Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study.

INTRODUCTION: Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC). METHODOLOGY: Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion. RESULTS: There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted. CONCLUSION: Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.

Association of standardized liver volume and body mass index with outcomes of minimally invasive liver resections.

INTRODUCTION: While minimally invasive liver resections (MILR) have demonstrated advantages in improved post-operative recovery, widespread adoption is hampered by inherent technical difficulties. Our study attempts to analyze the role of anthropometric measures in MILR-related outcomes. METHODS: Between 2012 and 2020, 676 consecutive patients underwent MILR at the Singapore General Hospital of which 565 met study criteria and were included. Patients were stratified based on Body Mass Index (BMI) as well as Standardized Liver Volumes (SLV). Associations between BMI and SLV to selected peri-operative outcomes were analyzed using restricted cubic splines. RESULTS: A BMI of ≥ 29 was associated with increase in blood loss [Mean difference (MD) 69 mls, 95% CI 2 to 137] as well as operative conversions [Relative Risk (RR) 1.63, 95% CI 1.02 to 2.62] among patients undergoing MILR while a SLV of 1600 cc or higher was associated with an increase in blood loss (MD 30 mls, 95% CI 10 to 49). In addition, a BMI of ≤ 20 was associated with an increased risk of major complications (RR 2.25, 95% 1.16 to 4.35). The magnitude of differences observed in these findings increased with each unit change in BMI and SLV. CONCLUSION: Both BMI and SLV were useful anthropometric measures in predicting peri-operative outcomes in MILR and may be considered for incorporation in future difficulty scoring systems for MILR.

Impact of non-liver-related previous abdominal surgery on the difficulty of minimally invasive liver resections: a propensity score-matched controlled study.

INTRODUCTION: The presence of previous abdominal surgery (PAS) has traditionally been considered to add difficulty to and increase risk of complications of laparoscopic procedures. This study aims to analyse the impact of non-liver-related PAS on the difficulty of minimally invasive liver resections (MILRs). MATERIALS AND METHODS: After exclusion of patients with concomitant major surgical procedures as well as previous liver resections, 515 consecutive patients undergoing MILR in Singapore General Hospital from 2006 to 2019 were analysed, consisting of 161 MILR in patients with previous abdominal surgery (WPAS) and 354 MILR in patients without previous abdominal surgery (WOPAS). Propensity score-matched (PSM) comparison was performed between WPAS and WOPAS groups. In addition, subgroup analysis was made comparing previous upper or lower abdominal surgery and open versus minimally invasive approach of PAS. Outcomes measured include those associated with operative difficulty such as open conversion rates, operative time, blood loss, as well as morbidity and mortality rates. RESULTS: MILR outcomes in patients WPAS are not inferior to those WOPAS. Overall open conversion rate was 8.2%, higher in patients WOPAS compared to patients WPAS (11.9% versus 3.5%, p = 0.015). Operating time (p = 0.942), blood loss (p = 0.063), intraoperative blood transfusion (p = 0.750), length of hospital stay (p = 0.206), morbidity (p = 0.217) and 30- and 90-day mortality (p = 1 & p = 0.367) were comparable between the two groups and subgroup analysis. CONCLUSION: Outcomes of MILR in patients with previous non-liver-related abdominal surgery are not inferior to patients without previous abdominal surgery.

Propensity-Score Matched Analyses Comparing Clinical Outcomes of Minimally Invasive Versus Open Distal Pancreatectomies: A Single-Center Experience.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) is being adopted increasingly worldwide. This study aimed to compare the short-term outcomes of patients who underwent MIDP versus open distal pancreatectomy (ODP). METHODS: A retrospective review of all patients who underwent a DP in our institution between 2005 and 2019 was performed. Propensity score matching based on relevant baseline factors was used to match patients in the ODP and MIDP groups in a 1:1 manner. Outcomes reported include operative duration, blood loss, postoperative length of stay, morbidity, mortality, postoperative pancreatic fistula rates, reoperation and readmission. RESULTS: In total, 444 patients were included in this study. Of 122 MIDP patients, 112 (91.8%) could be matched. After matching, the median operating time for MIDP was significantly longer than ODP [260 min (200-346.3) vs 180 (135-232.5), p < 0.001], while postoperative stay for MIDP was significantly shorter [median 6 days (5-8) versus 7 days (6-9), p = 0.015]. There were no significant differences noted in any of the other outcomes measured. Over time, we observed a decrease in the operation times of MIDP performed at our institution. CONCLUSION: Adoption of MIDP offers advantages over ODP in terms of a shorter postoperative hospital stay, without an increase in morbidity and/or mortality but at the expense of a longer operation time.

Short- and long-term outcomes after minimally invasive versus open spleen-saving distal pancreatectomies.

INTRODUCTION: This study aimed to compare the perioperative outcomes of patients who underwent minimally invasive spleen-preserving distal pancreatectomy (MI-SPDP) versus open surgery SPDP (O-SPDP). It also aimed to determine the long-term vascular patency after spleen-saving vessel-preserving distal pancreatectomies (SSVDPs). METHODS: A retrospective review of 74 patients who underwent successful SPDP and met the study criteria was performed. Of these, 67 (90.5%) patients underwent SSVDP, of which 38 patients (21 open, 17 MIS) had adequate long-term post-operative follow-up imaging to determine vascular patency. RESULTS: Fifty-one patients underwent open SPDP, whereas 23 patients underwent minimally invasive SPDP, out of which 10 (43.5%) were laparoscopic and 13 (56.5%) were robotic. Patients who underwent MI-SPDP had significantly longer operative time (307.5 vs. 162.5 min, P = 0.001) but shorter hospital stay (5 vs. 7 days, P = 0.021) and lower median blood loss (100 vs. 200 cc, P = 0.046) compared to that of O-SPDP. Minimally-invasive spleen-saving vessel-preserving distal pancreatectomy (MI-SSVDP) was associated with poorer long-term splenic vein patency rates compared to O-SSVDP (P = 0.048). This was particularly with respect to partial occlusion of the splenic vein, and there was no significant difference between the complete splenic vein occlusion rates between the MIS group and open group (29.4% vs. 28.6%, P = 0.954). The operative time was statistically significantly longer in patients who underwent robotic surgery versus laparoscopic surgery (330 vs. 173 min, P = 0.008). CONCLUSION: Adoption of MI-spleen-preserving distal pancreatectomy (SPDP) is safe and feasible. MI-SPDP is associated with a shorter hospital stay, lower blood loss but longer operation time compared to O-SPDP. In the present study, MI-SSVDP was associated with poorer long-term splenic vein patency rates compared to O-SSVDP.

Repeat hepatectomy versus radiofrequency ablation in management of recurrent hepatocellular carcinoma: an average treatment effect analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with high rates of recurrence post-resection. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) are the mainstays for managing recurrent HCC following initial curative resection. This retrospective study aims to determine the average treatment effect of RH and RFA in patients with recurrent HCC. PATIENTS AND METHODS: From 2000 to 2016, a total of 219 consecutive patients with recurrent HCC who underwent either RH or RFA were included in the study. The analysis was performed using inverse probability of treatment weighting (IPTW), and propensity score-matched (PSM) methods. RESULTS: The minor and major post-operative morbidity after propensity score-matched analysis for the RH group was 30.0% and 6.0%, respectively, and 19.2% and 0.0% (p = 0.1006), respectively, for the RFA group. After propensity score matching, the median OS for RH and RFA was 85.5 (IQR, 33.5-not reached) and 53.3 months (IQR, 27.5-not reached) (p = 0.8474), respectively. There was no significant difference in 90-day mortality between both groups (p = 0.1287). RH showed improved long-term overall survival over RFA at the third [71.3% versus 65.7% (p = 0.0432)], fifth [59.9% versus 45.4% (p = 0.0271)] and tenth [35.4% versus 32.2% (p = 0.0132)] year follow-up, respectively. Median time to recurrence was 11.1 (IQR, 5.0-33.2) and 28.0 months (IQR, 9.1-not reached) (p = 0.0225) for the RFA and RH group, respectively. CONCLUSIONS: RH confers a late survival benefit compared with RFA for patients with recurrent HCC despite a higher morbidity rate.

Comparison between short and long-term outcomes after minimally invasive versus open primary liver resections for hepatocellular carcinoma: A 1:1 matched analysis.

BACKGROUND: This study aims to compare the short- and long-term outcomes of patients undergoing minimally invasive liver resection (MILR) versus open liver resection (OLR) for nonrecurrent hepatocellular carcinoma (HCC). METHODS: Review of 204 MILR and 755 OLR without previous LR performed between 2005 and 2018. 1:1 coarsened exact matching (CEM) and 1:1 propensity-score matching (PSM) were performed. RESULTS: Overall, 190 MILR were well-matched with 190 OLR by PSM and 86 MILR with 86 OLR by CEM according to patient baseline characteristics. After PSM and CEM, MILR was associated with a significantly longer operation time [230 min (interquartile range [IQR], 145-330) vs. 160 min (IQR, 125-210), p < .001] [215 min (IQR, 135-295) vs. 153.5 min (120-180), p < .001], shorter postoperative stay [4 days (IQR, 3-6) vs. 6 days (IQR, 5-8), p = .001)] [4 days (IQR, 3-5) vs. 6 days (IQR, 5-7), p = .004] and lower postoperative morbidity [40 (21%) vs. 67 (35.5%), p = .003] [16 (18.6%) vs. 27 (31.4%), p = .036] compared to OLR. MILR was also associated with a significantly longer median time to recurrence (70 vs. 40.3 months, p = .014) compared to OLR after PSM but not CEM. There was no significant difference in terms of overall survival and recurrence-free survival. CONCLUSION: MILR is associated with superior short-term postoperative outcomes and with at least equivalent long-term oncological outcomes compared to OLR for HCC.

Actual 10-year survivors and 10-year recurrence free survivors after primary liver resection for hepatocellular carcinoma in the 21st century: A single institution contemporary experience.

BACKGROUND: At present, the majority of outcome studies of survival of hepatocellular carcinoma (HCC) post-liver resection (post-LR) present actuarial survival data, which often results in overestimation of survival. We sought to evaluate the actual 10-year survival post-LR for HCC and identify variables that are associated with long-term survival. METHODS: We performed a retrospective review of 600 consecutive patients who underwent primary LR for HCC from 2000 to 2010 at our institution. Twenty-eight patients (4.7%) with 90-day mortality and 125 patients who were lost to follow-up within 10 years were excluded leaving 447 patients who met the study criteria. RESULTS: There were 140 actual 10-year survivors of which 57 (40.7%) had a recurrence within 10 years. The actual 10-year overall survival (OS) rate of the 447 patients was 31.5% and the actual 10-year recurrence-free survival (RFS) was 18.6%. Multivariate analyses demonstrated that only age >65 years (OR, 0.29; p < .001) (OR, 0.973; p = .041) and presence of cirrhosis (OR. 0.37; p = .005) (OR, 0.31; p = .001) were independent factors negatively associated with actual 10-year OS and actual 10-year RFS, respectively. CONCLUSION: Approximately one-third of patients will survive over 10 years after LR for HCC. Amongst these 10-year survivors, 41% had developed recurrent cancer within 10-years of follow-up.

Impact of liver cirrhosis on the difficulty of minimally-invasive liver resections: a 1:1 coarsened exact-matched controlled study.

INTRODUCTION: The impact of liver cirrhosis on the difficulty of minimal invasive liver resection (MILR) remains controversial and current difficulty scoring systems do not take in to account the presence of cirrhosis as a significant factor in determining the difficulty of MILR. We hypothesized that the difficulty of MILR is affected by the presence of cirrhosis. Hence, we performed a 1:1 matched-controlled study comparing the outcomes between patients undergoing MILR with and without cirrhosis including the Iwate system and Institut Mutualiste Montsouris (IMM) system in the matching process. METHODS: Between 2006 and 2019, 598 consecutive patients underwent MILR of which 536 met the study inclusion criteria. There were 148 patients with cirrhosis and 388 non-cirrhotics. One-to-one coarsened exact matching identified approximately exact matches between 100 cirrhotic patients and 100 non-cirrhotic patients. RESULTS: Comparison between MILR patients with cirrhosis and non-cirrhosis in the entire cohort demonstrated that patients with cirrhosis were associated with a significantly increased open conversion rate, transfusion rate, need for Pringles maneuver, postoperative, stay, postoperative morbidity and postoperative 90-day mortality. After 1:1 coarsened exact matching, MILR with cirrhosis were significantly associated with an increased open conversion rate (15% vs 6%, p = 0.03), operation time (261 vs 238 min, p < 0.001), blood loss (607 vs 314 mls, p = 0.002), transfusion rate (22% vs 9%, p = 0.001), need for application of Pringles maneuver (51% vs 34%, p = 0.010), postoperative stay (6 vs 4.5 days, p = 0.004) and postoperative morbidity (26% vs 13%, p = 0.029). CONCLUSION: The presence of liver cirrhosis affected both the intraoperative technical difficulty and postoperative outcomes of MILR and hence should be considered an important parameter to be included in future difficulty scoring systems for MILR.

Preoperative Predictors of Futile Resection of Intraabdominal Extrahepatic Metastases from Hepatocellular Carcinoma.

BACKGROUND: The management of post-liver resection recurrence is often the life-limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post-resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post-metastasectomy. METHODS: We performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution. RESULTS: Of the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15-89 months). Twenty-one patients (84%) developed recurrence post-metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post-metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9-23.0)) compared to those who did not (89 months (95% CI 24.8-153.1), p = 0.004). CONCLUSION: Patients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post-metastasectomy.

Validation and comparison of the Iwate, IMM, Southampton and Hasegawa difficulty scoring systems for primary laparoscopic hepatectomies.

BACKGROUND: Various difficulty scoring systems (DSS) have been formulated to grade the complexity of laparoscopic hepatectomies (LH). This study aims to externally validate and compare 4 contemporary DSS including the Iwate, Institut Mutualiste Montsouris (IMM), Southampton and Hasegawa DSS in predicting the intraoperative technical difficulty and postoperative outcomes after LH. METHODS: Retrospective review of 548 consecutive patients who underwent LH of which 455 met the study inclusion criteria. Outcomes measures of technical difficulty included operation time, Pringles maneuver, blood loss and blood transfusion rate. Postoperative outcomes measured included morbidity, major morbidity and postoperative hospital stay. RESULTS: There was a statistically significant progressive increase in blood loss, blood transfusion rate, operation time and postoperative stay associated with all 4 DSS. There was also good calibration with respect to blood loss, operation time, Pringles maneuver, open conversion rate, postoperative morbidity, postoperative major morbidity and postoperative stay for all 4 DSS. The Southampton score demonstrated the poorest calibration in terms of operation time and discrimination in terms of application of Pringles maneuver and major morbidity amongst all 4 systems. CONCLUSION: All 4 DSS significantly correlated with outcome measures associated with intraoperative technical difficulty and postoperative outcomes. The Southampton DSS was the poorest system in our cohort of patients.

Changing trends in the clinicopathological features, practices and outcomes in the surgical management for cystic lesions of the pancreas and impact of the international guidelines: Single institution experience with 462 cases between 1995-2018.

INTRODUCTION: The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice. METHODS: 462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998-2006, 2007-2012 and 2013 to 2018. RESULTS: Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HRSG06 and HRFG12 CLP with a corresponding lower proportion of LRSG06 and LRFG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated. CONCLUSIONS: Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HRSG06 and HRFG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.

Pre-operative Imaging Characteristics in Histology-Proven Resected Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre. METHODS: Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed. RESULTS: Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group. CONCLUSIONS: A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.

Minimally Invasive Versus Open Pancreatectomies for Pancreatic Neuroendocrine Neoplasms: A Propensity-Score-Matched Study.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) are increasingly prevalent with modern imaging, and surgical excision remains mainstay of treatment. This study aims to perform a propensity-score-matched (PSM) comparison of perioperative and oncologic outcomes following minimally invasive pancreatectomy (MIP) versus open pancreatectomy (OP) for PNEN. METHODS: A retrospective review was performed on patients who underwent curative-intent surgery for PNEN at Singapore General Hospital from 1997 to 2018. A 1:1 PSM was performed between MIP and OP, after which both groups were balanced for baseline variables. RESULTS: We studied 134 patients who underwent surgery (36 MIP and 98 OP) for PNEN. Propensity-score-matched comparison between 35 MIP and 35 OP patients revealed that the MIP group had a longer operating time (MD = 75.0, 95% CI 15.2 to 134.8, P = 0.015), lower intraoperative blood loss (MD = - 400.0, 95% CI - 630.5 to - 169.5, P = 0.001), shorter median postoperative stay (MD = - 1.0, 95% CI - 1.9 to - 0.1, P = 0.029) and shorter median time to diet (MD = - 1.0, 95% CI - 1.9 to - 0.1, P = 0.039). There were no differences between both groups for short-term adverse outcomes and oncologic clearance. Overall survival (HR = 0.84, 95% CI 0.28 to 2.51, P = 0.761) and disease-free survival (HR = 0.57, 95% CI 0.20 to 1.64, P = 0.296) were comparable. CONCLUSION: MIP is a safe and feasible approach for PNEN and is associated with a lower intraoperative blood loss, decreased postoperative stay and time to oral intake, at the expense of a longer operative time compared to OP.

Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial.

OBJECTIVE: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). METHODS: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. RESULTS: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints. CONCLUSION: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy.

Changing trends and outcomes associated with the adoption of minimally invasive pancreatic surgeries: A single institution experience with 150 consecutive procedures in Southeast Asia.

BACKGROUND: Minimally invasive pancreatic surgeries (MIPS) are increasingly adopted worldwide. However, it remains uncertain if these reported experiences are reproducible throughout the world today. This study examines the safety and evolution of MIPS at a single institution in Southeast Asia. METHODS: This is a retrospective review of 150 consecutive patients who underwent MIPS between 2006 and 2018 of which 135 cases (90%) were performed since 2012. To determine the evolution of MIPS, the study population was stratified into 3 equal groups of 50 patients. Comparison was also made between pancreatoduodenectomies (PD), distal pancreatectomies (DP) and other pancreatic surgeries. RESULTS: One hundred and fifty patients underwent MIPS (103 laparoscopic, 45 robotic and 2 hand-assisted). Forty-three patients underwent PD, 93 DP and 14 other MIPS. There were 21 (14.0%) open conversions. There was an exponential increase in caseload over the study period. Comparison across the 3 time periods demonstrated that patients were significantly more likely to have a higher American Society of Anesthesiologists score, older, undergo PD and a longer operation time. The conversion rate decreased from 28% to 0% and increased again to 14% across the 3 time periods. Comparison between the various types of MIPS demonstrated that patients who underwent PD were significantly older, more likely to have symptomatic tumours, had longer surgery time, increased blood loss, increased frequency of extended pancreatectomies, increased frequency of hybrid procedures, longer post-operative stay, increased post-operative morbidity rate and increased post-operative major morbidity rate. CONCLUSION: The case volume of MIPS increased rapidly at our institution over the study period. Furthermore, although the indications for MIPS expanded to include more complex procedures in higher risk patients, there was no change in key perioperative outcomes.

Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the second most deadly cancer with late presentation and limited treatment options, highlighting an urgent need to better understand HCC to facilitate the identification of early-stage biomarkers and uncover therapeutic targets for the development of novel therapies for HCC. METHODS: Deep transcriptome sequencing of tumor and paired non-tumor liver tissues was performed to comprehensively evaluate the profiles of both the host and HBV transcripts in HCC patients. Differential gene expression patterns and the dys-regulated genes associated with clinical outcomes were analyzed. Somatic mutations were identified from the sequencing data and the deleterious mutations were predicted. Lastly, human-HBV chimeric transcripts were identified, and their distribution, potential function and expression association were analyzed. RESULTS: Expression profiling identified the significantly upregulated TP73 as a nodal molecule modulating expression of apoptotic genes. Approximately 2.5% of dysregulated genes significantly correlated with HCC clinical characteristics. Of the 110 identified genes, those involved in post-translational modification, cell division and/or transcriptional regulation were upregulated, while those involved in redox reactions were downregulated in tumors of patients with poor prognosis. Mutation signature analysis identified that somatic mutations in HCC tumors were mainly non-synonymous, frequently affecting genes in the micro-environment and cancer pathways. Recurrent mutations occur mainly in ribosomal genes. The most frequently mutated genes were generally associated with a poorer clinical prognosis. Lastly, transcriptome sequencing suggest that HBV replication in the tumors of HCC patients is rare. HBV-human fusion transcripts are a common observation, with favored HBV and host insertion sites being the HBx C-terminus and gene introns (in tumors) and introns/intergenic-regions (in non-tumors), respectively. HBV-fused genes in tumors were mainly involved in RNA binding while those in non-tumors tissues varied widely. These observations suggest that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts may occur during tumorigenesis. CONCLUSIONS: Transcriptome sequencing of HCC patients reveals key cancer molecules and clinically relevant pathways deregulated/mutated in HCC patients and suggests that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts likely occur during the process of tumorigenesis.

Critical Appraisal of the Impact of the Systematic Adoption of Advanced Minimally Invasive Hepatobiliary and Pancreatic Surgery on the Surgical Management of Mirizzi Syndrome.

BACKGROUND: Minimally invasive surgery (MIS) for Mirizzi syndrome (MS) remains a technically challenging procedure with a high open conversion rate. We critically evaluated the impact of the systematic adoption of MI-HBP surgery on the surgical outcomes of MS. METHODS: Ninety-five patients who underwent surgery for MS were retrospectively reviewed. Systematic adoption of advanced MI-HBP surgery started in 2012. The cohort was classified into a preadoption (2002-2012) (Era 1, n = 58) and post-adoption (2013-2017) (Era 2, n = 37). Furthermore, Era 2 was divided into a cohort operated by advanced minimally invasive surgeons (AMIS) (Era 2 AMIS, n = 19) and those by other surgeons (Era 2 others, n = 19). RESULTS: Comparison between Era 2 and Era 1 demonstrated a significant increase in the frequency of MIS attempted (89% vs 33%, p < 0.01), increase in the use of choledochoplasty (24% vs 2%, p < 0.01), increase operation time (180 min vs 150 min, p = 0.03) and significantly lower open conversion rate (24% vs 58%, p < 0.01). Comparison between Era 2 AMIS and Era 2 others demonstrated a significantly greater adoption of MIS (100% vs 78%, p = 0.046) with lower open conversion rate (5% vs 50%, p = 0.005). Comparison between all attempted MIS cases with open procedures demonstrated a significantly higher proportion of subtotal cholecystectomies performed (40% vs 23%, p = 0.04), choledochoplasty (17% vs 2%, p = 0.04) and shorter hospital stay (4 days vs 9 days, p < 0.01). CONCLUSIONS: Systematic adoption of advanced MI-HBP surgery allowed surgeons to perform MIS for MS more frequently and with a significantly lower open conversion rate. Patients who underwent successful MIS had the shortest hospital stay compared to patients who underwent open surgery or required open conversion.

Perioperative Outcomes of Laparoscopic Repeat Liver Resection for Recurrent HCC: Comparison with Open Repeat Liver Resection for Recurrent HCC and Laparoscopic Resection for Primary HCC.

BACKGROUND: This study aims to determine the safety and efficacy of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma (rHCC). METHODS: Twenty patients underwent LRLR for rHCC between 2015 and 2017. The control groups consisted of 79 open RLR (ORLR) for rHCC and 185 LLR for primary HCC. We undertook propensity score-adjusted analyses (PSA) and 1:1 propensity score matching (PSM) for the comparison of LRLR versus ORLR. Comparison of LRLR versus LLR was done using multivariable regression models with adjustment for clinically relevant covariates. RESULTS: Twenty patients underwent LRLR with three open conversions (15%). Both PSA and 1:1-PSM demonstrated that LRLR was significantly associated with a shorter stay, superior disease-free survival (DFS) but longer operation time compared to ORLR. Comparison between LRLR versus LLR demonstrated that patients undergoing LRLR were significantly older, had smaller tumors, longer operation time and decreased frequency of Pringle's maneuver applied. There was no difference in other key perioperative outcomes. CONCLUSION: The results of this study demonstrate that in highly selected patients; LRLR for rHCC is feasible and safe. LRLR was associated with a shorter hospitalization but longer operation time compared to ORLR. Moreover, other than a longer operation time, LRLR was associated with similar perioperative outcomes compared to LLR for primary HCC.

Preoperative Predictors Including the Role of Inflammatory Indices in Predicting Early Recurrence After Re-resection for Recurrent Hepatocellular Carcinoma.

BACKGROUND: Repeat liver resection (RLR) for recurrent HCC (rHCC) is a widely accepted treatment modality. However, early recurrence rate is high, frequently resulting in futile resection. We performed this study to evaluate preoperative factors, including the value of inflammatory indices, in predicting early (<1 year) recurrence in patients who underwent RLR for rHCC. This may help clinicians better select patients for RLR, while excluding cases in which RLR for rHCC would likely be futile. METHODS: This is a retrospective study of 80 patients where 90 operative cases of RLR and 84 cases of early recurrence (<1 year) post-RLR were evaluated. Preoperative predictors of early recurrence and overall survival (OS) were assessed. RESULTS: There were 31 (34.4%) early recurrences with a 5-year OS of 38.9%. Elevated platelet-to-lymphocyte ratio (PLR) >103.6 was a significant independent preoperative predictor of both early recurrence, relative risk (RR) 4.284 (P = 0.001) and OS, RR 2.139 (P = 0.027), while alphafetoprotein (AFP) ≥ 200 was a significant independent preoperative predictor of early recurrence only, RR 11.655 (P = 0.030). Patients were followed-up at a median of 14.3 months with 54.8% developing intrahepatic recurrences and 19.4% developing extrahepatic recurrences. CONCLUSION: Both, elevated PLR and AFP ≥ 200 were independent predictors of early (<1 year) recurrence after RLR for rHCC, while only an elevated PLR was an independent preoperative prognosticators of overall survival. Indication for RLR should be carefully discussed in patients with relapsed HCC with an elevated PLR, due to the potential of early recurrence and poor overall survival.