Drug of the month

A Question of Aesthetics

Take a look at the pictures shown below :

Which one do you think is a picture of  a "normal" street?

Now, take a look at the pictures of the uterine cervix below :

Which one do you think is "normal"?

If you thought the 1st street picture (above) is normal, I'd agree with you. If you thought that the cervix on the top is normal. Well, that's good! You are already half the way to becoming a colposcopist. The other half of becoming a colposcopist probably is co-ordinating with your pathologist!

I shall proceed to relate to you the reason for making the last statement. The colpophoto of the first cervix, is one of a 50 year old lady in whom smears have on and off since the year 2003 shown 'LSIL'(low-grade squamous intraepithelial lesion). Her PCR of a cervical swab for HPV DNA even showed positive in 2009. In between,  her Pap smear was normal. Colposcopically, the squamo-columnar junction was within the endocervix, and so the colposcopy was deemed inadequate. But consider, the cervix looked the same in 2009, as it did in 2003. Her PV examinations, and sonography of the pelvis were absolutely normal in 2003 as they were in 2009 (no bulkiness of the cervix, if you presume a growth was occurring in the endocervix).

In contrast, the second cervix, is one of a 30 year old lady who had a bad erosion during her second pregnancy. Her Pap smear following delivery (3 months after) was labeled as 'chronic cervicitis'. 4 years later, the erosion had become even more florid and appeared as shown above. Have a look at the same cervix stained with acetic acid :

Biopsy of the acetowhite area showed 'Polypoidal endocervical hyperplasia'. Now, how do you deal with such a pathology?

I have the following comments to make :

1. If  we are to understand that dysplasias (LSIL, HSIL, CIN, call it what you may!) are precursors of malignancy, they should progressively look worse, as the years go by. (I hope everyone agrees with me!) In the case of cervix no. 1, no change has occurred over 6 years, so I refuse to be alarmed in her case, inspite of the bogie of '+ve for HPV DNA' and LSIL being applied to her.
   
   Whereas, in the case of cervix no. 2, the erosion has worsened over just 4 years, acetowhite areas are seen. This cervix will have to be monitored more closely, inspite of the Pap showing just 'chronic cervicitis' and even a biopsy saying 'Polypoidal endocervical hyperplasia' (which doesn't fall in any accepted system of nomenclature at all). I have already cauterized the suspicious areas.
   
   
2. If I did not have documentation of what the cervix looked in 2003, I would be none the wiser, and unable to opine whether the lesion is going from bad to worse or remaining the same.
   
   So, I recommend to all my gynaecologist friends , try and document what you are seeing, either verbally, or by pictorial representation, or by photography. In the matter of colposcopy, we have video-colposcopes and photographic attachments to colposcopes, by which we can, today, very easily document permanently what the cervix looks like, at any one examination. This will certainly help us to keep our head on our shoulders, and not get 'unhinged' when faced with an odd pathology report. How many photos of your face (identity card) and yourself with family and friends  do you make in a lifetime? I have a sideboard cupboard filled with them! And we can't make the time, or take the expense of one photo of the cervix every 3 years? (Let's say a total of 15 photos over 40 years?)
   
   Would you like to live in a city with streets like the 1st picture? Or, would you like to live in the 2nd picture?  Living in the first picture takes its toll – you have to be vigilant, form 'ALMs' (in Mumbai that means citizen's committees or 'advanced locality management' bodies) take pictures from time to time and see that nothing amiss occurs. Or, you can just not bother, and live in the second picture. Similarly, you can see a cervix, and just ignore it (or worse still - just take a Pap smear without even seeing the cervix!). Or, you can decide to try and describe it, try and map it, take a Pap smear, do a colposcopy, take a colpophoto, try and follow-up. It's a question of aesthetics!

Dr. Milind R. Shah

Tutorials in Colposcopy

Contending with the Normal

Look at the picture below. A picture of a person's lips, magnified just a little. Actually this is pretty much like doing a colposcopy. Imagine that you had to describe and certify the medical condition of this pair of lips. Unfortunately, when, as a doctor, you are asked to opine on a photograph, and issue a written report, the question of whether you will be held medicolegally responsible 'clouds the senses', and one has the tendency to either ask for some further investigation or give a vague answer. This happens especially with the diagnosis of dysplasia, because it is a pre-cancer.

What would you put down on paper?

Let me give you some options :

1. Normal
2. Some shadows around the angles of the mouth. Needs further evaluation.
3. Picture is bad. No comment possible.
4. Frame of a pair of lips. Base of the nose and some part of the neck included. Basic anatomy preserved. Skin over pictured area is smooth. Areas of bleached effect and corresponding shadowing probably attributable to photographic technique and limitations.

Don't you agree that, if you had no more information about the subject in question, it would be difficult to comment on whether the lips in the picture are totally normal or not? But, if I tell you that this picture was part of a picture of a rock star, aged 26 years, who is currently one of the 'Top of the Charts', anyone would spontaneously say that this picture is perfectly normal. The colposcopic case shown here in this tutorial, is somewhat similar.

Look at the colpophotograph below. This lady was referred with a Pap smear saying 'mild dysplasia'.

So, we stain the cervix with acetic acid, and later with iodine (subsequent 2 frames)

What do we see? I have had students and doctors asking if the 5 – 6 o'clock area in the upper frame is not an acetowhite area. And, some asking whether the 12 – 1 o'clock area is not iodine-negative. At this juncture, I would say, 'step back'! Don't get confused with micro-anatomy. Look at the case in totality. Is this woman in the high-risk category for cervical neoplasia? I should tell you here, that this colpophoto is of a 53 year old, singly married, 'fidelous' woman (we need adjectives in today's day and age to indicate that the individual does not have multiple partners, besides specifying that she is married; I hope I don't start a jihad with my infidel, unconventional vocabulary).

We decided to give her a 1 month's course of estrogen cream vaginally, and follow-up with a repeat Pap thereafter. She did so, and the next Pap was absolutely normal. At a post-menopausal age, the number of basal cells in the Pap smear is more than in a normal smear. The nuclei are large, but regular. Still, if the age is not specified to the pathologist, it can result in the pathologist thinking in terms of 'LSIL' or dysplasia. Estrogen cream locally improves the maturation and restores normality to the Pap smear.

The process of neoplastic transformation begins at the squamo-columnar junction. It is therefore important to visualize the s-c junction. Well, the squamo-columnar junction is not seen in this colpophoto, so we actually would have to report that this colposcopy is inadequate. One would therefore ask : Why did we treat as we did (with estrogen cream) instead of asking for further investigation (endocervical curettage/hysteroscopy, etc) or just skirt our responsibility with a report of 'Inadequate colposcopy-refer back to the referring gynaecologist/physician/GP'. Well, as one gets more experienced in clinical practice one comes across situations which, intuitively, one knows the answer to. In a chronically infected cervix, one which has had multiple infections (HPV and otherwise), there is bound to be some sign of an old erosion. The process of the s-c junction retreating into the endocervix would be chequered. The previous Pap smears of the patient would not have been normal. The regular look of the cervix itself is an indication that the sexual history of this patient has been simple (as opposed to 'complex' in a woman with many partners, or whose partner was promiscuous).

Coming back to the picture of the lips! Were we to preserve this picture (even though the picture may not be so good and even if we did not know about the person being a current rock-star!), and have a look at the face 2 years down the line, we would be able to make out if there is any change occurring. This is my contention, and I hope you agree! Similarly, I exhort all those of you, who would do colposcopy, try to produce a colpophoto of the basic unstained cervix, the aceto-stained cervix and the iodine stained cervix, in print, which the patient should keep in her medical record file. When any other gynaecologist months/years down the line examines he/she would have the benefit of comparing with the previous condition of the cervix, and this is where, I believe, half of the value of 'Hard Copy Colposcopy' (again, excuse the unconventional vocabulary, but I think you'll understand) lies.

Let me touch upon the reporting of the 'lips'. If you recognize, and are prepared to admit, most of us write our clinical findings like option a). Some of us are 'doubting types' and would opt for option b). If you notice, there is no way you can fault any of the options. It is obvious that option d) is the most painstaking way to report. Consider what happens as a sequel to reporting in each of the above ways.

In option a), over a long period of time, one would get 'immune' to the grainy quality of the print, and tend to report normality even when the print quality has precluded the diagnosis of a minor 'dysplasia', especially in those cases where there is a lack of correlative information.

In option b), one would be subjecting a whole lot of patients to anxiety and unnecessary further evaluation.

In option c), one would be just condemning the entire procedure, unless the reporting person took the trouble to repeat the photograph (which has cost implications).

In option d), one accepts the current photograph, and has tried to analyze it from various aspects. The first aspect, is the gross anatomy (which can be disturbed in serious disease), the second is the skin contour, which is bound to be affected, as we are concerned about epithelial changes, and lastly the quality of the photograph. This report, enthuses us to preserve this print for future reference. It also keeps us aware of the need for improvement in photographic technique. Were we to preserve this print (as I mentioned before, in spite of its faults), we might, at a later date get some more qualifying information, which would help us 'build a case'. If a similar picture were taken after 3 years, we'd be able to compare and localize an area of change that might lead to the diagnosis of disease. It pays to be painstaking!

This would therefore essentially be a tutorial with the following intention : "Don't imagine a tiger that isn't there!" Remember to step back and take stock of the whole picture when faced with uncertain findings. And don't unnerve the patient with an uncertain posture. Think of what you want to do in the circumstances and advise with aplomb. And remember, if you provide a hard copy picture to the patient, even in the event of a minor slip in diagnosis, the patient always has your hard copy downstream in time, to compare with.

Dr. Milind R. Shah

In this event of pandemic of Swine flu, lot of discussion taking place about Swine flu in pregnancy as well as various drugs used for it.

As pregnant women are susceptible for severe complications as we see in any other viral infections, there is lot of concern about prophylactic use of drugs like Tamiflu during pregnancy. In pregnancy, there is more possibility of dehydration, pneumonia or premature labor as hormonal changes during pregnancy depress the immune system to protect the fetus.

In the event of a pandemic, drugs like Oseltamivir will be used for treatment or prophylaxis in pregnant women, either by choice or because the women don't know they are pregnant.

There is currently no reliable information on effects of this drug on a developing fetus, as we have not faced this problem before this.

The FDA has categorized this drug under the medical category "C". The data collected is insufficient to give a clear picture on the effects of Tamiflu on pregnant women and her developing fetus. As there were no human specimens the initial tests were conducted on rats and later on rabbits. Maternal toxicity was minimal in rats while in rabbit showed slight maternal toxicities. Skeletal abnormalities were observed in the cases where the doses were increased to 500 mg per kg of body weight per day.

A similar study was conducted on rats and rabbits for the effects of Tamiflu in lactating mothers. It was observed that Oseltamivir and Oseltamivir carboxylate are given out in the milk. A similar human study could not be conducted due to the lack of lactating mothers infected by the flu who are willing to contribute towards experimentation.

The conclusion of these studies was "Tamiflu should be prescribed to a pregnant woman only if the case justifies the potential benefit of the fetus."

Tamiflu (Oseltamivir) and Relenza (Zanamivir) are in the same class of drugs. But Tamiflu is a pill and liquid, while Relenza is a powder form that needs to be inhaled.

The main ingredient of the Tamiflu is the Oseltamivir phosphate, which belongs to group neuraminidase inhibitors. It acts by attacking the influenza virus in the body and stops it from spreading inside the body.

Each capsule of the medication contains seventy-five grams of the active drug. Recommended dosage is two capsules orally, one capsule in the morning and one in the evening for five days. For women who have been exposed to the influenza virus and who are taking this medicine as a preventive measure against the flu should take only one capsule in a day for seven days.

The Center for Disease Control and Prevention, (CDC) says that because a test result for the new H1N1, "Swine Flu" flu can take days, Tamiflu should be given to any pregnant patient with flu symptoms combines with likely contact with someone else with Swine Flu. Its known fact that this drug acts only if started early after contracting flu it need to be used despite not being recommended in pregnancy because the benefit of giving Tamiflu outweighs the risk. Simultaneously correction of hydration and treatment of fever with suitable antipyretics and adequate rest doesn't need more emphasis.