Tissue-Engineered Buccal Mucosa Urethroplasty—Clinical Outcomes

Introduction

Whilst buccal mucosa is the most versatile tissue for urethral replacement, the quest continues for an ideal tissue replacement for the urethra when substantial tissue transfer is needed. Previously we described the development of autologous tissue-engineered buccal mucosa (TEBM). Here we report clinical outcomes of the first human series of its use in substitution urethroplasty.

Methodology

Five patients with urethral stricture secondary to lichen sclerosus (LS) awaiting substantial substitution urethroplasty elected to undergo urethroplasty using TEBM, with full ethics committee support. Buccal mucosa biopsies (0.5 cm) were obtained from each patient. Keratinocytes and fibroblasts were isolated and cultured, seeded onto sterilised donor de-epidermised dermis, and maintained at air–liquid interface for 7–10 d to obtain full-thickness grafts. These grafts were used for urethroplasty in a one-stage (n = 2) or a two-stage procedure (n = 3). Follow-up was performed at 2 and 6 wk, at 3, 6, 9, and 12 mo, and every 6 mo thereafter.

Results

Follow-up ranged from 32 to 37 mo (mean, 33.6). The initial graft take was 100%, as assessed by visual inspection. Subsequently, one patient had complete excision of the grafted urethra and one required partial graft excision, for fibrosis and hyperproliferation of tissue, respectively. Three patients have a patent urethra with the TEBM graft in situ, although all three required some form of instrumentation.

Conclusions

Whilst TEBM may in the future offer a clinically useful autologous urethral replacement tissue, in this group of patients with LS urethral strictures, it was not without complications, namely fibrosis and contraction in two of five patients.     

Tissue-engineered buccal mucosa using silk fibroin matrices for urethral reconstruction in a canine model

Background

To investigate the feasibility of urethral reconstruction using tissue-engineered buccal mucosa (TEBM) with silk fibroin (SF) matrices in a canine model.

Materials and methods

Autologous oral keratinocytes and autologous fibroblasts were isolated, expanded, and seeded onto SF matrices to obtain TEBM. The TEBM was assessed using hematoxylin and eosin staining and scanning electron microscopy. A 5-cm urethral mucosal defect was created in 10 female canines. Urethroplasty was performed using TEBM in five canines in the experimental group and with SF matrices without cells in the five canines in the comparison group. Retrograde urethrography was performed after 6 mo of grafting. The urethral grafts were analyzed grossly and histologically.

Results

The oral keratinocytes and fibroblasts exhibited good biocompatibility with the SF matrices. TEBM could be constructed using SF matrices. The canines implanted with the tissue-engineered mucosa voided without difficulty. The retrograde urethrography revealed no sign of stricture. The histologic staining showed that epithelial cells developed gradually and exhibited stratified epithelial layers at 6 mo. In the comparison group, the canines had difficulty voiding, and the retrograde urethrography showed urethra stricture. The histologic staining showed that one to two layers of epithelial cells developed.

Conclusions

The TEBM using SF matrices could be a potential material for urethra reconstruction.     

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles

Purpose

After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa.

Methods

In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (¹³¹I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student’s t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals.

Results

In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-¹³¹I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacitiy of the transplanted ileal mucosa was significant (P < .05).

Conclusions

Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.     

Wound Complications After Kidney Transplantation in Nondiabetic Patients

Introduction

Impaired wound healing represents a common operative complication after kidney transplantation. This problem seems to be affected by factors related to surgical technique, drugs, and patient/graft peculiarities.

Patients and Methods

From January 2000 to December 2007, 350 consecutive kidney transplantations were performed in a population of nondiabetic patients. We evaluated the influence of various factors on impaired wound healing.

Results

Among 350 kidney transplantation patients, we observed 54 cases (15.43%) of impaired healing of the surgical incision: 36 (10.29%) with first level and 18 (5.14%) with second level wound complications. Factors related to complications were overweight and delayed graft function. Cyclosporine and tacrolimus had similar effects. However, all patients developing second level complications showed more risk factors. In our experience, postoperative lymphocele did not occur as an unique factor but became a significant risk factor when associated with another one. Patients who did not have reconstruction of the muscle layers showed a greater incidence of incisional complications.

Conclusion

Impaired healing of the surgical incision more or less seriously influenced outcomes of transplanted patients. This complication was common and usually related to the presence of more than one risk factor.     

Platelet-dense granule deficiency causes postoperative hemorrhage in patients receiving enoxaparin: a novel observation with dramatic clinical implications

Background

Inherent hemorrhage risk has impeded the universal adoption of low-molecular-weight heparin (LMWH) for venous thromboembolic prophylaxis in surgical patients. Coagulation pathway parameters and platelet numbers routinely are evaluated preoperatively; scant attention has been directed toward evaluation of platelet function. We hypothesized that administration of LMWH may unmask latent platelet dysfunction and result in postoperative hemorrhage.

Methods

Postoperative hemorrhage occurred in 15 (3.5%) of 423 consecutive patients undergoing laparoscopic gastric bypass. All patients received LMWH (enoxaparin, 40 mg) preoperatively. Hematologic evaluation included measurement of von Willebrand's factor level and activity, factor VIII level, and electron microscopic enumeration of platelet-dense granules.

Results

All patients had normal preoperative platelet counts and coagulation profiles. Ten patients underwent hematologic evaluation: coagulation pathway parameters were normal in all; however, all patients had a markedly decreased number of platelet-dense granules.

Conclusions

Platelet-dense granule deficiency may cause postoperative hemorrhage in patients receiving LMWH.     

The sartorius muscle flap: an important adjunct for complicated femoral wounds involving vascular grafts

Introduction

Femoral wound complications can threaten vascular grafts. Muscle flaps can be used to facilitate soft-tissue coverage and graft salvage. We report a series of sartorius flaps performed by vascular surgeons in the treatment of complicated femoral wounds.

Methods

Rotational sartorius flaps were performed to attempt salvage of underlying vascular grafts. We reviewed a prospective database to determine the outcomes of sartorius flaps on facilitating wound healing and graft salvage and patency.

Results

From 2005 to 2008, 21 sartorius flaps were performed in infected or threatened femoral wounds. Original operations included femoral endarterectomy with patch repair in 8, aortofemoral graft in 6, axillofemoral graft in 4, and femoral-distal bypass in 3 patients. Complete wound healing occurred in 18 patients (86%). Primary wound closure was achieved in 7 patients. Secondary wound closure was achieved in 11 patients with mean healing time of 2.3 months. All vascular reconstructions remained patent at the 9.5-month follow-up.

Conclusions

Sartorius muscle flaps are effective at facilitating complicated femoral wound healing while maintaining graft salvage and patency.     

Hepatic Neutrophil Activation During Reperfusion May Not Contribute to Initial Graft Function After Short Cold Ischemia in Human Liver Transplantation

Background

Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear.

Methods

In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated.

Results

Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7-1.0]; 1.4 [0.9-1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2-0.5]; 1.7 [1.3-3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation.

Conclusions

Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.     

Preemptive Living-Donor Renal Transplantation: Outcome and Clinical Advantages

Introduction

Kidney transplant recipients have a higher quality of life and consume fewer health care resources compared with patients on dialysis. However, optimal timing of transplantation has been controversial. Recent studies have clearly demonstrated that preemptive renal transplantation is associated with better graft survival, lower complications, and better cost-effective outcomes. We evaluated differential effects on long-term outcomes according to dialysis type/duration versus no dialysis.

Materials and Methods

We retrospectively analyzed 499 cases of first living-donor kidney transplantations performed in our center from January 1990 to January 2007. We compared 3 groups according to graft survival, acute and chronic rejection, postoperative complication, and delayed graft function rates. The mean duration of follow-up was 119.1 ± 47.2 months.

Results

Among 499 cases, 81 cases were preemptive renal transplantations with 418 cases hemodialysis [HD], 343 cases, peritoneal dialysis [PD] 75 cases) performed after dialysis. The 1-, 5-, and 10-year graft survival rates were 98.8%, 89.5%, 79.4% among the preemptive renal transplantation group and 92.4%, 78.2%, and 69.2% and 85.3%, 74.5%, and 68.2% (P = .03) in the dialysis groups (HD, PD), respectively. The differential effect of pretransplantation HD or PD was not significant. However, the graft survival rates in the HD group were not significantly higher than the PD group (P = .61). The duration of dialysis was not associated with graft survival.

Conclusion

We suggest that preemptive renal transplantation should be the first choice of treatment for patients with end-stage renal disease.     

An observational study of surgery-related activities between nurses and surgeons during laparoscopic surgery

Background

In the operating room (OR), nurse-surgeon coordination is essential to the success of a surgery.

Methods

This observational field study was conducted in the OR for selected laparoscopic surgeries to record surgery-related activities (SRAs) performed by the scrub nurses with different levels of OR experience. Those SRAs performed without instruction were defined as anticipatory movements.

Results

The scrub nurse spent 74% of OR time watching surgery and 35% of OR time performing SRAs. The intermediate skill nurses watch surgeon on 76% of the OR time and they performed 16 counts of anticipatory movements per procedure. Experienced nurses spent shorter amount of OR time (72%) watching surgery but they performed more anticipatory movements (20 counts) than the intermediate skill nurses. With basic cases, experienced and intermediate-skill nurses performed equal amounts of anticipatory movements; however, when assisting in complex cases, the experienced nurses performed significantly more anticipatory movements (24 counts) than the intermediate-skill nurses (16 counts).

Conclusions

Experienced nurses develop sophisticated cognition during their careers in the OR, which allows them to maintain their involvement with the surgical team consistently. The anticipatory movement and the eye gaze are 2 valuable behavioral markers for assessing team performance.     

Refinements in pectus carinatum correction: the pectoralis muscle split technique

Background

The standard approach for correction of pectus carinatum deformity includes elevation of the pectoralis major and rectus abdominis muscle from the sternum and adjacent ribs. A postoperative restriction of shoulder activity for several weeks is necessary to allow stable healing of the elevated muscles. To reduce postoperative immobilization, we present a modified approach to the parasternal ribs using a pectoralis muscle split technique.

Methods

At each level of rib cartilage resection, the pectoralis muscle is split along the direction of its fibers instead of elevating the entire muscle as performed with the standard technique. From July 2000 to May 2007, we successfully used this technique in 33 patients with pectus carinatum deformity.

Results

After the muscle split approach, patients returned to full unrestricted shoulder activity as early as 3 weeks postoperatively, compared to 6 weeks in patients treated with muscle flap elevation. Postoperative pain was reduced and the patients were discharged earlier from the hospital than following the conventional approach.

Conclusions

The muscle split technique is a modified surgical approach to the parasternal ribs in patients with pectus carinatum deformity. It helps to maintain pectoralis muscle vascularization and function and can reduce postoperative pain, hospitalization, and rehabilitation period.     

Stem cell factor, interleukin-16, and interleukin-2 receptor alpha are predictive biomarkers for delayed and slow graft function

Introduction

Delayed graft function (DGF) and slow graft function (SGF) due to ischemic and reperfusion injury (IRI) are common complications of deceased donor kidney transplantation. We tested whether a panel of serum and urine cytokines represent early biomarkers for DGF and SGF.

Methods

We collected serum and urine samples from 61 patients 48 hours posttransplantation and used a multiplex enzyme-linked immunosorbent assay (ELISA) technique to measure levels of 23 cytokines. Fourteen patients developed poor graft function (PGF), with 6 having DGF and 8 with SGF.

Results

Area under receiver operation characteristics curve (AUC) demonstrated the following: serum levels of SCF (0.88) and interleukin (IL) 16 (0.74).

Conclusions

This study showed that a select panel of cytokines measured early post kidney transplantation may predict poor graft function.     

Acellular porcine intestinal submucosa as fascial graft in an animal model: Applications for revision tympanoplasty

Objective

To demonstrate regeneration of muscle fascia appropriate for future harvest with the use of acellular porcine intestinal submucosa in a rat model.

Study Design

Animal cohort study.

Setting

Tertiary care academic medical center.

Subjects and Methods

Sixteen male Sprague-Dawley rats underwent excision of rectus abdominis muscle fascia. A sheet of acellular porcine intestinal submucosa was placed in the fascia harvest defect. Graft and underlying muscle were harvested at three-, six-, and nine-week intervals. Histologic examination, including immunohistology for anti-von Willebrand factor, was performed at each timepoint. Additional selected specimens were subjected to latex vascular perfusion casts to examine vessel growth patterns within the graft.

Results

Gross examination revealed a new tissue plane, indistinguishable from surrounding native fascia. Histology revealed an initial inflammatory response within the graft. Progressive influx of native tissue was noted over successive timepoints. Via collagen-specific staining, we noted progressive reorganization and maturation of the graft collagen matrix. At the final nine-week time point, a new loose connective tissue plane was reestablished between the graft and underlying muscle. Immunohistochemistry and latex perfusion both demonstrate an initial development of small capillaries that progresses over time to greater organization and arteriole formation.

Conclusion

Fascia regeneration may be possible with use of an acellular porcine intestinal submucosa graft in an animal model. Future studies may prove beneficial in restoring fascia in humans. Implications for potential advantages in tympanoplasty are discussed.     

Reversal of Graft Steatosis After Liver Transplantation: Prospective Study

Objective

To determine the risk factors for reversal of liver graft steatosis.

Patients and Methods

This prospective study included 70 patients (47 men and 23 women) who received steatotic liver grafts between July 2003 and February 2008. No grafts from prisoners were used in the study. Patients were divided into 3 groups according to degree of liver steatosis, as follows: mild (n = 29, group 1), moderate (n = 23, group 2), and severe (n = 18, group 3).

Results

The median (SD) degree of steatosis in liver grafts at transplantation was 15.7% (7.3%) in group 1, 26.3% (10.5%) in group 2, and 45.1% (8.3%) in group 3. Postoperative histologic analysis demonstrated dramatically decreased steatosis in all graft recipients.

Conclusion

Graft steatosis can be decreased substantially after liver transplantation. Factors for reversibility of steatosis include donor age, degree of macrovesicular steatosis, and cold ischemia time.     

Previous Intravenous Substance Use and Outcome of Liver Transplantation in Patients With Chronic Hepatitis C Infection

Background

End-stage liver disease due to hepatitis C viral (HCV) infection is the most common reason for liver transplantation. One of the major risk factors for infection with HCV is intravenous drug use (IVDU). The pretransplantation characteristics and outcome of liver transplantation in patients with chronic hepatitis C (CHC) infected after IVDU are poorly known.

Methods

We performed a retrospective cohort study in patients with CHC who underwent liver transplantation between 1998 and 2002 in Belgium. Seven patients with and 60 patients without a history of IVDU were compared.

Results

Patients with CHC infected after IVDU were primarily men, significantly younger, and affected more by genotype 2 or 3. There was no relapse in substance use. No patients required a second transplantation or developed surgical complications. Progression to fibrosis in the posttransplantation period seemed to be slower. Graft and patient survival, and compliance were similar in both groups.

Conclusions

Compared with patients in the non-IVDU group, patients with CHC infected after IVDU in complete remission have the same compliance, and patient and graft survival after liver transplantation. Therefore, patients with IVDU should not be excluded for liver transplantation because of HCV-induced cirrhosis.     

The recent decline in mammography rates is limited to low- to average-risk women

Introduction

There has recently been a decline in mammography rates noted in the general population. We sought to determine whether similar trends hold in high-risk populations.

Methods

Mammography rates from the National Health Interview Survey for 2000 and 2005 were analyzed for differences among risk-stratified populations of women over the age of 40.

Results

Although high-risk women (those with a personal of family history of breast cancer) were more likely to report having had a mammogram than lower risk women, they, too, showed a small decline in mammography rates. This, however, did not reach statistical significance. The decline in mammography rates in lower risk women, however, was significant and correlated with that of the general population.

Conclusions

The decline in breast cancer-screening rates noted over the past 5 years has been predominantly in lower-risk women.     

Risk factors and management of intra-abdominal infection after extended radical gastrectomy

Background

This study elucidated risk factors and management for intra-abdominal infection after extended radical gastrectomy.

Methods

From 1988 to 2004, 2,076 patients with gastric cancer underwent extended radical gastrectomy at Taipei Veterans General Hospital. Risk factors for intra-abdominal infection were determined by analyzing clinicopathological factors, operative procedure, combined organ resection, operative time, blood loss, and associated disease(s). Management modalities were summarized.

Results

The overall complication rate was 18.7%. Eighty (3.9%) patients were found to have intra-abdominal infections. Age, prolonged operation time, and combined organ resection were the precipitating factors. These patients were categorized into 3 groups: intra-abdominal abscess with adequate drainage, intra-abdominal abscess without anastomotic leakage, and intra-abdominal abscess because of leakage. Adequate drainage was the primary treatment. Mortality rate was 22.5% (18), and the most common cause of mortality was intra-abdominal abscess caused by leakage.

Conclusions

Although expert surgical skills can minimize the incidence of intra-abdominal infection, management also requires experience and training.     

Urethroplasty for strictures after phallic reconstruction: a single-institution experience

Background

Treatment recommendations for strictures after phalloplasty are lacking.

Objective

Our aim was to evaluate the outcome of urethroplasty for strictures after phalloplasty and to provide treatment recommendations based on this experience.

Design, setting, and participants

One hundred and eighteen urethroplasties were performed in 79 patients. Mean patient age was 37.6 yr. Mean follow-up was 39 mo.

Intervention

Different types of urethroplasty were used: meatotomy, Heineke-Mikulicz principle (HMP), excision and primary anastomosis (EPA), free graft urethroplasty (FGU), pedicled flap urethroplasty (PFU), two-stage urethroplasty (TSU), and perineostomy followed by urethral reconstruction (PUR).

Measurements

Stricture recurrence was defined as the need for additional instrumentation or surgery.

Results and limitations

Mean stricture length was 3.6 cm. Stricture location was at the meatus, phallic urethra, anastomosis, fixed part, and different locations in 18, 28, 48, 15, and 9 urethroplasties, respectively. Stricture recurrence was observed in 44 urethroplasties (41.12%). Stricture recurrence rate for meatotomy, HMP, EPA, FGU, PFU, TSU, and PUR was 25%, 42.11%, 42.86%, 50%, 40%, 30.3%, and 61.9%, respectively.

Conclusions

The main stricture location after phalloplasty is the anastomosis between the phallic and the fixed part. Urethroplasty for strictures after phalloplasty is associated with a relatively high recurrence rate.

Trial registration

EC UZG 2007/434.     

Use of simulect can reduce the incidence of acute rejection and demonstrates with superior 3-year patient and graft survival rates in renal transplantation

Background

Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation.

Objectives

We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated.

Method

Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid.

Results

There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%.

Conclusions

Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.     

The use of laparoscopic surgery in pregnancy: evaluation of safety and efficacy

Background

Laparoscopic surgery in pregnant women has become increasingly more common since the 1990s; however, the safety of laparoscopy in this population has been widely debated, particularly in emergent and urgent situations.

Methods

A retrospective chart review of all pregnant women following a nonobstetric abdominal operation at a University hospital between 1993 and 2007. Perioperative morbidity and mortality for the mother and fetus were evaluated.

Results

Ninety-four subjects were identified; 53 underwent laparoscopic procedures and 41 underwent open procedures. Cholecystectomy and appendectomy were performed in both groups with salpingectomy/ovarian cystectomy only in the laparoscopic group. No maternal deaths occurred, while fetal loss occurred in 3 cases within 7 days of the operation and in 1 case 7 weeks postoperatively. This and other perinatal complications occurred in 36.7% of the laparoscopic group and 41.7% of the open group.

Conclusion

Laparoscopic appendectomy and cholecystectomy appear to be as safe as the respective open procedures in pregnant patients; however, this population in particular remains at risk for perinatal complications regardless of the method of abdominal access.