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BACKGROUND AND AIMS: Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. APPROACH AND RESULTS: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33-0.91), p =0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29-1), p =0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20-0.91) p =0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14-1), p =0.05]. CONCLUSIONS: Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Rechazo de Injerto/prevención & control , Muerte , Hígado , Supervivencia de InjertoRESUMEN
OBJECTIVE: To compare the effect of liver transplantation (LT) on ileal pouch-anal anastomosis (IPAA) outcomes in patients with primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD). BACKGROUND: Patients with PSC-IBD may require both IPAA for colitis and LT for PSC. METHODS: Patients with PSC-IBD from out institutional pouch registry (1985-2022) were divided according to LT status and timing of LT (before and after IPAA) and their outcomes analyzed. RESULTS: A total of 160 patients were included: 112 (70%) nontransplanted at last follow-up; 48 (30%) transplanted, of which 23 (14%) before IPAA and 25 (16%) after. Nontransplanted patients at IPAA had more laparoscopic procedures [37 (46%) vs 8 (18%), P =0.002] and less blood loss (median 250 vs 400 mL, P =0.006). Morbidity and mortality at 90 days were similar. Chronic pouchitis was higher in transplanted compared with nontransplanted patients [32 (67%) vs 51 (45.5%), P =0.03], but nontransplanted patients had a higher rate of chronic antibiotic refractory pouchitis. Overall survival was similar, but nontransplanted patients had more PSC-related deaths (12.5% vs 2%, P =0.002). Pouch survival at 10 years was 90% for nontransplanted patients and 100% for transplanted patients (log-rank P =0.052). Timing of LT had no impact on chronic pouchitis, pouch failure, or overall survival. PSC recurrence was 6% at 10 years. For transplanted patients, graft survival was similar regardless of IPAA timing. CONCLUSIONS: In patients with PSC-IBD and IPAA, LT is linked to an increased pouchitis rate but does not affect overall and pouch survival. Timing of LT does not influence short-term and long-term pouch outcomes.
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Colangitis Esclerosante , Colitis Ulcerosa , Reservorios Cólicos , Enfermedades Inflamatorias del Intestino , Trasplante de Hígado , Reservoritis , Proctocolectomía Restauradora , Humanos , Reservoritis/etiología , Reservoritis/cirugía , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/cirugía , Reservorios Cólicos/efectos adversos , Colitis Ulcerosa/cirugía , Proctocolectomía Restauradora/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/cirugía , Anastomosis Quirúrgica/efectos adversosRESUMEN
OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Neoplasias Colorrectales/patología , Hepatectomía , Incidencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/secundarioRESUMEN
OBJECTIVE: We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS). SUMMARY BACKGROUND DATA: Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky. METHODS: Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality. RESULTS: Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates. CONCLUSIONS: This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.
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The utilization of split liver grafts can increase access to liver transplantation (LT) for adult patients, particularly when liver grafts are shared between 2 adult recipients. However, it is yet to be determined whether split liver transplantation (SLT) increases the risk of biliary complications (BCs) compared with whole liver transplantation (WLT) in adult recipients. This retrospective study enrolled 1441 adult patients who underwent deceased donor LT at a single-site between January 2004 and June 2018. Of those, 73 patients underwent SLTs. Graft type for SLT includes 27 right trisegment grafts, 16 left lobes, and 30 right lobes. A propensity score matching analysis selected 97 WLTs and 60 SLTs. Biliary leakage was more frequently seen in SLTs (13.3% vs. 0%; p <0.001), whereas the frequency of biliary anastomotic stricture was comparable between SLTs and WLTs (11.7% vs. 9.3%; p=0.63). Graft and patient survival rates of patients undergoing SLTs were comparable to those undergoing WLTs (p=0.42 and 0.57, respectively). In the analysis of the entire SLT cohort, BCs were seen in 15 patients (20.5%) including biliary leakage in 11 patients (15.1%) and biliary anastomotic stricture in 8 patients (11.0%) [both in 4 patients (5.5%)]. The survival rates of recipients who developed BCs were significantly inferior to those without BCs (p <0.01). By multivariate analysis, the split grafts without common bile duct increased the risk of BCs. In conclusion, SLT increases the risk of biliary leakage compared with WLT. Biliary leakage can still lead to fatal infection and thus should be managed appropriately in SLT.
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Enfermedades de las Vías Biliares , Trasplante de Hígado , Adulto , Humanos , Estudios Retrospectivos , Análisis por Apareamiento , Constricción Patológica , Resultado del Tratamiento , Supervivencia de InjertoRESUMEN
The management of giant inguinoscrotal hernias remains a challenge as a result of the loss of the intra-abdominal domain from long-standing hernia contents within the scrotum. Multiple techniques have been described for abdominal wall relaxation and augmentation to allow the safe return of viscera from the scrotum to the intraperitoneal cavity without adversely affecting cardiorespiratory physiology. Preoperative progressive pneumoperitoneum, phrenectomy, and component separation are but a few common techniques previously described as adjuncts to the management of these massively large hernias. However, these strategies require an additional invasive stage, and reproducibility remains challenging. Botulinum toxin A (BTA) has been successfully used for the management of complex ventral hernias. Its use for these hernias has shown reproducibility and a low side effect profile. In the present report, we describe our institutional experience with BTA for giant inguinal hernias in two patients and present a review of the literature. In one case, a 77-year-old man with a substantial cardiac history presented with a giant left inguinal hernia that was interfering with his activities of daily living. He had BTA six weeks prior to inguinal hernia repair. Repair was performed via an inguinal incision with a favorable return of the viscera into the peritoneum. He was discharged on the same day of the operation. A second patient, 78 years of age, had a giant right inguinoscrotal hernia. He had a significant cardiac history and was treated with BTA six weeks prior to inguinal hernia repair via a groin incision. Neither patient had complaints nor recurrence at 7- and 3-month follow-ups. While the literature on this topic is scarce, we found 13 cases of inguinal hernias treated with BTA as an adjunct. BTA might be a promising adjunct for the management of giant inguinoscrotal hernias in addition to or in place of current strategies.
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Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently.
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BACKGROUND: Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. METHODS: A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. RESULTS: Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% ( n =504) and 86.6% ( n =493). Five-year RFS and OS were 78.9% ( n =449) and 79.1% ( n =450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9-0.95). Tumour size greater than 3 cm ( P =0.012), increasing tumour number on imaging ( P =0.001) and explant pathology ( P <0.001) was associated with recurrence. Transplant within Milan ( P <0.001) or UCSF criteria ( P <0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence ( P <0.001) and reduced OS ( P =0.008). Chemoembolization was predictive of recurrence in the overall population ( P =0.043) and in those outside-Milan criteria ( P =0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS ( P <0.001) in the total cohort and predict both, RFS ( P =0.007) and OS ( P =0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts ( n =15/58, 25.6%, P =0.009). Donor age was associated with a higher HCC recurrence ( P =0.006). Both total ischaemia time (TIT) greater than 6hours ( P =0.016) and increasing TIT correlated with higher HCC recurrence ( P =0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence ( P =0.039) and reduced survival ( P =0.033). CONCLUSION: This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Trasplante de Hígado/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Medición de Riesgo , Estudios de Seguimiento , Anciano , Estudios Retrospectivos , Adulto , Factores de Riesgo , Recurrencia Local de Neoplasia , Estimación de Kaplan-MeierRESUMEN
The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.
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INTRODUCTION: Combination of immune-checkpoint inhibitor (ICI) and vascular endothelial growth factor (VEGF) antagonist has become the first line systemic treatment for advanced hepatocellular carcinoma (HCC). However, two-thirds of patients do not respond to ICI-based treatments and biomarkers for response remain elusive. METHODS: Patients with advanced HCC who received Atezolizumab/Bevacizumab combination or Nivolumab during 2016-2022 were identified in our Liver Cancer Database. Retrospective review of their clinical data was performed to investigate parameters that could be predictive of immunotherapy response. RESULTS: 96 patients received Atezolizumab/Bevacizumab (n=60) or Nivolumab (n=36). Median age at diagnosis was 67.1 years. 70 patients had received treatment and 26 patients were treatment naïve before starting immunotherapy. Mean pre-treatment AFP was 9780.7 (±32035) ng/mL. Confirmed objective response (complete or partial) was seen in 29% of the population (n=27). Disease remained stable in 12% (n=11) and progressed in 60% (n=56). On univariate analysis, pre-treatment AFP>400 ng/mL was associated with objective response (OR=4.5, 95% CI:1.7-11.9, p=0.0015), while white race (OR=0.35, 95% CI:0.13-0.92, p=0.030) and prior radiotherapy (OR=0.14, 95% CI:0.01-1.1, p=0.033) or systemic therapy with TKIs (OR=0.25, 95% CI:0.08-0.81, p=0.017) were associated with poor response. On multivariate analysis only AFP>400 ng/mL remained associated with response (OR=3.7, 95% CI:1.3-10.5, p=0.014). Overall survival (OS) at one and three years was 86% and 43% in responders, and 45% and 29% in non-responders, respectively. CONCLUSION: In our institutional experience, treatment naivety and pre-treatment AFP>400 ng/mL were associated with objective response. Prospective studies aimed at identifying factors associated with response to immunotherapy will aide patient selection.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Anciano , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Bevacizumab/uso terapéutico , alfa-Fetoproteínas/metabolismo , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Nivolumab/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , InmunoterapiaRESUMEN
(1) Background: The incidence of hepatocellular carcinoma (HCC) is rising, and current screening methods lack sensitivity. This study aimed to identify distinct and overlapping metabolites in saliva and plasma that are significantly associated with HCC. (2) Methods: Saliva samples were collected from 42 individuals (HCC = 16, cirrhosis = 12, healthy = 14), with plasma samples from 22 (HCC = 14, cirrhosis = 2, healthy = 6). We performed untargeted mass spectrometry on blood and plasma, tested metabolites for associations with HCC or cirrhosis using a logistic regression, and identified enriched pathways with Metaboanalyst. Pearson's correlation was employed to test for correlations between salivary and plasma metabolites. (3) Results: Six salivary metabolites (1-hexadecanol, isooctanol, malonic acid, N-acetyl-valine, octadecanol, and succinic acid) and ten plasma metabolites (glycine, 3-(4-hydroxyphenyl)propionic acid, aconitic acid, isocitric acid, tagatose, cellobiose, fucose, glyceric acid, isocitric acid, isothreonic acid, and phenylacetic acid) were associated with HCC. Malonic acid was correlated between the paired saliva and plasma samples. Pathway analysis highlighted deregulation of the 'The Citric Acid Cycle' in both biospecimens. (4) Conclusions: Our study suggests that salivary and plasma metabolites may serve as independent sources for HCC detection. Despite the lack of correlation between individual metabolites, they converge on 'The Citric Acid Cycle' pathway, implicated in HCC pathogenesis.
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BACKGROUND: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. METHODS: Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. RESULTS: Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6-38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p < 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. CONCLUSIONS: Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response.
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PURPOSE: Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool. METHODS: Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed. RESULTS: Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 v n = 11) and a greater genomic heterogeneity (P = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response (P = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively (P = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, P = .0419). CONCLUSION: Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.
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ADN Tumoral Circulante , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , ADN Tumoral Circulante/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/diagnósticoRESUMEN
INTRODUCTION: Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). METHODS: NSQIP hepatectomy database 2014-2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. RESULTS: There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19-0.72)], PHLF (HR 0.36 [0.15-0.86]), collections requiring drainage (HR 0.30 [0.15-0.63]), postoperative transfusion (HR 0.36 [0.21-0.61]), major (HR 0.45 [0.27-0.77]), and overall morbidity (HR 0.44 [0.31-0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45-0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. CONCLUSION: MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.
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Carcinoma Hepatocelular , Fallo Hepático , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Hepatectomía/efectos adversos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Fallo Hepático/etiología , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
INTRODUCTION: Colorectal cancer is a leading cause of cancer-related death worldwide. Metastatic liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach. Reports of liver transplantation in selected patients with unresectable CRLM have shown encouraging results compared to conventional forms of therapy. No study to date has examined the utility of liquid biopsy circulating tumor DNA (ctDNA) for evaluation of residual disease in this cohort of patients. We report a small series of liver transplantation in patients with CRLM in whom ctDNA was assessed peri-operatively. METHODS: Five patients underwent liver transplantation for unresectable CRLM or liver failure following CRLM treatment from 2018 to 2022. Clinical data, cross-sectional imaging, and serum biomarkers including peri-operative ctDNA were reviewed from electronic medical records. RESULTS: All patients are alive without radiologic evidence of disease at time of this publication. Median time of follow-up was 32 months (IQR 6.6-40 months). ctDNA was assessed before (4 patients) and after transplant (6 patients). One patient experienced a pulmonary recurrence that was resected, for whom pre-recurrence ctDNA was not available; the remaining patients have not experienced recurrence. Four patients are without evidence of ctDNA following transplant, and two demonstrate persistent ctDNA positivity post-transplant. Three of four patients with positive pre-transplant ctDNA remain ctDNA-negative post-transplant. CONCLUSIONS: Liver transplantation for liver-confined unresectable CRLM is emerging as a valid surgical option in selected patients. The significance of liquid biopsy in this population remains elusive due to lack of data. The clearance of ctDNA after transplant in these patients with metastatic disease and despite their immunosuppression is notable. The significance and usefulness of liquid biopsy in patient selection, surveillance, and as an indication for treatment warrant further investigation.