Anorectal Transplantation: The First Long-term Success in a Canine Model.

OBJECTIVE: Anorectal transplantation is a challenging procedure but a promising option for patients with weakened or completely absent anorectal function. SUMMARY BACKGROUND DATA: We constructed a canine model of anorectal transplantation, evaluated the long-term outcomes, and controlled rejection and infection in allotransplantation. METHODS: In the pudendal nerve function study, 6 dogs were randomly divided into 2 groups, transection and anastomosis, and were compared with a control using anorectal manometry, electromyography, and histological examination. In the anorectal transplantation model, 4 dogs were assigned to 4 groups: autotransplant, allotransplant with immunosuppression, allotransplant without immunosuppression, and normal control. Long-term function was evaluated by defecography, videography, and histological examination. RESULTS: In the pudendal nerve function study, anorectal manometry indicated that the anastomosis group recovered partial function 6 months postoperatively. Microscopically, the pudendal nerve and the sphincter muscle regenerated in the anastomosis group. Anorectal transplantation was technically successful with a 3-stage operation: colostomy preparation, anorectal transplantation, and stoma closure. The dog who underwent allotransplantation and immunosuppression had 2 episodes of mild rejection, which were reversed with methylprednisolone and tacrolimus. The dog who underwent allotransplantation without immunosuppression had a severe acute rejection that resulted in graft necrosis. Successful dogs had full defecation control at the end of the study. CONCLUSIONS: We describe the critical role of the pudendal nerve in anorectal function and the first long-term success with anorectal transplantation in a canine model. This report is a proof-of-concept study for anorectal transplantation as a treatment for patients with an ostomy because of anorectal dysfunction.

Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation.

INTRODUCTION: Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR. METHODS: We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods. RESULTS: No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium. CONCLUSIONS: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the liver's relative resistance to this immune response.

Hepatic Artery Thrombosis in Liver Transplantation in Adult Recipients Using Pediatric Deceased Donors.

INTRODUCTION: Routinely, pediatric donor (PD) grafts are allocated to pediatric liver transplantation (LT) recipients; however, occasionally they can be allocated for adult recipients (ARs). Some authors reported decreased patient/graft survival and higher vascular complications, such as hepatic artery thrombosis (HAT), in LT in ARs using PDs. METHODS: It is a retrospective study enrolling 1202 ARs undergoing LT using whole liver grafts during the period of January 2002 to April 2019. The patients were categorized according to donor age in 2 groups: PDs and adult donors (ADs). The variables were collected from the database including the graft to recipient weight ratio (GWRW) and the incidence of HAT and graft primary nonfunction (PNF). RESULTS: The AD group had 1152 patients, and the PD group had 50 patients. PNF occurred in 68 (5.66%) patients, and the distribution between the 2 groups were similar: 65 (5.64%) in the AD group, and 3 (6%) in the PD group (P = .915). HAT was diagnosed in 30 (2.6%) patients in the AD group and in 6 (12%) patients in the PD group. HAT was significantly higher in the PD group (P = .001). In the PD group, the GWRWs among patients diagnosed with HAT were similar (P = .152). CONCLUSION: HAT is higher in PDs, although it is a viable alternative with satisfactory results. Serial Doppler in the first week and early introduction of platelet antiaggregants and/or anticoagulants may be beneficial, albeit it is not clear if it could reduce the incidence of HAT.

Gastric fundus submucosa as a site for islets transplantation: An experimental study.

BACKGROUND: Islets of Langerhans transplantation is a promising alternative for glycemic control in patients with type 1 diabetes. The graft site is a factor that has large impact on the functioning of this transplant, and the stomach appears to be a promising location. Our objective is to describe a new experimental model for the grafting of Islets of Langerhans in rat stomachs. METHODOLOGY: Islets of Langerhans were extracted from 45 isogenic male rats of the Lewis lineage and transplanted into 9 isogenic rats of the Wistar lineage; 5 in the gastric body submucosa, and 4 in the gastric fundus submucosa. Normoglycemia was defined as two successive measurements of <250 mg/dL. No immunosuppression was used. The two groups glycemia control improvement were compared with t-student test. RESULTS: The results obtained following the transplantation of the islets in 9 rats showed between 995 and 2310 islets transplanted (mean of 1367). The rats from the gastric submucosa group had a better glycemic level improvement, with a confidence equal to 83.94%. CONCLUSION: Islets graft into the gastric fundus submucosa is a viable model with potential for adequate glycemic control. This model gives potential for new perspectives and future studies in this area.

[Attitude and opinion of medical students about organ donation and transplantation]. / Conhecimento e opinião de estudantes de medicina sobre doação e transplante de órgãos.

UNLABELLED: We analyzed the opinion and understanding of medical students about organ donation and transplantation. METHODS: 347 students voluntarily completed a questionnaire with 17 queries concerning organ donation and transplantation. They were analyzed to identify general tendencies and divided into five groups, according to their year of study (first through sixth year), to assess differences among the years. Students of the fifth and sixth years were placed in the same group. Results were analyzed by the Chi-square test. RESULTS: The intention to become a post mortem or living donor was of 89% and 90% respectively; however, only 62% were aware of living donation risks. 70% of the 347 students admitted regular or little knowledge of the subject, 90.2% considered organ transplantation an important issue for a medical graduation program, 76.9% considered informed/expressed consent the best organ donation criterion and 64.3% of them chose severity of patient disease as the best allocation condition. As students progressed in their studies their understanding about transplantation improved. Students of the fourth, fifth and sixth year manifested a negative attitude about organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners. CONCLUSION: This data show the great interest and positive attitude of medical students toward organ donation and transplantation, despite the fact that most of them admitted having insufficient knowledge on the subject. A negative attitude by students of the fourth, fifth and sixth year on organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners was also observed.

A New Pedicled Internal Mammary Osteomyocutaneous Chimeric Flap (PIMOC) for Salvage Head and Neck Reconstruction: Anatomic Study and Clinical Application.

Well-vascularized composite tissue offers improved outcomes for complex head and neck reconstruction. Patients with vessel-depleted necks and failed reconstructions require alternative reconstructive options. We describe a pedicled internal mammary artery osteomyocutaneous chimeric flap (PIMOC) for salvage head and neck reconstruction. Bilateral dissections of 35 fresh cadavers were performed to study individual tissue components and vascular pedicles to develop the PIMOC technique. The flap was then utilized in a series of patients with vessel-depleted neck anatomy. The PIMOC was dissected bilaterally in all cadavers and there were no statistical differences in vascular pedicle caliber or length with regards to laterality or gender. Five patients subsequently underwent this procedure. The flaps included a vertical rectus abdominis myocutaneous component and a 6th or 7th rib with adjacent muscle and skin to restore bone defects, internal lining, and external coverage. All donor sites were closed primarily. There were no flap losses and all patients gained improvements in facial contour, speech and swallow. Although technically complex, the PIMOC is reproducible and provides a safe and reliable option for salvage head and neck reconstruction. The harvest of the 6th or 7th rib and rectus abdominis muscle renders an acceptable donor site.

Allogeneic anorectal transplantation in rats: technical considerations and preliminary results.

Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies.

A canine model of laparoscopic segmental liver resection.

Laparoscopic hepatectomy has been recently proposed for the treatment of liver tumors, however there is a lack of experimental models to study surgical technique and the metabolic reactions after this procedure. The dog is an important animal for research but the laparoscopic hepatectomy model is not well established in this animal. We describe the surgical laparoscopic technique of left liver segmentectomy in the dog and the preliminary results of this procedure. Female dogs weighting more then 15 kg were used. Four transversal abdominal incisions (two of 1 cm and two of 0.5 cm) were made for the introduction of the video camera and the other laparoscopic instruments. The liver was inspected and the left lobe was mobilized through incision of the left triangular hepatic ligament. The vascular pedicle corresponding to the left medial lobe (corresponding to segment II) was identified, dissected, and clamped, delimiting a correspondent ischemic area. The hepatic parenchyma was divided according to the previous delimitation with minimum bleeding. The segment of the liver was then removed through an enlarged abdominal incision. The incisions were closed by continuous suture. The mean time of the procedure was forty minutes. We observed normal clinical evolution without any sign of complications due to the hepatic resection, and normal augmentation of body weight on follow-up of more than 3 months. Left hepatectomy in the dog is a viable procedure and may serve for surgical training and development of research projects in this field.

Intraportal versus Systemic Pentoxifylline Infusion after Normothermic Liver Ischemia: Effects on Regional Blood Flow Redistribution and Hepatic Ischemia-Reperfusion Injury.

Pentoxifylline (PTX) has been shown to have beneficial effects on microcirculatory blood flow. In this study we evaluate the potential hemodynamic and metabolic benefits of PTX during hepatic ischemia. We also test the hypothesis that portal PTX infusion can minimize the I/R injury when compared to systemic infusion. Methods. Twenty-four dogs (18.1 ± 0.7 kg) were subjected to portal triad occlusion (PTO) for 45 min. The animals were assigned to 3 groups: CT (control, PTO, n = 8), PTX-syst (PTO + 25 mg/Kg of PTX IV, n = 8), and PTX-pv (PTO + 25 mg/Kg of PTX in the portal vein, n = 8). Animals were followed for 120 min. Systemic hemodynamics, gastrointestinal tract perfusion, oxygen-derived variables, and liver enzymes were evaluated throughout the experiment. Results. Animals treated with PTX presented significantly higher CO in the first hour after reperfusion, when compared to the CT (~3.7 vs. 2.1 L/min, P < 0.05). Alanine aminotransferase (ALT) was similar in the PTX groups two hours after reperfusion but significantly higher in the CT (227 vs. ~64 U/L, P < 0.05). Conclusion. PTX infusion was associated with hemodynamic benefits and was able to minimize liver injury during normothermic hepatic I/R. However, local PTX infusion was not associated with any significant advantage over systemic route.

Conhecimento e opinião de estudantes de medicina sobre doação e transplante de órgãos / Attitude and opinion of medical students about organ donation and transplantation

OBJETIVOS: Analisar o conhecimento e a opinião de estudantes de medicina sobre doação e transplante de órgãos. MÉTODOS: Trezentos e quarenta e sete estudantes responderam, voluntariamente, questionário com 17 perguntas sobre doação e transplante de órgãos. Eles foram avaliados globalmente, para verificar tendências gerais, e agrupados de acordo com o seu ano no curso médico (primeiro ao sexto), para avaliar diferenças entre os períodos. Alunos do quinto e sexto ano foram reunidos em um só grupo. Os resultados foram analisados pelo teste Qui quadrado. RESULTADOS: A intenção de ser doador post mortem foi de 89 por cento e intervivo de 90 por cento, contudo, apenas 62 por cento sabiam dos riscos da doação intervivo. Entre os 347 estudantes, 70 por cento admitiram conhecimento regular, ruim ou péssimo do assunto, 90,2 por cento consideraram importante o tema transplante para a graduação médica, 76,9 por cento consideraram o consentimento informado/expresso como o melhor critério de doação e 64,3 por cento optaram pela gravidade da doença do paciente como melhor forma de alocação. O entendimento sobre transplante aumentou conforme o avanço no curso de graduação. Estudantes do quarto, quinto e sexto ano adotaram atitude negativa, em comparação aos dos anos iniciais, quanto à doação de órgãos para pacientes alcoólatras, não doadores, usuários de drogas ilícitas, estrangeiros e criminosos. CONCLUSÃO: Este trabalho demonstrou grande interesse e atitude positiva dos estudantes de medicina sobre doação e transplante de órgãos, embora a maioria tenha declarado conhecimento deficiente sobre o tema. Observamos também atitude negativa dos estudantes do quarto, quinto e sexto ano médico em relação à doação para alcoólatras, não doadores, usuários de drogas ilícitas, estrangeiros e criminosos.

We analyzed the opinion and understanding of medical students about organ donation and transplantation. METHODS: 347 students voluntarily completed a questionnaire with 17 queries concerning organ donation and transplantation. They were analyzed to identify general tendencies and divided into five groups, according to their year of study (first through sixth year), to assess differences among the years. Students of the fifth and sixth years were placed in the same group. RESULTS:were analyzed by the Chi-square test. RESULTS: The intention to become a post mortem or living donor was of 89 percent and 90 percent respectively; however, only 62 percent were aware of living donation risks. 70 percent of the 347 students admitted regular or little knowledge of the subject, 90.2 percent considered organ transplantation an important issue for a medical graduation program, 76.9 percent considered informed/expressed consent the best organ donation criterion and 64.3 percent of them chose severity of patient disease as the best allocation condition. As students progressed in their studies their understanding about transplantation improved. Students of the fourth, fifth and sixth year manifested a negative attitude about organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners. CONCLUSION: This data show the great interest and positive attitude of medical students toward organ donation and transplantation, despite the fact that most of them admitted having insufficient knowledge on the subject. A negative attitude by students of the fourth, fifth and sixth year on organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners was also observed.