Surgical phenotype of patients with peritoneal mesothelioma and a germline mutation.

BACKGROUND: This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM. METHODS: PM patients were selected from an ongoing prospective study that conducts germline testing of 82 susceptibility genes. Germline status was correlated with surgical data obtained from a prospectively collected database using univariate, multivariate, and receiver operating characteristic (ROC) analyses. RESULTS: Out of 88 PM patients enrolled between 2009 and 2019, 18 GMs (20.5%) were identified in BRCA1-associated protein 1 (BAP1) (n = 11, 12.5% of all patients), SDHA (n = 2) and WT1, CDKN2A, CHEK2, ATM, and BRCA2 (n = 1 patient each). Surgical procedures were performed in 71 patients, the most common of which were cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy (n = 61). Patients with GM presented with a higher prevalence of other prior cancers (61.1% vs. 31.4%, p = .02) and lower platelet count (251 [160-413] vs. 367 [196-780] K/µL, p = .005) compared to those without GM (n = 70). Survival outcomes did not differ significantly between the groups. Patients with BAP1 GMs were more likely to develop bicavitary disease and to present with lower platelet count and mitotic count score, and higher peritoneal cancer index (PCI, all p ≤ .04) compared with those without GM. On ROC analysis, the combination of PCI, platelet count and mitotic score yielded an area under the curve of 0.96 (95% CI, 0.91-1.0) for BAP1 GM detection among operated PM patients. CONCLUSION: Higher intraoperative tumor burden and lower platelet count and mitotic score are suggestive of BAP1 GMs in surgical PM patients and should prompt germline testing.

The progress of type II persisters of Escherichia coli O157:H7 to a non-culturable state during prolonged exposure to antibiotic stress with revival being aided through acid-shock treatment and provision of methyl pyruvate.

Persisters are a form of dormancy in bacteria that provide temporary resistance to antibiotics. The following reports on the formation of Escherichia coli O157:H7 E318 type II persisters from a protracted (8 days) challenge with ampicillin. Escherichia coli O157:H7 followed a multiphasic die-off pattern with an initial rapid decline (Phase I) of susceptible cells that transitioned to a slower rate representing tolerant cells (Phase II). After 24 h post-antibiotic challenge, the E. coli O157:H7 levels remained relatively constant at 2 log CFU/mL (Phase III), but became non-culturable within 8-days (Phase IV). The revival of persisters in Phase III could be achieved by the removal of antibiotic stress, although those in Phase IV required an extended incubation period or application of acid-shock. The carbon utilization profile of persister cells was less diverse compared with non-persisters, with only methyl pyruvate being utilized from the range tested. Inclusion of methyl pyruvate in tryptic soy agar revived non-cultural persisters, presumably by stimulating metabolism. The results suggest that persisters could be subdivided into culturable or non-culturable cells, with the former representing a transition state to the latter. The study provided insights into how to revive cells from dormancy to aid enumeration and control.

Visual and refractive outcomes of laser cataract surgery.

PURPOSE OF REVIEW: Femtosecond laser is a promising new technology for the field of cataract surgery. Early studies have investigated many factors including visual outcomes, complication rates, and financial overhead costs. This review analyzes the most recent clinical studies of visual and refractive outcomes in laser cataract surgery, including those that make comparisons to outcomes found in conventional phacoemulsification cataract surgery. RECENT FINDINGS: As femtosecond laser cataract surgery has only emerged recently, there is limited literature available regarding visual outcomes. Most but not all existing studies showed no statistically significant difference in visual acuity and mean absolute refractive error between laser and conventional cataract surgery cases. SUMMARY: The majority of studies examined found visual acuity or refractive outcomes of femtosecond laser to be statistically equivalent to those of conventional phacoemulsification cataract surgery. However, the learning curve involved with laser use may account for these early results, which could potentially improve as better technology and surgical techniques are developed. Further long-term outcomes studies are necessary to more accurately evaluate the benefits and drawbacks of femtosecond laser cataract surgery.

Endoscopic Ultrasound Predicts Risk of Occult Intra-Abdominal Metastases in Localized Gastric Cancer: A Validation Study.

Background: In gastric cancer (GC) patients without imaging evidence of distant metastasis, diagnostic staging laparoscopy (DSL) is recommended to detect radiographically occult peritoneal metastasis (M1). DSL carries a risk for morbidity and its cost-effectiveness is unclear. Use of endoscopic ultrasound (EUS) to improve patient selection for DSL has been proposed but not validated. We aimed to validate an EUS-based risk classification system predicting risk for M1 disease. Methods: We retrospectively identified all GC patients without positron emission tomography (PET)/computed tomography (CT) evidence of distant metastasis who underwent staging EUS followed by DSL between 2010 and 2020. T1-2, N0 disease was EUS "low-risk"; T3-4 and/or N+ disease was "high-risk". Results: A total of 68 patients met inclusion criteria. DSL identified radiographically occult M1 disease in 17 patients (25%). Most patients had EUS T3 tumors (n = 59, 87%) and 48 (71%) patients were node-positive (N+). Five (7%) patients were classified EUS "low-risk" and 63 (93%) were classified "high-risk". Of 63 "high-risk" patients, 17 (27%) had M1 disease. The ability of "low-risk" EUS to predict M0 disease at laparoscopy was 100% and DSL would have been avoided in five patients (7%). This stratification algorithm showed a sensitivity of 100% (95% confidence interval (CI): 80.5-100%) and a specificity of 9.8% (95% CI: 3.3-21.4%). Conclusions: Use of an EUS-based risk classification system in GC patients without imaging evidence of metastasis helps identify a subset of patients at low-risk for laparoscopic M1 disease who may avoid DSL and proceed directly to neoadjuvant chemotherapy or resection with curative intent. Larger, prospective studies are needed to validate these findings.

The impact of site-specific digital histology signatures on deep learning model accuracy and bias.

The Cancer Genome Atlas (TCGA) is one of the largest biorepositories of digital histology. Deep learning (DL) models have been trained on TCGA to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. However, we demonstrate that these features vary substantially across tissue submitting sites in TCGA for over 3,000 patients with six cancer subtypes. Additionally, we show that histologic image differences between submitting sites can easily be identified with DL. Site detection remains possible despite commonly used color normalization and augmentation methods, and we quantify the image characteristics constituting this site-specific digital histology signature. We demonstrate that these site-specific signatures lead to biased accuracy for prediction of features including survival, genomic mutations, and tumor stage. Furthermore, ethnicity can also be inferred from site-specific signatures, which must be accounted for to ensure equitable application of DL. These site-specific signatures can lead to overoptimistic estimates of model performance, and we propose a quadratic programming method that abrogates this bias by ensuring models are not trained and validated on samples from the same site.

Accuracy of Subclassification and Grading of Renal Tumors on Fine Needle Aspiration Cytology Alone.

BACKGROUND: Fine needle aspiration (FNA) of renal masses can distinguish between benign and malignant neoplasms in 73-94% of cases. Previous studies suggested the correct subclassification of renal cell carcinomas (RCCs) by cytomorphology can be achieved in up to 80% of cases. However, as RCCs become increasingly subclassified by molecular signatures, correct subclassification based on cytology alone is increasingly difficult. DESIGN: Two FNA passes (2 stained with Diff-Quik® and 2 with the Papanicolaou method) were performed on all fresh nephrectomy specimens for a 1-year period. There were 30 cases in this study, with 29 primary renal tumors and 1 case of metastatic lung adenocarcinoma. Each case was assigned a random number and came with 2 slides (1 from each staining method). Eight cytopathologists were asked to provide a diagnosis and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading if applicable. Fleiss' Kappa and Cohen's Kappa equations were used to look at inter-rater variability. RESULTS: When compared to the surgical pathology diagnosis, the average percent correct diagnosis for all cytopathologist was 35%. Chromophobe RCCs had the best average percent accuracy at 72% followed by clearcell RCC at 48%. Average accuracy for grading RCCs was 40%. Inter-rater variability among the cytopathologists for all RCC diagnoses was fair with a Fleiss' Kappa coefficient of 0.28. For the WHO/ISUP grade, the weighted coefficient for each pathologist ranged from 0.11 to 0.45, ranging from fair to moderate, respectively. CONCLUSIONS: Renal tumors are difficult to classify on cytopathology alone. Core needle biopsy and ancillary studies are necessary if diagnosis will change management.

Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma: An International Multi-Institutional Analysis.

OBJECTIVES: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM. METHODS: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions. RESULTS: Histologic subtype was concordant in 81% of cases (κ = 0.58). When compared with resection specimens, epithelioid morphology at biopsy had a positive predictive value (PPV) of 78.9% and a negative predictive value (NPV) of 93.5%; sarcomatoid morphology showed high PPV (92.9%) and NPV (99.3%), and biphasic morphology PPV was 89.7% and NPV was 79.7%. Agreement of the percentage of epithelioid morphology was fair (κ = 0.27). Nuclear grade and necrosis were concordant in 75% (κ = 0.59) and 81% (κ = 0.53) of cases, respectively. Nuclear grade showed moderate (κ = 0.53) and substantial (κ = 0.67) agreement from patients with and without neoadjuvant therapy, respectively, and necrosis showed moderate (κ = 0.47 and κ = 0.60) agreement, respectively, in the same subsets of paired specimens. CONCLUSIONS: Paired biopsy-resection specimens from pleural MM show overall moderate agreement in pathologic parameters. These findings may help guide postbiopsy management and triage of patients with MM.

Eosinophilic Renal Cell Tumors With a TSC and MTOR Gene Mutations Are Morphologically and Immunohistochemically Heterogenous: Clinicopathologic and Molecular Study.

Eosinophilic renal neoplasms have a wide spectrum of histologic presentations, and several studies have demonstrated a subtype of renal cell carcinomas (RCCs) associated with the tuberous sclerosis complex (TSC)/mammalian target of rapamycin pathway. A review of our institutional archives led to the identification of 18 cases of renal eosinophilic tumors with unusual morphology. Immunohistochemical analysis demonstrated that these could be separated into 3 groups: group 1 had solid architecture and morphology similar to chromophobe RCC but was negative for CK20 and vimentin, and had weak focal staining for CK7 and P504S; group 2 had solid architecture and morphology similar to either renal oncocytoma or chromophobe RCC, eosinophilic variant and had diffuse staining of CK7 and P504S, absent to weak staining of CK20, and negative staining for vimentin; and group 3 had solid, cystic and papillary architecture and was negative for CK7, except for 1 case, along with moderate to strong staining of CK20, P504S, and vimentin. The cases were then sent for next-generation sequencing to determine whether molecular pathogenic variants were present. In group 1, all 3 cases had mutations in TSC2. In group 2, pathogenic variants were identified in 3 genes: TSC1, TSC2, and MTOR. In group 3, genetic alterations and pathogenic variants were identified in TSC1 and TSC2. Our results support TSC/MTOR-associated neoplasms as a distinct group that exhibits heterogenous morphology and immunohistochemical staining.

Promoting Quality Face-to-Face Communication during Ophthalmology Encounters in the Electronic Health Record Era.

OBJECTIVE: To evaluate informatics-enabled quality improvement (QI) strategies for promoting time spent on face-to-face communication between ophthalmologists and patients. METHODS: This prospective study involved deploying QI strategies during implementation of an enterprise-wide vendor electronic health record (EHR) in an outpatient academic ophthalmology department. Strategies included developing single sign-on capabilities, activating mobile- and tablet-based applications, EHR personalization training, creating novel workflows for team-based orders, and promoting problem-based charting to reduce documentation burden. Timing data were collected during 648 outpatient encounters. Outcomes included total time spent by the attending ophthalmologist on the patient, time spent on documentation, time spent on examination, and time spent talking with the patient. Metrics related to documentation efficiency, use of personalization features, use of team-based orders, and note length were also measured from the EHR efficiency portal and compared with averages for ophthalmologists nationwide using the same EHR. RESULTS: Time spent on exclusive face-to-face communication with patients initially decreased with EHR implementation (2.9 to 2.3 minutes, p = 0.005) but returned to the paper baseline by 6 months (2.8 minutes, p = 0.99). Observed participants outperformed national averages of ophthalmologists using the same vendor system on documentation time per appointment, number of customized note templates, number of customized order lists, utilization of team-based orders, note length, and time spent after-hours on EHR use. CONCLUSION: Informatics-enabled QI interventions can promote patient-centeredness and face-to-face communication in high-volume outpatient ophthalmology encounters. By employing an array of interventions, time spent exclusively talking with the patient returned to levels equivalent to paper charts by 6 months after EHR implementation. This was achieved without requiring EHR redesign, use of scribes, or excessive after-hours work. Documentation efficiency can be achieved using interventions promoting personalization and team-based workflows. Given their efficacy in preserving face-to-face physician-patient interactions, these strategies may help alleviate risk of physician burnout.

Increased Lung Weights in Drug-related Fatalities.

This study is of autopsy data for potential validation as to whether increased weights of the lungs support toxic effects of drugs as the cause of death. This retrospective study compared data from 133 deaths resulting from the toxic effects of drugs with previously reported normal lung weights (Toxicol Mech Methods, 22, 2012, 159; Am J Forensic Med Pathol 33, 2012, 368). The lung weights and their standard errors were used in a two-sample independent t-test comparing the average drug-related death weight to the average control weights. To account for multiple comparisons, a Bonferroni-adjusted alpha level of 0.0125 was used. We are 98.75% confident that the mean right lung weight for female drug-related deaths is between 227 and 377 g greater than the mean right lung weight for female non-drug-related deaths. We are 98.75% confident that the mean right lung weight for male drug-related deaths is between 245 and 378 g greater than the mean right lung weight for male non-drug-related deaths.