[Spontaneous expulsion of a mesenchymal colonic tumor via the rectum]. / Spontanabgang eines mesenchymalen Kolontumors per vias naturales.

A 61-year-old male patient underwent a colonoscopy for cramp-like upper abdominal pain of 3 weeks duration. An endoscopically irresectable ulcerated mass was seen in the transverse colon. The patient spontaneously excreted in the feces a tumor node measuring 4.1â€¯× 3.5â€¯× 2.8 cm with the histological features of a submucosal lipoma 4 days after the colonoscopy. A benign lipoma confined to the submucosa was operatively confirmed. It is extremely rare for a tumor node to be shed in feces. If the benign nature of the entire lesion is doubtful, standard oncological procedures are advocated.

[Day Surgery for Endoscopic Inguinal Hernia Repair]. / Minimalinvasive Leistenhernienchirurgie ­ TEP ambulant.

BACKGROUND: Whereas international guidelines recommend day surgery for endoscopic inguinal hernia repair, this approach is still controversial in Germany. In the light of international guidelines and at the request of patients, we have established total extraperitoneal patch plastic (TEP) surgery in the outpatient setting in our hospital. METHODS: A retrospective analysis of all unilateral TEP procedures carried out between January 2013 and December 2015 in our outpatient surgery, focused on postoperative complications, conversion to admission and rate of recurrence. Patient satisfaction with the outpatient setting was evaluated by telephone interview. RESULTS: In the 3 year period analysed, 164 patients were admitted for day surgery. Outpatient surgery was carried out in 152 patients, whereas 12 patients had to be admitted overnight due to circulatory disturbance, pain or bleeding. A total of 102 patients could be questioned for follow-up. Hematoma developed in 9 patients, and recurrence of hernia in 3 patients. Infections or seromas were not described or detected. 88 patients were very satisfied with the outpatient procedure, and 82 patients would clearly prefer day surgery again. CONCLUSIONS: Unilateral endoscopic hernia repair is safe and can be performed in the outpatient setting without increased risk. Satisfaction and acceptance by the patients is high. There is a dramatic difference between day surgery and inpatient procedure in the costs for hernia repair and this is one of the major reasons why outpatient endoscopic hernia repair is still rare in Germany.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study.

BACKGROUND: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. METHODS: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. RESULTS: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. CONCLUSIONS: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.

Celiacobihepatic venous bypass for liver revascularization in a patient with intrahepatic contained rupture of a common hepatic artery aneurysm.

Visceral artery aneurysms are rare, often incidental findings due to unspecific or no symptoms. We report a unique case of a 54-year-old patient with a contained rupture of a common hepatic artery aneurysm, without panarteritis nodosa or immunoglobulin G4 association, into the right liver hilum, that led to shock, cholestasis, and liver function impairment. Aneurysm resection and cholecystectomy, followed by revascularization with a great saphenous vein celiacobihepatic bypass and Roux-en-Y hepaticojejunostomy were performed. The patient was discharged 13 days later. Liver function was normal, and the revascularization patency was confirmed at follow-up at 3 and 12 months.

Complete pathological remission of locally advanced, unresectable pancreatic cancer (LAPC) after intensified neoadjuvant chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) has an extremely poor prognosis. Results of neoadjuvant (radio-)chemotherapy approaches aiming at achieving resectability are currently not satisfactory. CASE REPORT: We report the case of a 67-year-old woman with histologically confirmed pancreas carcinoma that was not resectable on first surgical exploration who achieved a well-documented complete pathological remission (pCR). The carcinoma became resectable after consecutive neoadjuvant treatment with nanoparticle albumin-bound (nab)-paclitaxel/gemcitabine and FOLFIRINOX chemotherapy regimens. CONCLUSION: This is the first reported LAPC case in which neoadjuvant chemotherapy alone has been shown to lead to demonstrated pCR. CA19-9 levels, but not imaging criteria, were useful for response prediction and timing of the Whipple's procedure. The findings in this case suggest possible conceptual changes in the treatment approach for LAPC, and indicate that the new effective chemotherapy regimens should be integrated into clinical trials for LAPC.

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial.

BACKGROUND: The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. METHODS: This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. FINDINGS: Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53­1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. INTERPRETATION: Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. FUNDING: German Federal Ministry of Education and Research.

Pancreatic duct anatomy in the corpus area: implications for closure and anastomotic technique in pancreas surgery.

PURPOSE: Pancreatic anastomosis and stump closure after partial pancreatectomy is the most critical step in pancreas surgery due to a high percentage of postoperative fistulas. Whether transverse cut side branches or the main pancreatic duct presents the source of this leak is still unknown. Thus, better understanding of the anatomy of the pancreatic duct system in the resection area could significantly improve the surgical technique and reduce complications. METHODS: We investigated the anatomy of the pancreatic duct in 25 human cadaveric pancreata with focus on the corpus area. Contrast agent was instilled into the pancreatic duct, and computed tomography was used to visualize the duct system in detail. RESULTS: In addition to the main and accessory pancreatic duct in the head, an additional accessory duct was observed within the pancreas corpus in 16% of the cases. Within the plane of the portal vein, fewer transversely cut side branches were observed as compared to the resection planes 2-4 cm beneath. The number of side branches was independent of the presence of pancreatic fibrosis. CONCLUSIONS: From anatomical point of view, the resection level at the porto-mesenteric axis appears to be ideal. However, the presence of an accessory main duct has to be taken into account for sufficient surgical supply.

Exhaustive differentiation of alloreactive CD8+ T cells: critical for determination of graft acceptance or rejection.

BACKGROUND: The precise role that CD8+ T cells play in the rejection and acceptance of different types of allograft is unclear and has been shown to vary between donor-recipient combinations. METHODS: The response of adoptively transferred CD8+ T cells reactive to the donor alloantigen H2Kb was examined after transplantation of H2Kb liver, kidney, and heart grafts in mice. RESULTS: After transfer of 6 x 10(6) alloreactive CD8+ T cells to T-cell depleted syngeneic mice spontaneous long-term acceptance of liver grafts was observed, whereas kidney and heart grafts were acutely rejected. Within 5 days of liver transplantation, we found that the entire H2Kb-reactive T-cell pool was stimulated to proliferate and differentiate into memory or effector cells that were detectable within lymphoid tissues as well as the liver graft itself. However, despite the generation of effector or memory T cells, liver allografts were accepted, which correlated with the exhaustion or deletion of such cells. In contrast, although activation and proliferation of H2Kb-reactive CD8+ T cells was observed after transplantation of heart or kidney grafts, unactivated, H2Kb-reactive CD8+ T cells were still present in the spleen even long term. Interestingly, differences in the effector function of liver and kidney graft infiltrating donor-reactive CD8+ T cells were not detected after adoptive transfer into immunodeficient mice, despite a reduction in Th1-type cytokines within liver grafts. CONCLUSIONS: The rapid and extensive initial activation and differentiation of donor-reactive CD8+ T cells that occurs after liver transplantation leads to clonal exhaustion or deletion of the alloreactive CD8+ T-cell repertoire resulting in spontaneous tolerance induction.

Investigation into the onset and progression of transplant arteriosclerosis in a mice aortic retransplantation model.

Long-term function of vascularized human organ grafts is often limited by transplant arteriosclerosis and can lead to graft failure. Here, we have analyzed the impact of an initial rejection episode on the later development of transplant arteriosclerosis. Following transplantation of allogeneic abdominal aortic segments in mice, aortic grafts were retransplanted into either immunodeficient or syngeneic recipients. Retransplantation of grafts from immunocompetent into immunodeficient mice as early as 2 days after the primary transplant resulted in intimal proliferation and obstruction of the graft lumen 30 days after the primary transplant. In contrast, retransplantation of the grafts into donor syngeneic B10 recipients within 7 days did not result in the development of transplant arteriosclerosis. These data suggest that the adaptive immune system can induce intimal proliferation by an initial lethal hit that is sustained by the innate response. However our data demonstrate that development of chronic rejection can be inhibited, in this case by retransplantation into a syngeneic host.

The Transcription Factor NFATc1 Supports the Rejection of Heterotopic Heart Allografts.

The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used worldwide in transplantation medicine to suppress graft rejection. Both CsA and FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune receptor-mediated activation of lymphocytes. Downstream targets of CN in lymphocytes are the nuclear factors of activated T cells (NFATs). We show here that the activity of NFATc1, the most prominent NFAT factor in activated lymphocytes supports the acute rejection of heterotopic heart allografts. While ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of inducible NFATc1/αA isoform led to rejection of heart allografts in recipient mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells was accompanied by a reduction in number and cytotoxicity of graft infiltrating cells. In CD8+ T cells, NFATc1 controls numerous intracellular signaling pathways that lead to the metabolic switch to aerobic glycolysis and the expression of numerous lymphokines, chemokines, and their receptors, including Cxcr3 that supports the rejection of allogeneic heart transplants. These findings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation.

The specific monocarboxylate transporter (MCT1) inhibitor, AR-C117977, a novel immunosuppressant, prolongs allograft survival in the mouse.

Novel small molecular weight compounds that act by inhibiting the monocarboxylate transporter (MCT1) receptor have been found to cause profound inhibition of T-cell responses to alloantigen in vitro. Here, we have investigated the ability of one compound in this series, AR-C117977, a potent MCT1 inhibitor, to prevent the acute and chronic rejection of vascularized and nonvascularized allografts in the mouse. Treatment with AR-C117977 or cyclosporin A (CsA) administered at a dose of 30 mg/kg subcutaneously for 15 days to adult CBA. Ca (H2(k)) mice, commencing either 3 days or 1 day before transplantation, was found to prolong the survival of an allogeneic (C57BL/10 H2(b); NZW H2(z); or BALB/c H2(d)) heart, aorta, or skin allograft significantly compared with treatment with vehicle alone (median survival time [MST] AR-C117977 treated 15; 19 and 18 days [skin] and 73; 66 and 67 days ([heart] vs. vehicle treated 8, 8 and 9 days [skin] and 9, 8, 10 days [heart] for B10, NZW and BALB grafts, respectively). AR-C117977 also inhibited the development of transplant arteriosclerosis in aortic allografts partially, but was unable to inhibit alloantibody production after transplantation. The specific MCT1 inhibitor AR-C117977 has potent immunosuppressive properties in vivo effectively preventing acute but not chronic allograft rejection in the mouse.

Ochratoxin A: 13-week oral toxicity and cell proliferation in male F344/n rats.

Ochratoxin A (OTA) is nephrotoxic and a potent renal carcinogen. Male rats are most susceptible to OTA toxicity, and chronic administration of OTA (70 and 210 microg/kg bw) for 2 years has been shown to induce high incidences of adenomas and carcinomas arising from the straight segment of the proximal tubule epithelium. In contrast, treatment with a lower dose of 21 microg/kg bw did not result in increased tumor rates, suggesting a nonlinear dose response for renal tumor formation by OTA. Since the mechanism of OTA carcinogenicity is still largely unknown, this study was conducted to investigate early functional and pathological effects of OTA and to determine if sustained stimulation of renal cell proliferation plays a role. Male F344/N rats were treated with OTA for up to 13 weeks under conditions of the National Toxicology Program (NTP) bioassay. Cell proliferation in the renal cortex and outer stripe of the outer medulla (OSOM) was determined using bromodeoxyuridine incorporation and immunohistochemistry. Histopathological examination showed renal alterations in mid- and high-dose-treated animals involving single-cell death and prominent nuclear enlargement within the straight proximal tubules. Treatment with OTA at doses of 70 and 210 microg/kg bw led to a marked dose- and time-dependent increase in renal cell proliferation, extending from the medullary rays into the OSOM. No effects were evident in kidneys of low-dose-treated animals or in the liver, which is not a target for OTA carcinogenicity. A no observed effect level in this study was established at 21 microg/kg bw, correlating with the dose in the NTP 2-year bioassay that did not produce renal tumors. The apparent correlation between enhanced cell turnover and tumor formation induced by OTA indicates that stimulation of cell proliferation may play an important role in OTA carcinogenicity and provides further evidence for an epigenetic, thresholded mechanism.

The impact of pulmonary metastasectomy in patients with previously resected colorectal cancer liver metastases.

BACKGROUND: 40-50% of patients with colorectal cancer (CRC) will develop liver metastases (CRLM) during the course of the disease. One third of these patients will additionally develop pulmonary metastases. METHODS: 137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection. RESULTS: 39% of all patients with liver resection due to CRLM developed additional lung metastases. 44% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2% vs. 28.0%; p = 0.001). Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5% vs. 63.5%; p = 0.015). Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0% vs 78.6%; p = 0.034). However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945). CONCLUSION: The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases.

CD25+CD4+ regulatory T cells develop in mice not only during spontaneous acceptance of liver allografts but also after acute allograft rejection.

BACKGROUND: Liver grafts transplanted across a major histocompatibility barrier are accepted spontaneously and induce donor specific tolerance in some species. Here, we investigated whether liver allograft acceptance is characterized by, and depends upon, the presence of donor reactive CD25CD4 regulatory T cells. METHODS: CD25 and CD25CD4 T cells, isolated from CBA. Ca (H2) recipients of C57BL/10 (B10; H2) liver and heart allografts 10 days after transplantation, were transferred into CBA. Rag1 mice to investigate their influence on skin allograft rejection mediated by CD45RBCD4 effector T Cells. RESULTS: Fully allogeneic B10 liver allografts were spontaneously accepted by naive CBA.Ca recipient mice, whereas B10 cardiac allografts were acutely rejected (mean survival time=7 days). Strikingly, however, CD25CD4 T cells isolated from both liver and cardiac allograft recipients were able to prevent skin allograft rejection in this adoptive transfer model. Interestingly, CD25CD4 T cells isolated from liver graft recipients also showed suppressive potency upon adoptive transfer. Furthermore, depletion of CD25CD4 T cells in primary liver allograft recipients did not prevent the acceptance of a secondary donor-specific skin graft. CONCLUSIONS: Our data provide evidence that the presence of CD25CD4 regulatory T cells is not a unique feature of allograft acceptance and is more likely the result of sustained exposure to donor alloantigens in vivo.

Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma.

PURPOSE: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). PATIENTS AND METHODS: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. RESULTS: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. CONCLUSION: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE.

The role of the graft in establishing tolerance.

At the present time, clinical solid organ transplantation continues to rely on the use of non-specific immunosuppressive protocols in order to prevent graft rejection. However, these regimens bring with them complications related both to the global immunosuppression that they cause, and to toxicity related to individual drugs. The pursuit of protocols that will allow graft-specific tolerance thus remains a major goal of research both in animal models and in clinical practice. There is evidence that the graft itself may play an active part in establishing and maintaining donor-specific hyporesponsiveness and ultimately tolerance; the aim of this review is to analyze this role in more detail.

Impact of hepatic rearterialization on reperfusion injury and outcome after mouse liver transplantation.

BACKGROUND: Nonarterialized mouse liver transplantation is a well-established model for immunologic studies on rejection and tolerance mechanisms. However, the importance of graft arterialization has-in contrast to rat liver transplantation-not been thoroughly examined in the mouse model. The aim of the current study was to investigate the impact of arterial reconstruction on long-term graft survival, histologic alterations, ischemic liver damage, and early immunologic activation pathways. METHODS AND RESULTS: All recipients of arterialized (n=6) and nonarterialized (n=8) syngeneic liver grafts survived indefinitely. There were no differences in their histologic architecture, including no evidence of bile duct proliferation, periductal fibrosis, or alterations in serum transaminases, in long-term survivors from either group. Twenty-four hours after syngeneic liver transplantation, aspartate aminotransferase and alanine aminotransferase levels were increased to an equivalent extent in both groups, in agreement with early reperfusion injury and solitary traumatic injuries as assessed histologically (n=3 per group). Visualized by immunohistochemistry, intercellular adhesion molecule-1 expression was increased on sinusoidal and hepatic vein endothelium at both 1 and 100 days after transplantation, in both arterialized and nonarterialized grafts. Messenger RNA for interleukin-1, interferon-gamma, and tumor necrosis factor-alpha were measured by real-time polymerase chain reaction 24 hr after transplantation. No significant changes in the expression of cytokine mRNA levels were observed. CONCLUSIONS: Arterialization of mouse liver grafts does not appear to have a major impact on survival rate or the degree of immunologic activation. Therefore, the value of arterial reconstruction in mouse liver transplantation for experimental investigations is negligible.

Syngeneic bone marrow transduced with a recombinant retroviral vector to express endoplasmic reticulum signal-sequence-deleted major histocompatibility complex class-I alloantigen can induce specific immunologic unresponsiveness in vivo.

BACKGROUND: Long-term survival of fully allogeneic cardiac grafts can be induced in mice through transduction of recipient bone marrow cells (BMCs) with a recombinant retroviral vector encoding a single full-length major histocompatibility complex (MHC) class I alloantigen. This study investigated whether cell surface expression of the transduced MHC antigen was necessary for the induction of specific unresponsiveness. METHOD The signal sequence for translocation into the endoplasmic reticulum was deleted from H-2K (SDELKb). Syngeneic BMCs from CBA.Ca (H2k) recipients were transduced with an MFG retroviral vector encoding either wild-type Kb or the mutant SDELKb and reinfused in conjunction with an anti-CD4 therapy. Four weeks later, the recipients underwent transplantation with a fully allogeneic C57BL/10 cardiac graft. Graft survival and the development of transplant arteriosclerosis were assessed. RESULTS: Expression of both the wild-type Kb or SDELK in recipient CBA mice before transplantation resulted in prolonged survival of C57BL/10 grafts. Grafts from recipients pretreated with SDELKb developed 48%+/-22% intimal proliferation compared with 61%+/-21% in grafts from recipients pretreated with wild-type Kb. However, this difference did not reach statistical significance. CONCLUSION Cell surface expression, and therefore direct recognition, of an MHC class I alloantigen is not required to induce long-term survival of fully allogeneic cardiac grafts after retroviral transduction of recipient BMCs.

Platelet-endothelial cell adhesion molecule-1 (CD31) expression on donor endothelial cells attenuates the development of transplant arteriosclerosis.

BACKGROUND: Platelet-endothelial cell adhesion molecule(PECAM)-1 (CD31) is expressed on the surface of endothelial cells, platelets, monocytes, neutrophils, and certain T-cell subsets. Treatment of endothelial cells with anti-PECAM-1 antibody inhibits leukocyte transmigration. This study was designed to test the hypothesis that, in transplantation, the absence of PECAM-1 expression on donor endothelial cells would reduce the number of leukocytes transmigrating into the allograft, thereby attenuating the development of transplant arteriosclerosis. METHODS: PECAM-1 and PECAM (C57BL/6/H2 ) abdominal aortic allografts were transplanted into BALB/c (H2 ) recipients; syngeneic grafts were used as controls. Aortic grafts were analyzed by performing morphometry, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction for the detection of intragraft cytokine mRNA production. RESULTS: Intimal proliferation was exacerbated in PECAM-1 grafts (57+/-5% for PECAM-1 vs. 36+/-6% for PECAM-1; <0.005; n=6). The absence of PECAM-1 expression on donor endothelial cells did not reduce the overall number of graft-infiltrating cells significantly but instead resulted in a significant increase in infiltration by macrophages (F4/80 cells), leading to significantly elevated intragraft mRNA expression of inducible nitric oxide synthase. During the development of transplant arteriosclerosis, PECAM-1 donor endothelial cells were replaced by recipient PECAM-1 endothelial cells, a process that occurred only in the allogeneic situation. Endothelial replacement commenced 14 days after transplantation and was complete by day 30. CONCLUSIONS: These data suggest that PECAM-1 expression by donor endothelial cells attenuates the development of transplant arteriosclerosis, possibly by affecting macrophage infiltration.