Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes.

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Impact of AI-aided colonoscopy in clinical practice: a prospective randomised controlled trial.

OBJECTIVE: Colorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed polyps. The impact of artificial intelligence (AI) on adenoma and polyp detection rate (ADR, PDR) is yet to be established. DESIGN: We conducted a randomised controlled trial at Sahlgrenska University Hospital in Sweden. Patients underwent colonoscopy with or without the assistance of AI (AI-C or conventional colonoscopy (CC)). Examinations were performed with two different AI systems, that is, Fujifilm CADEye and Medtronic GI Genius. The primary outcome was ADR. RESULTS: Among 286 patients, 240 underwent analysis (average age: 66 years). The ADR was 42% for all patients, and no significant difference emerged between AI-C and CC groups (41% vs 43%). The overall PDR was 61%, with a trend towards higher PDR in the AI-C group. Subgroup analysis revealed higher detection rates for sessile serrated lesions (SSL) with AI assistance (AI-C 22%, CC 11%, p=0.004). No difference was noticed in the detection of polyps or adenomas per colonoscopy. Examinations were most often performed by experienced endoscopists, 78% (n=86 AI-C, 100 CC). CONCLUSION: Amidst the ongoing AI integration, ADR did not improve with AI. Particularly noteworthy is the enhanced detection rates for SSL by AI assistance, especially since they pose a risk for postcolonoscopy CRC. The integration of AI into standard colonoscopy practice warrants further investigation and the development of improved software might be necessary before enforcing its mandatory implementation. TRIAL REGISTRATION NUMBER: NCT05178095.

Endoscopic Surveillance of the Intestinal Allograft: Recommendations From the Intestinal Rehabilitation and Transplant Association Working Group.

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

Diagnostic yield for video capsule endoscopy in gastrointestinal graft- versus -host disease: a systematic review and metaanalysis.

BACKGROUND: The gastrointestinal tract is the second most involved organ for graft-versus-host disease where involvement of the small intestine is present in 50% of the cases. Therefore, the use of a non-invasive investigation i.e., video capsule endoscopy (VCE) seems ideal in the diagnostic work-up, but this has never been systematically evaluated before. OBJECTIVE: The aim of this systematic review was to determine the efficacy and safety of VCE, in comparison with conventional endoscopy in patients who received hematopoietic stem cell transplantation. METHOD: Databases searched were PubMed, Scopus, EMBASE, and Cochrane CENTRAL. All databases were searched from their inception date until June 17, 2022. The search identified 792 publications, of which 8 studies were included in our analysis comprising of 232 unique patients. Efficacy was calculated in comparison with the golden standard i.e., histology. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: The pooled sensitivity was higher for VCE at 0.77 (95% CI: 0.60-0.89) compared to conventional endoscopy 0.62 (95% CI: 0.47-0.75) but the difference was not statistically significant (p = 0.155, Q = 2.02). Similarly, the pooled specificity was higher for VCE at 0.68 (95% CI: 0.46-0.84) than for conventional endoscopy at 0.58 (95% CI: 0.40-0.74) but not statistically significant (p = 0.457, Q = 0.55). Moreover, concern for adverse events such as intestinal obstruction or perforation was not justified since none of the capsules were retained in the small bowel and no perforations occurred in relation to VCE. A limitation to the study is the retrospective approach seen in 50% of the studies. CONCLUSION: The role of video capsule endoscopy in diagnosing or dismissing graft-versus-host disease is not yet established and requires further studies. However, the modality appears safe in this cohort.

Endoscopic ultrasound in the monitoring of the intestinal allograft.

OBJECTIVE: Chronic rejection (CR) of the small intestinal allograft includes mucosal fibrosis, bowel thickening and arteriopathy in the outer wall layers and the mesentery. CR lacks non-invasive markers and reliable diagnostic methods. We evaluated endoscopic ultrasound (EUS) as a novel approach for monitoring of the intestinal allograft with respect to CR. DESIGN: In intestinal graft recipients, EUS and enteroscopy with ileal mucosal biopsy were performed via the ileostomy. At EUS, the wall thickness of the intestinal graft was measured in standard mode, whereas the resistive index (RI) of the supplying artery was assessed in pulsed Doppler mode. At enteroscopy, the intestinal mucosa was assessed. Findings were compared with histopathology and clinical follow-up. RESULTS: EUS was successfully performed in all 11 patients (adequate clinical course (AC) n=9; CR n=2) after a median interval of 1537 days (range: 170-5204), post-transplantation. The total diameter of the wall (layer I-V) was comparable in all patients. Meanwhile, the diameter of the outermost part (layer IV-V; that is, muscularis propria-serosa) was among the two CR patients (range: 1.3-1.4 mm) in the upper end of measurements as compared with the nine AC patients (range: 0.5-1.4 mm). The RI was >0.9 in both CR patients, while the RI was ≤0.8 in all AC patients. Both CR patients had abnormal findings at enteroscopy and histopathology and deceased during follow-up. CONCLUSION: EUS is a promising tool providing detailed information on the intestinal graft morphology and rheology, which may be used for assessment of potential CR in long-term follow-up of intestinal allograft recipients.

Graft assessment for acute rejection after intestinal transplantation: current status and future perspective.

Intestinal transplantation has since its inception evolved as a lifesaving treatment option for patients with irreversible intestinal failure who can no longer be sustained on parenteral nutrition. Improvement in short-term survival after transplantation has also justified the expansion of treatment indications. Unfortunately, success is somewhat limited by a plateau observed in long-term survival. The reason for this sub-optimal long-term result experienced in this cohort may in part be attributed to the intestinal graft with the lymphoid content it carries inflicting the host with multiple complications where acute cellular rejection is one of the most common causes for graft loss. Graft monitoring is for this reason of paramount importance and detection of rejection at an early stage essential to enable early instigation of treatment and successful reversal of the pathology. Due to the challenges in diagnosing acute rejection with a noninvasive marker we are still limited to a surveillance protocol using endoscopy and biopsies for the diagnosis of rejection. The purpose of our paper is to review the adequacy of different methods in monitoring the graft for acute rejection using biomarkers, endoscopy and imaging. In conclusion, the evidence base continues to support the use of histology for the diagnosis of acute rejection. The role of biomarkers are still debatable, although markers such as calprotectin might be beneficial in excluding an ongoing process.

The endoscopic surveillance of the transplanted small intestine: a single center experience and a proposal for a grading score.

OBJECTIVE: Microscopic examination of endoscopic biopsies forms the basis of acute cellular rejection (ACR) monitoring after intestinal transplantation (ITx). The endoscopy findings during acute rejection (AR) are known but a grading system for its severity is lacking. We designed and implemented a five-stage grading score based on acknowledged endoscopic features of AR, to allow a faster preliminary diagnosis of AR and intra- and interpatient comparisons. METHODS: Two investigators reviewed and graded the endoscopy reports after 28 ITx using a novel score and correlated the results with pathology findings. RESULTS: We reviewed 512 ileoscopies: 370 examinations (74%) were normal (G0), 59 had mild alterations (erythema, edematous villi-G1) and 36 showed moderate changes (erosions, blunted villi-G2); 17 ileoscopies revealed advanced changes (ulcerations, villus loss-G3). In 18 endoscopies the changes were severe (mucosal loss-G4). Inter-reviewer agreement was very good (kappa = 0.81). Biopsies from 86 endoscopy sessions (17%) indicated ACR with 63 cases having moderate or severe ACR. For mild ACR the sensitivity of the score was 29% and the specificity was 86% whereas the positive (PPV) and negative predictive values (NPVs) were 14% and 93% respectively. During advanced ACR the sensitivity and specificity were 92% and 86%, respectively whereas the PPV and NPV were 49% and 98% respectively. CONCLUSIONS: Endoscopy alone has a limited ability to reliably diagnose intestinal ACR. We suggest a novel grading score summarizing ACR findings and allowing comparisons between intestinal graft endoscopies.

Initial Experience of Video Capsule Endoscopy After Intestinal Transplantation.

BACKGROUND: Intestinal transplantation is a procedure which inflicts immunological and infectious complications that affect the transplanted graft, posing both diagnostic and therapeutic challenges. Video capsule endoscopy (VCE) offers easy access to the entire small intestine and presents itself as an interesting option. However, at present, no studies evaluating the usefulness of video capsule endoscopies in this setting have been published. Our aim was to evaluate the usefulness of VCE in detecting complications that arise after intestinal transplantation. METHODS: We included 7 adult patients with either isolated intestine (n = 1) or multivisceral grafts (n = 6). These patients underwent 12 VCE between 2004 and 2015 at the Sahlgrenska University Hospital. The median age was 42 (21-67) years (4 women/3 men). VCE was used in clinical situations where the conventional diagnostic methods failed to provide answers to the clinical question. RESULTS: Indications for the procedure were: suspicion of rejection (n = 4 examinations), gastrointestinal dysmotility (n = 4 examinations), high stomal output (n = 2 examinations), suspicion of lymphoproliferative disease in the transplanted graft (n = 1 examination), and clinical surveillance (n = 1 examination). The median time after transplantation for performing an examination was 740 (26-3059) days. VCE was useful in 83% of the examinations and the results influenced the planned management. The overall agreement between VCE findings and biopsies was moderate (κ = 0.54, P = 0.05) but increased when comparing the presence of inflammation/rejection (κ = 0.79, P < 0.001). CONCLUSIONS: VCE is a promising diagnostic method after intestinal transplantation. However, larger studies are needed to evaluate its potential risks and gains.

Fifteen years' experience of intestinal and multivisceral transplantation in the Nordic countries.

OBJECTIVE: Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure. METHOD: The authors included all Nordic patients transplanted between January 1998 and December 2013. Information on patients transplanted outside the Nordic region was collected through questionnaires. RESULTS: A total of 34 patients received different types of intestinal allografts. Currently, there are two Nordic transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n = 24, Helsinki, Finland n = 5). The remaining five patients were transplanted in the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life-threatening failure of PN (70%) caused primarily by intestinal motility diseases (59%). Allograft rejection was the most common complication and occurred in 79% of the patients followed by post-transplantation lymphoproliferative disorders (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and 65% respectively for the whole cohort and nutritional autonomy was achieved in 73% of the adults and 57% of the children at 1 year after transplantation. CONCLUSION: This collective Nordic experience confirms that intestinal transplantation is a complex procedure with many complications, yet with the possibility to provide long-term survival in selected conditions previously considered untreatable.

Survival of patients evaluated for intestinal and multivisceral transplantation - the Scandinavian experience.

OBJECTIVE: The current treatment of choice for patients with intestinal failure is parenteral nutrition, whereas medical therapy or resection is preferred for patients with neuroendocrine pancreatic tumors (NEPT) along with liver metastasis. As the survival of patients undergoing intestinal and multivisceral transplantation is improving, the discussion for expansion of treatment options has become a subject of debate. The aim was to investigate the outcome for patients referred for intestinal and multivisceral transplantation and to determine which patient group are the ones most likely to benefit the most from transplantation. METHODS: The authors included all patients evaluated for intestinal and multivisceral transplantation at the Sahlgrenska University Hospital and The Queen Silvia Children's Hospital center between February 1998 and November 2009. Patients were classified according to proposed treatment strategy, and the outcome was evaluated. RESULTS: A total of 43 adults and 19 children with either intestinal failure or NEPT with liver metastases were evaluated for transplantation. Of these patients, 15 adults and 5 children were transplanted. Transplantation was lifesaving for most children - all the children survived after transplantation, but 70% (4/6) died while awaiting transplantation. Among the adult patients with intestinal failure, the survival rate for patients considered to be stable on parenteral nutrition was higher than the transplanted adult patients. The survival rate of patients with NEPT was similar to the results seen among patients transplanted for intestinal failure. CONCLUSION: The results confirm the poor prognosis of patients with intestinal failure awaiting transplantation and indicate that different transplantation criteria may be applied for adults and children, especially when early transplantation is the preferred treatment. The role of multivisceral transplantation in patients with NEPT remains uncertain.