Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

Mortality and Causes of Death After Liver Transplantation: Analysis of Sex Differences in a Large Nationwide Cohort.

In the last few years, several studies have analyzed sex and gender differences in liver transplantation (LT), but none have performed a disaggregated analysis of both mortality and causes of death. Data from 15,998 patients, 11,914 (74.5%) males and 4,069 (25.5%) females, transplanted between 2000 and 2016 were obtained from the Liver Transplantation Spanish Registry. Survival analysis was applied to explore recipient sex as a risk factor for death. The causes of death at different follow-up duration were disaggregated by recipient sex for analysis. Short-term survival was higher in males, whereas long-term survival was higher in females. Survival at 1, 5 and 10 years post-transplant was 87.43%, 73.83%, and 61.23%, respectively, in males and 86.28%, 74.19%, and 65.10%, respectively, in females (p = 0.05). Post-LT mortality related to previous liver disease also presented sex differences. Males had 37% increased overall mortality from acute liver failure (p = 0.035) and 37% from HCV-negative cirrhosis (p < 0.001). Females had approximately 16% increased mortality when the liver disease was HCV-positive cirrhosis (p = 0.003). Regarding causes of death, non-malignancy HCV+ recurrence (6.3% vs. 3.9% of patients; p < 0.001), was more frequently reported in females. By contrast, death because of malignancy recurrence (3.9% vs. 2.2% of patients; p = 0.003) and de novo malignancy (4.8% vs. 2.5% of patients; p < 0.001) were significantly more frequent in male recipients. Cardiovascular disease, renal failure, and surgical complications were similar in both. In summary, male patients have lower short-term mortality than females but higher long-term and overall mortality. In addition, the post-LT mortality risk related to previous liver disease and the causes of mortality differ between males and females.

Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

Choledochal cysts surgical management: Retrospective and historical comparative analysis.

INTRODUCTION: Choledochal cysts are rare bile duct dilatations, which have higher prevalence in Asian population. The aim of the study was to analyze clinical and surgical results about biliary cysts management. In addition, a comparative historical analysis was performed. METHODS: Patients who underwent surgery between January 1988 and December 2019 in a single tertiary level center were retrospectively included. Demographic and clinical patient data; cyst types; diagnostic methods and surgical technique were analyzed, as well as short and long-term follow-up complications. A comparative descriptive study focus on the main historical series was also carried out. RESULTS: A total of seventeen patients were identified; 58.8% were men. The mean age at diagnosis was 39.9 years (SD: 20.54). The median follow-up was 5 years (IQR 1-15). The most frequent cysts were type I (41.2%). Abdominal pain was the most common presenting symptom (58.8%). Cystic excision with bilio-enteric anastomosis was the main procedure, it was underwent in 85, 7% type I cysts. 29.4% postoperative complications were recorded. Malignancy was not documented in any pathology specimen. CONCLUSIONS: Choledochal cysts are an uncommon disorder whose diagnosis requires a high level of suspicion. Surgical treatment depends on type of cyst. In most patients with choledochal cysts disease, complete cyst excision with bilio-enteric anastomotic reconstruction is the treatment of choice.

Virtual transparency in ϕ-OTDR using second order Raman amplification and pump modulation.

In distributed optical fibre sensors, distributed amplification schemes have been investigated in order to increase the measurement range while avoiding the limitation imposed by the fibre attenuation and the nonlinear effects. Recently, the use of Raman amplification with an engineered intensity modulation has been demonstrated as an efficient way to produce a virtually lossless trace employing a single-end configuration. In this paper, we propose the combination of this technique with a simultaneous second order Raman pumping scheme for increasing the measurement range. The optimal modulation profile has been numerically analyzed and we experimentally demonstrate a sensor able to detect perturbations along 70 km of fibre, with a minimal SNR penalty along the total length. Thanks to this new approach, the sensitivity in the worst point is considerably improved, and the ASD noise floor is also reduced. The measurement range is extended approximately 15 km compared with the equivalent first order pumping case.

An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

Choledochal cysts surgical management: Retrospective and historical comparative analysis. / Manejo quirúrgico de los quistes de colédoco: análisis retrospectivo y comparativa histórica.

INTRODUCTION: Choledochal cysts are rare bile duct dilatations, which have higher prevalence in Asian population. The aim of the study was to analyze clinical and surgical results about biliary cysts management. In addition, a comparative historical analysis was performed. METHODS: Patients who underwent surgery between January 1988 and December 2019 in a single tertiary level center were retrospectively included. Demographic and clinical patient data; cyst types; diagnostic methods and surgical technique were analyzed, as well as short and long-term follow-up complications. A comparative descriptive study focus on the main historical series was also carried out. RESULTS: A total of seventeen patients were identified; 58.8% were men. The mean age at diagnosis was 39.9 years (SD: 20.54). The median follow-up was 5 years (IQR 1-15). The most frequent cysts were tipe I (41.2%). Abdominal pain was the most common presenting symptom (58.8%). Cystic excision with bilio-enteric anastomosis was the main procedure, it was underwent in 85, 7% type I cysts. 29.4% postoperative complications were recorded. Malignancy was not documented in any pathology specimen. CONCLUSIONS: Choledochal cysts are an uncommon disorder whose diagnosis requires a high level of suspicion. Surgical treatment depends on type of cyst. In most patients with choledochal cysts disease, complete cyst excision with bilio-enteric anastomotic reconstruction is the treatment of choice.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

Leiomiosarcoma de vena cava inferior / Leiomyosarcoma of the inferior vena cava

No disponible

Protective Role of the Portocaval Shunt in Liver Transplantation.

BACKGROUND: Advances in medical management and surgical technique have resulted in stepwise improvements in early post-transplant survival rates. Modifications in the surgical technique, such as the realization of the portocaval shunt (PCS), could influence survival rates. The aim of this study was to evaluate the mortality rate for 12 months after liver transplantation, analyzing the causes and risk factors related to its development and assessing the impact that PCS could have on them. METHODS: A total of 231 recipients were included in the retrospective, longitudinal, and nonrandomized study. RESULTS: The overall survival of the transplant was 85.2% (197 patients). The most frequent cause of death was infection (38.2%), followed by the multiorgan failure of multiple etiology (23.5%). Most of the risk factors related to mortality correspond to variables of the postoperative period. The results of the multivariate analysis identified the main risk factors for death: the presence of surgical complications and the need for renal replacement therapy. In contrast, the performance of PCS exerted a protective effect, reducing the probability of death by 70%. CONCLUSIONS: Despite the good results obtained in several studies, there is still debate regarding the benefit of its realization. In our study, PCS was a factor associated with a reduction in mortality, with a markedly lower probability of adverse events. However, we agree with other authors on the need for larger and randomized studies to adequately determine the validity of such results.

Cystic Duct Bile Leak in Graft: An Unexpected Origin for Choleperitoneum After Liver Transplant.

From the beginning of liver transplant implementation, biliary anastomosis has been considered its weakness. An anastomotic bile leak is the most frequent cause of bile in the peritoneum (choleperitoneum) after liver transplant but not the only one. Here, we report a 58-year-old man with hepatitis C virus-related cirrhosis who had orthotopic liver transplant due to presence of hepatocellular carcinoma.During the immediate postoperative period, bile leakwas diagnosed on trans-Kehr cholangiography. Contrast extravasation was observed on the graft's cystic duct, and no contrast flow into the native biliary tract was demonstrated. Surgical intervention was required after endoscopic management failure. Bile leak through the cystic duct was repaired, and a Rouxen-Y bilioenteric diversion was performed. Biliary complications can significantly increase morbidity and mortality after liver transplant. Anastomotic bile leaks are the most frequent; however, other locations must not be dismissed as possible origins of leak. It is mandatory to consider underlying hepatic artery complications as thrombosis or stenosis. Treatment will depend on the leak origin, which are most times accessible to endoscopic retrograde cholangiopancreatography. However, other locations and the different treatment options must also be considered. It is also necessary not to forget the influence of bile leaks on biliary stenosis development in the long term and its contribution to increased patient morbidity and mortality.

Sinosanal undifferentiated carcinoma with liver metastasis: surgical management.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare tumor with poor prognosis and high incidence of distant metastasis, even when a good loco-regional control is achieved. CASE: We report the case of a 43-year-old female with SNUC diagnosis. Craniofacial resection with orbital exenteration and radiotherapy in tumor bed and lymph node chain was performed. After 10 months, SNUC hepatic relapse (sIII and sVIII) is diagnosed. We administered chemotherapy and then, surgical resection was carried out. After surgery, two new relapses were diagnosed, at 9 and 21 months where surgical management was performed in both cases. 56 months after SNUC diagnosis, the patient has no evidence of recurrence. DISCUSSION: Recommended oncological clinical guidelines for distant metastases in SNUC are chemotherapy. Surgical management in oligometastatic disease in SNUC should be considered.

Current allocation policy is favorable for patients with hepatocellular carcinoma waiting for liver transplantation.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) are a growing population of the transplantation waiting list (WL) for orthotopic liver transplantation (OLT). There is no consensus to prioritize these patients while on the WL. AIMS: To assess whether patients with HCC were more prioritized than non-HCC patients based on their WL survival as primary outcome. METHODS: Restrospective cohort study including patients listed for elective OLT from January 2013 to January 2016. RESULTS: 165 patients with cirrhosis were listed for OLT: 64 in the HCC group (38.78%) and 101 in the non-HCC group (61.22%). Outcomes (HCC vs. non-HCC) were: OLT in 75.51% vs. 64.37%; death or dropout due to worsening in 20.41% vs. 27.59%, and delisting because of improvement in 4.08% vs. 8.05%. HCC patients had a significantly higher WL survival rate (HR = 0.45; 95% CI: 0.21-0.96); lower MELD score at transplantation (21 [20-24] vs. 24 [20-30]; p = 0.021); higher delta-MELD - the difference between MELD at transplantation and MELD at listing time - (3 [2-6] vs. 0 [0-5]; p = 0.024) and longer waiting time until OLT (143 [70-233] vs. 67 [21-164] days; p = 0.008). CONCLUSION: Despite having to wait longer, patients with HCC showed higher WL survival than non-HCC patients.

Open-Cavity Spun Fiber Raman Lasers with Dual Polarization Output.

Random distributed feedback fiber Raman lasers, where the feedback mechanism is provided by Rayleigh backscattering, have attracted a good deal of attention since they were first introduced in 2010. Their simple and flexible design, combined with good lasing efficiency and beam quality properties, comparable to those of standard cavity lasers, have led to multiple applications, particularly in the fields of fiber sensing and optical communications. In spite of these advances, the polarization properties of random fiber Raman lasers, which can strongly affect their performance in both sensing and communications, have barely been explored so far. In this article we experimentally and theoretically study the polarization properties of different open-cavity laser designs, based on either standard transmission fibers or low polarization-mode-dispersion spun fibers. By using high-power, highly-polarized pumps, we demonstrate controllable polarization-pulling and simultaneous lasing at close wavelengths with different output polarization properties in random distributed feedback fiber Raman lasers. These results advance our understanding of the polarization dynamics in ultralong lasers, and pave the way to the design of novel fiber laser sources capable of polarization-sensitive sensing and distributed amplification.

40 GHz pulse source based on cross-phase modulation-induced focusing in normally dispersive optical fibers.

We theoretically and experimentally investigate the design of a high-repetition rate source delivering well-separated optical pulses due to the nonlinear compression of a dual-frequency beat signal within a cavity-less normally dispersive fiber-based setup. This system is well described by a set of two coupled nonlinear Schrödinger equations for which the traditional normally dispersive defocusing regime is turned in a focusing temporal lens through a degenerated cross-phase modulation process (XPM). More precisely, the temporal compression of the initial beating is performed by the combined effects of normal dispersion and XPM-induced nonlinear phase shift provided by an intense beat signal on its weak out-of-phase replica co-propagating with orthogonal polarizations. This adiabatic reshaping process allows us to experimentally demonstrate the generation of a 40 GHz well-separated 3.3 ps pulse train at 1550 nm in a 5 km long normally dispersive fiber.

Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period.

BACKGROUND & AIMS: Reinfection of the graft is the rule in patients with HCV cirrhosis undergoing liver transplantation, and HCV-RNA reaches pre-transplantation levels within the first month. Short-term intravenous silibinin monotherapy is safe and shows a potent in vivo anti-HCV effect. We aimed at evaluating the safety and antiviral effect of prolonged intravenous silibinin, started immediately before liver transplantation. METHODS: Single centre, prospective, pilot study, to assess the safety and effect on HCV-RNA kinetics during at least 21 days of intravenous silibinin monotherapy (20 mg/kg/day) in 9 consecutive HCV genotype 1 subjects, in comparison to a control, non-treated group of 7 consecutive prior transplanted subjects under the same immunosuppressive regimen (basiliximab, steroids, delayed tacrolimus, micophenolate). RESULTS: Intravenous silibinin led to significant, maintained and progressive HCV-RNA decreases (mean HCV-RNA drop at week 3, -4.1 ± 1.3 log(10)IU/ml), and lack of viral breakthrough during administration. Four patients (44%) reached negative HCV-RNA, maintained during silibinin treatment, vs. none in the control group, but HCV-RNA relapsed in all of them after a median of 21 days (16-28), following silibinin withdrawal. Partial responders to silibinin showed marked decreases in HCV-RNA when compared to controls, but lower than complete responders. There were no clinical adverse effects, and silibinin led to asymptomatic transient hyperbilirubinemia (week 2, 4.2 ± 2.2 vs. 2.5 ± 3.6 mg/dl; p=0.02). CONCLUSIONS: Prolonged intravenous silibinin monotherapy was safe in the immediate liver transplantation period, leading to a potent and time dependent antiviral effect and lack of HCV-RNA breakthrough during administration. However, HCV-RNA rebounded after withdrawal, and silibinin monotherapy did not avoid reinfection of the graft.

Multichannel Raman polarizer with suppressed relative intensity noise for wavelength division multiplexing transmission lines.

We propose a method of suppressing the relative intensity noise caused by polarization-dependent gain that is inherent to Raman polarizers (RPs). This method involves bit-synchronously scrambling the state of polarization of a pulse (bit) before the pulse enters the RP. The proposed solution works for RPs operating in a depleted regime and is compatible with multichannel configurations.