Use of TP4303 to identify prostate cancer cells in voided urine samples.

INTRODUCTION: Prostate cancer is the second most common malignancy in men worldwide. Genomic VPAC receptors are expressed on malignant prostate cancer cells and can be targeted and imaged optically by a peptide labeled fluorophore. The objective of our study was to assess the feasibility of detecting cancer of the prostate using a voided urine sample. MATERIALS AND METHODS: Patients ≥ 40 years old, with lower urinary tract symptoms and serum PSA > 4 ng/mL formed the study group. The first 50 mL of voided urine sample was collected and processed. The cells that were shed in the voided urine were fixed and stained with a peptide TP4303 and incubated. The slide was then stained with DAPI which binds with the DNA in the nucleus. All patients underwent a standard 12-core TRUS-guided prostate biopsy. RESULTS: A total of 318 patients were included in the study, of these 158 were histologically confirmed cancers. Voided urine samples were positive for VPAC receptors in 154 (97.46%) of these. The remaining 160 patients had no cancer on the HPR examination and none of these patients were positive for VPAC receptors. CONCLUSIONS: This study validates our belief that patients with prostate cancer shed malignant cells in the urine that can be identified by targeting the VPAC receptors. If these results are further validated by multicentric studies, then this could form the basis for indications for a preliminary prostate biopsy in patients with elevated serum PSA but normal digital examination or in patients needing a repeat biopsy.

Insights and Opinions of Critical Care Healthcare Professionals in the Management of Carbapenem-resistant Enterobacteriaceae Cases and Antibiotic-Resistant Infections in the Intensive Care Unit Setting: A Survey-Based Approach.

INTRODUCTION: A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-ß-lactamase 1 (NDM-1) is a carbapenemase that is resistant to ß-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains. AIM: The survey aimed to gather critical care healthcare professionals (HCPs') opinions on their current practices in managing infections acquired in the hospital and ICU settings, with a focus on CRE cases, specifically NDM-1 and other antibiotic-resistant infections. METHODS: Responses from critical care healthcare professionals, including online surveys and in-person interviews, to gain insights into the management of infections caused by multidrug-resistant bacteria. The findings related to the insights on the prevalence of bacterial flora, clinical experiences on efficacy and safety of meropenem sulbactam ethylenediaminetetraacetic acid (EDTA) (MSE) in CRE cases, and various combination therapies of antibiotics used to treat antibiotic-resistant infections in ICU setting were evaluated. RESULTS: Klebsiella pneumoniae bacteria were the most common bacteria in cultures, followed by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. NDM-1 was the type of carbapenemase found in around 50% of CRE patients. MSE is among the most preferred antibiotics besides colistin, polymyxin B, and ceftazidime avibactum for CRE cases and specifically for NDM-1 cases due to its high rate of efficacy and safety. CONCLUSION: The article concludes with a discussion on the antibiotics used in response to CRE cases, reporting that critical care HCP considers MSE with high efficacy and safe antibiotic combination and was used as both monotherapy and in combination with other antibiotics. The survey highlights the need for exploring and better understanding the role of MSE in the management of CRE infections, especially in NDM-1.

Neoadjuvant Chemotherapy Followed by Cystectomy: a Single-Center Experience.

Nearly 50% of patients with muscle-invasive bladder cancer treated with cystectomy alone will progress to metastatic disease. Surgery alone is not a sufficient therapy in a large number of patients with invasive bladder cancer. Systemic therapy with cisplatin-based chemotherapy has been shown to provide response rates in several bladder cancer studies. There have been multiple randomized controlled studies undertaken to define further the effectiveness of neoadjuvant cisplatin-based chemotherapy in advance of cystectomy. In this study, we have retrospectively reviewed our series of patients who underwent neoadjuvant chemotherapy followed by radical cystectomy for muscle-invasive disease. Between Jan 2005 and Dec 2019, 72 patients underwent radical cystectomy following neoadjuvant chemotherapy over a 15-year period. The data was retrospectively collected and analyzed. The median age was 59.84 ± 8.967 years (range, 43 to 74), and the ratio of male to female patients was 5:1. Of the 72 patients, 14 (19.44%) completed all the three cycles, 52 (72.22%) completed at least two cycles, and the remaining 6 (8.33%) completed only one cycle of neoadjuvant chemotherapy. A total of 36 (50%) patients died during the follow-up period. The mean and median survival of the patients was 84.85 ± 4.25 months and 91.0 ± 5.83 months respectively. Neoadjuvant MVAC should be offered to patients with locally advanced bladder cancer and who are candidates for radical cystectomy. It is safe and effective in patients with adequate renal function. The patients need to be carefully monitored for chemotherapy-induced toxic effects, and appropriate intervention is necessary in the event of severe adverse effects.

Risk Factors for Bladder Cancer: Results of a Survey of Hospital Patients.

Introduction: Several risk factors have been identified in the occurrence of bladder cancer. These include genetic and hereditary factors, smoking and tobacco use, increased body mass index, occupational exposure to certain chemicals and dyes, medical conditions such as chronic cystitis and infectious diseases such as schistosomiasis. This study aimed to evaluate risk factors in patients with bladder cancer. Materials and Methods: All patients presenting to the uro-oncology department of the hospital with imaging and histology confirmed bladder cancer were included in the study. Age- and gender-matched patients presenting to the department of urology with benign disorders were prospectively included as controls. All the study subjects and the controls completed a self-administered structured questionnaire. Results: Seventy-two (67.3%) of the participants with bladder cancer were males. The mean age of participants with bladder cancer was 59.24 ± 16.28 years. Most participants with bladder cancer worked as farmers (35.5%) or industrial workers (24.3%). Recent history of recurrent urinary tract infections was seen in 85 (79.4%) of the participants with bladder cancer and 32 (30.8%) of controls. Diabetes mellitus was more common among participants with bladder cancer. A significant number of participants with bladder cancer used tobacco and smoked compared to controls. Conclusions: This study highlights numerous potential biological and epidemiological factors that may act as a risk factors for bladder cancer. These factors could explain the gender differences observed in the incidence of bladder cancer. In addition, the study indicates the intense risk of tobacco products and smoking on the incidence of bladder cancer.

Voided urine test to diagnose prostate cancer: Preliminary report.

OBJECTIVES: Prostate cancer (PCa) is a common malignancy affecting elderly male. At present, PCa is estimated using serum prostate-specific antigen (PSA). Prostate biopsy remains the gold standard to confirm the diagnosis of PCa. In this preliminary study, we have assessed the feasibility of detecting PCa using voided urine by targeting the genomic vasoactive intestinal peptide receptor (VPAC) expressed on malignant PCa cells. MATERIAL AND METHODS: Patients ≥40 years old, with no lower urinary tract symptoms (LUTS) and serum PSA levels of <1.6 ng/mL formed the control group and patients ≥40 years old, with LUTS and serum PSA >2.6 ng/ mL formed the study group. Patients were advised to give the first 50 mL of voided urine sample for the detection of malignant markers by targeting the VPAC. The results of histopathological studies were then compared to the results of urine biomarker. RESULTS: The study revealed absence of malignant markers in 75 patients (control group). In the study group, all the 33 patients with adenocarcinoma were positive for malignant markers in the biomarker study and absence of malignant markers in the 32 patients with benign histology. The results of the biomarker studies and histopathology were consistent with each other. CONCLUSION: This preliminary study validates our belief that patients with PCa do shed malignant cells in the urine which can be identified by targeting the VPAC. The investigation is easy and our data appear to be highly encouraging and further serve as a simple, reliable, and a non-invasive tool in the detection of PCa.

Modified Inguinal Lymph Node Dissection in Groin-Negative Patients of Penile Cancer: Our Experience.

Cancer of the penis is an important health problem in India, causing significant morbidity. Involvement of locoregional lymph nodes is the most significant prognostic factor for patients with penile cancer. In this study, we reviewed clinical data of all patients who underwent modified inguinal lymph node dissection as a means to diagnose micro-metastasis in inguinal lymph nodes, and analysed the outcomes. We retrospectively reviewed the hospital clinical charts of patients treated for carcinoma of the penis. Inguinal and distant metastases were assessed by physical examination, ultrasound imaging of the inguinal region, computed tomography of the abdomen and pelvis and a chest radiograph. Patients with clinically negative inguinal lymph nodes underwent modified lymph node dissection (mILND) both to diagnose and stage the disease. Complications occurring during a 30-day period after surgery were defined as early and thereafter as late complications. A total of 40 patients with a mean age of 52.27±13.10 (range 25-73) years underwent mILND. Wedge biopsy from the primary lesion had revealed intermediate-risk disease in 22 (55%) patients and high-risk disease in 18 (45%) patients. Histopathological examination of the primary penile lesion revealed a pT1 lesion in 32 patients and a pT2 lesion in the remaining 8 patients. Fourteen (35%) of the 40 patients showed micro-metastases in the inguinal lymph nodes on frozen sections. The mean follow-up in these patients was 56.6±18.09 months. There were no instances of local or systemic recurrences seen in 38 (95%) patients within 5 years. Superficial lymph node dissection and where facilities are available DSLNB remain the standard of care in the management of patients with clinically groin-negative (cN0) intermediate- and high-risk groups. Modified inguinal lymph node dissection would be a safe and appropriate alternative to this in all centres that do not have access to newer modalities like DSLNB, video-endoscopic (VEIL) or robotic-assisted techniques.

Percutaneous nephrolithotomy in children.

INTRODUCTION: The high success rates of percutaneous nephrolithotomy (PCNL) in the clearance of large renal calculi has made it a primary mode of surgical management in adults. Similarly, in children too PCNL has been gaining ground and the indications for the same are on the rise. We retrospectively evaluated the safety and efficacy of this technique, in children below 18 years of age. MATERIALS AND METHODS: We retrospectively reviewed the inpatient, outpatient records, imaging films of all children with renal stones undergoing PCNL at our hospital. RESULTS: During the study period, 123 children underwent 129 PCNL at our centre for renal calculi. The mean age was 11.06 years and 87 (70.73%) of the children were males. The size of the stones varied from 15 to 37 mms in the longest diameter. A complete staghorn was noted in six (4.65%) and a partial staghorn in nine (6.97%) children. Supine PCNL was performed in 21 (16.2%) children and remaining 102 (83.7%) children underwent PCNL in prone position. The mean drop in haemoglobin was 1.24 gm%. Stone clearance was achieved in 122 (94.5%) children. Post-operatively four (3.1%) children needed blood transfusions due to excessive bleeding. CONCLUSIONS: Refinements in percutaneous access techniques, miniaturization of instruments, and technologic advances in energy sources for lithotripsy have led to improvement of outcomes and have lowered the morbidity rates in children following PCNL. It is a safe and effective means of clearing large volumes of renal calculi with minimal morbidity.

Association of erectile dysfunction and type II diabetes mellitus at a tertiary care centre of south India.

BACKGROUND AND AIMS: Erectile Dysfunction (ED) is more common in diabetic men and, unfortunately, occurs at an earlier age in diabetic patients when compared with the general population. The study aims to evaluate the independent predictors of ED in adult men with type 2 diabetes mellitus (DM) at a tertiary care center of South India. METHODS: A total of 720 men aged 30-70 years who had been diagnosed with type 2 DM were enrolled for the study from January 2017 to January 2020 from the outpatient diabetes clinic of the Hospital. All patients completed the abridged version of the International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: The mean age of the patients was (58.4 ± 7.8 years). 68.6% of subjects had varying degrees of erectile dysfunction, of which 54.6% had moderate to severe ED. 55.8% had poor glycemic control (HbA1c ≥ 7%). Subjects with ED had a longer duration of DM than those without ED (mean DM duration was 8.1 ± 4.9 years versus 4.4 ± 3.5 years; p < 0.001). Longer duration of DM, poor glycemic control, hypertension, peripheral arterial disease, testosterone deficiency were all independent predictors ED (p < 0.05). CONCLUSIONS: A high incidence of erectile dysfunction was observed in type 2 DM patients attending the diabetic clinic, and over half of the people affected were of moderate-to-severe in intensity. Poor glycemic control, testosterone deficiency, peripheral arterial disease were the modifiable risk factors for ED in diabetic subjects. At the same time, a longer duration of type 2 DM was noticed as a glaring non-modifiable risk factor, according to our study.

Adrenal leiomyosarcoma in a young adult male.

Leiomyosarcomas are known to typically originate from smooth muscle cell. Primary adrenal leiomyosarcoma is an extremely rare mesenchymal tumor associated with delayed diagnosis and poor prognosis. We report a rare case of leiomyosarcoma arising from the left adrenal gland in a 27-year-old male who presented with left side back ache. It was a solid mass of 9 × 6.5 × 7  cms situated superior to the left kidney. Left adrenalectomy was done and microscopic examination revealed a primary adrenal leiomyosarcoma.

Bleeding angiomyolipoma mimiking a ruptured adrenal tumour.

Angiomyolipoma is a benign neoplasm of the kidney, and is the most common renal tumour associated with haemorrhage. Risk of bleeding increases with the size of the angiomyolipoma. We report a case of spontaneous bleeding from an upper polar renal angiomyolipoma mimicking a spontaneous adrenal bleed from a pheochromocytoma.

Nephron Sparing Surgery for Synchronous Bilateral Wilms-Operative Steps.

Approximately 5% of children with Wilms tumor present with bilateral disease. The treatment challenge is to achieve a high cure rate while maintaining adequate long-term renal function. We report the feasibility and outcome of nephron sparing surgery in a child with bilateral Wilms tumor who was treated at our institution.

Low-Grade, Multiple, Ta Non-muscle-Invasive Bladder Tumors: Tumor Recurrence and Worsening Progression.

Nearly half of newly diagnosed cases of bladder cancer are low grade, noninvasive, and papillary tumors. The standard treatment for non-muscle-invasive bladder cancer (NMIBC) has been transurethral resection of the bladder tumor (TUR-BT) with or without adjuvant intravesical instillation (IVI) of chemotherapy or Bacillus Calmette-Guerin (BCG) therapy. NMIBC is known to be associated with high rates of recurrence and risk of progression. In this study, we have retrospectively analyzed the clinical outcome of initially diagnosed multiple low-grade Ta tumors, with a special focus on tumor recurrence and worsening progression (WP) pattern. We retrospectively reviewed 42 patients with primary, multiple, low-grade Ta bladder cancer. We defined WP as confirmed high-grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinico-pathological factors and tumor recurrence as well as WP pattern were analyzed. Tumor recurrence and WP occurred in 23 (54.76%) and 8 (19.04%) patients during follow-up (median follow-up: 57.38 months), respectively. WP to high grade/stage was seen in 8 patients. Multivariate analysis demonstrated that use of tobacco (p < 0.0001) and absence of IVI (p < 0.0001) were significant risk factors for tumor recurrence. The 5-year recurrence-free survival rate for non-tobacco users (74.0%) was significantly higher than that for tobacco users (42.5%, p = 0.0001), and also higher for patients receiving intravesical instillation (84.2 vs. 30.0% without IVI, p = 0.0001). Recurrence is common in patients with low-grade, Ta bladder cancer, especially in the setting of multiplicity. Recurrences occurred in 54.76% of patients and WP occurred in 19.04% of patients. Use of tobacco and non-use of IVI were strongly associated with high recurrence rate.

Frontiers of monoclonal antibodies: Applications in medical practices.

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.