Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

Evolving Trends in the Management of Duodenal Leaks After Pancreas Transplantation: A Single-Centre Experience.

Duodenal leaks (DL) contribute to most graft losses following pancreas transplantation. However, there is a paucity of literature comparing graft preservation approach versus upfront graft pancreatectomy in these patients. We reviewed all pancreas transplants performed in our institution between 2000 and 2020 and identified the recipients developing DL to compare based on their management: percutaneous drainage vs. operative graft preservation vs. upfront pancreatectomy. Of the 595 patients undergoing pancreas transplantation, 74 (12.4%) developed a duodenal leak with a median follow up of 108 months. Forty-five (61%) were managed by graft preservation strategies, with the rest being treated with upfront graft pancreatectomy. DL managed by graft preservation strategies had similar graft survival rates at 1 and 5-year compared to the matched cohort of population without DL (95% and 59% vs. 91% and 62%; p = 0.78). Multivariate analysis identified male recipient (OR: OR: 6.18; CI95%: 1.26-41.09; p = 0.04) to have higher odds of undergoing an upfront graft pancreatectomy. In appropriately selected recipients with DL, graft preservation strategies utilizing either interventional radiology guided percutaneous drainage or laparotomy with/without repair of leak can achieve comparable long-term graft survival rates compared to recipients without DL.

Medical Assistance in Dying (MAiD) as a Source of Liver Grafts: Honouring the Ultimate Gift.

OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.

Normothermic Ex Vivo Machine Perfusion of Discarded Human Pancreas Allografts: A Feasibility Study.

Pancreas transplantation is the only curative treatment for patients with complicated diabetes, and organ shortage is a common and increasing problem. Strategies to expand the donor pool are needed, and normothermic ex vivo perfusion of the pancreas has the potential to test and repair grafts before implantation. Between January 2021 and April 2022, six human pancreases, declined for transplantation or islet isolation, were perfused using a previously established method by our group. All 6 cases were successfully perfused for 4 h, with minimal edema. The mean age of the donors was 44.16 ± 13.8 years. Five grafts were obtained from neurological death donors, and one was obtained from a donation after cardiac death. The mean glucose and lactate levels decreased throughout perfusion and insulin levels increased. All 6 grafts were metabolically active during perfusion and histopathology showed minimal tissue injury and no edema. Human normothermic ex vivo perfusion of the pancreas is feasible and safe and has the potential to expand the donor pool. Future studies will focus on tests and biomarkers for the assessment of grafts.

Should advanced donor age be a deterrent in the utilization of grafts from donation after cardiac death in deceased donor liver transplantation? The Toronto experience.

BACKGROUND: Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. METHODS: Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. RESULTS: Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. CONCLUSION: Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.

A Comparison Between the Comprehensive Complication Index and the Clavien-Dindo Grading as a Measure of Postoperative Outcome in Patients Undergoing Gastrointestinal Surgery-A Prospective Study.

BACKGROUND: The Clavien-Dindo (CD) grading system reports the most severe of all the postoperative complications. The comprehensive complication index (CCI) sums up all the complications in postoperative period. We compared the CCI and CD to assess which of the two was a better measure of postoperative outcomes. MATERIALS AND METHODS: Between June 2015 and December 2016, we recorded the complications using CD grading and CCI in 1000 consecutive patients in our gastrointestinal and hepatopancreaticobiliary surgery unit. The outcome variables studied were postoperative length of hospital stay (LOS), postoperative intensive care unit (ICU) stay, and time to normal activity. The results were expressed as strength of correlation and predictive accuracy of the outcome variables. RESULTS: There were 600 males and 400 female patients, with a mean age of 50.3 y. A total of 788 (78.8%) elective and 212(21.2%) emergency procedures were performed. The overall 90-day/in-hospital mortality was 7.9%. Both CD and CCI showed a good correlation with LOS (r = 0.58; P = 0.001, r = 0.57; P = 0.001), ICU stay (r = 0.62; P = 0.002, r = 0.62; P = 0.001), and time to normal activity (r = 0.48; P = 0.01; r = 0.49; P = 0.01). The accuracy of CCI to predict the LOS (area under the curve [AUC] = 0.89; P < 0.001), ICU stay (AUC = 0.85; P < 0.001), and time to normal activity (AUC = 0.76; P < 0.001) was comparable to that of CD (AUC = 0.90; P < 0.001, AUC = 0.87; P < 0.001, AUC = 0.77; P < 0.001). CONCLUSIONS: Both CD and CCI were equally accurate in measuring the postoperative outcomes and in their ability to predict the same in patients undergoing gastrointestinal and hepatopancreaticobiliary surgeries. Considering the relative ease of determination of CD, it remains a more commonly used measure for assessing the severity of complications and outcomes compared to CCI.

Reanimating Pancreatic Grafts Subjected to Prolonged Cold Ischemic Injury Using Normothermic Ex Vivo Perfusion.

Background: Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model. Methods: The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients. Control grafts were subjected to cold storage (CS) in a University of Wisconsin solution for 21 to 24 h (n = 6), whereas the test group received an additional 3 h NEVP after CS of 21 h (n = 5). Results: The 3-d survival was 60% in the NEVP arm versus 0% in the control arm (P = 0.008; log rank). Graft parenchyma was 60% to 70% preserved in the NEVP arm at necropsy on gross appearance. In addition, the islet function was well preserved, and both the pancreas (including the islets) and the duodenal morphology were maintained histologically. The intravenous glucose tolerance test on the day of euthanasia was in the normoglycemic range for 80% of cases in the NEVP arm. Conclusions: Optimization of pancreas grafts exposed to extended CS with NEVP seems promising at rescuing and reanimating these grafts for transplantation, resulting in significantly improved survival in a porcine pancreas transplant model.

Disease-free survival after pancreatectomy for pancreatic neuroendocrine tumors: A 17-year single-center experience of 223 patients.

BACKGROUND: Metastasis or recurrence of pancreatic neuroendocrine tumors (pNETs) after pancreatectomy is an important source of postsurgical morbidity. This study aimed to define disease-free survival (DFS) in this population. METHODS: Patients who underwent pancreatectomy for pNETs between January 2005 and January 2022 were included. Clinicopathologic and survival data were collected, and the primary endpoint was DFS. Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were performed. RESULTS: Of the 223 patients, 144 (65%) distal/subtotal/partial pancreatectomies, 71 (32%) pancreaticoduodenectomies, 6 (3%) total pancreatectomies, and 2 (1%) enucleations were performed. Of the 223 patients, 45 (20%) experienced disease recurrence or metastasis after index pancreatectomy during the 17 years of the study. Nonfunctional pNETs (162 [73%]) were more common than hormonally functional subtypes. The 2- and 5-year DFSs were 82% and 76%, respectively. Kaplan-Meier analysis demonstrated that N1 node positive disease, size of ≥ 4 cm, lymphovascular invasion, perineural invasion, Ki-67 of ≥ 20%, and nonfunctional pNETs are significantly associated with a lower DFS (P < .05). Univariate Cox analysis identified the following predictors to be significantly associated with poorer DFS: larger tumor size (hazard ratio [HR], 1.16; 95% CI, 1.04-1.28), Ki-67 index of ≥ 20% (HR, 4.93; 95% CI, 2.00-11.44), perineural invasion (HR, 3.23; 95% CI, 1.40-7.89), open surgery (HR, 3.34; 95% CI, 1.03-1.33), node-positive disease (HR, 5.27; 95% CI, 2.28-13.26), and increased body mass index (HR, 1.10; 95% CI, 1.03-1.17) (P < .05). CONCLUSION: Of note, 1 in 5 patients who underwent resection developed recurrence or metastasis after pancreatectomy. Prognostic predictors of DFS in pNETs could help optimize treatment and enhance follow-up protocols to improve quality and reduce morbidity.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation.

Evaluating the Influences of Health Expenditure, Energy Consumption, and Environmental Pollution on Life Expectancy in Asia.

This study examines the effects of health expenditure, energy consumption, CO2 emissions, population size, and income on health outcomes in 46 Asian nations between 1997 and 2019. Cross-sectional dependence (CSD) and slope heterogeneity (SH) tests are utilized due to the close linkages between Asian nations as a result of commerce, tourism, religion, and international agreements. The research uses unit root and cointegration tests of the second generation after validating CSD and SH issues. Due to the results of the CSD and SH tests, it is clear that conventional methods of estimation are inappropriate, so a new panel method, the inter autoregressive distributive lag (CS-ARDL) model, is used instead. In addition to CS-ARDL, the study's results were checked with a common correlated effects mean group (CCEMG) method and an augmented mean group (AMG) method. According to the CS-ARDL study, higher rates of energy use and healthcare spending lead to better health outcomes for Asian countries over the long run. CO2 emissions are shown to be harmful to human health, according to the study. The influence of a population's size on health outcomes is shown to be negative in the CS-ARDL and CCEMG, but favorable in the AMG. Only the AMG coefficient is significant. In most instances, the results of the AMG and CCEMG corroborate the results of the CS-ARDL. Among all the factors influencing life expectancy in Asian countries, healthcare spending is the most influential. Hence, to improve health outcomes, Asian countries need to take the required actions to boost health spending, energy consumption, and long-term economic growth. To achieve the best possible health outcomes, Asian countries should also reduce their CO2 emissions.

Impact of organizational learning on sustainable firm performance: Intervening effect of organizational networking and innovation.

This research has analyzed the role of learning in an organization while measuring and managing sustainable organizational performance. Furthermore, our research has also included the intervening role of organizational networking and organizational innovation while analyzing the relationship between organizational learning and sustainable organizational performance. Our research has adopted a quantitative approach while using the survey method to collect data from 710 owners of the manufacturing sector belonging to the Small and Medium Enterprises SMEs operating in Laos. Informed consent was obtained from all participants for your research. Structure equation modeling SEM was used through partial least square PLS software to test the collected data's reliability and validity and test the hypothesis to meet the research objectives. The study's findings reveal that organizational learning is vital to organizational performance and success. Information sources (networks) moderate the relationship between innovation and organizational performance. Our findings confirm that innovation is disruptive if it is not well-informed and well-processed. The research concludes that organizational learning is very vital for sustainable organizational performance. The current research contributes to the body of knowledge by examining sustainable organizational performance from an entirely different perspective.

Intubation, Central Venous Catheter, and Arterial Line Placement in Swine for Translational Research in Abdominal Transplantation Surgery.

Translational surgical research models in swine are crucial for developing safe preclinical protocols. However, the success of the experimental surgeries does not solely rely on the research team's surgical skills; perioperative care and management procedures, like intubation, central venous line, and arterial line placement, are necessary and of the utmost importance for favorable experiment results. As it is uncommon for research teams to have anesthesiologists or any other staff other than the surgical team, the surgical team involved in translational research must acquire and/or develop the skills to perform the perioperative care. The purpose of this paper is to show the techniques of intubation, central venous catheter, and arterial line placement used and perfected at the Toronto Organ Preservation Laboratory over the last 10 years, to be used as a reference for future researchers joining either this team or any other lab performing translational research protocols in swine and/or abdominal transplantation.

Outcomes of pancreas transplantation in patients with underlying inflammatory bowel disease: a retrospective case series.

Despite having emerged as a definitive treatment for diabetes mellitus (DM), pancreas transplantation remains a formidable surgical task owing to complications like graft pancreatitis, enteric leaks, and rejection. This becomes more challenging in the setting of underlying bowel pathology, such as inflammatory bowel disease (IBD), which has a strong immune-genomic association of co-existence with DM. Risk of anastomotic leaks, dose adjustments of immunosuppressants and biologicals, and management of IBD flares constitute some of the major perioperative challenges calling for a protocol-based, systematic, multidisciplinary approach. Patients and methods: This was a retrospective case series of patients between January 1996 and July 2021, with all patients being followed up until December 2021. All consecutive patients with end-stage DM who underwent pancreas transplantation (alone, simultaneous with kidney transplantation or after kidney transplantation) and had pre-existing IBD were included in the study. A Comparison of 1-, 5-, 10-year survival was done with pancreas transplant recipients without underlying IBD using Kaplan-Meir curves. Results: Of the total 630 pancreas transplants performed between 1996 and 2021, eight patients had IBD, mostly Crohn's disease. Following pancreas transplantation, two of the eight patients had duodenal leaks, with one a requiring graft pancreatectomy. The 5-year graft survival rate for the cohort was 75% compared to 81.6% for the overall cohort of patients undergoing pancreas transplantation (P=0.48) with a median graft survival of 48.4 months compared to 68.1 months in the latter (P=0.56). Conclusion: The findings of the series provide a snapshot of the outcome of pancreas transplantation in the background of IBD, suggesting a graft and overall patient survival rates comparable with pancreas transplantation in patients without underlying IBD, with further validation of the findings required in a larger cohort of patients in the future.

Pancreas transplantation with grafts obtained from donation after cardiac death or donation after brain death results in comparable outcomes.

Introduction: Pancreas organ shortages and long recipient waitlist times are critical components that limit recipients from receiving a pancreas transplant. Over the last decade, our center has been using donation after cardiac death (DCD) donors as an adjunct to donation after brain death (DBD) donors to expand the organ pool. The aim of this study was to compare recipient and graft survival between DCD and DBD recipients. Methods: A retrospective single center propensity matched analysis (2011-2020) of 32 DCD vs 96 DBD pancreas transplants was performed. Results: 8-year recipient survival was similar between DCD and DBD groups (87.4% vs 92.7%, p=0.35) as was simultaneous kidney and pancreas transplant (SPK) 8-year kidney (88.9 vs 96.9%, p=0.219) and pancreas graft survival (77.4% vs 86.7%, p=0.344). There was no difference in vascular thrombosis rate between DCD and DBD pancreas grafts (3.1% vs 7.3%, p=0.73). DCD kidneys had a higher rate of DGF vs DBD kidneys (28.1% vs 6.3%, p=0.004), without any significant difference in long term kidney failure (12.5% vs 8.3%, p=0.5). Discussion: Recipients of DCD grafts demonstrate equivalent long-term patient and graft survival compared to DBD recipients for pancreas transplantation. Increased utilization of well selected DCD donors is a safe strategy to increase the donor pool.

Normothermic Ex Vivo Pancreas Perfusion for the Preservation of Pancreas Allografts before Transplantation.

Pancreas transplantation (PTx) is a curative treatment for people who live with the burden of a diagnosis of diabetes mellitus (DM). However, due to organ shortages and increasing numbers of patients being listed for PTx, new strategies are needed to increase the number of available grafts for transplantation. Static cold storage (SCS) is considered the gold standard for standard criteria organs. However, standard criteria donors (SCD) are becoming scarce and new strategies that can increase the rate of organ acceptance from extended criteria donors (ECD) are urgently needed. Normothermic ex vivo perfusion (NEVP) is one of the strategies that has become increasingly popular over the past couple of decades. This preservation method has already been used successfully in other organs (liver, kidneys, and lungs) but has been minimally explored in pancreas transplantation. The few papers that describe the method for pancreas show little success, edema being one of the major issues. The following manuscript describes the successful NEVP method and setup developed by our group to perfuse swine pancreas.

Surgical Tips and Tricks for Performing Porcine Pancreas Transplantation.

Despite the promising results of pancreas transplantation in type 1 diabetes mellitus and metabolic syndrome, the biggest concern around this state-of-the-art technique remains the paucity of organs deemed fit for transplantation. High intravascular resistance, delicate intraparenchymal capillary framework, and complex lobular anatomy around the mesenteric vasculature are what make this organ more susceptible to injury and less tolerant to trivial trauma compared to organs such as the liver and kidney. Meticulous surgical dissection and judicious tissue handling form the cornerstone of the entire exercise of pancreas transplantation. Owing to morphological similarity between the anatomy of the porcine pancreas to the surrounding mesenteric vessels and the organs when compared to the human anatomy, demonstration of the technique in the porcine model could help to most accurately extrapolate this to a human setting. The present article aims to outline the essential surgical tips and tricks that need to be followed, in order to ensure a higher success rate of transplantation of this highly susceptible organ in a porcine 3-day survival model.

Ectopic gall bladder: A case report.

Ectopic gall bladder under the left lobe of liver is a rare congenital anomaly of the position of gall bladder, which is mostly detected during surgery and causes technical difficulty at the time of operation. We operated a 64-year-old male who presented with gall stone disease and pre-operative ultrasound did not report any abnormality in position. On laparoscopy, it was found to be attached on the left side of falciform ligament under segment III. It was a true ectopic gall bladder without situs inversus. Early division of the falciform ligament and a careful and complete dissection of the gall bladder are advocated before clipping the cystic artery and duct to avoid complications. The present case report discusses about this rare anomaly and the available literature on the subject.

Spectrum of presentation in primary anorectal malignant melanoma and its management.

The article presents a series of four patients with primary anorectal melanoma presenting to our institute between 2016 and 2021. The primary objective of the series is to give an overview of the variable presentation of this rare entity from a high-volume colorectal tertiary care centre in a developing country. The patients ranged in age from 55 to 73 years and were mostly women (except one). The clinical presentation varied from bleeding per rectum to tenesmus and mucus in stools, overlapping with those of inflammatory bowel disease and primary anorectal adenocarcinoma. All patients were treated with surgery (laparoscopic or open), ranging from local excision to abdominoperineal resection. All our patients had a good outcome after surgery with no mortality at 30 or 90 days after surgery. The article aims to present a comprehensive overview of the various options of management with evidence from the surgical literature.

Single stage repair of anorectal malformation with rectovestibular fistula in adult.

Anorectal malformations are a wide spectrum of disorders, affecting both genders and rare adult presentation as with increased knowledge and advancements, the majority of cases are diagnosed and rectified at birth. This case is a classic example of delayed presentation caused by illiteracy and a lack of adequate health care in rural locations and highlights the uniqueness of this disease, presentation in adult age group and its management and effect on patient psychology and mental health. Because all low anorectal abnormalities can be treated in a single stage, neonatal assessment at birth and early referral to advanced health care centres are critical, with anterior or posterior sagittal anorectoplasty performed by the age of six months. Concerning the anomaly, parent education is an important aspect of patient care.