Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score (PRGS) in peritoneal metastasis

Context. Subtyping of periampullary adenocarcinoma into intestinal and pancreatobiliary subtypes has emerged as an important prognostic factor with potential therapeutic implications. This distinction on morphology alone is often difficult with significant interobserver variability. Objective. To analyze the usefulness of a panel of immunohistochemistry (IHC) markers as an aid to morphologic subtyping of periampullary adenocarcinoma. Design. A total of 172 periampullary adenocarcinomas were classified morphologically by 3 study pathologists. Interobserver agreement was assessed in each case. Cases were then typed using a predetermined IHC panel (comprising CK7, CK20, MUC1, and CDX2). Results. Morphologically, 66 (38.4%) cases were intestinal, 56 (32.6%) pancreatobiliary, 25 (14.5%) mixed, 16 (9.3%) poorly differentiated, 6 (3.5%) mucinous, and 3 (1.7%) signet ring cell adenocarcinoma. Concordant diagnosis was reached in 138 cases (80.2%) with moderate overall interobserver agreement (κ = 0.47). Concordance was higher in morphologically distinct mucinous (100%; κ = 0.94) and signet ring cell subtypes (100%; κ = 1.0) than in intestinal (84.6%; κ = 0.47) and pancreatobiliary (82.1%; κ = 0.43) types. Concordance was poor for mixed (64%; κ = 0.27) and poorly differentiated (68.8%; κ = 0.76) tumors. IHC subtyped 79 cases (46%) as pancreatobiliary, 73 (42.4%) as intestinal, and was inconclusive in 20 cases (11.6%). IHC helped classify 21 out of 25 (84%) mixed and 10 out of 16 poorly differentiated (62.5%) adenocarcinomas. Combination of histology and IHC classified 161 of the total 172 cases (93.6%). Conclusion. Use of an IHC panel aids in subtyping of periampullary adenocarcinomas, especially in tumors with mixed morphology and poor differentiation.

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386. The Role of Diagnostic Laparoscopy in Detecting Minimal Peritoneal Metastasis in Patients with Pancreatic Cancer Scheduled for Curative Resection

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2012.06.359 ◽

2012 ◽

Vol 38 (9) ◽

pp. 848

Author(s):

R. Lavy ◽

I. Gatot ◽

I. Markun ◽

Z. Shapira ◽

B. Chikman ◽

...

Keyword(s):

Pancreatic Cancer ◽

Peritoneal Metastasis ◽

Curative Resection ◽

Diagnostic Laparoscopy

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Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms222111496 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11496

Author(s):

Lucía Pascual-Antón ◽

Beatriz Cardeñes ◽

Ricardo Sainz de la Cuesta ◽

Lucía González-Cortijo ◽

Manuel López-Cabrera ◽

...

Keyword(s):

Ovarian Cancer ◽

Peritoneal Metastasis ◽

Abdominal Cavity ◽

Mesothelial Cell ◽

Metastatic Niche ◽

Mesenchymal Transition ◽

Disseminated Disease ◽

Carcinoma Associated Fibroblasts ◽

Peritoneal Mesothelial Cell

Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.

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Predictive Value of Pleural Cytology in the Diagnosis of Complicated Parapneumonic Effusions and Empyema Thoracis

Pulmonary Medicine ◽

10.1155/2020/7175451 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

John Ferguson ◽

Michal Kazimir ◽

Michael Gailey ◽

Frank Moore ◽

Earl Schott

Keyword(s):

Logistic Regression ◽

Pleural Fluid ◽

Predictive Value ◽

Interobserver Agreement ◽

Empyema Thoracis ◽

Cytologic Diagnosis ◽

Wilcoxon Rank Sum Test ◽

Sensitivity Specificity ◽

Fluid Cytology

Introduction. Complicated parapneumonic effusions (CPE) are distinguished from uncomplicated parapneumonic effusions (UPE) by the ability to resolve without drainage. Determinants include pleural pH, pleural glucose, and pleural LDH, along with microbiologic cultures. Inflammation mediated by neutrophil chemotactic cytokines leads to fibrinous loculation of an effusion, and the degree of this inflammation may lead to a CPE. One role of the pathologist is to evaluate for the presence of malignancy in a pleural effusion; however, the ability of the pathologist to distinguish a CPE from UPE has not been evaluated. Materials and Methods. A single-center retrospective study was performed on pleural cytology specimens from 137 patients diagnosed with a parapneumonic effusion or empyema over a five-year interval. Pleural cytology was characterized as either uncomplicated or complicated by two pathologists based on cellular composition and the presence or absence of fibrinous exudate in the fluid. Cohen’s kappa was calculated for interobserver agreement. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytologic diagnoses were calculated. Determinants of cytologic accuracy were assessed using Wilcoxon rank sum test, unpaired t-test, and logistic regression. Results. Kappa interobserver agreement between pathologists was 0.753. Pleural fluid cytology sensitivity, specificity, PPV, and NPV for CPE/empyema were 76.0%, 95% CI [65.0, 84.9]; 50%, 95% CI [29.1, 70.9]; 83.3%, 95% CI [76.7, 88.4]; and 38.7%, 95% CI [26.5, 52.5], respectively. The presence of pleural bacteria, elevated pleural LDH, and reduced pleural pH were nonsignificant determinants of cytologic accuracy. Logistic regression was significant for the presence of pleural bacteria (p=0.03) in determining a successful cytologic diagnosis. Conclusion. Pleural cytology adds little value to traditional markers of distinguishing a UPE from CPE. Inflammation on pleural fluid cytology is suggestive of empyema or the presence of pleural fluid bacteria.

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The role of staging laparoscopy in type 4 gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.35 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 35-35

Author(s):

Norihiko Sugisawa ◽

Etsuro Bando ◽

Yuichiro Miki ◽

Rie Makuuchi ◽

Hironobu Goto ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Metastasis ◽

Invasive Procedure ◽

Staging Laparoscopy ◽

Peritoneal Cytology ◽

Clinical Imaging ◽

Surgical Interventions ◽

Peritoneal Lavage Cytology ◽

Positive Peritoneal Cytology

35 Background: In type 4 gastric cancer, the incidence of peritoneal metastasis which was unexpectedly found during surgery was as high as 40 percent. It is very difficult to detect peritoneal metastasis in clinical imaging such as computed tomography or ultrasound before operation. Staging laparoscopy (SL) is considered to be an only minimal invasive procedure to detect peritoneal metastasis. However, the significance of SL had not yet been fully elucidated. The aim of this study is to assess the role of SL in type 4 gastric cancer. Methods: From September 2002 to March 2012, a total of 169 patients with type 4 gastric cancer who were diagnosed as not having distant metastasis in clinical imaging were enrolled in this study. SL was performed for 56 patients, and the other 113 patients underwent open laparotomy (OL) without SL. We retrospectively examined the incidence of peritoneal metastasis and positive peritoneal cytology and treatment courses in patients who underwent SL and OL. Results: In 56 patients undergoing SL, 23 (41%) had peritoneal metastasis and 40 (71%) had positive peritoneal cytology. Similarly, 54 (48%) had peritoneal metastasis and 86 (76%) had positive peritoneal cytology in 113 patients undergoing OL. There were no significant differences of the incidence of peritoneal metastasis and positive peritoneal cytology between the two groups. Subsequent treatments after SL or OL were diverse depends on patients condition and participating clinical trials, however, 17 (32%) in SL group and 13 (12%) in OL group were treated without surgical interventions. There was no morbidity and mortality in both SL group and OL group. In SL group, open surgery was performed soon afterword in 39 patients. Among them, 2 patients was failed to detect peritoneal metastasis by SL. Therefore the accuracy of detecting peritoneal metastasis in SL was 23/25 (92%). Conclusions: In type 4 gastric cancer, the incidence of peritoneal metastasis was around 40% and positive peritoneal lavage cytology was around 70% in both SL and OL. As SL is less invasive than OL, SL appears to be a useful way to detect peritoneal seeding and establish treatment strategy in patients with type 4 gastric cancer.

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Limitations of conventional approaches to identify myocyte nuclei in histologic sections of the heart

AJP Cell Physiology ◽

10.1152/ajpcell.00435.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. C1603-C1609 ◽

Cited By ~ 29

Author(s):

Keng-Leong Ang ◽

Lincoln T. Shenje ◽

Sean Reuter ◽

Mark H. Soonpaa ◽

Michael Rubart ◽

...

Keyword(s):

Confocal Microscopy ◽

Interobserver Agreement ◽

Rare Events ◽

Troponin T ◽

Immune Reactivity ◽

Optical Sectioning ◽

Accurate Identification ◽

Cytoplasmic Proteins ◽

Margin Of Error

Accurate nuclear identification is crucial for distinguishing the role of cardiac myocytes in intrinsic and experimentally induced regenerative growth of the myocardium. Conventional histologic analysis of myocyte nuclei relies on the optical sectioning capabilities of confocal microscopy in conjunction with immunofluorescent labeling of cytoplasmic proteins such as troponin T, and dyes that bind to double-strand DNA to identify nuclei. Using heart sections from transgenic mice in which the cardiomyocyte-restricted α-cardiac myosin heavy chain promoter targeted the expression of nuclear localized β-galactosidase reporter in >99% of myocytes, we systematically compared the fidelity of conventional myocyte nuclear identification using confocal microscopy, with and without the aid of a membrane marker. The values obtained with these assays were then compared with those obtained with anti-β-galactosidase immune reactivity in the same samples. In addition, we also studied the accuracy of anti-GATA4 immunoreactivity for myocyte nuclear identification. Our results demonstrate that, although these strategies are capable of identifying myocyte nuclei, the level of interobserver agreement and margin of error can compromise accurate identification of rare events, such as cardiomyocyte apoptosis and proliferation. Thus these data indicate that morphometric approaches based on segmentation are justified only if the margin of error for measuring the event in question has been predetermined and deemed to be small and uniform. We also illustrate the value of a transgene-based approach to overcome these intrinsic limitations of identifying myocyte nuclei. This latter approach should prove quite useful when measuring rare events.

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