Daratumumab Use Prior to Kidney Transplant and T Cell-Mediated Rejection: A Case Report.

There is growing interest in daratumumab in the solid organ transplant realm owing to the potential immunomodulatory effects on CD38-expressing cells, primarily plasma cells, as they have a key role in antibody production. In particular there is interest in use of daratumumab for desensitization and potential treatment for antibody-mediated rejection. However, ongoing investigation with daratumumab has shown potential immunologic concerns in vitro, with a significant increase in populations of CD4-positive cytotoxic T cells and CD8-positive helper T cells in both peripheral blood and bone marrow that could lead to acute T cell-mediated rejection in the solid organ transplant patient. To date, there are no published reports of an association with daratumumab use and T cell-mediated rejection in vivo. In this case report we present what is to our knowledge the first documented case of an early severe T cell-mediated rejection in a low-immunologic-risk living-donor kidney transplant recipient who received daratumumab for multiple myeloma maintenance prior to transplant.

Preemptive VAE-An Important Tool for Managing Blood Loss in MVT Candidates With PMT.

Explantation of native viscera in multivisceral transplant candidates, particularly in those with extensive portomesenteric thrombosis (PMT), carries considerable morbidity due to extensive vascularized adhesions. Preemptive visceral angioembolization has been previously described as a technique to minimize excessive blood loss during mobilization of the native viscera but is not well described specifically in patients with extensive PMT. METHODS: In a series of 5 patients who underwent mutivisceral transplant for PMT from June 2015 to November 2018, we performed preoperative superior mesenteric, splenic, and hepatic artery embolization to reduce blood loss during explanation and evaluated the blood loss and blood product utilization, as well as 30-day rates of infectious complications. RESULTS: Following preemptive embolization, median total blood loss was 6000 mL (range 800-7000 mL). The median transfusion requirements were as follows: 16 units packed red blood cells (range 2-47), 14 units fresh frozen plasma (range 0-29), 2 units cryoprecipitate (range 1-14), 4 units platelets (range 2-10), and 500 mL cell saver autotransfusion (range 0-1817). In the first 30 postoperative days, 2 out of 5 patients developed positive blood cultures and 3 out of 5 developed complex intra-abdominal infections. Two patients developed severe graft pancreatitis resulting in mycotic aneurysm of the aortic conduit; bleeding from the aneurysm led to 1 patient mortality. CONCLUSIONS: Preoperative embolization is an effective modality to mitigate exsanguinating blood loss during multivisceral transplant in patients with portomesenteric thrombosis; however, it is unclear if the resultant native organ ischemia during explant carries clinically relevant consequences.

Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor.

BACKGROUND: Donor-derived malignancy is a rare complication in patients who undergo organ transplant. Approaches to treatment have largely been individualized based on clinical circumstances given the lack of evidence-based guidelines, with therapeutic options ranging from discontinuation of immunosuppression and transplantectomy to the addition of chemotherapy or radiotherapy. Case Presentation. Herein, we describe a 60-year-old woman with metastatic donor-derived upper tract urothelial carcinoma (UTUC) discovered nine years postrenal transplant. Molecular diagnostic studies using polymerase chain reaction amplification of short tandem repeat alleles and HLA tissue typing proved that the urothelial carcinoma originated from donor tissue. She achieved sustained complete remission with transplant nephroureterectomy, retroperitoneal lymphadenectomy, immunosuppression withdrawal, and immunotherapy with pembrolizumab. Routine radiologic surveillance has demonstrated 15-month progression-free survival to date off pembrolizumab, and she is now under consideration for retransplantation. CONCLUSIONS: Immunotherapy using checkpoint inhibitors can serve as a novel treatment option for patients in the clinical predicament of having a solid organ transplant and simultaneous metastatic malignancy. In this report, we also discuss the oncogenic potential of BK virus, the use of checkpoint inhibitors in urothelial carcinoma, and the feasibility of retransplant for this patient population.

Correlation of preoperative imaging characteristics with donor outcomes and operative difficulty in laparoscopic donor nephrectomy.

This study aimed to understand the relationship of preoperative measurements and risk factors on operative time and outcomes of laparoscopic donor nephrectomy. Two hundred forty-two kidney donors between 2010 and 2017 were identified. Patients' demographic, anthropomorphic, and operative characteristics were abstracted from the electronic medical record. Glomerular filtration rates (GFR) were documented before surgery, within 24 hours, 6, 12, and 24 months after surgery. Standard radiological measures and kidney volumes, and subcutaneous and perinephric fat thicknesses were assessed by three radiologists. Data were analyzed using standard statistical measures. There was significant correlation between cranio-caudal and latero-lateral diameters (P < .0001) and kidney volume. The left kidney was transplanted in 92.6% of cases and the larger kidney in 69.2%. Kidney choice (smaller vs. larger) had no statistically significant impact on the rate of change of donor kidney function over time adjusting for age, sex and race (P = .61). Perinephric fat thickness (+4.08 minutes) and surgery after 2011 were significantly correlated with operative time (P ≤ .01). In conclusion, cranio-caudal diameters can be used as a surrogate measure for volume in the majority of donors. Size may not be a decisive factor for long-term donor kidney function. Perinephric fat around the donor kidney should be reported to facilitate operative planning.

The Volume-outcome Relationship in Deceased Donor Kidney Transplantation and Implications for Regionalization.

OBJECTIVE: The aim of this study was to investigate the volume-outcome relationship in kidney transplantation by examining graft and patient outcomes using standardized risk adjustment (observed-to-expected outcomes). A secondary objective was to examine the geographic proximity of low, medium, and high-volume kidney transplant centers in the United States. SUMMARY OF BACKGROUND DATA: The significant survival benefit of kidney transplantation in the context of a severe shortage of donor organs mandates strategies to optimize outcomes. Unlike for other solid organ transplants, the relationship between surgical volume and kidney transplant outcomes has not been clearly established. METHODS: The Scientific Registry of Transplant Recipients was used to examine national outcomes for adults undergoing deceased donor kidney transplantation from January 1, 1999 to December 31, 2013 (15-year study period). Observed-to-expected rates of graft loss and patient death were compared for low, medium, and high-volume centers. The geographic proximity of low-volume centers to higher volume centers was determined to assess the impact of regionalization on patient travel burden. RESULTS: A total of 206,179 procedures were analyzed. Compared with low-volume centers, high-volume centers had significantly lower observed-to-expected rates of 1-month graft loss (0.93 vs 1.18, P<0.001), 1-year graft loss (0.97 vs 1.12, P<0.001), 1-month patient death (0.90 vs 1.29, P=0.005), and 1-year patient death (0.95 vs 1.15, P=0.001). Low-volume centers were frequently in close proximity to higher volume centers, with a median distance of 7 miles (interquartile range: 2 to 75). CONCLUSIONS: A robust volume-outcome relationship was observed for deceased donor kidney transplantation, and low-volume centers are frequently in close proximity to higher volume centers. Increased regionalization could improve outcomes, but should be considered carefully in light of the potential negative impact on transplant volume and access to care.

Trends in Usage and Outcomes for Expanded Criteria Donor Kidney Transplantation in the United States Characterized by Kidney Donor Profile Index.

There has been increasing concern in the kidney transplant community about the declining use of expanded criteria donors (ECD) despite improvement in survival and quality of life. The recent introduction of the Kidney Donor Profile Index (KDPI), which provides a more granular characterization of donor quality, was expected to increase utilization of marginal kidneys and decrease the discard rates. However, trends and practice patterns of ECD kidney utilization on a national level based on donor organ quality as per KDPI are not well known. We, therefore, performed a trend analysis of all ECD recipients in the United Network for Organ Sharing (UNOS) registry between 2002 and 2012, after calculating the corresponding KDPI, to enable understanding the trends of usage and outcomes based on the KDPI characterization. High-risk recipient characteristics (diabetes, body mass index ≥30 kg/m2, hypertension, and age ≥60 years) increased over the period of the study (trend test p<0.001 for all). The proportion of ECD transplants increased from 18% in 2003 to a peak of 20.4% in 2008 and then declined thereafter to 17.3% in 2012. Using the KDPI >85% definition, the proportion increased from 9.4% in 2003 to a peak of 12.1% in 2008 and declined to 9.7% in 2012. Overall, although this represents a significant utilization of kidneys with KDPI >85% over time (p<0.001), recent years have seen a decline in usage, probably related to regulations imposed by Centers for Medicare & Medicaid Services (CMS). When comparing the hazards of graft failure by KDPI, ECD kidneys with KDPI >85% have a slightly lower risk of graft failure compared to standard criteria donor (SCD) kidneys with KDPI >85%, with a hazard ratio (HR) of 0.95, a confidence interval (CI) of 0.94-0.96, and statistical significance of p<0.001. This indicates that some SCD kidneys may actually have a lower estimated quality, with a higher Kidney Donor Risk Index (KDRI), than some ECDs. The incidence of delayed graft function (DGF) in ECD recipients has significantly decreased over time from 35.2% in 2003 to 29.6% in 2011 (p=0.007), probably related to better understanding of the donor risk profile along with increased use of hypothermic machine perfusion and pretransplant biopsy to aid in optimal allograft selection. The recent decline in transplantation of KDPI >85% kidneys probably reflects risk-averse transplant center behavior. Whether discard of discordant SCD kidneys with KDPI >85% has contributed to this decline remains to be studied.

Could the Use of an Enhanced Recovery Protocol in Laparoscopic Donor Nephrectomy be an Incentive for Live Kidney Donation?

INTRODUCTION AND BACKGROUND: Gastrointestinal (GI) recovery after major abdominal surgery can be delayed from an ongoing need for narcotic analgesia thereby prolonging hospitalization. Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway designed to facilitate early recovery after major surgery by maintaining preoperative body composition and physiological organ function and modifying the stress response induced by surgical exposure. Enhanced recovery programs (ERPs) in colorectal surgery have decreased the duration of postoperative ileus and the hospital stay while showing equivalent morbidity, mortality, and readmission rates in comparison to the traditional standard of care. This study is a pilot trial to evaluate the benefits of ERAS protocols in living kidney donors undergoing laparoscopic nephrectomy. METHODS: This is a single-center, non-randomized, retrospective analysis comparing the outcomes of the first 40 live kidney donors subjected to laparoscopic nephrectomy under the ERAS protocol to 40 donors operated prior to ERAS with traditional standard of care. Our ERAS protocol includes reduced duration of fasting with preoperative carbohydrate loading, intraoperative fluid restriction to 3 ml/kg/hr, target urine output of 0.5 ml/kg/hr, use of subfascial Exparel injection (bupivacaine liposome suspension), and postoperative narcotic-free pain regimen with acetaminophen, ketorolac, or tramadol. Short-term patient outcomes were compared using Pearsons's Chi-Squared test for categorical variables and the Kruskal-Wallis test for continuous variables. Additionally, a multivariate analysis was conducted to evaluate factors influencing patient length of stay and likelihood of readmission. RESULTS: ERAS protocol reduced the postoperative median length of stay decreased from 2.0 to 1.0 days (p=0.001). Overall pain scores were significantly lower in the ERAS group (peak pain score 6.0 vs. 8.00, p< 0.001; morning after surgery pain score 3.0 vs. 7.0, p=0.001; lowest pain score 0.0 vs. 2.0, p=0.016) despite the absence of postoperative narcotics. The average duration of surgery was shorter in the ERAS group (248 vs. 304 minutes, p<0.001). The average amount of intraoperative fluid used was significantly lower in the ERAS group (2500 ml vs. 3525 ml, p<0.001) without affecting the donor renal function. The incidence of delayed graft function was similar in the two groups (p=0.541). A trend toward lower readmission was noted with the ERAS protocol (12.8% vs. 27.5%, p=0.105). GI dysfunction was the most common reason for readmission. CONCLUSION: Application of an ERAS protocol in a laparoscopic living donor nephrectomy was associated with reduced length of hospitalization and improved pain scores related likely to intraoperative use of subfascial Exparel and a shorter duration of ileus. Restricted use of intraoperative fluids prevents excessive third spacing and bowel edema, enhancing gut recovery without adversely impacting recipient graft function. This study suggests that ERAS has the potential to enhance the advantages of laparoscopic surgery for live kidney donation through optimizing donor outcomes and perioperative patient satisfaction.

Intestinal transplantation.

Intestinal transplantation has now emerged as a lifesaving therapeutic option and standard of care for patients with irreversible intestinal failure. Improvement in survival over the years has justified expansion of the indications for intestinal transplantation beyond the original indications approved by Center for Medicare and Medicaid services. Management of patients with intestinal failure is complex and requires a multidisciplinary approach to accurately select candidates who would benefit from rehabilitation versus transplantation. Significant strides have been made in patient and graft survival with several advancements in the perioperative management through timely referral, improved patient selection, refinement in the surgical techniques and better understanding of the immunopathology of intestinal transplantation. The therapeutic efficacy of the procedure is well evident from continuous improvements in functional status, quality of life and cost-effectiveness of the procedure. This current review summarizes various aspects including current practices and evidence based recommendations of intestinal transplantation.

Effects of Ideal Versus Total Body Weight Dosage of Rabbit Antithymocyte Globulin on Outcomes of Kidney Transplant Patients With High Immunologic Risk.

OBJECTIVES: The optimal dose of rabbit antithymocyte globulin induction therapy in kidney transplant recipients with high immunologic risk lacks consensus. The purpose of this study was to evaluate the effect of using ideal body weight rather than total body weight for the weight-based dose calculations in this patient population. MATERIALS AND METHODS: Data were retrospectively collected on 89 adult patients who received rabbit antithymocyte globulin induction therapy for high immunologic risk kidney transplant. Hospital protocol changed from the use of cumulative rabbit antithymocyte globulin doses of 7.5 mg/kg total body weight to 7.5 mg/kg ideal body weight in 2009. Patients were separated into 2 cohorts based on the amount of rabbit antithymocyte globulin (in mg/kg total body weight) received. Rate of biopsy-proven acute rejection, patient survival, and allograft function were evaluated at 90 days and 1 year after transplant. Cost of induction therapy was also evaluated. RESULTS: Baseline demographics were predominantly similar between the 2 cohorts. No significant difference in maintenance immunosuppression was identified. Rates of biopsy-proven acute rejection at 90 days and 1 year were similar between ideal and total body weight cohorts (4.2% vs 0% at 90 days, P = .5; 8.7% vs 0% at 1 year, P = .13). Patient survival and allograft function were also similar. Median cost of rabbit antithymocyte globulin induction therapy per patient was lower in the ideal body weight cohort, but this difference was not statistically significant ($17 542 vs $19 934; P = .3). CONCLUSIONS: Our results suggest that use of ideal body weight for dose calculations of rabbit antithymocyte globulin induction therapy in high immunologic risk kidney transplant recipients at 7.5 mg/kg results in low rates of acute rejection with a safety profile similar to that shown with a total body weight dosage. Use of ideal body weight for lower cumulative doses may still need further evaluation in this patient population.

Update on surgical therapies for intestinal failure.

PURPOSE OF REVIEW: Parenteral nutrition enables long-term survival in patients with intestinal failure; however, it is associated with life-threatening complications necessitating alternative techniques of management to enable weaning parenteral nutrition and minimizing parenteral nutrition-associated comorbidities. This review aims at discussing the indications and techniques most commonly utilized for surgical management in a short gut. RECENT FINDINGS: Surgical therapy for short gut has evolved and undergone refinement in the past 30-40  years with the older procedures being largely abandoned and replaced by newer and refined techniques. Lengthening surgeries (longitudinal intestinal lengthening and tapering and serial transverse enteroplasty) are the most commonly applied procedures in a dilated bowel with intestinal transplantation option reserved as a last resort for recurrent life-threatening central venous line infections, progressive loss of central venous access, and development of progressive liver disease. SUMMARY: Management of intestinal failure requires a multidisciplinary approach to optimize intestinal rehabilitation and overall patient outcome. Although intestinal transplantation remains an excellent option for patients with severe life-threatening complications, autologous intestinal reconstruction appears to remain the better overall option.

The Surgical Approach to Short Bowel Syndrome - Autologous Reconstruction versus Transplantation.

BACKGROUND: Short bowel syndrome (SBS) is a state of malabsorption resulting from massive small bowel resection leading to parenteral nutrition (PN) dependency. Considerable advances have been achieved in the medical and surgical management of SBS over the last few decades. METHODS: This review discusses in detail the surgical approach to SBS. RESULTS: Widespread use of PN enables long-term survival in patients with intestinal failure but at the cost of PN-associated life-threatening complications including catheter-associated blood stream infection, venous thrombosis, and liver disease. The goal of management of intestinal failure due to SBS is to enable enteral autonomy and wean PN by means of a multi-disciplinary approach. Availability of modified enteral feeding formulas have simplified nutrition supplementation in SBS patients. Similarly, advances in the medical field have made medications like growth hormone and glucagon-like peptide (GLP2) available to improve water and nutrient absorption as well as to enable achieving enteral autonomy. Autologous gastrointestinal reconstruction (AGIR) includes various techniques which manipulate the bowel surgically to facilitate the bowel adaptation process and restoration of enteral nutrition. Ultimately, intestinal transplantation can serve as the last option for the cure of intestinal failure when selectively applied. CONCLUSION: SBS continues to be a challenging medical problem. Best patient outcomes can be achieved through an individualized plan, using various AGIR techniques to complement each other, and intestinal transplantation as a last resort for cure. Maximum benefit and improved outcomes can be achieved by caring for SBS patients at highly specialized intestinal rehabilitation centers.

Autologous gastrointestinal reconstruction: review of the optimal nontransplant surgical options for adults and children with short bowel syndrome.

Short bowel syndrome (SBS) results in loss of absorptive capacity of the development of gut, leading to malabsorption due to protein, energy, fluid, and electrolyte loss and imbalance while on enteral diet alone. Various nonsurgical and surgical therapeutic options that have emerged improve the survival outcome following SBS in both children and adults. An individualized, complex multidisciplinary approach to medical and surgical intestinal rehabilitation is needed to provide an opportunity for enteral autonomy to be possible in a patient with SBS. The remnant bowel plays a very pivotal role in autologous gastrointestinal reconstruction (AGIR) surgery. Intestinal transplantation, although promising and potentially life-saving for SBS, should be reserved for patients with failed AGIR or those who have no prospect for autologous enteral autonomy. This article reviews the evolution of nontransplant surgical management of patients with SBS.

Benign metastasizing leiomyoma: a rare cause of multiple pulmonary nodules.

Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules that occurs when uterine leiomyomas metastasize to the lung. The management of these lesions varies from resection and hysterectomy to nonsurgical treatments such as hormonal therapy. We report a case of a 45-year-old woman with multiple nodules of the right lung identified during preoperative imaging before her hysterectomy for uterine fibroids.