Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure.

OBJECTIVE: To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes. BACKGROUND: AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT. METHODS: This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates. RESULTS: Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant. CONCLUSION: These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers.

Acute graft versus host disease after liver transplantation: where do we stand?

Graft-versus-host disease (GVHD) is a rare complication after liver transplantation (LT), with an estimated incidence rate of 0.5% to 2% and a mortality rate as high as 75%. The classical target organs of GVHD include the intestines, liver, and skin. The damage of these organs is not easy to detect for the clinician as there is no widely accepted clinical or laboratory diagnostic tests; as a result, diagnosis and initiation of therapy are often delayed. Moreover, without prospective clinical trials to reference, evidence guiding therapy is limited. This review summarized the current knowledge, the potential applications and the clinical relevance of GVHD after LT, highlighting novel approaches in grading and management of GVHD.

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Accurate assessment of nonalcoholic fatty liver disease lesions in liver allograft biopsies by a smartphone platform: A proof of concept.

Macrovesicular steatosis (MS) is a major risk factor for liver graft failure after transplantation and pathological microscopic examination of a frozen tissue section remains the gold standard for its assessment. However, the latter requires an experienced in-house pathologist for correct and rapid diagnosis as well as specific equipment that is not always available. Smartphones, which are must-have tools for everyone, are very suitable for incorporation into promising technology to generate moveable diagnostic tools as for telepathology. The study aims to compare the microscopic assessment of nonalcoholic fatty liver disease (NAFLD) spectrum in liver allograft biopsies by a smartphone microscopy platform (DIPLE device) to standard light microscopy. Forty-two liver graft biopsies were evaluated in transmitted light, using an iPhone X and the microscopy platform. A significant correlation was reported between the two different approaches for graft MS assessment (Spearman's correlation coefficient: r = .93; p < .001) and for steatohepatitis feature (r = .56; p < .001; r = .45; p < .001). Based on these findings, a smartphone integrated with a cheap microscopy platform can achieve adequate accuracy in the assessment of NAFLD in liver graft and could be used as an alternative to standard light microscopy when the latter is unavailable.

Use of Artificial Intelligence as an Innovative Method for Liver Graft Macrosteatosis Assessment.

The worldwide implementation of a liver graft pool using marginal livers (ie, grafts with a high risk of technical complications and impaired function or with a risk of transmitting infection or malignancy to the recipient) has led to a growing interest in developing methods for accurate evaluation of graft quality. Liver steatosis is associated with a higher risk of primary nonfunction, early graft dysfunction, and poor graft survival rate. The present study aimed to analyze the value of artificial intelligence (AI) in the assessment of liver steatosis during procurement compared with liver biopsy evaluation. A total of 117 consecutive liver grafts from brain-dead donors were included and classified into 2 cohorts: ≥30 versus <30% hepatic steatosis. AI analysis required the presence of an intraoperative smartphone liver picture as well as a graft biopsy and donor data. First, a new algorithm arising from current visual recognition methods was developed, trained, and validated to obtain automatic liver graft segmentation from smartphone images. Second, a fully automated texture analysis and classification of the liver graft was performed by machine-learning algorithms. Automatic liver graft segmentation from smartphone images achieved an accuracy (Acc) of 98%, whereas the analysis of the liver graft features (cropped picture and donor data) showed an Acc of 89% in graft classification (≥30 versus <30%). This study demonstrates that AI has the potential to assess steatosis in a handy and noninvasive way to reliably identify potential nontransplantable liver grafts and to avoid improper graft utilization.

Liver transplantation for bariatric surgery-related liver failure: a systematic review of a rare condition.

BACKGROUND: Protein malnutrition and bacterial overgrowth occurring after bariatric surgery (BS) might cause severe liver failure (LF) needing liver transplantation (LT). OBJECTIVES: To evaluate indications and outcomes of LT for BS-related LF. SETTING: University hospital in France. METHODS: The EMBASE, MEDLINE, and COCHRANE central databases were systematically searched according to the PRISMA criteria from inception up through December 2017 for articles describing LT for LF after BS. RESULTS: Fourteen studies reporting 36 patients listed for LT, of which 32 underwent the procedure, were retained. The types of previously performed BS included jejunoileal bypass (n = 16), bilio-pancreatic diversion according to Scopinaro (n = 14) or with duodenal switch (n = 3), bilio-intestinal bypass (n = 1), long-limb Roux-en-Y gastric bypass (n = 1), and single anastomosis omega gastric bypass (n = 1). Liver failure developed a median of 20 months after BS (mean ± SD: 105 ± 121 mo; range, 5-300 mo). This interval of time was significantly shorter after biliopancreatic diversion than jejunoileal bypass (mean ± SD: 22 ± 21 mo versus 269 ± 27 mo; P = .0001). Four patients (11.1%) died while on the waiting list for LT, and 4 more (12.5%) died after LT. Morbidity and liver retransplantation were reported in 8 (25%) and 2 (6.2%) patients, respectively. Twenty-one patients (65.6%) had their BS procedure reversed (1 patient before, 15 patients during, and 5 patients after LT, respectively). Biopsy-proven steatosis recurrence after LT was reported in 6 patients (18.7%), 4 of whom did not have BS reversal. CONCLUSIONS: Severe LF occurring after BS, although rare, might require LT. When indicated, LT is effective at restoring liver function, even when BS reversal is performed synchronously.

Predicting the Severity of Pancreatic Fistula after Pancreaticoduodenectomy: Overweight and Blood Loss as Independent Risk Factors: Retrospective Analysis of 277 Patients.

Background: Risk factors for pancreatic fistula (POPF) occurrence after pancreaticoduodectomy (PD) are mostly known. Identifying those that are linked to clinically relevant POPF (Grades B and C) (CR-POPF) is critical, as CR-POPF is associated with more complications and a higher mortality rate. Methods: From 2004 to 2016, 270 consecutive patients who underwent PD in two academic centers were compared retrospectively according to the occurrence of CR-POPF. Results: A series of patients with a median age of 64.5 years (range 30.6-88.7 years) underwent PD. They were allocated to two groups: CR-POPF (Grades B and C)(n = 74; 27.4%) and without clinically relevant POPF (cr-POPF) (no fistula formation or Grade A) (n = 196). Pancreatic ductal adenocarcinoma was the main indication for the procedure (58.5%). Post-operative complications Clavien-Dindo I/II and Clavien-Dindo III/IV and in-hospital death occurred in 109 (40.4%), 67 (24.8%), and 18 (6.7%) patients, respectively. After univariate analysis, CR-POPF was associated with a Body Mass Index (BMI) >25 kg/m2 (p < 0.0001), pancreatic duct diameter <3 mm (p = 0.047), soft pancreas texture to palpation (p = 0.037), and peri-operative transfusion (p < 0.001). After multivariate analysis, high BMI (p = 0.026), transfusion (p < 0.001), length of hospital stay (p < 0.0001), and in-hospital death (p = 0.004) were associated with CR-POPF. Conclusions: In-hospital death and length of hospital stay after PD are related to CR-POPF. A BMI >25 kg/m2 and peri-operative blood transfusion are objective risk factors for CR-POPF.

Intraoperatively malpositioned stent as a complication of common bile duct injury during laparoscopic cholecystectomy.

Injuries occurring during laparoscopic bile duct exploration in the course of laparoscopic cholecystectomy may represent threatening complications and lead to inappropriate management. We present a case of patient with biliary colic who underwent laparoscopic cholecystectomy. During the procedure, a common bile duct injury occurred, compelling conversion to open approach, and the patient was treated using a manually inserted biliary stent. She was referred with severe right upper quadrant pain six weeks after the surgery. Investigation with endoscopic retrograde cholangiopancreatography showed a malpositioned biliary stent with completely extra-biliary trajectory. This is thought to be the first description of a malpositioned common bile duct stent through the common biliary duct as a complication of the commonly performed surgical procedure of bile duct exploration.

From deceased to bioengineered graft: New frontiers in liver transplantation.

In the worldwide context of graft shortage, several strategies have been explored to increase the number of grafts available for liver transplantation (LT). These include the use of marginal and living donors, split livers, and the improvement of marginal donor grafts (machine perfusion). However, recent advances in the understanding of liver organogenesis, stem cells, and matrix biology provide novel insights in tissue engineering. Today, the newest technologies and discoveries open the door to the development of new methods for organ implementation such as the recellularization of natural scaffolds, liver organoids, bio-printing, and tissue or generation of chimeric organs. These approaches might potentially to generate an unlimited source of grafts (allogenic or chimeric) which will be used in the near future for LT or as a temporary bridge toward LT. This qualitative review focuses on all methods of organ implementation and highlights the newest developments in tissue engineering and regenerative medicine.

Assessment of Liver Graft Steatosis: Where Do We Stand?

The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively "the ideal method" to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.

Modified Technique of Total Hepatectomy in Polycystic Liver Disease With Caval Flow Preservation: The Exposure Left Lateral Sectionectomy.

BACKGROUND: Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12% to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy to limit hazardous liver manipulation and improve exposure of inferior vena cava in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS). METHODS: From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, which allows for rapid and bloodless transection using electric scalpel. RESULTS: Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 minutes, and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 mL, and no patient required total caval clamping. All patients were alive at the end of the follow-up. CONCLUSIONS: ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation.

Nutritional issues in patients with obesity and cirrhosis.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Late Pancreatic Anastomosis Stricture Following Pancreaticoduodenectomy: a Systematic Review.

BACKGROUND: With an increasing postoperative survival and prolonged follow-up, late complications following pancreaticoduodenectomy (PD) have yet to be thoroughly described and analyzed. Among those, pancreatic anastomosis stricture may lead to severe consequences. METHODS: A systematic review focusing on pancreaticojejunostomy anastomosis (PJA) stricture. RESULTS: PJA stricture incidence reached 1.4-11.4% with a median time interval of 34 months after PD. No risk factor was identified. PJA stricture repercussions were inconsistent but postprandial abdominal pain and recurrent acute pancreatitis were the most common symptoms, followed by impaired pancreatic function. To confirm diagnosis, secretin-enhanced magnetic resonance cholangiopancreatography (SMRCP) sensitivity reached 56-100%. As impaired pancreatic function is not improved by any procedure, only PJA stricture leading to abdominal pain or acute pancreatitis should be considered for treatment. Endoscopic techniques (mainly ultrasound-assisted "rendezvous") should be proposed prior to surgical repair, with a morbidity, an overall technical and clinical success reaching 16.5-33% and 28.6-100% and 33-100%, respectively. Regarding surgical repair, overall morbidity varied between 14.3 and 33%, with a clinical success reaching 26.1-100%. Finally, total pancreatectomy with islet auto-transplantation should be considered only for pain intractable to medical management and recurrent acute pancreatitis which has failed medical, endoscopic, and traditional surgical management strategies. CONCLUSION: PJA stricture following PD is a late, unusual, and potentially serious complication. When there is currently no clear consensus, PJA stricture leading to abdominal pain or acute pancreatitis should be considered treatment. With increasing survival after PD, further studies should focus on late complications. CORE TIP: Stricture of pancraticojejunostomy is a late and potentially serious complication after pancreaticoduodenectomy. Incidence reaches 1.4-11.4% and no risk factor is identified. Symptoms are inconsistent but postprandial abdominal pain, recurrent acute pancreatitis, and impaired pancreatic function are the most frequent. To confirm diagnosis, secretin-enhanced magnetic resonance cholangiopancreatography is the best modality. Only PJA stricture leading to abdominal pain or acute pancreatitis should be considered for treatment. Endoscopic techniques (mainly ultrasound-assisted "rendezvous") should be proposed prior to surgical repair. Finally, total pancreatectomy with islet auto-transplantation should be considered only for pain intractable to medical management and recurrent acute pancreatitis which has failed medical, endoscopic, and traditional surgical management strategies.

Innovation in Surgery: Qualitative Analysis of the Decision-Making Process and Ethical Concerns.

BACKGROUND: Surgical innovation from surgeon's standpoint has never been scrutinized as it may lead to understand and improve surgical innovation, potentially to refine the IDEAL (Idea, Development, Exploration, Assessment, Long-term Follow-up) recommendations. METHODS: A qualitative analysis was designed. A purposive expert sampling was then performed in organ transplant as it was chosen as the ideal model of surgical innovation. Interviews were designed, and main themes included the following: definition of surgical innovation, the decision-making process of surgical innovation, and ethical dilemmas. A semistructured design was designed to analyze the decision-making process, using the Forces Interaction Model. An in-depth design with open-ended questions was chosen to define surgical innovation and ethical dilemmas. RESULTS: Interviews were performed in 2014. Participants were 7 professors of surgery: 3 in liver transplant, 2 in heart transplant, and 2 in face transplant. Saturation was reached. They demonstrated an intuitive understanding of surgical innovation. Using the Forces Interaction Model, decision leading to contemporary innovation results mainly from collegiality, when the surgeon was previously the main factor. The patient is seemingly lesser in the decision. A perfect innovative surgeon was described (with resiliency, legitimacy, and no technical restriction). Ethical conflicts were related to risk assessment and doubts regarding methodology when most participants (4/7) described ethical dilemma as being irrelevant. CONCLUSIONS: Innovation in surgery is teamwork. Therefore, it should be performed in specific specialized centers. Those centers should include Ethics and Laws department in order to integrate these concepts to innovative process. This study enables to improve the IDEAL recommendations and is a major asset in surgery.

Computer-assisted liver graft steatosis assessment via learning-based texture analysis.

PURPOSE: Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. METHODS: Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was [Formula: see text]. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern ([Formula: see text]), and gray-level co-occurrence matrix ([Formula: see text]) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. RESULTS: With the best-performing feature set ([Formula: see text]) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. CONCLUSIONS: This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR.

Surgery to Treat Symptomatic Mobile Cecum Syndrome Is Safe and Associated with Good Recovery Outcomes.

The mobile cecum syndrome includes a spectrum of conditions. The cecal volvulus represents the acute form, with typical feature of a bowel obstruction that needs immediate operative treatment. On the other hand, a chronic form of mobile cecum syndrome which is the most common form reported a history of intermittent crampy abdominal pain, distension, and constipation. In this study, five patients came to our attention during the last ten years, presenting different symptoms due to a mobile cecum. All patients were investigated by several diagnostic techniques according to the specific clinical setting. All patients were found to have the cecum and ascending colon unattached to the posterior peritoneum. Surgery was the treatment of choice. In our experience, the best diagnostic technique was computed tomography scan, especially if performed in the Trendelenburg position. We also propose virtual colonoscopy as a good option for diagnosis (in patients with chronic syndrome) and follow-up after surgery. In conclusion, laparoscopic approach guaranteed a good result, with no symptoms of recurrence, in both acute and elective treatments. The diagnosis of mobile cecum needs a high index of suspicion and a targeted radiological investigation. Surgery, especially laparoscopic cecopexy and appendectomy, is the recommended treatment.