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Context: Minimally invasive management (laparoscopic/robot assisted) is currently the standard of care for managing pelvi ureteric junction obstruction (PUJO). Open techniques of management of PUJO are well described in literature. However, there appears to be relative lack of description of minimally invasive techniques in the literature., Objective: This article is aimed at describing in detail, with images, the various techniques and modifications in laparoscopic or robot-assisted management of PUJO., Evidence Acquisition: A review of literature on PubMed was performed and all articles which detailed any technique of minimally invasive pyeloplasty were included., Evidence Synthesis: The various techniques of minimally invasive pyeloplasty as well as the authors' techniques are compiled and described in detail with intraoperative images., Conclusions: Operative techniques of minimally invasive pyeloplasty are not well described in literature. We have attempted to present a comprehensive resource of different techniques of minimally invasive pyeloplasty and the clinical scenarios in which they may be appropriate. This should prove to be a useful reference to the practicing urologist., Patient Summary: In this paper, we have compiled the various surgical techniques of treating obstruction at the PUJ of the kidney along with intraoperative photograph., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Urology Annals.)

Carbonic anhydrase isoforms IX and XII are overexpressed in hypoxic tumor cells regulating various physiological processes such as cell proliferation, invasion, and metastasis, resulting in the onset and spread of cancer. Selective inhibition of these enzymes is a promising strategy for anticancer therapy. Coumarin derivatives were identified as selective and potent inhibitors of these isoforms. This study reports 6-aminocoumarin sulfonamide and oxime ether derivatives linked through a chloroacetyl moiety tethered to piperazine and piperidone, respectively, showing selective inhibition against human carbonic anhydrase (hCA) IX and XII with K i ranging from 0.51 to 1.18 µM and 0.89-4.43 µM. While the sulfonamide derivative 8a exhibited submicromolar inhibition against hCA IX and XII with K i 0.89 and 0.51 µM, the oxime ether derivatives showed lower activity than the sulfonamides, with the compound 5n inhibiting hCA IX and hCA XII with a K i of 1.055 and 0.70 µM, respectively. The above results demonstrate the potential of these derivatives as selective, potent inhibitors of carbonic anhydrase IX and XII and provide a foundation for further optimization and development as effective anticancer agents. Further, the binding mode of the synthesized derivatives in the active site were examined using molecular docking and dynamic simulation studies., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Rhodanine and its derivatives are an important class of heterocycles with diverse biological properties, including anticancer, antibacterial, and anti-mycobacterial activities. In the present work, four series of new Rhodanine derivatives were synthesized and evaluated for their inhibitory activity against carbonic anhydrase I, II, IX, and XII isoforms. Interestingly, the tested compounds exhibited good inhibitory activity against the cytosolic isoform human carbonic anhydrase (hCA) II and tumor-associated hCA IX. While the Rhodanine-benzylidene derivatives (3a-l) and Rhodanine-hydrazine derivatives (6a-e) are found to be selective against hCA II, the Rhodanine-N-carboxylate derivatives (8a-d) are found to be highly selective toward hCA IX. The Rhodanine-linked isoxazole and 1,2,4-oxadiazole derivatives (8ba, 8da, and 8db) exhibited inhibitory activity against hCA II and hCA IX. Among the tested compounds, 3b, 3j, 6d, and 8db were found to inhibit hCA II with K i values of 9.8, 46.4, 7.7, and 4.7 µM, respectively. Furthermore, their mechanism of action is supported by molecular docking studies. Notably, the synthesized Rhodanine derivatives belong to a nonsulfonamide class of carbonic anhydrase inhibitors., (© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Background: In the authors' previous study, 4-(2-((3-methyl-4-oxo-2-thioxo/dioxothiazolidin-5-ylidene) methyl) hydrazineyl) benzonitriles were found to demonstrate potent antibacterial activity against Acinetobacter baumannii . Interestingly, the aforementioned compounds contain a 4-cyanophenylhydrazine motif. Materials & methods: Intrigued by this observation, the authors focused on preparing a library of 4-cyanophenylhydrazine derivatives and studied their detailed antibacterial potential. Results: This study led to the identification of a 4-cyanophenylhydrazine with potent inhibitory activity against carbapenem-resistant A. baumannii BAA-1605, with minimum inhibitory concentration (MIC) of 0.25 μg/ml and highest selectivity index of 640. The compound also demonstrated potent inhibition against multidrug-resistant A. baumannii isolates (MIC: 0.25-1 μg/ml). Conclusion: The identified 4-cyanophenylhydrazine compound exhibited synergistic activity with amikacin, tobramycin and polymyxin B against carbapenem-resistant A. baumannii BAA-1605.

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web-based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence., Competing Interests: None

Luliconazole is the first and only anti-fungal agent approved for the short-term treatment of superficial fungal infections. However, commercially available conventional topical dermal drug delivery cargo of luliconazole is associated with certain limitations, like lower skin permeation and shorter skin retention of drug. Therefore, the present review is an attempt to unravel the penetration hurdles in luliconazole topical dermal drug delivery. Moreover, we have also summarized the activity of functional nanomaterials-based drug delivery systems employed by the scientific fraternity to improve luliconazole efficacy in superficial fungal infections on a case-to-case basis. In addition, efforts have also been made to unveil the critically acclaimed mechanism of action of luliconazole against fungal cells. Under the framework of future prospects, we have analyzed the combination of luliconazole with isoquercetin using the in-silico docking technique for offering synergistic antifungal activity. Isoquercetin exhibited a good affinity for superoxide dismutase (SOD), a fungal target, owing to the formation of hydrogen bonds with Glu132, Glu133, and Arg143, in addition to a few hydrophobic interactions. On the other hand, luliconazole inhibited lanosterol-14α-demethylase, and consequently blocked ergosterol. In addition, nanotechnology and artificial neural network (ANN) derived integrated drug delivery systems may also be explored for augmenting the luliconazole therapeutic efficacy in topical fungal infections. Synergy of ANN models along with topical nanoscaled drug delivery may help to achieve critical quality attributes (CQA), leading to commercial success of luliconazole., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Herpes simplex virus (HSV) can be genetically altered to acquire oncolytic properties so that oncolytic HSV (oHSV) preferentially replicates in and kills cancer cells, while sparing normal cells, and inducing anti-tumor immune responses. Over the last three decades, a better understanding of HSV genes and functions, and improved genetic-engineering techniques led to the development of oHSV as a novel immunovirotherapy. The concept of in situ cancer vaccination (ISCV) was first introduced when oHSV was found to induce a specific systemic anti-tumor immune response with an abscopal effect on non-injected tumors, in the process of directly killing tumor cells. Thus, the use of oHSV for tumor vaccination in situ is antigen-agnostic. The research and development of oHSVs have moved rapidly, with the field of oncolytic viruses invigorated by the FDA/EMA approval of oHSV talimogene laherparepvec in 2015 for the treatment of advanced melanoma. Immunovirotherapy can be enhanced by arming oHSV with immunomodulatory transgenes and/or using them in combination with other chemotherapeutic and immunotherapeutic agents. This review offers an overview of the development of oHSV as an agent for ISCV against solid tumors, describing the multitude of different oHSVs and their efficacy in immunocompetent mouse models and in clinical trials.

This study describes technical implications and compares short-term outcomes after a dorsal versus ventral approach for double-face augmentation urethroplasty (DFAU) for treating a near-obliterated bulbar urethral stricture (BUS). This was a retrospective evaluation of a prospectively collected database of patients with BUS (<2 cm) who underwent DFAU. The choice between the approaches depended on (1) landmark identification (the relation between the bulbospongiosus muscle and the distal end of the stricture) and (2) corpus spongiosum width. In DFAU, inlay augmentation was at the level of the narrowed urethral plate (<6 Fr). Patient follow-up data (symptom score and uroflowmetry) were assessed every 3 mo for the first year, and every 6 mo thereafter. A successful outcome was defined as a normal urinary flow rate without obstructive voiding symptoms. Fifty-two patients underwent DFAU for BUS (dorsal approach, n  = 30; ventral approach, n  = 22). The maximum flow rate and symptom scores significantly improved in both groups. The overall success rates (86%) were similar. In conclusion, a dorsal approach for DFAU is versatile and can be considered in all circumstances. A ventral approach should be performed in patients with proximal BUS. The short-term outcomes were similar for both approaches., Patient Summary: We assessed whether double-face augmentation urethroplasty is a suitable option for treating near-obliterated bulbar urethral strictures using two free grafts for augmentation to improve the urinary flow. This operation can be performed using two methods and both techniques were safe with similar short-term outcomes., (© 2021 Published by Elsevier B.V. on behalf of European Association of Urology.)

Purpose: Extracellular matrix (ECM) component hyaluronan (HA) facilitates malignant phenotypes of glioblastoma (GBM), however, whether HA impacts response to GBM immunotherapies is not known. Herein, we investigated whether degradation of HA enhances oncolytic virus immunotherapy for GBM., Experimental Design: Presence of HA was examined in patient and murine GBM. Hyaluronidase-expressing oncolytic adenovirus, ICOVIR17, and its parental virus, ICOVIR15, without transgene, were tested to determine if they increased animal survival and modulated the immune tumor microenvironment (TME) in orthotopic GBM. HA regulation of NF-κB signaling was examined in virus-infected murine macrophages. We combined ICOVIR17 with PD-1 checkpoint blockade and assessed efficacy and determined mechanistic contributions of tumor-infiltrating myeloid and T cells., Results: Treatment of murine orthotopic GBM with ICOVIR17 increased tumor-infiltrating CD8 + T cells and macrophages, and upregulated PD-L1 on GBM cells and macrophages, leading to prolonged animal survival, compared with control virus ICOVIR15. High molecular weight HA inhibits adenovirus-induced NF-κB signaling in macrophages in vitro , linking HA degradation to macrophage activation. Combining ICOVIR17 with anti-PD-1 antibody further extended the survival of GBM-bearing mice, achieving long-term remission in some animals. Mechanistically, CD4 + T cells, CD8 + T cells, and macrophages all contributed to the combination therapy that induced tumor-associated proinflammatory macrophages and tumor-specific T-cell cytotoxicity locally and systemically., Conclusions: Our studies are the first to show that immune modulatory ICOVIR17 has a dual role of mediating degradation of HA within GBM ECM and subsequently modifying the immune landscape of the TME, and offers a mechanistic combination immunotherapy with PD-L1/PD-1 blockade that remodels innate and adaptive immune cells., (©2020 American Association for Cancer Research.)

Centrally located completely endophytic renal hilar tumors pose a technical challenge, especially during a minimally invasive surgery. Relation of the tumor to the renal vasculature decides the approach. Tumors placed anterior to the vasculature can be approached in the anterior trans-hilar manner. However, tumors placed posterior to the vasculature need a posterior approach, which is quite a difficult maneuver during transperitoneal laparoscopy. Adequate exposure to access the resection plane is the key principle. We describe a laparoscopic technique for enucleation of such tumors, applying the surgical principle of radial nephrotomy in the intersegmental plane which is usually performed to remove renal stones., Competing Interests: Conflicts of Interest: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Urology.)

Development of new anti-bacterial agents acting upon underexploited targets and thus evading known mechanisms of resistance is the need of the hour. The highly conserved and distinct bacterial fatty acid biosynthesis pathway (FAS-II), presents a validated and yet relatively underexploited target for drug discovery. FabI and its isoforms (FabL, FabK, FabV and InhA) are essential enoyl-ACP reductases present in several microorganisms. In addition, the components of the FAS-II pathway are distinct from the multi-enzyme FAS-I complex found in mammals. Thus, inhibition of FabI and its isoforms is anticipated to result in broad-spectrum antibacterial activity. Several research groups from industry and academic laboratories have devoted significant efforts to develop effective FabI-targeting antibiotics, which are currently in various stages of clinical development for the treatment of multi-drug resistant bacterial infections. This review summarizes all the natural as well as synthetic inhibitors of gram-positive and gram-negative enoyl ACP reductases (FabI). The knowledge of the reported inhibitors can aid in the development of broad-spectrum antibacterials specifically targeting FabI enzymes from S. aureus, S. epidermidis, B. anthracis, B. cereus, E. coli, P. aeruginosa, P. falciparum and M. tuberculosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To present our initial experience with double-face augmentation urethroplasty for near-obliterative bulbar urethral strictures and analyze the short-term outcomes., Material and Methods: We retrospectively evaluated a prospectively maintained database of patients with near-obliterative bulbar urethral strictures (>2 cm), who underwent double-face augmentation urethroplasty. The patients' demographic characteristics, clinical data, and data regarding the investigations conducted were analyzed. Near-obliterative urethral stricture was defined as lumen <6 Fr. Double-face urethroplasty was performed using a ventral approach, during which dorsal inlay and ventral onlay buccal mucosal graft (BMG) augmentation were performed. A successful outcome was defined as normal voiding without the need for any instrumentation to improve the urinary flow rate., Results: A total of 37 patients with a mean age of 50±11.7 years, who underwent this procedure were included in the study. The mean stricture length was 5.2±0.95 cm. The mean length of the dorsal inlay BMG augmentation was 3.1±0.5 cm and that of the ventral onlay BMG augmentation was 6.3±1.2 cm. Post-void dribbling (18.9%) was the most commonly reported complication. The maximum flow rates and symptom scores significantly improved in both groups compared with the preoperative parameters (p<0.001). The incidence of both erectile dysfunction and ejaculatory failure was reported in 6 (16.2%) patients; respectively. The overall success rate was 86.5% at a median follow-up period of 36 months (IQR: 26.5-43)., Conclusion: Double-face augmentation urethroplasty is a safe and feasible option for near-obliterative bulbar urethral strictures, and our study showed satisfactory short-term outcomes for the same.

Triple-negative breast cancer (TNBC) is a difficult-to-treat disease with high rates of local recurrence, distant metastasis, and poor overall survival with existing therapies. Thus, there is an unmet medical need to develop new treatment regimen(s) for TNBC patients. An oncolytic herpes simplex virus encoding a master anti-tumor cytokine, interleukin 12, (designated G47Δ-mIL12) selectively kills cancer cells while inducing anti-tumor immunity. G47Δ-mIL12 efficiently infected and killed murine (4T1 and EMT6) and human (HCC1806 and MDA-MB-468) mammary tumor cells in vitro . In vivo in the 4T1 syngeneic TNBC model, it significantly reduced primary tumor burden and metastasis, both at early and late stages of tumor development. The virus-induced local and abscopal effects were confirmed by significantly increased infiltration of CD45 + leukocytes and CD8 + T cells, and reduction of granulocytic and monocytic MDSCs in tumors, both treated and untreated contralateral, and in the spleen. Significant trafficking of dendritic cells (DCs) were only observed in spleens of virus-treatment group, indicating that DCs are primed and activated in the tumor-microenvironment following virotherapy, and trafficked to lymphoid organs for activation of immune cells, such as CD8 + T cells. DC priming/activation could be associated with virally enhanced expression of several antigen processing/presentation genes in the tumor microenvironment, as confirmed by NanoString gene expression analysis. Besides DC activation/priming, G47Δ-mIL12 treatment led to up-regulation of CD8 + T cell activation markers in the tumor microenvironment and inhibition of tumor angiogenesis. The anti-tumor effects of G47Δ-mIL12 treatment were CD8-dependent. These studies illustrate the ability of G47Δ-mIL12 to immunotherapeutically treat TNBC., (Copyright © 2020 Ghouse, Nguyen, Bommareddy, Guz-Montgomery and Saha.)

In the metastasis-targeted organs, angiogenesis is essential for the progression of dormant micrometastases to rapidly growing and clinically overt lesions. However, we observed changes suggesting angiogenic switching in the mouse lungs prior to arrival of tumor cells (i.e., in the premetastatic niche) in the models of breast carcinoma. This angiogenic switching appears to be caused by myeloid-derived suppressor cells recruited to the premetastatic lungs through complement C5a receptor 1 signaling. These myeloid cells are known to secrete several proangiogenic factors in tumors, including IL-1β and matrix metalloproteinase-9, and we found upregulation of these genes in the premetastatic lungs. Blockade of C5a receptor 1 synergized with antiangiogenic Listeria monocytogenes -based vaccines to decrease the lung metastatic burden by reducing vascular density and improving antitumor immunity in the lungs. This was mediated even when growth of primary breast tumors was not affected by these treatments. This work provides initial evidence that angiogenesis contributes to the premetastatic niche in rapidly progressing cancers and that inhibiting this process through immunotherapy is beneficial for reducing or even preventing metastasis., (Copyright © 2020 by The American Association of Immunologists, Inc.)

A facile synthetic strategy has been developed for the generation of structurally diverse N-fused heterocycles. The formation of fused 1,2,3-triazole indolo and pyrrolodiazepines proceeds through an initial Knoevenagel condensation followed by intramolecular azide-alkyne cycloaddition reaction at room temperature without recourse to the traditional Cu(I)-catalyzed azide-alkyne cycloadditions. The synthesized compounds were evaluated for their in vitro anti-cancer activity against the NCI 60 cell line panel. Among the tested compounds, 3a and 3h were found to exhibit potent inhibitory activity against many of the cell lines. Cell cycle analysis indicated that the compounds inhibit the cell cycle at sub G1 phase. The DNA- nano drop method, viscosity experiment and docking studies suggested these compounds possess DNA binding affinity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC 50 of 7.01 ± 0.20 µM and arresting MCF-7 cell growth at G2/M phase and S phase. Induction of apoptosis was confirmed by morphological changes like cell shrinkage, blebbing and cell wall deformation, dose dependent increase in the mitochondrial membrane potential (ΔΨm) and ROS levels. Further, dose dependent decrease in Gal-1 protein levels proves Gal-1 mediated apoptosis by 6g. Molecular docking studies were performed to understand the Gal-1 interaction with compound 6g. In addition, RP-HPLC studies showed 85.44% of 6g binding to Gal-1. Binding affinity studies by fluorescence spectroscopy and Surface Plasmon Resonance (SPR) showed that 6g binds to Gal-1 with binding constant (K a ) of 1.2 × 10 4  M -1 and equilibrium constant K D value of 5.76 × 10 -4 M respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Posterior hilar renal tumor extirpation by partial nephrectomy is a unique challenge for transperitoneal laparoscopy. We describe our novel technique of "polar flip" for these tumors. Kidney is rotated by around 45 -60 degrees after mobilisation so that lower pole faces anteriorly and upper pole faces posteriorly, thereby exposing the posterior surface for maneuverability. Technical highlights are hilar control, complete kidney mobilisation, initial flipping with dissection in Gil Vernet's plane to clip posterior segmental renal artery, en mass hilar clamping in normal lie, polar flipping, dissection in Gil Vernet's plane till renal sinus fat, completion of tumor excision, selective vascular ligation, renorhaphy and nephropexy., Competing Interests: Conflicts of interest: There are no conflicts of interest.

Objective: To present our transurethral enucleation with bipolar energy (TUEB) technique, wherein the enucleated adenoma is resected while keeping it attached near the verumontanum avoiding the need of a morcellator, and to evaluate the safety and short-term outcomes of our technique of TUEB for the treatment of symptomatic benign prostatic hypertrophy (BPH)., Methods: This was a retrospective evaluation of prospectively maintained database of patients with symptomatic BPH who underwent TUEB from January 2016 to September 2017. Patients with a minimum follow-up period of 6 months were included in the study. All patients were assessed using the international prostate symptom score (IPSS), uroflometry (Q-max), and transrectal ultrasonography (TRUS) of the prostate. TUEB was indicated for patients with total prostate volumes >60 g on TRUS. Postoperative outcome measures, including urinary incontinence, Q-max, and IPSS, were recorded at each follow-up visit., Results: A total of 103 patients underwent TUEB. The mean patient age was 64 ± 7 years, and the median operative time was 54 minutes (interquartile range [IQR]: 44-66). The median resected prostate weight was 39 g (IQR: 28-54 g), corresponding to approximately 87% of the assessed transitional zone volume. The mean postoperative hemoglobin drop of 1.08 ± 0.28 g/dL was clinically insignificant. There was significant improvement in the IPSS and Q-max postoperatively, when compared to baseline parameters (P < .05)., Conclusion: Our TUEB technique is safe and effective in treating symptomatic BPH with acceptable complications and favorable short-term outcomes. TUEB allows near-complete enucleation of a prostate adenoma, followed by resection, thus avoiding the need for a morcellator., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Though the overall safety of laparoscopic nephrectomy (simple or radical) is well established, for a novice it remains a challenge. The classical description of laparoscopic nephrectomy entails dissection either from caudal to cephalad side or vice versa. Herein we describe our "two window technique" for managing renal hilum during laparoscopic (simple/radical) nephrectomy. Our main intention in description of this technique is to reduce the level of apprehension for a novice urologist for performing laparoscopic nephrectomy. After colon mobilization, sequential lower and upper windows are created around the hilum following which hilar vessels are dissected circumferentially when the hilum is at a stretch by traction from either of the window. There are multiple potential advantages of this method which includes easier and safer dissection especially for novice in this field by giving a safety window of application of vascular clamp in cases of vascular bleeds. Intrahilar dissection in stretched condition becomes safer with vision from all around 360° for safe application of Hem-o-lok® clips. Due to the widely exposed field, injuries to adrenal vein and lumbar veins would be minimized and the chances of missed accessory vessel would be minimized. En mass hilar control with vascular clamp in cases of partial nephrectomy is possible with same approach as well as the en block stapling is feasible in cases of nephrectomy. This needs a validation across multiple centers with comparative studies before considering it as a standard of practice. We sincerely believe that this is safe and easily reproducible by a novice., Competing Interests: Conflicts of interest: There are no conflicts of interest.

Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient Kit mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the Kit mutations result in complex alterations of the immune system in addition to MC deficiency. We revisited the role of MCs in vaccination responses using Mcpt5-Cre R26 DTA/DTA and Cpa3 Cre/+ mice that lack connective tissue MCs or all MCs, respectively, but feature an otherwise normal immune system. These animals showed no impairment of T and B cell responses to intradermal vaccination with protein antigen plus complete Freund's adjuvant. Moreover, we demonstrate that the adjuvant effects of the MC secretagogue c48/80 in intradermal or mucosal immunization are independent of the presence of MCs. We hence find no evidence for a regulation by MCs of adaptive immune responses to protein antigens. The finding that immunological MC functions differ from those suggested by experiments in Kit mutants, emphasizes the importance of rigorous tests in Kit-independent MC-deficiency models.

Complement is an effector of innate immunity and a bridge connecting innate immunity and subsequent adaptive immune responses. It is essential for protection against infections and for orchestrating inflammatory responses. Recent studies have also demonstrated contribution of the complement system to several homeostatic processes that are traditionally not considered to be involved in immunity. Thus, complement regulates homeostasis and immunity. However, dysregulation of this system contributes to several pathologies including inflammatory and autoimmune diseases. Unexpectedly, studies of the last decade have also revealed that complement promotes cancer progression. Since the initial discovery of tumor promoting role of complement, numerous preclinical and clinical studies demonstrated contribution of several complement components to regulation of tumor growth through their direct interactions with the corresponding receptors on tumor cells or through suppression of antitumor immunity. Most of this work, however, focused on a role of complement in regulating growth of primary tumors. Only recently, a few studies showed that complement promotes cancer metastasis through its contribution to epithelial-to-mesenchymal transition and the premetastatic niche. This latter work has shown that complement activation and generation of complement effectors including C5a occur in organs that are target for metastasis prior to arrival of the very first tumor cells. C5a through its interactions with C5a receptor 1 inhibits antitumor immunity by activating and recruiting immunosuppressive cells from the bone marrow to the premetastatic niche and by regulating function and self-renewal of pulmonary tissue-resident alveolar macrophages. These new advancements provide additional evidence for multifaceted functions of complement in cancer.

Introduction: Transurethral resection of the prostate has been considered as the gold standard for benign prostatic hyperplasia (BPH). LASER enucleation procedures have emerged as a size-independent gold standard. The flip side of LASER procedures is the initial cost of investment and a long learning curve. Transurethral enucleation with bipolar (TUEB) has emerged as an alternative prostatic enucleation procedure. We present our initial experience in TUEB., Materials and Methods: Fifty patients with BPH and indications for surgery underwent TUEB from December 2014 to October 2015. Patients with prostate size >40 g were selected. All surgeries were done by a single urologist. Various parameters such as preoperative and postoperative International Prostate Symptom Score (IPSS) scores, Qmax (peak flow) scores, duration of surgery, duration of enucleation, drop in hemoglobin, postoperative pain scores, weight of morcellated tissue, and the incidence of stress urinary incontinence were measured., Results: The mean age was 58 years and mean prostatic size was 84 g. Sixteen patients had refractory urinary retention. The mean IPSS score in remaining patients was 24.5. The mean preoperative maximal flow rate (Qmax) on uroflowmetry was 9.3 mL/s. The mean overall duration of surgery was 83 min. The mean drop in hemoglobin was 0.9 g/dl. The mean postoperative pain scores at 12 and 24 h after surgery were 2.1 and 1.3. The mean weight of morcellated tissue was 48 g. Twenty-six patients had de novo transient stress urinary incontinence after surgery. The mean IPSS score after TUEB was 8.3 showing significant improvement in all aspects of IPSS. The mean post-TUEB Qmax on uroflowmetry was 25 mL/s., Conclusions: TUEB is an effective surgical management of BPH. TUEB allows enucleation of large adenomas in a single sitting, mimicking conventional open enucleation of the prostate while having all the advantages of a minimally invasive surgery., Competing Interests: Conflicts of interest: There are no conflicts of interest.

High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV)-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer. We analyzed HPV-induced epithelial hyperplasia and squamous cell carcinoma formation, as well as growth of tumors inoculated into the dermis, in mice lacking skin mast cells. Unexpectedly, the absence of mast cells had no effect on HPV-induced epithelial growth or angiogenesis, on growth kinetics of inoculated tumors, or on the immunological tumor micro-milieu. Thus, the conspicuous recruitment of mast cells into tumor tissues cannot necessarily be equated with important mast cell functions in tumor growth., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Laparoscopic or robotic-assisted laparoscopic radical prostatectomy (RALP) is a frequently used approach for localized carcinoma prostate. For intermediate and high-risk cancers, extended pelvic lymph node dissection (e-PLND), is often performed. Conventional e-PLND involves piecemeal retrieval of lymphatic tissue. We describe a novel technique of laparoscopic e-PLND, which involves en-masse removal of pelvic lymph nodes from each side, based on an overlying peritoneal scaffold., Materials and Methods: Fifteen cases of intermediate and high-risk carcinoma prostate underwent laparoscopic radical prostatectomy (LRP) with peritoneal scaffold based e-PLND within a period of 1 year. We describe the surgical techqniue and outcomes in terms of operative time and lymph nodes retrieved., Results: The mean operating times for "peritoneal scaffold" lymphatic dissection was 48 min (38-64). The total number of lymph nodes retrieved was 18 (14-22). There were no cases with postoperative lymph collection or hematoma., Conclusion: The "peritoneal scaffold" technique of e-PLND is a novel technique, which involves having a peritoneal scaffold to bind and hold all the lymphatic tissues together in its anatomical orientation during dissection. This enables complete retrieval of specimen during LRP and RALP.

Mast cells are critical promoters of adaptive immunity in the contact hypersensitivity model, but the mechanism of allergen sensitization is poorly understood. Using Mcpt5-CreTNF(FL/FL) mice, we show here that the absence of TNF exclusively in mast cells impaired the expansion of CD8(+) T cells upon sensitization and the T-cell-driven adaptive immune response to elicitation. T cells primed in the absence of mast cell TNF exhibited a diminished efficiency to transfer sensitization to naive recipients. Specifically, mast cell TNF promotes CD8(+) dendritic cell (DC) maturation and migration to draining lymph nodes. The peripherally released mast cell TNF further critically boosts the CD8(+) T-cell-priming efficiency of CD8(+) DCs, thereby linking mast cell effects on T cells to DC modulation. Collectively, our findings identify the distinct potential of mast cell TNF to amplify CD8(+) DC functionality and CD8(+) T-cell-dominated adaptive immunity, which may be of great importance for immunotherapy and vaccination approaches., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: With safe obstetric practices now globally available, most vesico-vaginal fistulas (VVF) presenting in recent times are secondary to various gynecologic surgeries. Most of them are supra-trigonal in location. Laparoscopic repair of VVF is gaining ground as an alternative to open repair of VVF. In this study, we describe our initial experience with a novel technique of laparoscopic VVF repair involving a limited transverse cystotomy for access and a single-layered barbed suture closure of bladder., Materials and Methods: Twenty cases of supra-trigonal VVFs following gynecologic surgeries were taken up for repair by our novel technique. The mean age of the patients was 32 years and the mean VVF size was 1.5 cm., Results: The mean operative time was 54 min. Estimated mean blood loss was 30 ml and the mean postoperative stay was 2.5 days. None of the patients had any recurrence with a mean follow-up of 14 months., Conclusion: The limited transverse cystotomy approach has advantages in decreasing the operative time, improving ease of laparoscopic suturing, allowing an automatic separation of suture lines and allowing for an easier anterior dissection of the bladder to reduce tension on the suture line if necessary. Further this approach provides excellent results in select patients of supra-trigonal VVF in terms of continence and postoperative bladder overactivity., (© 2015 S. Karger AG, Basel.)