- Reconstructive Surgery
- Breast Surgery
- Hand Surgery
- Global Surgery
M.D., Yale University (2014)
B.A., Johns Hopkins University (2009)
PURPOSE: Hand surgery outreach programs to low- and middle-income countries (LMICs) provide much-needed surgical care to the underserved populations and education to local providers for improved care. The cost-effectiveness of these surgical trips has not been studied despite a long history of such efforts. This study aimed to examine the economic impact of hand surgery trips to LMICs using data from the Touching Hands Project and ReSurge International. We hypothesized that hand surgery outreach would be cost-effective in LMICs.METHODS: We analyzed data on the cost of each trip and the surgical procedures performed. Using methods from the World Health Organization (WHO-Choosing Interventions That Are Cost-Effective [WHO-CHOICE]), we determined whether the procedures performed during the outreach trips would be cost-effective.RESULTS: For the 14 hand surgery trips, 378 patients received surgical treatment. Trips varied in the country where interventions were provided, the number of patients served, the severity of the conditions, and the total cost. The cost per disability-adjusted life-year averted ranged from United States (US)$222 to $1,525, all of which were very cost-effective according to WHO-CHOICE thresholds. The cost-effectiveness of global hand surgery was comparable to that of other medical interventions such as multidrug-resistant tuberculosis treatment in similar regions. We also identified a lack of standardized record keeping for these surgical trips.CONCLUSIONS: Hand surgeries performed in LMICs are cost-effective based on WHO-CHOICE criteria. However, a standardized record-keeping method is needed for future research and longitudinal comparison. Understanding the economic impact of hand surgery global outreach is important to the success and sustainability of these efforts, both to allocate resources effectively and to identify areas for improvement.TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.
View details for PubMedID 30579691
Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction.A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed.We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25).Mastectomy skin necrosis is significantly more likely to occur after autologous breast reconstruction compared with 2-stage expander implant-based breast reconstruction. Patients with autologous reconstructions are more readily treated with local wound care compared with patients with tissue expanders, who tended to require operative treatment of this complication. Patients considering breast reconstruction should be counseled appropriately regarding the differences in incidence and management of mastectomy skin necrosis between the reconstructive options.
View details for DOI 10.1097/SAP.0000000000001379
View details for PubMedID 29489546
Timing is an important consideration in patients undergoing mastectomy for breast cancer. While immediate reconstruction results in superior aesthetic outcomes, the need for postmastectomy radiation can often only be ascertained after review of surgical pathology. Delayed-immediate autologous reconstruction (DIAR) is a reconstructive approach that consists of mastectomy with tissue expander placement in the first stage and flap-based breast reconstruction in the second stage. We describe our institution's experience with DIAR to characterize the reasons in which patients opt for this reconstructive approach and analyze its ultimate outcomes.We conducted an institutional review board-approved retrospective chart review of all consecutive patients undergoing DIAR performed by the senior author from 2007 to 2016. Data gathered included demographics, operative techniques, and postoperative outcomes.In our study, 17 patients and 26 breasts underwent DIAR. Seven patients initially planned for and eventually underwent DIAR. Ten patients initially planned for implant-based reconstructions but ultimately underwent DIAR instead. Flap types included deep inferior epigastric perforator (n = 6), superficial inferior epigastric artery (n = 2), and muscle-sparing free transverse rectus abdominis myocutaneous (n = 18). The mean time between mastectomy and reconstruction was 208 days. Complications included tissue expander infection, vascular compromise, abscess formation, hematoma, and skin necrosis.The delayed-immediate approach allows for breast reconstruction with aesthetic and psychosocial benefits, while enabling postmastectomy radiation in patients with advanced disease. We describe modifications to DIAR, including use of a flap skin paddle and prolonged time between stages, which allow for broader applicability. We show that DIAR accommodates a range of patient preferences with few complications.
View details for DOI 10.1097/SAP.0000000000001380
View details for PubMedID 29620551
Patients with breast cancer frequently opt to undergo breast reconstruction after mastectomy. The timing and aesthetic outcome of the breast reconstruction may be affected by the need for radiation therapy (RT). Delayed-immediate autologous reconstruction (DIAR) is a novel surgical approach for patients in whom the need for adjuvant RT after mastectomy is preoperatively unknown.We sought to evaluate the difference in clinical outcomes, patient satisfaction, and cosmetic results between DIAR and patients who underwent delayed autologous reconstruction.A total of 19 DIAR and 19 delayed patients were retrospectively included.Patient demographics, surgical characteristics, and complications were obtained from patient files. Patients scored their satisfaction using the breast-Q questionnaire, and independent reviewers scored cosmetic outcomes, including skin quality/color, scar formation, symmetry, breast contour/size/position, and overall aesthetic outcome. The DIAR patients were matched to delayed patients based on age, body mass index, and unilateral or bilateral reconstruction.The median age in the delayed group was 48 years (range, 31-61 years) and 46 years (range, 29-64 years) in the DIAR group, with a median body mass index of 28.8 (range, 21.4-40.5) and 28.6 (range, 24-1.9), respectively.There were no significant differences in demographics between the two groups. In total, 16 patients underwent unilateral reconstruction and 22 patients bilateral reconstruction. Delayed-immediate autologous reconstruction was associated with a higher infection rate compared with delayed reconstruction, 8 and 1, respectively (P = 0.026). All infections in the DIAR group were tissue expander-related. The DIAR patients had significantly better breast contour/size/position and overall aesthetics compared with the delayed reconstruction group (P = 0.001). In addition, patients who did not receive RT had significant better cosmetic outcome (P < 0.001). There were no significant differences in patient satisfaction between the DIAR and delayed group.Delayed-immediate autologous reconstruction should be considered as an option for patients wanting autologous reconstruction when the need for RT remains unknown. Delayed-immediate autologous reconstruction demonstrates better breast contour/size/position and overall aesthetic outcome.
View details for PubMedID 29553980
Two-stage expander implant breast reconstruction is commonly performed after mastectomy. Salvage and long-term outcomes after development of complications have not been well described. We examined a single surgeon's experience to study the rate of reoperation secondary to complications after first-stage expander placement and to evaluate their outcomes. Better understanding of salvage techniques may help guide future management.We performed a retrospective analysis of consecutive patients who underwent placement of a tissue expander (TE) for breast reconstruction between December 2006 and August 2015 with the senior author. Patient demographics including age, body mass index, medical comorbidities, history of smoking, and history of radiation to the breast were collected. Surgical factors including timing of reconstruction (immediate vs delayed) and location of TE (total submuscular vs with acellular dermal matrix) were recorded. Complications were analyzed, as were patients who underwent reoperation in the setting of developing a complication.We analyzed 282 patients who underwent 453 implant-based breast reconstructions. Of these, 39 patients and 45 breasts required a reoperation after development of a postoperative complication. Return to the operating room was associated with higher body mass index (29 vs 24, P < 0.001), higher TE initial fill volume (299 mL vs 169 mL, P < 0.001), and preoperative radiation (31% vs 13%, P = 0.001). Complications resulting in reoperation included infection (60%), mastectomy skin necrosis (27%), and TE extrusion through thin mastectomy skin (11%). The affected TE was removed and exchanged in 17 patients (38%), autologous flap reconstruction occurred in 16 patients (36%), and TE was explanted without replacement in 12 patients (27%).Infectious complications including cellulitis and abscess formation accounted for most cases requiring reoperation after TE placement for breast reconstruction. More than a quarter of patients who underwent a reoperation ultimately lost their implants. Patients undergoing two-stage expander implant breast reconstruction should be appropriately counseled regarding the possibility of requiring a reoperation in the setting of developing a complication.
View details for DOI 10.1097/SAP.0000000000001382
View details for PubMedID 29489547
Mastectomy skin necrosis is a significant problem after breast reconstruction. This complication may lead to poor wound healing and need for implant removal, which may delay subsequent oncologic treatment. We sought to characterize factors associated with mastectomy skin necrosis and propose a management algorithm.A retrospective review was performed on consecutive patients undergoing implant-based breast reconstruction by the senior author from 2006 through 2015. Patient-level factors including age, race, body mass index, history of hypertension, history of diabetes, history of smoking, and history of radiation were collected. Surgical factors including type of mastectomy, location of implant placement, and immediate versus delayed reconstruction were collected. The incidence and treatment of mastectomy skin necrosis were analyzed.A total of 293 patients underwent either unilateral or bilateral implant-based breast reconstructions after mastectomy with a total of 471 reconstructed breasts. Mastectomy skin necrosis was observed in 8.1% of reconstructed breasts. Skin necrosis was not associated with age, hypertension, diabetes, prior radiation, or type of mastectomy. The incidence of skin necrosis was higher among smokers (17.9% vs 5.0%, P < 0.001), among patients with higher body mass index (11.4% vs 6.1%, P = 0.05), patients who underwent immediate reconstruction compared to delayed (9.6% vs 0%, P = 0.004), placement of expander under acellular dermal matrix compared with submuscular placement (12.0% vs 5.2%, P = 0.02), and use of higher initial expander fill volume compared with lower fill volume (11.4% vs 5.4%, P = 0.02).The median necrosis size was 8 cm. The median time to treatment was 15 days postoperatively. In 55% of patients minor necrosis was treated with clinic debridement, whereas 43% had larger areas of necrosis requiring operative debridement. The median size treated with clinic debridement was 5.5 cm, compared to 15 cm for operative debridement. All necrosis was treated in a timely fashion and did not delay adjuvant therapy.Mastectomy skin necrosis occurred in 8.1% of breasts after implant-based reconstruction. Necrosis less than 10 cm can be treated successfully with local debridement in the clinic setting. Timely and appropriate treatment of skin necrosis with debridement and primary closure expedites wound healing and facilitates tissue expander breast reconstruction.
View details for DOI 10.1097/SAP.0000000000001045
View details for PubMedID 28301366
Methyl bromide chemical burns are rare. Only two cases have been reported to date. The presentation of methyl bromide chemical burns is unusual. Patients with an acute exposure should be observed closely as the initial presentation can appear deceptively benign. The latency period lasts several hours prior to the development of chemical burn wounds. In this article, we review the literature on methyl bromide chemical burns and present our experience managing a patient with an extensive methyl bromide burn.
View details for DOI 10.1016/j.burns.2016.12.001
View details for PubMedID 28069343
Infection is a dreaded complication following 2-stage implant-based breast reconstruction that can prolong the reconstructive process and lead to loss of implant. This study aimed to characterize outcomes of reconstructions complicated by infection, identify patient and surgical factors associated with infection, and use these to develop an infection management algorithm.We performed a retrospective review of all consecutive implant-based breast reconstructions performed by the senior author (2006-2015) and collected data regarding patient demographics, medical history, operative variables, presence of other complications (necrosis, seroma, hematoma), and infection characteristics. Univariate and multivariate binomial logistic regression analyses were performed to identify independent predictors of infection.We captured 292 patients who underwent 469 breast reconstructions. In total, 14.1% (n = 66) of breasts were complicated by infection, 87.9% (n = 58) of those were admitted and given intravenous antibiotics, 80.3% (n = 53) of all infections were cleared after the first attempt, whereas the remaining recurred at least once. The most common outcome was explantation (40.9%; n = 27), followed by secondary implant insertion (21.2%; n = 14) and operative salvage (18.2%; n = 12). Logistic regression analysis demonstrated that body mass index (P = 0.01), preoperative radiation (P = 0.02), necrosis (P < 0.001), seroma (P < 0.001), and hematoma (P = 0.03) were independent predictors of infection.We observed an overall infectious complication rate of 14.1%. Heavier patients and patients who received preoperative radiation were more likely to develop infectious complications, suggesting that closer monitoring of high risk patients can potentially minimize infectious complications. Further, more aggressive management may be warranted for patients whose operations are complicated by necrosis, seroma, or hematoma.
View details for PubMedID 28831338
We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms.The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones.From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300?mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays.Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline.Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.
View details for DOI 10.1097/SLA.0000000000002004
View details for PubMedID 27611607
In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.
View details for DOI 10.1177/2324709615603722
View details for PubMedID 26904700
View details for PubMedCentralID PMC4748503
Deep sternal wound infection (DSWI) is a life-threatening complication that develops in 5% of patients undergoing median sternotomy. One feared complication is major bleeding, associated with up to 50% mortality. We characterized a series of patients who experienced major bleeding following DSWI. We included eight patients with DSWI who experienced major bleeding at our institution from 1990 to 2012. The median age was 70.9 (range, 47-81) and the cohort consisted of seven male patients and one female patient. All eight patients required emergent surgical repair for the bleeding and all survived past 30 days postoperatively from the repair.
View details for DOI 10.1055/s-0034-1376402
View details for Web of Science ID 000347953300012
View details for PubMedID 24875809
Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including ?-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.
View details for DOI 10.1097/SAP.0000000000000080
View details for Web of Science ID 000348146100020
View details for PubMedID 24401806
Although patients diagnosed with ductal carcinoma In Situ (DCIS) enjoy a favorable prognosis, recurrence after definitive management does occur in a subset of these patients. Factors influencing the development of recurrence remain poorly understood. A retrospective chart review of 205 consecutive patients who presented to an academic breast center with DCIS from 2000 to 2003 was conducted under an Institutional Review Board-approved protocol. With a median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with DCIS between 2000 and 2003 had a recurrence of their DCIS. The median age of all patients at the time of diagnosis of their initial DCIS was 55.5 years (range, 35.8 to 88.9 years). Patients who experienced tumor recurrence were more likely to have Grade 3 DCIS on initial diagnosis compared with patients without recurrence (72.7 vs 35.4%, P = 0.032). The odds ratio of tumor recurrence for high-grade compared with low-grade DCIS was 4.39. Patient age, race, tumor size, tumor histologic subtype, or histopathologic features was not associated with recurrence. Patients with high-grade DCIS are more likely to recur than patients with low-grade DCIS, and this seems to be more predictive of recurrence than other clinicopathologic markers.
View details for Web of Science ID 000354894000029
View details for PubMedID 25569065
Various surgical treatment modalities have been advocated for the treatment of Dupuytren's disease. However, recurrence following surgical treatment of Dupuytren's disease remains a common problem. Previous studies have demonstrated lower recurrence rates with use of a full-thickness skin graft. We therefore postulated that use of acellular dermal matrix may be associated with a similar outcome, based on the common inhibitory effect on underlying myofibroblasts. We performed a retrospective cohort study of 43 patients undergoing open fasciectomy for Dupuytren's disease from years 2005 to 2012 at our academic institution. Standard fasciectomies of the affected palmar and digital fascia were performed via Brunner incisions on all patients. Patients in the experimental group had a sheet of acellular dermal matrix (Alloderm; LifeCell, Bridgewater, NJ) sutured into the surgical bed with interrupted absorbable sutures before closure, whereas patients in the control group were not closed with acellular dermal matrix. Patients were then evaluated at follow-up for disease recurrence, defined as presence of Dupuytren's tissue in an area previously operated on with a contracture greater than that recorded following the surgical fasciectomy, or presence of contracture requiring surgery. Among our cohort of 43 patients, 23 (53.5%) were treated with acellular dermal matrix while 20 (46.5%) were not. The median age of our cohort was 66.5 years (range 54-91 years). The median follow-up was 1.8 years. During this follow-up period, recurrence of contracture was observed in 1 of 23 patients in the group receiving acellular dermal matrix, compared to 5 of 20 in the control group (P = 0.045). No differences in the incidence of minor wound complications were observed. Our novel technique of placement of acellular dermal matrix into the wound bed following fasciectomy for Dupuytren's disease may be an important surgical strategy to reduce recurrence rates in patients with Dupuytren's disease.
View details for DOI 10.1097/SAP.0000000000000133
View details for Web of Science ID 000360566300014
View details for PubMedID 24691328
The role of leptin in mediating calcium-related metabolic processes is not well understood.We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism.Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively).Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.
View details for DOI 10.1016/j.jamcollsurg.2013.11.013
View details for Web of Science ID 000336458000035
View details for PubMedID 24468228
Abdominal wall defects resulting from recurrent hernias, trauma, and radiation necrosis are difficult and challenging to repair given the high rates of recurrence and surgical morbidity. Complex abdominal wall defects often require the transposition of autologous material to bridge the fascial gap. We present a review of niche reconstructive techniques that have been used in complex abdominal wall repair. The specific techniques reviewed include use of delayed and tunneled pedicled tensor fascia lata myofascial flap, de-epithelialized flap closure, free latissimus dorsi myocutaneous flap with or without innervation, and abdominal wall transplant. These niche surgical techniques have great potential to reduce recurrence rates when used in the proper setting for complex abdominal wall reconstruction. More studies are needed to evaluate the relative use of these techniques with the more widely established surgical methods of reconstruction.
View details for Web of Science ID 000337744400012
View details for PubMedID 24887661
Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins. The patients were then treated with topical imiquimod for 8?weeks after which a repeat biopsy of the affected region showed no evidence of residual melanoma in situ. The use of topical imiquimod cream should be considered in the management of residual melanoma in situ of the plantar surface of the foot.
View details for DOI 10.1136/bcr-2014-203826
View details for PubMedID 25188932
Factors influencing the treatment of ductal carcinoma in situ with mastectomy and reconstruction are poorly understood.A retrospective cohort study of 196 patients presenting to one institution was performed.Forty-seven patients (24.0%) were treated with mastectomy, while 149 (76.0%) underwent breast-conserving surgery. Of the mastectomy patients, 28 (59.6%) elected for reconstruction. On bivariate analysis, patients who opted for mastectomy were younger than those treated with breast-conserving surgery (median age, 51.8 vs. 56.5 years; P = .017) and had higher grade tumors (50.0% vs. 34.6% grade 3, P = .009). Among patients treated with mastectomy, those who opted for reconstruction were younger than those forgoing reconstruction (49.4 vs. 56.9 years, P = .024). Race, ductal carcinoma in situ tumor size, and histologic subtype were not associated with the decision to pursue mastectomy or reconstruction (P > .05 for all).In patients with ductal carcinoma in situ, the decision to pursue mastectomy and reconstruction appears to be driven by younger patient age and higher tumor grade.
View details for DOI 10.1016/j.amjsurg.2013.07.001
View details for Web of Science ID 000326510600010
View details for PubMedID 24011572
We sought to determine factors predicting microinvasion and the prognostic role it plays in patients with ductal carcinoma in situ (DCIS).A retrospective cohort study of 205 consecutive patients presenting to the Yale Breast Center, New Haven, CT, was performed.Fifty-one (24.9%) patients had microinvasion on pathology. Patients with microinvasion had larger areas of DCIS and were more likely to have high-grade DCIS of the comedo and solid type associated with necrosis and microcalcifications. On multivariate analysis, none of these factors were independent predictors of microinvasion. With a median follow-up of 8.5 years, there was no difference in the recurrence rate or 5-year actuarial survival between those with microinvasion vs those with pure DCIS.Microinvasion was associated with more extensive DCIS, higher grade, comedo or solid histology, necrosis, and microcalcifications although none of these were found to be an independent predictor of microinvasion. Furthermore, the presence of microinvasion does not seem to significantly increase the risk of recurrence or decrease survival.
View details for DOI 10.1016/j.amjsurg.2013.01.039
View details for Web of Science ID 000326510500006
View details for PubMedID 23791403
Plastic surgery is the most competitive specialty in medicine. We sought to identify factors associated with the successful match of generation Y applicants into integrated plastic surgery residency.We utilized the most recent data from the Charting Outcomes in the Match published by the National Resident Matching Program in 2011. We had data on US senior or independent applicant status, Alpha Omega Alpha (AOA) status, attendance of top 40 medical schools, advanced degree status, and number of contiguous ranks within plastic surgery. Our main outcome measure was match status.A total of 81 out of 197 applicants (41.1%) successfully matched into integrated plastic surgery in the 2011 main match. US seniors matched at a significantly higher rate compared to independent applicants (44.0% vs 24.1%, P = 0.044). Matched US seniors were more likely to have AOA membership compared to unmatched US seniors (45.9% vs 27.7%, P = 0.014) and attend a top 40 medical school (52.7% vs 35.1%, P = 0.022). There were no differences in terms of advanced degrees between matched and unmatched US seniors. Unmatched US seniors were more likely to have 3 or fewer contiguous ranks of plastic surgery residency programs than matched US seniors (86.2% vs 68.9%, P = 0.007).US senior status, AOA membership, and attendance at a top 40 medical school are predictors of matching into integrated plastic surgery. Program directors need to be aware of the background of the millennial applicants to recruit and maintain top residents.
View details for DOI 10.1097/GOX.0b013e3182a47ed3
View details for PubMedID 25289227
Little is known about factors influencing time between diagnosis and definitive treatment in patients with ductal carcinoma in situ (DCIS). We sought to determine the factors influencing this delay time and implications on outcome. A retrospective review was performed of 127 patients with DCIS who were treated with definitive surgical excision at an academic center from 2000 to 2003. The mean time from diagnosis of DCIS to definitive surgical treatment was 39.5 days (range, 3 to 130 days). Age, race, tumor grade, and histopathologic features were not associated with time to definitive treatment (P > 0.05). However, patients who opted for breast-conserving surgery had a shorter time to definitive treatment compared with patients treated with mastectomy (mean time 32.9 vs 53.9 days, P < 0.001). Of patients undergoing mastectomy, those who opted for reconstruction did not have a prolonged time to treatment (55.0 vs 52.4 days, P = 0.880). Increased time between diagnosis and treatment (greater than 39.5 days) was not associated with worse prognosis in terms of overall survival (five-year actuarial survival: 93.0 vs 97.6%, P = 0.322). No demographic or histopathologic factors were associated with increased time to definitive treatment, although patients treated with mastectomy tended to have a longer diagnosis-to-treatment interval. However, the delay time was not associated with worse outcome.
View details for Web of Science ID 000336962000014
View details for PubMedID 23711263
Chromosomal instability is a potentially critical step in the development of colorectal cancer. The budding uninhibited by benzimidazole 1 (BUB1) gene is a highly conserved protein that plays a critical role at the spindle assembly checkpoint during cell division. BUB1 mutations function in a dominant-negative fashion and have been implicated in causing dysfunctional kinetochore attachments, premature chromatid separation, accelerated mis-segregation of whole chromosomes and aneuploidy. BUB1 mutations have been observed in patients with colorectal cancers. We report a remarkable case of BUB1 haploinsufficiency owing to a 1.7 Mb deletion of chromosome 2q13 in a 54-year-old man with no prior history of carcinoma. These mutant alleles were observed in both tissue from the hand and peripheral blood. Aneuploidy was not observed on cytogenetic analysis. These findings highlight the insufficiency of BUB1 haploinsufficiency to directly stimulate tumourigenesis, and suggest that other factors may be more critical to this process.
View details for DOI 10.1136/bcr-2013-008684
View details for PubMedID 23440991
There is a paucity of research comparing resident training experiences of university, community, and military-affiliated surgical programs.We reviewed a cross-sectional national survey (NEARS) involving all US categorical general surgery residents (248 programs). Demographics and level of agreement regarding training experiences were collected. Statistical analysis included chi-square, ANOVA, and hierarchical logistic regression modeling (HLRM).There were 4,282 residents included (82.4% response rate). The majority (69%) trained in university programs. Types of programs differed by sex mix (p < 0.001), racial makeup (p = 0.005), marital status profile (p = 0.002), and parental status profile (p < 0.001). Community residents were most satisfied with their operative experience (community 84.5%, university 73.4%, military 62.4%; p < 0.001), most likely to feel their opinions are important (76.0% vs 69.4% vs 67.9%, respectively; p < 0.001), and least likely to believe attendings will think worse of them if residents asked for help with patient management (12.6% vs 15.9% vs 14.7%, respectively; p = 0.025). Military residents were least likely to report that surgical training is too long (military 7.4%, community 14.0%, university 23.8%; p < 0.001). On HLRM, community programs were independently associated with residents feeling their opinions are important (odds ratio [OR] 1.91; p < 0.001), and reporting satisfactory operative experience (OR 4.73; p < 0.001). Residents training at military programs (OR 0.23; p = 0.002) or community programs (OR 0.31; p < 0.001) were less likely to feel that surgical training is too long, or that attendings will think worse of them if asked for help with patient care (community OR 0.19; p < 0.001; military OR 0.27; p = 0.004).Residents at university, community, and military programs report distinct training experiences. These findings may inform programs of potential targeted strategies for enhanced support.
View details for DOI 10.1016/j.jamcollsurg.2011.09.021
View details for Web of Science ID 000299054400011
View details for PubMedID 22075109
Many functionally essential ionizable groups are buried in the hydrophobic interior of proteins. A systematic study of Lys, Asp, and Glu residues at 25 internal positions in staphylococcal nuclease showed that their pK(a) values can be highly anomalous, some shifted by as many as 5.7 pH units relative to normal pK(a) values in water. Here we show that, in contrast, Arg residues at the same internal positions exhibit no detectable shifts in pK(a); they are all charged at pH ? 10. Twenty-three of these 25 variants with Arg are folded at both pH 7 and 10. The mean decrease in thermodynamic stability from substitution with Arg was 6.2 kcal/mol at this pH, comparable to that for substitution with Lys, Asp, or Glu at pH 7. The physical basis behind the remarkable ability of Arg residues to remain protonated in environments otherwise incompatible with charges is suggested by crystal structures of three variants showing how the guanidinium moiety of the Arg side chain is effectively neutralized through multiple hydrogen bonds to protein polar atoms and to site-bound water molecules. The length of the Arg side chain, and slight deformations of the protein, facilitate placement of the guanidinium moieties near polar groups or bulk water. This unique capacity of Arg side chains to retain their charge in dehydrated environments likely contributes toward the important functional roles of internal Arg residues in situations where a charge is needed in the interior of a protein, in a lipid bilayer, or in similarly hydrophobic environments.
View details for DOI 10.1073/pnas.1104808108
View details for Web of Science ID 000297249800026
View details for PubMedID 22080604
To characterize factors shaping surgery resident confidence and determine whether confidence is associated with future specialty training.Cross-sectional study.Survey administered at the 2008 American Board of Surgery In-Service Training Examination.All categorical general surgery residents.National Study of Expectations and Attitudes of Residents in Surgery survey.reported demographics and level of agreement for 46 items regarding confidence, training, and professional plans.Survey items "My operating skill level is appropriate" and "I may not feel confident enough to perform procedures independently before training completion." We compared demographics and responses among residents who did/not feel confident.Response rate was 77.4%. Residents who were female, single, or without children and at a lower postgraduate year had less confidence in their operating skill, as did residents at larger, university-based programs, in the northeastern United States. Residents worried about competence were more likely to believe specialty training was needed (71.2% vs 60.2%; P < .001). After adjustment, residents dissatisfied with training were less likely to believe their skills were level appropriate (odds ratio, 0.13; P < .001) as were residents not comfortable asking for help (odds ratio, 0.48; P < .001). After adjustment, women were twice more likely than men to worry about competence after training; single residents were 1.36 times more likely than married residents to believe their skills were not level appropriate. Program location, type, and size remained associated with confidence, as did satisfaction and comfort asking for help. Residents worried about skills were more likely to plan for fellowship.Sex, marital status, children, and postgraduate year are predictors of confidence, as are program location, type, and size. Residency programs may target modifiable factors contributing to low surgical confidence.
View details for Web of Science ID 000293857600004
View details for PubMedID 21844434
To characterize the demographics and attitudes of US general surgery residents performing full-time research.Cross-sectional national survey administered after the 2008 American Board of Surgery In-Service Training Examination.Two hundred forty-eight residency programs.General surgery residents.Survey administration.A third of categorical general surgery residents interrupt residency to pursue full-time research. To our knowledge, there exist no comprehensive reports on the attitudes of such residents.Four hundred fifty residents performing full-time research and 864 postgraduate year 3 (PGY-3) clinical residents completed the survey. Thirty-eight percent of research residents were female, 53% were married, 30% had children, and their mean age was 31 years. Residency programs that were academic, large, and affiliated with fellowships had proportionally more research residents compared with other programs. Research and PGY-3 residents differed (P < .05) on 10 survey items. Compared with PGY-3 residents, research residents were less likely to feel they fit well in their program (86% vs 79%, respectively), that their program had support structures if they struggled (72% vs 64%), or that they could turn to faculty (71% vs 65%). They were more likely to feel training was too long (21% vs 30%) and that surgeons must be specialty trained (55% vs 63%). In multivariate analyses, research residents believed surgical training was too long (odds ratio, 1.36) and they fit in less well at their programs (odds ratio, 0.71) (P < .05).Compared with PGY-3 residents, research residents report less satisfaction with important aspects of training, suggesting this is a vulnerable stage. Interventions could be targeted to facilitate support and better integration into the mainstream of surgical education.
View details for DOI 10.1001/archsurg.2011.12
View details for Web of Science ID 000291851500004
View details for PubMedID 21339415
The pK(a) values of internal ionizable groups are usually very different from the normal pK(a) values of ionizable groups in water. To examine the molecular determinants of pK(a) values of internal groups, we compared the properties of Lys, Asp, and Glu at internal position 38 in staphylococcal nuclease. Lys38 titrates with a normal or elevated pK(a), whereas Asp38 and Glu38 titrate with elevated pK(a) values of 7.0 and 7.2, respectively. In the structure of the L38K variant, the buried amino group of the Lys38 side chain makes an ion pair with Glu122, whereas in the structure of the L38E variant, the buried carboxyl group of Glu38 interacts with two backbone amides and has several nearby carboxyl oxygen atoms. Previously, we showed that the pK(a) of Lys38 is normal owing to structural reorganization and water penetration concomitant with ionization of the Lys side chain. In contrast, the pK(a) values of Asp38 and Glu38 are perturbed significantly owing to an imbalance between favorable polar interactions and unfavorable contributions from dehydration and from Coulomb interactions with surface carboxylic groups. Their ionization is also coupled to subtle structural reorganization. These results illustrate the complex interplay between local polarity, Coulomb interactions, and structural reorganization as determinants of pK(a) values of internal groups in proteins. This study suggests that improvements to computational methods for pK(a) calculations will require explicit treatment of the conformational reorganization that can occur when internal groups ionize.
View details for DOI 10.1016/j.jmb.2009.03.039
View details for Web of Science ID 000266930500004
View details for PubMedID 19324049
Previously we reported that Lys, Asp, and Glu residues at positions 66 and 92 in staphylococcal nuclease (SNase) titrate with pK(a) values shifted by up to 5 pK(a) units in the direction that promotes the neutral state. In contrast, the internal Lys-38 in SNase titrates with a normal pK(a). The crystal structure of the L38K variant shows that the side chain of Lys-38 is buried. The ionizable moiety is approximately 7 A from solvent and ion paired with Glu-122. This suggests that the pK(a) value of Lys-38 is normal because the energetic penalty for dehydration is offset by a favorable Coulomb interaction. However, the pK(a) of Lys-38 was also normal when Glu-122 was replaced with Gln or with Ala. Continuum electrostatics calculations were unable to reproduce the pK(a) of Lys-38 unless the protein was treated with an artificially high dielectric constant, consistent with structural reorganization being responsible for the normal pK(a) value of Lys-38. This reorganization must be local because circular dichroism and NMR spectroscopy indicate that the L38K protein is native-like under all conditions studied. In molecular dynamics simulations, the ion pair between Lys-38 and Glu-122 is unstable. The simulations show that a minor rearrangement of a loop is sufficient to allow penetration of water to the amino moiety of Lys-38. This illustrates both the important roles of local flexibility and water penetration as determinants of pK(a) values of ionizable groups buried near the protein-water interface, and the challenges faced by structure-based pK(a) calculations in reproducing these effects.
View details for DOI 10.1110/ps.073397708
View details for Web of Science ID 000255290600005
View details for PubMedID 18369193