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.