Cytomegalovirus Graft Duodenitis Diagnosed by Transanal Double-Balloon Endoscopy Technique in an Enteric-Drained Pancreas Transplant Recipient: A Case Report.

Duodenal graft complications are not uncommon after pancreas transplant (PTx). Although direct visualization and biopsy of the duodenal graft are important for accurate diagnosis and management, endoscopic access is often limited in cases of enteric-drained PTx. Herein, we present a case of cytomegalovirus (CMV) graft duodenitis that was successfully diagnosed by transanal endoscopy using the double-balloon technique. The patient was a 54-year-old woman who underwent simultaneous pancreas and kidney transplant for type 1 diabetes mellitus and end-stage kidney disease. Enteric drainage was established by anastomosing the graft duodenum to her ileum. One month after the transplant, she developed fever and complained of lower abdominal pain. Graft duodenitis was suspected by laboratory test and imaging study results. Transanal double-balloon endoscopy was performed, and the biopsy specimen of the mucosa of the graft duodenum revealed CMV duodenitis without histopathologic findings of acute rejection. The postendoscopy course was uneventful. Treatment with ganciclovir was promptly initiated, and the CMV duodenitis was resolved with good function of the pancreas graft. In patients who undergo PTx with establishment of exocrine drainage by enteroanastomosis to the recipient ileum, transanal double-balloon endoscopy might be a feasible and safe technique for the surveillance of duodenal graft complications, including CMV duodenitis.

Efficacy of Linear Stapler With Polyglycolic Acid Felt for Preventing Graft Duodenal Perforation After Pancreas Transplant.

OBJECTIVES: Graft duodenal perforation is a serious complication in pancreas transplantation. The aim of this study was to evaluate whether using a reinforced linear stapler during bench surgery in pancreas transplant affects the risk of graft duodenal perforation. MATERIALS AND METHODS: This retrospective study included 47 patients who underwent pancreas transplant at our institution from 2011 to 2020. A reinforced stapler with polyglycolic acid felt was used to dissect the graft duodenum during bench surgery in 16 of the 47 patients (reinforced group). A conventional linear stapler was used in the remaining 31 patients (conventional group). Demographic, perioperative, and postoperative parameters were compared between the reinforced group and the conventional group. RESULTS: Graft duodenal perforation occurred in 6 patients (19.4%) in the conventional group and in none of the patients in the reinforced group. Logistic regression analysis revealed no significant associations between donor- orrecipient-related factors and graft duodenal perforation. Among operative factors, use of a reinforced stapler was the only factor significantly associated with the risk of graft duodenal perforation (odds ratio = 0.12). CONCLUSIONS: The use of a reinforced stapler during dissection of the duodenum in bench surgery for pancreas transplant was associated with a lower risk of graft duodenal perforation than use of a conventional stapler.

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Uremia, and Insulin-Dependent Diabetes.

BACKGROUND Abdominal organ cluster transplantation for the treatment of upper abdominal end-stage diseases is a serious conundrum for surgeons. CASE REPORT We performed clinical assessment of quadruple organ transplantation (liver, pancreas, duodenum, and kidney) for a patient with end-stage liver disease, post-chronic hepatitis B cirrhosis, uremia, and insulin-dependent diabetes mellitus, and explored the optimal surgical procedure. Simultaneous classic orthotopic liver, pancreas-duodenum, and heterotopic renal transplantation was performed on a 46-year-old man. The process was an improvement of surgery implemented with a single vascular anastomosis (Y graft of the superior mesenteric artery and the celiac artery open together in the common iliac artery). The pancreatic secretions and bile were drained through a modified uncut jejunal loop anastomosis, and the donor's kidneys were placed in the right iliac fossa. The patient was prescribed basiliximab, glucocorticoid, tacrolimus, and mycophenolate mofetil for immunosuppression. The hepatic function recovered satisfactorily on postoperative day (POD) 3, and pancreatic function recovered satisfactorily in postoperative month (POM) 1. Hydronephrosis occurred in the transplanted kidney, with elevated creatinine on POD 15. Consequently, renal pelvic puncture and drainage were performed. His creatinine dropped to a normal level on POD 42. No allograft rejections or other complications, like pancreatic leakage, thrombosis, or localized infections, occurred. The patient had normal liver, renal, and pancreas functions with insulin-independent after POD 365. CONCLUSIONS Simultaneous classic orthotopic liver, pancreas-duodenum, and heterotopic renal transplantation is a promising therapeutic option for patients with insulin-dependent diabetes combined with end-stage hepatic and renal disease, and our center's experience can provide a reference for clinical multiorgan transplantation.

Delayed Bleeding of the Transplant Duodenum After Simultaneous Kidney-pancreas Transplantation: Case Series.

BACKGROUND: In simultaneous pancreas-kidney (SPK) transplant recipients, the majority of complications described in the literature, are early postoperative complications. However, there is growing attention for late complications associated with SPK transplantation. METHODS: In this case series, we present 3 cases, 2 enterically and 1 bladder-derived SPK transplant patients, with anastomotic hemorrhage of the donor duodenum as a very late complication, >10 years after transplantation (11, 22, and 18 y later, respectively). RESULTS: In our center, 122 SPK transplantations have been performed between January 1992 and June 2018. The 3 cases reported here are the only patients in our cohort presenting with delayed anastomotic hemorrhage of the donor duodenum (2.5%). In the first 2 patients, reintervention with reconstruction of the anastomosis was performed. A congestive and friable mucosa was seen, and the resection specimen showed enlarged and congestive submucosal veins in both patients. There was no recurrence of bleeding after reintervention. In the third patient, enteric derivation was not possible because of the extremely fragile intestinal tissue perioperatively, and a conservative approach was taken. As possible precipitating factors are concerned, all 3 of our patients were taking low-dose aspirin and/or clopidogrel as secondary cardiovascular prevention. CONCLUSIONS: Bleeding of the transplanted donor duodenum can present as a late complication, several years after SPK transplantation. The development of enlarged, congestive submucosal veins could play a role in these late bleedings, and antiplatelet therapy could be a precipitating factor. Further research is necessary to investigate the pathophysiology, the prevalence, optimal treatment, and the consequent influence on mortality, morbidity, and graft loss after SPK transplantation.

Protocol Duodenal Graft Biopsies Aid Pancreas Graft Surveillance.

BACKGROUND: Histological evaluation of the pancreas graft is usually done on demand resulting in significant delays. This analysis reports on endoscopic protocol duodenal graft biopsies at regular intervals to determine feasibility, safety, and monitoring benefits. METHODS: Protocol duodenal graft biopsies in 27 consecutive pancreas transplants (10 simultaneous pancreas kidney [SPK], 17 pancreas after kidney [PAK]) with a follow-up of a minimum of 12 months were performed at days 14, 30, 90, 180, 360, 430. University of Pittsburgh Medical Center classification for intestinal rejection was used. C4d staining was performed when antibody-mediated rejection was suspected. RESULTS: Overall patient and pancreas graft survival was 100% and 93% at a mean follow-up of 2.8 years. One hundred sixty-seven endoscopic biopsy procedures were performed in 27 grafts without any complication. Biopsies revealed rejection in 3 (30%) SPK recipients and in 15 (82%) of PAK recipients as early as 14 days posttransplant. Two patients underwent PAK retransplantation diagnosed with acute rejection at day 180. All except 1 recipient being treated for rejection, showed histological improvement following antirejection treatment. Following transient treatment success, a total of 3 pancreas grafts were lost for immunological reason. One loss was immediate despite antirejection treatment, 1 secondary to nonresolving rejection at 7 months and the third due to recurrent rejection 15 months posttransplantation. Additionally, biopsies detected vascular (venous thrombosis) and overimmunosuppression (cytomegalovirus infection) complications. CONCLUSIONS: Protocol graft duodenal biopsies detect complications after whole-organ pancreas transplantation, are useful in guiding therapy, and carry potential for improving outcome.

Ex vivo resection and intestinal autotransplantation for a large mesenteric desmoid tumor secondary to familial adenomatous polyposis: A case report and literature review.

RATIONALE: The mesenteric desmoid tumor requires special attention and the most demanding treatment. PATIENT CONCERNS: Here we present a rare case of a large mesenteric desmoid tumor secondary to familial adenomatous polyposis (FAP) in a 34-year-old man accepted the ex vivo resection, and intestinal autotransplantation. DIAGNOSES: A 34-year-old man was referred to our department with a 6-year history of intermittent hematochezia without any other discomfort after undergoing partial colectomy in February 2013, and 5 endoscopic mucosal resections of colon polyps between May 2012 and July 2015 due to pathological diagnosis of FAP. A computed tomography scan showed a huge abdominal mass with indistinct boundary at the root of the mesentery. The adjacent organs were pushed and most of the superior mesenteric artery branches were infiltrated. INTERVENTIONS: An en bloc resection (R0 resection), and an ex vivo resection followed by intestinal autotransplantation was performed. OUTCOMES: The patient was discharged from the hospital on the 25th day after the operation, and was regularly followed up after surgery with abdominal ultrasonography and laboratory-biochemical tests every month, and serial CT scans every 3 months which showed no evidence of tumor recurrence, thrombus, intestinal obstruction or abdominal infection so far. LESSONS: An ex vivo resection and intestinal autotransplantation appear feasible for cases with pathological lesions involving the vessels at the root of mesentry, and represents an attractive alternative for the management of mesenteric desmoid tumors.

Pancreas transplant rejection episodes are not revealed by biopsies of the donor duodenum in a prospective study with paired biopsies.

The surgical technique with duodeno-duodenal enteroanastomosis of pancreas transplants allows for representative endoscopic ultrasound-guided needle biopsies of the donor duodenum and the pancreas graft. We assessed whether histological findings in transplanted donor duodenal biopsies can indicate rejection in the transplanted pancreas. Since September 2012, a duodeno-duodenal enteroanastomosis has been the default technique for pancreas transplantations at our center. In 67 recipients we prospectively examined 113 endoscopic ultrasound-guided procedures with representative biopsies from the duodenum grafts and the pancreas grafts (97 per protocol and 16 on indication). All graft biopsies were evaluated according to established rejection criteria. A total of 22 biopsy-proven pancreas rejections were detected, with 2 matching duodenal biopsies showing rejection. This gives a sensitivity of 9% for detection of a pancreas rejection by duodenal biopsies. The other matching duodenal biopsies were either normal (n = 13) or indeterminate (n = 7). Rejection of the donor duodenum was found in only 6/113 biopsies, with 2 concurrent pancreas rejections. In conclusion, the donor duodenum is not a useful reporter organ for rejection in the pancreas graft.

Excessively Long Duodenum of the Pancreatic Graft Segment as a Rare Cause of Hyperammonemia After Simultaneous Pancreas-Kidney Transplant.

Simultaneous pancreas-kidney transplant is currently standard therapy to achieve long-term insulin-free euglycemia in patients with type 1 diabetes mellitus and concomitant end-stage kidney failure. A patient with symptoms of encephalopathy caused by hyperammonemia and with new-onset iron deficiency anemia was admitted to our institution 20 months after a simultaneous pancreas-kidney transplant. Detailed screening did not reveal any specific cause for the hyperammonemia, and despite standard treatment, hyperammonemia did not resolve. An abdominal computed tomographic scan was performed, which showed a distended duodenal segment of the pancreas graft. This was confirmed during exploratory laparotomy when the anastomosis between duodenum and ileum was dismantled and found not to be stenotic. The excessively long stumps of the duodenum were then dissected and shortened, and a new anastomosis between graft-duodenum and recipient-ileum was created. The operation was followed by an uncomplicated postoperative course in which the serum ammonia normalized on the first postoperative day and remained normal afterwards. An excessively long segment of the duodenum of the pancreatic graft may lead to encephalopathy with hyperammonemia after a simultaneous pancreas-kidney transplant. This emphasizes the need for meticulous preparation of the graft to avoid this complication.

Transcriptional and functional profiling defines human small intestinal macrophage subsets.

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.

Duodenal graft complications requiring duodenectomy after pancreas and pancreas-kidney transplantation.

Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow-up period of 126 months (range 23-198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin-independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n = 10, 71.5%) and refractory duodenal graft bleeding (n = 4, 28.5%). In patients with duodenal graft bleeding, a total duodenectomy was performed. In patients with duodenal graft perforation, preservation of a duodenal segment was possible in five patients but completion duodenectomy was necessary in one patient. After total duodenectomy, immediate enteric duct drainage was feasible in seven patients. In two patients, a pancreaticocutaneous fistula was created that was subsequently converted to enteric drainage in one patient. In the other patient, enteric fistulization occurred as a consequence of silent pressure perforation of the draining catheter on the ascending colon. After a mean follow-up period of 52 months (21-125), all patients were alive, well, and insulin-independent. An aggressive and timely surgical approach may permit graft rescue in patients with severe duodenal graft complications occurring after pancreas transplantation. Generalization of these results remains to be established.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Pancreas Transplantation After Liver Transplantation: A Case Report.

Our aim was to describe the clinical indications, surgical technique, and clinical outcomes of a pancreas transplantation, performed 4 years after liver transplantation, as treatment for new-onset, uncontrolled diabetes mellitus in a 53-year-old man. Liver transplantation was performed for end-stage liver disease secondary to hepatitis B virus infection and hepatocellular carcinoma. The patient had no history of diabetes prior to the liver transplantation. The decision to proceed with a pancreas transplantation was made when the patient's blood sugar levels could not be normalized despite insulin doses >100 IU/d. A modified cadaveric transplantation technique was used, with the recipient's inferior vena cava dissected for anastomosis with the portal vein of the graft, using a diamond-shaped patch procedure. Moreover, the right common iliac artery was anastomosed with a Y-graft in the pancreas graft, and the duodenum remnant of the graft was anastomosed to the recipient's duodenum using a side-to-side procedure. The 6-month postoperative follow-up included repeated endoscopic biopsy of the graft duodenum, with no evidence of thrombosis or rejection of the graft, with glucose level within normal limits without requirement for diabetic drugs. To our knowledge, this is the first reported case of pancreas transplantation after liver transplantation.

Modified Multivisceral Transplant After Acute Abdominal Trauma.

A 50-year-old man sustained blunt abdominal trauma in a motor vehicle accident. He underwent exploratory laparotomy on the day of trauma, and severe bleeding from the base of the small bowel mesentery was controlled by mass ligation and through-and-through suturing. After transfer to our center, repeat exploratory laparotomy showed ischemic small intestine, ischemic right colon, and severe pancreatic trauma. The severely injured organs were excised including the entire small bowel, pancreas, spleen, stomach, and right hemicolon. The next day, a modified multivisceral transplant was performed including stomach, pancreaticoduodenal complex, and small bowel transplant. Postoperative complications included an intra-abdominal collection that was drained percutaneously with ultrasonographic guidance and severe rejection that was treated with anti-thymocyte globulin. In summary, for select patients who have severe abdominal trauma may be treated with acute multivisceral transplant.

Intercellular adhesion molecular-1, Fas, and Fas ligand as diagnostic biomarkers for acute allograft rejection of pancreaticoduodenal transplantation in pigs.

BACKGROUND: The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. METHODS: Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. RESULTS: On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. CONCLUSION: ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.

[The combined transplantation of the pancreatoduodenal complex and kidney].

Patients with diabetic nephropathy comprise up to 30% of dialisis population. The treatment optimum for these patients remains the transplantation of pancreas and kidney. There were no successful attempts in Russia so long ago as the end of the previous century. The issue analyses the experience of the SCS (where the first successful transplantation of kidney-pancreas complex was conducted) and other Russian institutes, where the problem is elaborated. Flaws and advantages of the used operative methods of pancreas and Β-cells transplantation; early and long-term results are thoroughly discussed.

Immunological monitoring after pancreas transplantation.

PURPOSE OF REVIEW: After switching from bladder to enteric drainage, pancreas graft monitoring, particularly after solitary transplantation, has become an important issue. The aim of this work was to systematically review the relevant literature with regard to various biomarkers, imaging techniques, and pathologic evaluation of allograft tissue. RECENT FINDINGS: More recent studies including graft histology demonstrate the low specificity of pancreatic enzymes as a marker of acute rejection. On the other hand, most blood and serum markers are indicative of an activated immune status rather than rejection. Interestingly, the concomitantly transplanted kidney from the same donor does not seem to be a reliable surrogate marker. Although computed tomography or ultrasound-guided percutaneous biopsies of the pancreas are performed more frequently at present, the complication rate is still as high as 11%. In contrast, cystoscopic and enteroscopic biopsies of the duodenal part of the graft are associated with almost no complications. The few clinical studies dealing with the duodenum as surrogate marker for the pancreas report a high correlation between duodenum mucosal and pancreas parenchymal histology. SUMMARY: Pancreatic graft parenchymal biopsy remains the gold standard in diagnosing pancreatic rejection, as clinical parameters, pancreatic enzymes, noninvasive biomarkers, and surrogate renal biopsies are not reliable tools. Endoscopically obtained duodenal cuff biopsies are a less invasive alternative to percutaneous biopsies.

Intestinal and multivisceral transplantation in patients with chronic intestinal failure.

BACKGROUND: Patients with chronic intestinal failure are treated primarily with parenteral nutrition, often for many years. If serious complications arise for intravenous nutritional therapy, it is possible to perform intestinal or multi-organ transplantation in selected patients. We have established a collaboration with Professor Michael Olausson at Sahlgrenska University Hospital in Gothenburg and Professor Andreas Tzakis at the Jackson Memorial Hospital in Miami, USA, to provide an option for Norwegian patients with chronic intestinal failure. MATERIAL AND METHOD: Retrospective long-term study of seven patients (five in Gothenburg and two in Miami) with chronic intestinal failure who underwent intestinal or multi-organ transplantation (ventricle, duodenum, pancreas and small intestine) in the period 2001-2009. At the same time, liver and kidney transplantations were performed on six and two patients, respectively. RESULTS: Four of seven patients are alive and have a good quality of life 24-120 months after the transplantation. The graft function is satisfactory, so that the patients' food intake is mainly oral. Three patients died following a serious infection one, ten and 24 months, respectively, after transplantation took place. INTERPRETATION: Intestinal and multi-organ transplantation is a demanding and expensive treatment. Life-long multi-disciplinary follow-up of the patients is necessary after the transplantation in order to ensure early diagnosis of rejection and infections. Collaboration with international centres has given Norwegian patients with chronic intestinal failure an option of transplantation with satisfactory long-term results.