Robotic-Assisted Management of Ureteral Complications in Post-Renal Transplant Patients: A Case Series and Literature Review.

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019-2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16-70) and BMI of 33.8 (24.3-49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143-500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1-22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6-41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique.

The impact of colonic allograft inclusion on intestinal transplantation outcomes: Results from UNOS/OPTN database analysis.

BACKGROUND: Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. METHODS: We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx. RESULTS: Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p = .002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p <.001 and p = .004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. CONCLUSIONS: In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.

Robotic Assisted Transplant Nephrectomy: Case Series and Training Model for Improving Adoption.

Introduction: Open transplant nephrectomy for failed renal allograft is an invasive procedure associated with significant perioperative morbidity and mortality. Minimally invasive surgical approaches have improved a variety of patient outcomes for many surgeries. Thus, robotic assisted transplant nephrectomy (RATN) potentially offers significant patient benefit. Although previously reported, there remains a paucity of data on RATN outcomes and techniques. Methods: Four perfused, high-fidelity hydrogel models were created using previously described techniques and used for simulated RATN. Subsequently performed institutional cases were included for analysis. Intra- and postoperative variables along with patient demographics were retrospectively obtained through parsing of patient records. Results: Simulated nephrectomy time was 67.33 minutes (35.75 - 98.91). Five patients underwent RATN. There were four male and one female patients. The average age was 47 years. The most common indication was abdominal pain secondary to rejection (3/5). Mean blood loss was 188 mL; mean operative time was 243 minutes, and mean length of stay was 4.5 days. Intraoperatively there were two incidences of small cystotomies. One patient was readmitted within 30 days for intraabdominal abscess. Conclusion: This study adds to the growing literature around RATN, demonstrating the feasibility of the technique and reporting good outcomes for this cohort.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Page phenomenon in a transplanted kidney: is it salvageable?

A male in his late 70s with a history of an uncomplicated kidney transplantation 20 years prior was brought to the Emergency Department after experiencing blunt abdominal trauma following a motor vehicle collision. Imaging revealed a large perinephric haematoma, a retroperitoneal haematoma and multiple fractures. He was admitted to the intensive care unit where a renal haematoma was found to be expanding with ultrasonography (US) and developed renal dysfunction including anuria and hyperkalemia. His creatinine rose to twice his baseline and Doppler US showed elevated resistive indices, confirming extrinsic compression and causing a Page phenomenon. An open surgical exploration through the upper aspect of his Gibson incisional scar was performed followed by evacuation of the haematoma. An intraoperative US was done demonstrating good flow in the renal vessels. His postoperative course was uncomplicated and was discharged home with renal function back to baseline. On follow-up, he continued to have a good renal function.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Inferior Survival Is Associated With Socioeconomic Deprivation in Hepatocellular Carcinoma.

INTRODUCTION: Pernicious health disparities have been reported in patients with hepatocellular carcinoma (HCC). Few tools exist to screen patients in order to facilitate educational and outreach initiatives. We hypothesize that neighborhood-level socioeconomic metrics such as the Area Deprivation Index (ADI) can predict inferior outcomes in patients with early-stage HCC. METHODS: A single institution's retrospective review of patients with Surveillance, Epidemiology, and End Results Stage I HCC between 2000 and 2020 was conducted. Univariate and multivariate models were constructed to identify clinical and socioeconomic variables correlated with treatment-specific survival. Kaplan-Meier analysis was performed to compare survival differences between cohorts. RESULTS: A total of 558 patients were included in this study with newly diagnosed Surveillance, Epidemiology, and End Results Stage I HCC. Multivariate models demonstrated native model of end-stage liver disease, largest tumor size, insurance type, the distance to our transplant center, and the ADI score, a validated metric for a patient's socioeconomic status, are independent risk factors for worse overall survival (all P-values < 0.05). Concerningly, despite similar maximal tumor size, number of tumors, and native model of end-stage liver disease scores, patients from high ADI neighborhoods are 20% less likely to receive surgical treatment, especially liver transplantation. CONCLUSIONS: The ADI is a useful tool for identifying patients at the time of presentation who are at risk for inferior treatment for early stage HCC, and the ADI should be incorporated as a social vital sign.

A chronological review of 500 minimally invasive liver resections in a North American institution: overcoming stagnation and toward consolidation.

BACKGROUND: Although interest in expanding the application of minimally invasive liver resection (MILR) is high the world over, most of the extensive experience in MILR has been reported from Far East Asia and Europe and its adoption in North America is limited. The aim of this study was to review the experience of MILR in a single North American institute over a 15-year period, highlighting both the obstacles encountered and strategies adopted to overcome the stagnation in its uptake. METHODS: This study included 500 MILR cases between 2006 and 2020. Patient demographics, disease characteristics, surgical technique, and perioperative outcomes are summarized. The major hepatectomy rate and conversion rate were assessed according to case numbers (first 100, 101-300, and 301-500 cases) to assess chronological trends. RESULTS: Of 500, 402 MILRs were done by pure laparoscopic (80.4%), 67 were hand assisted (13.4%), and 31 were robotic (6.2%). The majority (64%) of cases were performed for malignancy (n = 320; 100 Hepatocellular carcinoma, 153 Colorectal metastases, 27 Intrahepatic cholangiocarcinoma, and others, 40, 64%). A total of 71 cases were converted to open (14.2%). The annual case number gradually increased over the first few years; however, case numbers stayed around 30 between 2009 and 2017. In this period, despite accumulating MILR experience, open conversion rates increased despite no change in major hepatectomy rate. After this period of long-term stagnation, we introduced crucial changes in team composition and laparoscopic instrumentation. Our MILR case number and major hepatectomy rate thereafter increased significantly without increasing conversion or complication rates. CONCLUSION: Our recovery from long-term stagnation by instituting key changes as detailed in this study could be used as a guidepost for programs that are contemplating transitioning their MILR program from minor to advanced resections. Establishing a formal MILR training model through proper mentorship/proctorship and building a dedicated MILR team would be imperative to this strategy.

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

Induction Therapy With Antithymocyte Globulin and Delayed Calcineurin Inhibitor Initiation for Renal Protection in Liver Transplantation: A Multicenter Randomized Controlled Phase II-B Trial.

BACKGROUND: Calcineurin inhibitor (CNI)-based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit antithymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. METHODS: This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (d 10) against upfront CNI commencement (standard of care [SOC]) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary endpoint was change in (delta) creatinine from baseline to month 12. RESULTS: Fifty-five patients were enrolled in each study arm. Mean tacrolimus levels remained comparable in both groups from day 10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9 mo (P = 0.03) but not at month 12 (P = 0.05). Estimated glomerular filtration rate levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1 y were similar between groups (16.3 versus 12.7%, P = 0.58). rATG showed no significant adverse effects. Survival at 12 mo was comparable between groups (P = 0.48). CONCLUSIONS: Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 y, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 d or lower target tacrolimus levels, with acceptable safety and treatment efficacy.

The Prognostic Utility of Intraoperative Allograft Vascular Inflow Measurements in Donation After Circulatory Death Liver Transplantation.

Donation after circulatory death (DCD) liver transplantation improves deceased donor liver use and decreases waitlist burden, albeit at an increased risk of biliary complications and inferior graft survival. Employing liver vascular inflow measurements intraoperatively permits allograft prognostication. However, its use in DCD liver transplantation is hitherto largely unknown and further explored here. DCD liver transplantation patient records at a single center from 2005 to 2018 were retrospectively scrutinized. Intraoperative flow data and relevant donor parameters were analyzed against endpoints of biliary events and graft survival. A total of 138 cases were chosen. The incidence of cumulative biliary complications was 38%, the majority of which were anastomotic strictures and managed successfully by endoscopic means. The ischemic cholangiopathy rate was 6%. At median thresholds of a portal vein (PV) flow rate of <92 mL/minute/100 g and buffer capacity (BC) of >0.04, both variables were independently associated with risk of biliary events (P = 0.01 and 0.04, respectively). Graft survival was 90% at 12 months and 75% at 5 years. Cox regression analysis revealed a PV flow rate of <50 mL/minute/100 g as predictive of poorer graft survival (P = 0.01). Furthermore, 126 of these DCD livers were analyzed against a propensity-matched group of 378 contemporaneous donation after brain death liver allografts (1:3), revealing significantly higher rates (P < 0.001) of both early allograft dysfunction (70% versus 30%) and biliary complications (37% versus 20%) in the former group. Although flow data were comparable between both sets, PV flow and BC were predictive of biliary events only in the DCD cohort. Intraoperative inflow measurements therefore provide valuable prognostication on biliary/graft outcomes in DCD liver transplantation, can help inform graft surveillance, and its routine use is recommended.

Conditional probability of graft survival in liver transplantation using donation after circulatory death grafts - a retrospective study.

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1-, and 3-year conditional HR of 1-year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long-term biliary complications.

Should We Be Utilizing More Liver Grafts From Pediatric Donation After Circulatory Death Donors? A National Analysis of the SRTR from 2002 to 2017.

BACKGROUND: Rates of withdrawal of life-sustaining treatment are higher among critically ill pediatric patients compared to adults. Therefore, livers from pediatric donation after circulatory death (pDCD) could improve graft organ shortage and waiting time for listed patients. As knowledge on the utilization of pDCD is limited, this study used US national registry data (2002-2017) to estimate the prognostic impact of pDCD in both adult and pediatric liver transplant (LT). METHODS: In adult LT, the short-term (1-year) and long-term (overall) graft survival (GS) between pDCD and adult donation after circulatory death (aDCD) grafts was compared. In pediatric LT, the short- and long-term prognostic outcomes of pDCD were compared with other type of grafts (brain dead, split, and living donor). RESULTS: Of 80 843 LTs in the study, 8967 (11.1%) were from pediatric donors. Among these, only 443 were pDCD, which were utilized mainly in adult recipients (91.9%). In adult recipients, short- and long-term GS did not differ significantly between pDCD and aDCD grafts (hazard ratio = 0.82 in short term and 0.73 in long term, both P > 0.05, respectively). Even "very young" (≤12 y) pDCD grafts had similar GS to aDCD grafts, although the rate of graft loss from vascular complications was higher in the former (14.0% versus 3.6%, P < 0.01). In pediatric recipients, pDCD grafts showed similar GS with other graft types whereas waiting time for DCD livers was significantly shorter (36.5 d versus 53.0 d, P < 0.01). CONCLUSIONS: Given the comparable survival seen to aDCDs, this data show that there is still much scope to improve the utilization of pDCD liver grafts.

Translating Biomarkers of Cholangiocarcinoma for Theranosis: A Systematic Review.

Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996-2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis.

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma.

PURPOSE: The current treatment outcomes in cholangiocarcinoma are poor with cure afforded only by surgical extirpation. The efficacy of targeting the tumoural endothelial marker CD105 in cholangiocarcinoma, as a basis for potential microbubble-based treatment, is unknown and was explored here. METHODS: Tissue expression of CD105 was quantified using immunohistochemistry in 54 perihilar cholangiocarcinoma samples from patients who underwent resection in a single centre over a ten-year period, and analysed against clinicopathological data. In vitro flow assays using microbubbles functionalised with CD105 antibody were conducted to ascertain specificity of binding to murine SVR endothelial cells. Finally, CD105-microbubbles were intravenously administered to 10 Balb/c nude mice bearing heterotopic subcutaneous human extrahepatic cholangiocarcinoma (TFK-1 and EGI-1) xenografts after which in vivo binding was assessed following contrast-enhanced destruction replenishment ultrasound application. RESULTS: Though not significantly associated with any examined clinicopathological variable, we found that higher CD105 expression was independently associated with poorer patient survival (median 12 vs 31 months; p = 0.002). In vitro studies revealed significant binding of CD105-microbubbles to SVR endothelial cells in comparison to isotype control (p = 0.01), as well as in vivo to TFK-1 (p = 0.02) and EGI-1 (p = 0.04) mouse xenograft vasculature. CONCLUSION: Our results indicate that CD105 is a biomarker eminently suitable for cholangiocarcinoma targeting using functionalised microbubbles.

Incidence of anastomotic stricture after Ivor-Lewis oesophagectomy using a circular stapling device.

BACKGROUND: Benign oesophageal strictures carry a significant level of morbidity, causing burdensome symptoms impacting on quality of life. Post-oesophagectomy anastomotic stricture rates as high as 41% have been reported in the literature. These can require endoscopic dilatation, often multiple times to relieve dysphagia. The aim of the present study was to determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures, and to identify any independent risk factors in their development. AIM: To determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures, and to identify any independent risk factors in their development. METHODS: We performed a retrospective analysis of a prospectively collected database of Ivor-Lewis oesophagectomy performed from 2004-2018 to determine the stricture rate. The database comprised a single-surgeon series of open, two-stage oesophagectomies with a circular stapled intra-thoracic anastomosis. Tumour location, histology, neoadjuvant chemotherapy, stapler size, T-stage and R-status were analysed to see if they could predict stricture formation. Stricture was defined as dysphagia requiring endoscopic dilatation. Patients with anastomotic leaks were excluded on the basis they would develop an anastomotic stricture. RESULTS: One hundred and seventy patients were collected in the database. Nineteen were excluded on the basis of anastomotic leak, perioperative death and early recurrence. One hundred and fifty-four patients (119 males, 35 females) with a mean age of 64 ± 10 years were eligible for analysis. A total of 15 patients developed strictures a median of 99 d (interquartile range: 84-133) after surgery, giving a Kaplan-Meier estimated stricture rate of 10% at one year. None of the factors considered were found to be significantly associated with strictures. CONCLUSION: In this study the stricture rate was 10%, with the majority occurring in the first 100 d after surgery. No significant independent factors were found in the development of strictures.