Colorectal cancer is the third most common malignancy worldwide. Metastases are present at diagnosis in 15–30% of patients, and 20–50% develop them during treatment. The liver is the most frequent site of spread. Recently, liver transplantation has emerged as a novel option for selected patients with unresectable colorectal liver metastases. A 50-year-old man with stage IIIC rectal adenocarcinoma received neoadjuvant radiochemotherapy with capecitabine followed by abdominoperineal resection and adjuvant capecitabine. Despite treatment, imaging revealed liver metastases, which were resected laparoscopically. Pathology examination confirmed metastatic adenocarcinoma consistent morphologically with the primary tumor, with negative surgical margins. Between July 2021 and April 2022, new metastases were treated with thermal ablation, but shortly thereafter a new unresectable lesion was found in segment VIII. The patient received FOLFIRI plus cetuximab, with partial response after six cycles. In May 2023, he underwent orthotopic liver transplantation from a deceased donor at the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw. This was one of the first cases of liver transplantation for colorectal cancer metastases in Poland and the first one using a telemedicine platform during qualification. No recurrence has been observed since transplantation, and the patient remains in complete remission to date. Despite advances in induction therapies, most patients with unresectable liver metastases require palliative systemic treatment, the efficacy of which is limited. This case highlights the potential of liver transplantation as a breakthrough treatment option in selected patients. Further studies are needed to evaluate its efficacy in broader patient populations.
Background/Objectives: The shortage of liver grafts remains a major challenge in transplantation. Full-left-full-right (FLFR) split liver transplantation (SLT) expands the donor pool by providing two grafts for small adult recipients. However, prolonged cold ischemia time (CIT) and ischemia-reperfusion injury (IRI) limit its success. Methods: We report a case of FLFR SLT utilizing ex situ dual hypothermic oxygenated machine perfusion (DHOPE) to mitigate IRI and enhance graft viability. A brain-dead donor's liver was split under continuous DHOPE, followed by simultaneous transplantation into two adult recipients. Results: Both recipients exhibited stable graft function at one-year follow-up. DHOPE effectively reduced CIT and optimized postoperative recovery, with no major complications beyond Clavien-Dindo Grade IIIb. Conclusions: This is the first reported FLFR SLT using ex situ DHOPE for two adult recipients, demonstrating its feasibility in reducing CIT and improving outcomes. Machine perfusion may become a standard in FLFR SLT.
Background: Hypothermic oxygenated machine perfusion has emerged as a strategy to alleviate ischemic-reperfusion injury in liver grafts. Nevertheless, there is limited data on the effectiveness of hypothermic liver perfusion in evaluating organ quality. This study aimed to introduce a readily accessible real-time predictive biomarker measured in machine perfusate for post-transplant liver graft function. Methods: The study evaluated perfusate analytes over a 90-day postoperative period in 26 patients randomly assigned to receive a liver graft following dual hypothermic machine perfusion in a prospective randomized controlled trial. Machine perfusion was consistently conducted end-ischemically for at least 120 min, with real-time perfusate assessment at 30-min intervals. Graft functionality was assessed using established metrics, including Early Allograft Dysfunction (EAD). Results: Perfusate lactate concentration after 120 min of machine perfusion demonstrated significant predictive value for EAD (AUC ROC: 0.841, p = 0.009). Additionally, it correlated with post-transplant peak transaminase levels and extended hospital stays. Subgroup analysis revealed significantly higher lactate accumulation in livers with post-transplant EAD. Conclusions: Liver graft quality can be effectively assessed during hypothermic machine perfusion using simple perfusate lactate measurements. The reliability and accessibility of this evaluation support its potential integration into diverse transplant centers.
Background: Glycoprotein-2 (GP2) IgA is a predictor of disease severity in primary sclerosing cholangitis (PSC). We examined GP2 ' s occurrence in the biliary tract, the site of inflammation. Methods: GP2 was analyzed using ELISA, immunoblotting, mass spectrometry, and immunohistochemistry. The samples included: 20 bile and 30 serum samples from PSC patients, 23 bile and 11 serum samples from patients with gallstone disease (GD), 15 bile samples from healthy individuals undergoing liver-donation surgery (HILD), 20 extracts of gallstones (GE) obtained during cholecystectomy, and 101 blood-donor sera. Results: Biliary GP2 concentrations were significantly higher in patients with PSC and GD than in HILD (p < 0.0001). Serum GP2 levels were similar in PSC and GD patients, and controls, but lower than in bile (p < 0.0001). GP2 was detected in all 20 GEs. Mass spectrometry identified GP2 in the bile of 2 randomly selected GD and 2 PSC patients, and in none of 2 HILD samples. GP2 was found in peribiliary glands in 8 out of 12 PSC patients, showing morphological changes in acinar cells, but not in GD-gallbladders. Conclusions: GP2 is present in bile of PSC and GD patients. It is synthesized in the peribiliary glands of PSC patients, supporting a pathogenic role for biliary GP2 in PSC.
Background:The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes.Methods:LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January-December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien-Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141).Results:A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively.Conclusions:This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives.
OBJECTIVE:To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD).BACKGROUND:There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors.METHODS:In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054).RESULTS:Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values.CONCLUSION:Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.
Abstract Background Despite inconsistent evidence, international guidelines underline the importance of perioperative hyperoxygenation in prevention of postoperative infections. Further, data on safety and efficacy of this method in liver transplant setting are lacking. The aim was to evaluate efficacy and safety of postoperative hyperoxygenation in prophylaxis of infections after liver transplantation. Methods In this randomized controlled trial, patients undergoing liver transplantation were randomly assigned to either 28% or 80% fraction of inspired oxygen (FiO2) for 6 postoperative hours. Infections occurring during 30-day post-transplant period were the primary outcome measure. Secondary outcome measures included 90-day mortality, 90-day severe morbidity, 30-day pulmonary complications, durations of hospital and intensive care unit stay, and 5-day postoperative bilirubin concentration, alanine and aspartate transaminase activity, and international normalized ratio (INR) (clinicatrials.gov NCT02857855). Results A total of 193 patients were included and randomized to 28% (n = 99) and 80% (n = 94) FiO2. With similar patient, operative, and donor characteristics in both groups, infections occurred in 34.0% (32/94) of patients assigned to 80% FiO2 as compared to 23.2% (23/99) of patients assigned to 28% FiO2 (p = 0.112). Patients randomized to 80% FiO2 more frequently developed severe complications (p = 0.035), stayed longer in the intensive care unit (p = 0.033), and had higher bilirubin concentration over first 5 post-transplant days (p = 0.043). No significant differences were found regarding mortality, duration of hospital stay, pulmonary complications, and 5-day aspartate and alanine transaminase activity and INR. Conclusions Postoperative hyperoxygenation should not be used for prophylaxis of infections after liver transplantation due to the lack of efficacy. Trial registration ClinicalTrials.gov NCT02857855. Registered 7 July 2016.
The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p < 0.05, p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p < 0.0001, respectively). Patient and graft survivals were significantly worse in the HAT Group (p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT.
Purpose: End-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) has been established as a procedure to mitigate the ischemia-reperfusion injury (IRI) of livers donated after cardiac death with only limited data regarding benefits for grafts donated after brain death (DBD). The aim of this study was to assess the effect of dHOPE on postoperative DBD liver function. Methods: In this single-center, prospective, randomized controlled trial, 104 adult patients undergoing liver transplantation were randomly assigned to receive a DBD liver graft treated with either (dHOPE) (n=26) or preserved conventionally under static cold storage (SCS) (n=78). The sample of flushing solution was tested in the SCS group and perfusate samples were regularly tested during dHOPE. The primary endpoint was postoperative early allograft dysfunction (EAD). Results: The lactate level measured in the SCS group had no value in the prediction of EAD (AUC 0.601; 95 CL 0.46 – 0.74; p=0.16). In the dHOPE group, the optimal cut-off for lactate level measured after 2 hours of dHOPE in the prediction of EAD was 3,45 mmol/L (area under the curve [AUC] 0.747; 95% CI 0.53 – 0.97; p=0.04), with positive and negative prediction values of 77,8% and 81,25%, respectively. The rates of EAD after dHOPE were 18,75% and 77,78% (RR 0.24; 95% CI 0.82 – 0.65; p=0.004) with low and high lactate level after 2 hours of machine perfusion, respectively. Conclusion: The lactate level in the perfusate after 2 hours of dHOPE may serves as a real-time biomarker for the prediction for EAD of DBD liver grafts before implantation.
BACKGROUND:Early liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival. METHODS:This retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival. RESULTS:The cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001). CONCLUSIONS:The early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.
IntroductionCalcifying nested stromal epithelial tumor (CNSET) is an extremely rare diagnosis among patients treated for primary hepatic neoplasms. There are only 45 cases reported worldwide. Histopathological characteristics are well-demarcated nests of spindle and epithelioid cells in a dense desmoplastic stroma with variable calcification and ossification. It is mostly diagnosed in children and young females. Treatment strategies implemented for the management of CNSET include radiofrequency ablation, transarterial chemoembolization, surgical resection, adjuvant and neoadjuvant chemotherapy, and liver transplantation. Given the small number of available cases, there are still no established standards of treatment for this neoplasm.Case PresentationA 28-year-old female diagnosed with CNSET presented mild abdominal pain, with normal laboratory values. The tumor was initially deemed unresectable, therefore, the patient was disqualified from liver resection. Further deterioration of the patient's clinical condition and local tumor progression led to qualification for liver transplantation. The patient underwent liver transplantation 1 year following initial diagnosis and a 12 months recurrence-free period was observed. During the course of treatment, she did not receive systemic chemotherapy, radiotherapy, or loco-regional treatment.ConclusionMultiple strategies have been implemented for the treatment of CNSET, with liver resection providing the best outcomes. Transarterial chemoembolization, radiofrequency ablation, and radiotherapy are reported to be insufficient in the management of this tumor. Various chemotherapy regimens turned out to be ineffective as well. There have been only eight reported cases of patients undergoing liver transplantation for CNSET, with tumor recurrence in two cases. CNSET appears to be a neoplasm with low malignancy potential, although an aggressive progression has subsequently been reported. Further investigation is still required in this field.
Background Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent. Methods This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay. Results Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) ( p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) ( p = 0.031). Conclusions Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.
Introduction: Incisional hernias are common and important long-term complications in oncological surgery. This study aimed to provide accurate data on the incidence and risk factors for the occurrence of incisional hernial after liver resections performed through subcostal incisions. Method: This prospective observational study included 55 patients after liver resections performed for suspected malignancy in the Department of General, Transplant and Liver Surgery of the Medical University of Warsaw. Incidence of incisional hernias was the primary outcome measure. Follow up was based on clinical assessment and ultrasonographic examination of the scar at least 12 months postoperatively. Logistic regression was applied for risk factor analysis. Odds ratios (ORs) were presented with 95% confidence intervals (95% CI). Results: Incisional hernias occurred in 18 of 55 patients (32.7%). On univariable analyses, male sex (p=0.020), body mass index (p=0.010), and arterial hypertension (p=0.006) increased the risk of incisional hernias. Arterial hypertension was the independent risk factor (OR 2.53; 95% CI 1.31-4.89). Incisional hernias occurred in 9 of 41 (22.0%) patients without arterial hypertension as opposed to 9 of 14 (64.3%) patients with arterial hypertension (p=0.007). Conclusion: Incisional hernias commonly occur after liver resections performed though subcostal incisions. Individual susceptibility, as reflected by arterial hypertension, is a major determinant of their development.
Introduction: Refusal to follow-up may affect the course of the ongoing randomized controlled trials (RCT). The aim of this study was to evaluate the impact of COVID-19 pandemic on follow-up refusal rate in an ongoing surgical RCT. Methods: The study group comprised 107 participants enrolled in an ongoing surgical RCT designed to compare mass with layered closure of transverse abdominal incisions with respect to incisional hernias. Study group was divided into patients who were scheduled to have follow-up visit before (pre-COVID) and after (post-COVID) April 1st 2020. Follow-up refusal rate was compared in both groups. Results: Follow-up refusal rate in pre-COVID group was 18.52% (10 out of 55 patients) , whereas in post-COVID group it was 50% (26 out of 52 patients; p=0.0004). Median value of age during scheduled follow-up day was 60 years and the distance from patients place of living was 151 km. The pandemic particularly increased refusal rate in patients living >151km from hospital (p <0.0001), patients older than 60 years (p=0.006), and in female patients (p=0.005). Conclusions: COVID-19 pandemic leads to remarkable increase in follow-up refusal rate among participants enrolled in RCT's, particularly in females, older patients, and in those living in a long-distance from the centre.
Introduction: Advanced glycation end products (AGEs), measured by skin autofluorescence (SAF), may interfere with extracellular matrix changing its mechanical properties. Data exist suggesting that accumulation of AGEs may influence incisional hernia formation. The aim of this study was to evaluate SAF as a predictor of incisional hernias after subcostal incisions. Methods: This prospective study comprised 54 patients (21 men and 33 women) with suspected or confirmed gastrointestinal malignancy who underwent subcostal laparotomy in the Department of General, Transplant, and Liver Surgery of the Medical University of Warsaw between September 2018 and June 2020. Patients were excluded from the study in case of the presence of preoperative hernias. The patients were screened for incisional hernia at follow up one to two years after the surgery using abdominal wall ultrasonography or CT. SAF, based on 3 measurements, was measured twice – before the surgery and during the follow up. Data on patient's BMI and diabetes were collected preoperatively. Results: Incisional hernia was diagnosed in 16 patients (29.6%). Median preoperative SAF was 2.0AU (IQR:1.8–2.5) and 2.4 (IQR:2.1–3.0) in patients without and with incisional hernia (p=0.160). There were also no differences in SAF measured during follow up visit between both groups – 2.0AU (1.8–2.5) and 2.1AU (1.8–2.4)(p=0.866). The lack of significant difference for SAF was unmodified by BMI>25 or diabetes (p=0.587, p=0.669, respectively). Conclusions: Although SAF may reflect tissue ageing and AGEs accumulation, the study does not provide evidence for increased AGEs accumulation in patients with incisional hernia after abdominal surgery.
Background. This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival. Methods. This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss. Results. The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P < .001 and 2.23; 95% CI 1.55-3.19; P < .001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was & GE;1030 and & GE;3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P < .001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P < .001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P = .924 and P = .629, respectively). Conclusions. Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.