Surgery Publications

Surgical Preferences of Patients at Risk of Hip Fractures: Hemiarthroplasty versus Total Hip Arthroplasty

Noor Alolabi et al. — Thu, 23 Feb 2012 18:28:14 PST

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients over 60 years is controversial. While much research has focused on the impact of total hip arthroplasty (THA) and hemiarthroplasty (HA) on surgical outcomes, little is known about patient preferences for either alternative. The purpose of this study was to elicit surgical preferences of patients at risk of sustaining hip fracture using a novel decision board.

METHODS: We developed a decision board for the surgical management of displaced femoral neck fractures presenting risks and outcomes of HA and THA. The decision board was presented to 81 elderly patients at risk for developing femoral neck fractures identified from an osteoporosis clinic. The participants were faced with the scenario of sustaining a displaced femoral neck fracture and were asked to state their treatment option preference and rationale for operative procedure.

RESULTS: Eighty-five percent (85%) of participants were between the age of 60 and 80 years; 89% were female; 88% were Caucasian; and 49% had some post-secondary education. Ninety-three percent (93%; 95% confidence interval [CI], 87-99%) of participants chose THA as their preferred operative choice. Participants identified several factors important to their decision, including the perception of greater walking distance (63%), less residual pain (29%), less reoperative risk (28%) and lower mortality risk (20%) with THA. Participants who preferred HA (7%; 95% CI, 1-13%) did so for perceived less invasiveness (50%), lower dislocation risk (33%), lower infection risk (33%), and shorter operative time (17%).

CONCLUSION: The overwhelming majority of patients preferred THA to HA for the treatment of a displaced femoral neck fracture when confronted with risks and outcomes of both procedures on a decision board.

A Comparison of Two Headless Compression Screws for Operative Treatment of Scaphoid Fractures

Ruby Grewal et al. — Tue, 30 Aug 2011 16:14:43 PDT

PURPOSE: The purpose of this study was to compare the interfragmentary compression force across a simulated scaphoid fracture by two commonly used compression screw systems; the Acutrak 2 Standard and the 3.0 mm Synthes headless compression screw.

METHODS: Sixteen (8 pairs; 6 female, 2 male) cadaver scaphoids were randomly assigned to receive either the Acutrak 2 or Synthes screw with the contralateral scaphoid designated to receive the opposite. Guide wires were inserted under fluoroscopic control. Following transverse osteotomy, the distal and proximal fragments were placed on either side of a custom load cell, to measure interfragmentary compression. Screws were placed under fluoroscopic control using the manufacturer's recommended surgical technique. Compressive forces were measured during screw insertion. Recording continued for an additional 60s in order to measure any loss of compression after installation was complete. The peak and final interfragmentary compression were recorded and paired t-tests performed.

RESULTS: The mean peak compression generated by the Acutrak 2 Standard was greater than that produced by the Synthes compression screw (103.9 ± 33.2 N vs. 88.7 ± 38.6 N respectively, p = 0.13). The mean final interfragmentary compression generated by the Acutrak 2 screw (68.6 ± 36.4 N) was significantly greater (p = 0.04) than the Synthes screw (37.2 ± 26.8 N). Specimens typically reached a steady state of compression by 120-150s after final tightening.

CONCLUSION: Peak interfragmentary compression observed during screw installation was similar for both screw systems. However, the mean interfragmentary compression generated by the Acutrak 2 Standard was significantly greater. Our study demonstrates that the Synthes headless compression screw experienced a greater loss of interfragmentary compressive force from the time of installation to the final steady state compression level. The higher post-installation compression of the Acutrak 2 Standard may be attributable to the greater number of threads throughout the entire length of the screw. The clinical significance of these results, are, at this point uncertain. We do demonstrate that a fully threaded design offers a more reliable compression that may translate to more predictable bony union.

Prevention of Hyperglycemia-induced Myocardial Apoptosis by Gene Silencing of Toll-like Receptor-4

Yuwei Zhang et al. — Mon, 14 Mar 2011 11:27:39 PDT

BACKGROUND: Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice.

METHODS: Diabetes was induced in C57/BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 μg of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay.

RESULTS: After 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast, treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically, caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA, but not in mice treated with control siRNA. Additionally, gene silencing of TLR4 resulted in suppression of apoptotic cascades, such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species (ROS) production and NADPH oxidase activity, suggesting suppression of hyperglycemia-induced apoptosis by TLR4 is associated with attenuation of oxidative stress to the cardiomyocytes.

CONCLUSIONS: In summary, we present novel evidence that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

Molecular Mechanisms and Treatment Strategies for Dupuytren's Disease

David B. O'Gorman et al. — Mon, 06 Dec 2010 19:30:07 PST

Dupuytren's disease (DD) is a common disease of the hand and is characterized by thickening of the palmar fascia and formation of tight collagenous disease cords. At present, the disease is incurable and the molecular pathophysiology of DD is unknown. Surgery remains the most commonly used treatment for DD, but this requires extensive postoperative therapy and is associated with high rates of recurrence. Over the past decades, more indepth exploration of the molecular basis of DD has raised the hopes of developing new treatment modalities. This paper reviews the clinical presentation and molecular pathophysiology of this disease, as well as current and emerging treatment. It also explores the implications of new findings in the laboratory for future treatment.

Ventilation/Perfusion after Liver Transplantation in Decompensated Cirrhosis

Vivian McAlister et al. — Thu, 23 Sep 2010 00:52:27 PDT

Intracerebral Co-transplantation of Liposomal Tacrolimus Improves Xenograft Survival and Reduces Graft Rejection in the Hemiparkinsonian Rat

A. Y. Alemdar et al. — Thu, 23 Sep 2010 00:52:26 PDT

Immunosuppression remains a key issue in neural transplantation. Systemic administration of cyclosporin-A is currently widely used but has many severe adverse side effects. Newer immunosuppressive agents, such as tacrolimus (TAC) and rapamycin (RAPA), have been investigated for their neuroprotective properties on dopaminergic neurons. These drugs have been formulated into liposomal preparations [liposomal tacrolimus (LTAC) and liposomal rapamycin (LRAPA)] which retain these neuroprotective properties. Due to the slower release of the drugs from the liposomes, we hypothesized that co-transplantation of either LTAC or LRAPA within a xenogeneic cell suspension would increase cell survival and decrease graft rejection in the hemiparkinsonian rat, and that a combination of the two drugs may have a synergistic effect. 6-hydroxydopamine-lesioned rats were divided to four groups which received intra-striatal transplants of the following: 1) a cell suspension containing 400,000 fetal mouse ventral mesencephalic cells; 2) the cell suspension containing 0.63 microM LRAPA; 3) the cell suspension containing a dose of 2.0 microM LTAC; 4) the cell suspension containing 2.0 microM LTAC and 0.63 microM LRAPA. Functional recovery was assessed by amphetamine-induced rotational behavior. Animals were killed at 4 days or 6 weeks post-transplantation, and immunohistochemistry was performed to look at the expression of tyrosine hydroxylase and major histocompatibility complex classes I and II. Only the group receiving LTAC had a decrease in rotational behavior. This observation correlated well with significantly more surviving tyrosine hydroxylase immunoreactive cells compared with the other groups and significantly lower levels of immunorejection as assessed by major histocompatibility complex class I and II staining. This study has shown the feasibility of using local immunosuppression in xenotransplantation. These findings may be useful in optimizing immunosuppression in experimental neural transplantation in the laboratory and its translation into the clinical setting.

Intestinal Allograft Rejection

Vivian C. McAlister et al. — Thu, 23 Sep 2010 00:40:02 PDT

Clinical Small Bowel Transplantation

Vivian C. McAlister et al. — Thu, 23 Sep 2010 00:30:41 PDT

Posttransplant Lymphoproliferative Disorders in Liver Recipients Treated with OKT3 or ALG Induction Immunosuppression

Vivian McAlister et al. — Tue, 21 Sep 2010 00:17:33 PDT

Immunosuppressive Requirements for Small Bowel/Liver Transplantation

Vivian McAlister et al. — Tue, 21 Sep 2010 00:17:32 PDT

Right Phrenic Nerve Injury in Orthotopic Liver Transplantation

Vivian C. McAlister et al. — Tue, 21 Sep 2010 00:05:33 PDT

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 48 adult liver recipients. Twelve patients who underwent liver resection (LR), in whom the suprahepatic vena cava was not clamped, were used as a comparison group. Diaphragm excursion by ultrasound and pulmonary function were performed preoperatively and postoperatively; transcutaneous phrenic nerve conduction studies were performed postoperatively. Right phrenic nerve injury and hemidiaphragm paralysis occurred in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both liver recipients and the patients who had LR. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position (29 +/- 9.8%) compared with those with some conduction (14 +/- 6.9%, P < 0.001). However, neither the time on the ventilator nor the hospital stay was significantly different in the latter two groups. Complete recovery of phrenic nerve conduction and diaphragm function took until nine months in some patients. Right phrenic nerve injury is common after OLT and it is the cause of right hemidiaphragm dysfunction.

Technique to Minimize the Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation

A. Roy et al. — Thu, 16 Sep 2010 17:31:05 PDT

Hepatic artery thrombosis is a life-threatening complication after pediatric liver transplantation. We reviewed our experience in 62 children who received 72 liver transplant (69 whole grafts and 3 reduced-size grafts) between January 1984 and December 1991. They ranged in age from 6 months to 16 years (mean 5.8 years). Fifteen children (22%) were under 2 years and 10 patients (14%) were between 2 and 5 years. Forty-eight grafts in older children (age: 1-16 years, x = 7 years had an anastomosis between the donor hepatic/celiac artery and the recipient hepatic of splenic artery (A-A). Three thromboses occurred in this group for an incidence of 6.2%. Two others types of arterial reconstruction were used in 24 children who were significantly younger (6-120 months, x = 47 months, p < 0.01). Eight grafts had an anastomosis between the donor celiac artery and the recipient aorta (A-Ao). No thromboses occurred in this group. Sixteen grafts were revascularized using a donor aortic conduit anastomosed to the recipient aorta (AC) with a 12.5% (2 to 16) incidence of thrombosis. The incidence of arterial thrombosis for the entire group was 6.9%. In conclusion, by using the recipient aorta for arterial reconstruction, a low incidence of hepatic artery thrombosis can be achieved even in the group of younger patients who are the highest risk for this complication.

Increased Cyclosporine Bioavailability from a Microemulsion Formulation in a Liver Transplant Recipient

I. S. Sketris et al. — Thu, 16 Sep 2010 17:18:33 PDT

Use of OKT3 Monoclonal Antibody as Induction Therapy for Control of Rejection in Liver Transplantation

William J. Wall et al. — Thu, 16 Sep 2010 17:12:08 PDT

This report details a single center's experience with OKT3 induction immunosuppression for liver transplantation. One hundred ninety-nine consecutive, unselected adult liver recipients received OKT3 therapy for 9-10 days combined with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two patients (26.1%) experienced 57 episodes of acute rejection. The median time of onset of rejection was 18 days after grafting. Seventy-eight percent of the rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and the need for OKT3 retreatment was infrequent. One year actuarial graft and patient survival was 79.7% and 82.3% respectively. Based on this evidence, it appears that OKT3 prophylaxis provides good control of acute rejection with a very low incidence of recurrent rejection.

Use of Rabbit Anti-thymocyte Globulin for Induction immunosuppression in High-risk Kidney Transplant Recipients

P. Belitsky et al. — Thu, 16 Sep 2010 17:01:16 PDT

Long-term Follow-up (5 and 10 years) in Recipients of HLA Identical Living Related Donor Kidney Grafts Receiving Continuous Cyclosporine Compared with Azathioprine

A. S. MacDonald et al. — Thu, 16 Sep 2010 17:01:15 PDT

Kidney Transplantation, the Halifax Experience

P. Belitsky et al. — Thu, 16 Sep 2010 17:01:14 PDT

In the absence of a national kidney sharing system in Canada, virtually all the cadaver kidneys we transplant come from donors within the 4 provinces we serve. Currently the only criteria we use for recipient selection of cadaver kidneys, apart from ABO blood group matching and a negative anti-T-cell crossmatch, are good HLA match and transplant wait-list seniority. All transplant recipients receive CsA-based immunosuppression. Antibody induction is used only for repeat transplants and pediatric transplants. Recipients of first cadaver kidney transplants with zero HLA-DR mismatches have significantly better graft survival than those with mismatches. Graft and patient survival rates for first cadaver transplants continue to improve within the CsA era, and are comparable to those seen in centers routinely using antibody induction and routine sequential quadruple immunosuppression. Chronic graft nephropathy continues to be the most important cause of graft loss after the first year, unchanged over the past 2 decades, followed closely by death with a functioning kidney. The latter is a more important cause of loss in recipients older than age 60, and in recipients of HLA-identical live donor transplants. Repeat cadaver transplant recipients have a 5-year graft survival rate today equivalent to that seen with first cadaver transplants. Graft loss from acute rejection is modest, but kidneys requiring rescue therapy for steroid-resistant rejection have significantly poorer one- and 5-year graft survival and ultimately are lost from rejection. Patients with HLA-identical live-related donor transplants have better long-term survival with CsA than with azathioprine due to a decrease in graft loss from chronic rejection. Pre-transplant sensitization has an adverse effect on graft survival for haploidentical but not HLA identical live-related transplants. Patients over age 60 have equivalent graft survival to younger recipients for at least 7 years, and should not be precluded from receiving transplants by age alone. Prolonged CIT > 24 hours is associated with a significantly increased incidence and duration of ATN and need for dialysis, significantly increased early and late graft loss from acute and chronic rejection respectively, significantly reduced QALY's, and significantly higher early and late costs of transplantation.

The Morbidity of Prolonged Wound Drainage after Kidney Transplantation

B. Kiberd et al. — Wed, 15 Sep 2010 17:13:58 PDT

PURPOSE: The consequences of prolonged wound drainage, defined as extravasation of more than 50 ml. fluid daily for more than 1 week through a drain or wound after renal transplantation, have not been well described in the literature. We examine the association of prolonged wound drainage with other clinical events, and its impact on hospitalization, and patient and graft survival.

MATERIALS AND METHODS: We prospectively documented prolonged wound drainage in 392 recipients of cadaver and live renal transplants from July 1993 to December 1997. Potential risk factors, associated outcomes within the first 6 months and effect on length of hospital stay due to prolonged wound drainage were determined.

RESULTS: Prolonged wound drainage was significantly associated with pre-transplantation weight, weight gain by post-transplantation day 3, delayed graft function and continuous ambulatory peritoneal dialysis on univariate analysis but only with delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7 additional days during the first hospitalization and overall 11.3 additional days during the first 6 months after transplantation independent of other co-morbid events, such as delayed graft function, rejection or cytomegalovirus disease.

CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation event that impacts patient outcomes and hospital resource use. Efforts to prevent this complication should be considered.

Effect of Recipient Sensitization (Peak PRA) on Graft Outcome in Haploidentical Living Related Kidney Transplants

A. Barama et al. — Wed, 15 Sep 2010 17:09:14 PDT

OBJECTIVE: To evaluate the influence of pre-transplant recipient sensitization on the outcome of 1-haploidentical live related donor (LRD) kidney transplants.

METHOD: We reviewed 141 consecutive cyclosporine-treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA = 0 (n = 97); group II, PRA = 1-50% (n = 24); and group III, PRA = 51-100% (n = 20).

RESULTS: Differences in PRA were associated with significant differences in short- and longer-term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p < 0.001). Increasing PRA was associated with shorter time-to-graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p < 0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p < 0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points.

CONCLUSIONS: Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.

Conversion to Rapamycin Immunosuppression in Renal Transplant Recipients: Report of an Initial Experience

Javier Dominguez et al. — Tue, 14 Sep 2010 00:37:52 PDT

BACKGROUND: The aim of this study is to evaluate the effects of RAPA conversion in patients undergoing cyclosporine (CsA) or tacrolimus (Tac) toxicity.

METHODS: Twenty renal transplant recipients were switched to fixed dose rapamycin (RAPA) (5 mg/day) 0 to 204 months posttransplant. Drug monitoring was not initially used to adjust doses. The indications for switch were chronic CsA or Tac nephrotoxicity (12), acute CsA or Tac toxicity (3), severe facial dysmorphism (2), posttransplant lymphoproliferative disorder (PTLD) in remission (2), and hepatotoxicity in 1. Follow-up is 7 to 24 months.

RESULTS: In the 12 patients switched because of chronic nephrotoxicity there was a significant decrease in serum creatinine [233+/-34 to 210+/-56 micromol/liter (P<0.05) at 6 months]. Facial dysmorphism improved in two patients. No relapse of PTLD was observed. Five patients developed pneumonia (two Pneumocystis carinii pneumonia, one infectious mononucleosis with polyclonal PTLD lung infiltrate) and two had bronchiolitis obliterans. There were no deaths. RAPA was discontinued in four patients, because of pneumonia in two, PTLD in one, and oral aphtous ulcers in one. RAPA levels were high (>15 ng/ml) in 7 of 13 (54%) patients.

CONCLUSIONS: RAPA conversion provides adequate immunosuppression to enable CsA withdrawal. However, when converting patients to RAPA drug levels should be monitored to avoid over-immunosuppression and adequate antiviral and Pneumocystis carinii pneumonia prophylaxis should be given.