Comparison of clinical outcome between laparoscopic and open hepatectomy of high difficulty score for hepatocellular carcinoma: a propensity score analysis.

BACKGROUND: Laparoscopic liver resection (LLR) of high difficulty score is technically challenging. There is a lack of clinical evidence to support its applicability in terms of the long-term survival benefits. This study aims to compare clinical outcomes between LLR and the open liver resection of high difficulty score for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From 2010 to 2020, using Iwate criteria, 424 patients underwent liver resection of high difficulty score by the laparoscopic (n = 65) or open (n = 359) approach. Propensity score (PS) matching was performed between the two groups. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: The laparoscopic group had significantly fewer severe complications (3% vs. 10.8%), and shorter median hospital stays (6 days vs. 8 days) than the open group. Meanwhile, the long-term oncological outcomes were comparable between the two groups, in terms of the tumor recurrence rate (40% vs. 46.1%), the 5-year overall survival rate (75.4% vs. 76.2%), and the 5-year recurrence-free survival rate (50.3% vs. 53.5%). The high preoperative serum alpha-fetoprotein level, multiple tumors, and severe postoperative complications were the independent poor prognostic factors associated with worse overall survival. The surgical approach (Laparoscopic vs. Open) did not influence the survival. CONCLUSION: LLR of high difficulty score for selected patients with HCC has better short-term outcomes than the open approach. More importantly, it can achieve similar long-term survival outcomes as the open approach.

The Impact of Involved Resection Margin on Recurrence and Survival After Pancreaticoduodenectomy for Periampullary Carcinoma, with Emphasis on Pancreatic Head Carcinoma.

BACKGROUND: The supposed adverse effect of involved resection margin during pancreaticoduodenectomy (PD) for periampullary carcinoma or pancreatic head carcinoma (CaP) on long-term oncological outcomes is still inconclusive. METHODS: This is a retrospective study on periampullary carcinoma undergoing PD. Patients with R0 (margin clear) resection were compared to patients with R1 (microscopically directly involved margin) resection. Patients with gross involved margin (R2 resection) were excluded. Long-term oncological outcomes measured included incidence and site of recurrent disease, overall survival (OS) and disease-free survival (DFS). A subgroup analysis was made on patients with CaP. RESULTS: Between January 2003 and December 2019, 203 PD were identified for present study. The incidence of R1 resection was common (12% in periampullary carcinoma and 20% in CaP). In periampullary carcinoma, R1 resection had greater proportion of CaP, lesser proportion of carcinoma of ampulla (CaA), more perineural invasion, more lymph node (LN) metastasis. R1 group had a shorter OS and DFS, but no difference in the incidence and site of recurrent disease. In the subgroup of CaP (91 patients), R1 group did not differ from R0 group except for more LN metastasis. There was no difference in incidence and site of recurrent disease, OS and DFS. On multivariable analysis, R1 resection was not an independent factor for OS and DFS for periampullary carcinoma or for CaP only. CONCLUSION: Involved resection margin was not uncommon. It was not associated with higher incidence of recurrent disease including local recurrence, and was not an independent prognosticator for OS and DFS.

Minimally invasive versus open liver resection for hepatocellular carcinoma: a propensity score matching analysis of 224 patients.

PURPOSE: To compare the peri-operative and long-term survival outcomes of minimally invasive liver resection (MILR) (robotic or laparoscopic) with open liver resection (OLR) in patients with hepatocellular carcinoma (HCC). METHODS: Data of patients who underwent liver resection for HCC were reviewed from a prospectively collected database. Outcomes of MILR were compared with those of OLR. A propensity score matching analysis with a ratio of 1:1 was performed to minimise the potential bias in clinical pathological factors. RESULTS: From January 2003 to December 2017, a total of 705 patients underwent liver resection for HCC. Amongst them, 112 patients received MILR and 593 patients received OLR. After propensity score matching, there were 112 patients in each of the MILR and OLR groups. Patients were matched by age, sex, hepatitis status, presence of cirrhosis, platelet count, albumin level, bilirubin level, alkaline phosphatase (ALP) level, alanine transferase (ALT) level, creatinine level, tumour differentiation, tumour size, tumour number, presence of tumour rupture, presence of vascular invasion, extent of liver resection (minor/major) and difficulty score. The 1-, 3- and 5-year overall survival rates were 94.4%, 90.4% and 82.3% in the MILR group vs 95.4%, 80.5% and 71.8% in the open group (p = 0.240). The 1-, 3- and 5-year disease-free survival rates were 81.0%, 63.1% and 55.8% in the MILR group vs 79.1%, 58.1% and 45.7 in the open group (p = 0.449). The MILR group demonstrated significantly less blood loss (p < 0.001), less blood transfusion (p = 0.004), lower post-operative complications (p < 0.001) and shorter hospital stay (p < 0.001) when compared with the OLR group. CONCLUSIONS: Our data shows MILR yielded superior post-operative outcomes to OLR, with comparable survival outcomes.

Is hepatic resection justified for non-colorectal non-neuroendocrine liver metastases? A systematic review and meta-analysis.

BACKGROUND: Hepatic resection (HR) is effective for colorectal or neuroendocrine liver metastases. However, the role of HR for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is unknown. This study aims to perform a systematic review and meta-analysis on long-term clinical outcomes after HR for NCNNLM. METHODS: electronic search was performed to identify relevant publications using PRISMA and MOOSE guidelines. Primary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were post-operative morbidity and 30-day mortality. RESULTS: There were 40 selected studies involving 5696 patients with NCNNLM undergone HR. Pooled data analyses showed that the 3- and 5-year OS were 40% (95% CI 0.35-0.46) and 32% (95% CI 0.29-0.36), whereas the 3- and 5-year DFS were 28% (95% CI 0.21-0.36) and 24% (95% CI 0.20-0.30), respectively. The postoperative morbidity rate was 28%, while the 30-day mortality was 2%. Subgroup analysis on HR for gastric cancer liver metastasis revealed the 3-year and 5-year OS of 39% and 25%, respectively. CONCLUSIONS: HR for NCNNLM may achieve satisfactory survival outcome in selected patients with low morbidities and mortalities. However, more concrete evidence from prospective study is warrant in future.

Development and validation of a novel nomogram predicting 10-year actual survival after curative hepatectomy for hepatocellular carcinoma.

INTRODUCTION: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), the associated 10-year long-term actual survival are rarely reported. This study aims to develop and validate a predictive nomogram for 10-year actual survivors with HCC. MATERIALS AND METHODS: From 2004 to 2009, 753 patients with curative hepatectomy for HCC (development set, n = 325; validation set, n = 428) were included. In development set, comparison of clinic-pathological data was made between patients surviving ≥10 years and those surviving <10 years. Good independent prognostic factors identified by multivariate analysis were involved in a nomogram development, which was validated internally and externally using validation set. RESULTS: On multivariate analysis, five independent good prognostic factors for 10-year survival were identified, including young age (OR = 0.943), good ASA status (≤2) (OR = 2.794), higher albumin level (OR = 1.116), solitary tumor (OR = 2.531) and absence of microvascular invasion (OR = 3.367). A novel nomogram was constructed with C-index of 0.801 (95% CI 0.762-0.864). A cut-off point of 167.5 had a sensitivity of 0.794 and specificity of 0.730. Internal validation using bootstrap sampling and external validation using validation set revealed C-index of 0.792 (95% CI, 0.741-0.853) and 0.761 (95% CI, 0.718-0.817). CONCLUSION: A novel nomogram for 10-year HCC survivor using age, ASA status, preoperative albumin, tumor number and presence of microvascular tumor invasion was developed and validated with high accuracy.

Robotic versus laparoscopic hepatectomy: application of the difficulty scoring system.

BACKGROUND: The development of robotic system may help to relieve the difficulties encountered during laparoscopic hepatectomy. A difficulty scoring system (DSS) was developed to assess the difficulty of various laparoscopic liver resection procedures. The aim of this study is to explore if the DSS is applicable in robotic hepatectomy and to compare the outcomes of robotic hepatectomy and laparoscopic hepatectomy among different difficulty levels. METHODS: Clinical data from all consecutive patients who underwent robotic and conventional laparoscopic hepatectomy at the Prince of Wales Hospital, Hong Kong, were prospectively collected and reviewed. The difficulty level of operations was graded using the DSS. Perioperative outcomes of robotic and conventional laparoscopic hepatectomy were compared at each difficulty level. RESULTS: A total of 107 and 94 patients underwent robotic and laparoscopic hepatectomy during the study period, respectively. Among them, 16 and 2 patients were operated for recurrent pyogenic cholangitis, respectively, and were excluded because no mark for tumour location can be assigned. For robotic hepatectomy, a higher DSS was significantly correlated with higher minor complication rate (p = 0.001), more intraoperative blood loss (p = 0.002), longer operation time (p < 0.001) and longer post-operative hospital stay (p < 0.001). The mean DSS scores of robotic and laparoscopic hepatectomy were 4.5 and 3.6, respectively. (p = 0.004). For cases with low (DSS 1-3) and intermediate (DSS 4-6) difficulty level, there was no significant difference in operative blood loss, operation time and overall complications rate. Only 2 cases (2.2%) with high difficulty level were operated with laparoscopic approach while 20% of patients operated with robotic approach had DSS > 6. CONCLUSIONS: DSS significantly correlated with surgical outcomes in patient who underwent robotic hepatectomy. Perioperative outcomes following robotic and conventional laparoscopic hepatectomy were similar in cases with low and intermediate difficulty. However, robotic system allowed minimally invasive approach in cases with higher difficulty level.

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

Impact of Intermittent Pringle Maneuver on Long-Term Survival After Hepatectomy for Hepatocellular Carcinoma: Result from Two Combined Randomized Controlled Trials.

BACKGROUND: Hepatectomy remains an important curative treatment for hepatocellular carcinoma (HCC). Intermittent Pringle maneuver (IPM) is commonly applied during hepatectomy for control of bleeding. Whether the ischemia/reperfusion injury brought by IPM adversely affects the operative outcomes is controversial. This study aims to examine whether the application of IPM during hepatectomy affects the long-term outcomes. METHODS: Two randomized controlled trials (RCT) have been carried out previously to evaluate the short-term outcomes of IPM. The present study represented a post hoc analysis on the HCC patients from the first RCT and all patients from the second RCT, and the long-term outcomes were evaluated. RESULTS: There were 88 patients each in the IPM group and the no-Pringle-maneuver (NPM) group. The patient demographics, type and extent of liver resection and histopathological findings were comparable between the two groups. The 1-, 3-, 5-year overall survival in the IPM and NPM groups was 92.0%, 82.0%, 72.1% and 93.2%, 68.8%, 58.1%, respectively (P = 0.030). The 1-, 3-, 5-year disease-free survival in the IPM and NPM groups was 73.6%, 56.2%, 49.7% and 71.6%, 49.4%, 40.3%, respectively (P = 0.366). On multivariable analysis, IPM was a favorable factor for overall survival (P = 0.035). Subgroup analysis showed that a clamp time of 16-30 min (P = 0.024) and cirrhotic patients with IPM (P = 0.009) had better overall survival. CONCLUSION: IPM provided a better overall survival after hepatectomy for patients with HCC. Such survival benefit was noted in cirrhotic patients, and the beneficial duration of clamp was 16-30 min. TRIAL REGISTRATION: NCT00730743 and NCT01759901 ( http://www.clinicaltrials.gov ).

Microwave ablation provides better survival than liver resection for hepatocellular carcinoma in patients with borderline liver function: application of ALBI score to patient selection.

BACKGROUND: Studies comparing microwave ablation (MWA) and liver resection are lacking. This study evaluates the survival of patients with hepatocellular carcinoma (HCC) treated with liver resection or MWA and the role of Albumin-Bilirubin (ALBI) score in patient selection for treatments. METHODS: This is a retrospective analysis of patients who received curative liver resection or MWA for HCC. Propensity score matching was used at a 1:1 ratio. The value of ALBI grade for patient selection was evaluated. Overall and disease-free survival were compared between two groups. RESULTS: Of the 442 patients underwent MWA or liver resection for HCC during the study period, 63 patients received MWA and 379 patients received liver resection. Propensity scoring matching analysis resulted in 63 matched pairs for further analysis. Subgroup analysis according to the ALBI grade was performed. Liver resection offered better overall and disease-free survivals in patients with ALBI grade 1. MWA provided a significantly better overall survival (p = 0.025) and a trend towards better disease-free survival (p = 0.39) in patients with ALBI grade 2 or 3. CONCLUSIONS: Liver resection offered superior disease-free survival to MWA in patients with HCC. The ALBI grade could identify patients with worse liver function who might gain survival advantage from MWA.

Comparison of long-term survival outcome after curative hepatectomy between selected patients with non-colorectal and colorectal liver metastasis: A propensity score matching analysis.

BACKGROUND: Liver resection is an established treatment of choice for colorectal liver metastasis (CLM). However, the role of hepatectomy for non-colorectal liver metastasis (NCLM) is less clear. PATIENTS AND METHOD: From 2004 to 2017, 264 patients received curative hepatectomy for NCLM (n = 28) and CLM (n = 236). Propensity score (PS) matching was performed between two groups, with respect to the significant confounding factors. Short-term and long-term outcomes were compared between PS matched groups. Univariate analysis was performed to identify prognostic factors affecting overall and recurrence-free survival. RESULTS: After PS matching, there were 28 patients in NCLM group and 56 patients in CLM group. With a median follow-up of 34 months, there was no significant difference in 5-year overall survival rate between NCLM and CLM groups (62% vs. 39%) (P = 0.370). The 5-year recurrence-free survival rate was also comparable between NCLM and CLM groups (23% vs. 22%) (P = 0.707). Use of pre-operative systemic therapy (hazard ratio: 2.335, CI 1.157-4.712), multifocal tumors (hazard ratio: 1.777, CI 1.010-3.127), tumor size (hazard ratio: 1.135, CI 1.012-1.273), R1 resection (hazard ratio: 2.484, CI 1.194-5.169) and severe complications (hazard ratio: 6.507, CI 1.454-29.124), but not tumor type (NCLM vs. CLM), were associated with poor overall survival. CONCLUSION: Hepatectomy for NCLM can achieve similar oncological outcomes in selected patients as those with CLM. Significant prognostic factors were identified associating with worse overall survival.

ERAS in minimally invasive hepatectomy.

Open hepatectomy is associated with significant post-operative morbidity and mortality profile. The use of minimally invasive approach for hepatectomy can reduce the post-operative complication profile and total length of hospital stay. Enhanced recovery after surgery (ERAS) programs involve evidence-based multimodal care pathways designed to achieve early recovery for patients undergoing major surgery. This review will discuss the published evidence, challenges and future directions for ERAS in minimally invasive hepatectomy.

Single-center experience on actual mid-term (≥5 years) and long-term (≥10 years) survival outcome in patients with hepatocellular carcinoma after curative hepatectomy: A bimodal distribution.

Analysis for actual mid-term (≥5 years) and long-term (≥10 years) survivors with hepatocellular carcinoma (HCC) following curative hepatectomy are rarely reported in the literature.This retrospective study aims to study the mid- and long-term survival outcome and associated prognostic factors following curative hepatectomy for HCC in a tertiary referral center.The clinical data of 325 patients who underwent curative hepatectomy for HCC were reviewed. They were stratified into 3 groups for comparison (Group 1, overall survival <5 years; Group 2, overall survival ≥5, and <10 years; Group 3, overall survival ≥10 years). Favorable independent prognostic factors for mid- and long-term survival were analyzed.A bimodal distribution of actual survival outcome was observed, with short-term (<5 years) survival of 52.7% (n = 171), mid-term survival of 18.1% (n = 59), and long-term survival of 29.2% (n = 95). Absence of microvascular invasion (OR 3.690, 95% CI: 1.562-8.695) was independent good prognostic factor for mid-term survival. Regarding long-term overall survival, young age (OR 1.050, 95% CI: 0.920-0.986), ASA grade ≤2 (OR 3.746, 95% CI: 1.325-10.587), high albumin level (OR 1.008, 95% CI: 0.920-0.986), solitary tumor (OR 3.289, 95% CI: 1.149-7.625) and absence of microvascular invasion (OR 4.926, 95% CI: 2.192-11.111) were independent good prognostic factors.Curative hepatectomy results in bimodal actual survival outcome with favorable long-term survival rate of 29.2%. Favorable independent prognostic factors (age, ASA grade, albumin level, tumor number, and microvascular invasion) are identified for overall survival.

Successful robotic extirpation of diaphragmatic seeding of hepatocellular carcinoma after previous rupture.

A 51-year-old man who was a hepatitis B carrier presented with ruptured hepatocellular carcinoma (HCC). Hepatic arterial embolization was performed for control of bleeding which was followed by staged open left lateral sectionectomy for tumor removal. Pathology confirmed a 3.5 cm ruptured subcapsular HCC in a cirrhotic liver with clear resection margin. However, the alpha-fetoprotein (AFP) increased from 14 to 72 µg/L after 7 months. A 1.7 × 0.8 cm nodule at left subdiaphragmatic region abutting on the spleen but no intrahepatic lesion was seen on computed tomography (CT). Dual tracer positron emission tomography suggested the nodule was a HCC seeding with no other recurrent tumor noted. Robotic exploration was offered to patient with the possibility of splenectomy. During operation, the nodule was adherent to the diaphragm with no splenic involvement. The lesion was locally excised. The diaphragmatic defect was closed with non-absorbable suture. Recovery was uneventful and the patient was discharged on postoperative day 4. Pathology confirmed HCC cells infiltrating to skeletal muscle and fibrous tissue. The resection margin was clear. Post-operatively AFP normalised. Serial abdominal CT and ultrasound revealed no evidence of recurrent disease. Patient had a disease-free survival of 47 months after excision of tumor seeding.

Pattern of disease recurrence and its implications for postoperative surveillance after curative hepatectomy for hepatocellular carcinoma: experience from a single center.

BACKGROUND: Hepatectomy is a widely accepted curative treatment for hepatocellular carcinoma (HCC). However, the disease frequently recurs after a curative hepatectomy. The objective of this study is to provide a better understanding of the pattern of disease recurrence and the risk factors involved so as to improve the postoperative surveillance. METHODS: A retrospective study for all patients receiving hepatectomy for HCC between 2003 and 2014 was performed. Emphasis was made on the timing and pattern of recurrent disease, and type of treatment given. RESULTS: There were 506 patients in the study. Median follow-up was 43.7 months. The 1-, 3-, 5-, 10-year overall and disease free survival were 89.5%, 74.1%, 63.9%, 49.0% and 69.5%, 54.3%, 43.4%, 30.9% respectively. Recurrent disease occurred in 267 patients, 47.2% occurred within 9 months of hepatectomy and 80.1% recurred only in liver. Median survival was shorter for recurrence occurring within 9 months compared with those occurring between 10 months and 2 years postoperatively (36.2 vs. 65.7 months, P<0.01) whilst less curative treatment was offered for patients with early (within 9 months) intrahepatic alone recurrence (22.2% vs. 51.7%, P<0.01). Multivariate analysis revealed tumor size >3.5 cm and history of rupture were risk factors for recurrence within 9 months. CONCLUSIONS: These findings suggest that recurrent diseases are common after curative hepatectomy for HCC and most recurrences occur in the remnant liver. Since almost half of recurrences occurred within first 9 months after hepatectomy, a more stringent postoperative surveillance with target imaging of liver in this period is needed. Early diagnosis of recurrent disease and curative retreatment hopefully can bring about a longer survival.