This is an abstract from the January 15, 2014 issue of American Journal of Respiratory and Critical Care Medicino that I just re-discovered this week and relates to one of my ongoing (and unrequited) obsession with epithelial-mesenchymal transition in lung cancer.
It appears that there are five major EMT regulatory genes (SNAI1, SLUG, ZEB1, ZEB2, and TWIST1) involved in EMT. But--the relative contribution and importance of each of these genes in the development and progression of non-small cell lung cancer is not clear.
This article adds another layer of complexity and I post it (rather belatedly) now because I find in it such an intriguing finding that a variant protein could have functional consequences that are observable as a clinical outcome with regard to COPD and NSCLC. Moreover, this variant was discovered to attenuate Snai1’s ability to specifically up-regulate mesenchymal biomarkers (i.e., fibronectin and vimentin) expression, and to promote EMT-like changes, including morphologic changes, cell migration, and invasion.
The Hemovigilance Module of the CDC's National Healthcare Safety Network has an open access Web application for assessing transfusion reactions that is available at www.trddx.com. This tool is based on the NHSN Hemovigilance Module Surveillance Protocol (itself an essential resource). This would be especially useful for general pathologists who infrequently have to assess transfusion reactions. This is also a wonderful educational tool for pathology residents and internal medicine residents rotating through hematology-oncology services.
Other features include a table showing which diagnoses have been ruled-in, excluded or not yet tested; optional questions for assigning severity and imputability for each diagnosis; a written summary with supporting evidence of which diagnoses were established as well as those that were excluded. Finally, the user has the ability to email the written summary as a PDF document.
I've really come to rely on this as a final check on myself and a first reference to guide pathology residents through the evaluation of a transfusion reaction.
The June 2014 issue of American Journal of Pathology has this state-of-the-art review, based on a recent NHBLI workshop, of the various attributes of the lung extracellular matrix and its role in normal lung and in the development of IPF.
This is an "open access' (FREE) article and you can get CME for it too!
Here's a choice figure that nicely summarizes the biochemical and mechanical interactions between the fibroblast and the ECM:
The June 2014 issue of Journal of Thoracic Oncology (abstract) features a thorough study of major known driver mutations (EGFR, KRAS, ERBB2, BRAF, PIK3CA, AKT1, RET, and ALK) in a series of 76 patients from Fudan University Shanghai Cancer Center with resected adenosquamous lung carcinoma (AdSqLC) by Wang et al. and compared this group with a group of 646 patients with resected adenocarcinoma (ADC) during the same study period. This is a nifty paper that will serve well as a useful contemporary reference when you next encounter a patient with adenosquamous lung carcinoma.
From their "Table 1" data, it is of note that they found significantly higher smokers in AdSqLC versus ADC.
Known mutant kinases were demonstrated in 57% (43/76) patients. EGFR mutations were the most common found (32%, 24/76) but were significantly lower compared to the ADC "control" group. EGFR mutation was significantly higher in never smokers compared to smokers as expected, but it is notable that the frequency of EGFR mutation was higher in glandular dominant AdSqLC than squamous dominant AdSqLC. Other gene mutations were similar to those found in ADC. While the frequency of driver mutations was similar between "classical" AdSqLC and poorly-differentiated ADC, the frequency of RET and ALK fusion genes was higher in solid growth glandular component-predominant AdSqLC versus classical AdSqLC.
Microdissection of 13 tumors showed the same mutation in both glandular and squamous components in 9 tumors but 4 of 13 cases showed mutations (KRAS-2, HER2, EGFR) only in the glandular component.
Survival data including 58 AdSqLC and 246 ADC patients showed no significant difference in relapse-free survival between classical AdSqLC, poorly-differentiated ADC, and solid-predominant AdSqLC. Both classical- and solid-types AdSqLC showed worse overall survival compared to well- and moderately-differentiated ADC.
This is a follow-up to my recent post on Herodotus describing 6th-century BC Babylonians relying on "social networking" for health care.
In Book 2 of The Histories, Herodotus comments on Egyptian medicine (ca. 500 BC). In opposition to Babylonian health care, Herodotus notes that in Egypt each physicianjust treats one illness. He comments dryly that "Doctors are everywhere."
Matsumura and colleagues from the National Cancer Center Hospital East in Chiba, Japan recently reported in the Journal of Thoracic Oncology (abstract) their study of the location of lymphatic permeation in relation to the tumor and the effect on outcome.
Since 2001, this group has been classifying lymphatic permeation in patients with resected NSCLC into 3 catagories: no lymphatic permeation (ly0), intratumoral permeation (ly1), and extratumoral permeation (ly2). This is a follow-up to a previous study reported in 2007 that found that NSCLC patients with ly2 developed more recurrence than patients with ly1--but long-term follow-up was short.
A couple of practical notes from their methods--
All cut surfaces containing the main tumor were submitted for histology. Victoria blue/van Gieson stain was performed on all tumor sections to evaluate for vascular invasion, lymphatic invasion, and pleural invasion and lymphatic invasion was confirmed by immunohistochemical staining for podoplanin (D2-40).
One thing that makes this study valuable is that 67% of patients included in this study were pT1, although it is noted that the median tumor size was 2.8 cm. Another is that median follow-up was 85 months.
5-year overall survival (5yOS) was significantly worse for ly2 (34%) versus ly0 (75%) and ly1 (63%). Both recurrence-free survival (RFS) and cancer-specific survival were also similarly worse between ly2 and ly0 and ly1 groups. Similar significant results in 5yOS were also observed when analyzed by pStage I: ly0--83%, ly1--79%, ly2--47%. But, unexpectedly (to me, anyhow), ly2 was still a significant prognostic factor in pStage II and pStageIII.
By multivariate analysis, worse 5yOS was associated with age ≥ 70, pT2-4, pN1-2, pleural invasion, intrapulmonary metastasis, vascular invasion, and ly2. Notably, ly2 had a higher HR (1.73) than pT2-4 (1.37), pN1-2 (1.63), and VPI (1.62).
The authors show that extratumoral lymphatic permeation has a marked negative prognostic impact on the recurrence-free period, disease-free survival, and overall survival. They opine that this feature should be evaluated for every case and included in the lung cancer staging system.
Thoughtful post regarding the relationship between blogging about academic articles and actual reading of the same.
When I blog about an article it is usually to call attention to an interesting, important, and provocative article that the average pathologist may not have seen from the usual list of journals or have had time to read. I try to give more about the article than one would get from the abstract and why the article may merit further review. It is impossible to thoroughly read even a small selection of the articles published every week/month that would be useful in one's daily work. My goal is to get interesting articles on my/the reader's conscience to get back to later.
I decided to tackle The Histories by Herodotus this summer, after having enjoyed reading Thucydides' The Peloponnesian War last summer, and came across a fascinating description of Babylonian medicine by Herodotus in Book 1 that I connected with social networking via the Internet. In contrast to Thucydides, Herodotus, called "the father of history" by Cicero, has many little asides and colorful and curious descriptions of the people, places, and culture of the late 6th/early 5th century eastern Mediterranean and Near East world, his "Oikoumene" or inhabited world.
At 1.197, Herodotus states that the Babylonians did not use physicians, but instead took their sick into the public square and allowed people who either suffered the same illness or saw someone else who did to advise the sick person. Further, it was not considered acceptable by the Babylonians to just pass by a sick person or not ask what disease he had!
I imagine such a sick man or woman being bombarded and overwhelmed with all kinds of diagnoses and advice about how to rid themselves of whatever was ailing them--kind of like when patients go online and search for their "disease," signs, symptoms, lab results, etc., right?! I see a similar phenomenon with the myriad groups focused on patients with different syndromes and diseases. I'm certainly not disparaging these at all--they are extremely useful to patients, families, and caregivers and serve to not only a resources for information but support and advocacy. I just find it interesting and fascinating that an ancient group of people did pretty much the same thing over 2,500 years ago!
I thought this would be a nice re-entry into more regular blogging again after a bit of hiatus.
Hope to post more on a plethora of recent articles on lung pathology, cancer biology, and transfusion medicine soon.