A quantitative analysis of the performance of computing architectures used in neural simulations.

BACKGROUND: Numerical solutions of neuron models are helping neuroscientists gain new insights into the behavior of neural systems. Although computing power is increasing, the complexity of the systems being simulated is also increasing. If the computation is not well matched to the computing hardware, simulations can take lengthy times to run, which can make it more difficult to draw inferences from those simulations and also to use them in feedback with living neurons such as in the dynamic clamp. NEW METHOD: In this paper, we perform a quantitative analysis to get a better sense of how much impact the hardware architectures can have on simulation performance. Three different architectures are implemented on the same hardware platform and compared with respect to simulation time, error, and resources used. RESULTS: The results indicate that a lookup table approach to evaluate functions can decrease simulation time by orders of magnitude with respect to the traditional approach of mathematical operations. COMPARISON WITH EXISTING METHOD(S): There are many different ways to implement a lookup table approach to evaluate a function. The method presented in this paper sacrifices some speed for greater generality and accuracy with respect to other published methods. CONCLUSIONS: Lookup tables with 32 interpolation points can dramatically speed up computation time of neural simulations without adding significant error. In this paper linear interpolation was used, but higher order interpolation could be used to further reduce simulation time.

Genetic variations in cancer-related significantly mutated genes and lung cancer susceptibility.

BACKGROUND: Cancer initiation and development are driven by key mutations in driver genes. Applying high-throughput sequencing technologies and bioinformatic analyses, The Cancer Genome Atlas (TCGA) project has identified panels of somatic mutations that contributed to the etiology of various cancers. However, there are few studies investigating the germline genetic variations in these significantly mutated genes (SMGs) and lung cancer susceptibility. PATIENTS AND METHODS: We comprehensively evaluated 1655 tagged single nucleotide polymorphisms (SNPs) located in 127 SMGs identified by TCGA, and test their association with lung cancer risk in large-scale case-control study. Functional effect of the validated SNPs, gene mutation frequency and pathways were analyzed. RESULTS: We found 11 SNPs in 8 genes showed consistent association (P < 0.1) and 8 SNPs significantly associated with lung cancer risk (P < 0.05) in both discovery and validation phases. The most significant association was rs10412613 in PPP2R1A, with the minor G allele associated with a decreased risk of lung cancer [odds ratio = 0.91, 95% confidence interval (CI): 0.87-0.96, P = 2.3 × 10-4]. Cumulative analysis of risk score built as a weight sum of the 11 SNPs showed consistently elevated risk with increasing risk score (P for trend = 9.5 × 10-9). In stratified analyses, the association of PPP2R1A:rs10412613 and lung cancer risk appeared stronger among population of younger age at diagnosis and never smokers. The expression quantitative trait loci analysis indicated that rs10412613, rs10804682, rs635469 and rs6742399 genotypes significantly correlated with the expression of PPP2R1A, ATR, SETBP1 and ERBB4, respectively. From TCGA data, expression of the identified genes was significantly different in lung tumors compared with normal tissues, and the genes' highest mutation frequency was found in lung cancers. Integrative pathway analysis indicated the identified genes were mainly involved in AKT/NF-κB regulatory pathway suggesting the underlying biological processes. CONCLUSION: This study revealed novel genetic variants in SMGs associated with lung cancer risk, which might contribute to elucidating the biological network involved in lung cancer development.

Wnt signaling pathway pharmacogenetics in non-small cell lung cancer.

Wingless-type protein (Wnt)/ß-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III-IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2-4). In multivariate analysis, survival correlates with SNPs for AXIN2 (rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2-4), Wnt-5B (rs12819505), CXXC4 (rs4413407) and WIF-1 (rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3-5 unfavorable genotypes, respectively (P=3.8 × 10(-9)). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months, P=4.7 × 10(-8)). None of the SNPs achieved significance in cohorts 2-4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of LEMD3, a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2-4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1.

Lymphaticovenular bypass surgery for lymphedema management in breast cancer patients.

Historically, the reported incidence of upper extremity lymphedema in breast cancer survivors who have undergone axillary lymph node dissection has ranged from 9% to 41%. In the past 2 decades, sentinel lymph node biopsy has become popular as a way to minimize the morbidity associated with axillary dissection without compromising the cure rate for breast cancer patients. However, even with sentinel node biopsy, the postoperative incidence of upper limb lymphedema in breast cancer patients remains at 4-10%. Lymphedema occasionally emerges immediately after surgery but most often appears after a latent period. Obesity, postoperative seroma, and radiation therapy have been reported as major risk factors for upper extremity lymphedema, but the etiology of lymphedema is still not fully understood. Common symptoms of upper limb lymphedema are increased volume and weight of the affected limb and increased skin tension. The increased volume of the affected limb not only causes physical impairments in wearing clothes and in dexterity but also affects patients' emotional and mental status. Surgical management of lymphedema can be broadly categorized into physiologic methods and reductive techniques. Physiologic methods such as flap interposition, lymph node transfers, and lymphatic bypass procedures aim to decrease lymphedema by restoring lymphatic drainage. In contrast, reductive techniques such as direct excision or liposuction aim to remove fibrofatty tissue generated as a consequence of sustained lymphatic fluid stasis. Currently, microsurgical variations of lymphatic bypass, in which excess lymph trapped within the lymphedematous limb is redirected into other lymphatic basins or into the venous circulation, have gained popularity.

Primary versus secondary postmastectomy reconstruction.

Many patients who undergo a mastectomy desire breast reconstruction. The reconstructive surgeon must ensure that the patient has reasonable expectations and motives. While immediate breast reconstruction generally results in a more aesthetically pleasing breast, the primary consideration is treating the cancer. Immediate breast reconstruction has not been shown to affect the oncologic outcome; however, the reconstructive surgeon should confer with other treatment team members to obtain a clear understanding of the stage of cancer and any necessary adjuvant treatments. The likelihood of tumor recurrence, extent of excision required, and need for postoperative radiation, as well as psychosocial and financial considerations, may affect whether immediate or delayed reconstruction is appropriate.

Secondary malignant lymphoedema after mastectomy in two dogs.

This case report describes the diagnosis of secondary malignant lymphoedema in two dogs that had undergone a mastectomy. A remarkable severe oedematous lesion associated with lameness in the right hindlimb was observed in both cases. Diagnostic imaging examinations, including direct pedal lymphangiography (case 1) and lymphoscintigraphy (case 2), showed obstruction of lymph flow in the lymphatics of the right hindlimbs. Although the recommended medical management and physiotherapy had been applied to resolve the problems, oedema did not improve in the damaged region in both cases. Results of histopathological examinations suggested that the cause of the obstructed lymph flow was neoplastic cells in the lymphatics of the right hindlimb in both dogs.

Management of advanced mandibular osteoradionecrosis with free flap reconstruction.

BACKGROUND: The purpose of this study was to assess the effectiveness of free tissue transfer for treatment of advanced mandibular osteoradionecrosis (ORN) in head and neck cancer patients. METHODS: We reviewed 29 patients who were treated for advanced mandibular ORN by radical resection and reconstruction with free flaps at our institution. All patients had either failed to respond to conservative treatment, including hyperbaric oxygen therapy and debridement or had pathological fracture due to ORN. RESULTS: Twenty-four vascularized bone (17 fibula, five iliac, and two scapula), four rectus abdominis myocutaneous, and one radial forearm fasciocutaneous free flaps were used. The complications occurred in 6 of 29 patients (21%). A total of four flaps (14%) were lost. The mean follow-up was 2 years 9 months. All patients had complete resolution of ORN symptoms. No evidence of ORN recurrence was observed in any patient. CONCLUSION: For advanced osteoradionecrosis of the mandible, radical resection followed by reconstruction using free flap provides a reliable means of obtaining good wound healing with acceptable aesthetic and functional results.

Lateral thoracic artery as a vascular variant in the supply to the free serratus anterior flap.

The authors describe a case in which the dominant blood supply to a subperiosteally-harvested serratus anterior muscle and rib composite myoosseous free flap came from the lateral thoracic artery. There were no other associated features in this patient to warn of the vascular variant. Reconstructive surgeons should be aware of possible variations in the vascular anatomy of this flap.

Reconstructive management of contralateral breast cancer in patients who previously underwent unilateral breast reconstruction.

When a patient who has had unilateral breast reconstruction presents with a new cancer on the opposite side, the reconstructive management of the second breast can be unclear. This study was performed to determine whether reconstruction of the second breast is oncologically reasonable and to evaluate the reconstructive options available to these patients. Patients who had mastectomy with unilateral breast reconstruction between 1988 and 1994 and who had a minimal follow-up of 5 years from the initial breast cancer were reviewed. Of 469 patients reviewed, 18 patients (4 percent) were identified who developed contralateral breast cancer. Mean age at the initial breast cancer presentation was 43 years (range, 26 to 57 years), and mean age at presentation with contralateral breast cancer was 48 years (range, 36 to 67). The mean interval between the initial and contralateral breast cancer presentations was 5 years (range, 1 to 10 years). Mean follow-up from the time of contralateral breast cancer was 5 years (range, 1 to 9 years). In most cases, contralateral breast cancer presented at an early stage (13 of 18 patients; 72 percent), and a shift to an earlier stage at presentation of the contralateral cancer was evident compared with the initial breast cancer. Of the 18 patients who developed contralateral breast cancer, 16 (89 percent) had no evidence of disease, one was alive with disease, and one died. Reconstructive management after the initial mastectomy included 16 transverse rectus abdominis myocutaneous flaps (seven free and nine pedicled), one latissimus dorsi myocutaneous flap with implant, and one superior gluteal free flap. Surgical management of the second breast after contralateral breast cancer included breast conservation in two patients, mastectomy without reconstruction in four, and mastectomy with reconstruction in 12. Reconstruction of the second breast included one free transverse rectus abdominis myocutaneous flap, three extended latissimus dorsi flaps, two latissimus dorsi myocutaneous flaps with implants, three implants alone, two Rubens flaps, and one superior gluteal free flap. No major complications were noted after the reconstruction of the second breast. The best symmetry was obtained when similar methods and tissues were used on both sides. The incidence of contralateral breast cancer after mastectomy and unilateral breast reconstruction is low. In most cases, contralateral breast cancer presents at an earlier stage compared with the initial breast cancer, and the prognosis is good. In patients who develop a contralateral breast cancer after mastectomy and unilateral breast reconstruction, the reconstruction of the second breast after mastectomy is oncologically reasonable and should be offered to provide optimal breast symmetry and a better quality of life. The best result is obtained when similar methods and tissues are used on both sides.

Coverage of skull base defects.

Successful reconstruction of the cranial base requires a knowledge of this complex anatomic area, a careful assessment of the defect, a healthy respect for the potential for ascending infection and meningitis, and reliable techniques to effectively contain the intracranial space with vascularized tissue. The first step in reconstruction is a secure dural repair, which must be covered by a healthy vascularized layer. The scalp contains galeal and pericranial flaps, which are usually incorporated into the reconstruction. Sometimes, along with local muscles such as the temporalis, these local tissues are all that is needed to complete the reconstruction. When the defects are larger and in irradiated beds, free tissue transfer has emerged as the most reliable method to bolster the dural repair.

Comparison of immediate and delayed free TRAM flap breast reconstruction in patients receiving postmastectomy radiation therapy.

Tumor pathologic features and the extent of nodal involvement dictate whether radiation therapy is given after mastectomy for breast cancer. It is generally well accepted that radiation negatively influences the outcome of implant-based breast reconstruction. However, the long-term effect of radiation therapy on the outcome of breast reconstruction with the free transverse rectus abdominis myocutaneous (TRAM) flap is still unclear. For patients who need postmastectomy radiation therapy, the optimal timing of TRAM flap reconstruction is controversial. This study compares the outcome of immediate and delayed free TRAM flap breast reconstruction in patients who received postmastectomy radiation therapy. All patients at The University of Texas M. D. Anderson Cancer Center who received postmastectomy radiation therapy and who also underwent free TRAM flap breast reconstruction between January of 1988 and December of 1998 were included in the study. Patients who received radiation therapy before delayed TRAM flap reconstruction were compared with patients who underwent immediate TRAM flap reconstruction before radiation therapy. Early and late complications were compared between the two groups. Early complications included vessel thrombosis, partial or total flap loss, mastectomy skin flap necrosis, and local wound-healing problems, whereas late complications included fat necrosis, volume loss, and flap contracture of free TRAM breast mounds. Late complications were evaluated at least 1 year after the completion of radiation therapy for patients who had delayed reconstruction and at least 1 year after reconstruction for patients who had immediate reconstruction. During the study period, 32 patients had immediate TRAM flap reconstruction before radiation therapy and 70 patients had radiation therapy before TRAM flap reconstruction. Mean follow-up times for the immediate reconstruction and delayed reconstruction groups were 3 and 5 years, respectively. The mean radiation dose was 50 Gy in the immediate reconstruction group and 51 Gy in the delayed reconstruction group. One complete flap loss occurred in the delayed reconstruction group, and no flap loss occurred in the immediate reconstruction group. The incidence of early complications did not differ significantly between the two groups. However, the incidence of late complications was significantly higher in the immediate reconstruction group than in the delayed reconstruction group (87.5 percent versus 8.6 percent; p = 0.000). Nine patients (28 percent) in the immediate reconstruction group required an additional flap to correct the distorted contour from flap shrinkage and severe flap contraction. These findings indicate that, in patients who are candidates for free TRAM flap breast reconstruction and need postmastectomy radiation therapy, reconstruction should be delayed until radiation therapy is complete.

Reconstructive management of cranial base defects after tumor ablation.

Successful reconstruction after cranial base tumor ablation is paramount in preventing potentially life-threatening complications. The purpose of this study was to evaluate experiences of cranial base reconstruction and to identify reconstructive management principles that may assist in achieving successful cranial base reconstruction. All cranial base reconstructions performed by the Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer Center between January of 1993 and September of 1999 were reviewed. Analyses were performed to assess the impact of location of defect, type of reconstruction, type of dural repair, and history of preoperative radiation and chemotherapy on rates of complications, and patient survival. The 77 patients who underwent cranial base reconstruction after tumor ablation during the study period had a mean age of 52 years (6 to 84 years). The mean follow-up period was 28.7 months (1 to 76 months). Squamous cell carcinoma, the most common histopathologic type, was present in 24 patients (31 percent), and 35 patients (45 percent) presented with recurrent disease. Location of defects involved region I (anterior) in 31 patients (40 percent), region II (anterior-lateral) in 18 (23 percent), region III (lateral-posterior) in six (8 percent), and more than one region in 22 (29 percent). Reconstructive methods included free flaps in 52 patients (68 percent), temporalis muscle flaps in 14 (18 percent), pericranial flaps in eight (10 percent), and other local flaps (two galeal, one scalp) in three (4 percent). Of the 52 free flaps, 18 (35 percent) were used in region I, 14 (27 percent) in region II, six (12 percent) in region III, and 14 (27 percent) in defects involving more than one region. Of the 14 temporalis muscle flaps, 13 (93 percent) were used for defects involving regions I or II and one (7 percent) was used for a defect involving region III. Of the 11 pericranial and other local flaps, nine (82 percent) were used in region I, one (9 percent) in region II, and one (9 percent) in a combination of regions II and III. Complications occurred in 21 patients (27 percent): three total flap losses (4 percent), three partial flap losses (4 percent), two cerebrospinal fluid leaks (3 percent), two cases of meningitis (3 percent), two abscesses (3 percent), five cases of delayed wound healing (6 percent), two hematomas (3 percent), one wound infection (1 percent), and one cerebrovascular accident (1 percent). Overall survival was 77 percent at 2 years and 58 percent at 4 years. The type of reconstruction, location of defect, type of dural repair, and history of preoperative radiation and chemotherapy had no significant association with the incidence of complications. Neither the type of reconstruction nor the location of defect showed a significant effect on patient survival. In this experience, local flaps, such as pericranial or temporalis muscle flaps, are good choices for reconstruction of smaller anterior or lateral cranial base defects. For defects that require larger amounts of soft tissue, free flaps are appropriate. With proper patient selection, successful cranial base reconstruction can be performed with either local or free flaps with a low incidence of complications.

Comparison of cost for DIEP and free TRAM flap breast reconstructions.

A recent article by Kaplan and Allen suggested that deep inferior epigastric perforator (DIEP) flap breast reconstruction was less expensive than reconstruction performed with free transverse rectus abdominis musculocutaneous (TRAM) flaps. To test that hypothesis, a series of patients who had undergone unilateral breast-mound reconstruction by the first author using DIEP or free TRAM flaps between November 1, 1996, and March 30, 2000, were reviewed. Bilateral reconstructions and reconstructions performed by other surgeons in the department were excluded to eliminate all variables except the choice of flap. All hours in the operating room and days in the hospital until discharge were included. Early readmissions for the treatment of complications were included, as were the costs of the mastectomy in the case of immediate reconstructions, but late revisions and nipple reconstructions were not. The totals were then converted into resource costs in 1999 dollars, and the DIEP and free TRAM flap groups compared. There were 21 DIEP flaps and 24 free TRAM flaps in the series. In this series, there was no significant difference between the cost of DIEP and free TRAM flap breast reconstruction.

Unilateral and bilateral hypogastric artery interruption during aortoiliac aneurysm repair in 154 patients: a relatively innocuous procedure.

OBJECTIVE: Hypogastric artery (HA) occlusion during aortic aneurysm repair has been associated with considerable morbidity. We analyzed the consequences of interrupting one or both HAs in the standard surgical or endovascular treatment of aortoiliac aneurysms (AIAs). METHODS: From 1992 to 2000, 154 patients with abdominal aortic aneurysms (n = 66), iliac aneurysms (n = 28), or AIAs (n = 60) required interruption of one (n = 134) or both (n = 20) HAs as part of their endovascular (n = 107) or open repair (n = 47). Endovascular treatment was performed with a variety of industry- or surgeon-made grafts in combination with coil embolization of the HAs. The standard surgical techniques included oversewing or excluding the origins of the HAs and extending the prosthetic graft to the external iliac or femoral artery. RESULTS: There were no cases of buttock necrosis, ischemic colitis requiring laparotomy, or death when one or both HAs were interrupted. Persistent buttock claudication occurred after 16 (12%) of the unilateral and 2 (11%) of the bilateral HA interruptions. Impotence occurred in 7 (9%) of the unilateral and 2 (13%) of the bilateral HA interruptions. Minor neurologic deficits of the lower extremity were observed in 2 (1.5%) of the patients with unilateral HA interruption. CONCLUSIONS: Although HA flow should be preserved if possible, selective interruption of one or both HAs can usually be accomplished safely during endovascular and open repair of anatomically challenging AIAs. We believe other comorbid factors such as shock, distal embolization, or the failure to preserve collateral branches from the external iliac and femoral arteries may have contributed to the morbidity in other reports of HA interruption.

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.

Postoperative morphine requirements of free TRAM and DIEP flaps.

In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay.

Recent advances in reconstructive surgery for soft-tissue sarcomas.

The size and complexity of wounds following soft-tissue sarcoma resection have increased over the years. Many advances have been made in reconstructive surgery during the past 30 years. These advances have occurred because of refined knowledge of muscle, skin, and fascial blood flow and through the development of free tissue transfer techniques. In this review, current methods of reconstruction following sarcoma resection are discussed, and advances are highlighted.

Enabling sutureless vascular bypass grafting with the exovascular sleeve anastomosis.

PURPOSE: We describe a technique for end-to-end sleeve anastomosis that may enable minimally invasive bypass grafting and characterize the tensile strength, stenosis rate, durability, and healing of the anastomosis. METHOD: An anastomotic device assembly consisting of a cable tie-type band with mobile teeth elements is mounted on the outer surface of a polytetrafluoroethylene graft. The graft is drawn over the artery resulting in a sleeve of vessel within the graft. As the band is tightened over an intraluminal obturator, the independently mobile anchoring teeth are driven through the graft into the artery. The tensile strength of the anastomosis was compared with sutured anastomosis during in vitro studies using cadaveric human femoral arteries. For in vivo studies on pigs and goats, we used a proximal exovascular sleeve anastomosis along with a distal sutured aortic anastomosis. Survival animals were studied by angiogram postoperatively and at the time of explantation. RESULTS: In vitro studies showed no difference in maximal tensile strength between sutured and exovascular anastomoses (10.5 +/- 2.7 lb vs 10.2 +/- 3.0 lb, P =.83). However, loss of continuous graft to artery interface occurred at lower loads in the sutured anastomoses (6.5 +/- 0.6 lb, P <.05). In total, all 24 pigs tested in nonsurvival or survival settings sustained a successful and leakproof anastomosis. Of the 13 nonsurvival cases, maximal epinephrine-induced hypertension sustained over 15 minutes (peak systolic blood pressure > 210-250 mm Hg) was tolerated without leakage in a subgroup of five animals (100%). All 11 survival pigs had no pseudoaneurysms or stenosis relative to sutured control anastomoses at 6 week explantation (8.2 +/- 1.25 mm vs 8.5 +/- 1.6 mm, P =.21). The three long-term survival goats had no pseudoaneurysm or stenosis after 40 weeks. Histologic examination confirmed healing of the aorta to graft with minimal neointimal hyperplasia. CONCLUSION: Exovascular sutureless anastomosis appears comparable to sutured anastomosis in stenosis rate, healing, and durability, with some advantages in tensile strength and rapidity of application.

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.