Evaluation of Fibroblast Growth Factor Receptor 3 (FGFR3) and Tumor Protein P53 (TP53) as Independent Prognostic Biomarkers in High-Grade Non-muscle Invasive Bladder Cancer.

Introduction Bladder cancer is a significant health issue with an increased recurrence and progression rate, requiring invasive follow-up, which shows a poor prognosis. In addition, the prognostic role of mutant fibroblast growth factor receptor 3 (FGFR3) and tumor protein P53 (TP53) is controversial; therefore, we investigated the methylation status and their altered gene expression in low- and high-grade non-muscle-invasive bladder cancer (NMIBC) subjects. Materials and methods This case-control study was conducted between 2020 and 2023, in which n = 115 tumor tissues (NMIBC n = 85) and (controls n = 30) were examined for FGFR3 and FGFR promoter methylation and expression using methylation-specific PCR (MSP) and real-time PCR. The multivariate regression analysis and Kaplan-Meier (KM) plots were used to establish the association of FGFR3 and TP53 with clinicopathological features and survival outcomes of NMIBC patients. Results High-grade NMIBC tumors showed substantial methylation patterns, with TP53 hypomethylated (p = 0.034) and FGFR3 hypermethylated (p = 0.046), as well as significant mRNA expression of Tp53 and FGFR3 (p = 0.001). The multivariate analysis shows FGFR3 and Tp53 were associated with recurrence-free survival with sensitivity (p = 0.045 (78%); 0.034 (70.7%)) and progression-free survival (p = 0.022(61.5%); 0.038 (69.2%)).  Conclusion The findings of this investigation indicate that FGFR3 hypermethylation and TP53 hypomethylation are independent prognostic indicators that aid in the evaluation of disease outcomes in high-grade NMIBC tumors.

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association.

INTRODUCTION: Bladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. MATERIAL AND METHODS: A total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. RESULT: In high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. CONCLUSION: The upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Transperitoneal Laparoscopic Pyelolithotomy in Pelvic Ectopic Kidneys: Experience From a Northern Indian Tertiary Care Institution.

Introduction The ectopic pelvic kidneys have a higher likelihood of developing renal stones due to urinary stasis caused by the abnormal position of the renal pelvis, altered course of the ureter, and kidney malrotation. This retrospective study highlights the safety, efficacy, and feasibility of performing transperitoneal laparoscopic pyelolithotomy in cases of pelvic ectopic kidney. Methodology The 15 patients with ectopic pelvic kidneys and nephrolithiasis underwent laparoscopic pyelolithotomy. The kidney was exposed either by moving the bowel or using a trans-mesocolic approach. A surgical procedure was performed to remove stones from the renal pelvis using laparoscopic forceps. Following the placement of a double J stent, the incision in the renal pelvis was closed. The procedure was completed after the intraperitoneal drain was inserted. Results A total of 15 patients underwent the transperitoneal laparoscopic pyelolithotomy procedure, with a male-to-female ratio of 3:2. The average age of the patients was 41 (25-58) years, while the average size of the stones was 3.8 cm. Additionally, seven (46.6%) patients had the presence of caliceal stones in conjunction with the pelvic stone. Out of the 15 patients, some had stones on the left side (n = 9, 60%), while others had stones on the right side (n = 6, 40%). The operation with an average duration was 125 minutes with a range of (90-190). Fourteen (93.3%) patients were found to be free of stones. A patient required extracorporeal shock wave lithotripsy (ESWL) to address a small caliceal residual stone measuring 8 mm. After just one session of ESWL, this stone was completely cleared. All stones were successfully removed, resulting in a 100% stone-free rate. Conclusions Laparoscopic pyelolithotomy is a highly effective and efficient procedure for treating large and numerous stones in the ectopic pelvic kidney. This method has a significant level of efficiency in removing stones with limited consequences.

A Pilot Study of Functional Outcomes in Adult Patients Treated With Valgus Intertrochanteric Osteotomy as a Primary Modality for Intracapsular Femoral Neck Fracture.

Background Intracapsular femoral neck fractures account for a majority of hip fractures. This study aimed to investigate the efficacy of valgus osteotomy as a primary treatment for intracapsular femoral neck fractures in adult patients aged 15-60 years, assessing its impact on functional outcomes and fracture union. Methodology A retrospective clinical analysis was conducted at the Department of Orthopedics and Traumatology, Osmania Government General Hospital, Hyderabad, India, focusing on patients treated with primary intertrochanteric valgus osteotomy for intracapsular femoral neck fractures. The study reviewed medical charts and radiographs of six patients aged between 15 and 60 years, diagnosed with recent isolated intracapsular femoral neck fractures, presenting between May 2019 and October 2021. The intervention involved Pauwels' intertrochanteric valgus osteotomy with various fixation methods. Main outcome measures included radiographic union, functional ability assessed by the Harris Hip Score, and evaluation for complications. Results All six patients achieved radiographic union at fracture and osteotomy sites, totaling a 100% success rate. The average follow-up duration was 14.8 months (12-20 months), with an average time of 5.1 months (2.5-6 months) from surgery to radiographic union. One patient experienced union with retroversion, while another developed avascular necrosis (AVN) by the study's conclusion. No instances of hardware failure or non-union were observed. The average Harris Hip Score obtained during the most recent clinical follow-up was 84, ranging from 69 to 94. All six patients regained independent walking ability without any support by the end of the follow-up period. Conclusion The combination of primary Pauwels' intertrochanteric valgus osteotomy with fixed-angle plating proves to be a highly effective method for addressing recent intracapsular femoral neck fractures, resulting in a 100% success rate in achieving union among the patient cohort.

Seasonal variation of HbA1c levels in diabetic and non-diabetic patients.

Background: Hemoglobin A1c (HbA1c) serves as a pivotal marker for long-term glycemic control. The Diabetes Control and Complications Trial (DCCT) established its relevance, yet gaps exist in understanding potential seasonal variations in HbA1c levels among diabetic patients. The study highlights the need to explore potential seasonal variations in HbA1c levels and their impact on diabetic patients. Materials and methods: This is an observational study conducted in a tertiary care hospital from January to December 2019, the study analyzed HbA1c levels in 8138 patients. Blood samples were collected using Potassium EDTA-containing vials and processed with an automated analyzer. Seasonal variations were explored using time series analysis. Results: Mean HbA1c levels peaked during the monsoon (June to September) and were lowest in autumn (October to November). Subgroup analysis revealed differences in patients with HbA1c values below and above 6.5 %. Those with controlled blood sugar showed higher levels in winter (December to February) and monsoon (June to September), while patients with HbA1c values ≥ 6.5 % exhibited significantly lower levels in monsoon (June to September) and autumn (October to November) compared to summer (March to May). Conclusion: In contrast to global trends, Indian patients demonstrated distinct seasonal variations in HbA1c levels. The highest levels during the monsoon (June to September) may be linked to reduced outdoor activity and dietary changes. The study emphasizes the need for tailored diabetes management considering seasonal influences. Further extensive, longitudinal studies across diverse Indian regions are recommended to comprehensively grasp the impact of seasonal changes on diabetes outcomes.

Utility of anticoagulation, pre-smearing and post-smearing hemolytic techniques on morphological assessment and reproducibility in fluid cytology.

Objective: Knowledge of proper collection, storage, preservation, and processing techniques is critical to ensuring proper handling and analysis of fluid cytology specimens. This study was conducted to determine the effect of anticoagulation, pre-smearing acetic acid treatment technique, and saline rehydration technique on morphological assessment, reproducibility, and reporting in fluid cytology. Material and Methods: The study was carried out in the cytopathology laboratory over 2 months (April-May 2022), where 100 effusion samples were analyzed. At least 20-40 mL of fluid was collected in heparinized and non-heparinized containers for each patient. Samples were processed in cytospin and stained with Giemsa and Papanicolaou stains. For 70 hemorrhagic specimens, an extra smear was prepared from the sediment and subjected to the saline rehydration technique as per the Indian Academy of Cytologists (IAC) guidelines. Seventy-three hemorrhagic specimens whose quantity received was more than 35 mL were subjected to the pre-smearing technique. These smears were evaluated for (a) the presence or absence of blue background/any other background staining, (b) cellularity, (c) cell morphology and (d) the presence/absence of microclots. Results: Heparinized samples showed no compromise in cellular morphology or cellularity although a blue background was observed in an occasional case. The pre-smearing technique had less background hemorrhage and preserved cell characteristics. The post-smearing saline rehydration technique did not compromise the cellularity but distorted morphology and showed background staining. Conclusion: The pre-smearing acetic acid treatment showed better-preserved cellularity and cytomorphology with the absence of background staining when compared to the post-smearing saline rehydration technique.

Metastasizing pleomorphic adenoma of the parotid gland: A common tumour with a very unusual presentation.

Metastasizing pleomorphic adenoma is recognized as a subtype of pleomorphic adenoma in WHO classification 5th edition of salivary glands. The controversy pertaining to the entity is the benign features of the disease even at a metastatic site. We present a rare case of left recurrent pre-auricular swelling in a young male reported as metastasizing pleomorphic adenoma. A nineteen-year-old male presented with left preauricular swelling seven years ago which was diagnosed as pleomorphic adenoma and underwent complete excision of tumour. The tumour recurred twice - two and five years after the surgery. At the second recurrence, the level II neck dissection showed multiple encapsulated deposits of pleomorphic adenoma having similar morphology in the cervical soft tissue with no features of high-grade transformation.

Comparison of liquid based cytology and conventional smears on lymph node aspirates: A cytomorphological study.

Objective: In an era of minimally invasive and rapid diagnostic technologies, fine-needle aspiration cytology (FNAC) is most useful when it comes to patients with lymphadenopathies especially of the cervical region. Liquid-based cytology (LBC) is an alternative processing method which is used for both gynecological and non-gynecological samples. Because of the remarkable advantages of LBC smears in gynecological samples, nowadays, many studies have been done to assess its utility in various other lesions. Hereby, with the help of this study, we would like to evaluate the efficiency of LBC smears in comparison to conventional FNAC smears conventional smears (CS) on lymph node aspirates. Material and Methods: A retrospective study was done over a 1-year period in which 253 cases of lymph node aspirates were included in the study. The slides were prepared using standard conventional and LBC techniques and compared for adequacy, cellularity, cell architecture, necrosis, background debris, presence of cells in monolayer sheets, and nuclear/cytoplasmic details. Results: Of the total 253 cases, 171 (67.6%) were and 67 (26.5%) were diagnosed as non-neoplastic and malignant, respectively. Although the LBC smears were useful in the diagnosis of malignant cases, they did pose some challenges especially in the non-neoplastic lymph node aspirates due to loss of the background necrosis. In addition, the cellular yield in LBC smears was low in comparison to CS. Conclusion: LBC smears from lymph node aspirates results in better diagnostic accuracy for malignant cases due to better cellular and nuclear details. However, for non-neoplastic etiology, it should not be considered better than CS as loss of the background necrosis and inflammation may result in an incorrect diagnosis.

Efficacy of intraoperative imprint cytology of sentinel lymph node in breast cancer.

Objective: The most important determinant of patient outcome in cases of breast carcinoma is the regional lymph node status. Intraoperative assessment of sentinel lymph nodes (SLNs) allows the surgeon to perform axillary lymph node dissection in the same sitting if required. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section. The present study aimed to determine the sensitivity, specificity, and accuracy of TIC with histopathological diagnosis as gold standard. Material and Methods: The lymph nodes sent for intraoperative examination were bisected along the long axis and touched onto clean glass slides followed by Toluidine blue and rapid Papanicolaou staining. The imprints were reviewed and the interpretation was conveyed to the surgeon. Thereafter, the biopsy was fixed in 10% formalin followed by paraffin embedding with hematoxylin and eosin staining. The specificity, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value were evaluated with histopathological diagnosis as gold standard. Results: A total of 60 patients who underwent resection surgery were included in the study. Majority (36.7%) of patients were in the age group 41-50 years with a mean age of 48.1 ± 10.6 years. There were 54 cases (90%) and 6 cases (10%) of invasive carcinoma of no special type (ductal) and lobular carcinoma, respectively. According to modified Bloom-Richardson scoring, the cases were categorized as Grade 1-6 cases (10%), Grade 2-36 (60%), and Grade 3-18 (30%). The sensitivity and specificity of TIC were 87.5% and 100%, respectively. The diagnostic accuracy of TIC in the diagnosis of metastasis in SLN was 90%. Conclusion: TIC is an easy-to-perform, cost-effective, rapid, and accurate technique for axillary lymph node evaluation, which also overcomes the need for a cryostat.

Cytomorphology of skin adnexal tumors and its correlation with histopathology in a tertiary care center.

Objectives: Even though fine-needle aspiration cytology (FNAC) can be successfully used for describing the cytomorphology of skin adnexal tumors and can help in identification of them as benign or malignant, histopathology remains the gold standard in confirmation of diagnosis. Skin adnexal tumors are a large and diverse group and are relatively less commonly encountered in routine practice; hence, knowledge of cytological features of these lesions is crucial for their appropriate management. The present study aims to evaluate the cytomorphological features of skin adnexal tumors on FNAC smears and their correlation with the histopathology. Material and Methods: This is a retrospective study of FNAC of 60 cases of subcutaneous and dermal swellings over a period of 4 years from August 2018 to August 2022 in a tertiary care center. Results: In the 60 cases of skin adnexal tumors evaluated, most cases were within the 2nd to 4th decade with male predominance. The FNA smears were helpful in picking up the nature of skin adnexal tumors, as in our case series, malignant lesions were 8.3% and benign were 91.7%. Majority adnexal lesions were of follicular or sebaceous differentiation. Histological diagnosis was available in 38 cases. Cytological diagnosis in 34 cases was concordant with histopathology. There was discrepancy observed in two cases which were reported as benign skin adnexal tumor but later turned out to be sebaceous carcinoma on histopathology. Conclusion: Even though histopathology being the gold standard for confirmation of diagnosis, in the current era of minimally invasive procedures, FNAC stands out as a valuable modality and can be a promising alternative to diagnose skin adnexal tumors and understand their cytomorphology as the data are limited about it.

Cytomorphology of mesenchymal lesions in a tertiary care centre and its correlation with histopathology.

Objectives: Fine needle aspiration cytology (FNAC) is a minimally invasive method for sampling a heterogenous lesion. It is one of the first-line investigations in the evaluation of soft tissue tumours. However, the heterogeneity of mesenchymal lesions pose a challenge to the cytological diagnosis. The present study aims at evaluation of the cytomorphological findings of mesenchymal lesions on FNAC along with their histopathological correlation. Material and Methods: This was a retrospective study conducted over a period of 1 year from January 2021 to January 2022. All the patients of cytologically diagnosed mesenchymal lesions on their FNA aspirates were included in the study. Cytomorphology of the May Grunwald Giemsa and Papanicolaou stained slides were examined and correlated with clinical and histopathological details wherever available. Results: Out of the 90 patients, 69 (76.7%) were males and 21 (23.3%) were females. Maximum number of cases were in 4-5th decade of life. The lower limb was found to be the most common site (57.8%) for the mesenchymal lesions. Majority of the cases on FNA in our study were found to be benign - 79 (87.8%), while only 11 cases were malignant (12.2%). On cytological examination, spindle cell lesions were most common followed by adipocytic lesions. Based on the cyto-histological correlation, sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of FNAC in diagnosis of mesenchymal lesion was 78.6%, 100%, 92.5%, 100% and 94.1% respectively. Conclusion: FNAC is a simple and minimally invasive tool that plays an important role in triaging patients with good specificity and sensitivity.

The relationship between BCG immunotherapy and oxidative stress parameters in patients with nonmuscle invasive bladder cancer.

INTRODUCTION: Environmental chemicals have been associated with the regulation of oxidative stress markers, which have the potential for the development of bladder cancer. However, limited studies on the function of oxidative stress parameters and nonmuscle invasive bladder cancer (NMIBC) in therapy response are available. Here we studied the oxidative stress parameters in response to BCG immunotherapy in NMIBC patients. MATERIAL AND METHODS: A total of 120 patients with NMIBC and treatment with BCG were enrolled and categorized into 2 groups on BCG response, 50 patients were BCG-responsive (BCG-R) and 70 were BCG-nonresponsive (BCG-N). BCG-R have no evidence of tumor recurrence or advancement after 1 year of BCG immunotherapy, but BCG-N has a recurrence of tumor after 3 to 6 months cycles of BCG instillation, as determined by cystoscopy. In all groups, we measured the levels of oxidative stress markers- malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT). RESULTS: The levels of oxidative stress markers viz. MDA, NO, and SOD in the BCG-N group were significantly higher (P < 0.001) than in the BCG-R group. Furthermore, the data demonstrated a significant correlation between oxidative stress marker and NMIBC T1 high grade and tumor size >2.5 cm. However, no statistically significant difference was found between studied groups with CAT. CONCLUSION: The findings suggest that the carcinogenesis of NMIBC is associated with oxidative damage of biomolecules and indicates the involvement of oxidative stress markers in the development and recurrence of NMIBC.; Therefore, it is critical to ensure the management for T1 high grade and tumor size of >2.5 cm for antioxidant protection.

Cellular mechanisms in the pathogenesis of interstitial lung diseases.

The interstitial lung diseases (ILDs) are a large, heterogeneous group of several hundred generally rare pulmonary pathologies, which show injury, inflammation and/or scarring in the lung. Although the aetiology of these disorders remains largely unknown, various cellular mechanisms have an important role in pathogenesis of fibrosis on the background of occupational, environmental and genetic factors. We have tried to provide new insights into the interactions and cellular contributions, analysing the roles of various cells in the pathogenesis of idiopathic pulmonary fibrosis.

Two Decadal Experiences in Managing Combined Obstetric Vesicovaginal and Rectovaginal Fistulas: A Study From Northern Indian Tertiary Hospital.

INTRODUCTION: A retrospective study of 28 patients with obstetric combined vesicovaginal fistula (VVF) and rectovaginal fistula (RVF) treated at our centre throughout the last two decades (2002 to 2022) has been conducted. MATERIAL AND METHOD: In 12 patients, a preoperative diverting colostomy was performed. Six patients had single-stage surgery (both VVF and RVF repair in the same operation) of which two cases required transabdominal repair and four required transvaginal repair. RESULT: All single-stage repairs (n=6) were successful in curing urine and faecal incontinence. In 22 patients, VVF was corrected initially via the transvaginal method with Martius flap interposition, followed by RVF repair three months later. In 2/22 patients, there was a leak after RVF repair; therefore, proximal diverting colostomy was performed, and RVF repair was repeated after six months. CONCLUSION: All cases had effective VVF and RVF repairs, and both urine and faecal incontinence were completely cured. This study suggests the collaborative engagement of a urologist and a surgical gastroenterologist results in an advantageous outcome for the surgical treatment of these intricate obstetric fistulas.

Fibroadenoma vulva: Experience based on FNA of vulvar lesion.

Vulval fibroadenoma is an extremely rare lesion, mostly seen in young adults. A 51-years-old woman presented with a painless, mobile, and pedunculated vulval mass. Fine-needle aspiration (FNA) was performed and was diagnosed as a benign fibroepithelial lesion possibly fibroadenoma vulva, which was later confirmed as fibroadenoma vulva histopathologically. It is just not rare to find fibroadenoma vulva, but this should also be kept as a differential when diagnosing such cytomorphology in FNA lesions. This is important to avoid unnecessary incisional biopsy before excision.

CYP1A1 gene polymorphism and heavy metal analyses in benign prostatic hyperplasia and prostate cancer: An explorative case-control study.

INTRODUCTION: The prostatic disorder is associated with benign prostatic hyperplasia (BPH) and prostate cancer (CaP). Evidently, prevalent transcription factors and signaling pathways define their relationship. The etiology of the prostatic disorder is multifactorial including heavy metal toxicity like lead (Pb), Cadmium (Cd), and genetic factors. This study elucidates the association between heavy metal toxicity Pb, Cd, and CYP1A1 gene polymorphism with BPH and CaP. METHODS: a case-control study with (BPH, n = 104), (CaP, n = 58) and (controls, n =107) patients. Heavy metal Pb and Cd estimation by atomic absorption spectrophotometer. The polymorphism of the CYP1A1 T>C (rs4646903) gene was analyzed byPCR-RFLP. RESULT: Higher levels of Pb and Cd were found in BPH and CaP followed by the control group (P-value: < 0.05). Pb and Cd show a significant correlation among prostate volume in CaP. Additionally, PSA, IPSS score, and pre void volume were positively co-related with Pb in BPH patients. The posthoc test defines the level of Pb and Cd as significantly elevated in the mutant genotype, highest among homozygous mutant genotype of CYP1A1gene among BPH. In CaP, Pb is significantly higher among the homozygous mutant type of CYP1A1 gene. The risk is also influenced by smoking, tobacco, and alcohol. CONCLUSION: The heavy metal toxicity Pb and Cd were reported to raise the risk of BPH and CaP. However, a person with heavy metal toxicity especially in BPH has a high-risk genetic susceptibility to the CYP1A1 gene in the north Indian population.