Susan Marie Lang

All Publications

• Trends in Uterine Cancer Mortality in the United States: A 50-Year Population-Based Analysis. Obstetrics and gynecology Somasegar, S., Bashi, A., Lang, S. M., Liao, C. I., Johnson, C., Darcy, K. M., Tian, C., Kapp, D. S., Chan, J. K. 2023

  Abstract

  To analyze mortality trends in uterine cancer in the United States over 50 years with an emphasis on age and race and ethnicity.Data on uterine cancer deaths from 1969 to 2018 were obtained from the National Center for Health Statistics. Trends were examined by age and race and ethnicity after adjustment for the hysterectomy rate and pregnancy.Uterine cancer mortality decreased between 1969 and 1997 (from 6.03 to 4.00/100,000) but increased between 1997 and 2018 (from 4.00 to 5.02/100,000). From 2001 to 2018, mortality rates increased by 1.25-fold across all age groups. In 2018, the mortality rate from uterine cancer for patients aged 70 years or older and 60-69 years was sixfold and threefold higher, respectively, than in younger patients (aged 50-59 years) (54.87/100,000 vs 27.80/100,000 vs 8.70/100,000). The mortality rate for non-Hispanic Black women was 2.2-fold higher than for non-Hispanic White, Hispanic, and non-Hispanic Asian or Pacific Islander women (17.6/100,000 vs 7.82/100,000, 6.54/100,000, and 4.24/100,000, respectively). On an intersection analysis of age and race, non-Hispanic Black women aged older than 60 years had a threefold higher mortality rate than non-Hispanic White women (72/100,000 vs 24/100,000). A notable finding was that young non-Hispanic Black and Hispanic women (30-39 years) had the highest annual increases in mortality at 3.3% and 3.8% per year compared with 2.2% in non-Hispanic White women.Since 2001, the uterine cancer mortality rate has increased across all four racial and ethnic groups examined, with the highest increase seen among non-Hispanic Black women. The largest increase in mortality was observed among younger non-Hispanic Black and Hispanic women.

  View details for DOI 10.1097/AOG.0000000000005321

  View details for PubMedID 37678887

• Differences in the mutational landscape directing targeted therapies for Black and White patients with endometrial cancer Eakin, C., Stewart, C., Somasegar, S., Lang, S., Aryasomayajula, C., Mysona, D., Salani, R., Argueta, C., Darcy, K., Tian, C., Kapp, D., Chan, J. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S205

  View details for DOI 10.1016/j.ygyno.2023.06.238

  View details for Web of Science ID 001079556100325

• Endometrioid compared to non-endometrioid uterine cancer: Which ones have more molecular targets for novel therapies? Stewart, C., Somasegar, S., Eakin, C., Lang, S., Aryasomayajula, C., Mysona, D., Salani, R., Argueta, C., Darcy, K., Tian, C., Kapp, D., Chan, J. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S172-S173

  View details for DOI 10.1016/j.ygyno.2023.06.181

  View details for Web of Science ID 001079556100270

• Patterns of care and predictors of overall survival in women diagnosed with serous tubal intra-epithelial carcinoma (STIC) Lang, S., Crafton, S., Miller, E., Krivak, T., Horne, Z. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S24-S25

  View details for DOI 10.1016/j.ygyno.2023.05.054

  View details for Web of Science ID 001057877600038

• Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer. Gynecologic oncology Garrett, A. A., Ricciuti, J., Lang, S. M., Burriss, M. E., Flanigan, M., O'Brien, E., Hay, C., Lesnock, J., Berger, J. L., Taylor, S. E. 2023; 175: 41-44

  Abstract

  The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer.All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics.One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts).In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

  View details for DOI 10.1016/j.ygyno.2023.05.067

  View details for PubMedID 37321154

• Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer. Gynecologic oncology Keunecke, C., Kulbe, H., Dreher, F., Taube, E. T., Chekerov, R., Horst, D., Hummel, M., Kessler, T., Pietzner, K., Kassuhn, W., Heitz, F., Muallem, M. Z., Lang, S. M., Vergote, I., Dorigo, O., Lammert, H., du Bois, A., Angelotti, T., Fotopoulou, C., Sehouli, J., Braicu, E. I. 2022

  Abstract

  BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach.OBJECTIVE: Our study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery.STUDY DESIGN: Firstly, "In silico" analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing. Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns.RESULTS: The Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC O0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of O0.797.CONCLUSION: The tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients.

  View details for DOI 10.1016/j.ygyno.2022.06.010

  View details for PubMedID 35738917

• Cell-based immunotherapies in gynecologic cancers. Current opinion in obstetrics & gynecology Lang, S. M., Dorigo, O. 1800; 34 (1): 10-14

  Abstract

  PURPOSE OF REVIEW: This review provides an update on recent developments in cell-based immunotherapy in gynecologic cancers.RECENT FINDINGS: Chimeric antigen receptor (CAR) technology has made significant progress allowing now for not only expressing CARs on T-cells, but also on other immune effector cells, such as natural killer cells and macrophages. Cell-based vaccines have started to show promising results in clinical trials.SUMMARY: Cell-based immunotherapies in gynecologic cancers continue to evolve with promising clinical efficacy in select patients.

  View details for DOI 10.1097/GCO.0000000000000760

  View details for PubMedID 34967809

• Linguistic Analysis of Letters of Recommendation for Vascular Surgery and Obstetrics and Gynecology Applicants Detects Differences in Attributable Strengths Based on Gender JOURNAL OF SURGICAL EDUCATION Go, C., Lang, S., Byrne, M., Brucha, D., Parviainen, K., Sachdev, U. 2021; 78 (5): 1535-1543

  Abstract

  We asked whether letters of recommendation (LOR) written for applicants to vascular surgery (VS), a field where men have traditionally predominated, differentially highlight attributes based on applicant gender. For comparison, LOR for applicants to Obstetrics and Gynecology (Ob/Gyn), a surgical field where women are highly represented were evaluated.We performed a cross-sectional review of LORs for students applying to VS or Ob/Gyn at our institution from 2017 to2018. Blinded to the gender of both the applicant and the letter author, investigators assessed word count per letter and used published rubrics to quantify how many words in the following categories: communal ("friendly"), able ("competent"), standout ("exceptional"), and grindstone ("hardworking"). Frequencies were reported as a function of specialty and gender.The study was performed at the University of Pittsburgh Medical Center and included letters written for applicants only to the stated residency programs at University of Pittsburgh Medical Center.LOR written for self-identified women and men applying to both residencies from US-based allopathic medical schools were de-identified and evaluated by blinded reviewers.One hundred and ninety-eight letters were reviewed for vascular surgery applicants. Two hundred letters were randomly selected from applications to Ob/Gyn as a comparison. Fifty-four vascular (27.8% women) and 63 Ob/Gyn (77.8% women) applicants were reviewed (p < 0.001 for gender). Licensing exam scores were higher for women than men applying to Ob/Gyn. Honor status was similar across fields and gender. Letters were shorter for VS applicants (p = 0.04). Gender-specific words (i.e., "lady" or "gentleman") were used more in VS letters (0.24 ± 0.50 vs 0.14 ± 0.42, p = 0.048). Ability words were more common (4.7 ± 2.6 vs 3.8 ± 2.1, p = 0.028) and grindstone adjectives were less common (3.4 ± 2.3 vs 4.5 ± 3.1, p = 0.024) in letters written for women compared to men VS applicants. Twenty-nine letters written for students applying to VS had honors status. While none written for women mentioned this achievement, 43% of those written for men did (p < 0.05). Letters for women applicants to Ob/Gyn contained more standout adjectives than those written for men (2.12 ± 2.2 vs 1.39 ± 1.25, p = 0.021).Reference letters for both specialties highlighted attributes differently depending on the gender of the applicant. Although this likely represents an unconscious process, care should be taken to limit potential biases in LOR which are "gatekeepers" to access and advancement.

  View details for DOI 10.1016/j.jsurg.2021.02.002

  View details for Web of Science ID 000695199700019

  View details for PubMedID 33745859

• Endothelial cell Pannexin1 modulates severity of ischemic stroke by regulating cerebral inflammation and myogenic tone JCI INSIGHT Good, M. E., Eucker, S. A., Li, J., Bacon, H. M., Lang, S. M., Butcher, J. T., Johnson, T. J., Gaykema, R. P., Patel, M. K., Zuo, Z., Isakson, B. E. 2018; 3 (6)

  Abstract

  Ischemic stroke is a leading cause of morbidity and mortality in the US; however, there currently exists only one effective acute pharmacological therapeutic intervention. Purinergic signaling has been shown to regulate vascular function and pathological processes, including inflammation and arterial myogenic reactivity, and plays a role in ischemic stroke outcome. Purinergic signaling requires extracellular purines; however, the mechanism of purine release from cells is unclear. Pannexin1 (Panx1) channels are potentially novel purine release channels expressed throughout the vascular tree that couples regulated purine release with purinergic signaling. Therefore, we examined the role of smooth muscle and endothelial cell Panx1, using conditional cell type-specific transgenic mice, in cerebral ischemia/reperfusion injury outcomes. Deletion of endothelial cell Panx1, but not smooth muscle cell Panx1, significantly reduced cerebral infarct volume after ischemia/reperfusion. Infiltration of leukocytes into brain tissue and development of cerebral myogenic tone were both significantly reduced when mice lacked endothelial Panx1. Panx1 regulation of myogenic tone was unique to the cerebral circulation, as mesenteric myogenic reactivity and blood pressure were independent of endothelial Panx1. Overall, deletion of endothelial Panx1 mitigated cerebral ischemic injury by reducing inflammation and myogenic tone development, indicating that endothelial Panx1 is a possible novel target for therapeutic intervention of ischemic stroke.

  View details for DOI 10.1172/jci.insight.96272

  View details for Web of Science ID 000428728100008

  View details for PubMedID 29563335

  View details for PubMedCentralID PMC5926909

• Malignant Brenner tumor of the ovary: Review and case report GYNECOLOGIC ONCOLOGY REPORTS Lang, S. M., Mills, A. M., Cantrell, L. A. 2017; 22: 26-31

  Abstract

  Ovarian neoplasms are a heterogeneous group of tumors with varying incidence in the general population. The most common are the surface epithelial tumors which include transitional cell tumors. Transitional cell tumors include both transitional cell carcinoma and Brenner tumor. The vast majority of Brenner tumors are benign, often incidental findings; however, malignant Brenner tumors (MBT) do occasionally occur. MBT present similarly to other ovarian neoplasms with abdominal pain and bulk symptoms. On imaging, these tumors demonstrate nonspecific findings. Microscopically, they demonstrate areas of conventional benign Brenner tumor juxtaposed with regions of frank malignancy showing marked cytologic atypia and infiltration. There is no consistent tumor marker for these tumors, but CA-125, CA 72-4 and SCC have been reported in singular instances. Tumors express several immunohistochemical markers of urothelial differentiation including uroplakin III, thrombomodulin, GATA3, p63, as well as cytokeratin 7. The primary treatment modality is surgical excision. Due to their rarity, the precise role and regimen of adjuvant chemo-radiation therapy for MBT has not been established. We herein review a case of MBT with emphasis on primary treatment and treatment of recurrent disease, including the use of adjuvant pelvic radiation, discuss the current state of the literature and standards of practice regarding this malignancy.

  View details for DOI 10.1016/j.gore.2017.07.001

  View details for Web of Science ID 000418510300007

  View details for PubMedID 28971141

  View details for PubMedCentralID PMC5608552

• Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla HYPERTENSION Stocker, S. D., Lang, S. M., Simmonds, S. S., Wenner, M. M., Farquhar, W. B. 2015; 66 (6): 1184-1190

  Abstract

  Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or polysynaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to cerebrospinal fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0 mol/L NaCl (5 µL/10 minutes) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the gamma-aminobutyric acid (GABAA) agonist muscimol abolished the sympathoexcitatory response to intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure. Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3 distinct populations based on discharge responses to intracerebroventricular infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%; 9/24), and type III no change (17%; 4/24). All neurons with slow conduction velocities were type I cells. Collectively, these findings suggest that acute increases in cerebrospinal fluid NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and arterial blood pressure.

  View details for DOI 10.1161/HYPERTENSIONAHA.115.05936

  View details for Web of Science ID 000364481400016

  View details for PubMedID 26416846

  View details for PubMedCentralID PMC5065924

• Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice PLOS ONE Lang, S. M., Kazi, A. A., Hong-Brown, L., Lang, C. H. 2012; 7 (6): e38910

  Abstract

  The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/-) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR(+/-) mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR(+/-) mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR(+/-) mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth.

  View details for DOI 10.1371/journal.pone.0038910

  View details for Web of Science ID 000305730900023

  View details for PubMedID 22745686

  View details for PubMedCentralID PMC3382153

• Deptor Knockdown Enhances mTOR Activity and Protein Synthesis in Myocytes and Ameliorates Disuse Muscle Atrophy MOLECULAR MEDICINE Kazi, A. A., Hong-Brown, L., Lang, S. M., Lang, C. H. 2011; 17 (9-10): 925-936

  Abstract

  Deptor is an mTOR binding protein that affects cell metabolism. We hypothesized that knockdown (KD) of Deptor in C2C12 myocytes will increase protein synthesis via stimulating mTOR-S6K1 signaling. Deptor KD was achieved using lentiviral particles containing short hairpin (sh)RNA targeting the mouse Deptor mRNA sequence, and control cells were transfected with a scrambled control shRNA. KD reduced Deptor mRNA and protein content by 90%, which increased phosphorylation of mTOR kinase substrates, 4E-BP1 and S6K1, and concomitantly increased protein synthesis. Deptor KD myoblasts were both larger in diameter and exhibited an increased mean cell volume. Deptor KD increased the percentage of cells in the S phase, coincident with an increased phosphorylation (S807/S811) of retinoblastoma protein (pRb) that is critical for the G(1) to S phase transition. Deptor KD did not appear to alter basal apoptosis or autophagy, as evidenced by the lack of change for cleaved caspase-3 and light chain (LC)3B, respectively. Deptor KD increased proliferation rate and enhanced myotube formation. Finally, in vivo Deptor KD (~50% reduction) by electroporation into gastrocnemius of C57/BL6 mice did not alter weight or protein synthesis in control muscle. However, Deptor KD prevented atrophy produced by 3 d of hindlimb immobilization, at least in part by increasing protein synthesis. Thus, our data support the hypothesis that Deptor is an important regulator of protein metabolism in myocytes and demonstrate that decreasing Deptor expression in vivo is sufficient to ameliorate muscle atrophy.

  View details for DOI 10.2119/molmed.2011.00070

  View details for Web of Science ID 000295954400008

  View details for PubMedID 21607293

  View details for PubMedCentralID PMC3188866