IMPORTANCE: Long-term oncologic outcomes of robotic surgery remain a hotly debated topic in surgical oncology, but sparse data have been published thus far. OBJECTIVE: To analyze short- and long-term ...outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) from Western high-volume centers to assess the safety, reproducibility, and oncologic efficacy of this technique. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated the outcomes of patients receiving RLR vs open liver resection (OLR) for HCC between 2010 and 2020 in 5 high-volume centers. After 1:1 propensity score matching, a group of patients who underwent RLR was compared with a validation cohort of OLR patients from a high-volume center that did not perform RLR. MAIN OUTCOMES AND MEASURES: A retrospective analysis was performed of prospectively maintained databases at 2 European and 2 US institutions of patients who underwent RLR for HCC between January 1, 2010, and September 30, 2020. The main outcomes were safety and feasibility of RLR for HCC and its oncologic outcomes compared with a European OLR validation cohort. A 2-sided P < .05 was considered significant. RESULTS: The study included 398 patients (RLR group: 125 men, 33 women, median IQR age, 66 58-71 years; OLR group: 315 men, 83 women; median IQR age, 70 64-74 years), and 106 RLR patients were compared with 106 OLR patients after propensity score matching. The RLR patients had a significantly longer operative time (median IQR, 295 190-370 minutes vs 200 165-255 minutes, including docking; P < .001) but a significantly shorter hospital length of stay (median IQR, 4 3-6 days vs 10 7-13 days; P < .001) and a lower number of admissions to the intensive care unit (7 6.6% vs 21 19.8%; P = .002). Incidence of posthepatectomy liver failure was significantly lower in the RLR group (8 7.5% vs 30 28.3%; P = .001), with no cases of grade C failure. The 90-day overall survival rate was comparable between the 2 groups (RLR, 99.1% 95% CI, 93.5%-99.9%; OLR, 97.1% 95% CI, 91.3%-99.1%), as was the cumulative incidence of death related to tumor recurrence (RLR, 8.8% 95% CI, 3.1%-18.3%; OLR, 10.2% 95% CI, 4.9%-17.7%). CONCLUSIONS AND RELEVANCE: This study represents the largest Western experience to date of full RLR for HCC. Compared with OLR, RLR performed in tertiary centers represents a safe treatment strategy for patients with HCC and those with compromised liver function while achieving oncologic efficacy.
Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma ...from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging.
We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18–65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov, NCT01387503.
Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4–11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60–85). 5-year tumour event-free survival was 76·8% (95% CI 60·8–96·9) in the transplantation group versus 18·3% (7·1–47·0) in the control group (hazard ratio HR 0·20, 95% CI 0·07–0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9–97·1) in the transplantation group versus 31·2% (16·6–58·5) in the control group (HR 0·32, 95% CI 0·11–0·92; p=0·035). The most common registered grade 3–4 serious adverse events were hepatitis C virus recurrence (three 13% of 23 patients) and acute transplant rejection (two 9%) in the transplantation group, and post-embolisation syndrome (two 9% of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation).
Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria.
Italian Ministry of Health.
Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events ...among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation.
We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status.
In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763−0.798). Five-year cumulative incidence of non−HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200−400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400−1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%−0.793%). Our model, based on patients’ level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P = .044) to predict which patients will survive for 5 years after liver transplantation.
We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415.
•This is a series of eight patients with advanced liver disease who developed Pneumocystis jirovecii pneumonia (PCP)•Advanced liver disease can be a risk factor for PCP•Prophylaxis for PCP could be ...considered in patients with decompensated cirrhosis
Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP.
All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series.
Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation.
Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.
OBJECTIVE:The aim of this study was to estimate probabilities of achieving the statistical cure from hepatocellular carcinoma (HCC) with hepatic resection (HR) and liver transplantation (LT).
...BACKGROUND:Statistical cure occurs when the mortality of a specific population returns to values of that of general population. Resection and transplantation are considered potentially curative therapies for HCC, but their effect on the residual entire life-expectancy has never been investigated.
METHODS:Data from 3286 HCC patients treated with LT (n = 1218) or HR (n = 2068) were used to estimate statistical cure. Disease-free survival (DFS) was the primary survival measure to estimate cure fractions through a nonmixture model. Overall survival (OS) was a secondary measure. In both, patients were matched with general population by age, sex, year, and race/ethnicity. Cure variations after LT were also adjusted for different waiting-list drop-outs.
RESULTS:Considering DFS, the cure fraction after LT was 74.1% and after HR was 24.1% (effect size >0.8). LT outperformed HR within all transplant criteria considered (effect size >0.8), especially for multiple tumors (>0.9) and even in presence of a drop-out up to 20% (>0.5). Considering OS, the cure fraction after LT marginally increased to 75.8%, and after that HR increased to 40.5%. The effect size of LT over HR in terms of cure decreased for oligonodular tumors (<0.5), became small for drop-out up to ∼20% (<0.2), and negligible for single tumors <5 cm (∼0.1).
CONCLUSION:As other malignancies, statistical cure can occur for HCC, primarily with LT and secondarily with HR, depending on waiting-list capabilities and efficacy of tumor recurrence therapies after resection.
Donation after circulatory death (DCD) in Italy constitutes a relatively unique population because of the requirement of a no‐touch period of 20 minutes. The first aim of this study was to compare ...liver transplantations from donors who were maintained on normothermic regional perfusion after circulatory death and suffered extended warm ischemia (DCD group, n = 20) with those from donors who were maintained on extracorporeal membrane oxygenation (ECMO) and succumbed to brain death (ECMO group, n = 17) and those from standard donors after brain death (donation after brain death DBD group, n = 52). Second, we conducted an explorative analysis on the DCD group to identify relationships between the donor characteristics and the transplant outcomes. The 1‐year patient survival for the DCD group (95%) was not significantly different from that of the ECMO group (87%; P = 0.47) or the DBD group (94%; P = 0.94). Graft survival was slightly inferior in the DCD group (85%) because of a high rate of primary nonfunction (10%) and retransplantation (15%) but was not significantly different from the ECMO group (87%; P = 0.76) or the DBD group (91%; P = 0.20). Although ischemic cholangiopathy was more frequent in the DCD group (10%), this issue did not adversely impact graft survival because none of the recipients underwent retransplantation due to biliary complications. Moreover, the DCD recipients were more likely to develop posttransplant renal dysfunction with the need for renal replacement therapy. Further analysis of the DCD group showed that warm ischemia >125 minutes and an Ishak fibrosis score of 1 at liver biopsy negatively impacted serum creatinine and alanine transaminase levels in the first posttransplant week, respectively. In conclusion, our findings encourage the use of liver grafts from DCD donors maintained by regional perfusion after proper selection.
Objectives
To assess the safety and long‐term results of hepatic resection of colorectal liver metastases (CLM) in older adults.
Design
Case–control.
Setting
Single liver and multivisceral transplant ...center.
Participants
Individuals with CLM: 32 aged 70 and older (older group) and 32 younger than 70 (younger group) matched in a 1:1 ratio according to sex, primary tumor site, liver metastases at diagnosis, number of metastases, maximum tumor size, infiltration of cut margin, type of hepatic resection, and hepatic resection timing.
Measurements
Postoperative complications and survival rates.
Results
There was no significant difference in preoperative clinical findings between the two study groups. The incidence of cumulative postoperative complications was similar in the older (28.1%) and younger (34.4%) groups (P = .10). One‐, 3‐, and 5‐year disease‐free survival rates were 57.6%, 32.9%, and 16.4%, respectively, in the younger group and 67.9%, 29.2%, and 19.5%, respectively, in the older group (P = .72). One‐, 3‐, and 5‐year participant survival rates were 84.1%, 51.9%, and 33.3%, respectively, in the older group and 93.6%, 63%, and 28%, respectively, in the younger group (P = .50).
Conclusions
Resection of colorectal liver metastases in older adults can be performed with low mortality and morbidity and offers a long‐time survival advantage to many of these individuals. Based on the results of this case–control study, older adults should be considered for surgical treatment whenever possible.
Abstract Background As compared with traditional laparoscopy, robotic-assisted surgery provides better EndoWrist instruments and three-dimensional visualization of the operative field. Studies ...published so far indicate that living donor nephrectomy using the robot-assisted technique is safe, feasible, and provides remarkable advantages for the patients. Methods From 5 papers reporting detailed descriptions of surgical technique for robotic assisted nephrectomy (RAN) in living donor kidney transplantation, we have gathered information about the surgical techniques as well as about patients’ intra- and postoperative outcome. Data from these articles were analyzed together with the data from our own experience (33 cases) so that the total number of analyzed cases was 292. Results In the analyzed populations, no case of donor death occurred, and no case developed complication above grade 2 of Clavien score. Perioperative complications occurred in 37 of the 292 patients (12.6%). Accidental acute hemorrhage occurred in 5 of the 292 cases (1.7%). The average overall intraoperative blood loss was 67.8 mL (range 10 to 1,500). The average warm ischemia time was 3.5 minutes (range .58 to 7.6). Conversion to the open technique occurred in only 4 cases (1.3%). The average overall operative time was 192 minutes (range 60 to 400). The average length of the hospital stay was 2.7 days (range 1 to 10). Conclusions Safety and feasibility of RAN are pointed out in all the reviewed article, both as hand-assisted and as totally robotic technique. RAN appears to be significantly easier for the surgeons and the results are comparable with the ones obtained with the pure laparoscopic technique.
Advances in the surgical and systemic therapeutic landscape of hepatocellular carcinoma have increased the complexity of patient management. A dynamic adaptation of the available staging-based ...algorithms is required to allow flexible therapeutic allocation. In particular, real-world hepatocellular carcinoma management increasingly relies on factors independent of oncological staging, including patients’ frailty, comorbid burden, critical tumour location, multiple liver functional parameters, and specific technical contraindications impacting the delivery of treatment and resource availability. In this Policy Review we critically appraise how treatment allocation strictly based on pretreatment staging features has shifted towards a more personalised treatment approach, in which expert tumour boards assume a central role. We propose an evidence-based framework for hepatocellular carcinoma treatment based on the novel concept of multiparametric therapeutic hierarchy, in which different therapeutic options are ordered according to their survival benefit (ie, from surgery to systemic therapy). Moreover, we introduce the concept of converse therapeutic hierarchy, in which therapies are ordered according to their conversion abilities or adjuvant abilities (ie, from systemic therapy to surgery).
Laparoscopic liver resection (LLR) has gained significant popularity over the last 10 years. First experiences of LLR compared to open liver resection (OLR) reported a similar survival and a better ...safety profile for LLR.
This is a retrospective analysis of prospectively collected data of all consecutive patients treated by liver resection for HCC on liver cirrhosis between January 2005 and March 2017. The choice of procedure (LLR vs OLR) was generally based on tumor localization, history of previous upper abdominal surgery and patient's preference. The type of resection and indication for surgery were unrelated to the adopted technique. Based on pre-operative variables and confirmed cirrhosis, a 1:1 propensity score matching (PSM) model was developed to compare outcomes of LLR and OLR in patients with HCC. Outcomes of interest included morbidity, mortality and long-term cure potential.
After-PSM, the LLR group demonstrated better perioperative results including: lower complication rate (50.7% in OLR vs 29.3% in LLR, p = 0.0035), significantly lower intra-operative blood loss (200 ml in OLR vs 150 ml in LLR, p = 0.007) and shorter hospital length of stay (median 9 days in OLR vs 7 days in LLR, p = 0.0018). Moreover there was no significant difference between the two groups in 3-year survival (76%, CI: 60%–86% in LLR vs 68%, CI: 55%–79% in OLR, p = 0.32) or recurrence-free survival rates (44%, CI: 28%–58%, vs 44%, CI: 31%–57%, p = 0.94).
Minor LLR appeared significantly safer compared to minor OLR for HCC. LLR was associated with fewer post-operative complication, lower operative blood loss and a shorter hospital stay along with similar survival and recurrence-free survival rates
PDF
