Gauhar Sultan

Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan.

BACKGROUND Renal cell carcinoma (RCC) is the most frequent form of kidney cancer in adults. Somatic mutations that inactivate the von Hippel-Lindau (VHL) gene are the most common cause of RCC. The frequencies of molecular changes in the VHL gene in RCCs vary among different populations. So far, a single chromosomal-based study has been reported from a South Asian population. This report presents, for the first time, the somatic changes and promoter hypermethylation in VHL in a cohort of 300 RCC patients from Pakistan. METHODS To identify mutations in the VHL gene, direct DNA sequencing was carried out. Epigenetic silencing was investigated by using methylation-specific polymerase chain reaction. RESULTS Our data showed molecular alterations in the VHL gene in 163 (54%) renal cell carcinoma patients. Somatic mutations were found in 87 (29%) patients and 35 novel mutations were identified. VHL promoter hyper-methylation analysis showed epigenetic changes in 106 (35%) out of 300 patients. Patients who had no evidence of molecular alterations in the VHL gene were significantly younger than patients who carried some molecular change. Molecular alterations in the VHL gene were not restricted to clear-cell RCCs (ccRCCs). CONCLUSIONS This is the first report that identifies molecular aberrations in the VHL gene from a South Asian population. The frequency of somatic mutation is lower and that of promoter hypermethylation is higher when compared with data from other parts of the world. The data has important implications in the population-specific application of tailored preventive and therapeutic regimens in non-familial RCCs.

Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis

BACKGROUND The Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC. METHODS A systematic literature search was carried out for studies published in the PubMed, EMBASE, Cochrane library, and Google Scholar from 1997 to December 2014. Results were stated as pooled odds ratios (ORs) for nonparametric data after heterogeneity analysis with 95% CI using fixed effect or random effect model. RESULTS We systematically selected 13 relevant studies after thorough searches from the databases. Data showed no association between the GSTM1 and the GSTT1 null genotypes and the risk of RCC (OR = 1.01; CI: 0.92-1.11; P = 0.89 for GSTM1 and OR = 1.14; CI: 0.91-1.42; P = 0.25 for GSTT1). No association was found when the data were stratified according to the geographical/ethnic basis, source of control, and the risk factor evaluation. Subgroup analysis of occupational exposure to pesticides showed an inverse association of the active genotypes of both GSTM1 and GSTT1 polymorphisms with the exposed group of RCC (P<0.00001 and P<0.00001, respectively). The combined null genotype of the GSTM1/GSTT1 significantly increased the susceptibility to RCC by 1.4-fold (P = 0.001). This association remained significant for the Asian populations in subgroup analysis (OR = 1.8; CI: 1.30-2.49; P = 0.0004). CONCLUSION In conclusion, this meta-analysis suggests that the 2 GSTs deletion polymorphisms independently have no association with the risk of RCC. However, combination of both deletions increases the risk of developing the RCC.

Right Sided Laparoscopic Donor Nephrectomy - Dream Comes True

Introduction Laparoscopic donor nephrectomy is being progressively accepted with considerably decreased morbidity and favorable graft function. Controversy persists about whether procurement of the right kidney can be done successfully by the laparoscopic approach. To date, most laparoscopic live donor nephrectomies have been performed on the left side because the shorter length of the right renal vein poses technical challenges for the transplant surgeon in implanting the kidney into the recipient. Right-sided operation is technically more difficult and much more challenging because retraction of the liver is usually required and because the shorter right renal vein increases the risk of allograft thrombosis. Nevertheless, despite difficulties there are certain advantages like lack of draining venous tributaries which shorten the time of surgery. Objective To evaluate the outcomes of right sided laparoscopic donor nephrectomy in Pakistani kidney donors. Materials and methods We collected retrospective live donor nephrectomy data from Single center from May 2014 – Feb 2017. Demographics and hospital records were reviewed. Laparoscopic donor nephrectomy (RLDN) of right side was compared with left sided live related laparoscopic donor nephrectomy (LLDN). Demographic data was recorded in laparoscopic patients along with open donor group. Intra and post-operative events and complication were also analyzed. Finally the graft outcome was evaluated in right sided and left sided laparoscopic group. Results A total of 458 patients who had laparoscopic donor nephrectomy were included in this study. Right laparoscopic donor nephrectomy was done in 46 cases. Out of which 30 were male and 16 female. Mean hospital stay was 3 days and mean operative time was approximately 3 hours on right side. All grafts were primary functioning and there was satisfactory drop in Serum creatinine. Postoperative complications were noticed in two cases including cellulitis of abdominal wall and conversion in one case because of bleeding. Conclusions The results for laparoscopic donor nephrectomy were comparable to Right sided kidneys can be harvested safely laparoscopically with excellent donor outcome as well as comparable graft function with left sided laparoscopic and open group.

Angiomyolipoma of the scrotum: report of a rarely seen case and review of the literature

Angiomyolipoma (AML) is a benign, histologically complex mesenchymal tumor arising mainly from the kidney and liver. The majority (80%) of these tumors arise as sporadic tumors, while 20% of them are associated with tuberous sclerosis. Extra-renal sites of AML, though rare, have been reported in literature. In this report, we describe a case of AML arising from the scrotal skin, and presenting as a scrotal mass. Although skin is the most commonly reported site after kidney and liver, scrotal skin AML presents as an intriguing mass in a region known for germ cell tumors which has been reported only once before. A 35-year-old male presented with scrotal swelling. His physical examination, laboratory investigations and imaging studies were non-specific. Excision of the lesion with subsequent histopathological examination revealed the true nature of the lesion. This lesion should be included in the differential diagnosis of scrotal masses.

SURGICAL ASPECTS OF LIVING RELATED RENAL TRANSPLANTATION: EXPERIENCE WITH 2800 CONSECUTIVE CASES AT SIUT: 2056

Introduction: The first successful renal transplant between two brothers was performed at Sindh Institute of Urology and Transplantation (SIUT) on 20th November 1985. This confirmed the technical feasibility of renal transplantation in Pakistan which is a country with 170 million population and 10,000 end stage renal failure patients need kidney transplantation. Moreover there is joint family system providing large pool of living donors. After that modification and technical refinements over the past 23 years have resulted in a safe and effective procedure for recipients with abnormal lower urinary tract and donors with multiple renal vessels and candidates for 2nd and 3rd renal transplants. Patients and Methods: Between November 1985 and January 2010, about 2800 renal transplants were performed at S.I.U.T., Karachi. Records of all cases were reviewed and retrospective data was analyzed for site of transplant, number of vessels, technique of ureteric reimplantation, use of stents, pre-operative procedures and surgical complications were noted. Post operative monitoring of graft was done with routine doppler ultrasound, biochemistry, drug levels, MAG-3 Scan, antegrade pyelography and CT scan. Post transplant complications were treated accordingly. Results: Out of 2800 patients 23 had neurogenic bladder, augmentation cystoplasty and mitrofanoff was done before transplant. In 255 patients multiple renal arteries were used and 55 patients received 2nd transplant. In over 2800 renal transplants right iliac fossa was the commonest site irrespective of right or left kidney taken as a donor. Left iliac transplant was done in only 77 ( 2.7% ) cases, where there was unsuitable vessels on the right side or in 2nd transplant, lower abdominal transplants were performed in children, in 2nd or 3rd transplants in 55 (1.9%). Commonly used technique for vascular anastomosis was renal vein to external iliac vein and renal artery to external iliac artery, however, common iliac vein and artery was used 7.1% of cases, while abdominal aorta and common iliac vein in children. In the initial 202 cases ureteric-neo cystostomy was performed by Lead Better-Politano technique, while in 2589 cases Lich Gregoir technique was used and in 7 cases Starzel technique was used. Stents were placed in over 37%. Of cases of all patients 5.6 developed urologic complication, 4.8% vascular complications and lymphocele in 1.3% and perinephric haematoma 1% and wound infection 1.6% cases. All those complications were treated appropriately. Conclusion: Transplant techniques have improved and we are transplanting patients with abnormal bladder and donors with multiple renal arteries with almost similar success rates compared to our classical single renal artery and normal lower urinary tracts.

OUTCOME OF HIGH VOLUME LIVE RELATED RENAL TRANSPLANTS IN A DEVELOPING COUNTRY: 854

Introduction Promulgation of transplant law in Pakistan in 2007 banned unrelated commercial transplants both of locals as well as foreigners. The shortfall of transplantation in the country lead to accusations from commercial centres that patients were dying due to shortage of living related donors. To overcome the shortfall high volume transplants were initiated at our centre from 3/week to 10-12/week. This paper reports the outcome of these transplants and its benefits to our centre by economics of scale and on the overall transplant outcome in the country. Methods Between August 2007 and January 2009, 594 live related renal transplants were performed at our centre. Immunosuppression was by triple drug regimen, cyclosporine 6mg/kg, steroid and Azathioprin or Tacrolimus/ steroid/MMF. Children <13 years, adults with 0-2 antigen match and re-transplant were given induction by IL-2 antagonist or ATG. Graft dysfunction were evaluated by renal biopsy, drug level and imaging. Economics of scale was calculated by using direct labour, direct material and overhead costs. All transplants were provided ‘free’ with life long medications and follow-up. Results The mean age of recipient was 29.2±11.1 with M:F ratio 1.1:1 and donor was 34.7±9.8 with M:F ratio of 1.1:1. Mean HLA match was 3.85±1.49 where 71 (11.1%) were 0-2 antigen match and 126 (21.2%) identical. Induction was given to 89 (11%), ATG in 30 and IL-2 in 59 patients. Of the 594, 112 (19%) experienced acute rejection episodes. The frequency of post transplant infections was CMV in 41 (6.9%), chicken pox in 18 (3.8%), TB in 8 (1.3%), UTI in 127 (21%), blood culture positive in 73 (12%). Overall surgical and medical complications were encountered in 36 (6.1%) and 52 (8.7%) respectively. Eleven patients died in the follow-up period, 8 with functioning graft. Overall graft survival at 6 months and 12 months was 98% and 95% respectively. The cost of transplant reduced from

Management of Stone Disease: 17 years experience of a stone clinic in a developing country

2000 before to

Treatment of Ureteric Calculi - Use of Holmium: YAG Laser Lithotripsy versus Pneumatic Lithoclast

1700 in the high volume period. Refusal rates within the family reduced from 52% to 15%. Early transplant with shorter time on dialysis reduced Hepatitis C positivity from 33% to 6%. Of the total 1000 live donor transplants performed for locals in the country before law in 2007 our contribution was 10-15%. However of the 800 transplants performed in 2008, our contribution increased to 431 (54%). The percent of recipients from other provinces increased from 10% to 40% in 2008. Our transplant numbers for 2009 were 544. Conclusions High volume transplants have provided excellent outcome for patients with economic benefits to our centre by economics of scale. These have helped maintain transplant activity in the country. Free transplants to the disfranchised of the society have increased credibility of transplantation as a successful mode of therapy where now family members come forward to donate.