Allograft Duodenal Cuff Biopsy as Surrogate in Evaluation of Pancreatic Transplant Rejection – A Multicenter Data Effort
Danni Holanda1, Cinthia B Drachenberg2, Marta I Minervini3, John C Papadimitriou2, Lois J Arend4, John S Odorico5, Marcelo Perosa6, Candice Roufosse7, Hanneke De Kort8, Henrik M Reims9, Finn P Reinholt9, Julio C Goldberg10, Eva Honsova11, Ludek Voska11, Erik Larsson12, Steven Paraskevas13, Surya Seshan14, Jose Torrealba15.
1Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, United States; 2Pathology, University of Maryland School of Medicine, Baltimore, MD, United States; 3Pathology, University of Pittsburgh Montefiore Hospital, Pittsburgh, PA, United States; 4Pathology, The Johns Hopkins University, Baltimore, MD, United States; 5Surgery, University of Wisconsin, Madison, WI, United States; 6Surgery, Universidade de Sao Paulo, Sao Paulo, Brazil; 7Pathology, Imperial College Hammersmith Hospital, London, United Kingdom; 8Experimental Immunology and Renal Transplant Unit, Leiden University Centre, Amsterdam, Netherlands; 9Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway; 10Transplantation, Instituto de Nefrologia Buenos Aires, Buenos Aires, Argentina; 11Pathology, Institute For Clinical And Experimental Medicine, Prague, Czech Republic; 12Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden; 13Surgery, McGill University Health Centre, Montreal, QC, Canada; 14Pathology, Weill Cornell Medical College, New York, NY, United States; 15Pathology, University of Texas Southwestern, Dallas, TX, United States
Introduction:Accurate diagnosis of pancreas rejection is required for early, targeted treatment and function preservation. Pancreas biopsy considered the gold standard presents with sampling issues and perceived procedural risks that limit its widespread use. Evaluation of the graft duodenal cuff, through upper endoscopy in intestine drained pancreas transplants has been proposed as a surrogate of pancreas biopsy but the utility of this approach has not been tested. In this multicenter effort we retrospectively evaluated pancreas and duodenal tissues collected simultaneously to correlate findings of acute cell-mediated rejection (ACR) in these two organs and offer interpretation of duodenal cuff biopsies as a potential diagnostic surrogate for its corresponding pancreas allograft.
Materials and Methods: A total of 88 cases were evaluated retrospectively from allograft pancreas performed between 1995 and 2015, with incidentally or intentionally obtained duodenal cuff mucosa from 11 reference tranplant centers in the North and South Americas, E.U. and U.K. These cases were re-analyzed and graded for ACR. Sixteen cases were excluded due to inadequate pancreas or duodenal sample, possible non-rejection biopsy findings or samples that were not simultaneously obtained. Of the remaining 72 cases, 50 were biopsies and 22 were explant cases. The cases were graded according to the Banff schema for grading pancreas allograft rejection (Drachenberg et al 2008) and from the schema for histologic grading of small intestine allografts (Wu et al 2008).
Results: Of the 72 cases, 20 cases showed a diagnosis of rejection. All 20 (100%) cases showed rejection in both pancreas and duodenal tissue. Fifty eight cases (80.5%) showed results that were concordant for a final diagnosis of rejection/suspicious for rejection or no evidence of rejection. Of the 14 (19.5%) cases that showed complete discordance (either suspected or diagnostic for rejection in pancreas but not duodenum or suspected or diagnostic for rejection in duodenum but not pancreas) 2 cases (2.7%) showed findings of rejection in the duodenum but not pancreas and 12 cases (16.6%) showed findings of rejection in pancreas but not in duodenum.
Discussion: In this cohort with simultaneous histological evaluation of pancreas parenchyma and graft duodenal cuff, a diagnosis of ACR in the duodenum showed a positive predictive value of 100% for pancreas ACR. Therefore evaluation of the duodenal cuff appears to be a useful surrogate in the absence of pancreas parenchyma in this setting. On the other hand, absence of rejection in the duodenum did not totally exclude rejecion in the pancreas, with a negative predictive value of 83%. Results that were graded as indeterminate (suspicious for) rejection in duodenum were not reliable and had both low PPV and NPV for pancreas rejection. Our results are encouraging and indicate the potential value of duodenal cuff evaluation, as well as the need for additional studies.
