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.

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.

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.

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study.

BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes.

Correction to: Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study.

In the original article, the institutional author the E-AHPBA DP-CAR study group was misspelled. It is correct as reflected here. The original article has also been corrected.

Effect of endoscopic failure on the results of internal surgical drainage in pancreatic pseudocyst.

BACKGROUND: The treatment of pancreatic pseudocysts has evolved during the past two decades. Endoscopic treatment (ET) has gradually become used as a first-line management even though it showed no significant superiority to surgical internal drainages (SIDs) in a recent randomized trial. The objective of the present work was to analyze the effect of ET failure on the results of SID in the global management of pancreatic pseudocysts. METHODS: A multicenter retrospective study (Clichy, Bordeaux, Nantes, and Rennes) was conducted between January 2000 and December 2012. The main criteria were as follows: (i) major postoperative complications (MPCs) (Clavien ≥ 3) and (ii) treatment failure in the first 12 mo. All factors that may affect these two parameters were tested in univariate and multivariate analyses, when necessary. RESULTS: One hundred nineteen patients, with a median age of 52 y (22-83) underwent SID, including 45 procedures (37.8%) performed after ET failure. Mortality and overall morbidity rates were 1.7% and 30.2%, respectively. Eighteen patients (15.1%) presented an MPC. Multivariate analysis revealed that failure of ET (odds ratio 3.04, confidence interval [1.04 to 9.5], P = 0.046) and BMI ≤20 (odds ratio 4.5, confidence interval [1.50; 15.5], P = 0.010) were independent risk factors of MPCs. The success of SID was 92.5% in the first year. In univariate analysis, the occurrence of an MPC was the only factor linked to the failure of SID (P = 0.029). CONCLUSIONS: Performing an SID after ET failure is associated with an increased risk of MPC. Close postoperative monitoring is recommended for these patients.

Effectiveness and risk of biliary drainage prior to pancreatoduodenectomy: review of current status.

Preoperative biliary drainage (PBD) prior to pancreatoduodenectomy (PD) has gained popularity as bridge management to resolve jaundice, but its role is being challenged as it is thought to increase morbidity. To clarify the current recommendations for PBD prior to PD, we reviewed the literature, including all relevant articles published in English up until December, 2015. There is increasing evidence that PBD causes bile infection, which is related to the morbidity of infectious complications. Results of transhepatic drainage are poorer than those of endoscopic stenting, especially in an oncologic setting, although it is still unclear whether metallic stents are superior to nasobiliary drainage. PBD should be avoided whenever possible and performed only in selected cases, such as the emergency setting, an inevitable long delay (>4 weeks) before PD, and jaundice-related anorexia. Seemingly, transhepatic drainage should be reserved for refractory cases if endoscopic drainage is not possible. Further studies comparing endoscopic drainage techniques, such as metallic stents and nasobiliary drainage, are required to assess the most effective technique of PBD. Bile infection should be prevented by adequate antibiotic prophylaxis and treated even in the absence of symptoms, and bile status should be assessed systematically.

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.

Abdominal emergencies after liver transplantation: Presentation and surgical management.

With an increasing number of liver transplantation (LT) and an enhanced overall survival, LT recipients are more likely to be admitted in emergency departments of general hospitals. Yet, in LT recipients, common but also benign symptoms may reveal a LT-related (or not) severe condition. To improve management of LT recipients by emergency physicians and general surgeons and potentially improve long-term outcomes, a clinical review was performed. Overall, CT scan and blood tests should be systematically performed. Immunosuppressive side effects should be excluded using blood tests. LT-related complications are more likely to occur during the first three months after LT, including mainly bile leak, arterial aneurysm, and pseudoaneurysm. Patients should be referred in emergency to tertiary centers. Non-LT-related complications and common abdominal conditions may also be diagnosed in LT recipients. Except in case of diffuse peritonitis or in hemodynamically unstable patients when surgical procedure should be performed, most conditions should be reassessed regarding the immunosuppressive treatment and the adhesive abdominal cavity.

Endovascular management of delayed post-pancreatectomy haemorrhage.

OBJECTIVES: To assess the patient outcome after endovascular treatment of delayed post-pancreatectomy haemorrhage (PPH) as first-line treatment. METHODS: Between January 2005 and November 2013, all consecutive patients referred for endovascular treatment of PPH were included. Active bleeding, pseudoaneurysms, collections and the involved artery were recorded on pretreatment CT. Endovascular procedures were classified as technical success (source of bleeding identified on angiogram and treated), technical failure (source of bleeding identified but incompletely treated) and abstention (no abnormality identified, no treatment performed). Factors associated with rebleeding were analysed. RESULTS: Sixty-nine patients (53 men) were included (mean 59 years old (32-75)). Pretreatment CT showed 27 (39 %) active bleeding. In 22 (32 %) cases, no involved artery was identified. Technical success, failure and abstention were observed in 48 (70 %), 9 (13 %) and 12 patients (17 %), respectively. Thirty patients (43 %) experienced rebleeding. Rebleeding rates were 29 %, 58 % and 100 % in case of success, abstention and failure (p < 0.001). Treatment failure/abstention was the only factor associated with rebleeding. Overall, 74 % of the patients were successfully treated by endovascular procedure(s) alone. CONCLUSION: After a first endovascular procedure for PPH, the rebleeding rate is high and depends upon the success of the procedure. Most patients are successfully treated by endovascular approach(es) alone. KEY POINTS: • After a first endovascular procedure for PPH the rebleeding rate is high • The rebleeding rate is significantly associated with initial technical success • Three-quarters of the patients are successfully treated by endovascular procedure(s) alone.

Cold ischemia time in liver transplantation: An overview.

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

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.

Small cell carcinoma of the breast. Report of a case.

The recognition of undifferentiated forms of endocrine tumors in the extrapulmonary sites is considered as extremely infequent. Immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung and as the pulmonary one, it is more aggressive than carcinoma without neuroendocrine differentiation. We report a case of a 68 years old woman with a primary small cell carcinoma of the breast gland presented as a palpable and mobile 2 cm mass, located in the upper outer quadrant of her right breast. It was treated with surgery and the diagnosis was made after surgical treatment, thanks to the immunohistochemical studies of tissue.

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.

Tako-tsubo cardiomyopathy as initial presentation of pheocromocytoma. A clinical case.

INTRODUCTION: Tako-tsubo cardiomyopathy is a rapidly reversible form of acute heart failure triggered by stressful events that occur more frequently in postmenopausal women. A central role is supposed to be played by catecholamines and the association with pheocromocytoma is rare. CASE PRESENTATION: We describe a patient admitted for abdominal pain and suffering of hypertension pharmacologically treated. During hospitalization the patient presented cephalea and precordial pain with nausea and profuse sweating. ECG showed ST elevation and deep negative T wave. Blood tests were moderately elevated. Echo-cardiography reported a left ventricular apex akynesia and hyperkynesia of the base while coronarography was negative. As hypertension persisted the suspicion of pheocromocytoma arose. Urinary and blood catecholamines were mildly elevated and echography and Magnetic Resonance revealed a left adrenal gland mass. The diagnosis of pheocromocytoma was thus confirmed Left laparoscopic adrenalectomy was performed after adequate stabilization and preoperative pharmacological preparation by hydration, a-and f-blockers. Intraoperatively blood pressure was controlled by nitroprussiate, rapid half life beta-blockers (esmolol cloridrate). Post-operative course was uneventful and arterial pressure returned to normal as well as catecholamines values. Patient was discharged on the 5th post-operative day Five months afterwards the patient had normal arterial pressure without anti-hypertensive therapy and symptom free. CONCLUSION: The case confirmed that tako-tsubo cardiomyopathy could be the first manifestation of tumors secreting catecholamines and that pheocromocytoma should be considered in patients with hypertension and acute stress-induced cardiomiopathy without evidence of acute coronary disease and with negative coronarography.

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.