Development of an Electrical Impedance Tomography Coupled Surgical Stapler for Tissue Characterization.

OBJECTIVE: This study explores the feasibility of coupling Electrical Impedance Tomography (EIT) to a standard-of-care laparoscopic surgical stapler, stapler+EIT, with the long-term goal of enabling intraoperative tissue differentiation for tumor margin detection. METHODS: Two custom printed-circuit-board-based electrode arrays with 60 and 8 electrodes, respectively, matching the stapler geometry, served as the jaws of an electrode-integrated surrogate stapler+EIT device. The device was evaluated through a series of simulations and bench-top imaging experiments of agar-gel phantoms and bovine tissue samples to evaluate the technique and determine optimal imaging parameters. RESULTS: Electrodes localized to only one jaw (the 60-electrode side) of the stapler outperformed a dual-jaw distribution of electrodes. Using this one-sided electrode array, reconstructions achieved an Area-Under-the-Curve (AUC) ≥ 0.94 for inclusions with conductivity contrasts of ≥30% for any size considered on measured agar-gel tests, and an AUC of 0.80 for bovine tissue samples. CONCLUSION: A stapler+EIT algorithm has been tuned and evaluated on challenging phantom tests and demonstrated to produce accurate reconstructions. SIGNIFICANCE: This work is an important step in the development of a surgical stapler+EIT technique for margin assessment.

Electrical Impedance Characterization of in Vivo Porcine Tissue Using Machine Learning.

The incorporation of sensors onto the stapling platform has been investigated to overcome the disconnect in our understanding of tissue handling by surgical staplers. The goal of this study was to explore the feasibility of in vivo porcine tissue differentiation using bioimpedance data and machine learning methods. In vivo electrical impedance measurements were obtained in 7 young domestic pigs, using a logarithmic sweep of 50 points over a frequency range of 100 Hz to 1 MHz. Tissues studied included lung, liver, small bowel, colon, and stomach, which was further segmented into fundus, body, and antrum. The data was then parsed through MATLAB's classification learner to identify the best algorithm for tissue type differentiation. The most effective classification scheme was found to be cubic support vector machines with 86.96% accuracy. When fundus, body and antrum were aggregated together as stomach, the accuracy improved to 88.03%. The combination of stomach, small bowel, and colon together as GI tract improved accuracy to 99.79% using fine k nearest neighbors. The results suggest that bioimpedance data can be effectively used to differentiate tissue types in vivo. This study is one of the first that combines in vivo bioimpedance tissue data across multiple tissue types with machine learning methods.

High-flow nasal oxygen availability for sedation decreases the use of general anesthesia during endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

AIM: To examine whether high-flow nasal oxygen (HFNO) availability influences the use of general anesthesia (GA) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and associated outcomes. METHODS: In this retrospective study, patients were stratified into 3 eras between October 1, 2013 and June 30, 2014 based on HFNO availability for deep sedation at the time of their endoscopy. During the first and last 3-mo eras (era 1 and 3), no HFNO was available, whereas it was an option during the second 3-mo era (era 2). The primary outcome was the percent utilization of GA vs deep sedation in each period. Secondary outcomes included oxygen saturation nadir during sedation between periods, as well as procedure duration, and anesthesia-only time between periods and for GA vs sedation cases respectively. RESULTS: During the study period 238 ERCP or EUS cases were identified for analysis. Statistical testing was employed and a P < 0.050 was significant unless the Bonferroni correction for multiple comparisons was used. General anesthesia use was significantly lower in era 2 compared to era 1 with the same trend between era 2 and 3 (P = 0.012 and 0.045 respectively). The oxygen saturation nadir during sedation was significantly higher in era 2 compared to era 3 (P < 0.001) but not between eras 1 and 2 (P = 0.028) or 1 and 3 (P = 0.069). The procedure time within each era was significantly longer under GA compared to deep sedation (P ≤ 0.007) as was the anesthesia-only time (P ≤ 0.001). CONCLUSION: High-flow nasal oxygen availability was associated with decreased GA utilization and improved oxygenation for ERCP and EUS during sedation.

Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women.

OBJECTIVE: We sought to assess the ability of human epididymis protein 4 (HE4) and CA-125 to distinguish among benign, borderline, and malignant pelvic masses in premenopausal women. STUDY DESIGN: We conducted a subset analysis of data from a prospective clinical trial that enrolled women undergoing surgery for an adnexal mass. Diagnostic performance of CA-125 and HE4 for epithelial ovarian cancer (EOC) detection in premenopausal women was determined. RESULTS: Of 229 premenopausal patients, 195 (85%) had benign masses, 18 (8%) had EOC, and 16 (7%) had borderline ovarian tumor. The sensitivity of CA-125 and HE4 for EOC detection was 83.3% and 88.9%, respectively. The specificity of CA-125 and HE4 was 59.5% and 91.8%, respectively. A normal HE4 level ruled out invasive cancer in 98% of women with an elevated CA-125. CONCLUSION: HE4 offers superior specificity compared to CA-125 for the differentiation of benign and malignant adnexal masses in premenopausal women.

The College of American Pathologists and National Society for Histotechnology workload study.

Limited data exist in regard to productivity and staffing in the anatomic pathology laboratory. In 2004, the National Society for Histotechnology (NSH) conducted a pilot study to examine productivity and staffing in the histology laboratory. After review of the data, The College of American Pathologists (CAP)/NSH Histotechnology Committee concluded that a larger survey was required to further address and expand on the pilot study findings. In 2007, a total of 2674 surveys were sent out to North American laboratories. From the responses, comparisons of laboratory demographics and productivity were examined by institution type and workload volume. Productivity was measured as the number of paraffin-embedded tissue blocks processed per full-time equivalent per year. This manuscript presents and discusses the data collected from the CAP/NSH Workload Study.

Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis?

RATIONALE: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. OBJECTIVES: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. METHODS: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. MEASUREMENTS AND MAIN RESULTS: Each observer's diagnosis was coded into one of eight categories. A kappa statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (kappa = 0.55-0.71) than within community centers (kappa = 0.32-0.44). Clinically significant disagreement was present between academic and community-based physicians (kappa = 0.11-0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. CONCLUSIONS: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.

Molecular subclassification of kidney tumors and the discovery of new diagnostic markers.

We analysed the expression profiles of 70 kidney tumors of different histological subtypes to determine if these subgroups can be distinguished by their gene expression profiles, and to gain insights into the molecular mechanisms underlying each subtype. In all, 39 clear cell renal cell carcinomas (RCC), seven primary and one metastatic papillary RCC, six granular RCC from old classification, five chromophobe RCC, five sarcomatoid RCC, two oncocytomas, three transitional cell carcinomas (TCC) of the renal pelvis and five Wilms' tumors were compared with noncancerous kidney tissues using microarrays containing 19,968 cDNAs. Based on global gene clustering of 3560 selected cDNAs, we found distinct molecular signatures in clear cell, papillary, chromophobe RCC/oncocytoma, TCC and Wilms' subtypes. The close clustering in each of these subtypes points to different tumorigenic pathways as reflected by their histological characteristics. In the clear cell RCC clustering, two subgroups emerged that correlated with clinical outcomes, confirming the potential use of gene expression signatures as a predictor of survival. In the so-called granular cell RCC (terminology for a subtype that is no longer preferred), none of the six cases clusters together, supporting the current view that they do not represent a single entity. Blinded histological re-evaluation of four cases of 'granular RCC' led to their reassignment to other existing histological subtypes, each compatible with our molecular classification. Finally, we found gene sets specific to each subtype. In order to establish the use of some of these genes as novel subtype markers, we selected four genes and performed immunohistochemical analysis on 40 cases of primary kidney tumors. The results were consistent with the gene expression microarray data: glutathione S-transferase alpha was highly expressed in clear cell RCC, alpha methylacyl racemase in papillary RCC, carbonic anhydrase II in chromophobe RCC and K19 in TCC. In conclusion, we demonstrated that molecular profiles of kidney cancers closely correlated with their histological subtypes. We have also identified in these subtypes differentially expressed genes that could have important diagnostic and therapeutic implications.

Inactivation of BHD in sporadic renal tumors.

Studies of families with Birt-Hogg-Dubé syndrome (BHD) have recently revealed protein-truncating mutations in the BHD gene, leading to tumorigenesis of the skin and of different cell types of kidney. To additionally evaluate the role of BHD in kidney tumorigenesis, we studied 39 sporadic renal tumors of different cell types: 7 renal oncocytomas, 9 chromophobe renal cell carcinomas (RCCs), 11 papillary RCCs, and 12 clear cell RCCs. We screened for BHD mutations and identified a novel somatic mutation in exon 13: c.1939_1966delinsT in a papillary RCC. We performed loss of heterozygosity (LOH) analysis on 28 matched normal/tumor sets, of which 10 of 28 (36%) demonstrated LOH: 2 of 6 (33%) chromophobe RCCs, 5 of 6 (83%) papillary RCCs, 3 of 12 (25%) clear cell RCCs, but 0 of 4 renal oncocytomas. BHD promoter methylation status was examined by a methylation-specific PCR assay of all of the tumors. Methylation was detected in 11 of 39 (28%) sporadic renal tumors: 2 of 7 (29%) renal oncocytomas, 1 of 9 (11%) chromophobe RCCs, 4 of 11 (36%) papillary RCCs, and 4 of 12 (33%) clear cell RCCs. Five tumors with methylation also exhibited LOH. Mutation and methylation were absent in 9 kidney cancer cell lines. Our results showed that somatic BHD mutations are rare in sporadic renal tumors. The alternatives, LOH and BHD promoter methylation, are the two possible inactivating mechanisms involved. In conclusion, unlike other hereditary kidney cancer-related genes (i.e., VHL and MET), which are cell type-specific, BHD is involved in the entire spectrum of histological types of renal tumors, suggesting its major role in kidney cancer tumorigenesis.

Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women.

PURPOSE: Previous studies of CA-125 levels from screening trials for ovarian cancer have indicated that serial CA-125 levels may identify cases better than a fixed CA-125 cutoff. We conducted a study to assess the screening performance of the risk of ovarian cancer calculation based on serial CA-125 levels from prospectively collected serum samples compared with a fixed CA-125 cutoff. PATIENTS AND METHODS: The calculation was applied to data from a prospective trial of screening for ovarian cancer involving 22,000 postmenopausal women older than 45 years. The analysis was performed using 33,621 CA-125 results from 9,233 women for whom two or more serial samples were available. All serum samples from the patients with ovarian cancer were obtained before clinical detection. Sensitivity and specificity levels for preclinical detection of index cancers were calculated for various cutoffs for the risk and a single CA-125 measurement, and receiver operator curves were constructed. RESULTS: The risk calculation significantly improved the area under the curve from 84% to 93% compared with a fixed cutoff for CA-125 (P =.01). For a target specificity of 98%, the risk achieved a sensitivity of 86% for preclinical detection of ovarian cancer, whereas CA-125 achieved a sensitivity of 62%. The estimates of performance are unbiased, because the risk calculation was derived independent of the data from this trial. CONCLUSION: These results provide the first evidence that preclinical detection of ovarian cancer using serial CA-125 levels interpreted with the risk calculation significantly improves screening performance compared with a fixed cutoff for CA-125. The results justify the incorporation of the risk calculation in a prospective, randomized, controlled trial.