Optimizing clinical cytology touch preparations for next generation sequencing.

Intraoperative diagnosis is routinely performed on cytology touch preparations (TPs) from core needle biopsies (CNBs). Current interest promotes their utility as an important source of patient tissue for clinical genomic testing. Herein we present whole genome structural variant analysis (SVA) from mate-pair sequencing (MPseq) and whole exome sequencing (WES) mutation calling in DNA directly whole genome amplified (WGA) from TPs. Chromosomal copy changes and somatic DNA junction detection from MPseq of TPs were highly consistent with associated CNBs and bulk resected tissues in all cases. While increased frequency coverage noise from limitations of amplification of limited sample input was significant, this was effectively compensated by natural tumor enrichment during the TP process, which also enhanced variant detection and loss of heterozygosity evaluations from WES. This novel TP methodology enables expanded utility of frequently limited CNB for both clinical and research genomic testing.

Patient-reported outcome domains for the esophageal CONDUIT report card: a prospective trial to establish domains.

BACKGROUND: Health-related quality of life (QoL) deteriorates immediately after esophagectomy. Patients may benefit from periodic assessments to detect increased morbidity on the basis of subjective self-reports. Using input from patients and health care providers, we developed a brief prototype for the esophageal conduit questionnaire (Mayo Clinic Esophageal Conduit Outcomes Noting Dysphagia/Dumping, and Unknown outcomes with Intermittent symptoms over Time after esophageal reconstruction [CONDUIT] Report Card) and previously used it in comparative research. The present study aimed to expand its content and establish health-related QoL and symptom domains of a patient-reported postesophagectomy conduit evaluation tool. METHODS: We expanded tool content by selecting items measuring patient-reported symptoms from existing questionnaires or written de novo. A multidisciplinary group of clinician content-matter experts approved the draft tool, together with a designated patient advocate. The expanded tool was administered to patients postesophagectomy from March 1 to November 30, 2016. We established domains of conduit performance for score reporting through data analysis with exploratory factor analyses. We assessed psychometric properties such as dimensionality, internal consistency, and inter-item correlations in each domain and compared content coverage with other existing measures intended for this patient population. For data that were missing less than 50% of patient responses, the missing values were imputed. RESULTS: Five multi-item domains were established from data of 76 patients surveyed after esophagectomy; single items were used to assess stricture and conduit emptying. For every multi-item domain, dominance of 1 factor was present. Internal consistency reliability estimates for the domains were 0.87, 0.78, 0.75, 0.80, and 0.83 and average inter-item correlations were 0.40, 0.50, 0.40, 0.33, and 0.73 for dysphagia, reflux, dumping-gastrointestinal symptoms, dumping-hypoglycemia, and pain, respectively. Some items observed to have lower inter-item correlation were reworded or flagged for removal at future validation. For reflux and dumping-related hypoglycemia, additional items were written after these analyses. CONCLUSIONS: The CONDUIT Report Card is a novel questionnaire for assessing QoL and symptoms of patients after esophageal reconstruction. It covers major symptoms of these patients and has good content validity and psychometric properties. The tool can be used to help direct patient care, guide intervention, and compare efficacy of different treatment options. TRIAL REGISTRATION: ClinicalTrials.gov identifier No. 02530983 on 8/18/2015.

Agreement Between Upper Digestive Disease App and Provider Evaluation of Esophagectomy Symptoms in a Mobile App Tool.

BACKGROUND: The objective of this study was to assess the criterion validity of score thresholds for the Upper Digestive Disease (UDD) App. METHODS: From December 15, 2017, to December 15, 2020, patients presenting after esophagectomy were offered the UDD App concurrent with a provider visit. This tool consists of 67 questions including 5 novel domains. Score thresholds were used to assign patients to a good, moderate, or poor category on the basis of domain scores. Providers were given performance descriptions for each domain and asked to assign patients to a category on the basis of their clinical evaluation. The weighted κ statistic was used to determine the magnitude of agreement between classifications based on the patients' UDD App scores and the providers' clinical evaluation. RESULTS: Fifty-nine patients in the study (76% male; median age, 63 years [interquartile range, 57-72 years]) reported outcomes using the UDD App. Providers reviewed between 1 and 10 patients at a median time of 296.5 days (interquartile range, 50-975 days) after esophagectomy. The magnitude of agreement between patients and providers was moderate for dysphagia (κ = 0.52; P < .001) and reflux (κ = 0.42; P < .001). Dumping-related hypoglycemia (κ = 0.03; P = .148), gastrointestinal complaints (κ = 0.02; P = .256), and pain (κ = 0.05; P < .184) showed minimal agreement, with providers underestimating the symptoms and problems reported by patients in these domains. CONCLUSIONS: Although there was agreement between UDD App assessment and provider evaluation of dysphagia and reflux after esophagectomy, there was discordance of scoring for dumping-related symptoms and pain. Future research is needed to determine whether thresholds for pain and dumping domains need to be revised or whether additional provider education on performance descriptions is needed.

Remotely operated robotic microscopy for rapid diagnosis of bronchoscopic cytology specimens.

BACKGROUND: Obtaining a diagnosis and treating pulmonary malignancies during the same anesthesia requires either an on-site pathologist or a system for remotely evaluating microscopic images. Cytology specimens are challenging to remotely assess given the need to navigate through dispersed and three-dimensional cell clusters. Remote navigation is possible using robotic telepathology, but data are limited on the ease of use of current systems, particularly for pulmonary cytology. METHODS: Air dried modified Wright-Giemsa stained slides from 26 touch preparations of transbronchial biopsies and 27 smears of endobronchial ultrasound guided fine needle aspirations were scored for ease of adequacy assessment and ease of diagnosis on robotic (rmtConnect Microscope) and non-robotic telecytology platforms. Diagnostic classifications were compared between glass slides and the robotic and non-robotic telecytology assessments. RESULTS: Compared to non-robotic telecytology, robotic telecytology had a greater ease of adequacy assessment and non-inferior ease of diagnosis. The median time to diagnosis using robotic telecytology was 85 s (range 28-190 s). Diagnostic categories were concordant for 76% of cases in robotic versus non-robotic telecytology and 78% of cases in robotic telecytology versus glass slide diagnosis. Weighted Cohen's kappa scores for agreement in these comparisons were 0.84 and 0.72, respectively. CONCLUSIONS: Use of a remote-controlled robotic microscope improved the ease of adequacy assessment compared to non-robotic telecytology and enabled strongly concordant diagnoses to be expediently rendered. This study provides evidence that modern robotic telecytology is a feasible and user-friendly method of remotely and potentially intraoperatively rendering adequacy assessments and diagnoses on bronchoscopic cytology specimens.

A prospective trial of CT-guided percutaneous microwave ablation for lung tumors.

Background: Percutaneous ablation is an alternative treatment for lung cancer in non-operable patients. This is a prospective clinical trial for percutaneous microwave ablation (pMWA) of biopsy-proven lung cancer to demonstrate safety and efficacy. Methods: A prospective trial from 6-1-2016 to 1-1-2019 enrolled patients with biopsy-proven primary or metastatic lung cancer <3 cm in size and 1 cm away from the pleura for pMWA with the Emprint Ablation System with Thermosphere Technology for Phase I analysis, (Clinicaltrials.gov; #NCT0267302). Patients were followed for 1 year with PET/CT and PET/MR to determine patterns of recurrence and efficacy of ablation. Results: After 12 patients consented for biopsy, 6 patients underwent treatment of 7 lesions, 3/6 women, median age of 67 (IQR, 65-70) years, body mass index (BMI): 27.8 (IQR, 21.4-32.1) kg/m2, lesion distance to pleura 24.4 (IQR, 13-38) mm, lesion size of 10.7 (IQR, 6-14) mm, and ablation duration time 5.9 (IQR, 3-10) minutes. pMWA were completed at 75 W. Twelve adverse events were reported (1 Grade 3, 3 Grade 2, and 8 Grade 1 events) with Grade 4 or 5 events. Mean % change after ablation in forced expiratory volume in one second (FEV1) was -2% and diffusion capacity for carbon monoxide (DLCO) was -1%. After 2-3 months, the lesions would decrease in size, rim thickness, fluorodeoxyglucose (FDG) activity, and T2 signal. FDG activity after 6 months was below blood pool in all cases. The ablation zones stabilized by 6-12 months. One patient expired during the study from pneumonia unrelated to ablation without local recurrence. Of the seven ablations during the 1 year follow-up, there was local tumor recurrence at 271 days following ablation at the apex of the ablation zone, subsequently successfully treated with percutaneous cryoablation (Cryo). Conclusions: pMWA appears to be a safe and effective mechanism for treatment of primary and secondary tumors of the lung, with possible preservation of pulmonary function.

Postsurgical Remote Patient Monitoring Outcomes and Perceptions: A Mixed-Methods Assessment.

Objective: To determine how postsurgical remote patient monitoring (RPM) influences readmissions and emergency visits within 30 days of discharge after operation and to understand patient and surgeon perspectives on postsurgical RPM. Patients and Methods: This study was conducted at a US tertiary academic medical center between April 1, 2021, and December 31, 2021. This mixed-methods evaluation included a randomized controlled trial evaluation of RPM after operation and a qualitative assessment of patients' and surgeons' perceptions of RPM's acceptability, feasibility, and effectiveness. Results: A total of 292 patients participated in the RPM trial, and 147 were assigned to the RPM intervention. Despite a good balance between the groups, results indicated no difference in primary or secondary outcomes between the intervention and control groups. The qualitative component included 11 patients and 9 surgeons. The overarching theme for patients was that the program brought them peace of mind. Other main themes included technological issues and perceived benefits of the RPM platform. The major themes for surgeons included identifying the best patients to receive postsurgical RPM, actionable data collection and use, and improvements in data collection needed. Conclusion: Although quantitative results indicate no difference between the groups, postsurgical RPM appears well-accepted from the patient's perspective. However, technological issues could eliminate the benefits. Hospitals seeking to implement similar programs should carefully evaluate which populations to use the program in and seek to collect actionable data.

Upper Digestive Disease App for Electronic Patient-Reported Outcomes: A Mixed Methods Pilot Study.

BACKGROUND: Patient-reported outcomes (PROs) can enable communication of symptoms, function, and quality of life. Mobile devices capture PROs electronically (ePRO). The purpose of this study was to determine the feasibility and acceptability of collecting ePROs in esophagectomy patients using the upper digestive disease application (UDD App). METHODS: A single-group, mixed methods design was used to address the study purposes. A convenience sample of esophagectomy patients was recruited after resumption of an oral diet from January 2020 to December 2020. Demographic characteristics (age, sex) and clinical data (surgical procedure) were obtained after informed consent. Participants used the UDD App for 1 year, followed by scripted telephone interviews. Descriptive statistics and thematic analyses of the interviews were the primary data analyses. RESULTS: Sixty-four patients were enrolled (80% male; 62.9 ± 12 years old). Of these, 50 patients initiated 108 evaluations through the UDD app, with 98% completing the questionnaire on the first attempt, indicating feasibility. A subset of 32 patients participated in the scripted telephone interview. Participants (74%) reported high computer literacy; all reported that using the UDD App was easier than or equivalent to a paper form. Interview themes revealed value of the app for identifying problems and enhanced communication with providers and caregivers, with an overall appreciation for the convenience of remote monitoring but concerns about data privacy. CONCLUSIONS: The UDD App is feasible and acceptable for collecting ePROs in esophagectomy patients. Future work will determine whether the UDD App improves symptoms, function, and quality of life.

Predictors of Patient-Reported Reflux After Esophagectomy.

BACKGROUND: Patient-reported reflux is among the most common symptoms after esophagectomy. This study aimed to determine predictors of patient-reported reflux and to ascertain whether a preserved pylorus would protect patients from symptomatic reflux. METHODS: A prospective clinical study recorded patient-reported reflux after esophagectomy from August 2015 to July 2018. Eligible patients were at least 6 months from creation of a traditional posterior mediastinal gastric conduit, had completed at least 1 reflux questionnaire, and had the pylorus treated either temporarily (≥100 IU Botox [onabotulinumtoxinA]) or permanently (pyloromyotomy or pyloroplasty). RESULTS: Of the 110 patients meeting inclusion criteria, the median age was 65 years, and 88 of the 110 (80%) were male. Botox was used in 15 (14%) patients, pyloromyotomy in 88 (80%), and pyloroplasty in 7 (6%). A thoracic anastomosis was performed in 78 (71%) patients, and a cervical anastomosis was performed in 32 (29%). Esophagectomy was performed for malignant disease in 105 of 110 (95%), and 78 of 110 (71%) patients were treated with perioperative chemoradiation. Multivariable linear regression analysis revealed that patient-reported reflux was significantly worse in patients with shorter gastric conduit lengths (P = .02) and in patients who did not undergo perioperative chemoradiation (P = .01). No significant difference was found between patients treated with pyloric drainage and those treated with Botox. CONCLUSIONS: The absence of perioperative chemoradiation therapy and a shorter gastric conduit were predictors of patient-reported reflux after esophagectomy. Although few patients had Botox, preservation of the pylorus did not appear to affect patient-reported reflux. Further objective studies are needed to confirm these findings.

Preliminary Normative Standards of the Mayo Clinic Esophagectomy CONDUIT Tool.

OBJECTIVE: To collect patient-reported outcomes after esophagectomy to establish a set of preliminary normative standards to aid in symptom-score interpretation. PATIENTS AND METHODS: Patients undergoing esophagectomy often have little understanding about postoperative symptom management. The Mayo Clinic esophageal CONDUIT tool is a validated questionnaire comprising 5 multi-item symptom-assessment domains and 2 health-assessment domains. A prospective nonrandomized cohort study was conducted on adult patients who have had esophagectomies using the CONDUIT tool from August 17, 2015, to July 30, 2018 (NCT02530983). The Statistical Analysis System v9.4 (SAS Institute Inc., Cary, NC) was used to calculate and analyze the scores. RESULTS: Over the study period, 569 patients were assessed for eligibility, and 241 patients consented and were offered the tool. Of these, 188 patients (median age: 65 years; range: 24 to 87 years; 80% male patients) had calculable scores. Of the 188 patients, 50 (26.6%) patients were identified as potential beneficiaries for educational intervention to improve symptoms (received moderate scores for a domain), and 131 (69.7%) patients were identified as needing further testing or provider intervention (received poor scores for a domain) based on the tool. CONCLUSION: The CONDUIT tool scores, when compared with standardized scales with established preliminary normative scores, could be used to identify and triage patients who need targeted education, further testing, or provider interventions. These score ranges will serve as the first set of normative standards to aid in the interpretation of conduit performance among providers and patients.

Standard setting for a novel esophageal conduit questionnaire: CONDUIT Report Card.

BACKGROUND: The purpose of this study was to establish the clinical thresholds for five domains (dysphagia, reflux, dumping-hypoglycemia, dumping-GI symptoms, pain) to support the use of the CONDUIT questionnaire as a screening tool to identify patients who might benefit from an educational or clinical intervention. METHODS: A panel of 16 experts met to develop descriptions of "poor," "moderate," and "good" conduit performance. They were trained to use the modified and extended Angoff standard-setting method. Each judge provided item ratings that reflected borderline good and borderline moderate patients. The average item ratings were summed and transformed to a 0-100 scale to derive final cut scores. Panelist evaluation of the process and confidence with the rating tasks were collected. RESULTS: Panelists expressed that the training on the method gave them information they needed to complete their assignment. Among other factors, their experience with patients was most influential on their ratings. On the 0-100 score scale, good/moderate cuts ranged from 7.2 to 20.8, and moderate/poor cuts ranged from 37.9 to 64.3, depending on domains and weights. Standard errors of one or both cut scores increased for dysphagia and dumping-GI with weighting. CONCLUSIONS: We described the selection and training of panelists and panelists' evaluations of the processes they were asked to follow in detail to defend the cut scores. Further prospective validation studies are underway to compare cut scores from this study and clinicians' judgments and further refine the categorization.

Survival in Surgical and Nonsurgical Patients With Superior Sulcus Tumors.

BACKGROUND: Treatments for superior sulcus tumor (SST) have evolved, with induction chemoradiotherapy providing an improved R0 resection rate. We reviewed the treatment and outcomes of SSTs in a single institution to identify prognostic factors and optimal treatment strategy. METHODS: Details of patients who underwent any type of treatment for SST from 1997 through 2014 were retrospectively collected. Survival was calculated by the Kaplan-Meier method. Proportional hazards regression was used to test the prognostic significance of factors in univariate and multivariate models. RESULTS: Eighty-nine patients were identified, 8 of whom had M1 disease and were excluded from the analysis. Of the 48 surgical patients, 44 received preoperative induction treatments, with 12 (25%) achieving a pathologic complete response (pCR), 23 with minimal residual disease, and 9 with gross residual disease. Complete resection was achieved in 40 surgical cases. As expected, nonsurgical patients had worse survival than did surgical patients (median survival, 2.1 versus 5.8 years; nonsurgical versus surgical hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2-3.7; p = 0.01). By multivariable Cox analysis, smoking status (HR, 4.4; 95% CI, 1.5-13.0; p = 0.01) and previous or concurrent malignancy (HR, 4.73; 95% CI, 1.6-13.9; p = 0.0.005) were prognostic factors for surgical patients. There were no statistically significant prognostic factors for nonsurgical patients. CONCLUSIONS: Chemoradiotherapy followed by surgical treatment is our favored treatment for operable candidates. Preoperative induction treatments were associated with a 25% pCR rate for surgical patients. Candidates for surgical therapy are expected to have longer survival than those who are not candidates for resection.

Safety of air travel in the immediate postoperative period after anatomic pulmonary resection.

OBJECTIVE: The study objective was to determine whether air travel in the immediate postoperative period after anatomic pulmonary resection is associated with increased morbidity or mortality. METHODS: All patients undergoing anatomic pulmonary resection at the Mayo Clinic (2005-2012) were identified and sent surveys querying their mode of transportation home after hospital dismissal and any complications encountered during or shortly after this travel. This included pneumonia, hospital readmission, deep venous thrombosis/pulmonary embolism, and specific pleural complications (pneumothorax, empyema, or chest tube placement). We compared the results of patients returning home by conventional ground travel with the results of patients using air travel. RESULTS: Surveys were sent to 1833 patients, and 817 responded (44.6% response rate). A total of 96 responders (11.8%) used air travel (median distance, 1783 km; range, 486-9684 km) compared with 278 km (range, 1-2618 km) for the 721 responders (88.2%) using ground travel (P < .0001). Male patients used air travel more than female patients (14.4% vs 9.3%; P = .02). Otherwise, no significant differences were observed between the 2 groups. The median duration of hospitalization was 5 days in both groups using air travel (range, 1-25 days) and ground travel (range, 1-42 days) (P = .83). There was no mortality due to postdismissal travel. The rates of major complication after hospital dismissal for those using air and ground travel were 8.3% and 7.8%, respectively (P = .87). CONCLUSIONS: Overall major complications are rare in the immediate posthospital dismissal period after lung resection. Air travel during this period was not associated with any significant increase in risk of complications when compared with conventional ground transportation and seems to be a safe option for patients after chest tube removal.

Optimal Timing of Urinary Catheter Removal After Thoracic Operations: A Randomized Controlled Study.

BACKGROUND: There are very few randomized trials confirming the belief that prolonged urinary catheterization increases urinary tract infections, and none of these have included a comparative analysis of patients with an epidural catheter in place. The aim of this prospective randomized trial was to determine if removal of the urinary catheter within 48 hours after a thoracic operation, as required by the Surgical Care Improvement Project (SCIP) Measure 9, leads to increases in urinary tract reintervention and lower rates of urinary tract infections. METHODS: From February 2012 to August 2014, patients undergoing a general thoracic surgical procedure in whom an epidural catheter was placed for analgesia were eligible for inclusion in the trial. Patients were randomized to urinary catheter removal within 48 hours of the operation completion or 6 hours after epidural catheter removal. RESULTS: The study enrolled 374 patients, 217 men (58%) and 157 women (42%). The 247 eligible and evaluated patients, 141 (57.1%) men and 106 (42.9%) women, were a median age of 61.5 years (range, 21 to 87 years). There were no statistically significant differences in any of the preoperative or operative categories between the two groups. Median length of stay was 5 days (range, 2 to 42 days) for all patients, and there was no difference between the two groups. Postoperatively, 19 patients (7.7%) required urinary catheter reinsertion after it was removed. A significantly greater number of patients in the early removal group required reinsertion of the urinary catheter (15 [12.4%] vs 4 [3.2%]); p = 0.0065). Patients whose urinary catheter was removed within 48 hours of the operation had a much higher rate of bladder scans postoperatively (59.5% [n = 72]) and required more in-and-out catheterization than those whose urinary catheter was removed 6 hours after the epidural analgesia was discontinued (31.0% [n = 39]; p < 0.0001). The only documented urinary tract infection in the entire cohort occurred in a patient whose urinary catheter was removed within 48 hours after the operation. No urinary tract infections developed in the 126 patients whose urinary catheter remained in place until the epidural catheter was removed. CONCLUSIONS: In a randomized control trial, patients with an epidural catheter in place after a general thoracic surgical operation have a higher rate of urinary problems when the urinary catheter is removed early, while the epidural catheter is still in place, compared with patients whose urinary catheter is removed after the epidural analgesia is discontinued.