Understanding Thyroidectomy Cost Variations Among National Cancer Institute-Designated Cancer Centers.

BACKGROUND: The cost of thyroidectomy varies across the USA, while the causes of this variation are poorly understood. We examined the cost of inpatient thyroidectomy among National Cancer Institute-designated cancer centers nationwide to determine why it differs. METHODS: A retrospective study of inpatient thyroidectomies was performed using the Vizient Clinical Data Base. Fifty-two of 70 eligible hospitals were grouped into five geographic regions (Mid-Atlantic and New England, East Central, South Atlantic, West Central, and Mountain and Pacific). We identified drivers of cost variation in the five geographic regions and used risk adjustment model to evaluate the rationality of cost from each hospital. RESULTS: Male sex, more extended hospital stays, and occurrence of complications were consistently associated with increased costs in all regions. Also, the cost was significantly lower in the Mid-Atlantic and New England region. The higher than expected costs did not correlate well with the case mix index among hospitals (p = 0.289), but the lower than expected costs were more common in high-volume hospitals. The average length of stay was the shortest in high-volume hospitals, which might account for the lower cost in the Mid-Atlantic and New England region; however, the overages of costs still varied widely among hospitals in all regions even if the length of stay was adjusted. CONCLUSIONS: Cost variation may result from both patient-related factors and volume-related practice pattern differences among hospitals. A more standard of care and charge transparency is still needed for patients seeking affordable care at cancer centers.

Disseminating universal genetic testing to a diverse, indigent patient population at a county hospital gynecologic oncology clinic.

OBJECTIVE: The universal genetic testing initiative (UGTI) is a quality improvement effort to increase rates of guideline-based genetic counseling (GC) and genetic testing (GT) of patients with potentially hereditary cancers. The UGTI was disseminated to a county hospital gynecologic oncology clinic that serves a diverse, indigent patient population. METHODS: Using the Model for Improvement quality improvement framework, interventions including integrated GC, clinic tracking, assisted GC referrals, and provider education were tested over 26 months. A retrospective data review included patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC) and endometrial cancers (EC) diagnosed between 9/1/12-8/31/16. Statistical analyses were performed to describe the population and to evaluate rates of recommendation and use of immunohistochemistry tumor testing (IHC), GC, and GT. RESULTS: A cohort of 241 patients (57 HGOC, 184 EC) were included. At the conclusion of the study 84.2% of HGOC patients were referred for GC, 89.6% (43/48) completed GC, and 90.7% (39/43) completed GT. Of EC patients, 81.0% were recommended to have IHC and 62.4% (93/149) completed IHC. Patients with HGOC diagnosed during dissemination of UGTI were significantly more likely to receive a recommendation for GC (p = 0.02) and to complete GT (p = 0.03) than those diagnosed before UGTI. Patients with EC were significantly more likely to complete IHC if diagnosed after UGTI than those diagnosed prior to dissemination (p < 0.001). CONCLUSIONS: The UGTI can be adapted to increase use of guideline-based cancer genetics services in a diverse, indigent, gynecologic cancer patient population.

Surgeon perception versus reality: Opioid use after breast cancer surgery.

BACKGROUND: Few guidelines exist for an opioid prescription after breast surgical oncology (BSO) procedures. We sought to characterize opioid prescribing and use patterns by surgery type. METHODS: Patients (n = 332) undergoing BSO procedure were surveyed one week postoperatively for opioid use. The surgeons were surveyed about pain management preferences surgery type. CPT codes were collected for 2017 to calculate the amount of opioids used by surgery type relative to surgeon preference. RESULTS: Mean oral morphine equivalent (OME) preferred prescription for surgeons who did not tailor prescriptions by surgery type (n = 7, group A) was 177, whereas for those who did tailor (n = 10, group B) varied from 137 to 257 OME. There was a significant difference in opioid use by surgery type: 32 OME for segmental mastectomy (SM) ± sentinel lymph node dissection (SLND), 63 for SM + axillary lymph node dissection (ALND), 76 for total mastectomy (TM) ± SLND, 115 for TM + ALND (P < 0.001). Considering the type of surgeries performed group A prescribers would have 229190 unused OME and group B would have 230826 in 1 year. CONCLUSION: Wide variation in opioid use by BSO procedure type was noted with substantial unused OME regardless ofprescribing preference. Evidence-based guidelines are needed to tailor analgesic prescriptions according to the need.

Improving patient access to an interventional US clinic.

A continuous quality improvement project was conducted to increase patient access to a neurointerventional ultrasonography (US) clinic. The clinic was experiencing major scheduling delays because of an increasing patient volume. A multidisciplinary team was formed that included schedulers, medical assistants, nurses, technologists, and physicians. The team created an Ishikawa diagram of the possible causes of the long wait time to the next available appointment and developed a flowchart of the steps involved in scheduling and completing a diagnostic US examination and biopsy. The team then implemented a staged intervention that included adjustments to staffing and room use (stage 1); new procedures for scheduling same-day add-on appointments (stage 2); and a lead technician rotation to optimize patient flow, staffing, and workflow (stage 3). Six months after initiation of the intervention, the mean time to the next available appointment had decreased from 25 days at baseline to 1 day, and the number of available daily appointments had increased from 38 to 55. These improvements resulted from a coordinated provider effort and had a net present value of more than $275,000. This project demonstrates that structural changes in staffing, workflow, and room use can substantially reduce scheduling delays for critical imaging procedures.

Anthracyclines React with Apurinic/Apyrimidinic Sites in DNA.

The combination of doxorubicin (Adriamycin) and cyclophosphamide, referred to as AC chemotherapy, is commonly used for the clinical treatment of breast and other cancers. Both agents target DNA with cyclophosphamide causing alkylation damage and doxorubicin stabilizing the topoisomerase II-DNA complex. We hypothesize a new mechanism of action whereby both agents work in concert. DNA alkylating agents, such as nitrogen mustards, increase the number of apurinic/apyrimidinic (AP) sites through deglycosylation of labile alkylated bases. Herein, we demonstrate that anthracyclines with aldehyde-reactive primary and secondary amines form covalent Schiff base adducts with AP sites in a 12-mer DNA duplex, calf thymus DNA, and MDA-MB-231 human breast cancer cells treated with nor-nitrogen mustard and the anthracycline mitoxantrone. The anthracycline-AP site conjugates are characterized and quantified by mass spectrometry after NaB(CN)H3 or NaBH4 reduction of the Schiff base. If stable, the anthracycline-AP site conjugates represent bulky adducts that may block DNA replication and contribute to the cytotoxic mechanism of therapies involving combinations of anthracyclines and DNA alkylating agents.

A Step Forward for Smart Clothes─Fabric-Based Microfluidic Sensors for Wearable Health Monitoring.

We report the first demonstration of fabric-based microfluidics for wearable sensing. A new technology to develop microfluidics on fabrics, as a part of an undergarment, is described here. Compared to conventional microfluidics from polydimethylsiloxane, fabric-based microfluidics are simple to make, robust, and suitable for efficient sweat delivery. Specifically, acrylonitrile butadiene styrene (ABS) films with precut microfluidic patterns were infused through fabrics to form hydrophobic areas in a specially controlled sandwich structure. Experimental tests and simulations confirmed the sweat delivery efficiency of the microfluidics. Electrodes were screen-printed onto the fabric-based microfluidic. A novel wearable potentiometer based on Arduino was also developed as the transducer and signal readouts, which was low-cost, standardized, open-source, and capable of wireless data transfer. We applied the sensor system as a standalone or as a module of a T-shirt to quantify [Ca2+] in a wearer's sweat, with physiological and accurate results generated. Overall, this work represents a critical step in turning regular undergarments into biochemically smart platforms for health monitoring, which will broadly benefit human healthcare.

Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma.

OBJECTIVE: • To evaluate the diagnostic accuracy of urine cytology for detecting aggressive disease in a multi-institutional cohort of patients undergoing extirpative surgery for upper-tract urothelial carcinoma (UTUC). METHODS: • We reviewed the records of 326 patients with urinary cytology data who underwent a radical nephroureterectomy or distal ureterectomy without concurrent or previous bladder cancer. • We assessed the association of cytology (positive, negative and atypical) with final pathology. Sensitivity and positive predictive value (PPV) of a positive (± atypical) cytology for high-grade and muscle-invasive UTUC was calculated. RESULTS: • On final pathology, 53% of patients had non-muscle invasive disease (pTa, pTis, pT1) and 47% had invasive disease (≥ pT2). Low-grade and high-grade cancers were present in 33% and 67% of patients, respectively. • Positive, atypical and negative urine cytology was noted in 40%, 40% and 20% of cases. Positive urinary cytology had sensitivity and PPV of 56% and 54% for high-grade and 62% and 44% for muscle-invasive UTUC. • Inclusion of atypical cytology with positive cytology improved the sensitivity and PPV for high-grade (74% and 63%) and muscle-invasive (77% and 45%) UTUC. Restricting analysis to patients with selective ureteral cytologies further improved the diagnostic accuracy when compared with bladder specimens (PPV > 85% for high-grade and muscle-invasive UTUC). CONCLUSIONS: • In this cohort of patients with UTUC treated with radical surgery, urine cytology in isolation lacked performance characteristics to accurately predict muscle-invasive or high-grade disease. • Improved surrogate markers for pathological grade and stage are necessary, particularly when considering endoscopic modalities for UTUC.

Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation.

OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek) and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331), 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1) and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668) patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta). The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin ß1.

Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin ß1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin ß1 than cells on the microfibers. Moreover, after partially blocking integrin ß1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin ß1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).

Social network analysis of the genetic structure of Pacific islanders.

Social network analysis (SNA) is a body of theory and a set of relatively new computer-aided techniques used in the analysis and study of relational data. Recent studies of autosomal markers from over 40 human populations in the south-western Pacific have further documented the remarkable degree of genetic diversity in this part of the world. I report additional analysis using SNA methods contributing new controlled observations on the structuring of genetic diversity among these islanders. These SNA mappings are then compared with model-based network expectations derived from the geographic distances among the same populations. Previous studies found that genetic divergence among island Melanesian populations is organised by island, island size/topography, and position (coastal vs. inland), and that similarities observed correlate only weakly with an isolation-by-distance model. Using SNA methods, however, improves the resolution of among population comparison, and suggests that isolation by distance constrained by social networks together with position (coastal/inland) accounts for much of the population structuring observed. The multilocus data now available is also in accord with current thinking on the impact of major biogeographical transformations on prehistoric colonisation and post-settlement human interaction in Oceania.

Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma.

PURPOSE: We evaluated the value of hydronephrosis, ureteroscopic biopsy grade and urinary cytology to predict advanced upper tract urothelial carcinoma. MATERIALS AND METHODS: We reviewed the charts of 469 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy or distal ureterectomy. Complete data on hydronephrosis (present vs absent), ureteroscopic grade (high vs low) and urinary cytology (positive vs negative) were available in 172 patients. The outcome was muscle invasive (pT2-pT4) or nonorgan confined (pT3 or greater, or lymph node metastasis) upper tract urothelial carcinoma. RESULTS: Of the patients 92 (54%) had hydronephrosis, 74 (43%) had high grade disease on ureteroscopic biopsy and 137 (80%) had positive cytology. On univariate analysis hydronephrosis (p <0.001), high ureteroscopic grade (p <0.001) and positive cytology (p = 0.03) were associated with muscle invasive and nonorgan confined disease. On multivariate analysis adjusting for tumor site, gender and age hydronephrosis and high ureteroscopic grade were associated with muscle invasive carcinoma (HR 12.0 and 4.5, respectively, each p <0.001) but cytology was not (HR 2.3, p = 0.17). However, all 3 variables were independently associated with nonorgan confined disease (HR 5.1, p <0.001; HR 3.9, p <0.001; and HR 3.1, p = 0.035, respectively). Combining these 3 tests incrementally improved the prediction of upper tract urothelial carcinoma stage. Abnormality of all 3 tests had 89% and 73% positive predictive value for muscle invasive and nonorgan confined upper tract urothelial carcinoma, respectively, but when all tests were normal, the negative predictive value was 100%. CONCLUSIONS: Preoperative evaluation for hydronephrosis, ureteroscopic grade and cytology can identify patients at risk for advanced upper tract urothelial carcinoma. Such knowledge may impact surgery choice and extent as well as the need for perioperative chemotherapy regimens.

From cells-on-a-chip to organs-on-a-chip: scaffolding materials for 3D cell culture in microfluidics.

It is an emerging research area to integrate scaffolding materials in microfluidic devices for 3D cell culture (organs-on-a-chip). The technology of organs-on-a-chip holds the potential to obviate the gaps between pre-clinical and clinical studies. As accumulating evidence shows the importance of extracellular matrix in in vitro cell culture, significant efforts have been made to integrate 3D ECM/scaffolding materials in microfluidics. There are two families of materials that are commonly used for this purpose: hydrogels and electrospun fibers. In this review, we briefly discuss the properties of the materials, and focus on the various technologies to obtain the materials (e.g. extraction of collagen from animal tissues) and to include the materials in microfluidic devices. Challenges and potential solutions of the current materials and technologies were also thoroughly discussed. At the end, we provide a perspective on future efforts to make these technologies more translational to broadly benefit pharmaceutical and pathophysiological research.

Harnessing Behavioral Economics Principles to Promote Better Surgeon Accountability for Operating Room Cost: A Prospective Study.

BACKGROUND: Operating room (OR) cost accounts for a significant portion of inpatient spending, but most surgeons are unaware of the costs of OR implants and supplies. We leveraged behavioral economics principles and a cost transparency tool to have an impact on discretionary OR spending (disposable supplies). STUDY DESIGN: We performed a single-institution, prospective study, from January to December 2018, across 3 departments: urology, thoracic, and endocrine. Two self-selected procedures per department were subjected to intraoperative supply cost (ISC) feedback via a custom dashboard and monthly email reports. Behavioral economics principles like choice overload, social ranking, and threshold effects were leveraged during study design. The primary outcome of percentage change in the department-level mean ISC, as determined via an interrupted time-series mixed effects model, was compared between the intervention year (2018) and "pre-baseline" (2016) and "baseline" (2017) years. RESULTS: A total of 2,853 procedures and 26 surgeons comprised our analytical sample. Costs decreased in 5 of the 6 procedures in 2018. On average, there was a significant monthly decrease in costs of approximately 0.5% over the study period (p = 0.0004). Post-intervention, there was a nonsignificant additional decrease of 0.6% in monthly cost (p = 0.0648). Overall cost significantly decreased by 20% due to the intervention (p < 0.0001). Similar results were noted on sensitivity analysis. There were no significant changes in the incidence of postoperative complication due to our intervention. CONCLUSIONS: Deployment of a cost feedback tool using behavioral economics principles resulted in a significant decrease in OR spending without negatively affecting complication rate.

Reassessing the environmental context of the Aitape Skull - The oldest tsunami victim in the world?

There is increasing recognition of the long-lasting effects of tsunamis on human populations. This is particularly notable along tectonically active coastlines with repeated inundations occurring over thousands of years. Given the often high death tolls reported from historical events though it is remarkable that so few human skeletal remains have been found in the numerous palaeotsunami deposits studied to date. The 1929 discovery of the Aitape Skull in northern Papua New Guinea and its inferred late Pleistocene age played an important role in discussions about the origins of humans in Australasia for over 25 years until it was more reliably radiocarbon dated to around 6000 years old. However, no similar attention has been given to reassessing the deposit in which it was found-a coastal mangrove swamp inundated by water from a shallow sea. With the benefit of knowledge gained from studies of the 1998 tsunami in the same area, we conclude that the skull was laid down in a tsunami deposit and as such may represent the oldest known tsunami victim in the world. These findings raise the question of whether other coastal archaeological sites with human skeletal remains would benefit from a re-assessment of their geological context.

Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma.

OBJECTIVE: The presence of hydronephrosis (HN) has been implicated as a predictor of poor outcomes for patients diagnosed with bladder cancer. Small, single institution preliminary reports suggest a similar negative relationship may exist for upper-tract urothelial carcinoma (UTUC). Herein, we attempt to validate the prognostic value of preoperative HN in a large, multi-institutional cohort of UTUC patients. MATERIALS AND METHODS: Data on 469 patients with localized UTUC from 5 tertiary referral centers who underwent a radical nephroureterectomy (91%) or distal ureterectomy (9%) without neoadjuvant chemotherapy were integrated into a relational database. Preoperative HN data, including presence vs. absence and high vs. low grade, were available in 408 patients. The association of HN with pathologic features was evaluated. RESULTS: A total of 254 men and 154 women with a median age of 69 years (IQR 15) were analyzed. Overall, 192 patients (47%) had ≥pT2 disease, 145 (36%) had non-organ-confined (NOC) cancers (≥pT3 and/or positive lymph nodes), and 298 (73%) had high grade UTUC on final pathology. Forty-six percent of patients had tumors in the renal pelvis, 27% in the ureter, and 27% in both locations. Preoperatively, 223 patients (55%) were noted to have ipsilateral HN (39% low grade and 61% high grade). Hydronephrosis was associated with ≥pT2 stage (P < 0.001), NOC disease (P < 0.001), and high grade cancers (P = 0.04). On multivariate analysis adjusting for gender, age, and tumor location, HN was an independent predictor of muscle invasive (HR 7.4, P < 0.001), NOC (HR 5.5, P < 0.001), and high pathologic grade (HR 1.6, P = 0.03) UTUC disease. CONCLUSION: The presence of preoperative HN was associated with advanced stage UTUC. This readily available imaging modality may improve preoperative risk stratification for UTUC patients thereby guiding use of endoscopic versus extirpative surgery as well as the need for neoadjuvant chemotherapy regimens.

High-grade ureteroscopic biopsy is associated with advanced pathology of upper-tract urothelial carcinoma tumors at definitive surgical resection.

BACKGROUND AND PURPOSE: Accurate assessment of upper-tract urothelial carcinoma (UTUC) pathology may guide use of endoscopic vs extirpative therapy. We present a multi-institutional cohort of patients with UTUC who underwent surgical resection to characterize the association of ureteroscopic (URS) biopsy features with final pathology results. PATIENTS AND METHODS: URS biopsy data were available in 238 patients who underwent surgical resection of UTUC. Biopsies were performed using a brush biopsy kit, mechanical biopsy device, or basket. Stage was classified as a positive brush, nonmuscle-invasive (

Characterization of renal ischemia using DLP hyperspectral imaging: a pilot study comparing artery-only occlusion versus artery and vein occlusion.

BACKGROUND AND PURPOSE: Renal artery-only (AO) occlusion, as opposed to artery and vein (AV) occlusion, has demonstrated some benefit in reducing renal insufficiency during warm ischemia. In this pilot study, we used digital light projection hyperspectral imaging (HSI) to construct a "real time" tissue oxygenation "map" to determine whether there are differences in renal tissue oxygenation during vascular occlusion with AO vs AV. MATERIALS AND METHODS: Renal vascular occlusion with either AO or AV was performed for 60 minutes in seven porcine renal units. Using HSI, the percentage of oxyhemoglobin (%HbO(2)) in the renal cortex was determined at 4-minute increments throughout the ischemic period and for 30 minutes after reperfusion. RESULTS: Average baseline %HbO(2) in all animals was approximately 70%. After vascular occlusion in both cohorts, %HbO(2) decreased by one third within 2 to 5 minutes, with a gradual decline in %HbO(2) over the remaining 55 minutes. Oxyhemoglobin profiles for AO and AV occlusion diverged significantly between 16 and 24 minutes after vascular occlusion (P = 0.0001 and 0.036, respectively), with a merging of the two curves occurring after approximately 36 minutes (P = 0.093). During reperfusion, average %HbO(2) improved to 72.4% after 25 to 30 minutes. CONCLUSION: In this pilot study, we demonstrate that renal tissue oxygenation drops rapidly after occlusion of the renal vasculature and returns to near baseline 30 minutes after reperfusion. In the porcine model, the %HbO(2) differs significantly between AO and AV occlusion for up to 35 minutes after ischemia onset, indicating a possible "ischemic window" in which AO occlusion may provide benefit over AV occlusion.

Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek) and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331), 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1) and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668) patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta). The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.