Sunil Shroff

Polymers as ureteral stents.

Ureteral stents find wide application in urology. The majority of patients with indwelling ureteral stents are at an increased risk of urinary tract infection. Stent encrustation and its associated complications lead to significant morbidity. This review critically evaluates various polymers that find their application as ureteral stents with regard to various issues such as encrustation, bacterial colonization, urinary tract infections, and related clinical issues. A complete literature survey was performed, and all the relevant articles were scrutinized thoroughly. We discuss issues of encrustation/biofilm formation, new approaches to their testing, polymers currently available for use, new biomaterials, coatings, and novel ureteral stent designs, thereby providing a complete update on recent advances in the development of stents. Finally, we discuss the future of biomaterial use in the urinary tract.

How deceased donor transplantation is impacting a decline in commercial transplantation-the Tamil Nadu experience.

India with a population of 1.2 billion has a renal transplantation rate of 3.25 per million population. The major cause of chronic kidney disease is hypertension and diabetes. The crude and age-adjusted incidence rates of end-stage renal disease are estimated to be 151 and 232 per million population, respectively, in India. There was a remarkable lack of knowledge in the public about deceased organ donation until a decade ago. However, the role played by the media and nongovernmental organizations in partnership with the government has emphasized and implemented deceased donor transplantation in certain states in India—to mention particularly, the Tamil Nadu model. In the last 2 years, deceased organ donation has reached 1.3 per million population in Tamil Nadu, thereby effectively eliminating commercial transplantation. There is no religious bar for organ donation. A central transplant coordinator appointed by the government oversees legitimate and transparent allocation of deceased organs both in the public and private facilities as per the transplant waiting list. This model also takes care of the poor sections of society by conducting donation and transplantation through government-run public facilities free of cost. In the last 2 years, deceased donor transplantation has been performed through this network procuring organs such as the heart, heart valves, lung, liver, kidneys, cornea, and skin. The infrastructural lack of immunological surveillance—including donor-specific antibody monitoring, human leukocyte antigen typing, and panel reactive antibody except in a few tertiary care centers—prevents allocation according to the immunological status of the recipient. This private-public partnership promoting deceased donor transplantation has effectively eliminated commercialization in transplantation in the state of Tamil Nadu with a population of 72 million which is a model for other regions of South Asia and developing countries.

Legal and ethical aspects of organ donation and transplantation

The legislation called the Transplantation of Human Organ Act (THO) was passed in India in 1994 to streamline organ donation and transplantation activities. Broadly, the act accepted brain death as a form of death and made the sale of organs a punishable offence. With the acceptance of brain death, it became possible to not only undertake kidney transplantations but also start other solid organ transplants like liver, heart, lungs, and pancreas. Despite the THO legislation, organ commerce and kidney scandals are regularly reported in the Indian media. In most instances, the implementation of the law has been flawed and more often than once its provisions have been abused. Parallel to the living related and unrelated donation program, the deceased donation program has slowly evolved in a few states. In approximately one-third of all liver transplants, the organs have come from the deceased donor program as have all the hearts and pancreas transplants. In these states, a few hospitals along with committed NGOs have kept the momentum of the deceased donor program. The MOHAN Foundation (NGO based in Tamil Nadu and Andhra Pradesh) has facilitated 400 of the 1,300 deceased organ transplants performed in the country over the last 14 years. To overcome organ shortage, developed countries are re-looking at the ethics of unrelated programs and there seems to be a move towards making this an acceptable legal alternative. The supply of deceased donors in these countries has peaked and there has been no further increase over the last few years. India is currently having a deceased donation rate of 0.05 to 0.08 per million population. We need to find a solution on how we can utilize the potentially large pool of trauma-related brain deaths for organ donation. This year in the state of Tamil Nadu, the Government has passed seven special orders. These orders are expected to streamline the activity of deceased donors and help increase their numbers. Recently, on July 30, 2008, the Government brought in a few new amendments as a Gazette with the purpose of putting a stop to organ commerce. The ethics of commerce in organ donation and transplant tourism has been widely criticized by international bodies. The legal and ethical principles that we follow universally with organ donation and transplantation are also important for the future as these may be used to resolve our conflicts related to emerging sciences such as cloning, tissue engineering, and stem cells.

Effect of uropathogens on in vitro encrustation of polyurethane double J ureteral stents

Polyurethane stents are used when there is an obstruction to the flow of urine. A majority of the patients with such stents are at the risk of urinary tract infection and salt encrustation. The present study is aimed at analyzing the in vitro encrustation of calcium oxalate and other salts in the presence of common uropathogens (E. coli and P. mirabilis) on films made from Tecoflex®, a commercial grade polyurethane. In the absence of uropathogens, sodium ions and ammonia favor calcium adsorption whereas magnesium ions greatly depress it, resulting in increased hydrophillicity of the stent. With E. coli, Mg ions enhance the encrustation of calcium, whereas the other salts decrease its deposition. In case of P. mirabilis, irrespective of the type of salt, it enhances calcium encrustation except in the presence of sodium ions. Adhesion of uropathogens to the stent surface was higher in the presence of bovine serum albumin. Understanding the dynamics between various salts and microorganism in the urine, and urine–stent interface would aid in designing stents that are inert, resist encrustation and biofilm formation.

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostate cancer risk in south Indian men

AbstractThe ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats ≤21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52-1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG ≤19/GGN ≤21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG ≤19/GGN > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG ≤19/GGN ≤21 and CAG ≤19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.

South Indian men with reduced CAG repeat length in the androgen receptor gene have an increased risk of prostate cancer.

AbstractThe androgen receptor (AR) gene possesses polymorphic CAG tandem repeats and the repeat length has been inversely related to the risk of prostate cancer (PCa). The distinct ethnic variation in the CAG repeat length may be correlated to differences in PCa risk in different populations. To evaluate the CAG repeat length in the AR gene and the implications for PCa, we screened 87 PCa patients and 120 control subjects from South India. The mean CAG repeat length in PCa patients was significantly smaller than that of controls (17.0 vs 20.7; P<0.001). Men with≤19 CAG repeats had a significantly increased risk of cancer compared to those with >19 CAG repeats (age-adjusted OR=7.01; 95% CI=3.52-13.94; P<0.001). However, no significant association was observed between CAG repeats and age of onset or prostate-specific antigen levels. Although there was a trend towards shorter CAG repeat length in high grades of cancer, it was not significant (P=0.085). Thus, our results suggest an association between short CAG repeats in the AR gene and PCa risk in South Indian men. Further, we propose that CAG repeats could be used as a prognostic marker for PCa diagnosis.

Longer (TA) n Repeat but Not A49T and V89L Polymorphisms in SRD5A2 Gene May Confer Prostate Cancer Risk in South Indian Men

Testosterone is converted to 5 alpha-dihydrotestosterone (DHT) by 5 alpha-reductase enzyme, which is encoded by the SRD5A2 gene. DHT is the main androgen responsible for prostate growth. We have analyzed the complete coding region of the SRD5A2 gene in 87 histologically confirmed prostate cancer (PC) patients, 40 benign prostatic hyperplasia (BPH) cases, and 96 control samples from southern parts of India. The study revealed the A49T site to be monomorphic, the V89L site to be highly polymorphic, and the (TA)(n) repeat site to be polymorphic with only 2 alleles in our populations. The distribution of V89L alleles between PC cases and controls was not significantly different; however, (TA)(9) alleles distributed differently between the 2 groups. BPH cases exhibited alleles similar to controls at all polymorphic sites. The sequencing of the whole coding region did not reveal any other known or novel polymorphism in this gene. Our study emphasizes that the (TA)(9) allele might confer certain PC risk but that A49T and V89L polymorphisms do not confer PC risk in South Indian men.

Histological reclassification, histochemical characterization and c-kit immunoexpression in renal cell carcinoma

Objectives: Renal cell carcinoma is the most lethal of all urologic malignancies. Several parameters such as histological subtype, nuclear grade and TNM staging help in determining the prognosis and treatment options. A newer therapeutic modality has been suggested based on expression of c-kit antigen by the tumor cells. This study was designed to evaluate various histological parameters and correlate them with c-kit expression. Materials and Methods: The study was done on 40 consecutive cases of renal epithelial tumors. Histological sections were reviewed and reclassified according to WHO (2004) classification and nuclear grade assessed. Hales colloidal iron stain was done to identify the chromophobe variant. Immunostaining with c-kit was done and its expression was studied. The results were correlated and statistical significance was assessed. Results: The age range was 31-81 years, with a male to female ratio of 2:1. Seventy per cent of the cases were clear cell RCC (ClRCC), 17.5% were chromophobe type, 7.5% were papillary RCCs and 5% cases were oncocytomas. Fuhrman nuclear grading revealed 60.5% cases to be of low grade and 39.5% high grade. Hales colloidal iron staining was positive in chromophobe RCC and oncocytomas, while it was negative in ClRCC. Immunostaining with c-kit was positive only in oncocytomas. Conclusions: Clear cell RCC was the most common histological subtype of RCC. Clear cell RCC known to have a poor prognosis, showed a statistically significant higher nuclear grade than chromophobe and papillary RCCs which have a better prognosis. Hales colloidal iron staining was extremely useful in distinguishing chromophobe RCC and oncocytoma from the granular cell variant of clear RCC. Our study revealed c-kit negativity in all RCC. As Imatinib could be ineffective in such tumors, its clinical activity has to be carefully assessed in such tumors through further studies.

Indian transplant registry.

An ‘Indian transplant registry’ has been established over the past two years due to the efforts of the Indian Society of Organ Transplantation. This society is about 20 years old with over 450 members who are doctors and basic scientist. The registry is currently in the first phase of its development and can be partly viewed at www.transplantindia.com. The endeavor has been undertaken with the objective of having a centralized repository of information of the various transplants that are being undertaken in India. In its first phase of the registry ‘Fast Fact’ retrospective short datasets are being captured that include the essential details of the transplant programme. The fast fact data includes the number of transplant done yearly, the sex ratio and type of transplant. So far thirteen major institutional data has been entered in the registry. In the second phase of the registry, over twenty fields are likely to be captured and all member institutions would be encouraged to enter the data prospectively. In the third phase data would be derived with ongoing audit features.. The society and its members have supported the formation of the registry and are enthusiastic about its potential.

State of deceased donor transplantation in India: A model for developing countries around the world

Renal replacement therapy (RRT) resources are scarce in India, with wide urban-rural and interstate disparities. The burden of end-stage renal disease is expected to increase further due to increasing prevalence of risk factors like diabetes mellitus. Renal transplantation, the best RRT modality, is increasing in popularity, due to improvements made in public education, the deceased donor transplantation (DDT) programme and the availability of free and affordable transplant services in government hospitals and certain non-governmental philanthropic organizations. There are about 120000 haemodialysis patients and 10000 chronic peritoneal dialysis patients in India, the majority of them waiting for a donor kidney. Shortage of organs, lack of transplant facilities and high cost of transplant in private facilities are major barriers for renal transplantation in India. The DDT rate in India is now 0.34 per million population, among the lowest in the world. Infrastructural development in its infancy and road traffic rules not being strictly implemented by the authorities, have led to road traffic accidents being very common in urban and rural India. Many patients are declared brain dead on arrival and can serve as potential organ donors. The DDT programme in the state of Tamil Nadu has met with considerable success and has brought down the incidence of organ trade. Government hospitals in Tamil Nadu, with a population of 72 million, provide free transplantation facilities for the underprivileged. Public private partnership has played an important role in improving organ procurement rates, with the help of trained transplant coordinators in government hospitals. The DDT programmes in the southern states of India (Tamil Nadu, Kerala, Pondicherry) are advancing rapidly with mutual sharing due to public private partnership providing vital organs to needy patients. Various health insurance programmes rolled out by the governments in the southern states are effective in alleviating financial burden for the transplantation. Post-transplant immunological and pathological surveillance of recipients remains a challenge due to the scarcity of infrastructure and other facilities.