Robert L Giuntoli

University of Louisville, Louisville, Kentucky, United States

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Publications (69)252.71 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to screen for depression and anxiety and to assess well-being among women diagnosed with gynecologic malignancies, identify factors associated with elevated depressive or anxiety symptoms, and further characterize the needs of those with elevated anxiety or depressive symptoms.
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 11/2014; 24(9):1700-8.
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    ABSTRACT: The aim of this study was to determine if a gynecologic cancer patient's comfort level discussing end-of-life care issues with her caregivers is related to her death anxiety level.
    International Journal of Gynecological Cancer 09/2014; · 1.94 Impact Factor
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    ABSTRACT: The study objective was to compare the ability to detect sentinel lymph nodes (SLN) in women with endometrial cancer (EC) or complex atypical hyperplasia (CAH) using fluorometric imaging with indocyanine green (ICG) versus colorimetric imaging with isosulfan blue (ISB).
    Gynecologic Oncology 05/2014; · 3.93 Impact Factor
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    ABSTRACT: The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
    Science translational medicine 02/2014; 6(224):224ra24. · 10.76 Impact Factor
  • C. Kushnir, N. Zhao, K. Frick, R. Giuntoli
    Gynecologic Oncology 10/2013; 131(1):260. · 3.93 Impact Factor
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    ABSTRACT: To examine whether adjuvant therapy after primary surgery for treatment of early-stage uterine leiomyosarcoma (LMS) improves recurrence and survival rates. A multisite, retrospective study of women diagnosed with Stage I-II high grade LMS from 1990-2010 was performed. All patients (pts) underwent primary surgery followed by observation (OBS), radiotherapy (RT), or chemotherapy (CT) postoperatively. One hundred eight patients were identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%) had stage II disease. The mean patient age was 55.4years and mean BMI was 28.0. Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39 (36.1%) received chemotherapy. After a median follow up of 41.8months, a recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS, 23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on treatment (p=0.413). However, extra-pelvic recurrences were significantly higher in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p=0.012). Additionally, recurrences were more likely to be successfully treated or palliated in those who initially received CT (p=0.031). On multivariate analysis, stage (p<0.001) and chemotherapy (p=0.045) were associated with overall survival. Women with early-stage, high grade uterine LMS experience high recurrence rates and poor survival outcomes, irrespective of adjuvant therapy. These rates are higher than previously reported in the literature. Although women treated with CT had similar recurrence rates as those treated with OBS or RT, treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic recurrence and improve survival.
    Gynecologic Oncology 09/2013; · 3.93 Impact Factor
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    ABSTRACT: To evaluate the influence of distance on access to high-volume surgical treatment for patients with uterine cancer in Maryland. The Maryland Health Services Cost Review Commission database was retrospectively searched to identify primary uterine cancer surgical cases from 1994 to 2010. Race, type of insurance, year of surgery, community setting, and both surgeon and hospital volume were collected. Geographical coordinates of hospital and patient's zip code were used to calculate primary independent outcomes of distance traveled and distance from nearest high-volume hospital (HVH). Logistic regression was used to calculate odds ratios and confidence intervals. From 1994 to 2010, 8529 women underwent primary surgical management of uterine cancer in Maryland. Multivariable analysis demonstrated white race, rural residence, surgery by a high-volume surgeon and surgery from 2003 to 2010 to be associated with both travel 50 miles or more to the treating hospital and residence 50 miles or more from the nearest HVH (all P < 0.05). Patients who travel 50 miles or more to the treating hospital are more likely to have surgery at a HVH (odds ratio, 6.03; 95% confidence interval, 4.67-7.79) In contrast, patients, who reside ≥50 miles from a HVH, are less likely to have their surgery at an HVH. (odds ratio, 0.37; 95% confidence interval, 0.32-0.42). In Maryland, 50 miles or more from residence to the nearest HVH is a barrier to high-volume care. However, patients who travel 50 miles or more seem to do so to receive care by a high-volume surgeon at an HVH. In Maryland, Nonwhites are more likely to live closer to an HVH and more likely to use these services.
    International Journal of Gynecological Cancer 07/2013; · 1.94 Impact Factor
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    ABSTRACT: OBJECTIVES: Uterine leiomyosarcoma (LMS) was traditionally staged by modified 1988 International Federation of Gynecology and Obstetrics (FIGO) staging criteria for endometrial adenocarcinoma. Contemporary methods of staging include the 2009 FIGO system for uterine LMS and the 2010 American Joint Committee on Cancer (AJCC) soft tissue sarcoma system. The aim of this study was to compare the accuracy of these 3 staging systems and a novel system in predicting disease-specific survival for patients with uterine LMS. METHODS: Patients, evaluated at our institution with uterine LMS from 1976 to 2009, were identified. Stage was assigned retrospectively based on operative and pathology reports. Staging systems performance was compared using confidence indices. RESULTS: We identified 244 patients with uterine LMS with sufficient information to be staged by all 3 systems. For each staging method, lower stage was associated with significantly improved disease-specific survival, P < 0.001. Patients with 2010 AJCC stage IA disease (low-grade, ≤5 cm) experienced no disease-specific deaths. We created a novel staging system, which used size and grade to stratify patients with disease confined to the uterus and/or cervix and combined the remaining patients with extrauterine disease as stage IV. Based on confidence index, the 2010 AJCC system and our novel system provided more accurate prognostic information than either of the 2 FIGO systems. CONCLUSIONS: Uterine LMS remains a clinically aggressive malignancy. Size and grade provided accurate prognostic information for patients with disease confined to the uterus and/or cervix. Patients with small, low-grade uterine LMS do not benefit from adjuvant therapy.
    International Journal of Gynecological Cancer 05/2013; · 1.94 Impact Factor
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    ABSTRACT: Papanicolaou (Pap) smears have revolutionized the management of patients with cervical cancers by permitting the detection of early, surgically curable tumors and their precursors. In recent years, the traditional Pap smear has been replaced by a liquid-based method, which allows not only cytologic evaluation but also collection of DNA for detection of human papillomavirus, the causative agent of cervical cancer. We reasoned that this routinely collected DNA could be exploited to detect somatic mutations present in rare tumor cells that accumulate in the cervix once shed from endometrial or ovarian cancers. A panel of genes that are commonly mutated in endometrial and ovarian cancers was assembled with new whole-exome sequencing data from 22 endometrial cancers and previously published data on other tumor types. We used this panel to search for mutations in 24 endometrial and 22 ovarian cancers and identified mutations in all 46 samples. With a sensitive massively parallel sequencing method, we were able to identify the same mutations in the DNA from liquid Pap smear specimens in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). Prompted by these findings, we developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear specimen without previous knowledge of the tumor's genotype. When applied to 14 samples selected from the positive cases described above, the expected tumor-specific mutations were identified. These results demonstrate that DNA from most endometrial and a fraction of ovarian cancers can be detected in a standard liquid-based Pap smear specimen obtained during routine pelvic examination. Although improvements need to be made before applying this test in a routine clinical manner, it represents a promising step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies.
    Science translational medicine 01/2013; 5(167):167ra4. · 10.76 Impact Factor
  • Gynecologic Oncology. 10/2012; 127(1):S12–S13.
  • Gynecologic oncology. 10/2012; 127(1 Suppl):S23.
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    ABSTRACT: Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion.
    Cancer Research 05/2012; 72(15):3744-52. · 9.28 Impact Factor
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    ABSTRACT: Objectives: To assess the importance and desired timing of end-of-life care (EOLC) discussions among women with gynecologic cancer. METHODS: A questionnaire related to EOLC issues was distributed to patients with gynecologic cancer. Answers were analyzed via SPSS using descriptive statistics. Contingency analysis was done to evaluate for differences among disease status and age regarding preferences for timing of discussions. RESULTS: Patients expressed that addressing EOLC is an important part of their treatment. Most patients were familiar with advanced directives (73.0%), do not resuscitate/do not intubate (88.5%), and hospice (97.5%). Designating someone to make decisions was significantly related to disease status (P = .03) and age (P = 0.02). CONCLUSIONS: Patients are familiar with basic EOLC with optimal timing for discussions at disease progression or when treatment is no longer available.
    The American journal of hospice & palliative care 04/2012;
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    ABSTRACT: The aim of this study was to determine if comprehensive surgical staging is a better predictor of outcome than incomplete staging for women with stage I noninvasive or minimally invasive (≤3 mm) uterine serous carcinoma (USC). Retrospective chart review was used to identify patients undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant clinical and pathologic data were extracted. Patients with noninvasive and minimally invasive (≤3-mm myometrial invasion) USC were identified. Stage was assigned based on the 2009 International Federation of Gynecology and Obstetrics endometrial cancer criteria. Survival curves were generated using the Kaplan-Meier method. We identified 63 patients with noninvasive or minimally invasive (≤3 mm) USC. Stages I, II, III, and IV disease were noted in 65% (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively. Lower stage was associated with a significantly improved disease-specific survival (P = 0.001). Comprehensive staging, including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the patients with stage I disease. There were no disease-specific deaths in the comprehensive staging group. Compared with incomplete staging, comprehensive staging was associated with a significantly improved disease-specific survival (P = 0.039). Patients with stage I noninvasive and minimally invasive USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may not benefit this patient population.
    International Journal of Gynecological Cancer 12/2011; 22(2):273-9. · 1.94 Impact Factor
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    ABSTRACT: Gynaecological oncologists, by conducting Phase II and III chemotherapy trials, have sought to improve survival in women with epithelial ovarian cancer. The greatest impact on survival has been the use of intraperitoneal chemotherapy in women who have had all visible disease removed. No change in drug regimen has had an impact on survival equivalent to that associated with complete cytoreduction or the use of intraperitoneal chemotherapy. Interestingly, these two treatment modalities (complete cytoreduction and intraperitoneal chemotherapy) have not been universally adopted. Most often it is the inability to achieve optimal cytoreduction in the upper abdomen that defines the limit of the cytoreductive effort, and ultimately the integration of intraperitoneal chemotherapy. The importance of identifying disease outside the abdominal cavity, along with achieving complete cytoreduction, is paramount, if the use of intraperitoneal chemotherapy is to be logically integrated in treatment algorithms for women with advanced-stage epithelial ovarian cancer. This report summarises pertinent literature on upper abdominal cytoreduction, discusses surgical techniques and introduces new data on women with epithelial ovarian cancer undergoing thoracoscopy, suggesting consideration of its incorporation into the surgical management of advanced epithelial ovarian cancer.
    BJOG An International Journal of Obstetrics & Gynaecology 11/2011; 119(2):202-6. · 3.76 Impact Factor
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    ABSTRACT: To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers. Levels of 14 currently promising ovarian cancer-related biomarkers, including CA125, macrophage inhibitory factor-1 (MIF-1), leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II (IGF-II), autoantibodies (AAbs) to eight proteins: p53, NY-ESO-1, p16, ALPP, CTSD, B23, GRP78, and SSX, were measured in the plasma of 151 ovarian cancer patients, 23 with borderline ovarian tumors, 55 with benign tumors and 75 healthy controls. When examined individually, seven candidate biomarkers (MIF, Prolactin, CA-125, OPN, Leptin, IGF-II and p53 AAbs) had significantly different plasma levels between type II ovarian cancer patients and healthy controls. Based on the receiver operating characteristic (ROC) curves constructed and area under the curve (AUC) calculated, CA125 exhibited the greatest power to discriminate the plasma samples of type II cancer patients from normal volunteers (AUC 0.9310), followed by IGF-II (AUC 0.8514), OPN (AUC 0.7888), leptin (AUC 0.7571), prolactin (AUC 0.7247), p53 AAbs (AUC 0.7033), and MIF (AUC 0.6992). p53 AAbs levels exhibited the lowest correlation with CA125 levels among the six markers, suggesting the potential of p53 AAbs as a biomarker independent of CA125. Indeed, p53 AAbs increased the AUC of ROC curve to the greatest extent when combining CA125 with one of the other markers. At a fixed specificity of 100%, the addition of p53 AAbs to CA125 increased sensitivity from 73.8% to 85.7% to discriminate type II cancer patients from normal controls. Notably, seropositivity of p53 AAbs is comparable in type II ovarian cancer patients with negative and positive CA125, but has no value for type I ovarian cancer patients. p53 AAbs might be a useful blood-based biomarker for the detection of type II ovarian cancer, especially when combined with CA125 levels.
    Gynecologic Oncology 06/2011; 122(3):560-6. · 3.93 Impact Factor
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    ABSTRACT: The goal of this study is to determine the feasibility of intravenous gemcitabine and an intraperitoneal platinum agent in the treatment of patients with ovarian cancer. We performed a retrospective chart review of patients with primary, persistent or recurrent ovarian cancer, who received intravenous gemcitabine and an intraperitoneal platinum agent. Patients received gemcitabine (750 mg/m²) intravenous on days 1 and 8 and cisplatin (100 or 60 mg/m²) intraperitoneal on day 1 every 21 - 28 days. An alternate regimen was composed of gemcitabine (750 mg/m²) intravenous and carboplatin (AUC 5) intraperitoneal on day 1 every 21 days. Dose reductions occurred at the discretion of the prescribing physician.Intravenous gemcitabine and an intraperitoneal platinum agent were administered to 12 patients with advanced primary or recurrent ovarian cancer. Myelosuppression was the most common toxicity. Grade 3 or 4 thrombocytopenia, neutropenia and anemia occurred in 7, 8 and 2 patients respectively. Dose reductions were required in 7 of 12 patients. 10 of 12 patients received 6 cycles of the regimen. Treatment was discontinued prior to 6 cycles in 2 of 12 patients secondary to progression in one case and to grade 4 neutropenia and thrombocytopenia in another.The combination of intravenous gemcitabine and an intraperitoneal platinum agent appears to be a feasible regimen in patients with ovarian cancer. The most common toxicity was myelosuppression, which resulted in dose reductions in almost half of the patients.
    Journal of chemotherapy (Florence, Italy) 06/2011; 23(3):163-7. · 0.83 Impact Factor
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    ABSTRACT: We report the clinicopathological and molecular characteristics of a rare uterine endometrioid carcinoma with a nongestational trophoblastic neoplastic component that was composed of both choriocarcinoma and epithelioid trophoblastic tumor. Molecular genetic analysis showed a clonal evolution from endometrioid carcinoma to trophoblastic tumor. The findings from this case have both diagnostic and biological implications that may inspire future studies on the pathogenic mechanisms by which cancer stem cells assume aberrant differentiation programs and the molecular switch(es) that initiates trophoblastic differentiation in adult tumor tissues.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2011; 30(2):117-20. · 2.07 Impact Factor
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    Teresa P Diaz-Montes, Robert L Giuntoli
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    ABSTRACT: Purpose. To characterize volume-based care of uterine cancer among women aged ≤50 years. Methods. The Maryland Health Service Cost Review Commission database was accessed for uterine cancer surgical cases from 1994 to 2005. Cross-tabulations and logistic regression models were used to evaluate for significant associations among volume-based care and other variables comparing women ≤50 years with those aged >50 years. Results. Women ≤50 years comprised 13.6% of the cases. Women ≤50 years were less likely to be managed by high-volume surgeons (31.6% versus 35.1%, P = 0.02). For women ≤50 years, there was a trend toward management at low-volume hospitals (52.0% versus 54.0%, P = 0.22). No deaths were reported among the group of women ≤50 years treated by high-volume providers or at high-volume centers. Women ≤50 years managed by high-volume surgeons had longer length of stay (P < 0.001) and higher adjusted cost of hospital-related care (P < 0.00). Women ≤50 years managed at high-volume centers had higher adjusted cost of hospital-related care (P = 0.01). Conclusion. Primary surgical care of young women with uterine cancer is often performed by low-volume providers.
    ISRN surgery. 01/2011; 2011:541461.
  • M. Johnson, R. Giuntoli, T. Diaz-Montes
    Gynecologic Oncology - GYNECOL ONCOL. 01/2011; 120.

Publication Stats

1k Citations
252.71 Total Impact Points

Institutions

  • 2013
    • University of Louisville
      Louisville, Kentucky, United States
  • 2004–2011
    • Johns Hopkins Medicine
      • • Department of Pathology
      • • Department of Gynecology & Obstetrics
      • • The Kelly Gynecologic Oncology Service
      Baltimore, MD, United States
  • 2007
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2003
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
    • Mayo Foundation for Medical Education and Research
      • Division of Gynecologic Surgery
      Scottsdale, AZ, United States
  • 2002
    • Mayo Clinic - Rochester
      • Department of Obstetrics & Gynecology
      Rochester, Minnesota, United States