H F Seigler

Duke University Medical Center, Durham, NC, United States

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Publications (264)994.01 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of general surgery training programs offer a dedicated research experience during the training period. There is much debate over the importance of these experiences with the added constraints placed on training surgeons including length of training, Accreditation Council of Graduate Medical Education limitations, and financial barriers. We seek to quantify the impact of a protected research experience on graduates of a university-affiliated general surgery training program. We surveyed all graduates of a single university-affiliated general surgery training program who completed training from 1989 to 1999. Data was obtained for 100 per cent of the subjects. Most graduates (72/73; 98.6%) completed a dedicated research experience (range: 1-5 years). Presently, 72.6 per cent (53/73) are practicing academic surgery and 82.5 per cent (60/73) are engaged in research activities. Fifty-one of 73 graduates (69.5%) have current research funding including 32.9 per cent (24/73) with National Institutes of Health funding. Of all graduates, 42.5 per cent (31/73) have become full professors with 20.2 per cent (15/73) division/section chiefs and 14.3 per cent (10/73) department chairmen or vice chairmen. Those trainees achieving a career in academic surgery were statistically more likely to have committed 2 or more years to a protected research experience during training (P < 0.05), fellowship training after general surgery residency (P < 0.01), and a first job at an academic institution upon completion of training (P < 0.001). Understanding the importance of resident research experiences while highlighting critical factors during the formative training period may help to ensure continued academic interest and productivity of future trainees.
    The American surgeon 07/2011; 77(7):907-10. · 0.92 Impact Factor
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    ABSTRACT: Hyperthermic isolated limb perfusion (HILP) and isolated limb infusion (ILI) are used to manage advanced extremity melanoma, but no consensus exists as to which treatment is preferable and how to monitor patients post-treatment. Using a prospectively maintained database, we reviewed our experience with melphalan-based HILP (which included 62 first-time and 10 second-time) and ILI (which included 126 first-time and 18 second-time) procedures performed in 188 patients. PET/CT was obtained 3 months postregional treatment for 1 year and then every 6 months thereafter. Overall response rate (complete response [CR] + partial response) of HILP was 81% (80% CI, 73-87%), and overall response rate from ILI was 43% (80% CI, 37-49%) for first-time procedures only. HILP had a CR rate of 55% with a median duration of 32 months, and ILI had a CR rate of 30% with median duration of 24 months. Patients who experienced a regional recurrence after initial regional treatment were more likely to achieve a CR after repeat HILP (50%, n = 10) compared with repeat ILI (28%, n = 18). Although the spectrum of toxicity was similar for ILI and HILP, the likelihood of rare catastrophic complication of limb loss was greater with HILP (2 of 62) than ILI (0 of 122). PET/CT was effective for surveillance after regional therapy to identify regional nodal and pulmonary disease that was not clinically evident, but often amenable to surgical resection (25 of 49; 51% of cases). In contrast, PET/CT was not effective at predicting complete response to treatment with an accuracy of only 50%. In the largest single-institution regional therapy series reported to date, we found that although ILI is effective and well-tolerated, HILP is a more definitive way to control advanced disease.
    Journal of the American College of Surgeons 04/2011; 213(2):306-16. · 4.50 Impact Factor
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    ABSTRACT: Differentiating pigmented skin lesions from malignant melanoma in the pediatric population has been a challenge. Despite guidelines describing clinical features and histopathologic criteria to distinguish these lesions, misdiagnoses still occur. We report our experience over 30 years in a pediatric population with malignant melanoma. We performed a retrospective review of 150 pediatric patients treated for malignant melanoma between 1973 and 2007 at our institution. Outcomes measured included age, Breslow thickness, Clark level of invasion, tumor location, local and distant failure rates, and overall survival. One hundred fifty pediatric patients were evaluated. The mean age was 15.1 years. The mean Breslow thickness was 2.05 mm and corresponding Clark level of invasion was 3.47. There were 43 known recurrences (29%); 29 distant, 14 nodal, and 7 local. Overall survival was 84% with a mean follow-up of 8.5 years. Sixteen patients (10.7%) were incorrectly diagnosed on initial pathologic examination. Overall survival in the misdiagnosed group was 66%. Pigmented skin lesions in the pediatric population represent a diagnostic challenge to pathologists and clinicians. Improvements in diagnostic techniques with rigorous characterization, as well as increased physician awareness, should lead to a reduction in errors of diagnosis.
    Journal of Pediatric Surgery 09/2009; 44(8):1514-21. · 1.38 Impact Factor
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    ABSTRACT: Isolated limb infusion (ILI) is a minimally invasive approach for treating in-transit extremity melanoma, with only two US single-center studies reported. Establishing response and toxicity to ILI as compared with hyperthermic isolated limb perfusion is important for optimizing future regional chemotherapeutic strategies in melanoma. Patient characteristics and procedural variables were collected retrospectively from 162 ILIs performed at 8 institutions (2001 to 2008) and compared using chi-square and Student's t-test. ILIs were performed for 30 minutes in patients with in-transit melanoma. Melphalan dose was corrected for ideal body weight (IBW) in 42% (n = 68) of procedures. Response was determined at 3 months by Response Evaluation Criteria in Solid Tumors; toxicity was assessed using the Wieberdink Limb Toxicity Scale. In 128 evaluable patients, complete response rate was 31%, partial response rate was 33%, and there was no response in 36% of patients. For all patients (n = 162), 36% had Wieberdink toxicity grade >or=3 with one toxicity-related amputation. On multivariate analysis, smaller limb volumes were associated with better overall response (p = 0.021). Use of papaverine in the circuit to achieve cutaneous vasodilation was associated with better response (p < 0.001) but higher risk of grade >or=3 toxicity (p = 0.001). Correction of melphalan dose for ideal body weight did not alter complete response (p = 0.345), but did lead to marked reduction in toxicity (p < 0.001). In the first multi-institutional analysis of ILI, a complete response rate of 31% was achieved with acceptable toxicity demonstrating this procedure to be a reasonable alternative to hyperthermic isolated limb perfusion in the management of advanced extremity melanoma.
    Journal of the American College of Surgeons 05/2009; 208(5):706-15; discussion 715-7. · 4.50 Impact Factor
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    ABSTRACT: Isolated limb infusion (ILI) is a recently described minimally invasive technique developed in Australia for delivering regional chemotherapy. This study examined the efficacy and toxicity of ILI, compared to hyperthermic isolated limb perfusion (HILP), in treating extremity in-transit melanoma. Variables from a prospective single institution database of 120 regionally treated melanoma patients (1995-2007) were compared using chi-square analysis. This included 61 consecutive ILI treatments in 58 patients and 59 HILP treatments in 54 patients. Response was defined at 3 months using the response evaluation criteria in solid tumors (RECIST). ILI was performed using melphalan (LPAM) and dactinomycin for 30 min after limb temperature reached 37 degrees C. HILP was performed using LPAM for 60 min after limb temperature reached 38.5 degrees C. For ILI (n = 61), the complete response (CR) rate was 30%, the partial response (PR) rate was 14%, and there was no response (NR) in 56% of patients. The median duration of CR was 12 months and 18% of patients experienced (grade >or=3) toxicity. HILP (n = 59) was associated with a better (P < 0.001) response rate (CR 57%, PR 31%, and NR 12%) however, more patients (32%) experienced grade >or=3 toxicity (P = 0.037). The dose of LPAM was corrected for ideal body weight (IBW) in 40 out of 61 ILI procedures, and 13 of 59 HILP procedures. This dosing modification was associated with decreased toxicity (P = 0.024) without diminishing response. ILI was found to be a well-tolerated alternative to HILP. While ILI does not appear to be as effective as HILP, it does seem to be associated with less morbidity.
    Annals of Surgical Oncology 06/2008; 15(8):2195-205. · 4.12 Impact Factor
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    ABSTRACT: The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not optimally recognize tumor cells normally expressing the constitutive proteasome. Using small interfering RNA (siRNA) transfection of DCs to inhibit expression of the 3 inducible immunoproteasome subunits in mature DCs, we found that such DCs expressed increased intracellular levels of constitutive proteasomes and presented an altered repertoire of tumor-antigenic peptides. When DCs generated from the monocytes of 3 patients with melanoma were transfected with immunoproteasome siRNA, induced to mature, and then trans-fected with RNA encoding defined melanoma antigens, these DCs were superior inducers of antigen-specific CTLs against autologous melanoma cells. This alteration of DC proteasome composition, which enhances the ability of mature antigen-loaded DCs to stimulate anti-tumor immune responses, may lead to more effective DC-based tumor immunotherapy.
    Blood 01/2008; 110(13):4341-50. · 9.78 Impact Factor
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    ABSTRACT: The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma. We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma. The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01). When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.
    The Journal of thoracic and cardiovascular surgery 02/2007; 133(1):104-10. · 3.41 Impact Factor
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    ABSTRACT: To analyze the Kraske procedure as an approach to mid-rectal disease. Twenty-two patients underwent a Kraske procedure at either Duke University Medical Center, the Durham Veterans Administration Medical Center, or the Durham Regional Hospital between 1992 and 1997. The clinical and pathologic characteristics of these patients were retrospectively analyzed and compared with previous published series. Of the 22 patients, 13 underwent resection of an adenocarcinoma and 9 underwent resection of a villous adenoma. Post-operative complications included four fecal fistulas (two of which required a temporary diverting colostomy), two wound infections, two cases of urinary retention, and one case of transient fecal incontinence. The Kraske procedure minimizes exposure of mid-rectal lesions without the morbidity of a major laparotomy. However, it does carry a moderate complication rate and thus should be utilized selectively in managing patients with mid-rectal tumors not amenable to other treatment options.
    Journal of Surgical Oncology 10/2006; 94(3):194-202. · 2.64 Impact Factor
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    ABSTRACT: In 2005, it is now estimated that one in 62 Americans have a lifetime risk of developing invasive melanoma. Melanoma of the ear accounts for 1% of all cases of melanoma and 14.5% of all head and neck melanomas. With this increase in incidence, plastic surgeons will likely have to treat and manage more of these patients in the future. A retrospective chart review was performed on 199 patients diagnosed with primary melanoma of the ear. Specimens were reviewed by same center dermatopathologists (Duke University Medical Center, Durham, NC) for standardization of histologic criteria in all but 10 patients. Surgical treatment and outcomes were reviewed and survival rates based on thickness and stage were calculated. Metastases information, anatomic location on the ear, and histologic subtype were recorded and analyzed. The median length of follow up was 3.3 years with a range of 0.4 to 24.9 years. Eighty-six patients were known to be dead at the last known follow-up date. The median survival time among these patients was 7.9 years. The most common histologic classification of the lesions were superficial spreading type (45.2%) and were most likely to be localized to the anterior helix (49.3%). One hundred sixty-one of 199 (80.9%) patients underwent wide local excision with local recurrence rate of 10.6%. Overall, 43.2% of patients developed a local recurrence or metastatic spread. Ulceration, thickness, and stage all negatively affected survival. This is the largest review of primary ear melanoma cases reported to date. Survival probabilities at 2, 5, and 10 years for melanoma of the ear based on thickness and stage are presented. Ulceration adversely affected survival probability (P < 0.003). Lesion excision with confirmed negative margins on permanent section pathology should be the goal of initial surgical therapy, and there is no apparent role for elective lymph node dissection in treatment of melanoma of the ear.
    Annals of Plastic Surgery 08/2006; 57(1):70-6. · 1.38 Impact Factor
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    ABSTRACT: Desmoplastic melanoma (DM) has been associated with higher local recurrence rates than other types of cutaneous melanoma. Current controversies regarding locoregional treatment strategies warrant further investigation. Retrospective review of a prospectively maintained melanoma database identified 129 patients with DM out of >12,500 melanoma patients referred for treatment from 1980 to 2003. Clinical and histopathologic characteristics, recurrence, and survival were analyzed. The median follow-up was 4.0 years. Of the 129 patients identified, 82 (63.6%) were male, and the median age was 55.2 years. American Joint Committee on Cancer staging was I, II, and III in 25.6%, 68.0%, and 6.4% of patients, respectively, and the mean tumor thickness was 4.42 mm. Overall survival was 76% at 5 years and 64% at 10 years; median survival was 13.0 years. A total of 51 patients (39.5%) experienced disease recurrence, with a median time to recurrence of 1.3 years. The first recurrence was local in 18 patients (14.0%), nodal in 18 patients (14.0%), and distant in 15 patients (11.6%), with median survivals of 6.7, 7.8, and 1.8 years, respectively. Statistically significant predictors of recurrence were a final positive margin status and stage, and predictors of overall survival were patient age and stage. Compared with other types of melanoma, DMs do demonstrate a tendency toward local recurrence, thus suggesting that narrower excision margins may not be appropriate in this population. Scrutiny of final surgical margins is critical to the local management of DM. In addition, the potential for regional nodal involvement must be considered at the time of diagnosis and during surveillance for disease recurrence.
    Annals of Surgical Oncology 06/2006; 13(5):728-39. · 4.12 Impact Factor
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    ABSTRACT: The incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival. A retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001. The median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett's esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)-not the degree of primary tumor response-predicted DFS. The nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.
    Annals of Surgical Oncology 04/2006; 13(3):340-6. · 4.12 Impact Factor
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    ABSTRACT: Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be identified in melanoma cell lines. We studied three metastatic melanoma cell lines that exhibited multiple morphologic forms in culture and demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342 dye, a technique known to enrich for stem cells in many tissues, to segregate cell populations. The cells with the greatest ability to efflux the dye were (1) small in size, (2) had the capacity to give rise to larger cell forms, and (3) had the greatest ability to expand in culture. The small cells were found to have a decreased proliferative rate and were less melanized. Large dendritic cells that appeared to be nonproliferative were identified in cultures. Treatment with cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell population but the residual proliferative capacity, both in vitro and in vivo, remained concentrated in the smaller cell fraction. Antigenic staining patterns were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100 (premelanosomal marker) favored the smaller cell population, while nerve growth factor receptor often labeled larger cells. Morphologic and antigenic heterogeneity remained intact after clonal purification. These findings are consistent with the behavior expected for a tumor based on stem cell biology; this finding has diagnostic and therapeutic implications for melanocytic neoplasias.
    Journal of Investigative Dermatology 02/2006; 126(1):142-53. · 6.19 Impact Factor
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    ABSTRACT: Analysis of multiple clinical and pathological factors in patients undergoing therapeutic hyperthermic isolated limb perfusion for extremity melanoma can identify variables with prognostic significance. Retrospective review of a prospectively collected limb perfusion database with a median follow-up interval of 32.2 months. Single-institution tertiary care surgical oncology unit. We report a series of 59 consecutive therapeutic hyperthermic isolated limb perfusion treatments (14 upper extremity and 45 lower extremity) in 54 patients with melanoma from January 1, 1995, through December 31, 2002, using a standard melphalan dosing protocol. At the time of perfusion, 31 cases had fewer than 10 lesions, with none greater than 3 cm in diameter. The remaining 28 cases had 10 or more lesions or at least 1 lesion greater than 3 cm in diameter. Response, recurrence, and survival were assessed in relation to multiple demographic, clinical, and technical variables using chi2, log-rank, and Kaplan-Meier survival analyses. The 3-year survival for the entire cohort was 54%. Thirty-three (56%) of the 59 perfusion treatments resulted in a persistent complete response of at least 6 months' duration. Statistical analysis showed that patients with no evidence of regional nodal involvement had a significantly lower incidence of distant recurrence (P = .02). Those patients achieving a complete response to therapy had a survival advantage (P = .03). In patients undergoing therapeutic hyperthermic isolated limb perfusion for in-transit melanoma, the ability to achieve a complete response following treatment, independent of regional nodal status, was the strongest predictor of long-term survival.
    Archives of Surgery 12/2005; 140(11):1115-20. · 4.10 Impact Factor
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    ABSTRACT: Cutaneous melanoma remains an ongoing public health threat, and the cornerstone of management continues to be early diagnosis and treatment. Unfortunately, primary melanomas may have atypical presentations, making early diagnosis difficult and causing significant treatment delays. In this report, an unusual case is presented in which a patient experienced the synchronous development of a melanoma in situ within a skin graft donor site and an invasive melanoma within the recipient skin graft site. This exceptional presentation of cutaneous melanoma is discussed to highlight key principles of skin grafting in relation to the management of malignant melanoma.
    Annals of Plastic Surgery 02/2005; 54(1):92-6. · 1.38 Impact Factor
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    Hilliard F Seigler
    Annals of Surgery 08/2004; 240(1):7-8. · 6.33 Impact Factor
  • Hilliard F Seigler
    Journal of Surgical Oncology 08/2004; 86(4):187-8. · 2.64 Impact Factor
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    ABSTRACT: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8 mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.
    International Journal of Radiation OncologyBiologyPhysics 04/2004; 58(3):779-85. · 4.52 Impact Factor
  • Paul J Mosca, Douglas S Tyler, Hilliard F Seigler
    Advances in Surgery 02/2004; 38:85-119.
  • Current Problems in Surgery 02/2004; 41(1):15-132. · 2.08 Impact Factor
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    ABSTRACT: Without Abstract
    Annals of Surgical Oncology 01/2004; 11. · 4.12 Impact Factor

Publication Stats

8k Citations
994.01 Total Impact Points

Institutions

  • 1971–2011
    • Duke University Medical Center
      • Department of Surgery
      Durham, NC, United States
  • 2002
    • University of Louisville
      • Department of Ophthalmology and Visual Sciences
      Louisville, KY, United States
  • 1992
    • University of South Florida
      • Department of Surgery
      Tampa, FL, United States
  • 1980–1986
    • Duke University
      • Department of Surgery
      Durham, North Carolina, United States
  • 1981
    • Hackensack University Medical Center
      Hackensack, New Jersey, United States
  • 1976
    • Emory University
      Atlanta, Georgia, United States