• Humans
• Surgical Clearance
• Retrospective Studies
• Liver Neoplasms/surgery
• Colorectal Neoplasms/surgery

• University Hospitals Birmingham
• University of Birmingham

• Colorectal Neoplasms/drug therapy
• Hepatic Artery
• Humans
• Indocyanine Green
• Infusion Pumps, Implantable
• Infusions, Intra-Arterial
• Liver Neoplasms/drug therapy
• Robotic Surgical Procedures

• Chemotherapy
• Colorectal liver metastases
• Hepatectomy

• ablation
• colorectal cancer
• colorectal liver metastases
• mortality
• postoperative morbidity
• resection
• surgery

• colorectal liver metastases
• patient selection
• two‐stage hepatectomy

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist.

Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a “gold standard”. RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist.

Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the “gold standard”, it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA.

Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

• colon cancer
• disease-free survival
• liver metastases
• recurrence
• resection
• resection margin

Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25–30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure.

The aim of this review is to depict the various interventions for liver parenchyma augmentation–assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates.

To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly “palliative” disease into a curative and sometimes in a “chronic” disease.

• Associating liver partition and portal vein ligation for staged hepatectomy
• Liver augmentation
• Liver surgery
• Portal vein embolization
• Transarterial chemoembolization
• Two-staged hepatectomy

• colorectal liver metastases
• liver resection
• local ablation
• multimodal
• oncological surgery

• Hemihepatectomy
• Liver metastases
• Liver regeneration

Liver malignancies are the fifth most common cause of death worldwide. Surgical intervention with curative intent is the treatment of choice for liver tumors as it provides long-term survival. However, only 20% of patients with metastatic liver lesions can be managed by curative liver resection. In most of the cases, hepatectomy is not feasible because of insufficient future liver remnant (FLR). Two-stage hepatectomy is advocated to achieve liver resection in a patient who is considered to not be a candidate for resection. Procedures of staged hepatectomy include conventional two-stage hepatectomy, portal vein embolization, and associating liver partition and portal vein ligation for a staged hepatectomy. Technical success is high for each of these procedures but variable between them. All the procedures have been reported as being effective in achieving a satisfactory FLR and completing the second-stage resection. Moreover, the overall survival and disease-free survival rates have improved significantly for patients who were otherwise considered nonresectable; yet, an increase in the morbidity and mortality rates has been observed. We suggest that this type of procedure should be carried out in high-flow centers and through a multidisciplinary approach. An experienced surgeon is key to the success of those interventions.

• Staged hepatectomy
• Portal vein embolization
• Portal vein ligation
• Colorectal liver metastasis
• Hepatocellular carcinoma
• Associated liver partition and portal vein ligation for staged hepatectomy

To avoid liver insufficiency following major hepatic resection, portal vein embolisation (PVE) is used to induce liver hypertrophy pre-operatively. Associating liver partition with portal vein ligation for staged hepatectomy assisted with radiofrequency (RALPPS) was introduced as an alternative method. A randomized controlled trial comparing PVE with RALPPS for the pre-operative manipulation of liver volume in patients with a future liver remnant volume (FLRV) ≤25% (or ≤35% if receiving preoperative chemotherapy) was conducted. The primary endpoint was increase in size of the FLRV. The secondary endpoints were length of time taken for the volume gain, morbidity, operation length and post-operative liver function. Between July 2015 and October 2017, 57 patients were randomised to RALPPS (n = 29) and PVE (n = 28). The mean percentage of increase in the FLRV was 80.7 ± 13.7% after a median 20 days following RALPPS compared to 18.4 ± 9.8% after 35 days (p < 0.001) following PVE. Twenty-four patients after RALPPS and 21 after PVE underwent stage-2 operation. Final resection was achieved in 92.3% and 66.6% patients in RALPPS and PVE, respectively (p = 0.007). There was no difference in morbidity, and one 30-day mortality after RALPPS (p = 0.991) was reported. RALPPS is more effective than PVE in increasing FLRV and the number of patients for surgical resection.

• ALPPS
• ALPPS-RF
• RALPPS
• hepatic resection
• portal vein embolisation
• portal vein ligation

• colorectal liver metastasis
• future liver remnant
• portal vein embolization
• two-stage hepatectomy

To evaluate safety and outcomes of a new technique for extreme hepatic resections with preservation of segment 4 only.

The new method of extreme liver resection consists of a two-stage hepatectomy. The first stage involves a right hepatectomy with middle hepatic vein preservation and induction of left lobe congestion; the second stage involves a left lobectomy. Thus, the remnant liver is represented by the segment 4 only (with or without segment 1, ± S1). Five patients underwent the new two-stage hepatectomy (congestion group). Data from volumetric assessment made before the second stage was compared with that of 10 matched patients (comparison group) that underwent a single-stage right hepatectomy with middle hepatic vein preservation.

The two stages of the procedure were successfully carried out on all 5 patients. For the congestion group, the overall volume of the left hemiliver had increased 103% (mean increase from 438 mL to 890 mL) at 4 wk after the first stage of the procedure. Hypertrophy of the future liver remnant (i.e., segment 4 ± S1) was higher than that of segments 2 and 3 (144% vs 54%, respectively, P < 0.05). The median remnant liver volume-to-body weight ratio was 0.3 (range, 0.28-0.40) before the first stage and 0.8 (range, 0.45-0.97) before the second stage. For the comparison group, the rate of hypertrophy of the left liver after right hepatectomy with middle hepatic vein preservation was 116% ± 34%. Hypertrophy rates of segments 2 and 3 (123% ± 47%) and of segment 4 (108% ± 60%, P > 0.05) were proportional. The mean preoperative volume of segments 2 and 3 was 256 ± 64 cc and increased to 572 ± 257 cc after right hepatectomy. Mean preoperative volume of segment 4 increased from 211 ± 75 cc to 439 ± 180 cc after surgery.

The proposed method for extreme hepatectomy with preservation of segment 4 only represents a technique that could allow complete resection of multiple bilateral liver metastases.

• Hepatectomy
• Colorectal liver metastases
• Hepatic congestion
• Liver regeneration
• Liver resection
• Liver failure

• Adult
• Aged
• Colorectal Neoplasms
• Female
• Hepatectomy/methods
• Hepatectomy/mortality
• Humans
• Hypertrophy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Liver Regeneration
• Middle Aged
• Retrospective Studies

• Complications
• Metastasis
• Outcome
• Surgery
• Systemic chemotherapy

• Radiofrequency assisted liver partition with portal vein ligation (RALPP)
• associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)
• liver resection
• portal vein ligation
• radio-frequency ablation
• two-stage

• Colorectal cancer (CRC)
• hepatectomy
• liver metastases
• portal vein embolization (PVE)
• radiofrequency ablation (RFA)

• Rectal cancer
• neoadjuvant
• primary first
• synchronous liver metastases

Several reports have presented conflicting results regarding the association between resection margins (RMs) and outcome after surgery for colorectal liver metastases (CLM), especially in the era of modern chemotherapy. The purpose of this study was to evaluate the impact of RMs on overall survival (OS), time to recurrence (TTR) and local recurrence (LR) status, particularly for patients treated with preoperative chemotherapy.

A combined retrospective (1998 to 2008) and prospective (2008 to 2010) cohort study of consecutive patients with CLM without extrahepatic disease treated with primary resection at a medium volume centre.

A total of 253 patients with known R status and 242 patients with defined margin width were included in the study. Patients were stratified according to margin width; A: R1, <1 mm (n = 48, 19%), B: 1 to 4 mm (n = 77), C: 5 to 9 mm (n = 46) and D: ≥10 mm (n = 71). Median time to recurrence was 12.8 months, and after five years 21.5% had no recurrence. LR (inclusive combined recurrence in other hepatic sites or extrahepatic) occurred in 40 (16.5%) cases, most frequently seen with RMs below 5 mm. Five-year OS was 42.5% in R0 and 16.1% in R1 resections (P = 0.011). Patients were also stratified according to preoperative chemotherapy (n = 88), and the difference in five-year OS between R0 (45.1%) and R1 (14.7%) was maintained (P = 0.037). By multiple Cox regression analysis R1 resections tended to an adverse outcome (P = 0.067), also when adjusting for preoperative chemotherapy (P = 0.081).

R1 resections for colorectal liver metastases predict adverse outcome. RMs below 5 mm increased the risk for LR and shortened the time to recurrence. Preoperative chemotherapy did not alter an adverse outcome in R1 vs. R0 patients.

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/administration & dosage
• Colorectal Neoplasms/pathology
• Combined Modality Therapy
• Disease Progression
• Embolization, Therapeutic
• Feasibility Studies
• Female
• Hepatectomy/methods
• Humans
• Italy
• Liver Neoplasms/drug therapy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Retrospective Studies
• Risk Factors
• Survival Rate
• Treatment Failure

• Adult
• Aged
• Colorectal Neoplasms/pathology
• Contrast Media
• Female
• Fluorescent Dyes
• Hepatectomy
• Humans
• Indocyanine Green
• Intraoperative Care
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Molecular Imaging/methods
• Multidetector Computed Tomography
• Multimodal Imaging/methods
• Neoplasm Micrometastasis
• Predictive Value of Tests
• Ultrasonography

• Aged
• Aged, 80 and over
• Colorectal Neoplasms
• Embolization, Therapeutic
• Female
• Hepatectomy
• Humans
• Hypertrophy
• Imaging, Three-Dimensional
• Liver/pathology
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Liver Regeneration
• Male
• Middle Aged
• Portal Vein
• Retrospective Studies
• Surgery, Computer-Assisted