Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases.

BACKGROUND AND OBJECTIVES: While preoperative treatment is frequently administered to CRLM patients, the impact of chemotherapy, with or without bevacizumab, on liver regeneration remains controversial. METHODS: The early and late regeneration indexes were defined as the relative increase in liver volume (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative treatment groups were compared. RESULTS: Preoperative chemotherapy details and volumetric data were available for 185 patients; 78 (42.2%) received preoperative chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev-), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the comparable clinicopathological characteristics and Resected Volume/Total Liver Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091, respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6% and 5.5%, respectively) were comparable between the no chemotherapy and Bev- groups (all P > 0.05). In multivariable analysis -adjusted for gender, age, portal vein embolization, preoperative chemotherapy, resected liver volume, tumor number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab independently predicted early liver regeneration (P = 0.019). CONCLUSION: Our findings suggest that preoperative bevacizumab administered along with chemotherapy was associated with enhanced volumetric restoration. Interestingly, this effect was more pronounced among patients who received oxaliplatin-based regimens and bevacizumab compared to those treated with irinotecan-based regimens and bevacizumab.

Increased kinetic growth rate during late phase liver regeneration impacts the risk of tumor recurrence after colorectal liver metastases resection.

BACKGROUND: Although experimental data strongly support the pro-tumorigenic role of postoperative liver regeneration, this hypothesis has not been clinically investigated. We aimed to examine the impact of liver regeneration determined by volumetric imaging on recurrence following resection of colorectal liver metastasis (CRLM). METHODS: Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp). Early and late kinetic growth rates (KGR) were defined as the postoperative increases in liver volume within 2-3 and 8-10 months from surgery, respectively, divided by the corresponding time interval. RESULTS: Median early and late KGR was 2.6%/month (IQR: -0.9 to 12.3) and 1.0%/month (IQR: -0.64 to 2.91), respectively. Late KGR predicted intrahepatic recurrence after 1 year from surgery (AUC 0.677, P = 0.011). Specifically, patients with a late KGR ≥1% had a higher cumulative risk of recurrence compared with patients with a KGR <1% (P = 0.038). In multivariate analysis, KGR ≥1% independently predicted recurrence (P = 0.027). DISCUSSION: A KGR ≥1% during the late regeneration phase was associated with increased risk of intrahepatic recurrence. These data may inform the timing of adjuvant therapy administration and focus surveillance strategies for high-risk patients.

Impact of Perioperative Phosphorus and Glucose Levels on Liver Regeneration and Long-term Outcomes after Major Liver Resection.

INTRODUCTION: The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy. METHODS: Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV2m-RLVp)/RLVp] and 7 months[(RLV7m-RLVp)/RLVp] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed. RESULTS: On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P > 0.05) and RLV/TLV at surgery (P = 0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P = 0.01) with these patients having increased risk for postoperative liver failure (P = 0.01). The inhibition of liver regeneration persisted at 7 months (P = 0.007) and was associated with a worse survival (P = 0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P = 0.02). CONCLUSIONS: Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.

Quantitative volumetric functional MR imaging: an imaging biomarker of early treatment response in hypo-vascular liver metastasis patients after yttrium-90 transarterial radioembolization.

PURPOSE: To evaluate the value of quantitative volumetric functional MR imaging in early assessment of response to yttrium-90-labeled ((90)Y) transarterial radioembolization (TARE) in patients with hypo-vascular liver metastases. MATERIALS AND METHODS: Seventy four metastatic lesions in 14 patients with hypo-vascular liver metastases after TARE were included in this retrospective study. Diffusion and contrast-enhanced MR imaging was performed before and early after treatment. All MR images were analyzed by two experienced radiologists. Response by anatomic metrics (RECIST, mRECIST, EASL) and functional metrics (ADC and arterial and venous enhancement) were reported in targeted and non-targeted lesions. A two-sample paired t test was used to compare the changes after TARE. A p value of <0.05 was considered statistically significant. RESULTS: The anatomic metrics did not show any significant changes in both targeted and non-targeted groups. Targeted lesions demonstrated an increase in mean volumetric ADC (23.4%; p = 0.01), a decrease in arterial and venous enhancement (-22.9% and -6.7%, respectively; p < 0.001 and p = 0.002, respectively) 1 month after treatment. Twenty one responding lesions (42%) by RECIST at 6 months demonstrated a significant increase in volumetric ADC (37.2%; p = 0.01), decrease in arterial and venous enhancement (-58.5% and -23.9%, respectively; p < 0.001) at 1 month post-treatment. Responding lesions did not change significantly by anatomic metrics. CONCLUSIONS: RECIST, mRECIST, and EASL criteria failed to stratify lesions into responders and non-responders early after TARE in hypo-vascular liver metastasis. Quantitative volumetric functional MR imaging could be a promising tool as a biomarker for predicting early response and can potentially be utilized in clinical trials.