Transmission of Lung Adenocarcinoma From a Single Donor in 2 Transplant Recipients: A Case Report With Literature Review.

Malignancies transmitted to recipients during solid organ transplants carry significant morbidity and mortality. We present 2 cases of adenocarcinoma of donor lung origin transmitted via liver and kidney transplant from a single donor. Both recipients developed metastatic adenocarcinoma of lung origin with p.L858R mutation in the epidermal growth factor receptor gene and a microsatellite signature of donor origin. Osimertinib was trialed in the liver recipient; however, it was discontinued because of hepatotoxicity and disease progression. Standard donor screening protocols limit malignancy transmission but do not include multicancer detection assays. As these technologies evolve, they may be implemented in donor screening.

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000-2019 UNOS/OPTN database.

This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p = .001). Over a median follow-up time of 4.5 years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p = .21), all-cause mortality was 8.3% vs. 11.8% (p = .51), and 1-year acute rejection was 11.0% vs. 9.3% (p = .36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0-10%, 11-20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0-10% GS (58.0%), 11-20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0-10% GS, 68.9% in 11-20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0-10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11-20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0-10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

Outcomes of kidney retransplantation after graft loss as a result of BK virus nephropathy in the era of newer immunosuppressant agents.

We conducted this study using the updated 2005-2016 Organ Procurement and Transplantation Network database to assess clinical outcomes of retransplant after allograft loss as a result of BK virus-associated nephropathy (BKVAN). Three hundred forty-one patients had first graft failure as a result of BKVAN, whereas 13 260 had first graft failure as a result of other causes. At median follow-up time of 4.70 years after the second kidney transplant, death-censored graft survival at 5 years for the second renal allograft was 90.6% for the BK group and 83.9% for the non-BK group. In adjusted analysis, there was no difference in death-censored graft survival (P = .11), acute rejection (P = .49), and patient survival (P = .13) between the 2 groups. When we further compared death-censored graft survival among the specific causes for first graft failure, the BK group had better graft survival than patients who had prior allograft failure as a result of acute rejection (P < .001) or disease recurrence (P = .003), but survival was similar to those with chronic allograft nephropathy (P = .06) and other causes (P = .05). The better allograft survival in the BK group over acute rejection and disease recurrence remained after adjusting for potential confounders. History of allograft loss as a result of BKVAN should not be a contraindication to retransplant among candidates who are otherwise acceptable.

Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles.

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.

Correlation of Somatic Genomic Alterations Between Tissue Genomics and ctDNA Employing Next-Generation Sequencing: Analysis of Lung and Gastrointestinal Cancers.

Next-generation Sequencing (NGS) of cancer tissues is increasingly being carried out to identify somatic genomic alterations that may guide physicians to make therapeutic decisions. However, a single tissue biopsy may not reflect complete genomic architecture due to the heterogeneous nature of tumors. Circulating tumor DNA (ctDNA) analysis is a robust noninvasive method to detect and monitor genomic alterations in blood in real time. We analyzed 28 matched tissue NGS and ctDNA from gastrointestinal and lung cancers for concordance of somatic genomic alterations, driver, and actionable alterations. Six patients (21%) had at least one concordant mutation between tissue and ctDNA sequencing. At the gene level, among all the mutations (n = 104) detected by tissue and blood sequencing, 7.7% (n = 8) of mutations were concordant. Tissue and ctDNA sequencing identified driver mutations in 60% and 64% of the tested samples, respectively. We found high discordance between tissue and ctDNA testing, especially with respect to the driver and actionable alterations. Both tissue and ctDNA NGS detected actionable alterations in 25% of patients. When somatic alterations identified by each test were combined, the total number of patients with actionable mutations increased to 32%. Our data show significant discordance between tissue NGS and ctDNA analysis. These results suggest tissue NGS and ctDNA NGS are complementary approaches rather than exclusive of each other. When performed in isolation, tissue and ctDNA NGS can each potentially miss driver and targetable alterations, suggesting that both approaches should be incorporated to enhance mutation detection rates. Larger prospective studies are needed to better clarify this emerging precision oncology landscape. Mol Cancer Ther; 17(5); 1123-32. ©2018 AACR.

Ethylene-vinyl alcohol copolymer endobiliary obliteration of hepatic segments in a patient with isolated bile leaks.

A 54-year-old woman with a symptomatic giant hepatic hemangioma underwent an extended left hepatic trisegmentectomy complicated by 250-350 mL/d postoperative bilious drainage. After 5 months of therapy, drainage was unabated, and the patient was no longer a surgical candidate. Sinography revealed three distinct isolated bile duct leaks involving segments 6, 7, and 8. Endobiliary segmentectomy was achieved by obliterating the isolated systems with ethylene-vinyl alcohol copolymer (Onyx; ev3, Plymouth, Minnesota) during three fluoroscopic procedures. Bilious leaks were successfully eliminated, and compensatory hypertrophy of noninvolved liver occurred. At 2 years from the last embolization procedure, the patient remained asymptomatic with no bilious leak.

Paired kidney donor exchanges and antibody reduction therapy: novel methods to ameliorate disparate access to living donor kidney transplantation in ethnic minorities.

BACKGROUND: Currently ethnic minority patients comprise 60% of patients listed for kidney transplantation in the US; however, they receive only 55% of deceased donor renal transplants and 25% of living donor renal transplants. Ethnic disparities in access to kidney transplantation result in increased morbidity and mortality for minority patients with end-stage renal disease. Because these patients remain dialysis dependent for longer durations, they are more prone to the development of HLA antibodies that further delay the possibility of receiving a successful kidney transplant. STUDY DESIGN: Two to 4 pretransplant and post-transplant plasma exchanges and i.v. immunoglobulin were used to lower donor-specific antibody levels to less than 1:16 dilution; cell lytic therapy was used additionally in some cases. Match pairing by virtual cross-matching was performed to identify the maximal exchange benefit. Sixty candidates for renal transplantation were placed into 4 paired kidney exchanges and/or underwent antibody reduction therapy. RESULTS: Sixty living donor renal transplants were performed by paired exchange pools and/or antibody reduction therapy in recipients whose original intended donors had ABO or HLA incompatibilities or both (24 desensitization and 36 paired kidney exchanges). Successful transplants were performed in 38 ethnic minorities, of which 33 were African American. Twenty-two recipients were white. Graft and patient survival was 100% at 6 months; graft function (mean serum creatinine 1.4 g/dL) and acute rejection rates (20%) have been comparable to traditional live donor kidney transplantation. CONCLUSIONS: Paired kidney donor exchange pools with antibody reduction therapy can allow successful transplant in difficult to match recipients. This approach can address kidney transplant disparities.

Evaluation of a modified circular stapler for use as a viscerotomy formation and closure device in natural orifice surgery.

BACKGROUND: The most challenging of the many hurdles surgeons must overcome to perform natural orifice translumenal endoscopic surgery (NOTES) safely is viscerotomy closure. The perfect device must be easy to deploy, suitable for use on any viscera, and able to create a rapid, reliable, and durable closure. The authors developed a novel device based on an existing circular stapler platform to create and then subsequently close a viscerotomy. The device was tested initially on an ex vivo porcine stomach model, then used on a survival canine model to confirm adequacy of gastric closure and rapidity of deployment. METHODS: Three study arms, each containing five stomachs, were used. For the experimental arm, a Surgassist (PMI, Langhorne, PA, USA) powered circular stapler (EEA) modified with an auger tip and premounted endoloops was used. This novel device was compared with two gold standard closure techniques: hand-sewn two-layer closure and linear stapled closure. Each stomach then was inflated slowly with dye, and the pressure at which each closure leaked was recorded. For evaluation of the closure's durability and ease of use, five mongrel dogs undergoing transgastric intraabdominal surgery had their gastrotomy formed and closed using the modified Surgassist stapler. Each animal was survived 14 days, then killed, after which a necropsy was performed. RESULTS: In the ex vivo model, the modified PMI EEA consistently achieved burst pressures exceeding 260 mmHg, which was statistically significant compared with either the hand-sewn closure or the linear stapled closure. In the survival group, all the animals survived for the 2-week study period without signs of sepsis. At necropsy, the closures were found to be intact. CONCLUSION: The prototype transvisceral purse-string device consistently produced a tight, safe, and reliable closure. It can be deployed and cinch-closed rapidly. This study suggests that this new device may be a promising option for use in NOTES.

Experimental in vivo canine model for gastric prolapse of laparoscopic adjustable gastric band system.

BACKGROUND: The most prevalent long-term complications in patients undergoing laparoscopic adjustable gastric band (LAGB) surgery are symmetric pouch dilation and gastric prolapse (slippage). However, no published data or a reliable model are available to evaluate the actual mechanism of band slippage or how to prevent it. The objective of the present study was to construct an animal model of anterior gastric band prolapse and to use this model to evaluate the effectiveness of various arrangements of gastrogastric sutures and gastric wraps in preventing prolapse. METHODS: The esophagus of male mongrel dogs was accessed through the left chest, and a pressure transducer and an insufflation catheter were introduced. An AP-S Lap-Band (Allergan, Irvine, CA) filled to 10 cm(3) was placed using the pars flaccida technique. A standardized cut of meat was placed into the esophagus to simulate food impaction at a tight LAGB. After the placement of multiple different gastrogastric suture configurations, air was insufflated into the gastric pouch by way of the esophagus. RESULTS: Prolapse, identical to that seen in clinical practice, was reliably reproduced in this model by increased esophageal pressure acting on a LAGB outlet obstruction. In addition, prolapse was reproduced with all gastrogastric configurations that did not secure the anterior gastric wall to within 1.5 cm of the lesser curve. CONCLUSION: The results of the present study support the theory that prolapse is caused by esophageal peristalsis against an occlusion at the level of the LAGB. In this canine model, gastrogastric sutures encompassing the anterior gastric wall were integral to preventing prolapse.