Representation of Women Authorship in the Top 5 Transplantation Journals in the United States.

BACKGROUND: In the United States, only 13% of transplant surgeons are women. We evaluated gender distribution and trends of American authorship over the past 10 y in high-impact solid organ transplantation journals to gain insight into the current status of women authorship in transplantation. METHODS: Original articles from 2012 to 2021 from the 5 highest-impact solid organ transplantation journals were extracted from Scopus. First and last author's gender was predicted using Genderize.io. Data of first and last authors, article type and topic, location, citation, and funding metrics were analyzed. Chi-square, logistic regression, and trend tests were performed where appropriate. Statistical significance was set at <0.05. RESULTS: Women's first and last authorship increased over time among all journals. There was an increase in women first authors in the American Journal of Transplantation and in senior women authors in Liver Transplantation and Transplantation . Significant differences in gender authorship in lung, intestine, pancreas, general, and islet cell transplantation were found. Women's last authorship was associated with 1.69 higher odds of having a woman first author when adjusting for year and journal. There was an increase in the rate of women's first and last author collaborations over the years. Women last authors had 1.5 higher odds of being funded by the National Institutes of Health over the years. CONCLUSIONS: Despite an increase in women transplant surgeons and physicians, the gap in women authorship in transplantation persists. Women's last authorship was associated with higher odds of having a woman first author, pointing to the importance of mentorship for women joining the transplant academia.

The power of partnership: Exploring collaboration dynamics in U.S. transplant research.

INTRODUCTION: Collaboration is one of the hallmarks of academic research. This study analyzes collaboration patterns in U.S. transplant research, examining publication trends, productive institutions, co-authorship networks, and citation patterns in high-impact transplant journals. METHODS: 4,265 articles published between 2012 and 2021 were analyzed using scientometric tools, logistic regression, VantagePoint software, and Gephi software for network visualization. RESULTS: 16,003 authors from 1,011 institutions and 59 countries were identified, with Harvard, Johns Hopkins, and University of Pennsylvania contributing the most papers. Odds of international collaboration significantly increased over time (OR 1.03; p â€‹= â€‹0.040), while odds of citation in single-institution collaborations decreased (OR 0.99; p â€‹= â€‹0.016). Five major scientific communities and central institutions (Harvard University and University of Pittsburgh) connecting them were identified, revealing interconnected research clusters. CONCLUSIONS: Collaboration enhances knowledge exchange and research productivity, with an increasing trend of institutional and international collaboration in U.S. transplant research. Understanding this community is essential for promoting research impact and forming strategic partnerships.

Regional and National Trends of Adult Living Donor Liver Transplantation in the United States Over the Last Two Decades.

Background and Aims: Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival. Methods: We retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed. Results: Of the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n=919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004-2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75-0.88). Conclusions: Following a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.

Conversion to resection post radioembolization in patients with HCC: recommendations from a multidisciplinary working group.

BACKGROUND: Transarterial radioembolization (TARE) with yttrium-90 (90Y) glass microspheres is an efficacious option for converting appropriately selected patients with borderline-resectable hepatocellular carcinoma (HCC) to surgical candidacy. METHODS: In 2018 and 2019, a diverse multidisciplinary group of surgical and interventional experts with experience using 90Y for downstaging and bridging to liver transplant convened to review peer-reviewed literature and personal experience in the use of 90Y to convert borderline resectable liver cancer patients to surgical candidacy. The working group included surgical oncologists specializing in liver cancer, liver transplant surgeons with experience in complex hepatobiliary surgery, and interventional radiologists with experience using 90Y. RESULTS: This document presents expert recommendations based upon the group's experience and consensus. CONCLUSIONS: By combining related evidence from the literature with expert experiences with TARE in surgical candidates, these recommendations aim to demonstrate the safety, efficacy, and feasibility of TARE in converting borderline-resectable patients to surgical options. The document also addresses the concerns about potential complications associated with TARE during the surgical intervention.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Massive Leiomyomatous Uterine Proliferation Following Kidney Transplantation: A Case Report and Literature Review.

Uterine fibroids are the most common benign uterine tumors affecting > 50% of premenopausal women. The incidence, burden and symptoms from uterine fibroids are higher in women of African descent compared to Caucasians. Despite increasing number of African American females being evaluated for and undergoing kidney transplantation (KT), perioperative management guidelines for uterine fibroids currently do not exist. We present a case of a 40 y/o African American female with known symptomatic uterine fibroids preoperatively and medically managed, who underwent a successful KT and 4 years later progressively developed massive leiomyomatous uterine proliferation, causing a complete lateral displacement of the transplanted kidney with severe hydronephrosis, transplant ureteral obstruction and secondary urinary tract infections with bacteremia. This obstruction required a percutaneous nephrostomy tube placement followed by an interval transabdominal hysterectomy, which was complicated by transplant ureteral transection requiring ureteral reimplantation, resulting in prolonged hospitalization, follow-up and outpatient antibiotic regimen. There is a need for management guidelines for uterine fibroids incidentally encountered during the KT evaluation process to avoid similar preventable post-KT complications in patient populations most commonly affected. Literature review and perioperative management/surveillance strategies are provided.

Deep Vein Thrombosis and Pulmonary Embolism in Liver Transplant Patients: Risks and Prevention.

UNLABELLED: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications estimated to occur in 5% to 10% of patients. There are limited data regarding DVT/PE in the early postoperative period in liver transplant patients. The aim of this study is to determine risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis. METHODS: We reviewed the records of 999 patients who underwent initial liver transplant between January 2000 and June 2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using subcutaneous (SQ) heparin was initiated. All patients that developed either upper/lower extremity DVT or PE within the first 30 days of transplant formed the cohort of this study. RESULTS: On multivariate analysis, only peripherally inserted central catheter (PICC) placement and SQ heparin were associated with DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in those with a PICC and did not receive heparin (P = 0.03). Mean time from transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P < 0.001). CONCLUSIONS: In this study, we demonstrated that PICC placement significantly increases the likelihood of DVT/PE in liver transplant recipients. Prophylactic SQ heparin effectively reduced DVT/PE events in this patient population.

Intrahepatic Cholangiocarcinoma in the Liver Explant After Liver Transplantation: Histological Differentiation and Prognosis.

BACKGROUND: The aim of this study was to evaluate the outcome of patients with intrahepatic cholangiocarcinoma (ICCA) incidentally found in the explanted liver after liver transplantation. MATERIAL AND METHODS: We retrospectively reviewed 1188 recipients undergoing liver transplantation from August 2003 to August 2014; 13 patients were found to have ICCA (1.1%). Recurrence-free survival (RFS) rate was compared between ICCA patients and the matched cohort of 39 patients with hepatocellular carcinoma (HCC). We also investigate the relevance of clinical and pathological parameters in recurrence of ICCA. RESULTS: ICCA patients showed significantly higher recurrence rate with lower 1-year and 3-year RFS rates than HCC patients (recurrence rate, 12.8% vs. 54.8%; 1-year and 3-year RFS rates, 94% and 84% vs. 67% and 42%). Of the 13 ICCA patients, 4 were diagnosed with a well-differentiated ICCA and 9 with a moderately-differentiated ICCA. There was no recurrence among those with a well-differentiated ICCA, whereas 78% recurred in the moderately-differentiated group. The median RFS time for the moderately-differentiated group was 13.0 months, yielding RFS rates of 56% at 1 year and 22% at 3 years. CONCLUSIONS: Liver transplantation in patients with a well-differentiated ICCA yielded excellent outcomes as compared to patients with a moderately-differentiated ICCA. This may allow consideration of transplantation in the setting of a well-differentiated ICCA, and obviate the need for adjuvant systemic treatment. Conversely, a moderately-differentiated ICCA carries a poor prognosis with a prohibitively high recurrence rate and poor survival. Liver transplantation should remain a contraindication in this group.

Peritransplant lymphopenia is a novel prognostic factor in recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC. RESULTS: HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/µL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/µL before LT and <500/µL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics. CONCLUSION: Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.

Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. METHODS: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. RESULTS: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. CONCLUSIONS: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.

Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy.

Minimally invasive procedures are considered to be safe and effective approaches to the management of surgical liver disease. However, this indication remains controversial for living donor hepatectomy. Between 2000 and 2011, living donor right hepatectomy (LDRH) was performed 58 times. Standard right hepatectomy was performed in 30 patients via a subcostal incision with a midline extension. Minimally invasive procedures began to be used for LDRH in 2008. A hybrid technique (hand-assisted laparoscopic liver mobilization and minilaparotomy for parenchymal dissection) was developed and used in 19 patients. In 2010, an upper midline incision (10 cm) without laparoscopic assistance for LDRH was innovated, and this technique was used in 9 patients. The perioperative factors were compared, and the indications for minimally invasive LDRH were investigated. The operative blood loss was significantly less for the patients undergoing a minimally invasive procedure versus the patients undergoing the standard procedure (212 versus 316 mL, P = 0.001), and the operative times were comparable. The length of the hospital stay was significantly shorter for the minimally invasive technique group (5.9 versus 7.8 days, P < 0.001). The complication rates were 23% and 25% for the standard technique and minimally invasive technique groups, respectively (P = 0.88). Patients undergoing minilaparotomy LDRH had a body mass index (24.0 kg/m(2)) similar to that of the hybrid technique patients (25.8 kg/m(2), P = 0.36), but the graft size was smaller (780 versus 948 mL, P = 0.22). In conclusion, minimally invasive LDRH can be performed without safety being impaired. LDRH with a 10-cm upper midline incision and without laparoscopic assistance may be appropriate for donors with a smaller body mass. Laparoscopic assistance can be added as needed for larger donors. This type of LDRH with a 10-cm incision is innovative and is recommended for experienced centers.

Transjugular intrahepatic portosystemic shunt following liver transplantation: can outcomes be predicted?

Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re-transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS.

No difference in clinical transplant outcomes for local and imported liver allografts.

In the United States, liver allograft allocation is strictly regulated. Local centers have the first option to accept a donor liver; this is followed by regional allocation for those donor livers not used locally and then by national allocation for those donor livers not accepted regionally. This study reviews the outcomes of all liver allografts used over 6 years (2001-2007) and evaluates initial and long-term function stratified by the geographic source of the donor liver allograft. The records for 845 consecutive deceased donor liver transplants at a single center were reviewed. The geographic origin of the allograft was recorded along with donor and graft characteristics to determine the probable reason for graft refusal. Within our local organ procurement organization, there is 1 liver transplant center, and within the region, there are 8 active centers. Early graft failure included any graft loss within 7 days of transplant, and initial function was measured with liver enzymes 30 days post-transplant. Graft survival and patient survival were evaluated with Kaplan-Meier and Cox survival modeling. Median follow-up was 43 months. The geographic distribution of organs included local organs (562, 66%), regionally imported organs (126, 15%), and nationally imported organs (157, 19%). There were no differences between the 3 groups in initial graft function, intraoperative death, or early graft loss. Survival curves for the 3 study groups demonstrated no difference in survival up to 5 years post-transplant. In conclusion, liver allografts rejected for use by a large number of transplant centers can still be successfully used without early graft function or long-term survival being affected.

A new vascular approach to the modified multivisceral graft procurement.

Modified multivisceral (MMV) transplantation including the stomach, pancreaticoduodenal complex and intestine requires preservation of the left gastric and splenic arteries. The previously described techniques require division of the hepatic artery proximal to the gastroduodenal artery leaving the liver transplant team with a very short and small caliber vessel. To increase MMV graft availability and provide the liver transplant team with an appropriate quality vessel, we developed the following technique. We also describe two cases where we used this method to support the technical feasibility of this procedure.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in intestinal and multivisceral transplantation.

BACKGROUND: Previous studies have failed to demonstrate a clinical difference between histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in clinical transplant outcomes for liver, pancreas, and kidney transplantation. This study compares HTK and UW in bowel transplantation with primary outcomes being graft and patient survival, early graft function, and episodes of rejection. METHODS: Data were extracted using a retrospective chart and medical record review of all bowel transplants between 2003 and 2007, and included both pediatric and adult grafts. Transplanted organs included isolated small bowel, modified multivisceral (bowel, pancreas, and stomach) and multivisceral (bowel, pancreas, stomach, and liver). Immunosuppression included induction with a steroid taper and antithymocyte globulin and anti-CD20 monoclonal antibody (rituximab), followed by maintenance with prograf monotherapy. Bowel surveillance was performed with twice weekly zoom endoscopy and biopsy. RESULTS: There were 54 patients transplanted with 57 grafts, 22 preserved in UW, and 37 in HTK. No differences were noted between the two solutions in initial graft function, appearance of bowel on initial endoscopy, and number of rejection episodes. There were no episodes of pancreatitis in the 44 multivisceral grafts which included a transplant pancreas (14 UW and 30 HTK). Kaplan-Meier survival analysis did not demonstrate a significant difference in graft or patient survival at 30- or 90-days posttransplant. CONCLUSIONS: Intestinal grafts preserved in UW and HTK demonstrate no difference in graft and patient survival at 30- and 90-days posttransplant. There were no differences noted in initial function, endoscopic appearance, rejection episodes, or transplant pancreatitis.

Addition of a total pancreatectomy and pancreas transplantation in a liver transplant recipient with intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are increasingly recognized in clinical practice. There are no published data suggesting a management approach for the potential organ transplant recipient with the incidental finding of this pre-malignant lesion. METHODS: The recipient was a 65-yr-old man with hepatocellular carcinoma in a background of Laennec's cirrhosis. During evaluation for transplant, he was found to have diffuse IPMN. This patient underwent liver transplantation with a planned simultaneous total native pancreatectomy and pancreas transplant from the same donor. RESULTS: The patient has had normal liver function and has been free of diabetes and exocrine insufficiency at 18 months post-transplant. CONCLUSION: IPMN in the potential transplant recipient should be managed more aggressively than in the general population because these patients will be committed to life-long immunosuppression. If a total pancreatectomy is contemplated, this is a unique opportunity to replace the pancreas with an allograft at the time of transplantation.

Initiation of an intestinal transplant program: the Indiana experience.

INTRODUCTION: Establishment of a new intestinal transplant (Itx) program in the United States entails significant programmatic costs and a steep learning curve. We report results of the first 4 years of the program at Indiana University. METHODS: Forty-six intestinal and multivisceral transplants (MVtx) were performed between 2003 and 2007. All organ procurements were performed by our team. Immunosuppression included an induction protocol combined with maintenance tacrolimus monotherapy. Scheduled rejection surveillance was with magnification endoscopy. RESULTS: Forty-three patients (13 children and 30 adults) received 10 Itx (22%), 5 modified MVtxs (11%), and 31 (MVtx, 67%). Recipient ages ranged from 3 months to 66 years, with median follow-up time of 15 months. Thirty-five patients are currently alive (81%). Patient and graft survival at 30 days was 85%/86% in pediatric and 93%/91% in adult; overall survival was 69%/64% in pediatric and 87%/75% in adult. Thirty patients (69%) experienced episodes of rejection. Multivisceral transplanted patients experienced less episodes of severe rejection (2/31, 6%) when compared with patients with isolated Itx and modified MVtxs. Retransplantation was performed in three patients with nonresponsive severe acute rejection. CONCLUSION: The Indiana University Intestinal and Multivisceral Transplant program experienced significant early graft loss and mortality among pediatric patients, but not among adults. This discrepancy resolved within 2 years of program initiation. After 4 years, adult and pediatric graft and patient survival statistics are similar to those at other programs.