Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.

Evaluation and management of complications from synthetic mesh after pelvic reconstructive surgery: a multicenter study.

OBJECTIVE: The purpose of this study was to describe the evaluation and management of synthetic mesh-related complications after surgery for stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP). STUDY DESIGN: We conducted a multicenter, retrospective analysis of women who attended 4 US tertiary referral centers for evaluation of mesh-related complications after surgery for SUI and/or POP from January 2006 to December 2010. Demographic, clinical, and surgical data were abstracted from the medical record, and complications were classified according to the Expanded Accordion Severity Classification. RESULTS: Three hundred forty-seven patients sought management of synthetic mesh-related complications over the study period. Index surgeries were performed for the following indications: SUI (sling only), 49.9%; POP (transvaginal mesh [TVM] or sacrocolpopexy only), 25.6%; and SUI + POP (sling + TVM or sacrocolpopexy), 24.2%. Median time to evaluation was 5.8 months (range, 0-65.2). Thirty percent of the patients had dyspareunia; 42.7% of the patients had mesh erosion; and 34.6% of the patients had pelvic pain. Seventy-seven percent of the patients had a grade 3 or 4 (severe) complication. Patients with TVM or sacrocolpopexy were more likely to have mesh erosion and vaginal symptoms compared with sling only. The median number of treatments for mesh complications was 2 (range, 1-9); 60% of the women required ≥2 interventions. Initial treatment intervention was surgical for 49% of subjects. Of those treatments that initially were managed nonsurgically, 59.3% went on to surgical intervention. CONCLUSION: Most of the women who seek management of synthetic mesh complication after POP or SUI surgery have severe complications that require surgical intervention; a significant proportion require >1 surgical procedure. The pattern of complaints differs by index procedure.

The "Pathology Passport": a redesign of the pathology elective experience to enhance medical student engagement and understanding of pathology as a clinical practice.

Given the trend of condensed preclinical curricula in medical schools nationwide, creating meaningful pathology learning experiences within the clinical and post-clinical curricula is important to both enhance student understanding of how pathology integrates into daily healthcare delivery and spark potential career interest in the field. While pathology electives are a common modality for medical students to explore pathology, they frequently render students passive observers of daily clinical workflows (often in grossing and sign-out rooms of surgical pathology). This can have a negative impact on student engagement with their pathology clinical teams and on their satisfaction with the pathology elective experience. As such, we aim to describe our institutional experience in creating a new pathology elective structure, the "Pathology Passport," which leverages intentional student engagement with existing pathology workflows and introduces a means of criterion-based grading. Data collected from student pre- and post-elective surveys demonstrate the elective's positive impact on students' perceived understanding of pathology and their overall learning experience. We hope that our resources can be leveraged at other institutions and even other non-pathology clerkship/elective rotations to promote active engagement of students in clinical workflows while providing clear expectations for grading.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Interrater reliability of the International Continence Society and International Urogynecological Association (ICS/IUGA) classification system for mesh-related complications.

OBJECTIVE: We sought to assess interrater reliability of the International Continence Society (ICS)/International Urogynecological Association (IUGA) classification system of vaginal mesh-related complications and compare this with several other available complication classification systems. STUDY DESIGN: This was a retrospective analysis of mesh-related complications in patients presenting after pelvic organ prolapse or incontinence surgery. The complications were classified by 2 independent reviewers using the ICS/IUGA classification system as well as 3 other available classification systems. Interrater reliability was assessed using percent agreement and the weighted κ statistic. RESULTS: The ICS/IUGA mesh complication classification system was found to have poor interrater reliability (κ = 0.15-0.78). The other systems yielded a κ that ranged from 0.18-0.60, but were too general or could only be applied to 68% of the complications. CONCLUSION: The complexity of the ICS/IUGA mesh complication system, the large number of categories, and lack of clarity likely contribute to its poor interrater reliability.

Small bowel obstruction after hysterectomy to treat benign disease.

STUDY OBJECTIVE: To estimate the incidence of small bowel obstruction (SBO) after hysterectomy performed because of benign indications and to compare the incidence of SBO after laparoscopic, vaginal, and abdominal hysterectomy. DESIGN: Single-center retrospective analysis of all hysterectomies performed to treat benign disease over 9 years (Canadian Task Force classification II-2). SETTING: University-affiliated tertiary medical center. PATIENTS: The study included 3229 women who underwent hysterectomy performed because of benign indications. INTERVENTIONS: International Classification of Diseases, 9th revision, codes were applied to eligible patients' medical records to identify those who potentially had an SBO. Again, the electronic medical record was reviewed to confirm the occurrence of SBO. The Fisher exact test was used to evaluate the relationship between SBO and categorical variables, and the Wilcoxon rank sum test was performed to evaluate the relationship between SBO and continuous variables. MEASUREMENTS AND MAIN RESULTS: During the 9-year study, 3229 women with benign disease underwent hysterectomy: 38.3% abdominal, 39.3% vaginal, and 22.3% laparoscopic. Seventeen of 3229 women (0.53%; 95% confidence interval, 0.32-0.86) who underwent hysterectomy were identified as having an SBO. Among hysterectomy types, the incidence of SBO was not statistically significant for abdominal hysterectomy (9 of 17), vaginal hysterectomy (5 of 17), or laparoscopic hysterectomy (3 of 17) (p = .58). There were no differences in demographic data between patients with and without SBO. Incidence rates for SBO were calculated on the basis of hysterectomy route. CONCLUSION: The incidence of SBO after hysterectomy performed because of benign indications is low. The hysterectomy route does not seem to affect risk of SBO.

Analyzing somatosensory axon projections with the sensory neuron-specific Advillin gene.

Peripheral sensory neurons detect diverse physical stimuli and transmit the information into the CNS. At present, the genetic tools for specifically studying the development, plasticity, and regeneration of the sensory axon projections are limited. We found that the gene encoding Advillin, an actin binding protein that belongs to the gelsolin superfamily, is expressed almost exclusively in peripheral sensory neurons. We next generated a line of knock-in mice in which the start codon of the Advillin is replaced by the gene encoding human placenta alkaline phosphatase (Avil-hPLAP mice). In heterozygous Avil-hPLAP mice, sensory axons, the exquisite sensory endings, as well as the fine central axonal collaterals can be clearly visualized with a simple alkaline phosphatase staining. Using this mouse line, we found that the development of peripheral target innervation and sensory ending formation is an ordered process with specific timing depending on sensory modalities. This is also true for the in-growth of central axonal collaterals into the brainstem and the spinal cord. Our results demonstrate that Avil-hPLAP mouse is a valuable tool for specifically studying peripheral sensory neurons. Functionally, we found that the regenerative axon growth of Advillin-null sensory neurons is significantly shortened and that deletion of Advillin reduces the plasticity of whisker-related barrelettes patterns in the hindbrain.

Early Stage HER2-Positive Breast Cancers Not Achieving a pCR From Neoadjuvant Trastuzumab- or Pertuzumab-Based Regimens Have an Immunosuppressive Phenotype.

BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+, CD8+, FoxP3+, and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor ß (TCRß) rearrangements and TCRß clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens. MATERIALS AND METHODS: Thirty pre- and post-neoadjuvant TCH (n = 4) or TCHP (n = 26) breast cancer tissues were identified. TILs were quantified manually using hematoxylin and eosin. CD4, CD8, FoxP3, and PD-L1 were stained using IHC. TCRß was evaluated using NGS. Immune infiltrates were compared between pCR and non-pCR groups using the Wilcoxon rank sum test. RESULTS: A pCR occurred in 15 (n = 15; 50%) cancers (TCH n = 2; TCHP, n = 13). Pretreatment TILs, CD4+, CD8+, FoxP3+, and PD-L1+ cells were not associated with response (P = .42, P = .55, P = .19, P = .66, P = .87, respectively. Pretreatment productive TCRß and TCRß clonality did not predict response, P = .84 and P = .40, respectively). However, post-treatment CD4+ and FoxP3+ cells (T-regulatory cells) were elevated in the non-pCR cohort (P = .042 and P = .082, respectively). CONCLUSION: An increase in regulatory T cells in non-pCR tissues suggests the development of an immunosuppressive phenotype. Further investigation in a larger cohort of samples is warranted to validate these findings.

Number bias for the discrimination of large visual sets in infancy.

This brief report attempts to resolve the claim that infants preferentially attend to continuous variables over number [e.g. Psychol. Sci. 10 (1999) 408; Cognit. Psychol.44 (2002) 33] with the finding that when continuous variables are controlled, infants as young as 6-months of age discriminate large numerical values [e.g. Psychol. Sci. 14 (2003) 396; Cognition 89 (2003) B15; Cognition 74 (2000) B1]. In two parallel experiments, we compare 6-month-old infants' ability to discriminate number and ignore continuous variables with their ability to form a representation of a cumulative surface area and ignore number. We find that infants discriminate a 2-fold change in number but fail to discriminate a 2-fold change in cumulative surface area. The results point to a more complicated relationship between discrete and continuous dimensions than implied by previous literature.