Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors.

BACKGROUND AND OBJECTIVE: Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. METHODS: In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG. RESULTS: Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes. CONCLUSIONS: These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

Optimizing outcomes and managing adverse events in locally advanced or metastatic urothelial cancer: a clinical pharmacology perspective.

INTRODUCTION: Bladder cancer (BC) is the sixth most common type of cancer with epithelial/urothelial and non-urothelial origins. Urothelial carcinoma (UC) involves neoplastic cells of epithelial origin and accounts for 90% of all BC cases. Current review aims to discuss the latest advances and challenges in the treatment of UC with an emphasis on clinical pharmacology considerations. AREAS COVERED: Data including clinical efficacy and safety outcomes as well as precautions reported in published clinical studies obtained from PubMed and package inserts were collected and summarized in the review. Recent decade saw the approval of multiple drugs for the treatment of BC in both adjuvant/neoadjuvant setting as well as for unresectable tumors. Checkpoint blockers (pembrolizumab, nivolumab, atezolizumab, and avelumab), antibody drug conjugates (enfortumab vedotin and sacituzumab govitecan) and targeted therapies (erdafitinib) are now available in first-line (cisplatin-ineligible), second-line and third-line settings along with conventional platinum-based chemotherapy. While the survival outcomes have improved especially in refractory and unresponsive patients, the response rates are relatively low and patient safety needs further optimization. EXPERT OPINION: Additional studies on combination therapies, dose adjustments in special populations and impact of anti-drug antibodies on drug exposure are needed to further improve clinical outcomes.

Clinically Important Misclassification of Aortic Valve Stenosis Severity Using Non-Invasive Techniques: Simultaneous Echocardiography and Cardiac Catheterization During Transcatheter Aortic Valve Implantation in Awake Patients.

BACKGROUND: Suitability for transcatheter aortic valve (AV) implantation (TAVI) is determined by using transthoracic echocardiography (TTE), although left-sided cardiac catheterization (LCC) provides directly measured pressure data. TAVI in awake patients permits simultaneous comparison of TTE and LCC under physiologically relevant left ventricular loading conditions. We hypothesized that clinically important discrepancies between TTE and LCC would be identified. METHODS AND RESULTS: TAVI was performed in 108 awake patients undergoing intra-procedural TTE and LCC between January 1, 2016 and December 31, 2016, based upon pre-procedure TTE data. Intra-procedural assessments simultaneously were performed before and after prosthesis implantation. Based upon mean trans-AV systolic ejection pressure gradient (MSEPG), AS was graded as: mild (<20 mm Hg; grade 1), moderate (20 - <40 mm Hg; grade 2), or severe (≥40 mm Hg; grade 3). In 79 of the 108 (73.1%) patients, intra-procedural TTE and LCC assessments were concordant. In 2 of the 108 (1.9%) patients, TTE overestimated AS severity by ≥1 grade. In 27 of the 108 (25.0%) patients, TTE underestimated AS severity by ≥1 grade. In total, AS severity reclassification occurred in 29 (26.9%) patients. Overall, TTE underestimated MSEPG by 8.9 ± 1.2 mm Hg (TTE MSEPG versus LCC MSEPG; P < .001). CONCLUSION: Current TTE criteria appear to frequently and importantly underestimate AS severity. Because decision-making regarding TAVI often exclusively is based upon TTE data, these findings suggest either a continued role for LCC in the diagnostic assessment of AS in patients who do not meet standard TTE criteria or lowering TTE cutoffs for TAVI.

Diffuse alveolar hemorrhage secondary to plastic fume exposure: A case report.

A 31-year non-smoker man, working in plastic making industry for 12 years presented with cough and streaking hemoptysis for 2 days. Computed tomography (CT) of chest showed patchy ground glass opacities with interlobular septal thickening in bilateral lung parenchyma. Fiber optic bronchoscopy (FOB) was done. Sequential lavage was taken which showed progressively increasing hemorrhagic fluid. His diffusion capacity for carbon monoxide (DLCO) was 38.08 mL/mmHg/Mi (126%) predicted on day 2 of admission, 32.36 ml/mmHg/Mi (106%) predicted on discharge and 39.63 mL/mmHg/Mi (130%) predicted on going back to work. He was diagnosed with plastic fume exposure related pulmonary alveolar hemorrhage.

Biomeasures and mechanistic modeling highlight PK/PD risks for a monoclonal antibody targeting Fn14 in kidney disease.

Discovery of the upregulation of fibroblast growth factor-inducible-14 (Fn14) receptor following tissue injury has prompted investigation into biotherapeutic targeting of the Fn14 receptor for the treatment of conditions such as chronic kidney diseases. In the development of monoclonal antibody (mAb) therapeutics, there is an increasing trend to use biomeasures combined with mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling to enable decision making in early discovery. With the aim of guiding preclinical efforts on designing an antibody with optimized properties, we developed a mechanistic site-of-action (SoA) PK/PD model for human application. This model incorporates experimental biomeasures, including concentration of soluble Fn14 (sFn14) in human plasma and membrane Fn14 (mFn14) in human kidney tissue, and turnover rate of human sFn14. Pulse-chase studies using stable isotope-labeled amino acids and mass spectrometry indicated the sFn14 half-life to be approximately 5 hours in healthy volunteers. The biomeasures (concentration, turnover) of sFn14 in plasma reveals a significant hurdle in designing an antibody against Fn14 with desired characteristics. The projected dose (>1 mg/kg/wk for 90% target coverage) derived from the human PK/PD model revealed potential high and frequent dosing requirements under certain conditions. The PK/PD model suggested a unique bell-shaped relationship between target coverage and antibody affinity for anti-Fn14 mAb, which could be applied to direct the antibody engineering towards an optimized affinity. This investigation highlighted potential applications, including assessment of PK/PD risks during early target validation, human dose prediction and drug candidate optimization.

Assessment of Sugarcane Germplasm ( Saccharum spp. complex) Against Red Rot Pathogen Colletotrichum Falcatum

ABSTRACT Red rot, caused by Colletotrichum falcatum Went is the most important disease of sugarcane in India inflicting substantial loss to both cane industry and cane growers. To keep in view the importance of red rot disease of sugarcane, 117 accession of sugarcane germplasm including different Saccharum species and Indian and foreign commercial hybrids were tested against red rot with Cf 07, Cf 08 & Cf 09 (national pathotypes) by plug method of inoculation. Out of 117, 6 were found resistant and 12 were moderately resistant against red rot and rest were moderately susceptible/susceptible/highly susceptible. Theses resistance and moderately resistant accession can be further utilize to produce resistance varieties against the most devastating pathogen of sugarcane.

Antifungal and phytotoxic activity of essential oil from root of Senecio amplexicaulis Kunth. (Asteraceae) growing wild in high altitude-Himalayan region.

This work was aimed to evaluate the essential oil from root of medicinally important plant Senecio amplexicaulis for chemical composition, antifungal and phytotoxic activity. The chemical composition analysed by GC/GC-MS showed the presence of monoterpene hydrocarbons in high percentage with marker compounds as α-phellandrene (48.57%), o-cymene (16.80%) and ß-ocimene (7.61%). The essential oil exhibited significant antifungal activity against five phytopathogenic fungi, Sclerotium rolfsii, Macrophomina phaseolina, Rhizoctonia solani, Pythium debaryanum and Fusarium oxysporum. The oil demonstrated remarkable phytotoxic activity in tested concentration and significant reduction in seed germination percentage of Phalaris minor and Triticum aestivum at higher concentrations. The roots essential oil showed high yield for one of its marker compound (α-phellandrene) which makes it important natural source of this compound.

Simulations of site-specific target-mediated pharmacokinetic models for guiding the development of bispecific antibodies.

Bispecific antibodies (BAbs) are novel constructs that are under development and show promise as new therapeutic modalities for cancer and autoimmune disorders. The aim of this study is to develop a semi-mechanistic modeling approach to elucidate the disposition of BAbs in plasma and possible sites of action in humans. Here we present two case studies that showcase the use of modeling to guide BAb development. In case one, a BAb is directed against a soluble and a membrane-bound ligand for treating systemic lupus erythematosus, and in case two, a BAb targets two soluble ligands as a potential treatment for ulcerative colitis and asthma. Model simulations revealed important differences between plasma and tissues, when evaluated for drug disposition and target suppression. Target concentrations at tissue sites and type (soluble vs membrane-bound), tissue-site binding, and binding affinity are all major determinants of BAb disposition and subsequently target suppression. For the presented case studies, higher doses and/or frequent dosing regimens are required to achieve 80 % target suppression in site specific tissue (the more relevant matrix) as compared to plasma. Site-specific target-mediated models may serve to guide the selection of first-in-human doses for new BAbs.

Recurrent hypoglycaemia: a delayed presentation of Sheehan syndrome.

Sheehan syndrome is a rare but potentially serious complication of postpartum haemorrhage. The diagnosis can often be delayed by many years as symptoms may be subtle. We report the case of a 45-year-old woman who presented to the medical emergency unit with acute onset altered sensorium. On further evaluation she was found to have severe hypoglycaemia which was corrected by giving intravenous dextrose. On detailed clinical evaluation, she had a history of agalactia and amenorrhoea following her last pregnancy which was 15 years ago. She had a history of excessive postpartum bleeding during her last delivery. MRI of the brain showed empty sella and hormonal evaluation revealed adenohypophyseal insufficiency as evident from decreased levels of cortisol, thyroid-stimulating hormone, triiodothyronine, free thyroxine, follicle-stimulating hormone, luteinising hormone and prolactin. Based on clinical, radiological and laboratory parameters her final diagnosis was Sheehan syndrome with hypoglycaemia.

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Polyscope: a new era in flexible ureterorenoscopy.

INTRODUCTION: Despite improvements in instrumentation and technology in flexible ureteroscopy, the issue of procedural and off-procedural damage remains a problem. The aim of our study was to highlight our initial experience in flexible ureteroscopy using polyscope, a new advancement in the era of flexible ureterorenoscopy. MATERIALS AND METHODS: In this study, we used an 8F modular flexible, steerable polyscope for diagnostic purposes and Dormia basket removal for small renal stones. Three outer disposable catheters were used with proper sterilization in 22 cases. RESULTS: The polyscope was used in six cases of undiagnosed hematuria, and biopsy was taken from pelvic growth in one patient, which turned out to be transitional-cell carcinoma. Polyscope was used for removal of residual stones or small stones (< 1 cm) using Dormia basket in 16 cases (from August 2008 to July 2009). The mean stone size was 7.5 mm. The vision achieved was excellent in all the cases. CONCLUSIONS: Minimally invasive techniques are preferred for treatment of renal stones. The problem of lower caliceal stone access has been solved with the primary and secondary deflection of modern flexible ureteroscopes. The modular design of polyscope makes it a more cost-effective option. Relatively cheap and disposable multilumen catheters preclude the need for sterilization of optic cable, thus decreasing the chances of handling-related damages. The chance of instrument-related infection is minimal. Besides, it can be used as a semirigid ureteroscope should the need arises.

Multivitamin and micronutrient treatment improves semen parameters of azoospermic patients with maturation arrest.

The study was undertaken to evaluate the efficacy of multivitamin and micronutrient supplementation in azoospermic patients with maturation arrest. A total of 35 azoospermic patients showing maturation arrest on testicular biopsy were recruited in this study. The patients were divided into two groups. Untreated group (n=11) without any treatment and treated group (n=24) who received multivitamins, micronutrients and co-enzyme Q10. The sperm concentration, motility and morphology were evaluated at monthly interval. The results showed reduction in liquefaction time and relative viscosity of the semen in the treated group. Further, in treated group there was appearance of spermatozoa (4.0 million/ml) exhibiting progressive motility (7%) and normal morphology (6%), even in the first follow up visit. The sperm count, motility and normal morphology increased significantly on subsequent visits. Within 3 months (3 visits) 2 pregnancies were reported. These observations indicate that multivitamin and micronutrient supplementation improve the qualitative and quantitative parameters of seminogram in patients with azoospermia of maturation arrest.

Management of superficial bladder carcinoma: time to rethink the treatment strategies in the era of orthotopic neo-bladder.

The objective of this study was to evaluate the recurrence and progression, on long-term follow-up, of patients with superficial bladder cancer managed with bladder sparing approach. A total of 48 patients with superficial bladder cancer, initially treated with bladder sparing approach between 1990 and 1992, were available for long-term follow-up ranging between 10 and 15 years; the remaining patients were lost to follow-up. All patients had undergone transurethral resection and adjuvant intravesical therapy. Recurrence was treated with resection and adjuvant therapy or radical cystectomy in cases of progression. Out of 48 study subjects, 11 had T1G1, 23 had T1G2 and 14 had T1G3 tumor. In the T1G1 group, 45.5% had recurrence. Four had single recurrence managed successfully with TURBT and intravesical therapy. One had multiple recurrences and underwent radiotherapy after the fifth recurrence. In the T1G2 group, 82.6% had recurrence and majority (60.8%) had multiple recurrences. Out of 14 cases with multiple recurrences, eight patients ultimately progressed to invasive bladder carcinoma and underwent radical cystectomy. Majority of these underwent ileal conduit because ileal neobladder could not be created due to severe fibrosis. All 14 patients with T1G3 had recurrence, of whom three (21.4%) had single recurrence. Out of the 11 other patients (78.6%) who had multiple recurrences, nine developed invasive bladder carcinoma and underwent radical cystectomy. Orthotopic neo-bladder could be performed only in one patient and the remaining had ileal conduit or Mainz pouch. We conclude that in the era of orthotopic neo-bladder offering good quality of life, radical cystectomy should be considered at the earliest opportunity in patients with aggressive superficial bladder cancer.

Substitution urethroplasty for anterior urethral strictures: buccal versus lingual mucosal graft.

AIM: To compare the results of substitution urethroplasty and donor site morbidity between buccal mucosal graft (BMG) and lingual mucosal graft (LMG). PATIENTS AND METHODS: Patients who underwent single-stage dorsal onlay free oral mucosal graft substitution urethroplasty by Barbagli's technique between January 2004 and August 2008 were included in this study. Patients who underwent buccal (cheek, lip) mucosal graft urethroplasty were included in group I and those who underwent LMG urethroplasty (tongue) were included in group II. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Exclusion criteria were stricture length <3 cm and complex strictures which required a multistage procedure. RESULTS: The results of urethroplasty were similar in both groups in terms of blood loss, duration of postoperative hospitalization, complications encountered at urethroplasty site, mean postoperative Q(max) and mean postoperative AUA symptom score. Early slurring of speech complications was seen in group II, but not in group I. The long-term complications of persistent oral discomfort, perioral numbness and tightness of the mouth were seen only in group I. CONCLUSION: LMG urethroplasty is a good substitute for BMG urethroplasty with equally good results of urethroplasty with lower donor site morbidity.

Molecular insights into substrate specificity of prostate specific antigen through structural modeling.

Prostate Specific Antigen's (PSA) role as a biomarker for prostate cancer is well established but the physiological role of its serine protease activity in the pathobiology of normal prostate and prostate carcinogenesis remains largely unknown. In light of recent studies that implicate PSA's enzymatic activity in the initiation and/or progression of prostate cancer, we performed a molecular modeling study of substrate binding at the catalytic site of PSA wherein a PSA-selective substrate (HSSKLQ) was docked in an acyl-enzyme conformation to a three-dimensional homology model of PSA. Additionally, virtual positional scanning studies were conducted to gain mechanistic insights into substrate recognition of PSA. Subsequently, 13 novel peptide substrates of 6-aa length and four peptide substrates with varying length were synthesized and assayed for PSA hydrolysis to evaluate the experimental validity of docking insights. Additionally, six novel aldehyde-containing transition state analog inhibitors were synthesized and tested for their inhibitory potencies. The experimental data on the hydrolysis rates of the newly synthesized substrates and inhibitory potencies of the aldehyde peptides agreed with the docking predictions, providing validation of the docking methodology and demonstrating its utility towards the design of substrate-mimetic inhibitors that can be used to explore PSA's role in the pathobiology of prostate cancer.

Neo-bladder vaginal fistula: an unusual complication after orthotopic urinary diversion.

Development of neo-bladder vaginal fistula is not an unknown complication after cystectomy and orthotopic urinary diversion in females. Compared to native bladder, the wall of the neo-bladder is much thinner that may render it vulnerable to fistulization. Injury to the vagina during cystectomy is the most important predisposing factor. Herein, we present a case of neo-bladder vaginal fistula and discuss the potential surgical and clinical factors contributing to its occurrence as well as the treatment options available.

Prostate-specific antigen is a "chymotrypsin-like" serine protease with unique P1 substrate specificity.

Prostate-specific antigen (PSA), a serine protease belonging to the human kallikrein family, is best known as a prostate cancer biomarker. Emerging evidence suggests that PSA may also play a salient role in prostate cancer development and progression. With large amounts of enzymatically active PSA continuously and selectively produced by all stages of prostate cancer, PSA is an attractive target. PSA inhibitors, therefore, may represent a promising class of therapeutics and/or imaging agents. PSA displays chymotrypsin-like specificity, cleaving after hydrophobic residues, in addition to possessing a unique ability to cleave after glutamine in the P1 position. In this study, we investigated the structural motifs of the PSA S1 pocket that give it a distinct architecture and specificity when compared to the S1 pocket of chymotrypsin. Using the previously described PSA substrate Ser-Ser-Lys-Leu-Gln (SSKLQ) as a template, peptide aldehyde based inhibitors containing novel P1 aldehydes were made and tested against both proteases. Glutamine derivative aldehydes were highly specific for PSA while inhibitors with hydrophobic P1 aldehydes were potent inhibitors of both proteases with K(i) values <500 nM. The crystal structure of PSA was used to generate a model that allowed GOLD docking studies to be performed to further understand the critical interactions required for inhibitor binding to the S1 pockets of PSA and chymotrypsin. In conclusion, these results provide experimental and structural evidence that the S1 specificity pocket of PSA is distinctly different from that of chymotrypsin and that the development of highly specific PSA inhibitors is feasible.

Testosterone and estradiol-17 beta dependent phospholipid biosynthesis in ovariectomized catfish, Heteropneustes fossilis (Bloch).

Effect of cumulative doses (7, 14 and 28 mg kg(-1) body weight) of testosterone (T) and estradiol-17 beta (E2) on total phospholipids (TP), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) in tissues were investigated during the gonadal recrudescence, in prespawning phase of the annual reproductive cycle in intact and ovariectomized freshwater catfish, Heteropneustes fossilis. After ovariectomy, the hepatic levels of TP and PE were elevated and remained unaffected for PC, PS and PE when compared with control. In general, T and E2 were stimulatory fora specific class ofphospholipid in tissues of intact and ovariectomized catfish. These effects were higher at 14 and 28 mg kg(-1) body weight in ovariectomized catfish whereas 7 mg kg(-1) body weight of T and E2 have pronounced effect in intact ovaries. In conclusion, the various phospholipid biosynthesis were under T and E2 dependent. Among the phospholipid, the PC was the main constituent and was sex steroid dependent biosynthesis during prespawning phase.

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

OBJECTIVE: To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. MATERIAL AND METHODS: Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. RESULTS: Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. CONCLUSIONS: Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

Lingual mucosal graft urethroplasty for anterior urethral strictures.

OBJECTIVE: To evaluate the effectiveness of a lingual mucosal graft (LMG) urethroplasty for anterior urethral strictures and the donor site complications. METHODS: A total of 30 patients underwent urethroplasty for anterior urethral strictures using dorsal on-lay of a LMG from March 2006 to December 2006. Most patients had balanitis xerotica obliterans as the etiology. The mean stricture length was 10.2 cm (range 3.7-16.5). Postoperatively, all patients underwent pericatheter urethrography at 3 weeks, followed by retrograde urethrography with micturating cystourethrography, and uroflowmetry at 3 and 6 months. Repeat uroflowmetry was done as, and when, required. RESULTS: The mean period of follow-up was 9 months (range 4-12). The overall success rate was 83.3%. The mean peak flow rate increased postoperatively from 4.36 mL/s to 35.5 mL/s at 3 months and 25.06 mL/s at 6 months of follow-up. One patient developed repeat stricture at the anastomotic site, and 4 patients developed recurrent meatal stenosis. CONCLUSIONS: The results of LMG urethroplasty were comparable to that of buccal mucosal graft urethroplasty. LMG is easy to harvest. Most importantly, the donor site complications were minimal without any functional or esthetic deficiency.