Surgical treatment for recurrent cholangiocarcinoma: a single-center series.

Purpose: The present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences. Methods: We carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed. Results: Eighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p< 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of <1 year, adjuvant CHT after resection of the primary tumor and undergoing surgery or CHT alone versus best supportive care were independent factors affecting mortality after CC recurrence in the multivariate analysis. Conclusion: Surgery or CHT alone improved patient survival after CC recurrence compared to best supportive care. Surgical treatment did not improve patient survival compared to CHT alone.

Renoportal Anastomosis and Its Complications: A Complex Case Report.

BACKGROUND: Renoportal anastomosis (RPA) is an effective technique in cases of complex portal vein thrombosis with the presence of a splenorenal shunt. The objective of this report is to describe the possible complications related to RPA. CASE REPORT: A 50-year-old man with alcohol-related and hepatitis C-related cirrhosis and 2 hepatocellular carcinomas underwent liver transplant. He presented a portal vein thrombosis Yerdel IV, a splenorenal shunt, and another shunt between the inferior mesenteric vein (IMV) and the perirectal plexus. During surgery, the flow of the left renal vein was 891 mL/min, and this rose to 1050 mL/min after IMV clamping. RPA was made through iliac vein graft interposition, and the IMV was ligated. Portal flow was 832 mL/min but drastically decreased because of mesenteric root compression. After finishing the liver transplant, a renoiliac graft percutaneous transhepatic stent was put in place. The patient presented graft dysfunction and acute kidney injury. On postoperative day +18, a second stent was put in place because of a thrombosis in the splenomesenteric confluence. The patient subsequently presented partial distal rethrombosis and a pancreaticoduodenal arteriovenous fistula, which required several embolizations. The patient developed ascites, recurrent gastrointestinal bleeding, and persistent bacterial peritonitis. Finally, a modified Sugiura procedure (without splenectomy) was performed, achieving a portal flow of 1800 mL/min. However, the patient developed sepsis and multiorgan failure, and died on postoperative day +70. CONCLUSIONS: Despite long-term patient and graft survival within accepted limits after LT, RPA is a challenging technique not exempt from complications.

Nonsplenorenal Spontaneous Portosystemic Shunts in Liver Transplant Attitude and Outcomes: A Single-Center Series.

BACKGROUND: Management of nonsplenorenal spontaneous portosystemic shunts (NSRSPSS) in liver transplant (LT) is controversial. Reports on the influence of its ligation suggest improvements in morbidity and survival. METHODS: Retrospective study of a single-center series. The objective was to analyze the outcomes and post-LT survival after the closure of NSRSPSS. RESULTS: Between January 2005 and April 2021 a total of 23 patients with NSRSPSS underwent LT. The shunt was superior mesenteric vein-vena cava in 12 (52.2%), inferior mesenteric vein-vena cava in 6 (26.1%), through the left gastric vein in 4 (17.4%), and portocava in 1 (4.3%). Seven patients presented portal vein thrombosis, with thrombectomy being performed in 5. Moreover, 21 patients had portoportal anastomosis, 1 patient required portal reconstruction at the splenomesenteric confluence, and 1 had a coronary-portal anastomosis. The NSRSPSS was closed in 22 cases (95.7%). The mean (SD) portal flow before and after the closure of NSRSPSS was 1395 (572) mL/min and 1773 (583) mL/min (104.4 [47.9] mL/min/100 g and 127.9 [4.9] mL/min/100 g, respectively). Six patients (26.1%) presented primary graft dysfunction, 13 (56.5%) acute kidney injury, and 9 (39%) ascites. Three arterial stenoses (13%), 2 biliary stenoses (8.6%), and 1 intrahepatic portal thrombosis (4.3%) occurred. Median intensive care unit and hospital stay was 5 days (range, 3-8 days) and 15 days (range, 13-21 days). After a mean follow-up of 5.18 (3.2) years, all patients except 1 are alive. CONCLUSIONS: The closure of the NSRSPSS during LT can optimize portal flow, with potential influence in morbidity and survival rates.

Totally laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases: a single-center case series.

BACKGROUND: The aim of the study is to analyze the feasibility, the safety and short- and medium-term survival of totally laparoscopic simultaneous resections (LSR) of colorectal cancer (CRC) and synchronous liver metastases (LM). METHODS: This is a retrospective study of a single-center series. Patients ASA IV, ECOG ≥ 2, major hepatectomies (≥ 3 segments), symptomatic CRC as well as low rectal tumors were excluded from indication. The difficulty level of all liver resections was classified as low or intermediate according to the Iwate Criteria. Dindo-Clavien classification for postoperative complications evaluation was used. RESULTS: 15 Patients with 21 liver lesions were included. Laparoscopic liver surgery was performed first in every case. Median size of the lesions was 20 mm (r 8-69). Major complications (Dindo-Clavien ≥ 3) occurred in 3 patients (20%); median hospital stay was 7 days (r 4-35), and only one patient (6.6%) was readmitted upon the first month from the surgery. 90-day mortality rate was 0%. After a median follow-up of 24 months (r 7-121), disease-free survival at 1, 2 and 3 years was 58%, 36% and 24%, respectively; overall survival at 1, 2 and 3 years was 92.3%. CONCLUSIONS: In selected patients, LSR of CRC and LM is technically feasible and has an acceptable morbidity rate and mid-term survival.

Similar Results in Liver Transplantation From Controlled Donation After Circulatory Death Donors With Normothermic Regional Perfusion and Donation After Brain Death Donors: A Case-Matched Single-Center Study.

Although good results have been reported with the use of normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation (LT), there is a lack of evidence to demonstrate similar results to donation after brain death (DBD). We present a single-center retrospective case-matched (1:2) study including 100 NRP cDCD LTs and 200 DBD LTs and a median follow-up of 36 months. Matching was done according to donor age, recipient Model for End-Stage Liver Disease score, and cold ischemia time. The following perioperative results were similar in both groups: alanine transaminase peaks of 909 U/L in the DBD group and 836 U/L in the cDCD group and early allograft disfunction percentages of 21% and 19.2%, respectively. The 1-year and 3-year overall graft survival for cDCD was 99% and 93%, respectively, versus 92% and 87%, respectively, for DBD (P = 0.04). Of note, no cases of primary nonfunction or ischemic-type biliary lesion were observed among the cDCD grafts. Our results confirm that NRP cDCD LT meets the same outcomes as those obtained with DBD LT and provides evidence to support the idea that cDCD donors per se should no longer be considered as "marginal donors" when recovered with NRP.

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation.

BACKGROUND: Tacrolimus trough levels (TTL) during the first weeks after liver transplantation (LT) have been related with long-term renal function and hepatocellular carcinoma recurrence. Nevertheless, the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate. AIM: To evaluate the effect of TTL during the first month on the long-term outcomes after LT. METHODS: One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied. Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 (n = 98) and > 10 ng/mL (n = 57). Multivariate analyses were performed to assess risk factors for patient mortality. RESULTS: Mean levels within the first month post-transplant were 7.4 ± 1.7 and 12.6 ± 2.2 ng/mL in the ≤ 10 and > 10 groups, respectively. Donor age was higher in the high TTL group 62.9 ± 16.8 years vs 45.7 ± 17.5 years (P = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% vs 15.8% (P = 0.02). Recipient features were generally similar across groups. After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in: Mean estimated glomerular filtration rate (P = 0.69), hepatocellular carcinoma recurrence (P = 0.44), de novo tumors (P = 0.77), new-onset diabetes (P = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; P = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups (P = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively (P = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively (P = 0.42). Early TTL was not an independent factor for patient mortality in multivariate analyses. CONCLUSION: Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.

A case of COVID-19 immediately after liver transplantation: Not only bad news.

COVID-19, the illness caused by the SARS-CoV-2 virus originated in December 2019 in Wuhan, China and has caused more 3,3 million cases and more than 230,000 deaths throughout the world, with 25,000 of them only in Spain, where the first case was diagnosed on January 31st, 2020. As COVID-19 is a "new" disease, we still do not have data on prognosis or treatment in transplant patients or on how to manage immunosuppression in this complex scenario. We present a case of COVID-19 diagnosed during the early postoperative period in a recipient whose liver transplantation was performed on late March during the lockdown in Spain, with donor and recipient previously negative rRT-PCR to SARS-CoV-2. In the first post-operative week the patient suffered COVID-19 pneumonia that was treated with immunosuppression minimization, oral Hydroxycloroquine and Azithromycin with favorable outcome. The patient was discharged on POD 21 without complications. To date, few early post-liver transplantation SARS-CoV-2 infected recipients have been published, but only one was an early postoperative infection. In our case the outcome was favorable, even though it was an early post -liver transplantation COVID-19 in a frail patient.

Endovascular Therapy of Arterial Complications Within the First Week After Liver Transplant.

BACKGROUND: Recent radiologic advances have made endovascular treatment a very successful option for arterial complications after liver transplant. This article presents our experience of using endovascular treatments during the first week after liver transplant. METHODS: This study is a retrospective, single-center analysis. Liver transplants performed between 2010 and 2018 were analyzed. All patients underwent Doppler ultrasonography on days 1 and 7. Endovascular therapy was indicated in hepatic artery thrombosis diagnosed early after transplant and in stenosis when hepatic narrowing was > 70%. Patients were treated with subcutaneous anticoagulant therapy and with antiplatelet agents after endovascular therapy. RESULTS: Seven patients (1.1%) were included in the study. Stenosis was the reason in 5 patients while 2 patients had symptoms of thrombosis. The first 2 patients were initially treated with angioplasty; both had restenosis and were treated with angioplasty and stent placement, respectively. The 5 most recent patients received stenting as a primary treatment. Two of these patients developed a new stenosis. No patient developed any hepatic artery complication related to the procedure, and only 1 patient experienced a postprocedure complication (femoral artery pseudoaneurysm), which was managed conservatively. No patient required retransplant. After a median follow-up of 48 months (range, 35-85 months) 1 patient had died, and the rest were alive and asymptomatic. CONCLUSIONS: Although there is scant experience of the use of endovascular therapy very shortly after liver transplant, recent advances in interventional radiology have made the technique feasible and safe, and it achieves a high success rate.

Long-Term Outcomes of Liver Transplantation in Patients With Pretransplant Renal Dysfunction Treated With Induction Therapy and Delayed Reduced De Novo Once-Daily Tacrolimus.

BACKGROUND AND AIM: Renal dysfunction is related to short- and long-term survival after liver transplantation. We present herein a retrospective analysis of our experience with liver transplantation in recipients with pretransplant renal dysfunction treated with induction therapy followed by delayed/reduced de novo once-daily tacrolimus. METHODS: Liver transplantations performed between April 2008 and August 2011 were included in this study. Pretransplant renal dysfunction was defined as estimated glomerular filtration rate <60 mL/min. Interleukin-2 receptor antagonists were used for induction therapy. Initial once-daily tacrolimus dose was 0.10 mg/kg/day or 0.07 mg/kg/day if combined with mycophenolate mofetil (MMF). Tacrolimus target trough levels were 4 to 6 ng/mL during the first post-transplant year and <4 ng/mL the rest of the follow-up. RESULTS: Nineteen patients comprised the study cohort with a median follow-up of 56.4 months (range, 11-78). Median day of tacrolimus introduction was 7 (range, 3-12). Once-daily tacrolimus was withdrawn in 6 patients (31.6%) due to evolution of renal dysfunction in all cases. At 5 years, 30% of the patients were under MMF monotherapy. Mean tacrolimus trough levels were maintained under 5 ng/mL. Mean estimated glomerular filtration rate at 5 years was 55.3 ± 12.7 mL/min. No patient needed hemodialysis or renal transplantation over the follow-up. Patient survival at 5 years was 78.9%. CONCLUSIONS: Induction therapy followed by delayed/reduced de novo once-daily tacrolimus and maintenance of low tacrolimus exposition during the follow-up is effective to maintain long-term renal function and to achieve favorable patient survival in liver transplant recipients with pretransplant renal dysfunction.

Long term recurrence free survival in a stage IV gallbladder cancer treated with chemotherapy plus trastuzumab and salvage liver resection.

Surgery is the only treatment for biliary tract cancer with long term survival. Unfortunately, most patients are diagnosed at stage IV with distant metastases. In these circumstances, life expectancy is less than one year due to aggressive tumour biology and a lack of effective systemic therapies. HER2 overexpression or amplification is predominantly seen in extrahepatic cholangiocarcinoma and gallbladder cancer (10-18%) and rarely in intrahepatic cholangiocarcinoma (1%). Trastuzumab is a monoclonal antibody that targets HER-2. We present a clinical case with a stage IV gallbladder cancer (liver and interaortocaval lymph node metastases), which presented progression during first-line chemotherapy treatment, which prompted a change in therapy to study the Her 2/Neu mutation which showed an intense positive overexpression. A combination of HER2/Neu-directed therapy (Trastuzumab) with second-line chemotherapy, was able to achieve a long term complete radiological, metabolic, and biochemical response. A curative intention surgery was performed and the patient is alive and recurrence-free at five years. To the best of our knowledge, we present a case which is the first report of a patient with a Stage IV gallbladder cancer who achieved a five-year survival without recurrence after a conversion therapy combining chemotherapy plus Trastuzumab and radical salvage surgery.

Favorable Outcomes After Liver Transplantation With Normothermic Regional Perfusion From Donors After Circulatory Death: A Single-center Experience.

BACKGROUND: Controlled donation after circulatory death (cDCD) has been associated with a high incidence of ischemic cholangiopathy and other perioperative complications. In an attempt to avoid these complications, we implemented an active protocol of cDCD liver transplant (LT) with normothermic regional perfusion (NRP) preservation. METHODS: This is a descriptive analysis of data collected from a prospective date base of cDCD LT preserved with NRP from January 2015 to June 2017 with a minimum follow up of 9 months. RESULTS: Fifty-seven potential cDCD donors were connected to the NRP system. Of these, 46 livers were transplanted over a 30-month period (80% liver recovery rate). The median posttransplant peak in alanine transaminase was 1136 U/L (220-6683 U/L). Seven (15%) patients presented postreperfusion syndrome and 11 (23%) showed early allograft dysfunction. No cases of ischemic cholangiopathy were diagnosed, and no graft loss was observed over a medium follow-up period of 19 months. Of note, 13 donors were older than 65 years, achieving comparable perioperative and midterm results to younger donors. CONCLUSIONS: As far as we know, this represents the largest published series of cDCD LT with NRP preservation. Our results demonstrate that cDCD liver grafts preserved with NRP appear far superior to those obtained by the conventional rapid recovery technique.

Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort.

The once-daily prolonged-release formulation of tacrolimus has been recently related with significant graft and patient mid-term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5-year retrospective analysis of a single-center cohort of liver transplant recipients treated de novo with once-daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow-up of 57.6 months (interquartile range, 46.6-69.0). Tacrolimus target trough levels were 5-10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once-daily tacrolimus was withdrawn in 35 (21.8%) patients during follow-up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy-proven acute rejection rate was 12.5% with no cases of steroid-resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m(2) at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End-Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once-daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391-1400 2016 AASLD.