Gregory R. D. Evans

Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve, long bone, intestine, or blood vessel.

Peripheral nerve injury: A review and approach to tissue engineered constructs

Eleven thousand Americans each year are affected by paralysis, a devastating injury that possesses associated annual costs of

Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.

7 billion (American Paralysis Association, 1997). Currently, there is no effective treatment for damage to the central nervous system (CNS), and acute spinal cord injury has been extraordinarily resistant to treatment. Compared to spinal cord injury, damage to peripheral nerves is considerably more common. In 1995, there were in excess of 50,000 peripheral nerve repair procedures performed. (National Center for Health Statistics based on Classification of Diseases, 9th Revision, Clinical Modification for the following categories: ICD‐9 CM Code: 04.3, 04.5, 04.6, 04.7). These data, however, probably underestimate the number of nerve injuries appreciated, as not all surgical or traumatic lesions can be repaired. Further, intraabodominal procedures may add to the number of neurologic injuries by damage to the autonomic system through tumor resection. For example, studies assessing the outcome of impotency following radical prostatectomy demonstrated 212 of 503 previously potent men (42%) suffered impotency when partial or complete resection of one or both cavernosal nerve(s). This impotency rate decreased to 24% when the nerves were left intact (Quinlan et al., J. Urol. 1991 ;145:380–383; J. Urol. 1991 ;145:998–1002). Anat Rec 263:396–404, 2001.

In vivo evaluation of poly(l-lactic acid) porous conduits for peripheral nerve regeneration

Free pedicled transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction is often advocated as the procedure of choice for autogenous tissue breast reconstruction in high-risk patients, such as smokers. However, whether use of the free TRAM flap is a desirable option for breast reconstruction in smokers is still unclear. All patients undergoing breast reconstruction with free TRAM flaps at our institution between February of 1989 and May of 1998 were reviewed. Patients were classified as smokers, former smokers (patients who had stopped smoking at least 4 weeks before surgery), and nonsmokers. Flap and donor-site complications in the three groups were compared. Information on demographic characteristics, body mass index, and comorbid medical conditions was used to perform multivariate statistical analysis. A total of 936 breast reconstructions with free TRAM flaps were performed in 718 patients (80.9 percent immediate; 23.3 percent bilateral). There were 478 nonsmokers, 150 former smokers, and 90 smokers. Flap complications occurred in 222 (23.7 percent) of 936 flaps. Smokers had a higher incidence of mastectomy flap necrosis than nonsmokers (18.9 percent versus 9.0 percent;p = 0.005). Smokers who underwent immediate reconstruction had a significantly higher incidence of mastectomy skin flap necrosis than did smokers who underwent delayed reconstruction (21.7 percent versus 0 percent;p = 0.039). Donor-site complications occurred in 106 (14.8 percent) of 718 patients. Donor-site complications were more common in smokers than in former smokers (25.6 percent versus 10.0 percent;p = 0.001) or nonsmokers (25.6 percent versus 14.2 percent;p = 0.007). Compared with nonsmokers, smokers had significantly higher rates of abdominal flap necrosis (4.4 percent versus 0.8 percent;p = 0.025) and hernia (6.7 percent versus 2.1 percent;p = 0.016). No significant difference in complication rates was noted between former smokers and nonsmokers. Among smokers, patients with a smoking history of greater than 10 pack-years had a significantly higher overall complication rate compared with patients with a smoking history of 10 or fewer pack-years (55.8 percent versus 23.8 percent;p = 0.049). In summary, free TRAM flap breast reconstruction in smokers was not associated with a significant increase in the rates of vessel thrombosis, flap loss, or fat necrosis compared with rates in nonsmokers. However, smokers were at significantly higher risk for mastectomy skin flap necrosis, abdominal flap necrosis, and hernia compared with nonsmokers. Patients with a smoking history of greater than 10 pack-years were at especially high risk for perioperative complications, suggesting that this should be considered a relative contraindication for free TRAM flap breast reconstruction. Smoking-related complications were significantly reduced when the reconstruction was delayed or when the patient stopped smoking at least 4 weeks before surgery.

local Recurrence Risk after Skin-sparing and Conventional Mastectomy: A 6-year Follow-up

The present study provides in vivo trials of poly(L-lactic acid) (PLLA) as a porous biodegradable nerve conduit using a 10 mm sciatic nerve defect model in rats. The PLLA conduits, fabricated by an extrusion technique, had an inner diameter of 1.6 mm, an outer diameter of 3.2 mm, and a length of 12 mm. They were highly porous with an interconnected pore structure (of 83.5% porosity and 12.1 microm mean pore size). The conduits were interposed into the right sciatic nerve defect of Sprague Dawley rats using microsurgical techniques; nerve isografts served as controls. Walking track analysis was performed after conduit placement monthly through 16 weeks. At the conclusion of 6 and 16 weeks, sections from the isograft/conduit and distal nerve were harvested for histomorphometric analysis. The right gastrocnemius muscle was also harvested and its weight was determined. All conduits remained intact without breakage. Moreover, no conduit elongated during the 16 weeks of placement. Walking track analysis and gastrocnemius muscle weight demonstrated increasing regeneration over the 16 weeks in both the conduit and isograft control groups, with control values significantly greater. The nerve fiber density in the distal sciatic nerve for the PLLA conduits (0.16+/-0.07) was similar to that for the control isografts (0.19+/-0.05) at 16 weeks. The number of axons/mm2 in the distal sciatic nerve for the PLLA conduits was lower than that for the isografts (13 800+/-2500 vs. 10700+/-4700) at 16 weeks. The results for PLLA were significantly improved over those for 75:25 poly(DL-lactic-co-glycolic acid) of a previous study and suggest that PLLA porous conduits may serve as a scaffold for peripheral nerve regeneration.

Effect of obesity on flap and donor-site complications in free transverse rectus abdominis myocutaneous flap breast reconstruction

In this study, the records of all patients at the University of Texas M. D. Anderson Cancer Center with T1 or T2 breast cancer who were treated between March of 1986 and November of 1990 with mastectomy followed by immediate breast reconstruction were reviewed for the presence of recurrent disease. Patients with in situ disease were not included. Patients were included in the study if a local recurrence occurred (regardless of the length of follow-up) or if a follow-up of 6 years or longer could be obtained. Patients were grouped according to the use or nonuse of skin-sparing mastectomy, by tumor stage, and by nuclear grade of the tumor. The series included 154 patients, of whom 114 had skin-sparing mastectomies and 40 had nonskin-sparing mastectomies. The local recurrence rate in the skin-sparing mastectomy group was 7.0 percent, whereas in the nonskin-sparing mastectomy group it was 7.5 percent. The sample size in the nonskin-sparing mastectomy group was too small for meaningful statistical analysis, but the data suggest that there is no clinically important difference in recurrence rates between the two groups. We conclude that the use of skin-sparing technique for early breast cancer patients does not significantly increase the risk of tumor recurrence after mastectomy.

Timing of pedicle thrombosis and flap loss after free-tissue transfer.

&NA; The purpose of this study was to assess the effect of obesity on flap and donor‐site complications in patients undergoing free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. All patients undergoing breast reconstruction with free TRAM flaps at our institution from February 1, 1989, through May 31, 1998, were reviewed. Patients were divided into three groups based on their body mass index: normal (body mass index <25), overweight (body mass index 25 to 29), obese (body mass index =30). Flap and donor‐site complications in the three groups were compared. A total of 936 breast reconstructions with free TRAM flaps were performed in 718 patients. There were 442 (61.6 percent) normal‐weight, 212 (29.5 percent) overweight, and 64 (8.9 percent) obese patients. Flap complications occurred in 222 of 936 flaps (23.7 percent). Compared with normal‐weight patients, obese patients had a significantly higher rate of overall flap complications (39.1 versus 20.4 percent; p = 0.001), total flap loss (3.2 versus 0 percent; p = 0.001), flap seroma (10.9 versus 3.2 percent; p = 0.004), and mastectomy flap necrosis (21.9 versus 6.6 percent; p = 0.001). Similarly, overweight patients had a significantly higher rate of overall flap complications (27.8 versus 20.4 percent; p = 0.033), total flap loss (1.9 versus 0 percent p = 0.004), flap hematoma (0 versus 3.2 percent; p = 0.007), and mastectomy flap necrosis (15.1 versus 6.6 percent; p = 0.001) compared with normal‐weight patients. Donor‐site complications occurred in 106 of 718 patients (14.8 percent). Compared with normal‐weight patients, obese patients had a significantly higher rate of overall donor‐site complications (23.4 versus 11.1 percent; p = 0.005), infection (4.7 versus 0.5 percent; p = 0.016), seroma (9.4 versus 0.9 percent; p < 0.001), and hernia (6.3 versus 1.6 percent; p = 0.039). Similarly, overweight patients had a significantly higher rate of overall donor‐site complications (19.8 versus 11.1 percent; p = 0.003), infection (2.4 versus 0.5 percent; p = 0.039), bulge (5.2 versus 1.8 percent; p = 0.016), and hernia (4.3 versus 1.6 percent; p = 0.039) compared with normal‐weight patients. There were no significant differences in age distribution, smoking history, or comorbid conditions among the three groups of patients. Obese patients, however, had a significantly higher incidence of preoperative radiotherapy and preoperative chemotherapy than did patients in the other two groups. A total of 23.4 percent of obese patients had preoperative radiation therapy compared with 12.3 percent of overweight patients and 12.4 percent of normal‐weight patients; 34.4 percent of obese patients had preoperative chemotherapy compared with 24.5 percent of overweight patients and 17.7 percent of normal‐weight patients. Multiple logistic regression analysis was used to determine the risk factors for flap and donor‐site complications while simultaneously controlling for potential confounding factors, including the incidence of preoperative chemotherapy and radiotherapy. In summary, obese and overweight patients undergoing breast reconstruction with free TRAM flaps had significantly higher total flap loss, flap hematoma, flap seroma, mastectomy skin flap necrosis, donor‐site infection, donor‐site seroma, and hernia compared with normalweight patients. There were no significant differences in the rate of partial flap loss, vessel thrombosis, fat necrosis, abdominal flap necrosis, or umbilical necrosis between any of the groups. The majority of overweight and even obese patients who undertake breast reconstruction with free TRAM flaps complete the reconstruction successfully. Both such patients and surgeons, however, must clearly understand that the risk of failure and complications is higher than in normal‐weight patients. Patients who are morbidly obese are at very high risk of failure and complications and should avoid any type of TRAM flap breast reconstruction. (Plast. Reconstr. Surg. 105: 1640, 2000.)

Choice of flap and incidence of free flap success

&NA; A series of 990 consecutive free flaps was reviewed to determine how often pedicle thrombosis occurred, when it occurred, and if the timing of thrombosis detection had any relationship to the probability of flap salvage. The overall thrombosis rate was 5.1 percent, and the flap loss rate was 3.2 percent. The majority (80 percent) of thrombi occurred within the first 2 postoperative days. Only 5 thrombi (10 percent) were known to have occurred after the third postoperative day. No flaps that developed thrombosis after the third postoperative day were salvaged successfully. Had flap monitoring been discontinued after the first 3 postoperative days, our results in this series would have been unchanged. Thrombosis of the vein (54 percent) was more common than arterial thrombosis (20 percent) or thrombosis of both artery and vein (12 percent). Almost all purely arterial thrombi (90 percent) occurred before the end of the first postoperative day, whereas 41 percent of all venous thrombi occurred later. We conclude that arterial monitoring is most critical immediately after surgery. Beginning on the second postoperative day, venous monitoring becomes progressively more important to flap success. The cost‐effectiveness of postoperative monitoring of free flaps is greatest during the first 2 days, after which it decreases significantly.

Reconstruction and the radiated breast: Is there a role for implants?

&NA; A review of 854 consecutive free flaps was performed to determine whether the choice of flap used for the reconstruction influenced the probability of a successful outcome. Flaps were grouped into nine categories: rectus abdominis, free transverse rectus abdominis myocutancous, radial forearm, jejunum, latissimus dorsi, fibula, scapula, iliac crest, and other. There were significant differences among the success rates of different flaps (p < 0.0001). Rectus abdominis‐based flaps used for breast or head and neck reconstruction had lower failure rates (0.9 percent) than did non‐rectus abdominis Haps (6.6 percent; p < 0.0001). Flaps requiring vein grafts had a higher rate of flap loss (18.4 percent) than did flaps that did not require vein grafts (2.9 percent; p < 0.0001). There was a strong trend favoring survival of flaps without a bone component (compared with osteocutaneous flaps), and a weaker trend favoring survival of flaps in nonobese patients (compared with flaps in obese patients). Smoking, age. and previous irradiation had no significant effect on flap failure rales. Surgeons should consider the flap success rate as one (but not necessarily the most important) factor in choosing the best reconstruction for any individual patient.

Abdominal Wall Strength, Bulging, and Hernia After Tram Flap Breast Reconstruction

The use of breast implants in irradiated patients is controversial. Recently, 39 irradiated implants were compared with 338 nonirradiated implants in 297 patients between January of 1975 and October of 1994 at The University of Texas M. D. Anderson Cancer Center. Tissue expanders and follow-up time of less than 6 months excluded patients from the study. Five groups of patients were identified. Group 1 consisted of 7 patients and 7 implants who received postoperative adjuvant radiotherapy after implant placement. Group 2 consisted of 5 patients and 7 implants who received preoperative adjuvant radiotherapy prior to implant placement. Groups 3 and 4 consisted of 2 and 12 patients (2 and 19 implants) placed beneath latissimus dorsi flaps who had postoperative and preoperative adjuvant radiotherapy, respectively. Group 5 contained 4 patients with 4 implants placed beneath a transverse rectus abdominis myocutaneous (TRAM) flap who had preoperative radiotherapy. All implants were placed submuscularly or beneath autogenous flaps. The average irradiated breast received 50 Gy. For statistical purposes, two categories were identified. Capsular contracture (Baker III or greater), pain, exposure, and implant removal in 6 of 14 implants that received radiotherapy were compared with similar complications in 33 of 266 implants without irradiation (p = 0.001). The second category contained 10 complications in 25 implants placed beneath autogenous reconstructions with radiotherapy compared with 6 of 72 similar complications in implants placed beneath autogenous reconstructions without radiotherapy (p = 0.000). Results showed that irradiation has significant negative effects on the reconstructive outcome with implants. Autogenous reconstruction did not appear to offer a protective role when placed over implants.(ABSTRACT TRUNCATED AT 250 WORDS)