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ABSTRACT: Current indications for radiation therapy in women with breast cancer are controversial and continue to be modified. Current indications for breast reconstruction in the setting of radiation therapy are also controversial and poorly defined. The purpose of this study is to analyze oncologic outcomes following various methods of breast reconstruction in the setting of radiation therapy. A retrospective review of 676 women who had breast reconstruction following mastectomy was completed. A total of 146 women had breast reconstruction either before or after radiation therapy and were analyzed. Response variables included tumor recurrence and patient demise for patients having autologous and prosthetic reconstruction. Explanatory variables included patient age, cancer stage, radiation therapy, diabetes mellitus, and tobacco use. Recurrence of tumor occurred in 29 of 146 women (19.8%), of which 27% was when radiation followed reconstruction and 14.9% was when radiation preceded reconstruction. Patient demise occurred in 8.9%, of which 11.9% was when radiation followed reconstruction and 6.9% was when radiation preceded reconstruction. The difference in tumor recurrence in the setting of radiation therapy before or after breast reconstruction was significant for autologous (P = 0.0146) and prosthetic (P = 0.0424) reconstruction. The difference in patient demise was significant for autologous reconstruction (P = 0.0380) but not for prosthetic reconstruction (P = 0.2827). These results imply that tumor recurrence and patient demise may be increased when radiation therapy is performed following breast reconstruction. The need for a prospective inquiry is validated.
Annals of Plastic Surgery 04/2008; 60(3):244-50. · 1.32 Impact Factor
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ABSTRACT: Soil pH may influence speciation and extractability of Pb, depending on type of vegetation in urban soil environments. We investigated the relationship between soil pH and Pb extractability at forest and turf grass sites in Baltimore, Maryland. Our two hypotheses were: (1) due to lower pH values in forest soils, more Pb will be in exchangeable forms in forested than in turfgrass soils and (2) due to the greater lability of exchangeable Pb in equilibrium with soil solution in forest soils, concentrations of this form will increase with depth more so than in the turfgrass soils, as related to organic matter content and pH. Soil samples were collected from three forested and three turfgrass sites to depths of 20 cm. Lead forms were determined using a sequential extraction technique. Soils under turfgrass and forest vegetation differed in the extractability of soil Pb (P < 0.01) for the Mn(III, IV)- and Fe(III)(hydr) oxide fraction. A greater Pb concentration was bound to this fraction under turfgrass (211 mg kg(-1), 69% of total Pb) than forested soils (67 mg kg(-1), 61% of total Pb), perhaps due to soil pH differences of 5.9 and 5.0, respectively. In the forested soils, as depth increased, the ratio of exchangeable-to-total Pb increased and the ratio of organically bound Pb-to-total Pb decreased. The results suggest changes in pH and organic matter content with depth affect the extractability of Pb, and these soil properties are affected differentially by grass versus tree vegetation in the urban soils investigated.
Environmental Monitoring and Assessment 12/2007; 146(1-3):1-17. · 1.40 Impact Factor
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Hassan Ashktorab,
Duane T Smoot,
Haleh Farzanmehr,
Marie Fidelia-Lambert, Bahram Momen,
Linda Hylind,
Christine Iacosozio-Dononue,
John M Carethers,
Ajay Goel,
C Richard Boland,
Francis M Giardiello
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ABSTRACT: African Americans (AAs) have a 1.5 times higher risk of colorectal carcinoma (CRC) than Caucasians. Gene silencing through CpG island hypermethylation has been associated with the genesis or progression of microsatellite instability (MSI) largely due to 1 target for hypermethylation being the DNA mismatch repair gene hMLH1; there is anecdotal evidence of an increased incidence of MSI among AAs. P16 and hMLH1 can be inactivated by hypermethylation of their respective promoter regions, abrogating the ability to regulate cell proliferation and repair processes. We studied such methylation, as well as hMHS2 expression in colorectal cancers from AA patients to determine if MSI is associated with epigenetic silencing. Experiments were conducted on matched normal and colon cancer tissues from AA patients (n = 51). A total of 5 microsatellite markers (D2S123, D5S346, D17S250, BAT25 and BAT26) were used to evaluate MSI status. P16 and hMLH1 promoter methylation status was determined following bisulfite modification of DNA and using methylation specific PCR, while immunohistochemistry (IHC) was used to examine expression of hMLH1 and hMSH2. A total of 22 (43%) cancers demonstrated microsatellite instability-high (MSI-H), while 27 were microsatellite stable (MSS) and 2 were microsatellite instability-low (MSH-L). Most of the MSI-H tumors were proximal, well differentiated and highly mucinous. Most patients in the MSI-H group were females (68%). The p16 promoter was methylated in 19 of 47 (40%) tumors. A total of 7 of these CRCs demonstrated MSI-H (33%). The hMLH1 promoter was methylated in 29 of 34 (85%) tumors, of which 13 CRCs demonstrated MSI-H (87%). hMLH1 and hMSH2 staining was observed in 66% and 38% of MSI-H tumors, respectively. Overall, the prevalence of MSI-H colorectal tumor was 2-3-fold higher, while the defect in the percentage expression of mismatch repair (MMR) genes (hMLH1 and hMSH2) was similar in AA patients compared to the U.S. Caucasian population. Similar numbers of AA MSS tumors with p16 and hMLH1 methylation likely indicate hemimethylation of genes that might reflect environmental or genetic influences that might be more common in the AA population.
International Journal of Cancer 11/2005; 116(6):914-9. · 5.44 Impact Factor
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ABSTRACT: The advantages of breast reconstruction using the deep inferior epigastric perforator (DIEP) flap and the muscle-sparing free transverse rectus abdominis musculocutaneous (TRAM) flap (MS-2) are well recognized. Both techniques optimize abdominal function by maintaining the vascularity, innervation, and continuity of the rectus abdominis muscle. The purpose of this study was to compare these two methods of breast reconstruction and determine whether there is a difference in outcome. The study considered 177 women who have had breast reconstruction using muscle-sparing flaps over a 4-year period. This includes 89 women who had an MS-2 free TRAM flap procedure, of which 65 were unilateral and 24 were bilateral, and 88 women who had a DIEP flap procedure, of which 66 were unilateral and 22 were bilateral. The total number of flaps was 223. Mean follow-up was 23 months (range, 3 to 49 months). For all MS-2 free TRAM flaps (n = 113), outcome included fat necrosis in eight (7.1 percent), venous congestion in three (2.7 percent), and total necrosis in two (1.8 percent). For the women who had an MS-2 free TRAM flap, an abdominal bulge occurred in three women (4.6 percent) after unilateral reconstruction and in five women (21 percent) after bilateral reconstruction. The ability to perform sit-ups was noted in 63 women (97 percent) after unilateral reconstruction and 20 women (83 percent) after bilateral reconstruction. For all DIEP flaps (n = 110), outcome included fat necrosis in seven (6.4 percent), venous congestion in five (4.5 percent), and total necrosis in three (2.7 percent) patients. For the women who had DIEP flap reconstruction, an abdominal bulge occurred in one woman (1.5 percent) after unilateral reconstruction and in one woman (4.5 percent) after bilateral reconstruction. The ability to perform sit-ups was noted in all women after unilateral reconstruction and in 21 women (95 percent) after bilateral reconstruction. These results demonstrate that there are no significant differences in fat necrosis, venous congestion, or flap necrosis after DIEP or MS-2 free TRAM flap reconstruction. The percentage of women who are able to perform sit-ups and the percentage of women who did not develop a postoperative abdominal bulge is increased after DIEP flap reconstruction; however, this difference is not statistically significant.
Plastic and reconstructive surgery 03/2005; 115(2):436-44; discussion 445-6. · 2.74 Impact Factor
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ABSTRACT: The etiology of lower abdominal bulge following breast reconstruction with the DIEP flap is uncertain. Most studies report an incidence that ranges from 0.7% to 5%. The purpose of this study was to review a set of factors that may predispose to a lower abdominal bulge. This was a retrospective review of 123 women who had breast reconstruction with the DIEP flap over a 4-year period. The reconstruction was unilateral in 93 women and bilateral in 30 women, totaling 153 flaps. Etiologic factors that were evaluated included patient age, diabetes mellitus, tobacco use, previous abdominal operations, unilateral or bilateral reconstruction, previous childbirth, aponeurotic plication to improve the natural abdominal contour, and use of Marlex mesh. A lower abdominal bulge occurred in 5 of the 123 women (4%), 2 following 30 bilateral reconstructions (6.6%) and 3 following 93 unilateral reconstructions (3.2%). Analysis of the factors for all women demonstrated diabetes mellitus in 1 (0.8%), tobacco use in 9 (7.3%), a prior abdominal operation in 55 (44.7%), previous childbirth in 95 (77%), aponeurotic plication in 49 (40%), and use of Marlex mesh in 4 (3.3%). Statistical analysis did not show any significant association between the explanatory factors and the occurrence of a lower abdominal bulge, except for a weak trend in women who had not been pregnant (P = 0.08). The results of this study demonstrate that the occurrence of a lower abdominal bulge following the DIEP flap is a random event that can occur in anyone. Pregnancy may confer a preventative effect as the collagen fibers strengthen to overcome the stretching forces. Techniques for prevention and treatment include intraoperative assessment of the anterior rectus sheath, use of an adjuvant material for reinforcement if unstable, and vertical plication for bulge repair.
Annals of Plastic Surgery 03/2005; 54(2):124-9. · 1.32 Impact Factor
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ABSTRACT: The prevalence of anastomotic failure resulting in return to the operating room and flap necrosis after microvascular breast reconstruction ranges from 1 to 5 percent. The purpose of this study was to review a set of factors that may be associated with this occurrence. Microvascular reconstruction of the breast was performed in 198 women from January of 1998 to July of 2002. The mean age for all women was 47.7 years. There were 158 unilateral and 41 bilateral reconstructions, for a total of 240 flaps. The specific flaps included the free transverse rectus abdominis musculocutaneous flap (n = 176), the deep inferior epigastric perforator flap (n = 58), and the superior gluteal artery perforator flap (n = 6). Upon recognition of anastomotic failure, women were immediately returned to the operating room. Factors that were considered relevant to anastomotic failure included the choice of recipient vessel, timing of reconstruction, previous chest wall radiation therapy, previous axillary lymph node dissection, tobacco use, diabetes mellitus, patient age, and hematoma. Patient follow-up ranged from 5 to 59 months. Descriptive statistics, Fisher's exact test, and exact logistic regression were used for analyses and to summarize data. Of the 240 flaps, return to the operating room was necessary for 20 (8.3 percent), total necrosis occurred in nine (3.8 percent), and the rate of flap salvage was 55 percent (11 of 20 flaps). Venous occlusion was responsible for 16 of the 20 returns and eight of the nine failures. Statistical analysis demonstrated that both return to the operating room and flap necrosis were significantly associated with venous occlusion, delayed reconstruction, and hematoma. Previous lymph node dissection and previous radiation therapy had only a weak association with return to the operating room. The results of this study demonstrate that venous occlusion is responsible for return to the operating room and flap necrosis in the majority of cases. Age, tobacco use, choice of recipient vessel, and diabetes mellitus were not associated with anastomotic failure. The significance of delayed reconstruction may be related to its frequent association with previous lymph node dissection and/or radiation therapy resulting in perivascular fibrosis.
Plastic & Reconstructive Surgery 08/2004; 114(1):74-82. · 3.38 Impact Factor
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ABSTRACT: The incidence of infection following breast reconstruction with expanders and implants ranges from 1 to 24 percent. Numerous factors associated with infection have been described; however, a one-variable at time setting and multifactorial analysis have not been performed. The purpose of this study was to analyze a set of factors that may predispose women to infection of the expander or implant. Between 1997 and 2000, a total of 168 implant reconstructions were performed in 130 women at a single institution. The mean age for all women was 48.2 years (range, 25 to 77 years). The factors that were analyzed included axillary lymph node dissection, chemotherapy, radiation therapy, tumor stage, timing of implant insertion, number of sides (unilateral versus bilateral), tobacco use, and presence or absence of diabetes mellitus. Statistical analysis was performed with stepwise logistic regression. Mean time to follow-up for all patients was 29 months (range, 12 to 47 months). Infectious complications occurred in 10 women (7.7 percent) and in 10 expanders or implants (5.9 percent). Infected implants were removed an average of 116 days following insertion (range, 14 to 333 days). Cultured bacteria included Staphylococcus aureus and Serratia marcescens. A significant association (p < 0.04) was detected between implant infection and radiation therapy. The chance for implant infection was 4.88 times greater for implants that were exposed to radiation therapy compared with those that were not. In addition, there was suggestive (p < 0.09) evidence that the chance of implant infection following lymph node dissection was 6.29 times higher than when no lymph nodes were removed. No significant association between implant infection and age, diabetes, tobacco use, tumor stage, timing of implant insertion, or chemotherapy was found.
Plastic & Reconstructive Surgery 09/2003; 112(2):467-76. · 3.38 Impact Factor
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Hassan Ashktorab,
Duane T Smoot,
John M Carethers,
Majid Rahmanian,
Rick Kittles,
Greg Vosganian,
Menaham Doura,
Emmanel Nidhiry,
Tammy Naab, Bahram Momen,
Shahid Shakhani,
Francis M Giardiello,
Shahed Shakhani
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ABSTRACT: Colorectal carcinoma (CRC) is the second most common cause of cancer death in the United States, and the rate of CRC is nearly 1.5 times higher in African-Americans (AA) than in Caucasians. Microsatellite instability (MSI) is observed in sporadic CRC reflecting promoter hypermethylation of the DNA mismatch repair gene hMLH1, and anecdotal evidence suggests an increased incidence of MSI among AAs. Additionally, p16 can be inactivated by hypermethylation of the promoter region, abrogating its ability to regulate cell proliferation. The objective of this study is to determine the frequency of MSI and p16 gene methylation in CRC from AA patients.
Experiments were conducted on serially collected archival samples of colon cancer and adjacent normal tissue (n = 22). Five microsatellite markers were used to measure MSI in tumors with direct comparison to normal tissue from the same patient. p16 promoter methylation status was determined by methylation-specific PCR.
Ten cancers (45%) demonstrated high MSI (MSI-H), 1 demonstrated low MSI, and the remaining 11 tumors were microsatellite stable. Most of the MSI-H tumors were proximal, well differentiated, and showed high levels of mucin production. Most patients in the MSI-H group were female (70%), whereas most of the microsatellite-stable group (81%) were male. Five of the 22 tumors (22%) had methylation of the p16 promoter.
Data provided here demonstrated that the incidence of MSI-H tumors was 3-fold higher in our study group of AA patients compared with data reported in nonracially selected but serially collected studies. Odds ratio analysis indicates that the chance of female patients having MSI-H was 11.7 times more than male patients (P < 0.03). The reason for this gender difference is unknown. These findings might reflect dietary differences or genetic polymorphisms that may be common in the AA population. Additional investigation in a larger patient population is needed before strong conclusion can be drawn.
Clinical Cancer Research 03/2003; 9(3):1112-7. · 7.74 Impact Factor
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ABSTRACT: Recent reports of breast reconstruction with the deep inferior epigastric perforator (DIEP) flap indicate increased fat necrosis and venous congestion as compared with the free transverse rectus abdominis muscle (TRAM) flap. Although the benefits of the DIEP flap regarding the abdominal wall are well documented, its reconstructive advantage remains uncertain. The main objective of this study was to address selection criteria for the free TRAM and DIEP flaps on the basis of patient characteristics and vascular anatomy of the flap that might minimize flap morbidity. A total of 163 free TRAM or DIEP flap breast reconstructions were performed on 135 women between 1997 and 2000. Four levels of muscle sparing related to the rectus abdominis muscle were used. The free TRAM flap was performed on 118 women, of whom 93 were unilateral and 25 were bilateral, totaling 143 flaps. The DIEP flap procedure was performed on 17 women, of whom 14 were unilateral and three were bilateral, totaling 20 flaps. Morbidities related to the 143 free TRAM flaps included return to the operating room for 11 flaps (7.7 percent), total necrosis in five flaps (3.5 percent), mild fat necrosis in 14 flaps (9.8 percent), mild venous congestion in two flaps (1.4 percent), and lower abdominal bulge in eight women (6.8 percent). Partial flap necrosis did not occur. Morbidities related to the 20 DIEP flaps included return to the operating room for three flaps (15 percent), total necrosis in one flap (5 percent), and mild fat necrosis in two flaps (10 percent). Partial flap necrosis, venous congestion, and a lower abdominal bulge were not observed. Selection of the free TRAM or DIEP flap should be made on the basis of patient weight, quantity of abdominal fat, and breast volume requirement, and on the number, caliber, and location of the perforating vessels. Occurrence of venous congestion and total flap loss in the free TRAM and DIEP flaps appears to be independent of the patient age, weight, degree of muscle sparing, and tobacco use. The occurrence of fat necrosis is related to patient weight (p < 0.001) but not related to patient age or preservation of the rectus abdominis muscle. The ability to perform a sit-up is related to patient weight (p < 0.001) and patient age (p < 0.001) but not related to preservation of the muscle or intercostal nerves. The incidence of lower abdominal bulge is reduced after DIEP flap reconstruction (p < 0.001). The DIEP flap can be an excellent option for properly selected women.
Plastic & Reconstructive Surgery 08/2002; 110(2):466-75; discussion 476-7. · 3.38 Impact Factor
