PATHOLOGY UCMS

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Diagnostic and Prognostic Information

Obtained on Fine-Needle Aspirates of

Primary Neuroblastic Tumors

Proposal for a Cytology Prognostic Score

Klijanienko J et al.

CRITICAL REVIEW by Vaibhav Girotra

This article is full of flaws. I m just pointing out a few of them:

1) The author should have made it clear whether 138 patients were diagnosed on clinical or radiological criteria and if clinical what exactly is the clinical criteria for diagnosis of neuroblastic tumours?

2) The exclusion criteria of 9 patients in the very first paragraph of materials and method is not clear :

6 patients were excluded because they had no MYCN data available- what does that mean , MYCN analysis is supposed to be done by author himself n now he is blaming patients for not having MYCN data with them(NOTE: in this study the author has done MYCN amplification on patients suspected of neuroblastic tumours clinically and radiologically. So the patients do not have MYCN data available with them already).

2 patients had ganglioneuromas with no genomic analysis – again the meaning is not clear as he has taken other cases of ganglioneuromas in his study and with no genomic analysis – only he knows what does it mean..

1 patient had cytological material insufficient for analysis- is understandable but after reading these lines again and again, I came to the conclusion that all 9 patients were excluded only because the cytological material was insufficient for analysis…that’s might be what he wanted to convey…

3) Now , clinicaliy 138 were diagnosed as neuroblastic tumours , radiologically 118 as primary neuroblastic tumours and MIBG showed 70 with metastatic foci but they have nowhere mentioned whether those 70 contained the remaining 20 (138-118) or not.

4) Further , FNA samples of 127 primary tumours was done under ultrasound guidance –from where does this figure of 127 came –only the author knows.

5) Core needle biopsy was performed on how many tumors has not been mentioned earlier and it appeared as if it was performed on all tumors.

6) The author has mentioned many results under materials and methods.

7) The aurthor switches from 129 to 138 patients as per his convenience- this adds to the confusion.

8) Later secret was disclosed that core needle biopsies were performed only on 63 of 138 case and so histo-cyto correlation was done in only half the cases and another 43 specimens were diagnosed after chemotherapy – which was of no use and 31 cases were not analysed histologically which again makes it 63+43+31=137 not 138.

9) Flowcytometric analysis was done only on 107 samples but reasons for not doing it on other samples is not specified.

10)Samples with <2×10⁶ cells were used for MYCN amplification and with 2 to 4 ×10⁶ cells were used for array CGH but MYCN was done on all 129 samples and array CGH was done on all samples which were not MYCN amplified i.e. 94 samples-adding to the confusion . Actually he should have written that array CGH was additionally done on samples with 2 to 4×10⁶ cells.

11) In the results in MKI section , he has mentioned that complete diagnostic and prognostic data were obtained on histology preparation in 52% cases but in the discussion he has just reversed the statement by putting not in between the above mentioned line.

12) In the results, he has mentioned that 27(77%) tumors demonstrated no differentiating or mature cells i.e.score 3 but in the table has shown it against the score 1 similarly he has wrongly written the figure for non-amplified tumors.

Vaibhav Girotra

CAVEAT: The following document attempts to outline a proposal for conduct of journal clubs in the department of Pathology, UCMS & GTBH. This is an evolving document, in its present state - far from complete. It is being circulated for your views on content, and feasibility. Your ideas are welcome; all attempts will be made to incorporate your valuable suggestions.

Background: Internationally, the conduct of Journal Clubs is undergoing a paradigm shift. The classical model of William Osler evolved when access to limited journals was restricted to a fortunate few; the need of the era was to disseminate information to the medical fraternity. In these days of “evidence based medicine”, and the explosion in technology, there is an excess of information; the problem is how to handle the overload, make sense of it (critical review), and use it for decision making.

Teaching with technology is a rapidly emerging area in science. Self-study is promoted as a major component of post-graduate education. Competence based learning, and the acquisition of skill sets underlie this proposal for conduct of the journal club.

A PROPOSAL FOR CONDUCT OF JOURNAL CLUBS AND SUBJECT SEMINARS IN THE DEPARTMENT OF PATHOLOGY, UCMS & GTBH

As currently conducted, the ostensible objective of the Journal Club (JC), is to inform the participants about published papers from the recent literature.

Current practice requires the presenter to

1. Select articles of interest

2. Make a presentation at the JC

Often, these skills are poorly developed and the exercise is reduced to a monotonous reading of the full text of articles from power-point slides.

To widen the scope of the journal clubs, and to provide a scaffolding for acquisition of skills, the following objectives are proposed:

AIM & OBJECTIVES OF JOURNAL CLUB

AIM: To promote an understanding of the basics of “Evidence Based Medicine”

OBJECTIVES:

1. Dissemination of information about exciting, new papers published in the medical literature

2. Acquisition of the following skills for residents (PG):

1. Searching the literature

2. Determining trends in published papers in an area of interest

3. Keeping abreast with recent advances in research

4. Critical review of published research

5. Creating/ Editing a Wiki

THE PROPOSAL

I. AN ON-LINE JOURNAL CLUB

To achieve objective 1 (mode: self-learning) Shift to an on-line journal club format. This is expected enable / encourage participants to read and respond to selected full-text articles at a time and place of their choosing.

To facilitate communication a departmental website, and a closed Google-group will be set up. Th SR posted to “class” may be required to monitor activity on these forums.

PG requirements for successful participation-

• In their 3 years of training, each PG will be required to post:

1 article in the 1st year

2 articles in the 2nd year

3 articles in the third year

(total of 84 articles/year)

• Each article must be accompanied by the PG’s review, not exceeding 10 sentences in a structured format.

Format (minimum requirements):

1. Reason for selecting this article

2. The research question (statement of)

3. Define the PICO (Population, Intervention, Controls, & Outcome) elements of the study

4. Study design (Descriptive/Analytical). If descriptive, sample survey/case series/census. If analytical, observational/experimental. If observational, cross sectional/prospective/retrospective etc.

5. One methodological strength of the manuscript

6. One methodological defect/shortcoming/flaw

Responses to the following:

1. What was original in the study?

2. Who is the study about? (was the study population clearly defined?)

3. Was the design sensible? (Why did you think it was appropriate to answer the research question?)

4. How was systematic bias avoided or minimized? (Comment on selection of inclusion and exclusion criteria)

5. Was assessment blind?

6. Were preliminary statistical questions addressed?

7. Limitations of the study

• The PGs will be assigned mentors/moderators to supervise choice of articles and write-up of the review.

• After approval by the supervisor, the article will be up-loaded onto the departmental website (PathologyUCMS.yolasite.com, in preparation)

Note: For articles in the public domain ( free, full text, open access) a link may be provided with the PG’s critique uploaded as a text file. For journal articles where the full text is not accessible through the college computers, a scanned copy of the article may be e- mailed to all participants. Since these will be dispatched as individual e-mails, there will be no infringement of copyright.

PG requirements for successful completion:

Each 1st year PG must post a response to at least 2 articles in a year. (All responses must be supported by at least one reference.) Similarly,

2nd year PG –must respond to at least 5 articles

3rd year PG – must respond to at least 10 articles

The faculty and SRs are encouraged to contribute.

ESSENTIAL READING

To achieve objective 1 the participants may be encouraged to read from the following two resources:

• Greenhalgh T. How to read a paper. The basics of evidence based medicine. BMJ books (publishers)

The e- copy of this book can be obtained from Divya Bansal, 2nd year PG, or downloaded from the net (free downloads are available).

• Guyatt G .et.al-A user’s guide to the medical literature. JAMA series. List available from <www.umdnj.edu/idsweb/shared/jama_users_guides.htm> The UCMS library subscribes to JAMA. The articles you need can be found in the stacks.

To disseminate information about research work in the department all faculty and residents may encouraged to post their own published work to the JC.

II. FACE TO FACE JOURNAL CLUB (THE “RU-BA-RU” JC)

(Note: This exercise incorporates “subject seminars” currently conducted on Mondays)

Objectives:

To demonstrate the basics of:

1. Searching the literature (I year)

2. Determining trends in published papers in an area of interest (II year)

3. Critical review of published research (III year)

Skills to be acquired: a) how to perform a good electronic search of the published literature; b) how a Cochrane review is done; c) how to extend recent advances; write a “letter to the editor in response to a published article; edit / start a wiki.

1. Electronic search of the literature

Recommended background exercises:

• Participants are encouraged to self-administer the complete free on-line Pub-Med tutorial on searching the literature. It takes about 4 hours from start to finish for the average user; and can be done in segments at a time of one's choosing.

• How Cochrane reviews work: take a tour and read a review at

http://www.thecochranelibrary.com/view/0/index.html By an extra-ordinary stroke of fore-sight and wisdom of our planners, the Cochrane library is freely accessible to users from India.

PG requirements for successful participation

I year PG:

Shall present 1 JC per year

• Skills to be demonstrated: ability to effectively search electronic databases of Medical literature such as Med-line, The Cochrane library, IndMed, Google scholar, and others.

The assigned moderator/mentor shall help the PG define an area for search. This may be:

• A problem encountered in reporting/teaching

• An area of interest

• An area where rapid recent advances in understanding have occurred

• Other (specify)

The presentation at the JC shall focus on the literature search providing answers to the following questions (incomplete list):

1. How the keywords were selected?

2. Which databases were searched?

3. How they were searched?

4. What were the results of the search?

5. How was the search narrowed/focused?

6. Why the search was considered relevant?

7. How could a subsequent search be improved?

1. 
   

2. IIyear PG:

3. shall present 2 JC in the year

4. Skills to be demonstrated- critical review of trends in emerging literature

The assigned mentor/moderator shall:

Help the PG define a broad area of research where there has been substantial change in understanding (e.g. PSA in prostate carcinoma, Barrett’s esophagus). The topic may be drawn from:

• A problem encountered in reporting/teaching

• An area of interest

• Other (specify)

The presentation at the JC shall focus on:

1. Trends in the literature in the minimum last 10 years (more, if relevant)

2. Identification of how and why previously held beliefs/practices changed

3. The current status of research in this area

Note: A I and II year PG may be assigned to a common moderator who may assign a common topic. The two could present the two aspects on the same topic in a single JC. (Please examine the possibility of including a III year PG in the group)

III year PG:

shall present 3 JC a year

Mode 1. Skills to be demonstrated: Ability to search for, and present recent advances that may have occurred following publication of a review in a journal or book.

Published reviews of recent advances are often referenced to between one to two years prior to the year of publication. (e.g. a review of the literature on prostate cancer published in 2012 may include references up to 2010, or sometimes, 2011).

The III year PG may be required to search the literature dating from the latest in the published review, to current. The presentation at the JC may consist of a review of the publications / advancements in the field since the published review.

Mode2. Skills to be demonstrated: Ability to write a “letter to the editor” in response to published articles.

The assigned mentor / moderator may supervise the PG in performing a literature search and critical evaluation of a published paper with a view to formulating a response in a “letter to the editor”.

[Note: for the beginner, it may be profitable to identify articles with simple methodology]

The response may utilize several strategies , some of which may be:

1. Support / contest Methodology of the paper with references

2. Support / contest the conclusions of the paper with additional data or references

3. Support / contest analysis of the authors' data, or view it from a different perspective

4. Support / contest references that may be incompletely / incorrectly cited

5. Support / contest authors' claims and assumptions

Desired outcome: when we write our own papers, awareness of the pitfalls may better equip us to prevent them. Each PG may be encouraged to submit at least 3 letters in the III year in the hope that at least one may be published. In appreciation, published letters will be up-loaded to the departmental web-site.

Mode 3. Skill to be demonstrated: Ability to edit / start a Wiki

Wikipedia, a community built site that has become the largest (on-line) encyclopedia, has surpassed the iconic Encyclopedia Britannica in scope, size, and accuracy of information. The beauty, and strength, of Wikipedia, some may erroneously think it is a flaw, is that anyone can start or edit a Wiki. Wikipedia is often the top result in any internet search for information.

Edit a wiki or start one, and etch your name in the pages of history. It is the knowledge base of the future. Learn more at www.en.wikipedia.org.