Douglas P. Slakey

Budd-Chiari Syndrome: Current Management Options

ObjectiveTo assess the outcomes of current treatment strategies for Budd-Chiari syndrome. Summary Background DataBudd-Chiari syndrome, occlusion or obstruction of hepatic venous outflow, is a disease traditionally managed by portal or mesenteric-systemic shunting. The development of other treatment options, such as catheter-directed thrombolysis, transjugular portosystemic shunting (TIPS), and liver transplantation, has expanded the therapeutic algorithm. MethodsThe authors reviewed the medical records of all patients diagnosed with Budd-Chiari syndrome at the Johns Hopkins Hospital during the past 20 years. ResultsA total of 54 patients were identified: 13 (24%) male patients and 41 (76%) female patients, ranging in age from 2 to 76 years (median 33 years). Twenty-one (39%) had polycythemia vera, 3 (5.6%) used estrogens, 11 (20%) had a myeloproliferative or coagulation disorder, and in 7 (13%) the cause remained unknown. Forty-three patients were treated with surgical shunting, 24 mesocaval and 19 mesoatrial. Actuarial survival rates at 1, 3, and 5 years after shunting were 83%, 78%, and 75%, respectively. Of 33 patients surviving more than 4 years, 28 (85%) had relief of clinical symptoms. Five patients required shunt revision and eight had radiologic procedures to maintain shunt patency. Primary and secondary shunt patency rates were 46% and 69% respectively for mesoatrial shunts and 70% and 85% respectively for mesocaval shunts. Clot lysis was successful as primary treatment in seven patients. TIPS was performed in three patients, one after a failed mesocaval shunt. During an average of 4 years of follow-up, these patients required multiple procedures to maintain TIPS patency. Six patients underwent liver transplantation. Of these, three had previous shunt procedures. Five of the transplant recipients are alive with follow-up of 2 to 9 years (median 6). ConclusionsBoth shunting and transplantation can result in a 5-year survival rate of at least 75%, and other treatment modalities may be appropriate for highly selected patients. Optimal management requires that treatment be directed by the predominant clinical symptom (liver failure or portal hypertension) and anatomical considerations and be tempered by careful assessment of surgical risk.

Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)–infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV‐coinfected patients and 2 control groups: 235 HCV‐monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3‐year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%‐71%] and 53% (95% CI = 40%‐64%) for the HCV/HIV patients and 79% (95% CI = 72%‐84%) and 74% (95% CI = 66%‐79%) for the HCV‐infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney‐liver transplantation (HR = 3.8), an anti‐HCV–positive donor (HR = 2.5), and a body mass index < 21 kg/m2 (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3‐year incidence of treated acute rejection was 1.6‐fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV‐coinfected LT patients versus HCV‐monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV‐coinfected recipients versus HCV‐infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes. Liver Transpl 18:716–726, 2012.

OPEN DONOR, LAPAROSCOPIC DONOR AND HAND ASSISTED LAPAROSCOPIC DONOR NEPHRECTOMY: A COMPARISON OF OUTCOMES

PURPOSE In experienced hands laparoscopic surgery has been shown to be safe for procuring kidneys for transplantation that function identically to open nephrectomy controls. While searching for a safer and easier approach to laparoscopic donor nephrectomy, hand assisted laparoscopic techniques have been added to the surgical armamentarium. We compare allograft function in patients with greater than 1-year followup who underwent open donor (historic series), classic laparoscopic and hand assisted laparoscopic nephrectomy. MATERIALS AND METHODS The charts of 48 patients who underwent open donor, laparoscopic donor or hand assisted laparoscopic nephrectomy were reviewed. Only patients with greater than 1-year followup and complete charts were included in our study. Of these patients 34 underwent consecutive laparoscopic live donor nephrectomy and 14 underwent open donor nephrectomy. Mean patient age plus or minus standard deviation (SD) was 36.5 +/- 8.4 years for donors and 29 +/- 17 for recipients at transplantation (range 13 months to 69 years). In the laparoscopic group 11 patients underwent the transperitoneal technique, and 23 underwent hand assisted laparoscopic nephrectomy. RESULTS Total operating time was significantly reduced with the hand assisted laparoscopic technique compared with classic laparoscopy, as was the time from skin incision to kidney removal and warm ischemic time. Average warm ischemic time plus or minus SD was 3.9 +/- 0.3 minutes for laparoscopic nephrectomy and 1.6 +/- 0.2 for hand assisted laparoscopy (p <0.05). Long-term followup of serum creatinine levels revealed no significant differences among the 3 groups. Comparison of those levels for recipients of open nephrectomy versus laparoscopic and hand assisted laparoscopic techniques revealed p values greater than 0.5. No blood transfusions were necessary. Complications included adrenal vein injury in 1 patient, small bowel obstruction in 2, abdominal hernia at the trocar site in 1 and deep venous thrombosis in 1. CONCLUSIONS Classic laparoscopic donor and hand assisted laparoscopic donor nephrectomies appear to be safe procedures for harvesting kidneys. The recipient graft function is similar in the laparoscopic and open surgery groups.

Laparoscopic living donor nephrectomy: advantages of the hand-assisted method.

INTRODUCTION The laparoscopic technique for living donor nephrectomy is a technically difficult procedure that has not yet gained widespread acceptance in the transplant community. The procedure may be more acceptable if alterations to the technique made it easier to perform and decreased operative times. METHODS In August 1998, we altered the laparoscopic procedure to include the use of a device allowing hand assistance. Subsequently, all living donor nephrectomies have been done using the hand-assisted method. In this article, the results of 10 cases performed using the original laparoscopic technique are compared with the results of 12 cases using the hand-assisted technique, and a brief description of modifications to the original technique is given. RESULTS No patients where turned down as living donors, and no contraindications to the pure or hand-assisted laparoscopic techniques where found. The hand-assisted technique significantly reduced the operative time (2.02+/-0.44 vs. 3.12+/-0.36 hr, P<0.05) and the warm ischemic time (1.23+/-0.54 vs. 3.91+/-0.53 min, P<0.05). The length of stay and recovery time to normal activities were not different between the pure laparoscopic and hand-assisted groups. CONCLUSION The advantages of the hand-assisted technique include the ability to use tactile sense to facilitate dissection, retraction, and exposure. In addition, the final stages of vascular stapling and kidney removal are more sure and rapid. The modifications of the laparoscopic technique presented here provide measurable and subjective improvements to laparoscopic living donor nephrectomy. The hand-assisted method of laparoscopic nephrectomy may make the operation available to more transplant centers.

Aging alters tissue resident mesenchymal stem cell properties

Tissue resident mesenchymal stem cells (MSCs) are known to participate in tissue regeneration that follows cell turnover, apoptosis, or necrosis. It has been long known that aging impedes an organisms repair/regeneration capabilities. In order to study the age associated changes, the molecular characteristics of adipose tissue derived MSCs (ASCs) from three age groups of healthy volunteers, i.e., young, middle aged, and aged were investigated. The number and multilineage differentiation potential of ASCs declined with age. Aging reduces the proliferative capacity along with increases in cellular senescence. A significant increase in quiescence of G2 and S phase was observed in ASCs from aged donors. The expression of genes related to senescence such as CHEK1 and cyclin-dependent kinase inhibitor p16(ink4a) was increased with age, however genes of apoptosis were downregulated. Further, an age-dependent abnormality in the expression of DNA break repair genes was observed. Global microRNA analysis revealed an abnormal expression of mir-27b, mir-106a, mir-199a, and let-7. In ubiquitously distributed adipose tissue (and ASCs), aging brings about important alterations, which might be critical for tissue regeneration and homeostasis. Our findings therefore provide a better understanding of the mechanism(s) involved in stem cell aging and regenerative potential, and this in turn may affect tissue repair that declines with aging.

Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells

The aim of the present study was to evaluate the potential of acellular dermal matrix as a carrier for delivery of stem cells to the site of soft tissue defect in a murine skin injury model and to determine the potential of stem cells delivered via such an approach to successfully engraft, survive and differentiate locally. We showed that adipose-derived stem cells delivered via this matrix survived after in vivo engraftment, spontaneously differentiated along vascular endothelial, fibroblastic and epidermal epithelial lineages and significantly improved wound healing. Furthermore, an organ survey for transplanted cells showed no evidence of a systemic distribution beyond the cutaneous wound site, indicating that the adipose-derived stem cell-dermal matrix construct provides a novel and effective method for anatomically focused cellular therapy. In conclusion, stem cell-seeded dermal matrix is an effective means for targeted in vivo cell delivery for enhanced soft tissue regeneration.

Robotic Transaxillary Thyroidectomy: An Examination of the First One Hundred Cases

BACKGROUND The influence of minimally invasive options has led to the application of new evolving techniques in thyroid surgery to eliminate visible neck scars. Here, we describe one authors experience with transaxillary robotic thyroidectomy and examine the effect of experience on determining the learning curve and improvements over time in operative performance. STUDY DESIGN With IRB approval, a prospective analysis of our surgical experience was performed. All patients underwent robotic transaxillary thyroidectomy by a single surgeon between September 2009 and June 2011. Principal outcomes measures included length of hospital stay, incidence of complications, and effect of obesity on outcomes. RESULTS One hundred consecutive operations were performed on 91 patients. Sixty-nine hemithyroidectomy, 22 total or near-total thyroidectomy, and 9 completion thyroidectomy procedures were performed. Of patients who underwent hemithyroidectomy, 21.7% were discharged within 4 hours; the remaining patients were discharged within 23 hours. Mean operative time for hemithyroidectomy was 108.1 ± 60.5 minutes, and for total or near-total thyroidectomy, mean operative time was 118.1 ± 51.3 minutes. Mean robot docking time was 9.1 ± 2.2 minutes for all cases. Obesity contributed to prolonged total operative time. Improvement in the length of time to perform components of the procedure was noted after 45 cases. Two cases required conversion to a cervical approach. There were no instances of permanent vocal cord palsy on postoperative laryngoscopy. CONCLUSIONS Here we report the largest experience of robotic gasless thyroid surgery in the United States. This novel technique provides excellent cosmetic results and can be performed as an outpatient procedure in selected group of patients. It is feasible and safe, however, has a lengthy learning curve.

Persistent High Glucose Concentrations Alter the Regenerative Potential of Mesenchymal Stem Cells

Type 2 diabetes is associated with numerous long-term complications. This study aims to investigate whether impaired function of tissue-resident multipotent cells play role in pathogenesis of allied complications. Adipose-tissue-derived mesenchymal stem cells (ASCs) derived from nondiabetic (nASCs) and diabetic (dASCs) donors were compared with regard to glucose metabolism, cell replication, apoptosis, and differentiation potential. The data evidenced that elevation of glucose reduces proliferative capacity of both dASCs and nASCs, but impacts dASCs more significantly. Incorporation of insulin enhanced cell replication especially in nASCs. dASCs show higher levels of cellular senescence and apoptosis than nASCs. Unlike nASCs, apoptosis is induced via intrinsic pathway in dASCs. Data also evidenced that high glucose concentrations cause prominent disparities in nASCs and dASCs in expression of genes involved in insulin resistance such as adiponectin and resistin. Some changes in gene expression were irreversible in dASCs when treated with insulin. Additionally, high glucose concentrations reduce osteogenic and chondrogenic potential of ASCs, but enhance adipogenic potential. These results indicate that in addition to involvement in insulin resistance, impaired function of mesenchymal stem cells that reside in adipose tissue as one of the major sources of adult stem cells might be responsible for complications related to diabetes type 2.

High body mass index and short- and long-term renal allograft survival in adults

Background. The effect of recipient obesity on kidney allograft survival remains enigmatic. The purpose of this study was to evaluate the effect of donor and recipient body mass index on graft survival. Methods. Retrospective study of 193 consecutive, adult renal transplants, with at least six months follow-up (mean 24±14.1 months). Patients were divided into two groups based upon body mass index (BMI), [weight (kg)/height (m2)]: normal (<30.0, n=137) and obese (≥30.0, n=56). Endpoints were graft loss, defined as either total loss of graft function (return to dialysis) or patient death with a functional graft. Unadjusted and adjusted multivariate analysis techniques, including Kaplan-Meier and Cox proportional hazards regression were used. Results. Individuals with a BMI ≥30 were not more likely to experience graft loss (O.R. 0.93, 95% C.I. 0.50, 1.72). Rates of acute rejection were not increased in obese recipients. While mortality was not increased in the BMI > 30 group, morbidity, especially surgical, had an increased incidence. The ratio of recipient to donor BMI did not influence graft survival. Conclusion. Obese recipients (BMI ≥30.0) were not at increased risk for graft failure. Additionally, matching donor and recipient BMIs would not appear to substantially improve transplant outcome. Obese recipients do have increased posttransplant morbidity and risk all the known health consequences associated with obesity. Careful evaluation and clinical management of obese patients allows for successful kidney transplantation with results equivalent to normal BMI patients.

Baseline glomerular size as a predictor of function in human renal transplantation.

BACKGROUND Nonimmune mechanisms have been implicated in chronic renal allograft injury. In experimental studies, a strong correlation exists between glomerular size and the degree of glomerular sclerosis that develops after subtotal nephrectomy. Therefore, we assessed the impact of glomerular maximal planar area (MPA) in baseline biopsy specimens of human renal allografts on later graft function. METHODS The MPA was measured, by point counting and by computer planimetry, in postperfusion biopsy specimens from 96 allograft kidneys from nonhypertensive donors that had functioned for at least 2 years. Clinical data were analyzed throughout a follow-up period averaging 7.46+/-2.46 years. RESULTS Both methods produced equivalent estimates of MPA. MPA proved to be a strong predictor of late renal allograft function, with a significant correlation (P = 0.02 to P < 0.01) between MPA at baseline and later serum creatinine level and creatinine clearance, beginning at 6 months after transplantation and persisting through follow-up. Creatinine level at discharge and occurrence of rejection were also independent predictors, whereas donor age, gender and race, cold ischemia time, cadaveric versus living donor, delay in initial function, and HLA mismatch did not predict clinical outcome. CONCLUSION Larger glomeruli at baseline, measured by a simple point-counting technique, provide an early predictor of risk for late allograft dysfunction and may identify a subpopulation of patients in whom treatment to prevent/ameliorate glomerular enlargement and/or hypertension may be efficacious.