One-Stage Hepatectomy Following Portal Vein Embolization for Colorectal Liver Metastasis

Background

Although portal vein embolization (PVE) has been applied for surgical resection of colorectal liver metastases (CLM), the clinical usefulness of liver surgery following PVE for CLM remains unknown.

Methods

A total of 115 patients were evaluated retrospectively. Among them, 49 underwent one-stage hepatectomy following PVE (PVE group). The remaining 66 patients underwent at least hemihepatectomy without PVE (non-PVE group). This analysis compared the short- and long-term outcomes between the PVE and non-PVE groups.

Results

There were no deaths in either group. Using the Clavien–Dindo classification, the rates of postoperative morbidity ≥ grade 1 were 34.7 % in the PVE group and 25.0 % in the non-PVE group (p = 0.26). The 3-year overall survival rates were 54.6 and 64.5 % in the PVE and non-PVE groups, respectively (p = 0.89). The multivariate analysis the variable performance/nonperformance of PVE was not detected as an independent predictor of poor survival.

Conclusions

Our one-stage hepatectomy policy of using PVE provides acceptable morbidity and favorable long-term outcomes.     

Percentage of Future Liver Remnant Volume Before Portal Vein Embolization Influences the Degree of Liver Regeneration After Hepatectomy

Background

Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration.

Methods

Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis.

Results

PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm³, respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r?=?0.63, p?<?0.0001). Multiple regression analysis showed that only %FLR-pre was independently correlated with posthepatectomy liver regeneration (p?=?0.027, odds ratio?=?13.8).

Conclusion

After PVE and the subsequent hepatectomy, liver regeneration was accomplished in a two-step manner. Liver regeneration was strongly influenced by the %FLR-pre.     

Does Preoperative Portal Vein Embolization Have Any Impact on the Outcome of Right-Side Hepatectomy for Klatskin Tumor?

Background and Aim

The clinical usefulness of portal vein embolization (PVE) for Klatskin tumor is not well established. The authors explored the change in liver volume and function before and after major hepatectomy and evaluated the effect of PVE.

Methods

Thirty-three consecutive patients who underwent right hepatectomy with an initial future liver remnant (FLR)?≤?30 % for Klatskin tumors at Seoul National University Hospital were included.

Results

Eleven patients underwent PVE, and eight patients received right trisectionectomy. PVE induced a mean FLR increase of 19.3 % after a mean of 15.8 days. At postoperative month 1, liver volume and liver hypertrophy ratio was comparable between PVE and no-PVE group. For patients with an initial FLR?≤?20 %, postoperative liver hypertrophy rate of PVE group was comparable to no-PVE group. Liver function tests were not affected by PVE or the initial FLR. Postoperative liver hypertrophy ratio was negatively correlated with the initial FLR (hypertrophy ratio (%)?=?326.7–0.4×initial FLR (ml), P?=?0.001). There was no severe PVE-related morbidity, and postoperative morbidity rate was comparable in PVE and no-PVE group.

Conclusion

The postoperative liver hypertrophy ratio, final liver volume, or liver function tests were not affected by PVE. Postoperative liver hypertrophy was related to the initial FLR.     

Can Plasma Bile Salt, Triglycerides, and apoA-V Levels Predict Liver Regeneration?

Background

Preoperative portal vein embolization (PVE) is used to increase the future remnant liver (FRL) in patients requiring extensive liver resection. Computed tomography (CT) volumetry, performed not earlier than 3–6 weeks after PVE, is commonly employed to assess hypertrophy of the FRL following PVE. Early parameters to predict effective hypertrophy are therefore desirable. The aim of the present study was to assess plasma bile salt levels, triglycerides (TG), and apoA-V in the prediction of the hypertrophy response during liver regeneration.

Methods

Serum bile salt, TG, and apoA-V levels were determined in 20 patients with colorectal metastases before PVE, and 5 h, 1, and 21 days after PVE, as well as prior to and after (day 1–7, and day 21) subsequent liver resection. These parameters were correlated with liver volume as measured by CT volumetry (%FRL-V), and liver function was determined by technetium-labeled mebrofenin hepatobiliary scintigraphy using single photon emission computed tomography.

Results

Triglyceride levels at baseline correlate with volume increase of the future remnant liver (FRL-V) post-PVE. Also, bile salts and TG 5 h after PVE positively correlated with the increase in FRL volume (r = 0.672, p = 0.024; r = 0.620, p = 0.042, resp.) and liver function after 3 weeks (for bile salts r = 0.640, p = 0.046). Following liver surgery, TG levels at 5 h and 1 day after resection were associated with liver remnant volume after 3 months (r = 0.921, p = 0.026 and r = 0.981, p = 0.019, resp). Plasma apoA-V was increased during liver regeneration.

Conclusions

Bile salt and TG levels at 5 h after PVE/resection are significant early predictors of liver volume and functional increase. It is suggested that these parameters can be used for early timing of volume assessment and resection after PVE.     

Sequential Transcatheter Arterial Chemoembolization and Portal Vein Embolization versus Portal Vein Embolization Only before Major Hepatectomy for Patients with Hepatocellular Carcinoma

Purpose

To evaluate the safety and efficacy of sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) prior to surgery in hepatocellular carcinoma (HCC) patients and to compare the clinical outcome of the combined procedure with that of a matched group of patients undergoing PVE alone.

Patients and Methods

From 1997 to 2008, 135 patients with HCC underwent sequential TACE and PVE (n = 71) or PVE alone (n = 64) before right hepatectomy. PVE was performed mean 1.2 months after TACE. In both groups, computed tomography (CT) and liver volumetry were performed before and 2 weeks after PVE to assess degree of left lobe hypertrophy.

Results

Baseline patient and tumor characteristics were similar in the two groups. After PVE, the chronological changes of liver enzymes were similar in the two groups. The mean increase in percentage future liver remnant (FLR) volume was higher in the TACE + PVE group (7.3%) than in the PVE-only group (5.8%) (P = 0.035). After surgery, incidence of hepatic failure was higher in the PVE-only group (12%) than in the TACE + PVE (4%) group (P = 0.185). Overall (P = 0.028) and recurrence-free (P = 0.001) survival rates were significantly higher in the TACE + PVE group than in the PVE-only group.

Conclusion

Sequential TACE and PVE before surgery is a safe and effective method to increase the rate of hypertrophy of the FLR and leads to longer overall and recurrence-free survival in patients with HCC.     

ALPPS Offers a Better Chance of Complete Resection in Patients with Primarily Unresectable Liver Tumors Compared with Conventional-Staged Hepatectomies: Results of a Multicenter Analysis

Background

Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4–8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1–2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection.

Methods

A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence.

Results

Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26–49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7).

Conclusions

This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries.     

Influence of Preoperative Chemotherapy on CT Volumetric Liver Regeneration Following Right Hemihepatectomy

Background

An increasing number of patients undergo major liver resection following preoperative chemotherapy. Liver regeneration may be impaired in these patients, predisposing them to postoperative liver dysfunction. The aim of the present study was to evaluate the effects of preoperative chemotherapy on liver regeneration after partial liver resection.

Methods

Patients planned to receive right hepatectomy either with (group B) or without (group A) prior chemotherapy were identified retrospectively from a prospective multi-institutional database created in the conduct of a national randomized controlled trial (RCT). Prior chemotherapy was neither an inclusion nor an exclusion criterion of the trial. Future remnant liver volume (FRLV) was calculated by measuring total functional liver volume and resection specimen on preoperative computed tomography (CT) scans. Remnant liver volume after 7 days (V _RLV7days) was measured on scheduled postoperative CT scans. The early regeneration index 7 days after surgery (RI _early) was calculated as [(V _RLV7days ? FRLV) / FRLV] × 100 %. Data are expressed as median (interquartile range).

Results

A total of 72 patients were enrolled: 45 in group A and 27 in group B. For the whole group, the liver remnant showed a 58 % (39 %) increase in volume at day 7 (1) day. The RI _early was not significantly different between groups A and B, 60 % (36 %) and 50 % (43 %), respectively (p = 0.47). The RI _early was significantly lower in patients who had undergone more than six cycles of chemotherapy.

Conclusions

Preoperative chemotherapy does not seem to have a negative impact on early liver regeneration after partial liver resection.     

Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Background

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown.

Methods

All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach.

Results

A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI.

Conclusions

Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.     

Evaluation of Chemotherapy-Associated Liver Injury in Patients with Colorectal Cancer Liver Metastases Using Indocyanine Green Clearance Testing

Background

Systemic chemotherapy may render initially unresectable colorectal cancer liver metastases resectable. Histopathologic examinations of resected nontumoral liver tissue revealed chemotherapy-associated liver injuries, which was recognized to impair the function of the remnant liver. We therefore evaluated whether indocyanine green (ICG) plasma clearance helps to assess chemotherapy-induced liver damage.

Methods

Data of 101 liver resections performed between 2006 and 2008 for colorectal liver metastases were analyzed for this study. Eighteen patients had liver resection without preoperative treatment, whereas 83 patients underwent neoadjuvant chemotherapy before surgery. ICG clearance was assessed by pulse densitometry before surgery.

Results

Comparison of ICG retention clearances demonstrated that patients pretreated with systemic chemotherapy had a significantly lower plasma disappearance rate (ICG-PDR; 19.3 ± 5.9 vs. 23.1 ± 3.8%/min; P = 0.002) and a significantly elevated ICG retention rate at 15 min (7.9 ± 6.6 vs. 3.8 ± 1.9%; P < 0.001). The percentage of subjects with an abnormal ICG-PDR (≤18%/min) was significantly higher in the pretreated group (48.2% vs. 5.6%; P = 0.001). Patients with an ICG-PDR of ≤18 had a prolonged postoperative hospital stay and experienced four times more complications in their postoperative course.

Conclusions

ICG clearance helps to identify patients with impaired liver function after neoadjuvant chemotherapy and aids in the estimation of the postoperative risk of morbidity after liver resection for colorectal liver metastases.     

Safety and Efficacy of Portal Vein Embolization Before Planned Major or Extended Hepatectomy: An Institutional Experience of 358 Patients

Introduction

Portal vein embolization (PVE) stimulates hypertrophy of the future liver remnant (FLR) and may improve the safety of extended hepatectomy. The efficacy of PVE was evaluated.

Methods

Records of 358 consecutive patients who underwent PVE before intended major hepatectomy at our institution from 1995 through 2012 were retrospectively reviewed.

Results

One hundred twelve patients (31.3 %) had right PVE alone; 235 (65.6 %) had right PVE plus segment IV embolization. The first-session PVE completion rate was 97.8 %. The PVE complication rate was 3.9 %. The median pre-PVE and post-PVE standardized FLRs were 19.5 % (interquartile range, 15.0–25.9) and 29.7 % (interquartile range, 22.5–38.2), respectively. Two hundred forty patients (67.0 %) underwent potentially curative resection. Sixty-two patients (25.8 %) had major post-hepatectomy complications; rates of postoperative hepatic insufficiency and 90-day liver-related mortality were 8.3 and 3.8 %, respectively. The proportion of patients with colorectal liver metastasis increased from 38.6 % before 2005 to 78.2 % in 2010–2012. Despite increased use of preoperative chemotherapy, postoperative hepatic insufficiency and 90-day liver-related mortality rates dropped from 10.6 and 4.1 %, respectively, before 2010 to 2.9 and 2.9 %, respectively, in 2010–2012.

Conclusions

PVE can be safely performed with minimal morbidity. Most patients can proceed to extended hepatectomy, which is associated with a minimal mortality rate.     

Stroke Volume Response to Liver Graft Reperfusion Stress in Cirrhotic Patients

Introduction

In patients with advanced cirrhosis, stressful stimuli may reveal a silent reduced cardiac performance. During liver transplantation (LT), graft reperfusion strongly stresses the heart and may unmask latent myocardial dysfunction.

Aim

The objective of this study was to assess heart response to acutely increased preload after liver graft reperfusion and correlate this response with preoperative data and outcome.

Methods

Preoperative clinical, echocardiographic, and hemodynamic data, and patient outcome were retrospectively recorded for 235 liver recipients who had no known cardiac disease. Myocardial dysfunction was defined as less than 10 % increase of stroke volume after graft reperfusion (non-responder).

Results

We found 84 (35.7 %) non-responder patients. The non-responders showed higher Model for end-stage liver disease scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure gradient (p = 0.055), and hyperdynamic state than responders. The percentages of patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also higher among non-responders. Independent predictors of inadequate cardiac response in the multivariate analysis were low preoperative systemic vascular resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15–4.82; p = 0.027] and enlargement of LAD (OR 2.08, 95 % CI 1.49–2.74; p = 0.044). Non-response was associated with higher rates of early cardiovascular events [hazard ratio (HR) 2.84, 95 % CI 1.09–4.22; p = 0.039] and higher length of intensive care unit stay (p = 0.038). No differences were found in 1-year survival rates.

Conclusions

Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke volume response to unclamping of portal vein, is very prevalent. SVRI and LAD were independent predictors of inadequate responses. This condition deserves special attention since it may aggravate the early postoperative course of LT.     

Portal Vein Embolization Reduces Postoperative Hepatic Insufficiency Associated with Postchemotherapy Hepatic Atrophy

Background

The risk of postoperative hepatic insufficiency (PHI) is increased among patients with significant postchemotherapy hepatic atrophy. The primary aim of this study was to evaluate whether the liver regeneration stimulated by portal vein embolization (PVE) can protect against PHI.

Methods

Clinicopathological features of 177 patients treated with preoperative chemotherapy followed by PVE and hepatectomy were reviewed. Degree of atrophy was defined as the ratio of percentage difference in total liver volume (estimated by manual volumetry) to standardized liver volume. Kinetic growth rate (KGR, degree of hypertrophy [absolute % change in future liver remnant volume] divided by the number of weeks after PVE) and PHI events were compared between patients with degree of atrophy <10 vs ≥10%. Risk factors for the PHI were assessed using logistic regression.

Results

Seventy patients (40%) experienced significant hepatic atrophy ≥10% following preoperative chemotherapy. PHI rates were not significantly increased in patients who experienced significant hepatic atrophy (5.6 vs 8.6%, P = 0.443). KGR <2%/week (odds ratio, 8.10, P = 0.037) was the sole independent preoperative predictor of PHI. KGR ≥2% was associated with decreased PHI in both patients with <10% atrophy (0 vs 9.5%, P = 0.035) and ≥10% atrophy (2.6 vs 16.0%, P = 0.044).

Conclusions

Even in high-risk patients with ≥10% degree of atrophy from preoperative chemotherapy, KGR ≥2% mitigates the deleterious effects of hepatic atrophy and significantly reduces PHI to almost zero. In these high-risk patients, PVE with KGR calculation remains the most important preoperative technique to reduce liver failure after major hepatectomy.

     

Metabolic Response to Preoperative Chemotherapy Predicts Prognosis for Patients Undergoing Surgical Resection of Colorectal Cancer Metastatic to the Liver

Background

Biological characteristics of colorectal cancer liver metastases (CRCLM) are increasingly recognized as major determinants of patient outcome. The purpose of this study was to evaluate the prognostic value of metabolic response to preoperative chemotherapy as quantified by ¹⁸F-FDG positron emission tomography (PET) for patients undergoing liver resection of CRCLM.

Methods

All patients (n = 80) who had staging PET before liver resection for CRCLM at Austin Health in Melbourne between 2004 and 2011 were included. Thirty-seven patients had PET and CT imaging before and after preoperative chemotherapy. Semiquantitative PET parameters—maximum standardized uptake variable (SUV_max), metabolic tumour volume (MTV), and total glycolytic volume (TGV)—were derived. Metabolic response was determined by the proportional change in PET parameters (?SUV_max, ?MTV, ?TGV). Prognostic scores, CT RECIST response, and tumour regression grading (TRG) were also assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan–Meier survival and multivariate analysis.

Results

Semiquantitative parameters on staging PET before chemotherapy were not predictive of prognosis, whereas all parameters after chemotherapy were prognostic for RFS and OS. Only ?SUV_max was predictive of RFS and OS on multivariate analysis. Patients with metabolically responsive tumours had an OS of 86 % at 3 years vs. 38 % with nonresponsive or progressive tumours (p = 0.003). RECIST and TRG did not predict outcome.

Conclusions

Tumour metabolic response to preoperative chemotherapy as quantified by PET is predictive of prognosis in patients undergoing resection of CRCLM. Assessing metabolic response uniquely characterizes tumour biology, which may allow future optimization of patient and treatment selection.     

Usefulness of Contrast-Enhanced Intraoperative Ultrasonography (CE-IOUS) in Patients with Colorectal Liver Metastases after Preoperative Chemotherapy

Aims

The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques.

Methods

From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography.

Results

Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n?=?9), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n?=?4), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p?=?0.047), resolution of at least one metastasis (p?=?0.011), and small liver metastases (largest lesion size ≤20 mm) after chemotherapy (p?=?0.007).

Conclusion

In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate.     

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

Purpose

Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).

Methods

Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n?=?134), or chemotherapy alone (group 2, n?=?57). We compared demographics, surgical characteristics, and perioperative course.

Results

Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p?=?0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p?=?0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p?=?0.56.

Conclusion

Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.     

Predictors for Early Recurrence After Hepatectomy for Initially Unresectable Colorectal Liver Metastasis

Background

Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.

Methods

We retrospectively studied 46 patients who underwent hepatectomy after chemotherapy for initially unresectable colorectal liver metastasis from 1997 to 2010.

Results

Recurrences occurred within 6 months after hepatectomy in 13 patients (37 %). The median survival time of 21.2 months and the 5-year survival rate of 0 % after hepatectomy in patients with recurrence within 6 months were significantly worse than those in patients with recurrence more than 6 months after hepatectomy. Recurrence in less than 6 months was significantly correlated with impossibility of anticancer therapy for recurrence after hepatectomy (p?=?0.01). Eight or more hepatic tumors after chemotherapy were the only predictor of recurrence within 6 months (p?=?0.01; odds ratio 9.6; 95 % confidence interval 1.5–60.6).

Conclusion

Recurrence within 6 months was significantly correlated with a poorer outcome following surgery for initially unresectable colorectal liver metastasis. Surgical indication for initially unresectable colorectal liver metastasis with eight or more hepatic tumors after chemotherapy should be considered carefully in the light of mental and physical status, co-morbidity, and alternative treatment plans.     

Evaluation of the Usefulness of the Indocyanine Green Clearance Test for Chemotherapy-Associated Liver Injury in Patients with Colorectal Cancer Liver Metastasis

Background

The indocyanine green (ICG) clearance test is reported to be useful for the preoperative evaluation of hepatic functional reserve. However, the ICG clearance test has not been sufficiently investigated in patients with colorectal liver metastasis after chemotherapy. The aim of the present study was to evaluate whether the ICG clearance test is a useful parameter for the preoperative detection of chemotherapy-associated liver injury.

Methods

Ninety-four patients undergoing liver resection for colorectal liver metastasis after chemotherapy were studied. The medical records for each case were retrospectively reviewed. They underwent pathological assessment to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. In addition, the correlation between the pathological score and the ICG retention rate at 15 min (ICG-R15) was analyzed.

Results

Sinusoidal injury was observed in the 31 of 94 patients. Steatohepatitis was observed in the 40 of 94 patients. There was no strong correlation between the preoperative ICG-R15 value and the sinusoidal pathological score (r = 0.117, P = 0.261). There was no strong correlation between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r = 0.215, P = 0.037).

Conclusions

It was difficult to predict the degree of chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is necessary to estimate the hepatic functional reserve based on a combination of several clinical indicators without relying on the ICG test, in order to perform a safe radical liver resection.     

Sinusoidal Obstruction Syndrome Impairs Long-Term Outcome of Colorectal Liver Metastases Treated with Resection after Neoadjuvant Chemotherapy

Background

Chemotherapy-induced liver injury is a considerable problem in patients undergoing surgery for colorectal liver metastases, since an increase in postoperative morbidity and mortality has been observed. We investigated whether liver damage had further implications on long-term outcome in these patients.

Materials and Methods

Liver specimens from 196 patients resected for colorectal liver metastases were evaluated for chemotherapy-associated hepatic damage in the nontumorous liver. Injury patterns were correlated with recurrence free (RFS) and overall survival (OS). Factors leading to sinusoidal injury were identified.

Results

Patients who developed grade 2 or 3 sinusoidal dilatation had a significantly shorter RFS (hazard ratio [HR] 2.05; 95% confidence interval [95% CI] 1.23–3.39, P = .005) and OS (HR 2.90; 95% CI 1.61–6.19, P < .001), compared to patients without this alteration. Those patients also had significantly more intrahepatic recurrences (66.7% vs 30.5%, P = .003). Other patterns of chemotherapy-associated liver damage (nonalcoholic steatohepatitis, fibrosis) were not associated with impaired survival. Factors indicating sinusoidal injury were oxaliplatin-based chemotherapy, tumor size >5 cm, and elevated alkaline phosphatase or gamma glutamyltransferase.

Conclusions

Sinusoidal obstruction syndrome due to oxaliplatin-based chemotherapy may not only compromise perioperative outcome, but can lead to early recurrence and decreased survival in the long term. Strategies to prevent this condition are clearly needed.     

Prognostic Impact of Positive Surgical Margins After Resection of Colorectal Cancer Liver Metastases: Reappraisal in the Era of Modern Chemotherapy

Background

The purpose of the present study was to assess the prognostic impact of positive surgical margins (R1) after liver resection (LR) of colorectal liver metastases (CRLM) in the era of modern chemotherapy regimens. R1 resection is a negative prognostic factor after LR of CRLM. The significance of R1 margins in the era of effective chemotherapy is unknown.

Methods

From January 2000 to December 2009, 215 patients (177 men: 62 %; median age 60 years; range 30–84 years) underwent LR of CRLM. The LR was considered R1 (margin <1 mm) in 49 patients (23 %) and R0 in 166 patients (77 %). Overall, 108 (50 %) patients received preoperative chemotherapy and 156 (72 %) patients received postoperative chemotherapy.

Results

With a median follow-up of 36 months (range 1–141 months), the 5-year overall survival (OS) rate (47 vs 40 %; p = 0.05) and the disease-free survival (DFS) rate (36 vs 23 %; p = 0.006) were significantly lower in the R1 group. Recurrence developed in 152 patients (71 %) and the rate of recurrence was significantly higher (84 vs 67 %; p = 0.02) in the R1 group. On multivariate analysis, N+ status of the colorectal primary tumor (p = 0.008), presence of radiologically occult disease (p = 0.04), and R1 resection (p = 0.03) were independent adverse predictors of OS. The N+ status of the primary tumor (p = 0.003) and R1 resection (p = 0.02) were independent adverse predictors of DFS. On multivariate analysis use of postoperative chemotherapy was the only independent predictor of improved DFS (p = 0.02) in the R1 group.

Conclusions

A positive resection margin remains a significant poor prognostic factor after LR of CRLM in the era of modern chemotherapy. Postoperative chemotherapy reduces recurrence rates after R1 resection of CRLM.     

The diagnostic value of 99m-Tc GSA scintigraphy for liver function and remnant liver volume in hepatic surgery: a retrospective observational cohort study in 27 patients

Background

The aim was to analyze hepatic hypertrophy after portal vein embolization (PVE) and Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) to determine whether clinical circumstances associated with major hepatic resections correlated with remnant growth.

Methods

Data was abstracted from a retrospectively maintained database on 27 patients undergoing hepatic resection followed by PVE and the ALPPS procedure between October 1, 2007 and December 31, 2016. The increasing rate of liver volume and remnant liver LU15 was defined as the percentage-point difference between the liver volume and remnant liver LU15 before and after the intervention or surgery. And correlation between kinetic growth rate (KGR) of liver and future remnant liver volume or remnant liver LU15 was analyzed.

Results

The degree of hypertrophy (DH) of volume and LU15 was significantly greater after ALPPS (volume: 40.3% and LU15: 65.0%) than after PVE (volume: 22.7% and LU15: 48.8%) (P <?0.05). KGR of volume and LU15 was significantly greater after ALPPS (volume: 19.0 cm³/day and 2.00%/day) (LU15: 0.61 /day and 1.82%/day) than after PVE (volume: 3.89 cm³/day and 0.42%/day) (LU15: 0.19 /day and 0.63%/day) (P <?0.001). An inverse correlation between KGR and initial remnant liver volume was observed. And a positive correlation between KGR and LU15 was observed.

Conclusion

Future remnant liver volume and KGR was greater after the ALPPS procedure than after PVE. Liver hypertrophy is related to the expected remnant liver volume and total liver function. This study suggested that total liver function and initial remnant liver volume might be a new indication of hepatectomy after PVE and ALPPS in the case of insufficient remnant liver volume.