When to perform hepatic resection for intermediate-stage hepatocellular carcinoma.

UNLABELLED: Transcatheter arterial chemoembolization (TACE) is the first-line therapy recommended for patients with intermediate hepatocellular carcinoma (HCC). However, in clinical practice, these patients are often referred to surgical teams to be evaluated for hepatectomy. After making a treatment decision (e.g., TACE or surgery), physicians may discover that the alternative treatment would have been preferable, which may bring a sense of regret. Under this premise, it is postulated that the optimal decision will be the one associated with the least amount of regret. Regret-based decision curve analysis (Regret-DCA) was performed on a Cox's regression model developed on 247 patients with cirrhosis resected for intermediate HCC. Physician preferences on surgery versus TACE were elicited in terms of regret; threshold probabilities (Pt) were calculated to identify the probability of survival for which physicians are uncertain of whether or not to perform a surgery. A survey among surgeons and hepatologists regarding three hypothetical clinical cases of intermediate HCC was performed to assess treatment preference domains. The 3- and 5-year overall survival rates after hepatectomy were 48.7% and 33.8%, respectively. Child-Pugh score, tumor number, and esophageal varices were independent predictors of survival (P<0.05). Regret-DCA showed that for physicians with Pt values of 3-year survival between 35% and 70%, the optimal strategy is to rely on the prediction model; for physicians with Pt<35%, surgery should be offered to all patients; and for Pt values>70%, the least regretful strategy is to perform TACE on all patients. The survey showed a significant separation among physicians' preferences, indicating that surgeons and hepatologists can uniformly act according to the regret threshold model. CONCLUSION: Regret theory provides a new perspective for treatment-related decisions applicable to the setting of intermediate HCC.

Survival Benefit of Liver Transplantation Versus Resection for Hepatocellular Carcinoma: Impact of MELD Score.

BACKGROUND: We sought to measure the impact of model for end stage liver disease (MELD) score, tumor staging, and microvascular invasion (MVI) on the relative survival benefit of liver transplantation (LT) versus liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: The study population comprised 1,106 HCC patients with cirrhosis undergoing LR from one Eastern (n = 424) and two Western (n = 682) surgical units. Exclusion criteria were very large (>10 cm) tumors, macrovascular invasion, and metastases. We identified three tumor stages: stage I (within Milan, n = 806), stage II (beyond Milan within Up-to-7, n = 123), and stage III (beyond Milan and Up-to-7, n = 177). Patient survival after LR was compared to that predicted after LT by the Metroticket calculator in relationship with staging, MVI, and MELD score using Monte Carlo simulation. RESULTS: Two hundred eighty-three patients (26 %) with a MELD score of ≥10 had an acceptable 5-year survival after LR of 47 %, while that of patients with a low MELD score was 67 % (p < 0.0001). Mean 5-year LT benefit was -4.50 months (95 % confidence interval [CI] -4.73 to -4.27) for patients with a MELD score of <10, and 0.81 months (95 % CI 0.58 to 1.04) for those with a MELD score of ≥10. MELD score and MVI were the strongest predictors of transplant survival benefit. LT reached a survival benefit, versus LR only in HCC patients with a MELD score of ≥10 and without MVI (3.08 months, 95 % CI 2.78 to 3.39), whatever the tumor stage. CONCLUSIONS: LT proved to be harmful in patients with resectable HCC with a low MELD score (<10) or with aggressive tumors (with MVI). As a result of a shortage of donors, only selected resectable tumors with a MELD score of ≥10 should be considered for transplantation.

How Long Does It Take to Acquire Mastery of Performance in Laparoscopic Living Donor Nephrectomy? A Center-Based and Surgeon-Based Operative Time CUSUM Analysis.

BACKGROUND: The safety of laparoscopic donor nephrectomy (LDN) has been widely documented, but its challenging learning curve (LC) requires an insightful assessment to expand its application. The aim of this study was to evaluate LC of LDN in a high-volume transplant center. METHODS: Three hundred forty-three LDNs performed from 2001 to 2018 were evaluated. CUSUM analysis based on the operative time was used to assess the number of cases required to reach mastery in the technique for both the entire surgical team and for the 3 main surgeons considered separately. Analysis of association between demographics, perioperative characteristics, and complications within the different LC phases was conducted. RESULTS: Mean operative time was 228.9 minutes. Mean length of stay was 3.8 days and mean warm ischemia time (WIT) was 170.8 seconds. Surgical and medical complication rates were 7.3% and 6.4%, respectively. The CUSUM-LC showed a requirement of 157 cases (for surgical team) and 75 cases (for single surgeons) to reach competence in the procedure. Patient baseline characteristic showed no differences among the LC phases. Compared with the initial LC phase, hospital stay was significantly lower at the end of the LC whereas WIT results were longer in the LC descendent phase. CONCLUSIONS: This study confirms the safety and efficacy of LDN, with a low rate of complications. This analysis suggests that about 75 procedures are required to reach competence and 93 cases to achieve mastery level of skill for a single surgeon. It can be hypothesized that, in a high-volume transplant enter, the time to guarantee training in LDN is compatible with the duration of a clinical fellowship.

Robotic Versus Laparoscopic Donor Nephrectomy: A Retrospective Bicentric Comparison of Learning Curves and Surgical Outcomes From 2 High-volume European Centers.

BACKGROUND: Although laparoscopic donor nephrectomy (LDN) represents the gold-standard technique for kidney living donation, robotic donor nephrectomy (RDN) settled as another appealing minimally invasive technique over the past decades. A comparison between LDN and RDN outcomes was performed. METHODS: RDN and LDN outcomes were compared, focusing on operative time and perioperative risk factors affecting surgery duration. Learning curves for both techniques were compared through spline regression and cumulative sum models. RESULTS: The study analyzed 512 procedures (154 RDN and 358 LDN procedures) performed between 2010 and 2021 in 2 different high-volume transplant centers. The RDN group presented a higher prevalence of arterial variations (36.2 versus 22.4%; P = 0.001) compared with the LDN cohort. No open conversions occurred; operative time (210 versus 195 min; P = 0.011) and warm ischemia time (WIT; 230 versus 180 s; P < 0.001) were longer in RDN. Postoperative complication rate was similar (8.4% versus 11.5%; P = 0.49); the RDN group showed shorter hospital stay (4 versus 5 d; P < 0.001). Spline regression models depicted a faster learning curve in the RDN group ( P = 0.0002). Accordingly, cumulative sum analysis highlighted a turning point after about 50 procedures among the RDN cohort and after about 100 procedures among the LDN group.Higher body mass index resulted as an independent risk factor for longer operative time for both techniques; multiple arteries significantly prolonged operative time in LDN, whereas RDN was longer in right kidney procurements; both procedures were equally shortened by growing surgical experience. CONCLUSIONS: RDN grants a faster learning curve and improves multiple vessel handling. Incidence of postoperative complications was low for both techniques.

Variable activation of phosphoinositide 3-kinase influences the response of liver grafts to ischemic preconditioning.

BACKGROUND/AIMS: The efficacy of ischemic preconditioning (IPC) in preventing reperfusion injury in human liver transplants is still questioned. Phosphoinositide-3-kinase (PI3K) is essential for IPC development in rodent livers. This work investigates whether PI3K-dependent signals might account for the inconsistent responses to IPC of transplanted human livers. METHODS: Forty livers from deceased donors were randomized to receive or not IPC before recovery. PI3K activation was evaluated in biopsies obtained immediately before IPC and 2 h after reperfusion by measuring the phosphorylation of the PI3K downstream kinase PKB/Akt and the levels of the PI3K antagonist phosphatase tensin-homologue deleted from chromosome 10 (PTEN). RESULTS: IPC increased PKB/Akt phosphorylation (p = 0.01) and decreased PTEN levels (p = 0.03) in grafts, but did not significantly ameliorate post-transplant reperfusion injury. By calculating T(2h)/T(0) PKB/Akt phosphorylation ratios, 10/19 (53%) of the preconditioned grafts had ratios above the control threshold (IPC-responsive), while the remaining nine grafts showed ratios comparable to controls (IPC-non-responsive). T(2h)/T(0) PTEN ratios were also decreased (p < or = 0.03) only in IPC-responsive grafts. The patients receiving IPC-responsive organs had ameliorated (p < or = 0.05) post-transplant aminotransferase and bilirubin levels, while prothrombin activity was unchanged. CONCLUSIONS: Impaired PI3K signaling might account for the variability in the responses to IPC of human grafts from deceased donors.

Lower Urinary Tract Symptoms in Kidney Transplant Recipients and Timing of Treatment With TURP: Impact on Renal Graft Survival and Function.

BACKGROUND: With the aging of recipients of renal transplantation (RT) one of the emerging issues is the incidence of low urinary tract symptoms (LUTS), which may have negative consequences on the graft survival and function. The aim of our study was to assess the influence of LUTS and the treatment with transurethral resection of the prostate (TURP) on the outcome of RT. MATERIALS AND METHODS: We collected data from men over 55 who underwent RT at our center from January 2007 to December 2016. We analyzed the incidence of LUTS; the rate of treatment with TURP; the eGFR (estimated glomerular filtration rate) at 6 months and 1, 3, and 5 years from transplantation; and graft survival. RESULTS: Fifty-five patients out of 268 experienced LUTS, and 19 of them had a bladder outlet obstruction (BOO). Patients experiencing BOO had a significantly higher hazard ratio (HR) of graft failure (HR 5.7, CI 1.56-21.4) compared to the other recipients. Of the 18 patients treated with TURP, 10 received the procedure within 6 months from the LUTS onset. They had a significantly absolute eGFR improvement at 6 months from the intervention (+14.25 mL/min ± 8.10) compared to the patients treated later (-8.4 mL/min ± 14.43). DISCUSSION: We showed the negative effects of LUTS on kidney graft function and survival. Although TURP is the standard therapy for such an issue, the best timing for it still has to be defined. Our experience supports the need for an early treatment of the LUTS for promoting the outcome of the RT.

A new liver transplant priority for patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Patients with hepatocellular carcinoma on the waiting list for liver transplantation are excluded due to causes related to liver failure and tumor progression. We analyze the various factors to suggest a new liver transplant priority. METHODOLOGY: We evaluated the outcome on the list of 309 patients with hepatocellular carcinoma and causes of drop-out from the list were divided as death, "too sick" and tumor progression. The impact of model for end stage liver disease score, tumor stage and waiting time on the causes of drop-outs was evaluated. RESULTS: During the study period, 197 patients had a liver transplantation, 50 were still on the list and the remaining 62 were removed from the list (28 deaths, 30 tumor progressions, and 4 "too sick"). The receiver operating characteristic curves analysis showed that the model for end stage liver disease score predicted the rate of deaths on the list at 1-year (p<0.001). The waiting time and the tumor stage predicted the rate of drop-outs for tumor progression at 1-year on the list (p<0.05). CONCLUSIONS: Patients with hepatocellular carcinoma on the waiting list should have priority based on their model for end stage liver disease score, waiting time with tumor and tumor stage.

Blood transfusions and steatohepatitis are independent risk factors for complications following liver resection for colorectal cancer liver metastases.

The aim of the present study was to evaluate the risk factors for postoperative complications following liver resection for colorectal cancer liver metastases. Patients who underwent hepatic resection for colorectal cancer liver metastases were stratified according to chemotherapy administration and body mass index (BMI) to eliminate potential confounding factors. A univariate analysis was conducted to identify potential risk factors for postoperative complications following liver resection. Variables that exhibited a potential association were evaluated by multivariable logistic regression analysis to identify those independently associated with postoperative morbidity. Between January 2012 and March 2012, 100 patients underwent hepatic resection for liver metastases from colorectal carcinoma at the Treviso Regional Hospital (Treviso, Italy) and at the Regina Elena National Cancer Institute (Rome, Italy). Of the 100 patients, 61 received preoperative oxaliplatin- or irinotecan-based chemotherapy. A total of 25 the patients had a BMI of ≥28 kg/m2. On univariate analysis, BMI ≥28 kg/m2 was found to be positively correlated with the presence of steatosis (P<0.01) and steatohepatitis (P<0.01). The administration of preoperative chemotherapy was correlated with the development of steatosis (P<0.01), steatohepatitis (P=0.02) and postoperative complications (P=0.03). Even following stratification for the use of preoperative chemotherapy, BMI ≥28 kg/m2 maintained its positive association with steatohepatitis. On multivariate analysis, steatohepatitis (P=0.005, HR=0.118, 95% CI: 0.027-0.518) and blood transfusions (P=0.001, HR=0.131, 95% CI: 0.038-0.452) were independently associated with postoperative complications. BMI ≥28 kg/m2 (P=0.004, HR=8.30, 95% CI: 2.39-28.7) and irinotecan treatment (P=0.016, HR=0.16, 95% CI: 0.037-0.711) were independent risk factors for steatohepatitis. In conclusion, steatohepatitis and perioperative blood transfusions were found to be the main determinant of postoperative complications following liver resection for colorectal liver metastases. Overweight patients may be more prone to the cytotoxic effects of irinotecan, harboring a higher risk of developing steatohepatitis.

Liver allocation for hepatocellular carcinoma: a European Center policy in the pre-MELD era.

BACKGROUND: Policies to decrease dropout during waiting time for liver transplantation (LT) are under debate. METHODS: We evaluated the allocation system from 1996 to 2003, when recipients had priority related to Child-Pugh score and donors >60 years were mainly offered to recipients with hepatocellular carcinoma (HCC). The outcomes of 656 patients with chronic liver disease (142 HCC and 514 non-HCC) listed for LT were prospectively evaluated, considering recipient and donor features. RESULTS: Transplantation and dropout rates were similar between HCC and non-HCC patients: 64.1% vs. 70.6% and 26% vs. 22.6%. Multivariate analysis showed the probability of being transplanted within 3 months was related to Child-Pugh score >10 and to HCC, whereas the probability of being removed from the list within 3 months was only related to Child-Pugh score >10. HCC patients had a lower median waiting time (97 vs. 197 days, P<0.001), a higher rate of donors > 60 years (50.5% vs. 33.5%, P<0.005) and with steatosis (31.6% vs. 14.3%, P<0.01), but a lower Child-Pugh score (9.1+/-2.1 vs. 9.6+/-1.7, P<0.05) than non-HCC patients. The 5-year patient survival was comparable since registration on the list and since LT: 56.9% and 77% in the HCC group vs. 61.4% and 79% in the non-HCC patients. Donors > 60 years affected outcome after LT in the non-HCC group, but not in the HCC patients. CONCLUSION: By allocating donors >60 years mainly to HCC patients, we controlled dropout without affecting their survival and the outcome of non-HCC patients.