Kristine Marie Zanotti

University Hospitals | uhhospitals · Obstetrics and Gynecology

High-Grade Serous Carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP-inhibitors (PARPi) have become the mainstay of HGSC targeted therapy, given that these tumors are driven by a high degree of genomic instability and Homologous Recombination (HR) defects. Nonetheless, ~30% of patients initially respond to treatment, ultima...

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. End...

High-Grade Serous Carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP-inhibitors (PARPi) have become the mainstay of HGSC targeted therapy, given that these tumors are driven by a high degree of genomic instability and Homologous Recombination (HR) defects. Nonetheless, only ∼30% of patients initially respond to treatment, u...

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma–specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined....

Background: Minimally invasive surgery is the preferred approach for performing many gynecologic procedures. Occasionally, supraumbilical port placement may be preferable to optimize visibility and maneuverability although the risks of complications are less well characterized compared to umbilical entry. Methods: We conducted a retrospective re...

Computation-based drug-repurposing/repositioning approaches can greatly speed up the traditional drug discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug-repositioning candidates for epithelial ovarian cancer (EOC) have not been undertaken. Here, we present a novel drug discovery strat...

Objective: Metabolic syndrome (MS) is characterized by dyslipidemia, diabetes, cardiovascular disease, and cancer. In addition to general obesity, the distribution of body fat is also independently associated with the MS. We sought to validate whether a novel quantitative technique utilizing CT morphometric ratios (CTMRs) to measure adipose distrib...

INTRODUCTION: UO is common in patients with newly diagnosed CC. Management of UO commonly occurs with stent or nephrostomy placement (NT). The success rates for AG and RG stents amongst this group have not been reported. We sought to document performance of these procedures to inform comparative effectiveness studies. METHODS: Medical records of pa...

Background. The objective of this study was to determine whether female surgical residents underestimate their surgical abilities relative to males on a standardized test of laparoscopic skill. Methods. Twenty-six male and female general surgery residents and 25 female obstetrics and gynecology residents at two academic centers were asked to predic...

Study objectives: To identify morphometric characteristics of obese patients that best predict pulmonary intolerance to robotic pelvic surgery using a novel method for quantifying adipose distribution. Design: Retrospective study (Canadian Task Force classification II-2). Setting: University hospital. Patients: Fifty-nine patients with endom...

Background: The relationship of race and endometrial cancer (EC) outcomes is controversial. Published literature documents that EC mortality is 2.5 times more likely in African Americans (AA) than their Caucasian peers. Conflicting data were reported regarding prevalence of obesity, co-morbidities including diabetes, unfavorable histology in AA bes...

Background: Psychiatric disorders are common among gynecologic cancer patients. Anxiety and depression are the most common diagnoses in this population. While rates reported in the literature are as high as 30%, few studies examine the impact of psychiatric illness in gynecologic cancer patients. The purpose of this study was to examine the associa...

Objective: The physiologic stress of carbon dioxide pneumoperitoneum and steep trendelenburg affect the obese patient disproportionately and physiologic intolerance still limits the application of RPS in this population. The objective of the study was to identify morphometric characteristics of obese patients that best predict pulmonary tolerance t...

Objectives: As utilization of the robotic laparoscopy platform expands to an increasing number of surgeons for cases of increasing technical complexity, there is a great need to better understand the factors associated with its high cost. A percentage of surgeries intended to be performed robotically are converted to laparotomy, either for technica...

Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells,...

We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to...

The progressive and chronic nature of this disease can have a substantial impact on both quality of life and functioning of women who suffer from the disease. While medical treatment can be sufficient therapy for many women with endometriosis, medical therapies are often inadequate for the severest cases. The anatomic changes of adhesions/fibrosis...

The aim of this study was to evaluate the tolerability and efficacy of poly(ADP-ribose) polymerase (PARP) inhibition by veliparib during cytotoxic topotecan administration with filgrastim or pegfilgrastim neutrophil support in women with persistent or recurrent uterine cervix cancer. This phase I-II trial examined twice-daily oral veliparib (10 mg)...

Whereas previous studies have shown that lymphovascular space invasion (LVSI) is associated with an increased risk for recurrent endometrioid endometrial cancer and worse survival, the magnitude of this risk in relationship to the other high-risk features is poorly understood. Our aim was to study the impact of LVSI in comparison with the other hig...

The primary objective was to examine the safety and feasibility of robotic-assisted laparoscopy in a cohort of women treated surgically for stage III and IV endometriosis. The secondary objective was to explore whether the stage of endometriosis affected surgical outcome. In this cohort study, 43 women with severe endometriosis were treated with ro...

Objective: Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods: We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone...

Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who ha...

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After men...

The study aim was to compare outcomes in women with high-grade endometrial cancer (EC) who underwent surgical staging via minimally invasive surgery (MIS) versus laparotomy. This is a retrospective, multi-institutional cohort study of patients with high-grade EC who were comprehensively surgically staged by either MIS or laparotomy. Demographic, su...

The vaginal apex is the most common site of recurrence in patients with endometrial cancer. Although studies demonstrate that <1% of asymptomatic vaginal recurrences are detected by routine vaginal cytology alone, many practitioners still include it as part of the routine surveillance in these patients after hysterectomy. To further evaluate the ef...

Adnexal masses are commonly encountered in gynecologic practice and often present both diagnostic and management challenges. This is partly because of the fact that the majority of adnexal masses that are identified represent benign entities that do not necessarily require active intervention, yet a small subset will represent malignant processes t...

To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC). Biochemical recurrence was defined as a rising CA-12...

Survival has significantly improved for women diagnosed with cancer during the reproductive years. The majority of these women will desire children after completion of their cancer therapy. Future fertility often is eliminated or impaired by surgical removal of reproductive organs for the treatment of gynecologic cancers or by radiation or chemothe...

Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. A retrospective, multi-institution...

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients. A retrospective, multi-institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (O...

To compare surgical and survival outcomes of patients with early-stage endometrial cancer (EC) who underwent total laparoscopic hysterectomy (TLH) or laparoscopic-assisted vaginal hysterectomy (LAVH) +/- lymphadenectomy. Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). Two tertiary care academic medical centers...

To determine recurrence patterns and survival outcomes of stage II uterine papillary serous carcinoma (UPSC) patients treated by various modalities with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy (RT). A retrospective, multi-institution study of women with stage II UPSC diagnosed from 1992 to 2006 was performed. Al...

To characterize the incidence of skin toxicity of pegylated liposomal doxorubicin (PLD) administered at a lower dose (40 mg/m(2)) in the treatment of advanced gynecologic malignancies. Medical charts of all patients who initiated PLD at a starting dose of 40 mg/m(2) from 1997 to 2003 for the treatment of gynecologic cancers were retrospectively rev...

Our strategy for cervical cancer screeing is being revolutionized by our new understanding of how human papillomavirus (HPV) contributes to carcinogenesis and the natural history of cervical cancer. The American Cancer Society and the American College of Obstetricians and Gynecologists now recommend combined HPV and Papanicolaou (Pap) testing for c...

There are limited data available in the oncology literature regarding the risk of thrombocytopenia associated with carboplatin-based second-line treatment of ovarian cancer, outside the setting of patients participating in clinical trials. To examine this clinically-relevant issue, we conducted a retrospective review of the medical records of women...

Preclinical and clinical data have demonstrated the importance of schedule in optimizing the cytotoxic potential of topotecan, one of the most active agents in ovarian cancer. The availability of oral topotecan permits the exploration of the clinical utility of prolonged treatment programs employing this drug. Patients with platinum/taxane resistan...

Carboplatin hypersensitivity is an increasingly recognized toxicity in individuals receiving >6 cumulative courses of this important antineoplastic agent. We wished to determine if a novel multi-pronged approach to re-treating patients with a high risk for this potentially serious side effect could permit the safe delivery of this class of cytotoxi...

The protocol was designed to examine the biological effects and clinical activity of interferon-beta in patients with platinum/taxane-resistant ovarian cancer. Patients with resistant ovarian and fallopian tube cancers and primary peritoneal carcinoma were treated with recombinant human interferon-beta (Rebif, Serono International) at doses ranging...

Limited information is available regarding the influence of the duration of a prior response on the length of a subsequent response to platinum chemotherapy in recurrent ovarian cancer. We retrospectively reviewed the medical records of women with ovarian cancer treated at the Cleveland Clinic from 1993 through April 2003 who received two or more p...

A previously reported phase 2 trial suggested substantial clinical activity associated with the combination of a platinum agent and tamoxifen in the treatment of platinum-resistant ovarian cancer. We wished to confirm or refute this observation in a patient population with well-characterized platinum-resistant disease. Patients with ovarian or fall...

Pegylated liposomal doxorubicin (PLD) is currently utilized in the management of several solid tumors. While PLD has been shown to be less cardiotoxic than doxorubicin, the safety of prolonged administration (e.g., >or=6 cycles) of the agent remains undefined. A retrospective chart review was performed of the Cleveland Clinic experience from 1997 t...

There are very limited data in the oncology literature regarding the survival of women with both platinum and taxane-refractory ovarian cancer. To examine this issue, we retrospectively reviewed the survival of patients treated on one (or more) of four previously reported nonrandomized single-agent phase 2 trials (topotecan, liposomal doxorubicin,...

While the clinical utility of the serum CA-125 antigen level in demonstrating objective evidence of regression or progression of disease in women with ovarian cancer is well-established, the relationship between both the absolute value of this tumor maker, or its rate of change over time, and the short-term clinical course (e.g., development of can...

Tamoxifen, a well-tolerated oral hormonal agent with biological activity in ovarian cancer, is a potentially attractive option in asymptomatic patients with recurrent disease. Unfortunately, the clinical utility of the drug in this specific setting has not been well documented. A retrospective review was conducted of patients with cancers of the ov...

Objective. There exists limited information in the medical literature regarding the incidence and severity of carboplatin-associated neutropenia, outside the setting of a clinical trial. We wished to examine this issue in a large single institution experience involving patients receiving both single agent and combination carboplatin-based chemother...

Our goal in this nonrandomized phase 2 trial was to evaluate the toxicity and obtain preliminary data on the potential efficacy of a novel three-drug combination regimen (carboplatin-paclitaxel-irinotecan) when employed as initial therapy of advanced ovarian cancer or as second-line treatment in the setting of a prolonged (>or=12 months) treatment-...

Carboplatin-associated hypersensitivity is increasingly recognized as a potentially serious toxicity when this agent is administered for more than six total cycles. Our group has used a predictive skin test in women with gynecologic cancers who have previously received more than six cumulative cycles of platinum-based chemotherapy. Thirty minutes b...

Previously reported data have suggested the lack of complete cross-resistance between docetaxel and paclitaxel in ovarian cancer. We wished to evaluate the biological and clinical activity of docetaxel in a patient population with well-characterized platinum and paclitaxel-refractory ovarian cancer. In this single-institution phase 2 trial, 30 wome...

While the importance of the sequence of administration of cisplatin and paclitaxel on the degree of observed neutropenia has been documented, there is limited information available in the oncology literature to determine whether there exists sequence-dependent toxicity for the combination of carboplatin plus paclitaxel. Patients with advanced gynec...

To evaluate the efficacy and toxicity of pegylated liposomal doxorubicin in patients with advanced endometrial cancer. Pegylated liposomal doxorubicin was administered at a dose of 40 mg/m2, and repeated on an every 28-day schedule. A total of 19 patients were enrolled in this phase 2 trial. Fourteen patients had received prior chemotherapy (carbop...

There is a need to find agents with activity in platinum and taxane refractory ovarian cancer to be employed as second-line therapy in the malignancy. Limited clinical trial experience has suggested that gemcitabine possesses activity in this clinical setting. We wished to further define the level of activity of gemcitabine in women with well-chara...

Despite the high objective response rate of advanced ovarian cancer to combination platinum/taxane-based chemotherapy, the majority of patients ultimately experience disease progression. Thus, there is a need to find new management strategies that can improve upon the results of existing therapies. We are currently conducting a phase II trial to ex...

The establishment of clinical features identifying patients at a heightened risk for the development of carboplatin hypersensitivity may assist in the management of this important toxicity. Based on a previous report suggesting a history of "bee sting" allergy predicted for paclitaxel hypersensitivity, we attempted to determine if there was a relat...

Human papillomaviruses (HPVs) are associated with a spectrum of diseases, ranging from common warts to invasive carcinoma of the genital tract. The clinical manifestations of HPV infection depend on the viral subtype, the immune status of the patient, and environmental co-carcinogens. Infection with HPV is often asymptomatic, which makes viral dete...

Ovarian Sertoli-Leydig cell tumors are uncommon neoplasms originating from specialized gonadal stroma capable of differentiating into both Sertoli- and Leydig-cells. Many of the clinical characteristics associated with this tumor are related to the degree of histologic differentiation and the presence or absence of a retiform pattern and/or heterol...

A high incidence of moderate to severe hypersensitivity reactions (HRs) is noted in patients who have been treated with multiple courses of carboplatin. Presently, there is no reliable way to predict which patients may be at risk for this potentially severe adverse reaction. We developed a skin-test protocol to identify patients at high risk for HR...

Acute hypersensitivity reactions (HSRs) are an unpredictable and potentially catastrophic complication of treatment with chemotherapeutic agents. Reactions may affect any organ system in the body and range widely in severity from mild pruritus to systemic anaphylaxis. Certain classes of chemotherapeutic agents, such as the taxanes, platinum compoun...

Gynecologic cancers are among the most common malignancies in reproductive-age women. Approximately 3% of women diagnosed with a malignancy of the reproductive tract will have a coexisting pregnancy. A pregnant woman with a gynecologic malignancy presents a significant challenge for the clinician for many reasons. Considerable diagnostic delay is c...

The aim of this study was to evaluate the ability of paclitaxel to achieve a second clinical response in patients with recurrent epithelial ovarian carcinoma who responded to standard therapy with platinum and paclitaxel in the initial setting. Thirty-four patients with epithelial ovarian who demonstrated a complete response to paclitaxel and plati...

Gynecologic cancers are among the most common malignancies in women. The implementation of population-based Papanicolaou (Pap) smear screening has resulted in a significant reduction in the incidence and mortality of cervical cancer. Despite its successes, failures in Pap smear screening do exist. Although a great deal of scientific and media atten...

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. Thi...

Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalanc...

To determine whether there is evidence for allelic imbalance (AI) on chromosome 17p13 in early-stage epithelial ovarian tumors. Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome 17p13 by polymerase chain reaction (PCR) amplification....