Combined intestine and kidney transplantation in a patient with encapsulating peritoneal sclerosis: case report.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis characterized by fibrosis and calcification of the intestine that, in severe cases, can progress to intestinal failure and total parenteral nutrition dependency. Medical and surgical interventions carry a poor prognosis in these patients. We describe a case of a 36-year-old female with end-stage kidney disease and severe EPS not amenable to surgical intervention who underwent a combined intestinal and kidney transplantation. At 3 years posttransplantation, the patient has normal intestinal and kidney function. This represents, to our knowledge, the first report of severe EPS and end-stage kidney disease treated with a combined transplant.

Graft outcomes of living donor renal transplantations in elderly recipients.

BACKGROUND: Despite the ever-lengthening renal transplant waiting lists, without more donors, living donors serve as a treatment option for patients on dialysis. In the past, patients of advanced age were not considered to be candidates for living donor renal transplantation. Therefore, this study sought to analyze whether older age affects the outcome of living donor renal transplantation. METHODS: A total of 527 primary living donor renal transplantations were performed between January 1, 1995 and January 1, 2006. The subjects were divided into 2 subgroups based on patient age at the time of transplantation. The elder group included all recipients at least 60 years vs the control group of younger patients. RESULTS: Significant differences were observed in readmission rate (elder group, 44%; young group, 31.33%; P = .031) and patient survival rate (P < .001). No significant difference was noted in graft survival rate (P = .201), acute rejection rate (elder group, 10.6%; young group, 13.3%; P = .7), serum creatinine level, or length of stay (elder group, 8.51 days; young group, 6.31 days; P = .083). CONCLUSIONS: Our results confirm that elder patients may benefit from living donor renal transplantation.

Beneficial outcomes of a steroid-free regimen with thymoglobulin induction in pancreas-kidney transplantation.

BACKGROUND: Steroid-free immunosuppressive regimens are becoming more common in pancreas transplantation, with persistent concerns regarding its safety and efficacy. METHODS: We performed a retrospective chart review of 87 pancreas transplant recipients-22 simultaneous pancreas-kidney transplants, 48 pancreas-after-kidney transplants, and 17 pancreas transplant alone-who underwent transplantation within the period of January 2000 to November 2006 and who received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. We compared one group on a steroid-free regimen (n = 25) with another on a steroid-based regimen (n = 62). RESULTS: At 6 months, there was no kidney graft loss and no significant difference between groups (steroid-free vs steroid-based groups) in patient survival (100% vs 96.8%), pancreas graft survival (96.0% vs 93.5%), acute rejection (4.0% vs 11.3%), hospitalization for any cause (60.0% vs 51.6%), infection requiring hospitalization (16.0% vs 32.3%), or incidence of BK viremia (0% vs 3.2%). CMV viremia occurred less in the steroid-free group (0% vs 17.7% in the steroid-based group, P = .024). The estimated glomerular filtration rate (eGFR) at 6 months was higher in the steroid-free group (74.8 vs 55.7 mL/min/1.73 m2 in the steroid-based group, P = .001), with fewer occurrences of a 25% decline in eGFR (33.3% among the steroid-free group vs 61.7% among steroid-based group, P = .019), despite similar average tacrolimus exposure (11.7 +/- 3.7 vs 12.2 +/- 2.7 ng/dL, P = .478). CONCLUSIONS: A steroid-free regimen with thymoglobulin induction followed by tacrolimus and mycophenolate mofetil for maintenance in pancreas transplantation was safe and effective in preventing rejection, with reduced incidence of CMV infection and better-preserved kidney function.

Distribution of interstitial cells of Cajal and nitrergic neurons in normal and diabetic human appendix.

The objective of this study was to determine the distribution of enteric nerves and interstitial cells of Cajal (ICC) in the normal human appendix and in type 1 diabetes. Appendixes were collected from patients with type 1 diabetes and from non-diabetic controls. Volumes of nerves and ICC were determined using 3-D reconstruction and neuronal nitric oxide synthase (nNOS) expressing neurons were counted. Enteric ganglia were found in the myenteric plexus region and within the longitudinal muscle. ICC were found throughout the muscle layers. In diabetes, c-Kit positive ICC volumes were significantly reduced as were nNOS expressing neurons. In conclusion, we describe the distribution of ICC and enteric nerves in health and in diabetes. The data also suggest that the human appendix, a readily available source of human tissue, may be useful model for the study of motility disorders.

Prevalence and clinical course of BK virus nephropathy in pancreas after kidney transplant patients.

The influence of BK virus nephropathy (BKVN) in pancreas after kidney (PAK) transplantation is unclear. A retrospective analysis of PAK transplants performed at our center was conducted to determine the impact of BKVN. Among 40 PAK transplants performed using sequential immunosuppression, four patients developed BKVN, as defined by a >20% rise in serum creatinine and BK viremia (BK plasma load >4 log copies/mL), at a median of 19 months following PAK. In all four patients, treatment of BKVN consisted of reduction in tacrolimus, cessation of mycophenolate mofetil, and introduction of leflunomide. With this approach, two patients experienced improvement or stabilization of renal function. The remaining two patients progressed to dialysis dependence despite treatment. Plasma BK load < or =5 log copies/mL was associated with graft preservation. Gender, age, delay between transplants, cumulative Thymoglobulin dose, and type of kidney donor were not associated with BK virus infection. Pancreas graft rejection or dysfunction was not observed with the above immunosuppression modification. Mean amylase and lipase > or =6 months following BKVN treatment remained normal. BKVN is an important cause of kidney allograft loss in PAK patients. Screening and early treatment of BKVN may enable preservation of kidney and pancreas grafts.

Donor kidney volume and outcomes following live donor kidney transplantation.

Pre-donation kidney volume and function may be crucial factors in determining graft outcomes in kidney transplant recipients. We measured living donor kidney volumes by 3D helical computed tomography scanning and glomerular filtration rate (GFR) by (125)I-iothalamate clearances in 119 donors, and correlated these values with graft function and incidence of acute rejection at 2 years post-transplantation. Kidney volume strongly correlated with GFR (Pearson r= 0.71, p < 0.001). Body size and male gender were independent correlates of larger kidney volumes, and body size and age were predictors of kidney function. The effects of transplanted kidney volume on graft outcome were studied in 104 donor-recipient pairs. A transplanted kidney volume greater than 120 cc/1.73 m(2) was independently associated with better estimated GFR at 2 years post-transplant when compared to recipients of lower transplanted kidney volumes (64 +/- 19 vs. 48 +/- 14 mL/min/1.73 m(2), p < 0.001). Moreover, recipients of lower volumes had a higher incidence of acute cellular rejection (16% vs. 3.7%, p = 0.046). In conclusion, kidney volume strongly correlates with function in living kidney donors and is an independent determinant of post-transplant graft outcome. The findings suggest that (1) transplantation of larger kidneys confers an outcome advantage and (2) larger kidneys should be preferred when selecting from otherwise similar living donors.

Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study.

OBJECTIVE: To compare portal and systemic venous drainage of pancreas transplants and demonstrate an immunologic and survival superiority of portal venous drainage. SUMMARY BACKGROUND DATA: Traditionally, solitary pancreas transplants have been performed using systemic venous and bladder drainage, but more recently, the advantages of enteric drainage have been well documented. Although physiologic benefits for portal venous drainage have been described, the impact of portal venous drainage, especially with solitary pancreas transplants, has yet to be determined. METHODS: Since August 1995, 280 pancreas transplants with enteric duct drainage were analyzed. One hundred and seventeen were simultaneous pancreas and kidney (SPK), 63 with systemic venous drainage (SV) and 54 with portal venous drainage (PV). The remainder were solitary transplants; 97 pancreas after kidney (PAK; 42 SV and 55 PV) and 66 transplants alone (PTA; 26 SV and 40 PV). Immunosuppressive therapy was equivalent for both groups. RESULTS: The groups were similar with respect to recipient characteristics and HLA matching. Thirty-six month graft survival for all transplants was 79% for PV and 65% for SV (P =.008). By category, SPK graft survival was 74% for PV and 76% for SV, PAK graft survival was 70% for PV and 56% for SV, and PTA graft survival was 84% for PV and 50% for SV. The rate of at least one rejection episode was also significantly higher in the SV group. At 36 months, for all pancreas transplants, the rejection rate was 21% for PV and 52% for SV (P <.0001). For SPK, rejection rates were 9% for PV and 45% for SV. For PAK, rejection rates were 16% for PV and 65% for SV, and for PTA 36% for PV and 51% for SV. The rejection rates for kidneys following SPK were also lower in the PV group (26% versus 43% for SV). Furthermore, the grades of rejection were milder in PV for all transplants (P =.017). By multivariate analysis, portal venous drainage was the only parameter that significantly affected rejection. CONCLUSION: Graft survival and rejection is superior for PV. These clinical findings are consistent with published reports of experimentally induced portal tolerance and strongly argue that PV drainage should be the procedure of choice for pancreas transplantation.

Pancreas transplantation: contemporary surgical techniques.

Since its inception more than 30 years ago, vascularized pancreas transplantation has undergone considerable progress. Given the unique complications associated with transplantation of this organ, modifications in surgical technique have been necessary to improve outcomes. As a result of these surgical advances and improvements in organ preservation and immunosuppression, contemporary graft survival rates approach 90% at 1 year. Despite this level of success, the technique of pancreas transplantation remains controversial. Future efforts to reduce morbidity and minimize immunosuppression will enable pancreas transplantation to remain an important therapeutic option for selected patients with type 1 diabetes mellitus.

Symmetry breakdown in ground state dissociation of HD+

Experimental studies of the dissociation of the electronic ground state of HD+ following ionization of HD by fast proton impact indicate that the H++D(1s) dissociation channel is more likely than the H(1s)+D+ dissociation channel by about 7%. This isotopic symmetry breakdown is due to the finite nuclear mass correction to the Born-Oppenheimer approximation which makes the 1ssigma state 3.7 meV lower than the 2psigma state at the dissociation limit. The measured fractions of the two dissociation channels are in agreement with coupled-channels calculations of 1ssigma to 2psigma transitions.

Contemporary management of renal cell carcinoma with coexistent renal artery disease: update of the Cleveland Clinic experience.

OBJECTIVES: To treat concurrent renal cell carcinoma (RCC) and renal artery disease (RAD), which pose an unusual and challenging management dilemma. METHODS: Before June 1998, 48 patients presented with localized RCC and RAD affecting all the functioning renal parenchyma. These patients were grouped into four distinct categories: group 1, a solitary kidney with RCC and RAD (n = 8); group 2, bilateral RCC and coexistent RAD (n = 9); group 3, unilateral RCC and contralateral RAD (n = 15); and group 4, unilateral RCC and bilateral RAD (n = 16). The most common cause of RAD was atherosclerosis (n = 40), followed by medial fibroplasia (n = 5), renal artery aneurysm (n = 2), and arteriovenous malformation (n = 1). RESULTS: All patients underwent complete surgical excision of RCC. A nephron-sparing operation was performed preferentially (44 patients), and bilateral renal cancer operations were staged. Eleven patients underwent surgical renal vascular reconstruction in conjunction with either partial (n = 9) or radical (n = 2) nephrectomy. In 2 patients, renal revascularization was accomplished by percutaneous transluminal angioplasty before tumor excision. No perioperative deaths occurred. Postoperatively, preservation of renal function was achieved in 47 patients; 1 patient required chronic dialysis. The overall and cancer-specific 5-year patient survival rates in this series were 66% and 90%, respectively. At a mean follow-up of 58 months, 28 patients were alive with no evidence of malignancy. Six patients died of metastatic RCC, and 14 died of unrelated causes with no evidence of malignancy. CONCLUSIONS: Nephron-sparing surgery combined with selective renal arterial reconstruction can yield gratifying results in this complex patient population.

The actin-based nanomachine at the leading edge of migrating cells.

Two fundamental parameters of the highly dynamic, ultrathin lamellipodia of migrating fibroblasts have been determined-its thickness in living cells (176 +/- 14 nm), by standing-wave fluorescence microscopy, and its F-actin density (1580 +/- 613 microm of F-actin/microm(3)), via image-based photometry. In combination with data from previous studies, we have computed the density of growing actin filament ends at the lamellipodium margin (241 +/- 100/microm) and the maximum force (1.86 +/- 0.83 nN/microm) and pressure (10.5 +/- 4.8 kPa) obtainable via actin assembly. We have used cell deformability measurements (. J. Cell Sci. 44:187-200;. Proc. Natl. Acad. Sci. USA. 79:5327-5331) and an estimate of the force required to stall the polymerization of a single filament (. Proc. Natl. Acad. Sci. USA. 78:5613-5617;. Biophys. J. 65:316-324) to argue that actin assembly alone could drive lamellipodial extension directly.

Atheroembolic renal disease: effect on morbidity and survival after revascularization for atherosclerotic renal artery stenosis.

PURPOSE: Atheroembolic renal disease is increasingly found in older patients with general atherosclerosis. We evaluated the impact of atheroembolic renal disease on morbidity and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 44 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis and concomitant intraoperative renal biopsy. Renal biopsy specimens were reviewed by a pathologist and evaluated for the presence or absence of atheroemboli, and the presence and severity of arteriolar nephrosclerosis. Postoperative patient data were reviewed to evaluate survival, and the incidence of renal and systemic morbid events. Patients were followed for 1 to 14.5 years (median 6.2) after surgical revascularization. RESULTS: Atheroembolic renal disease was identified in the intraoperative biopsy specimen in 16 patients (36%, group 1) and was absent in 28 (64%, group 2), termed groups 1 and 2. Atheroembolic renal disease correlated significantly with decreased patient survival. The 5-year survival in groups 1 and 2 was 54 and 85%, respectively (p = 0.011). Similarly the incidence of systemic atherosclerotic complications was significantly higher in group 1 than group 2 (86 versus 58%, p <0.05). In addition, renal or renovascular complications developed in more group 1 than group 2 patients (p = 0.07). There was no significant association between the presence or severity of arteriolar nephrosclerosis and postoperative survival or morbid events. CONCLUSIONS: Our results indicate that atheroembolic renal disease is associated with decreased survival and an increased incidence of atherosclerotic morbid events after surgical revascularization for atherosclerotic renal artery stenosis. This information may be useful for therapeutic decision making in patients with atherosclerotic renal artery stenosis.

Renal cryosurgery: experimental evaluation of treatment parameters.

OBJECTIVES: Cryosurgery represents a minimally invasive alternative for the management of small or equivocal lesions of the kidney. We evaluated the relationship between ultrasonographic appearance and intrarenal temperatures and the effect of renal artery occlusion on the efficacy of the freezing process in a canine model. METHODS: Ten animals were treated with intraparenchymal cryoablative therapy with (n = 5) or without (n = 5) renal artery occlusion using a rapid freeze technique. Intrarenal temperatures were measured 1.0 cm away from the cryoprobe at various times during the freezing process. The distance from the cryoprobe to the ice ball as monitored by ultrasonography was also determined. The contralateral kidney was removed to facilitate studies of renal function and all animals were killed on day 28 for autopsy and histopathologic examination. RESULTS: A target temperature of less than -20 degrees C was achieved 3.1 mm behind the ice ball in all animals tested. The ice ball stabilized at a radius of 16 mm with prolonged treatment, suggesting that multiple probes will be required to treat renal lesions greater than 2.5 cm in diameter. Renal artery occlusion did not significantly alter the freezing process and provided no practical advantage. Renal function remained stable (final serum creatinine level 1.5 mg/dL or less) in all but 1 animal in which an obstructive stricture of the ureteropelvic junction developed. Effective tissue ablation was confirmed at the treatment site in all instances. CONCLUSIONS: Renal cryoablative therapy is a nephron-sparing modality that can be delivered in a safe, efficacious, and reproducible manner. The treatment parameters defined in this study should allow for intelligent patient selection and rational administration of renal cryotherapy.

Efficacy of multimodality therapy in advanced renal cell carcinoma.

OBJECTIVES: The integration of systemic biologic response modifier (BRM) therapy and surgery to treat metastatic renal cell carcinoma (RCC) is an evolving approach. The purpose of this study was to evaluate the efficacy of this form of multimodality therapy in patients with metastatic RCC. METHODS: Between 1988 and 1996, 14 patients at our institution underwent initial BRM therapy followed by surgical resection of primary and metastatic RCC lesions. Patient records were reviewed to determine the response to BRM therapy, progression-free survival rate, and overall survival rate. The mean follow-up for the entire group was 43.5 months. RESULTS: After BRM therapy, 9 patients manifested an objective response and 5 patients had stable disease. All patients were then rendered disease-free by surgical excision of residual or recurrent metastatic lesions and the primary tumor. The cancer-specific survival rate at 3 years was 81.5%. Currently, 7 patients are alive and disease-free (mean follow-up 41.4 months), 3 patients are alive with recurrent disease (mean survival 48.3 months), 3 patients died of metastatic disease (mean survival 27.9 months), and 1 patient died of an unrelated cause 54.4 months after therapy. CONCLUSIONS: The results of this study suggest that adjunctive surgery after BRM therapy can extend the survival of selected patients with metastatic RCC. Aggressive surgical resection of stable or responding lesions after BRM therapy should be considered in the management of these patients.

Nephron-sparing surgery in a renal allograft.

A 48-year-old woman underwent renal transplantation of an organ from a living related donor in 1978. She experienced excellent graft function for 18 years. Recent evaluation for hypertension revealed two large solid masses involving the allograft. Nephron-sparing excision of two renal cell carcinomas was performed with preservation of renal function. Genitourinary malignancies in transplant recipients and partial nephrectomy in renal allografts are reviewed.

Comparative evaluation of cine-esophagogram with esophageal manometry in assessing esophageal motility in progressive systemic sclerosis.

BACKGROUND: Esophageal manometry is considered the gold standard in the diagnosis of esophageal motility disorders. Cine-esophagogram using barium is also a good investigation to screen patients for motor disorders of the esophagus. Comparison between these two investigations has not often been reported in patients with progressive systemic sclerosis (PSS). AIM: To determine relative merits of cine-esophagogram and esophageal manometry in detecting esophageal motor dysfunction in PSS patients. METHODS: Thirty-five patients with PSS irrespective of esophageal symptoms underwent esophageal manometry and cine-esophagogram, results and their were compared. RESULTS: Sensitivity and specificity of cine-esophagogram as compared to manometry were 96.1% (95% CI 88.7%-100%) and 55.5% (95% CI 23%-87.9%) respectively. Its positive predictive value was 86%. CONCLUSION: While esophageal manometry can identify esophageal motor disorder in PSS, cine-esophagogram can be resorted to in doubtful situations, for confirmation of diagnosis.

Nephron sparing surgery in patients with metastatic renal cell carcinoma.

PURPOSE: We evaluated the role of nephron sparing surgery in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: A total of 15 patients with metastatic renal cell carcinoma underwent nephron sparing surgery and treatment of metastases, including 4 who received adjunctive biological response modifier therapy. The 9 patients in group 1, who previously underwent contralateral nephrectomy for renal cell carcinoma and complete resection of all metastases, presented for treatment of localized renal cell carcinoma in the remaining kidney with no other evidence of disease. The 6 patients in group 2 presented with localized renal cell carcinoma requiring nephron sparing surgery and concomitant distant metastases. Mean postoperative followup was 30.4 months. RESULTS: Of 9 patients in group 1, 6 (66.7%) were disease-free at a mean of 31.3 months after nephron sparing surgery and 102.2 months after detection of metastatic disease, while 3 (33.3%) died at a mean of 53.3 and 73.0 months, respectively. Among the 6 patients in group 2, 4 (66.7%) were disease-free at a mean followup of 16.8 months and 2 (33.3%) died at a mean of 20.5 months postoperatively. Of the 4 patients who received adjunctive biological response modifier therapy 3 were disease-free at a mean of 12.7 months and 1 died 7 months after treatment. Satisfactory overall renal function was preserved in 14 of 15 patients after nephron sparing surgery. CONCLUSIONS: We conclude that nephron sparing surgery can provide effective treatment for select patients with renal cell carcinoma and previously or recently treated metastatic disease.

Mycophenolate mofetil immunosuppression in rat pancreas allotransplantation.

Prolongation of pancreas allograft survival has been difficult to achieve in rodent models despite use of immunosuppression regimens that successfully increase graft survival of other organs. The purpose of this study was to evaluate a new immunosuppressive agent, mycophenolate mofetil (MM), for its ability to prevent rejection in a rat pancreas transplant model. In addition, using congenic strains of rats, the efficacy of MM in rat pancreas transplantation was treated in the context of isolated class I or class II major histocompatibility (MHC) differences. MM in doses of 12.5 to 37 mg/kg significantly prolonged BUF to LEW heart transplant survival beyond a 14-day course of therapy thereby demonstrating its immunosuppressive efficacy. In similar pancreas transplant experiments, however, most grafts were rejected during the period of MM administration. Combination therapy with MM and cyclosporine did not extend pancreas survival beyond that achieved with MM alone (Mean Survival Time of 13.8 +/- 2.7 vs 11.7 +/- 1.6 days, respectively). Conversely, combined therapy with MM and antilymphocyte serum achieved a mean survival for BUF to LEW pancreas transplants of 52.3 +/- 24.8 days, which was significantly longer than that observed for either MM (11.7 +/- 1.6) or ALS (18.0 +/- 7.6) alone. MM therapy doubled pancreas allograft survival when used in the face of class I MHC disparity and compared to controls (19.5 +/- 1.0 vs 10.0 +/- 1.9 days) but did not prolong grafts that were disparate at only the class II locus (12.6 +/- 1.5 vs 12.0 +/- 1.2 days, respectively, for MM vs control). These data indicate that MM may not be an effective single agent immunosuppressive for pancreas transplantation except when MHC disparity is limited to the class I locus.