A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients.

BACKGROUND: Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. METHODS: Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. RESULTS: The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. CONCLUSIONS: The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

Can urodynamic diagnosis of dysfunctional voiding/external sphincter nonrelaxation be made on two-channel pressure-flow study without video-urodynamics, electromyography, or urethral pressure profilometry? Plateau detrusor pattern in perspective.

AIMS: urodynamic diagnosis of dysfunctional voiding/external-sphincter nonrelaxation (DV/EUSD) needs assistance of specialized testing namely urethral pressure profilometry (UPP), electromyography (EMG), and/or videofluoroscopy (VUDS). We aimed to find a predictive model based on standard pressure-flow study without need for specialized testing. MATERIAL AND METHODS: In this retrospective study (2017-2021), clinical and urodynamic data of adult men and women presenting with voiding dysfunction was collected. Mandatory inclusion criteria were availability of all-(1) findings of clinical examination and neurological status, (2) a valid filling cystometry and pressure-flow study (with active detrusor contraction), (3) a final clinic-urodynamic diagnosis. Voiding cystourethrography (VCUG) was performed to confirm the location of obstruction. RESULTS: Data of 218 participants (178♂, 40♀) was eligible. Plateau detrusor contraction pattern was observed in 89.0% of men and 86% of women with DV/EUSD; whereas only 7.5% men and no women with other obstructions demonstrated this pattern. Forward likelihood Logistic regression analysis revealed presence of plateau pattern, lower bladder outlet obstruction index (BOOI), and smaller difference between Pdetmax and PdetQmax highly predictive of presence of DV/EUSD in men as per the following equation-Y = -9.900 + (0.085 × BOOI) + (0.123 × pdetmax - pdetQmax) + (4.061 × detrusor pattern). A kattan-type nomogram was constructed based on the above equation. In women, presence of plateau pattern alone was highly predictive of DV/EUSD. CONCLUSION: Diagnosis of DV/EUSD can be accurately predicted using parameters of three-channel urodynamics (plateau pattern, BOOI, Pdetmax-pdetQmax) minimizing need for specialized testing.

Primary angiosarcoma of the seminal vesicle.

Angiosarcomas are rare but highly aggressive malignancies originating from lymphatic or vascular endothelial cells and may arise from any site in the body. Angiosarcomas of the genitourinary tract, especially of seminal vesicle origin, are extremely rare with only five reported cases. Surgery forms the mainstay of therapy in localised disease while adjuvant therapies are still being refined. We present the case of a 40-year old gentleman who presented with lower urinary tract symptoms and, on evaluation, was found to have a localised angiosarcoma originating in right seminal vesicle and offered laparoscopic resection, adjuvant paclitaxel (12 weekly cycles) and adjuvant radiation therapy (66 gray in 30 fractions). He developed a peritoneal nodular recurrence after 6 months of radiotherapy that was successfully salvaged with excision and metronomic chemotherapy, which he is currently receiving. Localised angiosarcomas need multimodality management despite small size. Attempts should be made for surgical salvage of limited recurrences whenever feasible.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting.

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta.

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

Challenges in the management of localized Ewing sarcoma in a developing country.

Survival in pediatric Ewing sarcoma (ES) lags in low- and middle-income countries (LMICs). This study analyzed factors contributing to a lower outcome in an LMIC center. A retrospective case review of children with localized ES treated from January 2011 till December 2017 was performed. Neoadjuvant chemotherapy with alternating cycles of vincristine, doxorubicin, cyclophosphamide; and ifosfamide, etoposide was administered 3-weekly for 48 weeks. Reassessment was planned for week 12, followed by local therapy (surgery/radiotherapy or both) tailed by adjuvant chemotherapy. Forty-eight patients with mean age 8 years (range: 0.7-14) were evaluated. Extremity and central axis tumors were seen in 25 (52%) and 23 (48%) patients. Three patients died of neutropenic sepsis and five abandoned therapy. Local therapy included primary surgery, radiotherapy and a combination of surgery and radiotherapy in 7 (16%), 20 (45%) and 17 (39%) patients. The 3-year event-free survival (EFS) and disease-free survival (DFS) for the cohort were 47.7 ± 11% and 57.6 ± 11.2%. Time to local therapy >16 weeks was associated with inferior DFS vs. local therapy administered within 16 weeks [46.6 ± 12.4 vs. 63.9 ± 19.4, p=.046]. Older age, axial site, large size and incomplete surgical resection did not predict relapse/progression. Patients who received wide local excision, as local therapy, had 100% DFS. Coordinated efforts to ensure timely therapy can improve outcome in pediatric ES. Abandonment and treatment-related mortality (TRM) are additional challenges that need to be tackled in LMICs.

Role of preoperative MR volumetry in patients with renal cell carcinoma for prediction of postoperative renal function after radical nephrectomy and nephron sparing surgery.

PURPOSE: Preoperative computed tomography or magnetic resonance (MR) imaging are commonly used for radiological evaluation of renal cell carcinoma (RCC) before radical nephrectomy or nephron sparing surgery(NSS). This study aimed to assess the role of MRI for predicting postoperative renal function by preoperative estimation of renal parenchymal volume and correlation with glomerular fi ltration rate (GFR). MATERIALS AND METHODS: A prospective observational study was conducted from February 2015 to October 2016 at a tertiary care hospital in northern India. MR imaging was done on 3 Tesla MR scanner (Signa Hdxt General Electrics, Milwaukee, USA). MR volumetry was used to estimate the renal parenchymal volume. GFR was measured in all patients using Tc99m Diethyl-triamine-penta-acetic acid using Russell's algorithm. Such measurement was done preoperatively, and postoperatively 3 months after surgery. RESULTS: 30 patients with suspected RCC underwent NSS (n=10) and radical nephrectomy (n=20). Median tumour volume was 175.7cc (range: 4.8 to 631.8cc). The median volume of the residual parenchyma on the affected side was 84.25±41.97cc while that on the unaffected side was 112.25±26.35cc. There was good correlation among the unaffected kidney volume and postoperative GFR for the radical nephrectomy group (r=0.83) as well as unaffected kidney volume, total residual kidney volume and residual volume of affected kidney with postoperative GFR for the NSS group (r=0.71, r=0.73, r=0.79 respectively; P<0.05). CONCLUSION: Preoperative residual parenchymal volume on MR renal volumetry correlates well with postoperative GFR in patients with RCC undergoing radical nephrectomy or NSS.

Efficiency of a novel non-monotonic segmented leaf sequence delivery of Varian MLC for non-split IMRT fields.

AIM: Development of bidirectional non-monotonic segmented leaf sequence (NSLS) MLC delivery technique compatible with Varian MLC for non-split IMRT fields reducing total monitor units (TotalMU) and the number of segments (NS) simultaneously and assessment of its efficiency using a plan scoring index (PSI). MATERIALS AND METHODS: The optimal fluence of IMRT plans of ten patients of lung carcinoma, calculated using Eclipse TPS version 11.0 (Varian Medical Systems, Palo Alto, CA, USA), was used to generate the segmented MLC fields using our newly developed equally spaced (ES) reducing level and NSLS algorithms in MATLAB® version 2011b for 6-10 intensity levels. These MLC fields were imported into the plans with the same field setup and the final dose was recalculated. The results were compared with those of commercially available multiple static segments (MSS) leaf motion calculation (LMC) algorithm and few previously published algorithms. Plan scoring index (PSI) and degree of modulation (DoM) was calculated to compare the quality of different plans for the same patient. RESULTS: The average differences in TotalMU and NS with respect to MSS algorithm are -3.80% and -14.28% for the NSLS algorithm, respectively. The calculated average PSI and DoM is 0.75, 2.51 and 0.91, 2.41 for the MSS and NSLS algorithms, respectively. CONCLUSIONS: IMRT plans generated using the NSLS algorithm resulted in the best PSI, DoM values among all the leaf sequencing algorithms. Our proposed NSLS algorithm allows bidirectional delivery in Varian medical linear accelerator which is not commercially available. NSLS algorithm is efficient in reducing the TotalMU and NS with equivalent plan quality as that of MSS.

Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first-line treatment of patients with nonsquamous non-small cell lung cancer using pemetrexed-based chemotherapy: The PEMVITASTART randomized trial.

BACKGROUND: Vitamin B12 and folic acid (FA) supplementation (B12-FAS) reduces hematologic toxicity with pemetrexed-based chemotherapy (PEM). However, the basis for recommending 1 week of B12-FAS before PEM initiation has never been proven in a randomized trial. METHODS: An open-label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) was conducted to compare hematologic toxicity between patients with locally advanced/metastatic nonsquamous non-small cell lung cancer who initiated PEM after 5 to 7 days of B12-FAS (delayed arm [DA]) versus those who received B12-FAS simultaneously (≤24 hours) with PEM initiation (immediate arm [IA]). Every 3 weeks, all enrolled patients received pemetrexed (500 mg/m2 ) AND either cisplatin (65 mg/m2 ) OR carboplatin (area under the curve = 5.0 mg/mL per minute) on day 1 for a maximum of 6 cycles. Supplementation consisted of oral FA 1000 µg daily and intramuscular vitamin B12 1000 µg every 3 weeks. The primary outcome was any grade of hematologic toxicity and secondary outcomes included grade 3/4 hematologic toxicity, the relative dose intensity delivered, and changes in serum levels of B12/FA/homocysteine. RESULTS: Of 161 patients (IA, n = 81; DA, n = 80) recruited, 150 (IA, n = 77; DA, n = 73) received ≥1 cycle and were included in a modified intention-to-treat analysis. Baseline anemia prevalence was 34.7% (IA, 32.5%; DA, 37%; P = .56). The incidence of any grade anemia, leukopenia, neutropenia, and thrombocytopenia was 87% versus 87.7% (P = .90), 37.7% versus 28.8% (P = .25), 20.8% versus 15.1% (P = .36), and 31.2% versus 16.4% (P = .04), respectively, in the IA and DA, respectively. Grade 3/4 cytopenias and median relative dose intensities delivered (pemetrexed, 93.5%; platinum, 91%) were similar in both arms. After cycle 3 (compared with baseline), serum homocysteine levels were lower, whereas FA and B12 levels were higher. In the DA, serum FA and B12 levels on day 1 of cycle 1 (after 5-7 days of B12-FAS) were significantly higher than at baseline, but homocysteine levels were similar. CONCLUSIONS: Simultaneous B12-FAS initiation with a pemetrexed-platinum doublet chemotherapy regimen is feasible and does not lead to enhanced hematologic toxicity. Serum homocysteine levels are unaffected by 5 to 7 days of B12-FAS.

Human papillomavirus 16 infection alters the Toll-like receptors and downstream signaling cascade: A plausible early event in cervical squamous cell carcinoma development.

OBJECTIVE: Toll-like receptors constitute an important component of innate immune mechanism. HPV is a known etiological factor of cervical cancer and is known to interfere with the expression of TLRs and downstream signaling pathway. It remains poorly understood whether HPV modulates the expression of TLRs. Hence, understanding HPV mediated immune alterations might aid in identifying novel therapeutic targets. The aim was to study the relative gene expression of TLRs & downstream signaling pathway in cervical carcinoma. METHODS: Cervical squamous cell carcinoma (CSCC) and normal cervical tissues were obtained. Subsequent to HPV genotyping, mRNA expression profiling using PCR Array was performed. Protein expression of relevant genes with western blot was studied. Levels of cytokines in cervicovaginal washes were estimated using a Luminex multiplex platform. RESULTS: All cases of cervical cancer were HR-HPV positive and predominant subtype was HPV16 (71.1%). Significant TLR4 upregulation and TLR2,7 downregulation were observed in HR-HPV infected cervix. TLR4,7 demonstrated low expression in CSCC. Molecules from cancer allied pathways; RELA, AKT, CDKN2A, and MDM2 demonstrated upregulation in CSCC. Protein expression data corroborated with gene expression profile. A diminished level of Th1 cytokines TNF-α, IFN-É£, IL-17, and IL-12 was observed in CSCC. Significantly increased levels of IL-1ß, IL-6 and IL-2 were detected in HR-HPV infected cervix. Kaplan Meier curve demonstrated high TLR4 and low TLR7 expression was associated with poor prognosis. CONCLUSION: The study demonstrates the HPV mediated dampening of the innate immune response in CSCC and provides support for exploring potential TLR2, 7 agonists as an adjunct therapy in CSCC patients.

Safety and outcome of percutaneous nephrolithotomy in patients with solitary kidney: A tertiary care center experience.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) for stones in solitary kidney poses a significant challenge and potential threat for acute kidney injury or progression of chronic kidney disease (CKD). We present our experience of PCNL in solitary functioning kidney (SFK) to evaluate the safety, efficacy, and postoperative complications and highlight the differences between these outcomes with respect to the stage of CKD. METHODS: We carried out a retrospective study of patients with SFK, who underwent PCNL at our center from April 2010 to March 2018. Patients who had a minimum of 6 months of follow-up were included. Patients were classified into CKD groups based on the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Group 1 included Stages 1, 2, and 3A and Group 2 included Stages 3B, 4, and 5. Postoperative complications and stone-free rate were recorded and graded according to the Clavien-Dindo classification and compared between the two groups. RESULTS: We had a total of 128 patients (Group 1 - 84 and Group 2 - 44). Stone-free rate after the first PCNL was higher in Group 1 as compared to Group 2 (88.1% [n = 74] vs. 50% [n = 22], P = 0.02). Overall, 48 patients (37.5%) had postoperative complications, but most were minor. Clavien Grade 1 and 2 complications were seen in 34 patients (Group 1, n = 18 and Group 2, n = 16, P = 0.069), whereas Grade 3 and 4 complications were seen in 14 patients (Group 1, n = 2 and Group 2, n = 12, P < 0.001), respectively. Need for postoperative (number of sessions) dialysis was seen with increased frequency in patients with higher chronic kidney stages (Group 1 vs. Group 2; 6 vs. 22 sessions, P < 0.001). CONCLUSION: PCNL in SFK is safe, with satisfactory outcome, but patients with advanced CKD stage have higher risk of complications including need for dialysis and may require multiple sessions for complete stone clearance. Hence, they should be managed at high output tertiary centers.

A retrospective analysis of complications of laparoscopic left donor nephrectomy using the Kocak's modification of Clavien-Dindo system.

INTRODUCTION: Kocak described a modification of Clavien-Dindo classification system (CDCS) for reporting procedure-related complications in laparoscopic donor nephrectomy (LDN). We used the Kocak modification in grading and reporting the severity of complications in patients who underwent LDN and in evaluating various parameters that predict them. METHODS: In all, 1430 patients who underwent left LDN from 2000 to 2016 were included in this study. All data was retrospectively collected and analyzed for complications occurring in the postoperative period. All complications were classified according to the four grades of Kocak-modified CDCS. RESULTS: 124 patients (8.6%) suffered a total of 235 postoperative complications. Most of the complications were Grade I and Grade II (Grade I: 79.5% [n = 187] and Grade II 16.2% [n = 38]), 2.5% of the complications were Grade III (n = 6) and Kocak Grade IVa complications occurred in three patients. There was one death (Grade IVb: 0.4%, overall mortality rate: 0.06%). The incidence of complications was significantly greater for male patients, those with body mass index ≥25 kg/m2, and if the operating surgeon had ≤ 1 year of experience in performing LDN surgery. CONCLUSION: LDN is a safe procedure with low morbidity. The rate of complications is 8.6% and most of these complications are of low grade. The use of a standardized system for reporting the complications of LDN allows appropriate comparison between reported data.

Ureterocalicostomy for Reconstruction of Complicated Ureteropelvic Junction Obstruction in Adults: Long-Term Outcome and Factors Predicting Failure in a Contemporary Cohort.

PURPOSE: Ureterocalicostomy is a well established treatment option in patients who have recurrent ureteropelvic junction obstruction with postoperative fibrosis and a relatively inaccessible renal pelvis. We evaluated the long-term outcome of ureterocalicostomy and factors predicting its failure. MATERIALS AND METHODS: We retrospectively analyzed data on 72 patients who underwent open or laparoscopic ureterocalicostomy from 2000 to 2014. Variables that may affect the outcomes of ureterocalicostomy were assessed with regard to primary pathology findings, patient age, serum creatinine, preoperative renal size (less than and greater than 15 cm), renal cortical thickness (less than and greater than 5 mm), hydronephrosis grade and preoperative renal function (glomerular filtration rate less than and greater than 20 ml/minute/1.73 m2). The surgery outcome was calculated in terms of success or failure. Factors predicting failure were evaluated by univariate and multivariate analysis. Failure was defined as an additional procedure required postoperatively due to persistent symptoms and/or followup renal scan showing persistent significant obstruction with deterioration of renal function on at least 2 occasions 3 months apart. Patients with less than 2-year followup were excluded from study. RESULTS: We analyzed data on 72 patients who underwent ureterocalicostomy during this period. Mean ± SD age of the study group was 28.9 ± 12.3 years and mean baseline serum creatinine was 1.1 ± 0.3 mg/dl. The mean glomerular filtration rate was 27.8 ± 11.6 ml/minute/1.73 m2 and mean cortical thickness of the operated kidney was 7 ± 3.86 mm. Common indications for ureterocalicostomy were failed previous pyeloplasty and/or endopyelotomy in 35 patients (48.6%) and secondary ureteropelvic junction obstruction after pyelolithotomy or percutaneous nephrolithotomy in 24 (33.3%). The most common complication was urinary tract infection, which was seen in 22 patients (30.6%). At a mean followup of 60.3 ± 13.6 months 50 patients (69.5%) had a successful outcome. Treatment failed in 22 patients (30.5%), including 6 who required nephrectomy, while 13 were treated with frequent changes of Double-J® stents or with balloon dilation. In 3 patients ureterocalicostomy was repeated. The rate of failed ureterocalicostomy was higher in patients with a low preoperative glomerular filtration rate (less than 20 ml/minute/1.73 m2), attenuated cortical thickness (less than 5 mm) and higher creatinine (greater than 1.7 mg/dl) on univariate analysis. However, on multivariate analysis poor cortical thickness and a low glomerular filtration rate were independent predictors of failure. CONCLUSIONS: Ureterocalicostomy is an acceptable salvage option with a satisfactory long-term outcome. Patients with a low preoperative glomerular filtration rate (less than 20 ml/minute/1.73 m2) and a thinned out cortex (less than 5 mm) showed a poor outcome after ureterocalicostomy.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

BACKGROUND: To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). MATERIAL AND METHODS: Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. RESULTS: The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume, number of fractions and volume of brain receiving atleast 8 Gy of radiation. CONCLUSION: DFGKRS is feasible for large AVMs with a fair nidus obliteration rate and acceptable toxicity. Cumulative prescription dose seems to be the most significant independent predictor for outcome following DFGKRS with 29-30 Gy resulting in a fair nidus obliteration with least adverse events.

Cluster of Differentiation 44 (CD44) Gene Variants: A Putative Cancer Stem Cell Marker in Risk Prediction of Bladder Cancer in North Indian Population.

CD44 is involved in cancer-cell growth, invasion, proliferation and metastasis and is also a causal factor for acquisition of resistance to apoptosis. Therefore we evaluated different SNPs of CD44 gene viz. CD44rs187116 A/G, CD44rs4755392 A/T, CD44rs187115 C/T, CD44rs13347 C/T and CD44 rs353639 G/T for bladder cancer risk in North Indian population. 240 bladder cancer patients and 270 cancer free controls were recruited in this study. Genotyping was done by PCR-RFLP for CD44rs187116 A/G. However, CD44rs4755392 A/T, CD44rs187115 C/T, CD44rs13347 C/T and CD44 rs353639 G/T were genotyped by allelic discrimination Taqman® assay. Statistical analysis was done by SPSS. In-silico analysis was done using F-SNP. We found reduced risk in variant genotype, TT of rs4755392 (p = 0.011) as well as in variant allele, T (p = 0.045). No risk was seen in rs13347, heterozygous genotype, CT (p = 0.023) and variant allele, T (p = 0.007). The dominant model, CT + TT also revealed reduced risk (p = 0.009). A marginal risk was seen in dominant model, GT + TT of rs353639 (p = 0.044) and reduced risk in variant allele T (p = 0.040). A significant manifold risk was seen in smokers carrying variant genotype, TT of CD44rs353639 G/T (p = 0.038, OR 1.960). Haplotypic analysis revealed significant association in 4 sets viz. TCCGG p = 0.005, TTCGA p = 0.039, ACTGG p = 0.008 and TCTGA p = 0.006. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs187115, rs13347 and rs353639. Our study suggests that rs353639 shows a marginal risk for bladder cancer susceptibility, whereas rs4755392 and rs13347 have reduced risk of bladder cancer and rs187115 and rs187116 had no effect on bladder cancer susceptibility in North Indians.

Genetic Variation in CD166 Gene and Its Association with Bladder Cancer Risk in North Indian Population.

Adhesion molecules play a key role in cancer progression and tumorigenesis. Genetic polymorphism of adhesion molecules may alter the normal functioning thereby leading to bladder cancer susceptibility. Hence we aimed to evaluate three SNPs of CD166 gene (CD166rs6437585 C/T, CD166rs10511244 C/T, and CD166rs1157 A/G) in bladder cancer patients and normal controls of North Indian population. A total of 270 healthy controls and 240 confirmed bladder cancer patients were recruited for this study. Three SNPs of CD166 gene viz. CD166rs6437585 C/T, CD166rs10511244 C/T, and CD166rs1157 A/G were selected for this study. CD166rs6437585 C/T and CD166rs10511244 C/T were genotyped by Taqman allelic discrimination assay and CD166rs1157 A/G was genotyped by PCR-RFLP. The statistical analysis was done using the SPSS software, version 16.0 (SPSS, Chicago, IL), and p < 0.05 was considered statistically significant. Haplotypic analysis was done by using SNP analyzer version 1.2A. CD166rs6437585 C/T and CD166rs10511244 C/T showed significant association with reduced risk in bladder cancer while CD166rs1157 A/G showed significant high risk along with association at genotypic and allelic levels. Haplotypic analysis showed 1.8-folds risk in CCG combination, whereas CTA and TCG showed significant association with reduced risk. Further stratification on the basis of smoking, tumor grade/stage and BGC therapy revealed no association of these three polymorphic sites of CD166. Our study suggests that CD166rs6437585 C/T and CD166rs10511244 C/T are predictive for the reduced risk of bladder cancer, whereas CD166rs1157 A/G had shown significant association with high risk of bladder cancer in North Indians. This somehow suggests that CD166rs1157 A/G can be used as a marker for risk prediction of bladder cancer.

Vesicocutaneous fistula after sliding hernia repair.

Sliding inguinal hernias are usually direct inguinal hernias containing various abdominal viscera. The incidence of bladder forming a part of an inguinal hernia, called as "scrotal cystocele," is 1-4%. The risk of bladder injury is as high as 12% when repairing this type of hernia. This case report emphasizes this aspect in a 65-year-old man who presented with urinary leak through the scrotal wound following right inguinal hernia repair.

Rare presentation of urachal adenocarcinoma with skip metastasis to colon.

Urachal carcinoma is a rare malignancy constituting <1% of bladder malignancies. The disease arises from a malignant transformation of rests of enteric epithelium in the urachus. Most common sites of metastasis are lung, liver, and bone. We report a postoperative case of urachal carcinoma presenting with distant metastasis to lung and skip lesions in colon. As both urachal and colon carcinoma share common histopathological features, most of the literature suggested using chemotherapy regimens similar to those recommended for colon malignancies. There are no randomized trials till date regarding the management of urachal adenocarcinomas except for the primary treatment being surgery.

Factors Influencing Compliance to Radical Treatment of Middle Thoracic Esophageal Cancer: An Audit from a Regional Cancer Centre.

BACKGROUND: The aim of this study is to identify the factors responsible for interruption of planned treatment in patients of carcinoma mid-thoracic esophagus and also discuss the strategies for improving treatment completion rates. MATERIALS AND METHODS: Patients with nonmetastatic mid-thoracic esophageal cancer who received treatment by multimodality approach using chemotherapy, radiation, and/or surgery were retrospectively analyzed. Factors influencing compliance with planned treatment completion were evaluated, and their significance was determined using multivariate Cox regression analysis. RESULTS: Ninety-one patients were reviewed. Median follow-up period was 11 months. Of 15 patients planned with neoadjuvant chemoradiation followed by surgery (Group 1), only 6 (40%) could complete the treatment. Similarly, only 19 out of 36 patients (52.8%) completed the planned definitive chemoradiation (Group 2). Furthermore, of forty patients planned with definitive radiotherapy (Group 3), 29 patients only (72.5%) completed this schedule. The rate of completion of therapy was worst in Group 1. The most common reason for noncompletion of planned treatment was nutritional inadequacy and excessive weight loss in all groups. In addition, chemotherapy-induced myelosuppression (P = 0.05) was the factor leading to treatment interruption in Group 2 and radiation-induced acute mucositis (P = 0.02) and lost to follow-up (P = 0.02) were the factors in Group 3. CONCLUSIONS: Rate of treatment completion significantly impacts survival rates. Nutritional inadequacy was the most common factor for noncompletion of planned treatment. A well-trained management team consisting of oncologist, dietitian, and psychotherapist can help overcome these factors and thereby improve the treatment completion rates.