Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial.

Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

Post-transplant inflammatory cytokine signature adds value for predicting tumor recurrence after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Cytokines are key regulators of post-transplant inflammation responses which reconstitute post-transplant hepatic and systemic environments to influence the likelihood of tumor relapse. This study investigated the prognostic value of post-transplant cytokines on tumor recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted in prospectively collected 150 adult HCC patients who received liver transplantation from 1997 to 2015. The post-transplant 41 inflammatory cytokines were quantified by multiplexing analysis and determined their prognostic value for predicting post-LT tumor recurrence by receiver operative characteristic analysis. A prediction model for post-LT tumor recurrence was generated by the logistic regression and internally validated Bootstrapping and compared with external prediction models. RESULTS: Post-transplant circulating CCL11, IFNα2, and IL17A cytokines were identified to be significant predictors of post-LT tumor recurrence and survival. A prediction score composed of the post-transplant 3-cytokine (P3C) signature, UCSF criteria, and pre-LT AFP was established. The P3C-UCSF-AFP score significantly predicted post-LT tumor recurrence and poor survival both in deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). The P3C-UCSF-AFP score was validated to significantly predict post-LT 2-year and 5-year tumor recurrence, outperforming the RETREAT score, French AFP model, up-to-seven, UCSF criteria, and Milan criteria. Importantly, the P3C-UCSF-AFP score could cost-effectively stratify high-risk recipients subjected to a refinement of post-recurrence survival. CONCLUSION: The integrated P3C-UCSF-AFP score not only compensated for the pre-LT unpredictability and predicted post-LT tumor recurrence accurately, but also guided the clinical refinements of post-LT surveillance and therapeutic strategies in transplant oncology.

Impact of Time to Recurrence on Survival Outcome of Salvage Liver Transplantation.

BACKGROUND: Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. METHODS: Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan-Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. RESULTS: Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. CONCLUSION: Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.

Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant.

BACKGROUND AND AIMS: There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS: Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS: SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.

The Risk of Going Small: Lowering GRWR and Overcoming Small-For-Size Syndrome in Adult Living Donor Liver Transplantation.

OBJECTIVE: The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR). BACKGROUND: The standard GRWR in LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients. METHODS: Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 2: 0.6%0.8%). RESULTS: There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R2 = 0.834) and these figures differed within a ±â€Š10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was <35 years and steatosis >10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS): 5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients [24/26 (92.3%)] survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis. CONCLUSIONS: Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach.

Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End-Stage Liver Disease and Hepatorenal Syndrome.

BACKGROUND AND AIMS: Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End-Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). APPROACH AND RESULTS: Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention-to-treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT-LDLT, whereas those who had none belonged to ITT-deceased donor liver transplantation (DDLT) group. ITT-overall survival (OS) was analyzed from the time of listing. Three hundred twenty-five patients were listed (ITT-LDLT n = 212, ITT-DDLT n = 113). The risk of delist/death was lower in the ITT-LDLT group (43.4% vs. 19.8%, P < 0.001), whereas the transplant rate was higher in the ITT-LDLT group (78.3% vs. 52.2%, P < 0.001). The 5-year ITT-OS was superior in the ITT-LDLT group (72.6% vs. 49.5%, P < 0.001) for patients with MELD > 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P < 0.001). Waitlist mortality was the highest early after listing, and the distinct alteration of slope at survival curve showed that the benefits of ITT-LDLT occurred within the first month after listing. Perioperative outcomes and 5-year patient survival were comparable for patients with MELD > 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long-term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT-LDLT reduced the hazard of mortality (hazard ratio = 0.387-0.552) across all MELD strata. CONCLUSIONS: The ITT-LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long-term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.

Strategy on timing of ALPPS stageⅡbased on increase in remnant liver volume / 中华肝胆外科杂志

Objective:To study the safety and efficacy on timing of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) stageⅡbased on increase in remnant liver volume.Methods:19 patients (male: female 13: 6; average age 53 years) with liver tumors treated by ALPPS from April 2014 to December 2020 were retrospectively studied. Patients with FLV/ESLV (future liver volume/ estimated standard liver volume) increase of more than 50% within 1 week followed by stageⅡALPPS were included into the rapid group ( n=8). Those who failed to have 50% increase in FLV/ESLV within 1 week were included into the control group ( n=11). The two groups were compared in the ALPPS stage II in operating time, blood loss, postoperative complications, mortality rate and hospital stay. Results:All 19 patients underwent ALPPS stage II uneventfully. One patient in the control group died from liver failure within 30 days of operation. The operation time (3.2±1.8)h, blood loss (554±227) ml and postoperative hospital stay (12.6±2.4) d in the rapid group were significantly better than those in the control group (4.7±2.2) h, [(760±314) ml, (18.2±6.4) d (all P<0.05)]. The two groups had similar complication rates in both post stageⅠ[37.5%(3/8) vs. 45.4%(5/11)] , or stageⅡ [37.5%(3/8) vs. 36.4%(4/11)] (both P>0.05). Conclusion:Rapid increase in FLR volume of more than 50% within a week was safe and feasible to proceed to ALPPS stage II. This conclusion needs to be confirmed by further studies using large sample sizes.

Model for End-Stage Liver Disease With Additional Criteria to Predict Short-Term Mortality in Severe Flares of Chronic Hepatitis B.

BACKGROUND AND AIMS: The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. APPROACH AND RESULTS: Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low (<25%) compared with > 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P < 0.001). In this MELD bracket, the 28-day mortality was 0%, 12.1%, 23.8%, 59.4%, and 78.8% for the presence of zero, one, two, three, and four criteria, respectively. CONCLUSIONS: MELD score at any time points can accurately predict the short-term mortality. Patients with MELD ≥ 28 should be worked up for liver transplantation, and those with MELD = 28-32 with three to four at-risk criteria, or MELD ≥ 32 should be listed.

Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis.

BACKGROUND & AIMS: The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. METHODS: This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. RESULTS: A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. CONCLUSIONS: De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. LAY SUMMARY: The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

PostOperative ST-segment elevation: not a blocked coronary artery, then what?

ST-segment elevation is well known for its diagnostic value for transmural myocardial infarction due to acute thrombotic occlusion of a coronary artery, and often requires emergency reperfusion therapy. However, ST segment is by no means pathognomonic for acute coronary events. Here, we report a case of ST-segment elevation after hepatectomy secondary to an unusual etiology.

Technical note on ALPPS for a patient with advanced hepatocellular carcinoma associated with invasion of the inferior vena cava.

Patients with hepatocellular carcinoma have a very short life expectancy if they receive no surgical intervention. A relatively new surgical technique termed "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) has been employed for inducing rapid hypertrophy of the future liver remnant for patients waiting for hepatectomy. As portal vein embolization may not result in satisfactory hypertrophy before tumor progression occurs, ALPPS can be an alternative for patients with advanced hepatocellular carcinoma. Herein we describe an ALPPS procedure with tumor thrombectomy for a patient who had a small left liver lobe and a large hepatocellular carcinoma involving the whole right liver lobe and the middle hepatic vein and extending into the inferior vena cava. In the first-stage operation, the right portal vein was controlled and divided with a Hemolock. The right hepatic artery was well protected. Hepatic transection was performed with a 1-cm margin from the tumor. The middle hepatic vein trunk was preserved. Ten days afterwards, there was significant hypertrophy of the left lateral section of the liver, and the second-stage operation was conducted. Extended right hepatectomy and tumor thrombectomy were performed under sternotomy and total vascular exclusion. The patient had good recovery and was free of disease 10 months after the operation. ALPPS may be a good treatment option even for patients with advanced disease if carried out at high-volume centers.

Clinical factors affecting rejection rates in liver transplantation.

BACKGROUND: With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection. METHOD: We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors. RESULTS: Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P<0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR. CONCLUSIONS: Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

Durability of small-for-size living donor allografts.

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals.

The friendly incidental portal vein thrombus in liver transplantation.

Improved outcomes have been shown in liver transplantation (LT) with portal vein thrombosis (PVT). However, PVT is still discovered incidentally during surgery despite careful preoperative imaging. Data are limited comparing the outcomes of incidental PVT with PVT diagnosed via preoperative imaging before LT. This study aims to compare the overall outcomes of patients with PVT. From 2008 to 2012, 369 patients had LT, and 58 patients with PVT were identified. They were divided into those with non-PVT (group 0; n = 311), preoperatively identified PVT (group 1; n = 28), and incidental PVT (group 2; n = 30). The demographics, characteristics, preoperative assessment, and postoperative outcomes were compared. A survival analysis was also performed. Baseline characteristics and preoperative evaluations of all 3 groups were comparable (P > 0.05) except for Model for End-Stage Liver Disease score, tumor status, platelet levels, and serum bilirubin. A multivariate analysis only showed a high serum bilirubin level to be a predictor of PVT (P = 0.004; odds ratio, 3.395; 95% confidence interval, 1.467-7.861). Postoperative outcomes were also comparable (P > 0.05). Compared to group 2, group 1 had more patients with a Yerdel classification of 3 or 4 with more extensive surgical intervention required (P = 0.02). The survival analysis in all 3 groups was comparable with 5-year survival rate of 87.4%, 84.6%, and 91.8% in group 0, 1, and 2, respectively (P = 0.66). In conclusion, recipients with PVT undergoing LT can have similar outcomes as the non-PVT patients even if PVTs were discovered incidentally. Discovery of incidental PVT only requires thrombectomy with no substantial change of treatment strategy, and the outcome is not adversely affected because most incidental PVTs are of a lower Yerdel grade. Preoperative imaging is useful to identify those with a higher Yerdel grade to allow planning of surgical strategy during transplantation.

Treatment strategy to improve long-term survival for hepatocellular carcinoma smaller than 5 cm: major hepatectomy vs minor hepatectomy.

BACKGROUND: The extent of hepatectomy for solitary hepatocellular carcinoma (HCC) <5 cm is controversial. METHODS: This is a retrospective review of patients with solitary HCC <5 cm, who underwent liver resection in a tertiary referral centre in Hong Kong between January 1989 and December 2009. Baseline demographics, liver function, peri-operative outcomes, and overall survival were compared. RESULTS: A total of 348 cirrhotic patients with a solitary HCC <5 cm underwent either major hepatectomy (n = 93) or minor hepatectomy (n = 255). Child-Pugh status did not differ, 98.9 vs. 96.1 % (p = 0.319); all patients who underwent major and minor hepatectomy were classified as Child-Pugh status A. Patients who underwent major hepatectomy had a larger median tumor size (4.0 vs. 2.5 cm, p < 0.001) and they also had more advanced stage of disease (stage I/II/IIIa: 10.8/55.9/33.3 vs. 26.7/52.9/20.4 %, p = 0.002). Median operative time for major hepatectomy was significantly longer (415 vs. 248 min, p < 0.001) and entailed greater blood loss (0.9 vs. 0.5 l, p < 0.001). Despite larger tumor size and more advanced stage of disease in the major hepatectomy group, hospital mortality (5.4 vs. 2.0 %, p = 0.185), complication rates (30.1 vs. 23.1 %, p = 0.234), and transfusion rate (10.8 vs. 11.4 %, p = 0.862) were the same between the two groups. Overall survival was significantly better for those who underwent major hepatectomy, with a median survival of 147.5 vs. 92.1 months (p = 0.043), and they had a better 5- and 10-year disease-free survival rate (57.3 vs. 40.2, 38.1 vs. 18.9 %, p = 0.003). In subgroup analysis, the 10-year survival for patients with stage II HCC and tumor <5 cm was 68.6 vs. 36.6 % in those who received minor hepatectomy alone (p = 0.027). CONCLUSIONS: Major hepatectomy provided better long-term survival benefit in patients with HCC <5 cm, particularly in those with stage II disease.

Resection strategies for hepatocellular carcinoma.

Liver resection is the treatment of choice and standard of care in patients with hepatocellular carcinoma (HCC). The ultimate goal of liver resection in HCC patients is to resect primary tumor with an adequate margin while preserving as much functional liver parenchyma as possible. Tremendous improvements in perioperative outcomes after liver resection have been achieved in the past three decades. The overall and disease-free survival rates have also improved. Liver resection is feasible and safe even in cirrhotic patients. This is a result of more accurate preoperative evaluation of liver function, the ability to manipulate future liver remnant volume, the use of anatomical resection and an anterior approach, meticulous surgical techniques to achieve bloodless liver resection, and better perioperative care. The purpose of this review is to highlight the importance of different resection strategies for HCC that in turn have contributed to the safety and improvement in long-term outcomes after liver resection.

Direct incision versus submucosal tunneling as a method of creating transgastric accesses for natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy: randomized controlled trial.

AIM: The optimal approach for creating accesses for transgastric peritoneoscopy is still uncertain. The present study aims to assess the feasibility of carrying out transgastric submucosal tunnel (SMT) peritoneoscopy and to determine whether this approach improves or restricts access to various sectors within the peritoneal cavity. METHODS: This was a randomized comparative study carried out in an in-vivo survival porcine model. Sixty-six beads in six swine were visualized and touched via gastrotomies created by either direct incision (DI) or SMT. The influence of the type of gastrotomy on improving or restricting access to particular sites within the peritoneal cavity for natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy was compared. The main outcome measurements were localization score of beads, overall procedural time, morbidities and mortalities. RESULTS: A significantly higher mean (SD) localization score was observed in peritoneoscopies carried out in the DI group (P < 0.001). Both the visualization and the touching scores were significantly better with the DI technique, and the overall yield of NOTES peritoneoscopy with DI and SMT were 72.73% and 60.6%, respectively (P = 0.043). Significantly more beads that were not touched in the SMT group were located in the sub-phrenic area (P = 0.013). The overall procedural time was significantly shorter in the DI group (P = 0.004). No major morbidities or mortalities occurred in any procedures. CONCLUSIONS: SMT resulted in lower visualization and touching scores for transgastric NOTES peritoneoscopy. Alternate methods to improve the diagnostic yield to the sub-phrenic area are required.

A double-blinded randomized controlled trial of laparoendoscopic single-site access versus conventional 3-port appendectomy.

OBJECTIVE: The aim of the current study was to perform a multicentered prospective double-blinded randomized controlled trial comparing laparoendoscopic single-site access (LESS) versus conventional three-port laparoscopic appendectomy (TPLA). BACKGROUND: The clinical benefits and disadvantages of LESS appendectomy are uncertain. METHODS: Between October 2009 and March 2011, consecutive patients admitted with clinical or radiological evidence of appendicitis were randomly assigned to receive either LESS or TPLA. The main outcome measurement was overall pain score. Secondary outcome measurements included operative time, conversion rates, morbidity rates, activity pain scores, activity scores, patient satisfaction, and cosmesis scores. RESULTS: During the study period, 200 patients were recruited to the study. There were no significant differences in the morbidity rates, operative time, conversion rates, and postoperative recovery. There were also no differences in the overall pain score and pain score at rest. However, patients in the LESS group experienced significantly more pain upon coughing or standing and required more intravenous analgesics (P = 0.001, 0.038, and 0.035, respectively). Wound cosmesis and satisfaction scores on the contrary were better in the LESS group (P = 0.002 and P = 0.052). No differences in the quality-of-life assessments were present at 2 weeks after operation. CONCLUSIONS: LESS and conventional appendectomy resulted in similar perioperative outcomes. However, LESS appendectomy resulted in worst pain scores upon exertion and required a higher dosage of intravenous analgesics when compared with TPLA. On the contrary, wound cosmesis and satisfaction scores were better in the LESS group. Hence, adoption of the technique for appendectomy will depend on patient preferences and the presence of local expertise.