ALPPS and the endless pursuit of hepatic resectability.
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ABSTRACT:
SUBMITTER: Byrne M
PROVIDER: S-EPMC9577993 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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ALPPS and the endless pursuit of hepatic resectability.
Byrne Matthew M Ruffolo Luis I LI Hernandez-Alejandro Roberto R
Hepatobiliary surgery and nutrition 20221001 5
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Project description:ObjectiveThe aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT).BackgroundRadical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression.MethodsA prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention.ResultsBaseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS.ConclusionALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
| S-EPMC5916470 | biostudies-literature
Project description:BACKGROUND: The aim was to assess the value of laparoscopy and laparoscopic ultrasonography (LUS) in selecting patients for resection of colorectal hepatic metastases. METHODS: Sixty patients with potentially resectable colorectal hepatic metastases after helical computer tomography (CT) and scheduled to undergo laparoscopy and LUS were studied retrospectively. Primary outcome measurement was the number of cases in which laparoscopy and LUS resulted in a change of therapeutic approach. RESULTS: Of the 60 patients, 59 patients were examined by LUS and/or laparoscopy. The small intestine was perforated due to adhesions in two patients, necessitating open exploration in one of them. In 17 patients (29%) the combined laparoscopic procedure yielded results prohibiting resection; another 6 patients were denied resection on other grounds. Of the 36 patients who underwent open exploration, 31 underwent resection. Combined laparoscopy and LUS predicted resectability correctly in 86% of the patient group. Compared with resection, the sensitivity of both CT and LUS to detect lesions was 91%. DISCUSSION: Laparoscopy and LUS can avoid open exploration without resection in a substantial number of patients considered eligible for resection of colorectal hepatic metastases based on CT. LUS does not seem to detect more metastases than CT.
| S-EPMC2020565 | biostudies-other
Project description:BackgroundWhile ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR).MethodsThis cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula.ResultsA total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male.ConclusionsHeight, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.
| S-EPMC9796398 | biostudies-literature
Project description:Background & aimAssociating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) is a creative strategy for enlarging the future liver remnant (FLR) and increasing the tumor resectability rate. However, the indications for ALPPS must have a certain limit when the FLR is too small. We aimed to establish a modified ALPPS model with more widen applicability in rats.MethodsAn extreme ALPPS model was established in rodents with only a 6.5% FLR. The portal vein (PV) was subjected to restriction to different degrees, then the portal vein pressure (PVP) was measured. Then, different modifications of ALPPS, including hepatic artery restriction (HAR), gradual portal vein restriction (GPVR), and GPVR-associated HAR (HAR+GPVR), were applied in the extreme ALPPS models.ResultsPVL or PVR provoked an immediate increase in the PVP. The PVP in the PVR -1.28 mm, PVR -0.81 mm, PVR -0.63 mm, and PVL groups was 11.05±1.57 cmH2O, 16.18±1.92 cmH2O, 20.66±1.99 cmH2O, and 24.10±3.33 cmH2O, respectively, and the corresponding 3-day survival rate was 100%, 90.09%, 36.33% and 0, respectively. Then, in the extreme ALPPS model, the growth ratio of the FLR in the control, HAR, GPVR, and HAR+GPVR groups was 0.43±0.21, 0.50±0.16, 4.80±0.86, and 7.40±2.56, and as a consequence, the corresponding 30-day survival rate was 9.09%, 15.38%, 84.61% and 92.90%, respectively.ConclusionALPPS itself has a limit, and high PVP after PVL contributes to postoperative death in the extreme ALPPS model. Furthermore, a modified method for extreme ALPPS is proposed, i.e., GPVR+HAR in place of PVL, which significantly improves the survival rate of extreme hepatectomy in rat models.
| S-EPMC10521515 | biostudies-literature
Project description:Conventional transarterial chemoembolization (c-TACE), a common regimen for initially unresectable hepatocellular carcinoma, provides a chance of resection for 10% patients. This study found that TACE plus hepatic artery chemotherapy infusion (TACE-HAIC) had a higher conversion rate to resection, better survival outcome and comparable advent event, compared with c-TACE. Objective: To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin. Background: Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients. Methods: The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared. Results: The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%; P < 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%; P = 0.107 [RECIST]; 65.9% vs 16.7%; P < 0.001 [mRECIST], respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate [HR]: 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34–1.17; P = 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all P > 0.05). Conclusions: TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.
| S-EPMC10455427 | biostudies-literature
Project description:Cancer immunotherapy relies on either restoring or activating the function of adaptive immune cells, mainly CD8+ T lymphocytes. Despite impressive clinical success, cancer immunotherapy remains ineffective in many patients due to the establishment of tumor resistance, largely dependent on the nature of tumor microenvironment. There are several cellular and molecular mechanisms at play, and the goal is to identify those that are clinically significant. Among the hematopoietic-derived cells, monocytes are endowed with high plasticity, responsible for their pro- and anti-tumoral function. Indeed, monocytes are involved in several cancer-associated processes such as immune-tolerance, metastatic spread, neoangiogenesis, and chemotherapy resistance; on the other hand, by presenting cancer-associated antigens, they can also promote and sustain anti-tumoral T cell response. Recently, by high throughput technologies, new findings have revealed previously underappreciated, profound transcriptional, epigenetic, and metabolic differences among monocyte subsets, which complement and expand our knowledge on the monocyte ontogeny, recruitment during steady state, and emergency hematopoiesis, as seen in cancer. The subdivision into discrete monocytes subsets, both in mice and humans, appears an oversimplification, whereas continuum subsets development is best for depicting the real condition. In this review, we examine the evidences sustaining the existence of a monocyte heterogeneity along with functional activities, at the primary tumor and at the metastatic niche. In particular, we describe how tumor-derived soluble factors and cell-cell contact reprogram monocyte function. Finally, we point out the role of monocytes in preparing and shaping the metastatic niche and describe relevant targetable molecules altering monocyte activities. We think that exploiting monocyte complexity can help identifying key pathways important for the treatment of cancer and several conditions where these cells are involved.
| S-EPMC6691342 | biostudies-literature
Project description:BackgroundMany patients with bi-lobar liver tumours are not eligible for liver resection due to an insufficient future liver remnant (FLR). To reduce the risk of posthepatectomy liver failure and the primary cause of death, regenerative procedures intent to increase the FLR before surgery. The aim of this systematic review is to provide an overview of the available literature and outcomes on the effectiveness of simultaneous portal and hepatic vein embolization (PVE/HVE) versus portal vein embolization (PVE) alone.MethodsA systematic literature search was conducted in PubMed, Web of Science, and Embase up to September 2022. The primary outcome was resectability and the secondary outcome was the FLR volume increase.ResultsEight studies comparing PVE/HVE with PVE and six retrospective PVE/HVE case series were included. Pooled resectability within the comparative studies was 75 per cent in the PVE group (n = 252) versus 87 per cent in the PVE/HVE group (n = 166, OR 1.92 (95% c.i., 1.13-3.25)) favouring PVE/HVE (P = 0.015). After PVE, FLR hypertrophy between 12 per cent and 48 per cent (after a median of 21-30 days) was observed, whereas growth between 36 per cent and 67 per cent was reported after PVE/HVE (after a median of 17-31 days). In the comparative studies, 90-day primary cause of death was similar between groups (2.5 per cent after PVE versus 2.2 per cent after PVE/HVE), but a higher 90-day primary cause of death was reported in single-arm PVE/HVE cohort studies (6.9 per cent, 12 of 175 patients).ConclusionBased on moderate/weak evidence, PVE/HVE seems to increase resectability of bi-lobar liver tumours with a comparable safety profile. Additionally, PVE/HVE resulted in faster and more pronounced hypertrophy compared with PVE alone.
| S-EPMC9702575 | biostudies-literature
Project description:Liver cancer is one of the most lethal malignant tumors in the world, and surgical resection is the main treatment for liver cancer. Liver failure due to insufficient residual liver volume is a fatal complication after hepatectomy. How to effectively increase the residual liver volume after hepatectomy and improve the safety of hepatectomy has always been a problem to be solved in liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively reduces the occurrence of liver failure due to insufficient residual liver volume after hepatectomy, thereby increasing the probability of radical resection by inducing rapid proliferation of residual liver tissue. However, the molecular mechanism of residual liver tissue regeneration after primary ALPPS (combined liver partition and portal vein ligation) remains unclear. Here, we found that lots of circular RNAs (circRNAs) are upregulated after ALPPS in pig liver cells; then, we identified the orthologous circRNA in humans and pigs to detect their function in liver regeneration. The results showed that loss of circ-0067724 and circ-0016213 could suppress liver cell proliferation. Together, these findings suggest that circ-0067724 and circ-0016213 play an important role in liver cell proliferation, and this may help us to find new strategies to promote liver regeneration.
| S-EPMC9213876 | biostudies-literature
Project description: Not available
| S-EPMC5891425 | biostudies-literature
Project description:BackgroundThe associating liver partitioning and portal vein occlusion for staged hepatectomy (ALPPS) procedure is gaining interest because it brings hope to patients who cannot undergo radical surgical resection due to insufficient remnant liver volume. However, the indications and technical aspects of this procedure are still under debate. This report demonstrates the technical aspects of the first two-stage robotic ALPPS for HCC.Case presentationA 55-year-old man with type II portal vein variation was diagnosed with hepatocellular carcinoma. Preoperative 3D reconstruction of the liver based on CT showed a future liver remnant/standard liver volume (FLR/SLV) of 24.45%. The ALPPS procedure was performed using the da Vinci Si system. At the first stage of the operation, we removed the gallbladder and ligated the right anterior branch of the portal vein and the right posterior branch. Following blocking of the hepatic hilum, the liver parenchyma was removed 1 cm away from the right side of the falciform ligament in an incision manner from the top to the bottom and from shallow to deep. The second-stage operation was performed on the 12th postoperative day with a FLR/SLV of 45.13%. During this step, the right hemiliver plus left medial section was separated and removed. Postoperative pathology showed a negative margin. The operative times were 195 and 217 min, respectively. Estimated blood loss was 250 and 500 ml, respectively. There was no need for transfusion or hospitalization in intensive care. The patient was discharged on the 6th postoperative day. Recovery was uneventful after both stages, and the patient did not present any sign of liver failure. Elevation of liver enzymes was minimal. The patient had no evidence of the disease 14 months after the procedure.ConclusionsThe two-stage robotic ALPPS procedure is a safe and feasible technique for select patients with HCC.
| S-EPMC7898755 | biostudies-literature