Citations

Introduction The implementation of cervical cancer screening and human papillomavirus (HPV) vaccination has significantly reduced cervical cancer rates. However, it remains the fourth most common cancer among women globally. Barriers to screening include personal, health system, and insurance factors. Methods To address these barriers, a “Saturday Pap smear Clinic” was established to increase accessibility. The study included female patients aged 21 to 65 from Southeast Minnesota, USA, who attended the clinic from September 2021 to April 2023. Results A total of 357 women attended the Saturday clinic, with a median age of 44 years; 70.6% were White. Abnormal Pap smear results were found in 13.8% of attendees, with 7.8% testing positive for HPV. Additional health maintenance was addressed. The majority of patients had a physician primary care provider (58.3%), followed by residents (26.3%), and nurse practitioner/physician associates (15.4%). Discussion The clinic demonstrated a high fill rate of 86.15%, indicating demand for non-traditional appointment times. Despite this, disparities in access were noted, with primarily White and English-speaking women utilizing the clinic. The clinic showed improved outcomes compared to national screening rates, highlighting the importance of timely preventative care.

Background The incidence of cervical cancer has decreased by 70% since the 1950s. Preventative measures include vaccination against HPV strains and Papanicolaou tests. Early identification of cervical cancer through routine screening can significantly improve patient outcomes. Materials and methods At our academic institution, Community Internal Medicine (CIM) Clinic, 63% of female patients aged 21–65 were compliant with cervical cancer screening. The opening of the ‘Saturday Pap Smear Clinic’ sought to address barriers by offering non-traditional appointment times on Saturday mornings with an all female staff. Our aim was to increase the cervical cancer screening rate by 1% within 12 weeks. Our team compared CIM (intervention) and family medicine (FM) (control) compliance rates from September 2021 to January 2022. Messages were sent to the patient indicating non-compliance and offering options to complete screening. Results At the start of this study, 5239 CIM patients were cervical cancer screening non-compliant. Postintervention, cervical screening rates among non-compliant women within CIM improved by 1.2%. The intervention cohort, CIM patients, had a significant improvement in compliance compared with the control group, FM patients. White women between the ages of 50 and 65 comprised the majority of patients who used the ‘Saturday Pap Smear Clinic’. Conclusions The availability of Saturday appointments for cervical cancer screening completion can enhance cervical cancer screening compliance among eligible women. Eliminating barriers for women can improve health outcomes.

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone. Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening. Design: Pragmatic observational study. Methods: Adult women aged 21–64 years who were eligible for a Papanicolaou test at a Midwest Community Internal Medicine practice underwent cervical cancer screening using the Papette or spatula with cytobrush from 18 August 2021 through 1 February 2022. Cluster sampling was used across the practice. Pathology reports were then analyzed to compare the number of satisfactory versus unsatisfactory results between the two collection techniques. Results: We collected results for 756 Pap tests. The test results were satisfactory with the Papette 93.8% of the time compared with 93.0% for the spatula with cytobrush. Conclusion: The Papette is not inferior to a spatula with cytobrush as a collection method for Pap tests.

105 Background: Screening for cervical cancer with pap smears and HPV testing can improve patient outcomes by allowing for early identification of cervical cancer. The Minnesota Community Measure and Mayo Clinic's goal is to have a cervical cancer screening rate of 82% (Detailed Report-Cervical Cancer Screening, 2020). Healthy People 2030 aims to have a cervical cancer screening rate of 83.4% (Increase the proportion of females who get screened for cervical cancer -C-09, 2021). Community Internal Medicine cervical cancer screening rates are below this level at 63.09% compliance, with 5,239 patients non-compliant, who are eligible for cervical cancer screenings. Olmsted County only offers acute services on the weekends with no primary care services, which leaves women who work during the week or have childcare/caregiver issues with no options on the weekend or evenings when they have availability to attend appointments. Methods: Based on guidelines for pap smear screening (women ages 21-65), 14,195 women were identified within CIM to be eligible for screening. Of those, 5,239 were due for screening. The Saturday Pap Smear Clinic had 88 available spots. We aimed to improve cervical cancer screening rates among non-compliant women within Community Internal Medicine by 1% (52 women, total noncompliant women = 5,239) by January 2021 without adversely impacting coverage of existing clinic hours. Results: The electronic medical record (EMR), EPIC, was utilized to identify all patients who were eligible for a pap smear based on current guidelines (Total eligible = 14,195; Sample size/non-compliant: 5,239 patients) within Community Internal Medicine (CIM) of the Baldwin Building in Rochester, MN. Interventions included: surveys that were sent to patients via the Patient Portal. Advertising for the Saturday Clinic included Primary Care News, E-boards, Posters, Social Media, SCOPE, Mayo News, and Providers. The Saturday clinic allowed time outside the traditional hours. One unique feature of the clinic is that all females staffed it during clinic hours in an attempt to alleviate some of the fear/anxiety. After completion of the pilot Saturday Pap Clinic, pap smear compliance from the Saturday Pap Clinic alone arose 1.2% (62 patients) within CIM. Conclusions: Post-intervention, cervical screening rates among non-compliant women within Baldwin CIM improved by 1.2% (62 women total).

Abstract Introduction: A new isodicentric variant of del(20q) was recently described; namely ider(20)(p11.2)del(20)(q11.2q13.3). The frequency and clinical significance of this anomaly are not yet established. This anomaly is usually missed in routine cytogenetic studies and the common commercial FISH probe, D20S108, does not distinguish between del(20q) and ider(20q). The goals of this study were to determine 1) the frequency and hematopathology of patients (pts) with ider(20q) and 2) the best cytogenetic methods to distinguish among various del(20q) anomalies. Methods: We selected 12 pts referred for chromosome studies with -20,+mar to look for evidence of ider(20q). For comparison, we also randomly selected 12 pts with classical del(20q). Up to 10 bone marrow metaphases were studied for each of these 24 pts using FISH with probes for 20pter, JAG1 (20p12), centromere 20, D20S108 (20q12) and 20qter. We also studied 200 interphase nuclei from each pt using D20S108 and 20qter probes. We reviewed cytogenetic results for a consecutive series of pts in our hematological practice between 9/1/05 and 12/31/05 to establish the frequency of ider(20q). Blood and marrow slides were available for microscopic evaluation in 9 of 12 pts. with ider(20q). Results: By metaphase FISH, each of the 12 pts with del(20q) were 20pter+, JAG1+, D20S108- and 20qter+ indicating an interstitial deletion. Each of the 12 pts with ider(20q) were 20pter-, JAG1-, D20S108-- and 20qter++ indicating an isodicentric chromosome with an interstitial del(20q) on either side of the centromere. The ider(20q) is best detected using probe for D20S108 and 20qter. By FISH each pt with ider(20q) had a mixture of cells with del(20q) and ider(20q), though cells with only del(20q) were not usually detected by chromosome studies. One pt had a subclone with two copies of ider(20q). Interphase FISH identified del(20q) and ider(20q) in each specimen. Hematopathology studies of 9 pts with ider(20q) indicated acute myeloid leukemia (AML) with multilineage dysplasia in 1 and myelodysplastic syndrome in 8 (refractory cytopenia with multilineage dysplasia (RCMD) in 3, RCMD with ringed sideroblasts in 3, atypical myelodysplastic/myeloproliferative disease in 1, and refractory anemia with excess blasts-2 (RAEB-2) in 1). Additional chromosome anomalies were detected in the pts with AML with multilineage dysplasia and RAEB-2. Six pts had dysgranulopoiesis in addition to dysmegakaryopoiesis and/or dyserythropoiesis. Among 5,744 pts in our hematological clinical practice screened by interphase FISH, ider(20q) was seen in 8, but 8 of 78 pts with del(20q) also had ider(20q). Discussion: In clinical practice ider(20q) is common in hematological disorders and occurs in 0.14% of all pts and in 10% of pts with del(20q). This figure may underestimate the true frequency of ider(20q) because novel FISH studies with D20S108 and 20qter are required to confirm its presence. When G-banding preparations indicate -20,+mar, then ider(20q) should be suspected. The literature is sparse but pts with ider(20q) appeared to have a more consistent presentation of multilineage dysplasia with additional involvement of the granulocytic series than pts with del(20q). These results suggest that it is helpful to distinguish among various forms of del(20q) in clinical practice using both chromosome and FISH studies with D20S108 and 20qter.

Abstract Background: Results of conventional cytogenetic studies on specimens processed without B-cell mitogens are usually normal in B-CLL: this observation is often attributed to lack of mitotic B-CLL cells. Using metaphase FISH with D13S319, we now have evidence that these apparently normal mitotic B-CLL cells often exhibit submicroscopic interstitial deletions in 13q14. This observation indicates B-CLL cells do divide in unstimulated cultures, but the abnormal metaphases are not detected because the abnormalities are submicroscopic and represent a low percentage of proliferating cells. Methods: We studied 12 patients with B-CLL who had normal metaphases by conventional cytogenetics, but abnormal interphase nuclei by FISH with D13S319. This cohort consisted of 7 females and 5 males who ranged in age from 50 to 87 years. Clinical information was available for 11 patients: Rai stages were 0, I, II, III, or IV for 6, 1, 1, 2, and 1 patients, respectively; 8 patients received treatment and 3 have died. Conventional cytogenetic studies and metaphase FISH were done on bone marrow specimens that were processed by standard 24 and 48-hour unstimulated cultures with Chang Medium BMC. Interphase FISH studies were done on blood or bone marrow (collected within 3 days of specimens for conventional cytogenetic studies) using probes to detect anomalies of chromosomes 6, 11, 12, 13, 14 and 17. For each patient, metaphase FISH was done with commercial probes from Vysis Inc., Downers Grove, IL for D13S319/13q34 using leftover fixed cells from conventional cytogenetics studies. Results: Metaphase FISH results were normal for 3 bone marrow specimens: the remaining 9 specimens had 1.9 to 13.8% metaphases with interstitial deletions of 13q14. One patient had a cytogenetically visible chromosome 13 deletion in 2.2% of metaphases. In the remaining 8 specimens, the size of the abnormal 13 was similar to the normal 13 homolog and other acrocentric chromosomes. By comparison, interphase FISH revealed 13 to 93% nuclei with 13q-x1 or 13q-x2. Seven patients had additonal anomalies in their interphase nuclei; 3 had 11q-, 2 had 17p-, 1 had +12 and 1 had +IGH. Conclusions: This investigation indicates that metaphase FISH detects submicroscopic deletions in chromosome 13 as well as infrequent mitotic B-CLL cells in patients who have normal conventional cytogenetic results. Therefore, metaphase FISH is a novel and useful technique to detect abnormal mitotic cells in B-CLL in cultures without special B-cell mitogens. The prognostic significance of abnormal metaphase FISH results is still under investigation. We speculate that this method will allow for identification of more aggressive proliferating disease even in so-called “favorable” prognostic groups based on interphase FISH results.

Abstract Background: Loss of p53 is detected by fluorescence in situ hybridization (FISH) in interphase nuclei in 8–10% of patients with B-CLL and has been associated with aggressive disease and poor response to therapy. Results of chromosome studies suggest loss of p53 is often due to structural anomalies of chromosome 17 rather than monosomy 17. To characterize chromosome 17 anomalies in B-CLL, we used interphase and metaphase FISH to study a series of patients with this disorder. Methods: We studied 16 patients with B-CLL who had chromosome 17 anomalies detected by conventional chromosome studies or interphase FISH. The study cohort consisted of 8 females and 8 males (age 54 – 73 years). Clinical data was available for 15 patients: Rai stages were I, II, III and IV for 1, 2, 6 and 6 patients, respectively; 14 patients received treatment and 10 have died. Metaphase and interphase FISH studies were performed using left-over fixed bone marrow or peripheral blood cell pellets from conventional cytogenetic studies. To identify recurrent chromosome 17 breakpoint cluster regions, patients were first studied with p53(17p13.1) and D17Z1(centromere17), and then with FISH probes for SMS(17p11.2) and RARA(17q21). For patients retaining the SMS probe site, we did FISH for HNPP(17p11.2–12) and D17Z1(centromere17). A total of 200 interphase nuclei and up to 20 metaphases were analyzed by each probe set. Results: The karyotype was normal for 3 patients and complex involving various abnormalities of chromosome 17 for the remaining 13. All patients showed loss of one p53 probe site with retention of both chromosome 17 centromeres. The SMS locus was absent in 13 patients indicating a breakpoint cluster region between the centromere and SMS probe site. In the remaining 3 patients, HNPP was absent, but the SMS probe site was retained indicating chromosome breakage between the SMS and HNPP probe sites. Metaphase FISH results indicate loss of p53 was due to an isochromosome 17p11.2 in 4 patients and an unbalanced translocation involving 17p11.2 in 12 patients. Conclusions: This study shows that loss of p53 in B-CLL cells is due to isochromosome formation or unbalanced translocations that involve a ~6,400 kb breakpoint cluster region adjacent to the centromere on the short arm of chromosome 17. Importantly, our findings indicate that loss of p53 is not due to loss of chromosome 17, simple deletions of p53, or chromosome breakage near the p53 locus. The region between the centromere and HNPP on chromosome 17 is known to be rich in low copy repeats and homologous DNA sequences are dispersed throughout the genome. In somatic cells, these repeats can result in pairing of the same or different chromosomes; crossing over within these homologous regions can result in translocations or isochromosomes. Undoubtedly, this genetic mechanism plays an important role in the origin of structural anomalies of chromosome 17 in B-CLL.

Abstract This phase 1 clinical trial evaluated the safety and effects of autologous dendritic cells (DC) injected to patients in late chronic or accelerated phase of chronic myelogenous leukemia (CML). Seven patients with a median age of 63 years (range 55–78) entered the trial. Median time from diagnosis to registration was 38 months (range 16–94). Two patients were in the accelerated phase of disease based on the presence of additional bone marrow chromosomal abnormalities, all other patients were in chronic phase. Prior therapies included hydroxyurea and alpha interferon with or without cytosine arabinoside. Four patients were on therapy with imatinib mesylate during the course of the trial, two were treated before imatinib became available and one was previously intolerant of imatinib. CD14+ monocytes were selected from a leukapheresis product by clinical grade immunoadsorption (Miltenyi Biotec). The monocytes were matured to CD83+ and bcr-abl+ DC after 10 days in culture with X-VIVO 15 medium with 1% human AB serum, GM-CSF, IL-4, as the base culture media followed by maturation mediated by TNF-alpha, IL-6 and prostaglandin E2. The first patient entered had a positive mycoplasma reaction by polymerase chain reaction at the time of his first DC injection, the cells were not given and he was withdrawn from the study. The other six patients were treated in two cohorts of three patients and received four injections each of 3x106 DC and 15x106 DC per injection, respectively. CML-DC injections were generally well tolerated and all non-hematologic toxicities were ≤ grade 2. All injections were given intra-nodally into a cervical lymph node except in the first patient where the DCs were injected subcutaneously. We observed no major clinical responses, but the white blood cell counts normalized or were maintained at normal level in four patients during therapy. Three patients experienced a transient reduction in the percentage of bcr-abl+ cells suggesting that the treatment may have affected the cells in a leukemia specific manner. We detected vascular endothelial growth factor (VEGF) in the plasma prior to therapy. In four of five patients, VEGF levels decreased by more than 75 percent during therapy. T cells isolated from patients’ blood and incubated with autologous CML DC before, during and after therapy showed increased proliferation and secretion of interferon gamma during the course of therapy. DCs from three patients were transfected with a recombinant replication-defective adenovirus carrying the gene for IL-2 under a constitutively active promoter. IL-2 secreted by transfected dendritic cells enhanced in vitro T cell proliferation and interferon gamma release and these effects increased with increasing numbers of DC injections. This study demonstrates that CML-DC can be prepared from the blood of patients treated with imatinib mesylate, that they can be administered safely and that progress of therapy is accompanied by an increase in DC-specific T cell reactivity and a decrease in circulating VEGF.

Abstract Background: Multiple myeloma (MM) has been studied by conventional cytogenetics and fluorescence in situ hybridization using DNA probes (FISH) on interphase nuclei and metaphase cells, but the relative clinical significance of proliferating (metaphase) versus non-proliferating (interphase) cells at diagnosis is poorly understood. We investigated a consecutive series of 154 patients (pts) with newly diagnosed untreated MM, and compared results for metaphase and interphase cells with survival. Methods: Bone marrow within 30 days of diagnosis was analyzed by standard cytogenetics. Leftover cells were stored at −70°C. Interphase and metaphase FISH was done using probes for IGH, FGFR3, CCND1, c-MAF, D13S319, LAMP1, p53 and D17Z1 to detect t(4;14), t(11;14), t(14;16) and chromosome 13 or 17 anomalies, respectively. We analyzed <10 metaphases and 200 unselected interphase nuclei for each FISH probe set for each pt. Survival rates were estimated using Kaplan-Meier and differences in survival curves compared using log-rank test. Results: 61 (39.6%) pts had abnormal metaphases by cytogenetics (43 pts) and/or FISH (46 pts): 12 (19.7%) had t(11;14) by cytogenetics (3 pts) and/or FISH (11 pts), 11 (18.0%) had t(4;14) by FISH but not cytogenetics, and 3 (4.9%) had t(14;16) by FISH but not cytogenetics. Metaphases with 13q- were seen in 30 pts (49.2%). Interphase FISH results were abnormal for 133 (86.3%) pts: mean percent neoplastic nuclei was 26.9 ± 21.6 (3.9 to 99.0). Mean percent plasma cells was 54.7 ± 24.6 (3.0 to 99.0). Each of the 61 pts with abnormal metaphases was also abnormal in interphase nuclei. Median survival for pts with ≥50% (20 pts) abnormal nuclei was 202 days vs. 1351 days for pts with <50% (134 pts) (p<0.001). Median survival for pts with abnormal metaphases (61 pts) was 587 days vs. 1404 days for pts with normal metaphases (93 pts) (p=0.002). Median survival was 381 days for 30 pts with 13q- metaphases compared with 1404 days for 38 pts with normal metaphases and 13q- interphase nuclei (p<0.001). Metaphase and interphase analysis along with other potential risk factors (hemoglobin <10, serum calcium ≥11, serum creatinine ≥2, plasma cell labeling index and percent bone marrow plasma cells) were evaluated by multivariate analysis using a stepwise selection in a Cox proportional hazards model. Only the observation of 13q- in metaphases or ≥50% abnormal interphase nuclei were significant predictors of survival. Conclusions: Analysis of metaphases at diagnosis is important to detect proliferating disease which is a strong indicator of poor prognosis. Metaphase FISH is a necessary adjunct to conventional cytogenetics to detect cryptic t(4;14) and t(14;16), and accurately detect prognostic chromosome anomalies such as 13q-. Observing a 13q- in metaphase cells is a strong predictor of survival compared with observing 13q- in only interphase nuclei. At diagnosis, analysis of interphase nuclei is efficient, identifies an abnormal clone in 86% of pts and defines a subset of patients with ≥50% nuclei that have a poor prognosis. Since analysis of metaphases gives better prognostic information, interphase FISH is not a substitution in the cytogenetic work up of patients with MM.

4565 Background: The efficient delivery of adjuvant therapy after radical prostatectomy (RP) in patients with prostate cancer is limited by the lack of biomarkers, beyond clinicopathologic factors, that are able to assess the risk of clinically significant disease progression. Previously, routine FFPE patient specimens from the Mayo Clinic Radical Prostatectomy Registry with long term follow-up were selected to develop a genomic classifier (GC) to predict clinical progression. Here, we present the validation of a GC in a cohort of patients at high risk of disease progression. Methods: A case-cohort study of high-risk RP patients from the Mayo Clinic (N=219) was used to validate the genomic classifier (GC) for predicting clinical progression (defined by positive bone or CT scan post-RP). Its performance was compared to a multivariable clinical classifier (CC) and a genomic-clinical classifier (GCC) which combines GC with established clinicopathologic variables. Concordance index, Cox modeling and decision curve analysis were used to compare the different models. Results: GC and GCC were predictive of clinical progression in the high-risk cohort with c-indices of 0.79 and 0.82, respectively, compared to the clinical classifier (0.70). Multivariable survival analysis showed that the majority of prognostic information of GCC came from the GC with a minor contribution from Gleason score. Decision curve analysis showed that GCC had a higher overall net benefit compared to CC over a wide range of ‘decision-to-treat’ thresholds for the risk of progression. Conclusions: In this high-risk cohort, GC and GCC classifiers showed improved performance over CC in prediction of clinical progression. GC is an independent prognostic factor in this cohort and captures the majority of prognostic information. GC and GCC’s prognostic performance and their usefulness in guiding decision-making in the adjuvant setting after RP need further testing in studies of additional prostate cancer risk groups.