Lee S. Cummings

Autotransplantation of Solitary Kidney With Renal Artery Aneurysm Treated With Laparoscopic Nephrectomy and Ex Vivo Repair: A Case Report

INTRODUCTION Renal artery aneurysms (RAA) are extremely rare clinical entities with associated morbidities including hypertension and rupture. Although most RAA can be treated with in vivo repair or endovascular techniques, these may not be possible in patients with complex RAA beyond the renal artery bifurcation. We report a case of RAA in a patient with a solitary kidney that we treated successfully by extracorporeal repair and autotransplantation and the 2-years follow-up. CASE REPORT A 64-year-old woman with a history of right nephrectomy for renal cell carcinoma presented with RAA found on routine computed tomography (CT). Preoperative workup demonstrated a 2.2 × 2.1 × 3-cm aneurysm in the distal left renal artery that was not amendable to in vivo or endovascular repair. The patient underwent a laparoscopic-assisted left nephrectomy, ex vivo renal artery aneurysm repair, and autotransplantation. She did well postoperatively and in clinic follow-up was found to have a creatinine of 1.2 mg/dL at the end of 2 years and stable blood pressure control. DISCUSSION This patient with RAA in her solitary kidney was successfully treated with laparoscopic-assisted nephrectomy, ex vivo repair, and autotransplantation. Her creatinine was stable postoperatively despite absence of a second kidney.

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.

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.

Modification of the HeRO Graft Allowing Earlier Cannulation and Reduction in Catheter Dependent Days in Patients with End Stage Renal Disease: A Single Center Retrospective Review

After creation of an arteriovenous fistula or placement of an arteriovenous graft, several weeks are required for maturation prior to first cannulation. Patients need an alternative way to receive hemodialysis during this time, frequently a catheter. After multiple failed access attempts, patients can run out of options and become catheter dependent. At our institution, we place HeRO grafts in eligible patients who have otherwise been told they would be catheter dependent for life. By combining the HeRO graft system with a Flixene graft, patients are able to remove catheters sooner or avoid placement as they can undergo cannulation for hemodialysis the next day. Utilizing this novel technique, twenty-one patients over a two-year period with various forms of central venous stenosis, catheter dependence, or failing existing arteriovenous access have been successfully converted to stable long term noncatheter based upper extremity access.

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.

Comparative Proteogenomic Analysis of Right-sided Colon Cancer, Left-sided Colon Cancer and Rectal Cancers Reveal Distinct Mutational Profiles.

To understand the molecular differences between right-sided colon cancer (RCC), left-sided colon cancer (LCC) and rectal cancer, we analyzed colorectal tumors at the DNA, RNA, miRNA and protein levels using previously sequenced data from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center. Clonal evolution analysis identified the same 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 dynamics and selection of downstream mutations were distinct in all three anatomical locations, with some similarities noted between LCC and rectal cancer. We found a potentially targetable alteration APC R1450* specific to RCC that has not been previously described. Differential gene expression analysis revealed multiple genes within the homeobox, G-protein coupled receptor binding and transcription regulation families were dysregulated in RCC, LCC, and rectal cancers and may have a pathological role in these cancers. Further, using a novel in silico proteomic analytic tool developed by our research group, we found distinct central or hub proteins with unique interactomes in each location. Protein expression signatures were not necessarily concordant with the tumor profiles obtained at the DNA and RNA levels, underscoring the relevance of post-transcriptional events in defining the biology of these cancers beyond molecular changes at the DNA and/or RNA level. Ultimately, not only tumor location and the respective genomic profile but also protein-protein interactions will need to be taken into account to improve treatment outcomes of colorectal cancers. Further studies that take into account the alterations found in this study may help in developing more tailored, and perhaps more effective, treatment strategies. Author summary Patients with right-sided colon cancer (RCC) has a worse prognosis compared to left-sided colon cancer (LCC). Recent data has also shown that wild-type RAS metastatic RCC’s have poor outcomes when treated with the combination of chemotherapy and anti-EGFR therapy compared to LCC and rectal cancers. Therefore, There is an urgent unmet need to understand the molecular differences between RCC, LCC, and rectal cancers. In this study, we demonstrate clonal evolutionary trajectory and the order of mutations in RCC, LCC, and rectal cancers are distinct with some similarities between LCC and rectal cancers. The order of the mutations that lead to the acquisition of crucial driver alterations may have prognostic and therapeutic implications. We also discovered a novel targetable alteration, APC R1450* to be significantly enriched in early, late and metastatic RCC but not in LCC and rectal cancers. Amazingly, proteomic signatures were discordant with DNA and RNA levels. These distinct differences in DNA, RNA and post-transcriptional events may contribute to their unique clinicopathological features. Conflict of Interest Statement Ashiq Masood Advisory board and speaker Bureau Bristol-Myers Squibb and Boehringer Ingelheim Janakiraman Subramanian Advisory board - Astra Zeneca, Pfizer, Boehringer Ingelheim, Alexion, Paradigm, Bristol-Myers Squibb Speakers Bureau - Astra Zeneca, Boehringer Ingelheim, Lilly Research Support - Biocept and Paradigm Arif Hussain Advisory board – Novartis, Bayer, Astra Zeneca Consultant – Bristol-Myers-Squibb All other authors have no conflict of interest.