Long-term implantation of preadipocyte-seeded PLGA scaffolds.

Studies were performed in a long-term effort to develop clinically translatable, tissue engineered adipose constructs for reconstructive, correctional, and cosmetic indications. Rat preadipocytes were harvested, isolated, expanded ex vivo, and seeded within PLGA scaffolds. Preadipocyte-seeded and acellular (control) scaffolds were implanted for 1-12 months. Explanted scaffolds were stained with osmium tetroxide, processed, and counterstained using H&E. Quantitative histomorphometric analysis was performed on all tissue sections to determine the amount of adipose tissue formed. Analyses revealed maximum adipose formation at 2 months, followed by a decrease at 3 months, and complete absence of adipose and PLGA at 5-12 months. These results extend a previous short-term study (Tissue Engineering 1999;5:134) and demonstrate that adipose tissue can be formed in vivo using tissue engineering strategies. However, the long-term maintenance of adipose tissue remains elusive.

Preadipocyte seeded PLGA scaffolds for adipose tissue engineering.

Adipose tissue equivalents have not been addressed as yet despite the clinical need in congenital deformities, posttraumatic repair, cancer rehabilitation, and other soft tissue defects. Preadipocytes were successfully harvested from rat epididymal fat pads of Sprague-Dawley and Lewis rats and expanded ex vivo. In vitro cultures demonstrated full differentiation of preadipocytes into mature adipocytes with normal lipogenic activity. The onset of differentiation was well-controlled by regulating preadipocyte confluency. Poly(lactic-co-glycolic) acid (PLGA) polymer disks with 90% porosity, 2.5 mm thick, 12 mm diameter, pore size range of 135-633 microm were fabricated and seeded with preadipocytes at 10(5) cells/mL. Disks in vitro demonstrated fully differentiated mature adipocytes within the pores of the disks. Short-term in vivo experiments were conducted by implanting preseeded disks subcutaneously on the flanks of rats for 2 and 5 weeks. Histologic staining of harvested disks with osmium tetroxide (OsO4) revealed the formation of adipose tissue throughout the disks. Fluorescence labeling of preadipocytes confirmed that formed adipose tissue originated from seeded preadipocytes rather than from possible infiltrating perivascular tissue. This study demonstrates the potential of using primary preadipocytes as a cell source in cell-seeded polymer scaffolds for tissue engineering applications.

Lower extremity salvage after radical resection of malignant tumors in the groin and lower abdominal wall.

BACKGROUND: Resection of a large malignant tumor in the groin often leaves a substantial soft-tissue defect that makes wound closure difficult. Nevertheless, palliation and lower extremity salvage is frequently possible if the tumor is widely excised and the wound closed with well-vascularized tissue; however, few data are available on patients undergoing such procedures. STUDY DESIGN: We retrospectively examined our experience with limb salvage in 25 patients undergoing radical groin resection for metastatic or recurrent malignant tumors between April 1, 1991 and April 8, 1996. RESULTS: Defect size ranged from 15 to 735 cm2 (mean, 238.5 cm2). Tumor resection included part of the abdominal wall in 14 patients and the femoral vessels in 5 patients. Defects were most commonly repaired with a vertical rectus abdominis myocutaneous flap (56%). Mean hospital stay was 10.4 days, and mean followup was 15.5 months. Although the complication rate was 68%, the limb salvage rate was 100%, and normal ambulation was achieved in 88% of patients. The most frequent complications were chronic lymphedema (42%) and seroma (29%). There was one perioperative death (4%). CONCLUSIONS: Functional limb salvage after radical resection of the groin and lower abdominal wall is very successful, has an acceptable morbidity rate, does not prolong hospital stay, and contributes significantly to the patient's quality of life. Chronic lymphedema is a frequent complication after this treatment but can be managed successfully with conservative techniques.

Osseous free flaps for orbit and midface reconstruction.

Osseous free flaps were used for reconstruction of the orbit and midface in 10 patients. The reconstruction was done at the time of tumor resection in two patients (20%) and secondarily in eight patients (80%). Nine patients (90%) had previously received radiotherapy. The flaps used were fibula (four), radial forearm (two), scapula (two), and split iliac crest (two). Flap loss occurred in one patient. Complications occurred in 2 of 10 (20%) patients. The results were classified as good in seven patients, fair in two, and poor in one. The patient classified as having a poor result was the one who sustained the flap loss; he refused further surgery. Reconstruction was directed to the maxilla in five patients, the orbit in two, and both in three. The radial forearm flap was best used for orbit-only reconstruction because of the small amount of bone required. The fibula, iliac crest, and scapula were best used for larger defects involving the maxilla. Osseointegrated dental implants were used successfully in three patients. Osseous free flaps are indicated for midface reconstruction when bony support is needed and previous irradiation prevents the use of nonvascularized grafts.

Comparison of the rectus abdominis free flap with the pectoralis major myocutaneous flap for reconstructions in the head and neck.

The pectoralis major myocutaneous flap (PMMF) is often used in the reconstruction of large head and neck defects. Unfortunately, its use is associated with a high incidence of minor complications, can distort the contour of the neck, and may cause significant donor site deformity, especially in women. This study compared 30 patients with major head and neck cancer-related defects who underwent reconstruction with a rectus abdominis free flap (RAFF) with 39 patients with similar defects who underwent reconstruction with the PMMF. The complication rate found in the RAFF group (13%) was significantly lower than that found in the PMMF group (44%; p = 0.0145). Flap necrosis was found in 10% of the PMMF group, whereas none was found in the RAFF group. The aesthetic outcome was also better in patients who had reconstructions with the RAFF. We conclude that, for most major head and neck defects, reconstruction methods that utilize the RAFF and other free tissue transfer techniques are preferable when the requisite equipment and expertise are available.

Influence of prior radiotherapy on the development of postoperative complications and success of free tissue transfers in head and neck cancer reconstruction.

The purpose of this study was to determine whether prior radiotherapy had any effect on the development of postoperative complications in patients undergoing microvascular tissue transfers for reconstruction of head and neck cancer. A prospective database was used to review 354 consecutive patients who had a total of 368 free tissue transfers limited to the head and neck during the 4-year period from July 1988 to June 1992. Postoperative complications in 167 patients who received preoperative radiotherapy (XRT) were compared with those of 187 patients who did not undergo radiotherapy preoperatively (NR). No statistical differences in complications or flap loss between the two groups were noted using the chi 2 test or Fisher's exact test (p > 0.2). Total flap loss occurred in 5.3% of the XRT group (9 of 169) and 5.0% of the NR patient group (10 of 199), and partial flap loss occurred in 4.1% of the irradiated patients and 2.5% of the nonirradiated patients. Major wound complications requiring additional surgery occurred in 16% of the XRT group and 11% of the NR group. Minor wound complications that did not require further surgery occurred in 21% of the irradiated patients and 18% of the nonirradiated patients. No significant difference in the timing or dose of preoperative radiation, previous neck dissection, or anastomotic type could be documented in failed versus successful flaps (two-tailed t-test, p > 0.80, and chi 2, p > 0.2). Our results show that, in a large group of cancer patients undergoing free tissue transfers to the head and neck, prior radiotherapy or surgery did not predispose them to a higher rate of acute flap loss or wound complications than their nonirradiated cohorts.

The radial forearm free flap for head and neck reconstruction: a review.

BACKGROUND: The radial forearm free flap has become a workhorse flap in head and neck reconstruction. Its lack of bulk, ease of dissection, vascularity, and malleability are among its many advantages. PATIENTS AND METHODS: A review of 157 radial forearm free flaps performed in 155 patients between March 1988 and June 1994 at The University of Texas M.D. Anderson Cancer Center was undertaken to determine outcome. Patient age ranged from 22 to 80 years (mean 56). There were 79 men and 76 women. Follow-up ranged from 2 to 75 months. The most prevalent neoplasm was squamous cell carcinoma (n = 129). RESULTS: The most frequent tumor staging was T3, N0, M0. Various defects were observed; however, those requiring floor-of-mouth coverage were most common (n = 95). Partial or segmental mandibular resection was seen in 42. An osseous component was included in the radial forearm flap in 9 patients, and 64 patients had undergone some form of previous tumor resection. Fifty-seven patients received preoperative irradiation and 52, postoperative. The internal jugular vein (n = 131) and the external carotid artery (n = 134) were the most frequent recipient sites for microvascular anastomosis. Vein grafts were needed in 4 cases, and end-to-side anastomoses were most commonly performed. Total flap loss occurred in 7 cases (4.5%) and partial flap loss in 1 (0.6%). For total flap loss, salvage was accomplished by a second radial forearm free flap in 2 cases and alternative rotational flaps in 5. Other complications (infection, hematoma, fistula formation, etc.) were seen in 34%. Donor-site difficulties were seen in 21 cases. CONCLUSION: The radial forearm free flap offers a variety of reconstructive options for the head and neck. Its low flap loss and complication rates offer the best choice for oral lining restoration if bulk is not required.

Aesthetically successful mandibular reconstruction with a single reconstruction plate.

Aesthetically successful mandibular reconstruction can be performed with free fibular flaps and with a single low-profile reconstruction plate. The keys to aesthetic success are accurate bending of the reconstruction plate, accurate alignment of the bone, and maintenance of the lower border of the mandible. If only the mandible and overlying oral lining are missing, the results can be indistinguishable from normal. In massive defects that include other structures besides the mandible, however, excellent aesthetic results can be difficult or impossible. Massive soft tissue deficits and heavy doses of postoperative radiation therapy can impact severely the aesthetic quality of the result. Patients should be aware of these limitations and have appropriately realistic expectations.

Reconstruction of the pharynx and cervical esophagus using free jejunal transfer.

Although FJT has been perceived as unreliable, current FJT survival rates of 94% or greater, FJT salvage rates of up to 100%, and perioperative mortality of 6% or less demonstrate that FJT is a safe, reliable, one-stage method of reconstructing partial and circumferential pharyngoesophageal defects. FJT is associated with some morbidity; however, the procedure is well tolerated, and swallowing function is restored in 80% or more of patients within an average of 9 to 12 days after surgery. The success of the technique requires careful attention to details, such as designing the flap to avoid vein grafts, selecting large recipient vessels with high blood flow, careful in setting of the flap, meticulous microvascular anastomotic technique, close postoperative monitoring, and early, aggressive treatment of infection. If FJT failure should occur, a repeat FJT should be performed in the immediate postoperative period to increase the possibility of salvage and to decrease the risk of infection and mortality.

Rehabilitation of a midface defect with reconstructive surgery and facial prosthetics: a case report.

This paper reports a case in which reconstruction of a midface defect was accomplished by using microvascular surgery with free tissue transfer of the fibula for a 55-year-old man with squamous cell carcinoma in the nasal vestibule and nasal wall. This technique was developed and first used to reconstruct mandibular defects. Using a surgical template during the midface reconstruction can help the surgeon place the graft in a position that will complement the definitive facial prosthesis, as illustrated in this report.

Lower back reconstruction: an approach to wound closure in the cancer patient.

Repair of the lower back wound in the patient with cancer presents the surgeon with a plethora of challenges. Frequently, the wide range of the surgeon's armamentarium of flaps must be used to provide stable wound coverage. We present the reconstruction techniques used in five patients with cancer who had lower back wounds below T10 and of at least 100 cm2. The approach we used to evaluate the lower back wound and to determine surgical techniques and options for reconstruction is discussed.

Deep-plane cervicofacial rotation-advancement flap for reconstruction of large cheek defects.

The blood supply and reliability of cervicofacial rotation-advancement flaps for cheek reconstruction can be improved significantly by dissecting the flap in the deep plane (i.e., below the superficial musculoaponeurotic system and the platysma). This modification, similar in technique to that used in composite or deep-plane face lift, was used successfully in seven patients, including several heavy cigarette smokers who were unlikely to have achieved a successful outcome with a conventional cervicofacial flap. No facial nerve weaknesses were observed. We now believe that the deep plane is the level of choice for dissection of cervicofacial flaps when used for reconstruction of cheek or other facial defects.

Lateral thigh free flap in head and neck reconstruction.

To understand the role of the lateral thigh flap in head and neck reconstruction, we performed injection studies and anatomic dissections in 2 fresh and 61 preserved cadaver extremities followed by 10 clinical cases involving defects after tumor ablation. The flap, based on the third perforator of the profunda femoris artery, is designed on the posterolateral aspect of the distal thigh. The pedicle courses through the biceps short head, allowing optional transfer of this muscle. Defects of the oral cavity, pharynx, cervical esophagus, and external skin were successfully restored. One flap was unsuccessful because of intraoperative injury to the vascular pedicle. Compared with the radial forearm flap, the lateral thigh flap provides more tissue and the donor scar is more easily hidden, but the vascular pedicle is shorter, of smaller caliber, and more variable. The lateral thigh flap provides thin, pliable, and reliable tissue for a variety of needs in properly selected patients.

The osteocutaneous free fibula flap: is the skin paddle reliable?

This clinical and anatomic study was undertaken to see if the skin paddle of the osteocutaneous fibula flap could be made more reliable. Eighty cadaver limbs were dissected to evaluate the type, number, and location of the cutaneous perforators supplying the lateral leg. Three types of perforators were identified: septocutaneous, musculocutaneous, and a type we termed septomuscular, which does not actually run within the muscle substance but is adherent to the muscle. Although not a true musculocutaneous perforator, it should be treated as such clinically. Musculocutaneous perforators were found to be more numerous and more proximal than the septocutaneous perforators. Eighteen clinical cases demonstrate a 33 percent skin paddle survival when dissected as a septocutaneous flap and a 93 percent skin paddle survival when dissected as a septomusculocutaneous flap. In using the osteocutaneous fibula flap, it is recommended that a cuff of soleus and flexor hallucis longus be incorporated into the flap to help ensure flap viability.

Use of the AO plate for immediate mandibular reconstruction in cancer patients.

Free vascularized bone grafts have revolutionized mandibular reconstruction, yet their use in all mandibulectomy patients is not always necessary. A recently developed alternative to bony reconstruction has been the use of the AO reconstruction plate. We compared the use of the AO reconstruction plate with immediate free bone graft mandibular reconstruction in 31 patients. Reconstruction plates were used in 20 and immediate free bone grafts were used in 11 patients. The overall success rate for use of the plate was 15 of 20 (75 percent). There were 6 anterior reconstructions, of which only 2 (33 percent) were successful. This is opposed to 13 of 14 (93 percent) lateral reconstructions that were successful in lateral plate placements. There were 11 immediate composite free flaps: 4 iliac crest, 4 scapula, 2 fibula, and 1 composite radial forearm flaps. Six repairs were for anterior defects, and there were 5 full-thickness defects, 3 of which were in the anterior position. All 11 flaps were successful. In conclusion, we believe the reconstruction plates are a useful adjunct for mandibular replacement in the head and neck cancer patient but should be reserved for lateral defects. For anterior reconstructions, even in patients with locally advanced disease, free-tissue transfer of composite osteocutaneous flaps is the reconstructive method of choice.

Abdominal wall strength, bulging, and hernia after TRAM flap breast reconstruction.

The incidence of postoperative abdominal bulge, hernia, and the ability to do sit-ups was reviewed in a series of 268 patients who had undergone free TRAM (FTRAM) or conventional TRAM (CTRAM) flap breast reconstruction. Minimum follow-up was 6 months. Patients were divided into four groups: unilateral FTRAM (FT1P; n = 123), double-pedicle bilateral FTRAM (FT2P; n = 45), single-pedicle CTRAM (CT1P; n = 40), and double-pedicle or bilateral CTRAM (CT2P; n = 60). The incidence of abdominal bulges (3.8 percent) and hernia (2.6 percent) was similar in the four groups. Synthetic mesh, however, was required for reinforcement of donor site closure twice as often in the CTRAM patients. The ability to perform sit-ups was greatest in the FT1P group (63.0 percent), slightly lower in the CT1P group (57.1 percent), still lower in the FT2P group (46.2 percent), and lowest in the CT2P group (27.1 percent; p = 0.0005). Patients reconstructed with an FTRAM flap were more likely to be able to do sit-ups (58.3 percent) than were those reconstructed with a CTRAM flap (38.2 percent; p = 0.0074). Patients who had only one muscle pedicle used were more likely to be able to do sit-ups (61.7 percent) than were those who had two muscle pedicles used (35.6 percent; p = 0.0003). We conclude that the incidence of abdominal bulge or hernia is relatively independent of the type of TRAM flap used and the number of muscle pedicles harvested. On the other hand, postoperative abdominal strength, as measured by the ability do sit-ups, is influenced significantly by both of these factors.

Breast reconstruction with myocutaneous flaps in previously irradiated patients.

Breast reconstructions performed with latissimus dorsi and transverse rectus abdominis myocutaneous (TRAM) flaps in 82 patients with a history of previous chest-wall irradiation were compared with similar reconstructions in 202 nonirradiated patients to determine whether prior irradiation was associated with more frequent complications and to determine the success rate of breast reconstruction using distant flaps in irradiated patients. The mean dose of radiation administered was 5637 cGy. Complications in the reconstructed breast were more frequent in the irradiated patients (39 percent) than in the nonirradiated patients (25 percent; p = 0.03). In the irradiated group, breast complications were more common in reconstructions performed with the latissimus dorsi flap (63 percent) than in those performed with the TRAM flap (33 percent; p = 0.063). Aesthetic outcomes also were slightly poorer in the irradiated patients. Although complications were more common and aesthetic outcomes not as good in previously irradiated patients, we do not consider such irradiation to be a contraindication to breast reconstruction.

A single center's experience with 308 free flaps for repair of head and neck cancer defects.

Since its inception at our institution in 1988, microvascular reconstructive surgery has become an integral part of the treatment of head and neck cancer patients. This review of 308 free flaps performed over the last 4 years was done to evaluate the complication and flap loss rates and to investigate which factors may contribute to these rates. The overall complication rate was 36.1 percent, the vessel thrombosis rate was 6.8 percent, the flap loss rate was 5.5 percent, and the flap salvage rate was 19.0 percent. Multifactorial analysis of delayed reconstruction, tobacco use, alcohol consumption, previous radiation therapy, previous surgery, and use of vein grafts showed that only previous surgery and the use of vein grafts led to significantly higher rates of flap loss (p < 0.01 for both).

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

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 > or =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 normal-weight 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.

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

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.