Introduction Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for r... more Introduction Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for repair exist, and refinements in techniques can lead to “successful” outcomes. Review of the literature demonstrates that outcomes studies are scarce and mostly limited to comments on closure rate. We have experienced “success” in our own series with 100% closure rate, regardless of fistula etiology and comorbidities (radiation, inflammation, etc). However, long-term outcomes, including various complications and quality of life changes, have previously been underreported. Methods Critical analysis of various outcomes after fistula repair in 14 patients was performed. Patients were surveyed and interviewed with regard to problems before and after fistula repair to obtain objective data focusing on their experience and outcomes. Conclusions are based on physician assessment and patient surveys 1 year after fistula repair and at least 6 months after ostomy reversal and are discussed within t...
Introduction: After promising early outcomes in the use of absorbable biologic mesh for complex a... more Introduction: After promising early outcomes in the use of absorbable biologic mesh for complex abdominal wall reconstruction, significant criticism has been raised over the longevity of these repairs after its 2-year resorption profile. Methods: This is the long-term (5-year) follow-up analysis of our initial experience with the absorbable polymer scaffold poly-4-hydroxybutyrate (P4HB) mesh compared with a consecutive contiguous group treated with porcine cadaveric mesh for complex abdominal wall reconstructions. Our clinical analysis was performed using Stata 14.2 and Excel 16.16.23. Results: After a 5-year follow-up period, the P4HB group (n = 31) experienced lower rates of reherniation (12.9% vs 38.1%; P = 0.017) compared with the porcine cadaveric mesh group (n = 42). The median interval in months to recurrent herniation was similar between groups (24.3 vs 20.8; P = 0.700). Multivariate logistic regression analysis on long-term outcomes identified smoking (P = 0.004), African American race (P = 0.004), and the use of cadaveric grafts (P = 0.003) as risks for complication while smoking (P = 0.034) and the use of cadaveric grafts (P = 0.014) were identified as risks for recurrence. The long-term cost analysis showed that P4HB had a $10,595 per case costs savings over porcine cadaveric mesh. Conclusions: Our study identified the superior outcomes in clinical performance and a value-based benefit of absorbable biologic P4HB scaffold persisted after the 2-year resorption timeframe. Data analysis also confirmed the use of porcine cadaveric grafts independently contributed to the incidence of complications and recurrences. Mini-abstract: Long-term clinical and financial outcomes for abdominal wall reconstruction utilizing a biological absorbable mesh.
INTRODUCTION Rectovaginal fistulas are notorious for both their morbidity and their difficulty to... more INTRODUCTION Rectovaginal fistulas are notorious for both their morbidity and their difficulty to treat effectively. A variety of methods for repair has been described; however, there is no consensus on the ideal repair. A better understanding of the anatomical relationship of fistulas to the anal sphincter and detrusor muscles is one of the components necessary to develop an effective treatment plan for repair and preservation of sphincter mechanics. METHODS A review of the literature was conducted to determine the types of methods typically used by reconstructive surgeons for repair of rectovaginal fistulas. A critical clinical analysis of our series of 10 patients was performed to determine optimal strategies for and pitfalls of repair in the context of recent reports in hopes of refining surgical techniques. RESULTS Detailed anatomical understanding of the relationship of fistulas to the surrounding sphincter muscles is described. Etiology of the fistula and its anatomical relationship to the surrounding sphincter complex is used to help develop an algorithm for repair. Suprasphincteric fistulas will necessitate a laparotomy for repair, intersphincteric fistulas will often require muscle interposition with recreation of the vaginal and rectal walls, and low/transphincteric fistulas will require local flaps mostly for coverage and repair of the sphincter muscles. CONCLUSIONS Complex rectovaginal fistulas are both debilitating for the patient and extremely difficult to manage. Plastic surgeons are often involved in such cases only after previous attempts at repair have failed. The success of surgery in treating these patients with rectovaginal fistulas depends on a variety of factors. Unfortunately, the available literature describing these repairs lacks uniform guidance regarding approach to repair. Herein, we attempt to detail the possible anatomical variations of fistulas in relationship to the sphincter muscles to begin the discussion necessary for the development of an algorithm for repair that considers preservation of sphincter mechanism function.
Introduction: Retrobulbar hemorrhage is a rare, progressive, sight-threatening emergency. Standar... more Introduction: Retrobulbar hemorrhage is a rare, progressive, sight-threatening emergency. Standardized treatment algorithms for it exist in the literature; however, their efficiency is uninterpretable in most nonophthalmic settings. This paper reviews retrobulbar bleeding, the pathophysiology of vision loss, and the therapeutic modalities and their efficacy in addressing such visual damage. Case Report: We present the unfortunate case of an 82-year-old male with coronary artery disease on anticoagulants who presented for a vitrectomy for a vitreous hemorrhage secondary to eccentric disciform degeneration under general anesthetic with an accompanying retrobulbar block. He subsequently developed a retrobulbar hemorrhage at some point post-operatively. He presented to his surgeon 18-hours after the operation with no light perception on ophthalmologic examination as well as facial ecchymosis and proptosis. Efforts to reduce his intraocular pressure were successful, but there was no retu...
Successful parathyroidectomy requires advanced surgeon experience. We aim to examine population c... more Successful parathyroidectomy requires advanced surgeon experience. We aim to examine population characteristics at risk of being managed by low-volume surgeons. A cross-sectional study was performed utilizing the Nationwide Inpatient Sample database, 2004 to 2009. The study population included adult inpatients who underwent parathyroidectomy for primary hyperparathyroidism. A total of 3,503 discharge records were included. Men, Hispanics, and those with Medicaid/Medicare health coverage were more likely to be managed by low-volume surgeons (P < .05 each). Low-volume surgeons were more likely to operate in rural (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.95 to 8.16; P < .001) or nonteaching hospitals (OR, 2.15; 95% CI, 1.42 to 3.27; P < .001). Southern region of the United States had a high prevalence of low-volume surgeons compared with other regions (Southern: 51.3%, Northeast: 24.3%, Midwest: 25.6%, and West: 27.6%, P < .001). Operations by the low-volume ...
Plastic and reconstructive surgery. Global open, 2017
Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and s... more Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and stem cells that possess the ability to inhibit infection, improve healing, and stimulate regeneration. A meta-analysis was performed examining randomized controlled trials comparing amniotic tissue products with standard of care in nonhealing diabetic foot ulcers including PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A search of 3 databases identified 596 potentially relevant articles. Application of selection criteria led to the selection of 5 randomized controlled trials. The 5 selected randomized controlled trials represented a total of 311 patients. The pooled relative risk of healing with amniotic products compared with control was 2.7496 (2.05725-3.66524, P < 0.001). The current meta-analysis indicates that the treatment of diabetic foot ulcers with amniotic membrane improves healing rates in diabetic foot ulcers. Furthe...
Several reports have proposed that increased vascular flow on color Doppler sonography may be ass... more Several reports have proposed that increased vascular flow on color Doppler sonography may be associated with malignancy in thyroid nodules. Others have described no correlation between the presence of flow and risk of malignancy. The purpose of this study was to determine whether the vascularity of a thyroid nodule can aid in the prediction of malignancy by performing a meta-analysis of the current literature. Independent reviewers conducted a systematic review of publications from PubMed, EMBASE, and the Cochrane Database of Systematic Review using the following keyword searches: &amp;amp;quot;vascular thyroid nodule&amp;amp;quot;, and &amp;amp;quot;vascular malignant thyroid nodule&amp;amp;quot;. Outcomes included vascular flow pattern, nodule size, calcifications, echogenicity, margins, and shape. Data were extracted following review of appropriate studies, and outcome differences were calculated using analysis of variance and the Bonferroni method. Eighty-nine publications were identified and 14 prospective studies met inclusion criteria totaling 4,154 thyroid nodules, 1,419 (34%) of which were malignant. Thirty-three percent of malignant thyroid nodules had no vascular flow, while 17% had peripheral and 50% had internal vascular flow. There was no significant difference in vascular flow (95% CI: -14.329, 4.257), or peripheral vascular flow rate between malignant and benign thyroid nodules (95% CI: -29.254, 4.313). Also, there was no significant difference in internal vascularity between malignant and benign thyroid nodules (95% CI: -72.067, 2.824). It appears that utilization of vascular flow on color Doppler sonography may not accurately predict malignancy in thyroid nodules. Further studies are warranted to investigate the predictive role of increased vascularity in diagnosing suspicious thyroid nodules.
Resistance to chemotherapy is a significant impediment to the treatment of breast cancer. More th... more Resistance to chemotherapy is a significant impediment to the treatment of breast cancer. More than 30% of breast cancer patients present with intrinsic resistance to chemotherapy; almost all who initially respond will develop acquired resistance. Resistant tumors frequently exhibit constitutive activation of numerous survival signaling pathways, including ERK, AKT, NF-kB, and STAT3. We have reported that the circadian hormone melatonin inhibits the growth of both ERa+/ERa- breast cancers and, as well as the daytime induced phospho-activation of ERK1/2, AKT and NF-kB in breast tumor xenografts. We also demonstrated that dim light at night (dLAN), by decreasing nocturnal melatonin, resulted in constitutive phospho-activation of ERK1/2, CREB, NF-kB, and STAT3, promoting resistance to tamoxifen and doxorubicin therapy. Here we tested the hypothesis that dLAN, via phospho-activation of ERK1/2 and STAT3, promotes resistance to paclitaxel (Pax). Female nude rats with “tissue-isolated” MCF-7 breast cancer xenografts were housed in photoperiodic conditions of either LD 12:12, 12:12dLAN (0.2 lux), or 12:12dLAN supplemented with nighttime melatonin (0.05 og/ml) in the drinking water, with lights on at 0600 hrs and off at 1800 hrs. When estimated tumor weights reached 2.5 g, animals were treated daily with either diluent or Pax i.p. (4oa/kg) 2 h prior to onset of dLAN or dLAN with nighttime melatonin supplementation. Blood samples collected during the mid-dark phase (2400 hrs) showed elevated nocturnal melatonin in the LD 12:12 group, but significantly suppressed melatonin in the dLAN group. Tumor xenografts from rats housed in dLAN showed a 3-fold decrease in latency-to-onset and a 2.8-fold increased growth rates vs. those from rats receiving melatonin supplementation. Tumor cAMP levels, linoleic acid, and tumor metabolism (Warburg effect) were significantly elevated in dLAN tumors. Numerous signaling pathways including ERK1/2, RSK2, and STAT3, were phospho-activated and others including AKT and HER2/3 were elevated at 2400 hrs by dLAN but repressed in dLAN melatonin supplemented tumors. Tumors from dLAN rats showed intrinsic resistance to Pax, whereas those in LD 12:12 or dLAN and supplemented with nighttime melatonin rapidly regressed. These findings show that temporally coordinated and integrated metabolic and signal transduction mechanisms, particularly the STAT3 pathway, underlying human breast cancer growth, can be activated by the host9s exposure to LAN with profound effects culminating in rapid tumor progression and the development of resistance to chemotherapy. Citation Format: Steven M. Hill, Shulin Xiang, Robert T. Dauchy, Lulu mao, Lin Yuan, Adam Hauch, Victoria P. Belancio, Melissa A. Wren-Dail, David Pointer, Peter W. Lundberg, Whitney M. Summers, David E. Blask. Circadian/melatonin disruption by dim light at night drives paclitaxel resistance in breast cancer via activation of stat3. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 874.
The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society, 2015
While robotic surgery has seen much success in the treatment of gynecologic malignancies, the tec... more While robotic surgery has seen much success in the treatment of gynecologic malignancies, the technical aspects of this approach raise concern for spreading tumor cells within the peritoneal cavity and to trocar sites. To date, robotic trocar site metastases have been identified following surgery for both endometrial and cervical cancer.
The Journal of the Louisiana State Medical Society Official Organ of the Louisiana State Medical Society, Sep 1, 2014
Exit-site infections involving peritoneal dialysis catheters are a cumbersome issue that can be d... more Exit-site infections involving peritoneal dialysis catheters are a cumbersome issue that can be difficult to manage. Such infections are usually due to gram-positive organisms and are often treated successfully with oral and/or topical antibiotics. Infections associated with Mycobacterium sp. are much more rare and difficult to treat. We report our experience with four cases of exit-site infections with Mycobacterium sp. in the New Orleans area, along with a review of risk factors and current literature.
Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of m... more Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue-isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumor cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13-hydroxyoctadecadienoic acid (13-HODE). Here we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumor proliferative activity, aerobic glycolysis (Warburg effect), and LA metabolic signaling in tissue-isolated LMS xenografts perfused in situ with this blood. Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumor LA uptake, 13-HODE release, as well as significant reductions in tumor cAMP levels, DNA content, and [(3) H]-thymidine incorporation into DNA. Furthermore, melatonin completely suppressed the phospho-activation of ERK 1/2, AKT, GSK3β, and NF-kB (p65). The addition of S20928, a non-selective melatonin antagonist, reversed these melatonin inhibitory effects. Moreover, in in vitro cell culture studies, physiological concentrations of melatonin repressed cell proliferation and cell invasion. These results demonstrate that nocturnal melatonin directly inhibited tumor growth and invasion of human LMS via suppression of the Warburg effect, LA uptake, and other related signaling mechanisms. An understanding of these novel signaling pathway(s) and their association with aerobic glycolysis and LA metabolism in human LMS may lead to new circadian-based therapies for the prevention and treatment of LMS and potentially other mesenchymally-derived solid tumors. This article is protected by copyright. All rights reserved.
Introduction Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for r... more Introduction Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for repair exist, and refinements in techniques can lead to “successful” outcomes. Review of the literature demonstrates that outcomes studies are scarce and mostly limited to comments on closure rate. We have experienced “success” in our own series with 100% closure rate, regardless of fistula etiology and comorbidities (radiation, inflammation, etc). However, long-term outcomes, including various complications and quality of life changes, have previously been underreported. Methods Critical analysis of various outcomes after fistula repair in 14 patients was performed. Patients were surveyed and interviewed with regard to problems before and after fistula repair to obtain objective data focusing on their experience and outcomes. Conclusions are based on physician assessment and patient surveys 1 year after fistula repair and at least 6 months after ostomy reversal and are discussed within t...
Introduction: After promising early outcomes in the use of absorbable biologic mesh for complex a... more Introduction: After promising early outcomes in the use of absorbable biologic mesh for complex abdominal wall reconstruction, significant criticism has been raised over the longevity of these repairs after its 2-year resorption profile. Methods: This is the long-term (5-year) follow-up analysis of our initial experience with the absorbable polymer scaffold poly-4-hydroxybutyrate (P4HB) mesh compared with a consecutive contiguous group treated with porcine cadaveric mesh for complex abdominal wall reconstructions. Our clinical analysis was performed using Stata 14.2 and Excel 16.16.23. Results: After a 5-year follow-up period, the P4HB group (n = 31) experienced lower rates of reherniation (12.9% vs 38.1%; P = 0.017) compared with the porcine cadaveric mesh group (n = 42). The median interval in months to recurrent herniation was similar between groups (24.3 vs 20.8; P = 0.700). Multivariate logistic regression analysis on long-term outcomes identified smoking (P = 0.004), African American race (P = 0.004), and the use of cadaveric grafts (P = 0.003) as risks for complication while smoking (P = 0.034) and the use of cadaveric grafts (P = 0.014) were identified as risks for recurrence. The long-term cost analysis showed that P4HB had a $10,595 per case costs savings over porcine cadaveric mesh. Conclusions: Our study identified the superior outcomes in clinical performance and a value-based benefit of absorbable biologic P4HB scaffold persisted after the 2-year resorption timeframe. Data analysis also confirmed the use of porcine cadaveric grafts independently contributed to the incidence of complications and recurrences. Mini-abstract: Long-term clinical and financial outcomes for abdominal wall reconstruction utilizing a biological absorbable mesh.
INTRODUCTION Rectovaginal fistulas are notorious for both their morbidity and their difficulty to... more INTRODUCTION Rectovaginal fistulas are notorious for both their morbidity and their difficulty to treat effectively. A variety of methods for repair has been described; however, there is no consensus on the ideal repair. A better understanding of the anatomical relationship of fistulas to the anal sphincter and detrusor muscles is one of the components necessary to develop an effective treatment plan for repair and preservation of sphincter mechanics. METHODS A review of the literature was conducted to determine the types of methods typically used by reconstructive surgeons for repair of rectovaginal fistulas. A critical clinical analysis of our series of 10 patients was performed to determine optimal strategies for and pitfalls of repair in the context of recent reports in hopes of refining surgical techniques. RESULTS Detailed anatomical understanding of the relationship of fistulas to the surrounding sphincter muscles is described. Etiology of the fistula and its anatomical relationship to the surrounding sphincter complex is used to help develop an algorithm for repair. Suprasphincteric fistulas will necessitate a laparotomy for repair, intersphincteric fistulas will often require muscle interposition with recreation of the vaginal and rectal walls, and low/transphincteric fistulas will require local flaps mostly for coverage and repair of the sphincter muscles. CONCLUSIONS Complex rectovaginal fistulas are both debilitating for the patient and extremely difficult to manage. Plastic surgeons are often involved in such cases only after previous attempts at repair have failed. The success of surgery in treating these patients with rectovaginal fistulas depends on a variety of factors. Unfortunately, the available literature describing these repairs lacks uniform guidance regarding approach to repair. Herein, we attempt to detail the possible anatomical variations of fistulas in relationship to the sphincter muscles to begin the discussion necessary for the development of an algorithm for repair that considers preservation of sphincter mechanism function.
Introduction: Retrobulbar hemorrhage is a rare, progressive, sight-threatening emergency. Standar... more Introduction: Retrobulbar hemorrhage is a rare, progressive, sight-threatening emergency. Standardized treatment algorithms for it exist in the literature; however, their efficiency is uninterpretable in most nonophthalmic settings. This paper reviews retrobulbar bleeding, the pathophysiology of vision loss, and the therapeutic modalities and their efficacy in addressing such visual damage. Case Report: We present the unfortunate case of an 82-year-old male with coronary artery disease on anticoagulants who presented for a vitrectomy for a vitreous hemorrhage secondary to eccentric disciform degeneration under general anesthetic with an accompanying retrobulbar block. He subsequently developed a retrobulbar hemorrhage at some point post-operatively. He presented to his surgeon 18-hours after the operation with no light perception on ophthalmologic examination as well as facial ecchymosis and proptosis. Efforts to reduce his intraocular pressure were successful, but there was no retu...
Successful parathyroidectomy requires advanced surgeon experience. We aim to examine population c... more Successful parathyroidectomy requires advanced surgeon experience. We aim to examine population characteristics at risk of being managed by low-volume surgeons. A cross-sectional study was performed utilizing the Nationwide Inpatient Sample database, 2004 to 2009. The study population included adult inpatients who underwent parathyroidectomy for primary hyperparathyroidism. A total of 3,503 discharge records were included. Men, Hispanics, and those with Medicaid/Medicare health coverage were more likely to be managed by low-volume surgeons (P < .05 each). Low-volume surgeons were more likely to operate in rural (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.95 to 8.16; P < .001) or nonteaching hospitals (OR, 2.15; 95% CI, 1.42 to 3.27; P < .001). Southern region of the United States had a high prevalence of low-volume surgeons compared with other regions (Southern: 51.3%, Northeast: 24.3%, Midwest: 25.6%, and West: 27.6%, P < .001). Operations by the low-volume ...
Plastic and reconstructive surgery. Global open, 2017
Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and s... more Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and stem cells that possess the ability to inhibit infection, improve healing, and stimulate regeneration. A meta-analysis was performed examining randomized controlled trials comparing amniotic tissue products with standard of care in nonhealing diabetic foot ulcers including PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A search of 3 databases identified 596 potentially relevant articles. Application of selection criteria led to the selection of 5 randomized controlled trials. The 5 selected randomized controlled trials represented a total of 311 patients. The pooled relative risk of healing with amniotic products compared with control was 2.7496 (2.05725-3.66524, P < 0.001). The current meta-analysis indicates that the treatment of diabetic foot ulcers with amniotic membrane improves healing rates in diabetic foot ulcers. Furthe...
Several reports have proposed that increased vascular flow on color Doppler sonography may be ass... more Several reports have proposed that increased vascular flow on color Doppler sonography may be associated with malignancy in thyroid nodules. Others have described no correlation between the presence of flow and risk of malignancy. The purpose of this study was to determine whether the vascularity of a thyroid nodule can aid in the prediction of malignancy by performing a meta-analysis of the current literature. Independent reviewers conducted a systematic review of publications from PubMed, EMBASE, and the Cochrane Database of Systematic Review using the following keyword searches: &amp;amp;quot;vascular thyroid nodule&amp;amp;quot;, and &amp;amp;quot;vascular malignant thyroid nodule&amp;amp;quot;. Outcomes included vascular flow pattern, nodule size, calcifications, echogenicity, margins, and shape. Data were extracted following review of appropriate studies, and outcome differences were calculated using analysis of variance and the Bonferroni method. Eighty-nine publications were identified and 14 prospective studies met inclusion criteria totaling 4,154 thyroid nodules, 1,419 (34%) of which were malignant. Thirty-three percent of malignant thyroid nodules had no vascular flow, while 17% had peripheral and 50% had internal vascular flow. There was no significant difference in vascular flow (95% CI: -14.329, 4.257), or peripheral vascular flow rate between malignant and benign thyroid nodules (95% CI: -29.254, 4.313). Also, there was no significant difference in internal vascularity between malignant and benign thyroid nodules (95% CI: -72.067, 2.824). It appears that utilization of vascular flow on color Doppler sonography may not accurately predict malignancy in thyroid nodules. Further studies are warranted to investigate the predictive role of increased vascularity in diagnosing suspicious thyroid nodules.
Resistance to chemotherapy is a significant impediment to the treatment of breast cancer. More th... more Resistance to chemotherapy is a significant impediment to the treatment of breast cancer. More than 30% of breast cancer patients present with intrinsic resistance to chemotherapy; almost all who initially respond will develop acquired resistance. Resistant tumors frequently exhibit constitutive activation of numerous survival signaling pathways, including ERK, AKT, NF-kB, and STAT3. We have reported that the circadian hormone melatonin inhibits the growth of both ERa+/ERa- breast cancers and, as well as the daytime induced phospho-activation of ERK1/2, AKT and NF-kB in breast tumor xenografts. We also demonstrated that dim light at night (dLAN), by decreasing nocturnal melatonin, resulted in constitutive phospho-activation of ERK1/2, CREB, NF-kB, and STAT3, promoting resistance to tamoxifen and doxorubicin therapy. Here we tested the hypothesis that dLAN, via phospho-activation of ERK1/2 and STAT3, promotes resistance to paclitaxel (Pax). Female nude rats with “tissue-isolated” MCF-7 breast cancer xenografts were housed in photoperiodic conditions of either LD 12:12, 12:12dLAN (0.2 lux), or 12:12dLAN supplemented with nighttime melatonin (0.05 og/ml) in the drinking water, with lights on at 0600 hrs and off at 1800 hrs. When estimated tumor weights reached 2.5 g, animals were treated daily with either diluent or Pax i.p. (4oa/kg) 2 h prior to onset of dLAN or dLAN with nighttime melatonin supplementation. Blood samples collected during the mid-dark phase (2400 hrs) showed elevated nocturnal melatonin in the LD 12:12 group, but significantly suppressed melatonin in the dLAN group. Tumor xenografts from rats housed in dLAN showed a 3-fold decrease in latency-to-onset and a 2.8-fold increased growth rates vs. those from rats receiving melatonin supplementation. Tumor cAMP levels, linoleic acid, and tumor metabolism (Warburg effect) were significantly elevated in dLAN tumors. Numerous signaling pathways including ERK1/2, RSK2, and STAT3, were phospho-activated and others including AKT and HER2/3 were elevated at 2400 hrs by dLAN but repressed in dLAN melatonin supplemented tumors. Tumors from dLAN rats showed intrinsic resistance to Pax, whereas those in LD 12:12 or dLAN and supplemented with nighttime melatonin rapidly regressed. These findings show that temporally coordinated and integrated metabolic and signal transduction mechanisms, particularly the STAT3 pathway, underlying human breast cancer growth, can be activated by the host9s exposure to LAN with profound effects culminating in rapid tumor progression and the development of resistance to chemotherapy. Citation Format: Steven M. Hill, Shulin Xiang, Robert T. Dauchy, Lulu mao, Lin Yuan, Adam Hauch, Victoria P. Belancio, Melissa A. Wren-Dail, David Pointer, Peter W. Lundberg, Whitney M. Summers, David E. Blask. Circadian/melatonin disruption by dim light at night drives paclitaxel resistance in breast cancer via activation of stat3. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 874.
The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society, 2015
While robotic surgery has seen much success in the treatment of gynecologic malignancies, the tec... more While robotic surgery has seen much success in the treatment of gynecologic malignancies, the technical aspects of this approach raise concern for spreading tumor cells within the peritoneal cavity and to trocar sites. To date, robotic trocar site metastases have been identified following surgery for both endometrial and cervical cancer.
The Journal of the Louisiana State Medical Society Official Organ of the Louisiana State Medical Society, Sep 1, 2014
Exit-site infections involving peritoneal dialysis catheters are a cumbersome issue that can be d... more Exit-site infections involving peritoneal dialysis catheters are a cumbersome issue that can be difficult to manage. Such infections are usually due to gram-positive organisms and are often treated successfully with oral and/or topical antibiotics. Infections associated with Mycobacterium sp. are much more rare and difficult to treat. We report our experience with four cases of exit-site infections with Mycobacterium sp. in the New Orleans area, along with a review of risk factors and current literature.
Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of m... more Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue-isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumor cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13-hydroxyoctadecadienoic acid (13-HODE). Here we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumor proliferative activity, aerobic glycolysis (Warburg effect), and LA metabolic signaling in tissue-isolated LMS xenografts perfused in situ with this blood. Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumor LA uptake, 13-HODE release, as well as significant reductions in tumor cAMP levels, DNA content, and [(3) H]-thymidine incorporation into DNA. Furthermore, melatonin completely suppressed the phospho-activation of ERK 1/2, AKT, GSK3β, and NF-kB (p65). The addition of S20928, a non-selective melatonin antagonist, reversed these melatonin inhibitory effects. Moreover, in in vitro cell culture studies, physiological concentrations of melatonin repressed cell proliferation and cell invasion. These results demonstrate that nocturnal melatonin directly inhibited tumor growth and invasion of human LMS via suppression of the Warburg effect, LA uptake, and other related signaling mechanisms. An understanding of these novel signaling pathway(s) and their association with aerobic glycolysis and LA metabolism in human LMS may lead to new circadian-based therapies for the prevention and treatment of LMS and potentially other mesenchymally-derived solid tumors. This article is protected by copyright. All rights reserved.
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Papers by Adam Hauch