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Summary Background The risk of BIA-ALCL for patients with textured breast implants has been estimated between 1/2832 and 1/30,000 women. Existing studies estimating the numbers exposed and at risk, may have under reported cases, and/or lacked comprehensive follow-up. Our objective is to determine the risk of BIA-ALCL in a defined cohort of patients reconstructed with macro-textured breast implants and consistently followed long-term. Methods A prospective cohort study was conducted in patients who underwent breast reconstruction by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC) from December 1992 to December 2017. Major events related to implants were prospectively recorded. We identified cases of BIA-ALCL by cross-checking clinical, pathology and external records data. Patients were followed until lymphoma occurrence or last follow-up. The primary outcomes were incidence rate per person-years and cumulative incidence. Results From 1992 to 2017, 3546 patients underwent 6023 breast reconstructions, mainly after breast cancer removal, or contralateral prophylactic mastectomy, using macro-textured surface expanders and implants. All reconstructions were performed by a single surgeon (PGC). Median follow-up was 8.1 years (range, 3 months – 30.9 years). Ten women, 1/354, developed ALCL after a median exposure of 11.5 years (range, 7.4–15.8 years). Overall risk of BIA-ALCL in our cohort is 1/355 women or 0.311 cases per 1000 person-years (95% CI 0.118 to 0.503). Discussion This study, the first to evaluate the risk of macro-textured breast implants from a prospective database with long term follow-up, demonstrates that the incidence rate of BIA-ALCL may be higher than previously reported. These results can help inform implant choice for women undergoing breast reconstruction.

e20028 Background: Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), a subtype of ALCL, arises as a seroma in the space between the implant and the capsule, or as an adjacent mass. BIA-ALCL appears to be related to textured-surface implants, after 7-10 years of exposure. We conducted two large cohort studies. The 1st, a retrospective series (Sutton, 2019) assessed the incidental findings of masses or seromas in 1070 women with breast implants undergoing MR for FDA recommended screening for silent ruptures of silicone implants. Incidental finding of seromas or breast masses on MRI were found in 18/1070 (1.7%) women, of which 1/15 had BIA-ALCL, and was symptomatic at the time of MRI. The 2nd, a prospective study (Cordeiro, 2020) defined the incidence of BIA-ALCL (1/355) in a cohort of 3546 women with textured implants followed long term. Within this cohort, there were 28 clinically relevant delayed seromas (0.79%), 8 of which were BIA-ALCL (28.5%). We hypothesize that combining these databases will inform whether asymptomatic women with textured implants may benefit from MR to r/o BIA-ALCL. Methods: The two IRB approved databases were merged. Patients with incidental findings of seroma on MRI were identified. A majority of the MRIs in this merged cohort were performed to follow the FDA recommended screening for silent ruptures. We identified all clinically relevant late seromas sent to hematopathology to r/o BIA-ALCL by cross checking pathology reports containing the words “lymphoma” or “anaplastic” or “ALCL”. Results: 572 women were included in both studies: followed long term and received an MRI after a median time of 7.4 years after breast reconstruction. 8 of 572 women had an incidental finding of seroma on random MRI, and 2 had capsular masses. None of these 10 asymptomatic women have developed BIA-ALCL to date (median follow-up 9 years). 11 of 572 women had a symptomatic seroma or mass, 4 of which later developed BIA-ALCL, a fifth patient was found to have BIA-ALCL on a PET/CT + lymph node, despite being asymptomatic. Median time from last MR to lymphoma was 5 years (3-8 years). Conclusions: In this merged cohort of patients with textured breast implants, incidence of BIA-ALCL in patients with symptomatic late seromas is around 30%, while seromas found incidentally on MR of asymptomatic patients were negative for BIA-ALCL.

BACKGROUND Postmastectomy radiation therapy is increasingly indicated in patients with node-positive breast cancer. The authors prospectively evaluated long-term outcomes in patients with two-stage implant-based reconstruction and postmastectomy radiation therapy to the permanent implant. METHODS A cohort of 1415 patients operated on by a single surgeon from 1998 to 2010 was evaluated annually. Outcomes were recorded prospectively. Complication rates were compared between irradiated and nonirradiated implants, including reconstructive failure (implant loss), complications (e.g., capsular contracture), aesthetic results, and satisfaction. Predicted implant loss and replacement rates were examined by irradiation status with Kaplan-Meier analysis and the log-rank test. RESULTS A total of 2133 breast implant reconstructions with a mean follow-up of 56.8 months (range, 12 to 164 months) were included. Three hundred nineteen implants received radiation. Implant loss occurred in 9.1 percent of irradiated implants and 0.5 percent of nonirradiated implants (p < 0.01). Capsular contracture grade IV was present in 6.9 percent of irradiated and 0.5 percent of nonirradiated implants (p < 0.01). There was no difference between groups regarding implant replacement. Ninety-two percent of irradiated patients had good to excellent aesthetic result, and 94.2 percent would choose implants again. Predicted implant loss rates were 17.5 percent and 2.0 percent for irradiated and nonirradiated implants, respectively, at 12 years (p < 0.01), and predicted implant replacement rates were 12.7 percent and 8.8 percent, respectively, at 8 years (p = not significant). CONCLUSIONS This is the largest prospective long-term outcomes evaluation in women with immediate tissue expander/implant reconstruction and postmastectomy radiation therapy. Most patients had a good to excellent aesthetic result and preserve their reconstruction at 12 years. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

Introduction:Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is an indolent subtype of ALCL, arising in the space between the implant and the capsule. BIA-ALCL seems to be directly related to the exposure to breast implants, and usually happens more than 7 years from implant placement. In 2011 the Food and Drug administration released the first safety communication on the risk of BIA-ALCL for women with breast implants, raising awareness of the disease. In 60-70% of the cases BIA-ALCL presents as a delayed seroma, a non-resolving fluid collection around breast implants arising after at least 1 year from implant placement. In previous studies, the risk of developing a late seroma ranged between 0.05% to 0.1% for people with textured surface breast implants. Among those with delayed seromas, the risk of BIA-ALCL has been estimated from retrospective cohorts to be 10%. (McGuire 2017, Clemens 2017, Maxwell 2015, Di Napoli 2017). Methods:A prospective cohort study was conducted in the population that underwent breast reconstruction with textured breast implants after mastectomy for breast cancer by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC). Patients were enrolled from December 1992 to December 2017 at the time of tissue expander insertion, underwent long-term follow up and major events related to implants were prospectively recorded. We actively started looking for BIA-ALCL in late seromas in early 2011. All cases of BIA-ALCL were analyzed by our hematopathology service at MSKCC. We identified all late seromas sent to hematopathology to exclude BIA-ALCL by cross checking all the pathology reports containing the words "lymphoma" or "anaplastic" or "ALCL" in this population. We calculated the cumulative incidence of clinically relevant late seromas, considering death as a competing risk with the statistical program R version 3.5.1. Results:Between 1992 and 2017, 3521 women underwent breast reconstruction with textured surface expanders followed by permanent textured breast implants. Median age at surgery was 48 years (range 18-88), 1056 (30.0%) underwent unilateral reconstruction and 2464 (70.0%) bilateral reconstruction. Reason for mastectomy was lobular carcinoma in 675 (19.1%), 116 in situ, ductal carcinoma in 2529 (71.8%), 591 in situ, other histology in 59 (1.7%), unknown in 257 (7.3%). Besides surgery, additional treatments for breast cancer were: chemotherapy in 1015 (28.8%), radiotherapy in 285 (8.1%), chemo and radiotherapy in 706 (20.0%), none in 1514 (43.0%). Median follow up of the cohort was 8.2 years (range 3.4 months - 26.4 years). After a median exposure of 9 years (range 1.8 - 15.8 years), 28 women developed a clinically relevant delayed seroma, and 8 were diagnosed with BIA-ALCL (28.5% of the late seromas). The first late seroma was analyzed with flow cytometry in February 2011. All seromas sent to pathology were clinically relevant (main symptom was swelling of the breast - in 15 patients, tenderness/fullness of the breast - in 5 patients, asymmetry - in 3 patients, capsule contracture - in 5 patients). Three patients had previous drainage of peri-implant fluid that was not analyzed in pathology. 2 additional cases of BIA-ALCL were diagnosed in this population, one on an internal mammary chain lymph node biopsy, without fluid collection, and another with a capsular mass and lymph node involvement. Rate of late seroma accounting for the varying follow-up and death as a competing event was 1.6% at 15 years. Rough percentage getting a seroma was 0.79%, 1/126 women exposed. All the 28 samples were analyzed with cytology, and 22/28 with flow cytometry including CD30. 14/28 (50%) of these women removed the implants for several reasons, 3/28 (10.7%) immediately exchanged the implants with another textured surface device. Conclusions:in this population of breast cancer patients receiving textured breast implant reconstructions, the incidence of clinically relevant seromas and BIA-ALCL seems higher than previously reported. Similarly, the ratio of patients testing positive for BIA-ALCL on the total number of seromas analyzed higher than previously estimated. We believe these results will be informative for people with breast reconstructions after breast cancer and their surgeons, to better estimate the risk of seroma and BIA-ALCL with textured implants. Disclosures Cordeiro: Inamed: Research Funding; Acelity: Research Funding; Allergan: Research Funding. Dogan:Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; Corvus Pharmaceuticals: Consultancy; Roche: Consultancy, Research Funding. Horwitz:Seattle Genetics: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Trillium: Research Funding; Kyowa Hakko Kirin: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Astex: Consultancy; Portola: Consultancy; Affimed: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Kura: Consultancy; Celgene: Consultancy, Research Funding; Affimed: Consultancy; Trillium: Research Funding; Forty-Seven: Research Funding; Miragen: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; Affimed: Consultancy; ADCT Therapeutics: Research Funding; Trillium: Research Funding; ADCT Therapeutics: Research Funding; Innate Pharma: Consultancy; Affimed: Consultancy; Forty-Seven: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy; Portola: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Mundipharma: Consultancy; Mundipharma: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Innate Pharma: Consultancy; Aileron: Research Funding; Innate Pharma: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Miragen: Consultancy; Miragen: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy; Kura: Consultancy; Kura: Consultancy; Aileron: Research Funding; ADCT Therapeutics: Research Funding; Innate Pharma: Consultancy; Astex: Consultancy; ADCT Therapeutics: Research Funding; Astex: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Astex: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Forty-Seven: Research Funding; Infinity/Verastem: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Aileron: Research Funding; Kura: Consultancy; Trillium: Research Funding; Portola: Consultancy; Forty-Seven: Research Funding.

Background The deep inferior epigastric perforator (DIEP) flap is a major advance in breast reconstruction, but many surgeons are reluctant to use it because of concerns about a higher flap loss rate when compared with free/muscle-sparing transverse rectus abdominis myocutaneous (TRAM) flaps. Previous studies, however, have not statistically analyzed the relationship of patient characteristics to outcome. This study evaluates the authors' institutional experience with immediate postoperative complications following DIEP and free/muscle-sparing TRAM flaps. Methods Results of 200 consecutive free/muscle-sparing TRAM and DIEP flaps performed by two surgeons at a single institution between 2003 and 2005 were reviewed using a prospectively maintained database. The incidence of flap complications was compared. Patient demographics, procedure type, diagnosis, adjuvant treatment, and complications were recorded. Outcome variables included total and partial flap loss, infection, seroma, hematoma, wound-healing problems, fat necrosis, and mastectomy flap necrosis. Results One hundred forty-three patients were treated with 159 free/muscle-sparing TRAM flaps and 41 DIEP flaps. The demographics of the two groups were statistically similar. No statistically significant differences were noted in total or partial flap loss. Conclusions In the authors' series, the use of the DIEP flap did not result in more postoperative flap-related complications when compared with the free/muscle-sparing TRAM flap. Furthermore, no patient characteristics were statistically associated with a more successful result. The authors conclude that in patients whose anatomy reveals perforators of adequate size, the DIEP flap is a safe and reliable procedure for breast reconstruction.

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

Background:Postmastectomy radiotherapy is increasingly common for patients with advanced breast cancer. The optimal timing and sequence of mastectomy, reconstruction, and radiotherapy remains unresolved for patients choosing immediate two-stage prosthetic reconstruction.Methods:Long-term outcomes we

Management of recurrent soft tissue sarcomas often involves surgical resection and adjuvant brachytherapy. This study reviews our experience in the management of these patients and proposes a logical approach toward reconstruction. All patients who underwent soft tissue sarcoma resection, adjuvant brachytherapy, and soft tissue flap reconstruction (pedicled or free) during the 10-year period from 1991 to 2000 were included in this study. There were 17 patients (14 male, 3 female) with a mean age of 51 years (range, 16-80 years). Soft tissue sarcomas were distributed in the lower extremity (n = 9), upper extremity (n = 5), and trunk (n = 3). Reconstruction was accomplished by regional transposition flaps (n = 10) and free tissue transfer (n = 7). The average defect size was 143 cm 2 . Patients received 5 to 12 (mean, 8) brachytherapy catheters. The brachytherapy dose delivered ranged from 1600 to 4500 cGy (mean, 3773 cGy). Brachytherapy catheters were loaded with radioactive sources between 5 and 7 days postoperatively. All flaps in this series survived. One patient required return to the operating room for revision of a venous thrombosis with flap salvage. Closed suction drainage tubes were left in place until after the brachytherapy catheters were removed to avoid dislodging the catheters. Two patients developed postradiation partial-thickness skin necrosis with delayed secondary wound healing. This study demonstrates that soft tissue reconstruction in the setting of sarcoma resection and brachytherapy catheter placement is safe and efficacious. Postoperative wound healing complications can be minimized through coordination among the ablative surgeon, reconstructive surgeon, and radiation oncologist. Specifically, placement of microvascular anastomoses well away from the radiation target area is indicated whenever possible. Finally, removal of closed suction drainage tubes should be deferred until after the brachytherapy catheters are removed to minimize complications resulting from catheter dislodgement.

Osseous free flaps have become the preferred method for reconstructing segmental mandibular defects. Of 457 head and neck free flaps, 150 osseous mandible reconstructions were performed over a 10-year period. This experience was retrospectively reviewed to establish an approach to osseous free flap mandible reconstruction. There were 94 male and 56 female patients (mean age, 50 years; range 3 to 79 years); 43 percent had hemimandibular defects, and the rest had central, lateral, or a combination defect. Donor sites included the fibula (90 percent), radius (4 percent), scapula (4 percent), and ilium (2 percent). Rigid fixation (up to five osteotomy sites) was used in 98 percent of patients. Aesthetic and functional results were evaluated a minimum of 6 months postoperatively. The free flap success rate was 100 percent, and bony union was achieved in 97 percent of the osteotomy sites. Osseointegrated dental implants were placed in 20 patients. A return to an unrestricted diet was achieved in 45 percent of patients; 45 percent returned to a soft diet, and 5 percent were on a liquid diet. Five percent of patients required enteral feeding to maintain weight. Speech was assessed as normal (36 percent), near normal (27 percent), intelligible (28 percent), or unintelligible (9 percent). Aesthetic outcome was judged as excellent (32 percent), good (27 percent), fair (27 percent), or poor (14 percent). This study demonstrates a very high success rate, with good-to-excellent functional and aesthetic results using osseous free flaps for primary mandible reconstruction. The fibula donor site should be the first choice for most cases, particularly those with anterior or large bony defects requiring multiple osteotomies. Use of alternative donor sites (i.e., radius and scapula) is best reserved for cases with large soft-tissue and minimal bone requirements. The ilium is recommended only when other options are unavailable. Thoughtful flap selection and design should supplant the need for multiple, simultaneous free flaps and vein grafting in most cases.

Nitric oxide is a radical with vasodilating properties that protects tissues from neutrophil-mediated ischemia-reperfusion injury in the heart and intestine. Previous studies in our laboratory suggested that L-arginine, a nitric oxide precursor, can protect skin flaps from ischemia-reperfusion injury. In this study, we examined the effects of L-arginine on the survival of myocutaneous flaps in a large animal model and established whether this effect was mediated by nitric oxide and neutrophils. Two superiorly based 15 x 7.5 cm epigastric myocutaneous island flaps were dissected in 15 Yorkshire pigs weighing 45 to 50 kg. One of the flaps was subjected to 6 hours of arterial ischemia and then reperfused for 4 hours (ischemia-reperfusion flaps), whereas the other flap was used as a non-ischemic control (non-ischemia-reperfusion flaps). The flaps were divided into four groups: control non-ischemia-reperfusion flaps that received only saline (group I); ischemia-reperfusion flaps that were treated with saline (group II); and flaps treated with either L-arginine (group III) or Nomega-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase competitive inhibitor, plus L-arginine in equimolar amounts (group IV). These drugs were administered as an intravenous bolus 10 minutes before the onset of reperfusion, followed by a 1-hour continuous intravenous infusion. Full-thickness muscle biopsies were taken at baseline, 3 and 6 hours of ischemia, and 1 and 4 hours of reperfusion. The biopsies were evaluated by counting neutrophils and measuring myelo-peroxidase activity. At the end of the experiment, skeletal muscle necrosis was quantified using the nitroblue tetrazolium staining technique, and a full-thickness biopsy of each flap was used for determination of water content. Statistical analysis was performed using analysis of variance and the Newman-Keuls test. Non-ischemia-reperfusion flaps showed no muscle necrosis. Ischemia-reperfusion flaps treated with saline had 68.7 +/- 9.1 percent necrosis, which was reduced to 21.9 +/- 13.6 percent with L-arginine (p < 0.05). L-NAME administered concomitantly with L-arginine demonstrated a necrosis rate similar to that of saline-treated ischemia-reperfusion flaps (61.0 +/- 17.6 percent). Neutrophil counts and myeloperoxidase activity after 4 hours of reperfusion were significantly higher in ischemia-reperfusion flaps treated with L-NAME and L-arginine as compared with the other three groups (p < 0.05). Flap water content increased significantly in ischemia-reperfusion flaps treated with saline and L-NAME plus L-arginine versus non-ischemia-reperfusion flaps (p < 0.02) and L-arginine-treated ischemia-reperfusion flaps (p < 0.05). There was no difference in flap water content between ischemia-reperfusion flaps treated with L-arginine and non-ischemia-reperfusion flaps. Administration of L-arginine before and during the initial hour of reperfusion significantly reduced the extent of flap necrosis, neutrophil accumulation, and edema due to ischemia-reperfusion injury in a large animal model. This protective effect is completely negated by the use of the nitric oxide synthase blocker L-NAME. The mechanism of action seems to be related to nitric oxide-mediated suppression of ischemia-reperfusion injury through neutrophil activity inhibition.

Background: Free tissue transfer has become an important method for reconstructing complex oncologic surgical defects, allowing single stage reconstruction in most instances. The purpose of this study is to review a single center's experience with free flap reconstruction and describe trends that have evolved with respect to technique and donor site selection. Methods: A retrospective review of 400 consecutive free flap reconstructions performed in 396 patients over 10 years was done. Regional applications include the head and neck (63%), trunk and breast (16%), lower extremity (16%), and upper extremity (5%). Donor sites include the fibula (109), rectus abdominis (93), forearm (72), latissimus dorsi (51), scapula (26), gluteus (25), jejunum (16), and five others (8). Microvascular anastomoses were performed to large-caliber vessels using a continuous suture technique; end-to-end anastomoses were preferred. Flaps were designed to avoid the need for vein grafts. Postoperative flap monitoring included clinical observation, conventional Doppler ultrasonography, surface temperature probes, and pinprick testing. Results: The overall free flap success rate was 97%. Twenty-eight flaps (7%) were reexplored, of which seventeen were salvaged (61%). Surviving flaps resulted in a healed wound that did not delay postoperative radiation or chemotherapy. The complication rate was 14%. The mean duration of hospitalization was 21 days, with an average cost of $40,000. Conclusions: The use of fewer, reliable donor sites to reconstruct the vast majority of oncologic defects and the simplification of the microsurgical process have contributed to the success of free tissue transfer in this series.

Pedicled flaps and microsurgical free tissue transfers are increasingly being used for reconstruction in the elderly and poorer risk patient. The use of systemically administered vasoactive agents to date has been avoided because of the fear that systemic levels of these agents perioperatively (particularly the vasopressors) might decrease blood flow and compromise the viability of the flap. There are no large-animal, real-time hemodynamic studies that support or disprove this belief. The objectives of this study were to (1) develop a musculocutaneous flap model in the pig that allows accurate, simultaneous monitoring of systemic and flap hemodynamic parameters such as flow and resistance and (2) identify the effects of commonly used vasoactive substances (dopamine, dobutamine, and phenylephrine) at clinically used levels on systemic and flap pressure/flow relationships. Vertically based rectus abdominis musculocutaneous flaps were raised in 8 anesthetized, 50- to 55-kg pigs, and a flow probe was placed around the artery. Catheters within the pulmonary artery and aorta were used to measure cardiac output and aortic root pressures. Measures of arterial blood pressure, cardiac output, and musculocutaneous flap flow were obtained at baseline and during the administration of varying doses of dopamine dobutamine and phenylephrine. Cardiac output increased significantly with low and high doses of dopamine and dobutamine, but decreased with increasing doses of phenylephrine. Flap flow, on the other hand, is increased only with dobutamine but remains unchanged with dopamine despite increased cardiac output. Flap flow decreases with high doses of phenylephrine. Flap flow also decreases relative to cardiac output with both dopamine and dobutamine. We conclude that (1) phenylephrine clearly affects flap flow adversely in a large-animal musculocutaneous model and therefore should be avoided, (2) dopamine does not affect total flap flow at either low or high doses despite increasing cardiac output, (3) dobutamine increases both flap flow and cardiac output, and (4) both dopamine and dobutamine should still be used with caution because the flap flow is not equally increased relative to total cardiac output. Possible changes in systemic and flap metabolic demand induced by these vasopressor drugs may therefore still be injurious to the flaps.

The objective of this study was to examine whether the administration of L-arginine, a precursor of nitric oxide and substrate of nitric oxide synthase, prior to reperfusion could lead to decrease in neutrophil-mediated tissue injury and improved flap survival. Epigastric island skin flaps were elevated in 70 rats and rendered ischemic. Thirty minutes prior to reperfusion, the rats were treated with intraperitoneal saline (n = 15), L-arginine (n = 15), D-arginine (n = 15), or N omega-nitro-L-arginine methylester plus L-arginine in equimolar amounts (n = 15). Flap survival at 7 days and neutrophil counts at 24 hours were evaluated. Flap necrosis as expected in the sham group of animals (n = 10) was 0.0 percent, while the control (saline-treated) animals had 59.6 percent necrosis. Animals treated with L-arginine demonstrated a significant decrease in flap necrosis to 12.7 percent. This protective effect was almost completely negated by N omega-nitrol-L-arginine methylester, which significantly increased flap necrosis to 49.3 percent and was much less pronounced with D-arginine (28.6 percent). Neutrophil counts were significantly decreased in flaps from L-arginine-treated and sham animals versus both saline and N omega-nitro-L-arginine methylester-treated groups. We conclude that administration of L-arginine prior to reperfusion can significantly reduce the extent of flap necrosis and flap neutrophil counts due to ischemia-reperfusion injury. This protective effect is completely negated by nitric oxide synthase inhibition. Since L-arginine reduces the number of neutrophils within the flap and the extent of flap necrosis only in the presence of active nitric oxide synthase, we hypothesize that this protective effect of L-arginine on ischemia-reperfusion injury is secondary to a nitric oxide-mediated suppression of neutrophil-mediated injury.

In this report, we discuss application of the noninvasive technology of ultraviolet fluorescence spectroscopy to the metabolic analysis of normal and compromised myocutaneous flaps. Acute changes in tissue redox states during ischemia and reperfusion were determined analysis of changes in the fluorescence spectrum of reduced nicotinomide adenine dinucleotide (NADH). Analysis of the system for NADH fluorescence showed good correlation between excitation spectra recorded at 450 nm from pure beta-NADH and those recorded from porcine rectus abdominis myocutaneous flaps. Sequential measurements of surface fluorescence were obtained from six flaps subjected to 6 hours of warm arterial ischemia and 4 hours of reperfusion. Results were compared with spectra obtained from six contralateral nonischemic control flaps. A significant mean increase in NADH fluorescence (49 percent; p < 0.05) was demonstrated within 30 minutes of vascular occlusion. Fluorescence intensity continued to increase throughout the ischemic period, reaching 320.5 percent of baseline values at 6 hours. Reperfusion resulted in the prompt return of fluorescence intensity to baseline levels. These results show that fluorescence spectroscopy of endogenous NADH is a sensitive and reliable indicator of vascular occlusion in experimental myocutaneous flaps.

Background: Microvascular free tissue transfer is a reliable method for reconstruction of complex surgical defects. However, there is still a small risk of flap compromise necessitating urgent reexploration. A comprehensive study examining the causes and methods of avoiding or treating these complications has not been performed. The purpose of this study was to review the authors' experience with a large number of microvascular complications over an 11-year period. Methods: This was a retrospective review of all free flaps performed from 1991 to 2002 at Memorial Sloan-Kettering Cancer Center. All patients who required emergent reexploration were identified, and the incidence of vascular complications and methods used for their management were analyzed. Results: A total of 1193 free flaps were performed during the study period, of which 6 percent required emergent reexploration. The most common causes for reexploration were pedicle thrombosis (53 percent) and hematoma/bleeding (30 percent). The overall flap survival rate was 98.8 percent. Venous thrombosis was more common than arterial thrombosis (74 versus 26 percent) and had a higher salvage rate (71 versus 40 percent). Salvaged free flaps were reexplored more quickly than failed flaps (4 versus 9 hours after detection; p = 0.01). There was no significant difference in salvage rate in flaps requiring secondary vein grafting or thrombolysis as compared with those with anastomotic revision only. Conclusions: Microvascular free tissue transfer is a reliable reconstructive technique with low failure rates. Careful monitoring and urgent reexploration are critical for salvage of compromised flaps. The majority of venous thromboses can be salvaged. Arterial thromboses can be more problematic. An algorithm for flap exploration and salvage is presented.

The repair of complex chest wall defects presents a challenging problem for the reconstructive surgeon. Although the majority of such defects could be repaired with the use of local and regional musculocutaneous flaps, more complicated cases require increasingly sophisticated reconstructive techniques. This study reviews the experience at a single cancer center with chest wall reconstruction over a decade. A retrospective review was undertaken for each patient who underwent chest wall reconstruction from 1992 to 2002. Patient demographics and variables, including pathologic diagnosis, extent of resection, size of defect, method of reconstruction, and outcome were evaluated. There was a total of 113 patients, 88 females and 25 males. The average age was 58 years (range, 19-88 years). The most common diagnoses were breast cancer and sarcoma. The average area of the chest wall defect after resection was 266 cm. One hundred fifty-seven musculocutaneous or muscle flaps were performed for reconstruction of the chest wall. Eleven percent of patients underwent reconstruction with autologous free tissue transfer. One hundred six patients underwent a single operation. Seven patients required a second operation for salvage of a complication. In 19 cases (15%), more than 1 flap was used simultaneously to complete the reconstruction. Eighty-four percent of the patients achieved stable chest wall reconstruction with no complications. Seven patients (4%) had partial (>10%) flap loss. The most common remaining postoperative complications were delayed wound healing (3% of patients), infection (2.5%), and hematoma (2.5%). Immediate chest wall reconstruction is safe, reliable, and can most often be accomplished with 1 operation. A variety of flaps, both single and in combination, could be used to achieve definitive coverage of the chest wall after extirpative surgery. The reconstructive choice is dependent on factors such as size of the defect, location on the chest wall, arc of rotation of the flap, and availability of recipient vessels. Based on this single institutional experience over a decade, an algorithm to chest wall reconstruction is provided.

The objective of this study was to examine the role of mast cells and their principal product, histamine, in ischemia/reperfusion injury. Cromolyn sodium, diphenhydramine, and cimetidine were administered to ischemic flaps just before reperfusion and evaluated for flap survival, mast cell count, neutrophil count, and myeloperoxidase levels. Epigastric island skin flaps were elevated in 49 rats; they were rendered ischemic by clamping the artery for 10 hours. Thirty minutes before reperfusion, the rats were treated with intraperitoneal saline (n = 11), cimetidine (n = 11), diphenhydramine (n = 11), or cromolyn sodium (n = 10). Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts, and myeloperoxidase levels were evaluated 12 hours after reperfusion. Flap necrosis in the sham group of animals (n = 6) was 0.0 percent, as expected, whereas the control group (saline-treated animals) had 47.3+/-33.4 percent necrosis. Animals treated with diphenhydramine and cimetidine demonstrated a significant decrease in flap necrosis to 17.7+/-8.8 percent and 19.4+/-14.7 percent, respectively. This protective effect was not seen with cromolyn sodium (44.3+/-35.6 percent). Both neutrophil and mast cell counts were significantly decreased in flaps from antihistamine-treated and sham animals versus both saline- and cromolyn sodium-treated groups. The administration of diphenhydramine and cimetidine before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion. This protective effect is not seen with cromolyn sodium. The protective effect of antihistamines on flap necrosis might be related to the decrease in neutrophils and, possibly, mast cells within the flap.

The present study was designed (1) to determine whether a free jejunal transfer in a large animal model can develop collateral circulation that is adequate to maintain viability after division of the pedicle and (2) to determine the earliest time pedicle ligation is safe after transplantation. A 15-cm jejunal segment was transferred to the necks of 18 dogs weighing 25 to 35 kg. The bowel segment was inset longitudinally under the skin on one side of the neck, partially covered by the neck muscles, and the mesenteric vessels were anastomosed to recipient vessels in the neck. The proximal and distal bowel stomas were exteriorized through skin openings 12 cm apart and matured. The dogs were subjected to ligation of the vascular pedicle at different intervals: postoperative day 7 (group I, n = 3), day 14 (group II, n = 5), day 21 (group III, n = 5), and day 28 (group IV, n = 5). Blood perfusion was measured in the proximal and distal bowel stomas before pedicle division (control) and 24 hours later using hydrogen gas clearance and fluorescein dye. Bowel necrosis was analyzed using planimetry. The bowel was also stained with hematoxylin and eosin and factor VIII, and new blood vessels were counted. Mean values (+/- standard deviation) were compared with control values for each test and with normal values in the intact bowel using analysis of variance with Neumann-Keuls post-hoc test for multiple comparisons. No jejunal free flaps survived when the vascular pedicle was divided 1 week postoperatively. Bowel survival was 60 percent at 2 weeks, 83 percent at 3 weeks, and 100 percent at 4 weeks. Hydrogen gas clearance values (ml/min/100 g) were 49.6 +/- 8.7 in the mucosa of the intraabdominal jejunum and 37.9 +/- 9.4 in the jejunum that was transferred to the neck before division of the pedicle. Twenty-four hours after pedicle division, hydrogen gas clearance values were 2.8 +/- 6.4 in group I (p < 0.05), 22.4 +/- 12.4 in group II, 23.9 +/- 9.3 in group III, and 34.2 +/- 7.5 in group IV. FluoroScan readings in the transferred jejunum were 201 +/- 7.2 in the control group, 9.3 +/- 2.8 in group I (p < 0.05), 79.1 +/- 10.6 in group II, 66.2 +/- 7.3 in group III, and 164 +/- 11.9 in group IV. New vessel formation as identified by factor VIII staining correlated with increasing bowel perfusion and flap survival rate. Bowel neovascularization, perfusion, and survival increased progressively 1 week after transfer. Significant portions of the transferred bowel will neovascularize and survive as early as 2 weeks postoperatively. However, a minimum of 4 weeks before ligation of the pedicle is necessary to maximize flap perfusion and guarantee survival.