Wednesday, March 30, 2016

Interview with Dr. Nagendra Mishra- Leading IC Specialist in India

Dr. Nagendra Mishra is considered an international expert and a pioneer in India in treating Interstitial Cystitis(IC). He has treated patients and has dedicated years of research in understanding IC. Numerous research papers were published under his credit. He is the founder member of International Painful Bladder Society (IPBS) based in Amsterdam. In 2002 he conducted an international survey on IC along with Jane Meijlink from Netherlands. In this interview he speaks on a wide range of issues involving IC. Dr. Mishra is based in Ahmedabad and also runs an IC support group from his centre in Ahmedabad.

Q) Do you think the awareness about IC is increasing in India?
A) When I was trained in urology some 25 years back it was believed that IC is a disease of western world and does not exist in INDIA. The symptoms of IC are very much similar to tuberculosis and all the patients of IC were being treated as tuberculosis of genitourinary symptoms. However, now the awareness about IC is increasing in INDIA. Awareness amongst Urologists is good but poor amongst Family Physicians, Gynaecologists, General Physicians and Surgeons who see most of these patients first.

Q) When did you first diagnose IC?
A) My tryst with IC started when some of the patients diagnosed as tuberculosis and adequately treated did not respond. I did augmentation cystoplasy in one of these patients for thimble bladder and realized that the patient did not have thick fibrous thimble bladder but some other pathology. This is how I made my first diagnosis of interstitial cystitis I have treated around 900 patients of IC till 2015. In India male to female patient ratio is 2:3. 
Q) What are the symptoms of IC?
A) The symptoms of IC patients are by no means uniform. These symptoms are related to urological, gynecological, gastrointestinal and pelvic floor organs. The hallmark of IC is a triad of pain, frequency and urgency. Pain is the most important symptom. Pain is felt in urethral, genital and /or rectal regions.  Pain may be continuous or related to the micturition cycle. Sometimes patients cannot define the exact location of pain and feel it is situated deep in the pelvis. Some patients mention burning, pressure sensation of urinary discomfort instead of pain. Males may complain of painful ejaculation while women present with dyspareunia.

Frequency more than eight times is considered abnormal. While most of the patients with IC have frequency and urgency, it is not a must. Patients with normal frequency and without urgency can also have IC. Nocturia may or may not be present. In other words, patients can have a variety of different symptom combinations.

Initially a patient may have only one symptom and develop the fully-fledged syndrome over a span of 5 years. IC is a chronic disease, so the above-mentioned symptoms must be present for more than 4 weeks to diagnose IC.

Q) IC is often confused with UTI- your thoughts.
A) As the symptoms are same IC always looks like UTI. Infection gets treated with antibiotics but IC persists. IC should be considered if symptoms of Urinary Infection continue for more than a month. IC should also be considered in those patients of urinary tract infection who do not improve after adequate therapy.
A typical patient of IC may present with triad of pain frequency and urgency but few patients may present with unusual symptoms like incomplete evacuation, dribbling, desire to pass urine immediately after micturition, difficulty in sitting and walling with urinary symptoms, anal discomfort. These symptoms are not mentioned in the standard textbooks but patients commonly complain like that. I feel that these symptoms must be included in the textbooks. These symptoms are not due to obstruction but they are felt by the patients as they pass little amount of urine every void and have problems of increased sensation. 

Q) What are the investigations required to ascertain IC?
A) On examination, the patient is essentially normal except for suprapubic tenderness or anterior vaginal wall tenderness in females and prostatic tenderness in males.
Urine analysis, urine culture, and sonography of kidney, ureter and bladder are important investigations for the exclusion of other diseases with similar symptoms. On ultrasonography, presence of a small capacity bladder (normal bladder wall thickness) with normal upper tracts should raise the suspicion of IC. I do urine routine, urine culture and sonography in all the patients and if they all are normal I subject the patient to cystoscopy and hydrodistension. 

Voiding diary, urodynamics, potassium test and symptom scales are not routinely done in all the patients. Voiding diary can be helpful  in a patient where there is doubt about the voiding pattern as it shows that patients void small quantities every time. Some of severe cases of IC may void 50 times in the day. 

In my practice I never do Urodynamics and PST. There is no role of CT Scan or MRI and should not be done. Urodynamics and potassium tests are not very important and are considered optional tests. It is believed that urodynamics does not give any additional information and should be reserved for those patients where OAB is also suspected. Intravesical PST (Potassium Sensitivity test) detects the permeability of bladder epithelium.  This test has been shown to be positive in 75% of patients with IC and is also positive in patients with detrusor instability, radiation cystitis and bacterial cystitis.  This test is not diagnostic of IC. It has its own drawbacks and is painful. PST is therefore not recommended.

Q) How important is Cystoscopy and hydrodistension for IC?
A) I am a strong supporter of Cystoscopy and therapeutic Hydrodistension.
Cystoscopy with or without hydrodistension is a very controversial investigation. While Europeans feel that cystoscopy with bladder biopsy is essential to diagnose IC, others feel that there is no need to perform cystoscopy.  In the presence of hematuria, cystoscopy becomes mandatory to rule out malignancy in patients over the age of 40 years. Glomerulations are present in around 80 percent cases of IC.
 I use a protocol of staged treatment. All the patients are subjected to cystoscopy and therapeutic hydrodistension after their urine culture, urine routine and sonography are normal. Hydrodistension is a very controversial modality of treatment but gives immediate relief in most of the patients. A few patients also enjoy long-lasting benefit. If a patient remains symptom-free after hydrodistension for more than a year, it can be repeated when the symptoms develop again. On cystoscopy under anasthesia if patient has less than 150 ml capacity he is advised for surgical therapy.
Only Cystoscopy can detect Hunner's lesion . Hunners lesion can be treated. 

Q) What is the standard treatment for IC?
A) As the etiopathology is multifactorial, it is logical to treat the patients with multimodal therapy. Treatment options available are hydrodistension, oral therapy, intravesical therapy, intravesical botox injection, interstim, fulguration and resection of Hunner’s lesion, behavioural and physical therapy. In India botox has not been found effective and there has been no experience of interstim.
The problem with BPS/IC is its uncertainty in responding to treatment. There is no way to know which patient will respond to which treatment.  A staged treatment policy has been our standard approach with all patients treated with the same protocol. Staged therapy has been followed over the last 15 years and minor changes are made depending on advances in understanding the disease, the response of the patient and the availability of the therapeutic agent. The AUA guideline 2011 recommended staged therapy as the preferred way to manage BPS/IC. We have no experience of physical therapy behavioural therapy and interstim so it is not included in our protocol. Similarly we have not found intravesical botox injection effective so have removed it from our protocol and do not offer it to the patients. Behaviour modification and stress management are first line treatments as per AUA guidelines. Physical therapy is mentioned as 2nd line therapy in the same guidelines.

Q) What are the oral drugs recommended for IC?
A) As there is no cure for patients of BPS/IC, the aim of management is to decrease the symptoms and make the patient comfortable. Oral drugs include:
 Amitriptyline hydrochloride, Hydroxyzine hydrochloride, Gabapantin , Pentosan Polysulphate and Cyclosporin are important oral agents. Recently doubts have been raised about effectiveness of PPS.

Q) What are the dietary changes advised?

A) In India some patients get flare up with very spicy and hot food. No diet related cause is found in most of the patients. Normally all patients are advised to drink less fluid and it helps them but some patients can’t tolerate concentrated urine due to less water intake and forced to drink more water.

Q) Tell us about your experience at your Centre.
A) From 1993 to December 2014, we have seen around 900 IC patients and performed cystoscopy in 316 patients (196 women and 120 men). Female to male ratio is 3:2. Recently 133 patients seen from 2001 onwards were contacted and asked about their present disease compared to initial presentation. Mean follow-up was 6.8 years. Four patients had died so we have follow-up details of 129 (79 women and 50 men) patients over a period of 14 years. The response was evaluated using a Global Response Assessment (GRA) scale. A total of 58% had excellent improvement, 22% patients had no improvement or worsened, 9% had mild improvement and 13% moderate improvement. These patients were treated with modalities of treatment which were available at the time of presentation. PPS only became available in India in 2010.

The patients are subjected to re-hydrodistension if they have done well for more than a year on previous hydrodistension and other therapies are not working. Experience with botox injection is not good. We have not seen typical Hunner’s lesion in our patients but have seen red patches in three cases. Interstim (neuromodulation) has not been performed in any patient. Around 8% of patients had less than 200 cc capacity bladder on distension under anaesthesia and have been advised surgery. We have done augmentation cystoplasty in five patients with refractory BPS/IC with excellent results.

Q) Being a pioneer in IC treatment in India what would be your advice to other doctors dealing with IC patients.

A) My first advice would be to be empathetic towards the patients and follow these guidelines:

·     Suspect IC if patient prefers to move by train over road transport as toilet facility is available in train.

·     Patient goes to toilet during consultation with physician.

·    IC can be present even if cystoscopic findings are normal.

·    IC can be present in normal capacity bladder.

·    Do not say to the patient that he/she does not have any disease as all the reports are normal.

·    Do not send the patient to psychiatrist.

·    Do not do anything which causes pain to the patient.

·    Do not do hysterectomy for urinary symptoms.

·    Do not follow NIH 1987-88 guidelines.

·    Do not do cystoscopy without anesthesia.

·    Do not hydrodilate bladder at the time of cystoscopy by increasing the height of the reservoir.


Q) What else do you think is required for IC? 

A) A big change is needed in the IC world. There is a need to draw up a definition and establish criteria for the disease. It is also believed that the new definition and criteria should be evidence-based and should not be only opinion-based. All the researchers agree that it is very difficult task but that a start has to be made. Until the final diagnostic criteria are established, there is a need to work together. There is a need to follow a common algorithm so that a large amount of data can be collected and compared. There should be a working algorithm for history-taking, physical examination, investigations, cystoscopy, biopsy and treatment. Furthermore, basic research has to be done to find cure for this debilitating condition. Even in mid of 2015, no consensus on name, definition, etiopathology and management of BPS/IC exists. Advances in molecular biology point to inflammation as one of the etiologies. It is hoped that these advances will lead to the development of novel therapies and delivery methods to treat BPS/IC. It appears that a lot of research has been covered, but a great deal is still needed to reach the ultimate goal.






Tuesday, March 29, 2016

Interstitial Cystitis- How I was diagnosed

Do you suffer from frequent UTI? Do you suffer from frequent urination and urgency to urinate? Do you suffer from burning urethra and vagina? Do you suffer from lower abdominal pain? If yes, then read this post. I am not a medical practitioner and this post is written from a patient’s point of view. However my suggestion is if you have the symptoms discussed in the following post then please visit an Urologist. Why I emphasise on an Urologist is something you will learn from my experience.

 Just two days after my son’s sixth birthday, I felt this excruciating pain for the first time. It was accompanied by urinary frequency and burning sensation. I was not new to UTI; therefore I thought it to be another round of UTI. Living in India most women have experienced UTI at some or the other point of her life. Poor toilet hygiene, lack of cleanliness and lack of toilet facilities are the main reason for the prevalence of UTI in India. I had my first UTI right after my honeymoon and my gynaecologist said that it was common for newlywed women to get UTI and it is known as honeymoon Cystitis.

After my honeymoon with cystitis was over I started getting UTI very frequently, usually twice a year. It used to go away in a day or two after taking a round of antibiotics.  However 2015 was different. I started getting UTI (supposedly) almost every month. I also noticed that this time around my infection was not going away with antibiotics and the whole thing was accompanied by debilitating pain. So much so that I used to not be able and do for usual chores.

My gynaecologist was convinced that it was nothing but UTI and she gave me antibiotics and all kinds of creams to apply externally. The antibiotic didn’t work and the creams and vaginal wash made my burning miserable. I was being asked by my gynae to do urine test almost every alternate day. My urine reports came normal. There were no signs of infection. I also had no signs of external infection as well. Clinically I was fine.

She asked me to do an ultrasonography and that report was also normal. My gynaecologist was convinced that the pain and burning that I was talking about was simply in my head and I had no infection and I was absolutely fine. I literally had to plead to her to give me pain medication as I was being unable to bear the pain. I don’t blame her because going by my reports and external examination everything was indeed fine. Clinically it was impossible for any doctor to see anomaly.

It was August 2015, my pain and burning was killing me. I called my gynae and she again asked me to do a urine routine test, the reports came out normal as usual and my doc was irritated. Irrespective of being one of the best gynaecologists in India she obviously had no knowledge about IC. She is not the only one in January 2005 a conference was held in India where most IC patients complained that gynaecologists often tell that IC does not exist. The scenario is similar even in western countries where IC patients are often referred to psychiatrists.  That day my husband suggested that lets go to an Urologist. So far I always thought that Urologists were for men and never went to any. But as the saying goes “beggars are no choosers”. I was in such a threshold that I had no choice, therefore I went.

Initially my Urologist also said that it was nothing but UTI, however the only difference was he was listening to every single detail that I was talking about. He didn’t negate my pain as figment of the imagination. Another thing he did was he underlined a small line in my previous USG report and said that I have issues with urine retention, something that was previously overlooked.

My quality of life suffering, most days I was not able to get up from the bed. I couldn’t eat, I couldn’t sleep, throughout the day I was urinating at least 30 times, and each trip to the bathroom was a nightmarish experience was burning and pain. But this time even though I was in extreme pain yet I had hope. My urologist was working with me and he never neglected even a minuscule symptom that I talked about.

It took about three months to get diagnosed. The name of my disease was interstitial cystitis (IC). I had never heard about this disease before and my first reaction was is this some kind of a cancer? I turned to Google for information and read extensively. Till 2011 it was believed that IC doesn’t exist in India and it is only common about white females. But Dr. Nagendra Mishra a leading IC specialist from Ahmedabad believes that IC was prevalent in India however it used to not get diagnosed. Most frequently IC is diagnosed as UTI, normal cystitis, bladder cancer, neurogenic bladder, incontinence, and even tuberculosis. As the IC symptom flares up during menstrual periods. Many women even went for hysterectomy due to wrong diagnosis.

In India the awareness regarding IC is still less. Even general physicians and gynaecologist to whom women usually go are unaware about IC. Even in western countries it takes years to get diagnosed with IC. It is a common joke in our IC network that the fifth doctor would be able to diagnose.

Interstitial Cystitis or BPS is often considered incurable and some people are of the opinion that it is auto immune disorder. The only medicine for IC so far is Pentosan Polysulphate which coats the wall of the bladder. It is sold as Elmiron in western countries however in India we have a generic version.

Interstitial Cystitis is an invisible disease. Its symptoms vary from person to person and thus it is very difficult to diagnose. Most urologists follow a process of elimination to reach to their conclusion. Urodynamics studies and cystoscopy are definitely there for more comprehensive results however as I am not a doctor I would not like to elaborate on it.

The objective of creating this blog is to raise awareness regarding Interstitial Cystitis. Here I would like to be as comprehensive as possible regarding IC. Hope this would help fellow IC sufferers in India.