Utilization of pelvic lymph node dissection in patients undergoing robot-assisted radical prostatectomy in India versus the United States - A Vattikuti Collective Quality Initiative database analysis.

BACKGROUND: The utilization and extent of pelvic lymph node dissection (PLND) varies depending on the disease and practice patterns. AIMS: This study compares practice patterns in utilization of PLND between Indian and United States (US) practices. SETTINGS AND DESIGN: We focused on 415 patients (204 India; 211 US) prostate cancer patients treated with robot-assisted radical prostatectomy, between 2015 and 2016, within the Vattikuti Collective Quality Initiative database. SUBJECTS AND METHODS: Utilization of PLND and number of nodes removed were evaluated for the entire cohort, and after stratifying for Country of treatment and D'Amico risk groups. Logistic regression tested the relationship between PLND and country of treatment, after adjusting for disease risk. RESULTS: Indian patients had a higher risk distribution (D'Amico high-risk 53.4% in India vs. 27% in the US; P< 0.001) compared to their US counterparts. Overall, 193/204 (94.6%) Indian patients underwent PLND versus 181/211 (85.8%) US patients (P = 0.003). When stratified based on disease risk, PLND was performed more frequently in Indian patients with low-risk disease (81.0% vs. 41.4%,P= 0.008), but not in those with intermediate and high-risk disease. On multivariable analysis, Indian patients had a 2.57-fold higher probability of undergoing PLND than their US counterparts (P = 0.02). The analysis of the number of lymph nodes removed showed similar trends. CONCLUSIONS: Indian patients are more likely to undergo PLND than US patients. This is, especially true for patients with low-risk disease, who are unlikely to benefit from this procedure. Efforts should focus on optimizing the utilization of PLND, and deliver it only when there is clinical indication.

ABO-incompatible renal transplantation in developing world - crossing the immunological (and mental) barrier.

ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.

Paired kidney exchange transplantation: Maximizing the donor pool.

In the last decade, paired kidney exchange (PKE) transplantation has gained popularity worldwide as a viable alternative for end stage renal disease (ESRD) patients who have incompatible or sensitized donors. This study presents our experience with PKE transplantation and compares outcome between PKE and non-PKE renal transplant recipients. Between February 2010 and November 2013, 742 transplants were performed, of which 26 (3.5%) were PKE transplantations. All were two-way exchanges. PKE recipients were significantly older than non-PKE (46.73 ± 9.71 vs. 40.08 ± 13.36 years; P = 0.012) while donor ages were comparable. PKE patients had significantly higher number of HLA mismatches (5.03 ± 1.14 vs. 3.49 ± 1.57; P < 0.0001). After a median follow-up of 20 months (range: 3-47 months), there was no significant difference in patient survival (PKE 96.16% vs. non-PKE 96.65%; P = 0.596) and death censored graft survival (PKE 96.16% vs. non-PKE 96.37%; P = 1). Mean serum creatinine at 1 month and at last follow-up was lower in PKE versus non-PKE group (0.98 ± 0.33 vs. 1.3 ± 0.61 mg/dl; P = 0.008 and 0.96 ± 0.30 vs. 1.27 ± 0.57 mg/dl, P = 0.006, respectively). Biopsy proven acute rejection rate was 11.5% in PKE group and 16.89% in non-PKE patients (P = 0.6). To conclude, paired kidney donation is an excellent way of increasing the donor pool and needs to be promoted to overcome the shortage of suitable kidney in our country.

Optimum duration of splinting after endopyelotomy.

OBJECTIVE: Endopyelotomy is a well-accepted modality of treatment for pelviureteral junction (PUJ) obstruction, but the time period of stenting is debatable. The present study was aimed at evaluating the optimum duration and effectiveness of splinting after endopyelotomy. PATIENTS AND METHODS: Twenty-nine consecutive patients with primary PUJ obstruction were randomized to have an external splint (for economic reasons) for 2 weeks or 4 weeks. Thirteen patients in each group were available for evaluation. The groups were comparable in age, sex, symptoms, and preoperative glomerular filtration rate (GFR). All patients underwent antegrade endopyelotomy with placement of an 8F-12F polyethylene splint across the PUJ. A nephrostogram was performed after removal of splint at 2 or 4 weeks. Nondraining units were managed by putting in a 6F double-J stent for 6 weeks and considered failures. Patients were evaluated at 3, 6, and 12 months for symptomatic improvement, change in GFR, and drainage pattern on a diuretic renogram. RESULTS: At 1 year, a nonobstructed curve pattern was seen in 70% and improvement in GFR in 54% of the patients in the 2-weeks group, whereas in the 4-weeks group, these values were 54% and 39%, respectively. All patients in the 4-weeks group and 90% of those in the 2-weeks group were symptom free at 1 year of follow-up. Morbidity in terms of tube-related complications was comparable. CONCLUSION: Two weeks of splinting is as effective as 4 weeks in the successful outcome of endopyelotomy.

Inhibition of lipoprotein lipase activity by high density lipoprotein & apolipoproteins C, E & A in rhesus monkeys.

Experiments were conducted to study the effects of high density lipoprotein (HDL) and apolipoproteins C, E, and A on lipoprotein lipase activity in rhesus monkeys. The lipoprotein lipase activity was inhibited up to 32 +/- 6 per cent by monkey HDL. This inhibition was considerably decreased (2 +/- 0.02%) by using apolipoprotein-poor HDL. Apolipoproteins C and E inhibited the hydrolysis of activated intralipid by monkey lipoprotein lipase to a maximum of 83 +/- 7 and 57 +/- 5 per cent respectively. Apolipoprotein A produced little inhibition of lipoprotein lipase activity. The results of these studies demonstrate that HDL and apolipoproteins compete with the substrate for the binding to lipoprotein lipase in rhesus monkeys.

Upper urinary tract stone analysis using X-ray diffraction: results from a tertiary referral centre in northern India.

BACKGROUND: The spectrum of urinary stone disease has changed considerably in India from the common childhood bladder stone to the more frequent upper tract calculi. We analysed the gravel retrieved from the upper urinary tract using X-ray diffraction analysis in an attempt to evaluate the composition of the stones. METHODS: We analysed 434 upper urinary tract calculi from May 1993 to June 1994 obtained endourologically, as well as by extracorporeal shock wave lithotripsy and open surgery. The stones were analysed using a Phillips compact X-ray diffractometer (PW1840). The PC-APD software was used for data collection and peak search. The phase matching was done by the software using the JCPDS reference database. RESULTS: Oxalate stones comprised 97% of the total stones with calcium oxalate monohydrate forming 90% and calcium oxalate dihydrate and mixed stones forming the remainder. Struvite stones were found in 1.4%, while uric acid and apatite stones were less than 1%. There were no cystine calculi. Seventy per cent of calcium oxalate monohydrate and 40% of calcium oxalate dihydrate stones were pure. All the struvite and apatite calculi were almost pure. Only 15% of staghorns did not consist of oxalate. Nine of the ten stones in children were of the calcium oxalate monohydrate variety. The stone composition in females was similar to that in males. CONCLUSIONS: X-ray diffraction data indicate that urinary stone disease in north India is different from that in the western world. Calcium oxalate monohydrate stones predominate. These stones are hard to break and have a different metabolic origin from those consisting of calcium oxalate dihydrate. These findings might help in selecting the most appropriate method of treatment in north India and they indicate directions in which further metabolic studies might be planned.

Multimodality approach to renal and ureteric calculi.

BACKGROUND: Minimal or non-invasivemethods for treating renal or ureteric calculi have reduced the incidence of open surgery in the West to less than 1%. Before using these methods routinely in India we need to take into account the social and economic needs of our patients and the cost-effectiveness of the therapy. METHODS: Over a period of 16 months we analysed the results of 596 renal units with renal and ureteric calculi managed by (a) extracorporeal shock wave lithotripsy, (b) percutaneous litholapaxy, (c) ureteroscopy, (d) open surgery and (e) various combinations of a, b, c and d. RESULTS: Out-patient lithotripsy achieved a satisfactory outcome in pelvic (69% complete clearance, 21% minor residue), middle calyceal (84% complete clearance, 5% minor residue) and non-impacted ureteric calculi (93% complete clearance) with limited stone bulk. Percutaneous procedures had a better and quicker outcome than lithotripsy when the stone bulk was greater than 400 mm2 because it required a larger number of shock waves, repeated sittings and pre-lithotripsy stenting. Primary percutaneous debulking with adjunct lithotripsy for staghom calculi had a satisfactory outcome in 80% cases, while lithotripsy monotherapy usually failed. Percutaneous extraction resulted in a 95% success rate for large impacted upper ureteric calculi. Seventy-sixper cent of ureteric calculi below the pelvic brim were retrieved using ureteroscopy alone. Open surgery either primarily or after failure of other modalities was offered to 6.4% of the patients. It was the procedure of choice for large staghorn calculi with major stone bulk spread over various calyces, for multiple large pelvicalyceal calculi, and for calculi associated with congenital anomalies. CONCLUSION: In India lithotripsy should only be used when a quick and satisfactory outcome is expected, otherwise an appropriate minimally invasive method or surgical stone removal should be advised.

Carcinoma bladder: comparative evaluation of urinary cytology, excretory urography and ultrasonography.

A total of 63 patients with 85 bladder tumors were evaluated with excretory urography (IVU), ultrasonography and urine cytology, before being subjected to cystosocopy and biopsy. An attempt was made to evaluate accuracy of detection by different modalities, individually and combined together. Untrasonography and IVU detected 90 percent and 75 percent of tumors respectively while cytology was positive in 63 percent patients. Ultrasonography was superior to IVU, and, Urinary cytology, despite its low catch, could detect few cases where both the previous mentioned modalities had failed. Larger tumors situated on posterior and lateral walls were consistently detected by ultrasonography. Tumor staging by ultrasonography correlated well with final staging in infiltrating tumors. Thus it is concluded that the two non-invasive procedures, sonography and urine cytology must be routinely used for evaluation of fresh cases and in follow up of bladder tumors.

Early corticosteroid withdrawal regimen in a living donor kidney transplantation program.

Steroids have been the essential component of transplant immunosuppression. Recently, with availability of better immunosuppressive agents, many centers have started steroid free transplant with good success rates. We analyzed the outcomes of early corticosteroid withdrawal (CSW) protocol in our living donor kidney transplant programme. We included 73 patients on CSW protocol on basiliximab + tacrolimus and mycophenolate mofetil and compared them with 67 recipients on similar regimen with corticosteroids (CSs). CSW group received prednisolone 40 mg on day 1, which was stopped on day 5. Outcomes were evaluated in terms of acute rejection (AR), infections, new onset diabetes after transplant (NODAT), renal function and graft or patient loss. In CSW group, 15/73 (20.5%) patients developed AR, when compared to 5/67 (7.5%) in CS group, (P = 0.02). Biopsy proven acute rejection was seen in 12/72 (16.6%) in CSW group and 5/67 (7.5%) in CS (P = 0.1). One patient in CSW group developed antibody mediated rejection. NODAT was similar (9% in CS vs. 3.7% in CSW, P = 0.09), but infections were higher in CSW group (20.5% vs. 7.5%, P = 0.02). Mean serum creatinine was similar at 6 months (1.24 ± 0.6 in CS and 1.25 ± 0.3 in CSW, P = 0.9). Graft survival was 100% and 97% (P = 0.1) and patient survival was 98.6% and 98.5% (P = 0.9) in CSW and CS groups. Early corticosteroid withdrawal with basiliximab induction was associated with increased risk of AR but did not have any effect on short term graft and pateint survival.

Opioids and clonidine modulate cytokine production and opioid receptor expression in neonatal immune cells.

OBJECTIVE: Opioids and clonidine, used in for sedation, analgesia and control of opioid withdrawal in neonates, directly or indirectly activate opioid receptors (OPRs) expressed in immune cells. Therefore, our objective is to study how clinically relevant concentrations of different opioids and clonidine change cytokine levels in cultured whole blood from preterm and full-term infants. STUDY DESIGN: Using blood from preterm (≤ 30 weeks gestational age (GA), n=7) and full-term ( ≥ 37 weeks GA, n=19) infants, we investigated the changes in cytokine profile (IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α), cyclic adenosine monophosphate (cAMP) levels and µ-, δ- and κ- opioid receptor (OPR) gene and protein expression, following in-vitro exposure to morphine, methadone, fentanyl or clonidine at increasing concentrations ranging from 0 to 1 mM. RESULT: Following lipopolysaccharide activation, IL-10 levels were 146-fold greater in cultured blood from full-term than from preterm infants. Morphine and methadone, but not fentanyl, at >10(-5) M decreased all tested cytokines except IL-8. In contrast, clonidine at <10(-9) M increased IL-6, while at >10(-5) M increased IL-1ß and decreased TNF-α levels. All cytokine changes followed the same patterns in preterm and full-term infant cultured blood and matched increases in cAMP levels. All three µ-, δ- and κ-OPR genes were expressed in mononuclear cells (MNC) from preterm and full-term infants. Morphine, methadone and clonidine, but not fentanyl, at >10(-5)M decreased the expression of µ-OPR, but not δ- or κ-OPRs. CONCLUSION: Generalized cytokine suppression along with downregulation of µ-OPR expression observed in neonatal MNC exposed to morphine and methadone at clinically relevant concentrations contrast with the modest effects observed with fentanyl and clonidine. Therefore, we speculate that fentanyl and clonidine may be safer therapeutic choices for sedation and control of opioid withdrawal and pain in neonates.

Renal transplantation across ABO barrier.

In India, patients without a compatible blood group donor are usually excluded from renal transplantation. For young patients, it is a difficult therapeutic choice to stay on long-term dialysis. We describe the case of a 19-year-old male patient who had blood group O +ve and had no compatible donor in the family. His mother was B +ve and was willing to donate. The patient had an initial anti-B antibody titer of 1:512 and underwent antibody depletion with plasmapheresis (11 sessions) and intravenous immunoglobulin (IVIG) 100 mg/kg after every plasmapheresis. He also received rituximab 500 mg for 3 days prior to transplant and was induced with basiliximab. At the time of transplant, his anti-B titers were <1:8. Post-operatively, he required four sessions of plasmapheresis and IVIG as his titers rebounded to 1:64. The titers then spontaneously subsided to <1:16 and have stayed at the same level for 6 months post-transplant. The patient continues to have normal renal function with a creatinine of 1.4 mg/dl% and has had no episodes of rejection.

Comparison of azathioprine with mycophenolate mofetil in a living donor kidney transplant programme.

There are conflicting data regarding the comparative efficacy of mycophenolate mofetil (MMF) versus azathioprine (AZA) as maintenance immunosuppressive agent in kidney transplantation. The data are even less in combination with tacrolimus (TAC) in living donor kidney transplantation. A total of 205 living donor kidney transplants, on TAC-based triple drug immunosuppression were included in the study. A total of 113 patients received AZA and rest 92 were on MMF based protocol. TAC levels were monitored and graft biopsy was done whenever rejection was suspected. The outcomes were evaluated in terms acute rejection (AR) episodes at 1 year, infections, renal function, graft loss, and death between two groups. The study group comprised 163 males (79.5%) and 42 (20.5%) females. The mean age of patients was 42.4±11.8 years in the AZA group and 39.4 ±13.4 in the MMF group (P=0.09). The mean duration of follow-up was 491.7±240.7 and 478.8±334.4 days respectively in the AZA and MMF groups (P=0.75). Thirty-seven of 92 (40.2%) patients in the MMF group and 70/113 (61.9%) patients in the AZA group received IL-2 RAb induction (P=0.002). 32 patients (15.6 %) developed AR within a year. The incidence of AR was similar in patients who received MMF (12/92, 13%) and those who received AZA (20/113, 17.5%), (P=0.36). There was no difference in the incidence of AR in the subgroup of patients who received IL-2 RAb compared to those who did not receive induction in the two groups (5/37 vs. 7/55 in the MMF group and 10/70 vs. 10/43 in the AZA group, P=0.72). The incidence of infections was similar in the two groups (19/92, 20.6% vs. 25/113, 22.1%, P=0.79). Three patients developed CMV disease, of which two were in the MMF group. Graft loss occurred in 7/205 (3.4%) and death in 8/205 (3.9%) patients. Six of eight patients who died had functioning grafts. The rate of graft loss (3/92 vs. 4/113, P=0.97) and death (5/92 vs. 3/113, P=0.27) was similar in two groups. The overall patient survival was 94.5% and death censored graft survival was 97.4%. Cost comparison suggests AZA to be 6-10 times cheaper than MMF. This study suggests that, in tacrolimus-based immunosuppression, azathioprine may be as good as MMF as maintenance immunosuppressive drug in living donor kidney transplantation. It is also a more cost-effective immunosuppression.

Kidney transplantation in a patient with HIV disease.

Human immunodeficiency virus (HIV) disease was considered an absolute contraindication to kidney transplantation until recently. The main reason was the concern regarding the side effects of immunosuppressive drugs in already immunocompromised patients. Kidney transplantation is considered to be the best form of renal replacement therapy in most patients with kidney failure. Nowadays, many world medical centers are successfully doing kidney transplantation in HIV patients with kidney failure. However, HIV disease is still considered a contraindication to kidney transplantation in most Indian centers. Here, we report a case of a patient with HIV infection and ESRD, who underwent successful kidney transplantation in our center.

Diagnostic utility of hepatitis C virus core antigen in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis are at high risk for Hepatitis C virus infection. Anti-HCV antibody detection is widely used for screening this infection but is not sensitive for window period detection. An ELISA to detect the HCV Core Antigen has recently become available. OBJECTIVES: To investigate the utility of the HCV core Antigen ELISA in the detection of HCV infection in hemodialysis patients and to compare with 3rd generation ELISA validated by real-time PCR. METHODS: Two hundred fifty hemodialysis patients were included in the study. Anti-HCV antibodies and Total HCVcAg was determined by third generation ELISA kits. HCV RNA was determined using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and sensitivity of the two assays was confirmed by estimating viral load using real-time PCR. RESULTS: Forty-three out of 250 (17.2%) patients were positive for anti-HCV antibodies and HCVcAg. 13/250 (5.2%) were positive for HCVcAg but anti-HCV negative, which is statistically significant (P<0.05). All 13 were confirmed viremic by in-house nested RT-PCR leading to specificity of 100%. Viral load of 49,258+/-28,682 copies/mL were detected in HCVcAg positive cases in comparison to 239,383+/-107,805 copies/mL in the only anti-HCV positive group (P<0.001). False negative cases for HCVcAg assay accounted for 2/250 (0.8%) in which the viral load was 306+/-461 copies/mL which was significantly lower in comparison to HCVcAg positive group (P<0.001, t-test=9.982). CONCLUSIONS: Total HCVcAg ELISA is an accurate serological marker for early identification of HCV infection, than is possible by currently used serological assay. It will be useful for patients undergoing hemodialysis who have a longer window period due to immunosuppressed state. It is both a cost-effective and a less labor-intensive alternative to PCR, enhancing its clinical utility.

Objective evaluation of the outcome of endopyelotomy using Whitaker's test and diuretic renography.

OBJECTIVES: To assess the role of Whitaker's test (WT) and 99mTc-diethylene triamine penta-acetic acid diuretic renography (DRG) in determining objectively the outcome of endopyelotomy, and to rationalize the frequency and timing of such evaluation after endopyelotomy. PATIENTS AND METHODS: Thirty-one patients (age > 15 years) were prospectively evaluated after percutaneous endopyelotomy. WT was performed at 4-6 weeks via the nephrostomy maintained for external drainage, 24 h after removing the splint. DRG was performed at 3, 6 and 12 months, and then annually. RESULTS: WT performed 24 h after removing the splint diagnosed pelvic pressures in the unobstructed range (< 15 cmH2O) in 21 of the 24 patients were also evaluated with DRG at 3 months. An intra-pelvic pressure of > 15 cmH2O was correlated with a pattern of obstruction on DRG in all three units. Despite an unobstructed WT in 18 patients, categorization of DRG drainage showed disparity in six cases. All six renal units had a large pelvic area (> 15.0 cm2 in two and > 20.0 cm2 in four) and/or a poor renal function (separate glomerular filtration rate [GFR] of < or = 25 ml/min in four of the six units). The drainage pattern on DRG was unevaluable in two renal units as the function was poor (separate GFR < 15 ml/min). During the first year, the drainage pattern on DRG improved in four cases. When followed beyond one year, the drainage pattern deteriorated at 2 years in only one of 14 evaluated renal units with an initial unobstructed WT. CONCLUSION: Using objective methods of evaluation, endopyelotomy was successful in relieving obstruction in 87% of cases. If inaccuracies in the interpretation of DRG, i.e. a large pelvic capacity and poor renal function, are accounted for, the results of WT as early as 24 h after removal of the splint correlated with DRG. Drainage patterns on DRG did not deteriorate during the first year. An early post-operative evaluation with WT or DRG, as appropriate, is thus sufficient evidence of the success of the procedure. Evaluations repeated during the first year after endopyelotomy may be unnecessary.