume. The Ki-67 labeling index of metastatic lesions was 46.6 ؎ 7.2% in the PVE group and 35.4 ؎ 12.6% in the non-PVE group (P ‫؍‬ .013). Long-term survival was similar in the PVE and non-PVE groups, however, disease-free survival was significantly poorer in the PVE group than in the non-PVE group (P ‫؍‬ .004). We conclude that PVE increases tumor growth and probably is associated with enhanced recurrence of disease. Although PVE is effective in extending indications for surgery, patient selection for PVE should be cautious. (HEPATOLOGY 2001;34:267-272.)Hepatic resection provides the only chance for cure in patients with colorectal metastases. To extend indications for hepatectomy, hemihepatic portal vein embolization (PVE) has been performed in selected patients. 1-3 PVE induces homolateral atrophy of the portion of the liver scheduled for resection and contralateral compensatory hypertrophy of the remnant liver, thus decreasing the risk of postoperative liver failure. PVE is indicated when the remnant liver is expected to be very small, i.e., about 40% smaller than preoperative liver volume, or when tumor spread requires a right hemihepatectomy with partial resection of the left side of the liver. 4,5 The positive effects of PVE on hepatic function must be weighed against recent evidence suggesting that this procedure may promote oncogenesis. Elias et al., have reported that after PVE liver metastases may grow more rapidly than liver parenchyma. 6 This assumption was based on a study of only 5 patients who had tumors in the nonembolized lobe of the liver, rather than the embolized lobe. In addition, they focused on tumor growth in the nonembolized lobe. Consequently, their findings were considered too premature to warrant contraindication of PVE in patients with colorectal metastases. 7,8 When used in combination with arterial chemoembolization, PVE suppresses growth of hepatocellular carcinoma (HCC). 9 Long-term results of HCC resection after PVE have recently been shown to be better than or...

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“…The area of tumor was automatically generated, and the total area of tumor was multiplied by the thickness plus gap to obtain the volume of tumor. The doubling time (DT) of tumor volume was calculated with the following equation: DT = (T -T 0 ) log 2/(log V-log V 0 ), where T-T 0 indicates the length of time between two measurements, and V 0 and V denote the tumor volume at two consecutive points of measurement [14].…”

Section: Imaging Analysismentioning

confidence: 99%

Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

et al. 2008

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We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55+/-0.88 days and final size of 216.2+/-150.4 mm(3) at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system.

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Relationship between Doubling Time of Liver Metastases from Colorectal Carcinoma and Residual Primary Cancer

Cited by 19 publications

References 6 publications

Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization

Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

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