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INTRODUCTION: Gallbladder cancer is an aggressive cancer with short median survival from the time of diagnosis. Improved understanding of the pathological molecular mechanisms of gallbladder carcinogenesis is important to refine the diagnosis, prognosis, and also to develop novel targeted therapies for patients with advanced Gallbladder cancer (GBC) malignancy. Ki-67 is a marker of cell proliferation and its detection by immunohistochemistry is considered to be an effective method for the detection of prognosis in several tumors. In the present study, we have analyzed expression of immunohistochemical marker Ki-67 in gallbladder carcinoma and its correlation with clinicopathological and radiological parameters. MATERIALS AND METHODS: This prospective observational study was conducted from December 2017 to July 2020. The patients of newly diagnosed gallbladder cancer were enrolled as per the inclusion and exclusion criteria defined in the study protocol. Contrast-enhanced computer tomography of the chest and abdomen and serum tumor markers such as carbohydrate antigen (CA)-19.9, carcinoembryonic antigen, and CA 125 were done. Immunohistochemical expression of Ki-67 was evaluated on biopsy tissue from the gallbladder mass. RESULTS: Fifty newly diagnosed patients of carcinoma gallbladder were included in the present study. The correlation was studied between clinicodemographic parameters and Ki-67, but no association was found with age, gender, and symptoms. There was a weak positive correlation between Ki-67 and direct bilirubin, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase (P = 0.094; 0.126; 0.542; and 0.328, respectively). There was a weak positive correlation between body mass index (Kg/m2) and Ki-67, but this correlation was not statistically significant (P = 0.304). CONCLUSIONS: Ki-67 is a marker of proliferation and it correlated with histological differentiation, jaundice and liver function tests, presence of stones, and location of metastases but did not correlate with stage and extent of disease.
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INTRODUCTION: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging. MATERIALS AND METHODS: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry. RESULTS: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively. CONCLUSIONS: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.
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INTRODUCTION: Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients. MATERIALS AND METHODS: All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled. RESULTS: A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC. CONCLUSIONS: Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.
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INTRODUCTION: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) have been reported in previous studies to assess the prognosis of gall bladder cancer (GBC) individually and in combination. However, the evidence of utility of preoperative CA 19-9, CEA and carbohydrate antigen 125 (CA 125) in determining the resectability and prognosis of GBC is still lacking. In the present study we correlated the serum levels of tumor markers CA 19-9, CEA and CA 125 individually and combined to determine the resectability and prognosis of the GBC. MATERIALS AND METHODS: Seventy one diagnosed patients of GBC between January 2018 and September 2019 were included in the present study. Serum CA 19-9, CEA and CA 125 were determined by chemiluminescence. Receiver operating characteristic (ROC) curve was used to evaluate the role of tumor markers in determining the resectability of GBC. The Kaplan Meier survival curves were made and log rank analysis was performed to assess the prognostic role of tumor markers in terms of overall median survival. RESULTS: All the three tumor markers CA19-9, CEA and CA 125 showed high discriminatory power in determining the resectability with respective area under curve of 0.76, 0.68 and 0.78 as determined by ROC. Median survival in patients with high serum CA 19-9, CA 125 was significantly lower than patients with normal serum CA 19-9, CA 125 whereas no significant difference was observed in case of CEA. CONCLUSION: The present study suggested that CA 19-9, CEA and CA 125 can predict resectability in GBC and raised levels of CA 19-9 and CA 125 can predict poor prognosis in patients with elevated levels.
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INTRODUCTION: Gall bladder cancer (GBC) tends to present in advanced stages, therefore, early diagnosis of GBC is necessary. There is no ideal single tumor marker available presently for the diagnosis and prognosis of GBC. Platelet distribution width (PDW) is an early marker for activated platelets and has been used in a variety of tumors to assess prognosis. This study was designed to evaluate the utility of PDW in identifying GBC patients and its association with tumor markers, staging and resectability of GBC. MATERIALS AND METHODS: This cross sectional study was done on 100 patients of GBC and 100 age- and sex- matched healthy controls. PDW was evaluated and compared between GBC and healthy controls. Receiver-operating characteristics was plotted to determine optimal cut-off for identifying GBC patients and to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PDW. Correlation between serum tumor markers (carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125) and PDW were evaluated. Association of PDW with hyperbilirubinemia, staging and resectability of GBC was also studied. RESULTS: A significantly higher PDW with a median of 18.1 was observed in GBC as compared to healthy controls with median value of 13. PDW was found to have a very high sensitivity (90%), specificity (95%), PPV (94%) and NPV (90%) in identifying GBC at cut-off of 16 with area under the curve (AUC) of 0.97. An increase of PDW was observed with increasing stage and unresectable GBC. However, it was not statistically significant. Significant positive correlation was observed between PDW and all three serum tumor markers and good positive correlation with r = 0.61 was observed with CA 19-9. CONCLUSION: PDW was associated with GBC and may be considered as a cost- effective marker in adjunct to other investigations for the diagnosis of GBC.
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Autophagy is an evolutionarily conserved intracellular catabolic process that recycles and degrades proteins, organelles and pathogens. It is an endogenous defence mechanism regulating multiple cellular pathways like apoptosis, inflammation, immune response and pathogen clearance and acts as a modulator of pathogenesis. This article highlights the emerging role of autophagy in inflammation and regeneration of human dental pulp. It emphasizes exploring autophagy and autophagy agonists as potential targets for the development of novel therapeutic interventions.
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Rhabdomyosarcoma (RMS) is the third most common extra-cranial sarcoma occurring in childhood, adolescents, and young adults (AYAs); and is rare in adults. Literature about RMS mainly considers RMS in AYAs, either with that in the children or adults, even though histological, molecular, and clinical characteristics of RMS in AYAs are significantly different from either of the two. Herein, we report a case of prostatic embryonal RMS, in a 17-year-old boy, along with the review of literature of prostatic RMS, with emphasis on AYAs. Our patient presented with clinical complaints of acute urinary retention, Grade IV prostatomegaly and, low serum prostate-specific-antigen (0.11ng/dl). The diagnosis was clinched by prostatic biopsy, which revealed diffuse 'small round blue cell' tumour admixed with larger rhabdomyoblasts, displaying positivity for desmin and myogenin, on immunohistochemistry. Clinicians should be mindful that RMS is found in all age groups ranging from childhood to adults; however, the clinical, histological, and molecular features are different. RMS in AYAs is often treated according to the guidelines provided for the paediatric age group. Treatment mostly comprises a multimodality approach, including surgery with/without chemo- and radiotherapy. Prognosis in AYAs is worse than in children but is better than in adults. Thus, early diagnosis gains utmost importance to provide comparatively more probability of rendering treatment and, hopefully, a better quality of life.
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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has multiple epigenetic modifications including post-transcriptional regulation by microRNAs (miRNAs) as well as alterations in molecular pathways due to mutations. Examining these miRNAs and location-specific molecular alterations is essential to understanding the intricacies of HNSCC and directing focused diagnoses and treatments. AIM: To investigate tobacco-related changes in the expression of miRNAs and proteins with clinicopathological parameters of HNSCC and disease-modifying personal habits like tobacco and alcohol use. METHODOLOGY: The study concentrated on oropharyngeal cancers using immunohistochemistry and reverse transcription-polymerase chain reaction. Expression of microRNAs mir15a, mir20b, mir21, mir31, mir33b, mir146a, mir155, mir218, mir363 and mir497 and immunohistochemical expression of P53 and PIK3CA were correlated with grade, stage and personal habits like tobacco and alcohol intake. RESULTS: mir21 and mir15a are under-expressed in higher grades with a trend towards statistical significance (P-value of 0.094 and 0.056 by one-way analysis of variance (ANOVA) on ΔCT values). mir155 and mir146a are overexpressed in stage IV tumours while mir 31 is under-expressed in stage IV tumours but statistical significance was not reached. mir497 showed overexpression in tobacco users, but these results were limited by many tumours not showing any amplification for the miRNA and statistical significance was not reached. There was no statistically significant association found between immunohistochemical expression of p53 and PIK3CA with grade, stage or personal habits. CONCLUSION: Through the deciphering of complex miRNA patterns and their relationships with clinicopathology, this study attempted to increase our understanding of HNSCC. Some candidate miRNAs showing probable association with grade, stage and personal habits were identified, but larger studies are needed to confirm or refute the importance of these miRNAs.
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Background: Accurate prediction of ovarian masses preoperatively is crucial for optimal management of ovarian cancers. Objective: The objective of this study was to identify the risk of malignancy index (RMI) incorporating menopausal status, serum carbohydrate antigen 125 levels, and imaging findings for presurgical differentiation of benign from malignant ovarian masses and to evaluate the diagnostic ability of four different RMIs. Materials and Methods: Women presenting with ovarian masses from August 2018 to January 2020 were evaluated preoperatively with detailed history, examination, imaging, and tumor markers. RMI 1-4 was calculated for all patients. Evaluation of the diagnostic utility of four different RMIs for preoperative identification of malignancy was based on the increment of the area under the receiver operating characteristic curve. Histopathological diagnosis was used as the gold standard test. Results: One hundred and twenty-one patients fulfilling the eligibility criteria were enrolled in this study. Benign tumors constituted 61 (50.4%) out of 121 cases, followed by malignant tumors and borderline tumors constituting 49 (40.49%) cases and 11 (9.09%) cases, respectively. The sensitivity of RMIs 1, 2, 3, and 4 was 77.0%, 63%, 77.0%, and 77.0%, respectively, and the specificity was 84%, 86%, 77%, and 71%, respectively. The RMI 2 had higher specificity at predicting malignancy than other RMIs while diagnostic accuracy was highest in RMI 1. Conclusion: The RMI method is a simple and cost-effective technique in preoperative differentiation of ovarian masses.
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Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.
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Squamous cell carcinoma (SCC) of lower gastrointestinal tract is a rare tumor and duodenum is the most common site of involvement. In addition, involvement of jejunum by SCC is further exceptionally rare, and only nominal cases are present world literature. Being a very infrequent finding, a clinician and a pathologist must be aware of this rare entity. Diagnosis requires histopathology along with clinico-radiological correlation since merely histopathology is unable to differentiate between primary and metastatic tumor. Treatment modality is totally different in primary and secondary tumor of lower gastrointestinal tract. Being an extremely rare case of primary SCC of jejunum in an elderly female makes it eligible to be acknowledged at the global platform of medical literature.
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Carcinoma de Células Escamosas , Jejuno , Humanos , Feminino , Idoso , Jejuno/cirurgia , Jejuno/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , ÍndiaRESUMO
Background: This study aimed to compare the diagnostic performance of carcinogenic antigen (CA) 125, (HE)-4 (Human epididymis protein 4), and ultrasound (International Ovarian Tumor Analysis [IOTA]) Simple Rules individually and to derive a composite score in the differentiating ovarian cancer from benign ovarian mass. Subjects and Methods: Consecutive patients (n = 100) with pelvic mass admitted during February 2018-August 2019 were included prospectively. Patients with either known case of epithelial ovarian cancer (EOC) or metastatic EOC were excluded. The primary outcome was to assess the sensitivity and specificity of CA-125, HE-4, and IOTA Simple Rules in predicting benign from malignant mass independently, while secondary outcome was derivation of a new model incorporating these variables using multivariate logistic regression analysis to predict benign from malignant lesions. Receiver operator curve (ROC) was drawn to redefine the best-performing cutoff values and difference between area under the ROC (AUROC) were compared by DeLong's method. Results: Out of 100 cases of adnexal mass selected, the sensitivity and specificity of CA-125 were 73.8% and 77.6%, HE-4 were 90.5% and 87.9%, and IOTA Simple Rules were 92.9% and 81.0%. CA-125, HE-4, and IOTA Simple Rules were independently associated with the likelihood of malignancy/borderline (P < 0.001). The area under the curve for the "composite score" (AUC = 0.93) was the highest and was significantly better than that of CA-125 (AUC = 0.786) (P = 0.004 using DeLong's test) and comparable with HE-4 (AUROC = 0.90; P = 0.128 using DeLong's Test). Conclusion: The sensitivity and specificity of HE-4 and IOTA Simple Rules for predicting malignant ovarian tumor was better than those of CA-125. The diagnostic performance of "composite score" was comparable to those of either HE-4 or IOTA Simple Rules and significantly better than CA-125.
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Background: Females having a large proportion of gallbladder carcinoma (GBC) and a higher incidence of gallstones pointed toward the role of sex hormones in GBC development. In this study, we evaluated the expression of Estrogen receptor (ER), Progesterone receptor (PR), and Her2/neu and their correlation with tumor markers and clinicopathological parameters in the GBC. Methods: A total of 50 patients of GBC and 42 patients in control group undergoing surgery for other conditions were taken. The patient's biopsy sample's paraffin block was tested for ER, PR, and Her2/neu expression by immunohistochemistry. Results: ER and PR had no significant expression in GBC and control group, but Her2/neu had 16% expression in GBC, significantly associated with the degree of differentiation with 62.5% (n-5) being well-differentiated; 75% of Her2/neu positive were in stages III and IV. Her2/neu did not correlate with tumor markers despite expression. Conclusions: Her2/neu amplification is a small step in validating that option so it could be included in the treatment and prognostication of GBC.
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Neoplasias da Mama , Neoplasias da Vesícula Biliar , Humanos , Feminino , Biomarcadores Tumorais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias da Vesícula Biliar/genética , Receptores de Progesterona/metabolismoRESUMO
Background: An epidermoid cyst is a benign keratin-filled cyst, commonly located in the face, scalp, neck, and trunk. Although it is a common benign cystic neoplasm, large series of analyses in English literature are still scarce. To comprehend the clinical and pathological variation of epidermoid cysts in the sub-Himalayan region of India, as well as their clinical implications for late diagnosis, a retrospective study on epidermoid cysts was conducted. Materials and Methods: This was a retrospective observational study conducted on 217 cases of epidermoid cyst subjected for fine-needle aspiration cytology over a period of 3.6 years (from 2018 to 2021). The clinical details and other epidemiological data were archived from the pathology requisition forms. Results: It showed slight male preponderance with head and neck site as the most common area. Most patients were adults. Few uncommon sites were also seen namely breast, parotid, epididymis, and tonsils. Few large lesions were identified measuring up to 10 cm. The skin changes were seen in 5.5% cases, 0.9% cases show extreme ulceration, and 4.1% cases show foreign body giant cell reactions. Due to the province's steep terrain and limited access to medical services, the majority of patients arrived at out patient department (OPD) late. Conclusion: The findings suggest that fine-needle aspiration can be used as a quick diagnostic test even in remote areas by the general practitioner who can send the slides for evaluation to a pathologist. Many times, clinically looking epidermoid cyst can reveal certain challenging entities such as a biphasic fibroepithelial tumor with cystic squamous metaplasia and proliferating pilar tumor in our series. The study of this lesion is also needed for early diagnosis as long-standing lesion may rupture and cause requirement of extensive treatment followed cosmetic impairment.
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Circulating tumor cells (CTC) are a recent technique which is a potentially important prognostic factor in many solid tumors. There are many techniques of detecting CTCs, but they usually implement costly techniques like EpCAM targeted detection, fluorescence-based diagnosis, or magnetic bead based positive or negative selection. The diagnostic utility of simple cytomorphological diagnosis after routine staining of CTCs have been rarely studied. We aimed to detect CTCs in 24 patients clinically suspected to have Urinary Bladder Cancer using a simple but efficient patented filtration technology (ScreenCell™), followed by optical microscopic visualization after routine May-Grunwald-Giemsa (MGG) staining. The detected CTCs were then tested for association with the histologic type, lamina propria invasion, deep muscle invasion and the T-stage. Out of the 24 patients tested, one was found to have papilloma, nine had low grade urothelial carcinoma, 13 had high grade urothelial carcinoma and one had poorly differentiated adenocarcinoma. Of these, two LGUC, eight HGUC and one adenocarcinoma had detectable CTC. Presence of CTCs had a statistically significant association with Lamina propria invasion (P = .006) and T-stage (P = .02), and a trend toward significance for differentiating LGUC from HGUC (P = .10). These results suggest that cytomorphological detection of CTC is likely to be clinically useful in diagnosis and prognostication of urinary blader cancers. These findings need to be confirmed on studies with larger sample sizes.
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Adenocarcinoma , Carcinoma de Células de Transição , Células Neoplásicas Circulantes , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Células Neoplásicas Circulantes/patologia , CitologiaRESUMO
OBJECTIVE: The oral squamous cell carcinoma (OSCC) treatment protocol depends upon lymph node metastasis. Elective neck dissection for early-stage OSCC (pT1/T2) elective neck dissection reduces the morbidity rate. It also reduces the overall survival and thus it becomes important to detect lymph node metastasis in early-stage OSCC. MATERIAL AND METHOD: Various histomorphological parameters have been studied to predict nodal metastasis in early-stage OSCC. We aim to evaluate these parameters in the context of nodal metastasis. 78 cases of early-stage OSCC were included in the study with histopathologic parameters like tumor size, grade, tumor depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), worst pattern of invasion (WPOI), and lymph node level. RESULTS: Out of the 78 patients, 32 patients had lymph node metastasis. T stage, DOI, LVI, and WPOI showed statistically significant deviance from the null model (P-values of 0.007, 0.01, 0.04 and 0.02 respectively). The Odds Ratio (OR) of T stage, DOI, LVI and WPOI were 4.45 (95% C.I =1.47-14.1), 4.4 (95% C.I =1.32-15.88), 8.12 (95% C.I =1.002-198.20), and 3.39 (95% C.I =1.24-9.74) respectively. On multivariate analysis (Firth logistic regression) using DOI, LVI, and WPOI as independent variables, only T-stage and WPOI retained statistical significance. CONCLUSION: The prognostic information supplied by evaluating DOI, LVI, and WPOI warrants the inclusion of these parameters in the standard reporting format for all cases of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Neoplasias Bucais/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
To compare the clinical, cystoscopic, and pathological characteristics of bladder cancer in patients younger than 40 years of age and those of patients older than 40 years of age. We conducted a prospective observational study at our department from September 2019 to February 2021 to compare the clinico-pathological characteristics of young and old patients with biopsy proven bladder cancer after a transurethral resection of bladder tumour. The patients were managed according to standard guidelines. Two hundred sixty-eight patients of bladder cancer were included in the analysis. Out of these, 58 patients were < 40 years of age and 210 were > 40 years. The mean age of two groups were 31.43 ± 6.30 vs 59.08 ± 9.87 years. With respect to tumour grade, 36.2% (versus 17.6%) of young patients had low grade tumour, and 58.6% had high-grade tumour (versus 82.4%). In the young population, 63.8% patients had NMIBC (versus 61.9%) and 36.2% had MIBC (versus 38.1%). Even in the NMIBC group, a large majority of young patients had high-risk disease (51.4%). The incidence of bladder cancer is on the rise in the northern belt of India, especially in the younger age group. High exposure to smoke and heavy metals in drinking water/occupation are the major risk factors. Majority of young patients aged < 40 years had a high-grade disease on presentation and a large subset had muscle invasive bladder cancer, contrary to previously reported studies.
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Introduction Urothelial carcinomas are the most common types of bladder tumors that have recently shown a changing trend in treatment protocols with the introduction and approval of immune checkpoint inhibitors. The most important immune checkpoint lies with the PD-1-PD-L1 axis. Although multiple drugs have been approved, there is uncertainty about patient selection criteria and diagnostic assays. Recent studies related to the laboratory-developed tests have opened up the horizon of PD-1 and PD-L1 immunohistochemistry even at resource-constrained laboratories. We propose to study these immunohistochemistry markers in our laboratory using newer clones. Materials and Methods We selected 116 consecutive cases of transurethral bladder tumor resection from our laboratory archive and applied PD-1 and PD-L1 immunohistochemistry. The study was approved by the institution's ethics committee. Results We found high expression of PD-1 and PD-L1 in urothelial carcinoma even with different cut-offs of PD-L1. Muscle invasion, lamina invasion, and grade of carcinoma had a statistically significant effect on the expression; however, age and sex did not affect the expression. Conclusion Based on our current study, we can conclude that the clones used in our study show high expression in urothelial carcinoma and can aid in patient selection and treatment protocol, irrespective of age and sex.
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The increasing incidence of urinary bladder carcinoma is alarming. Approximately seventy percent of these patients are non-muscle invasive bladder cancer (NMIBC). Restage transurethral resection of bladder tumor (TURBT) is the current recommendation for any T1 and or high-grade non muscle invasive bladder cancers (NMIBC) to accurately stage the malignancy. The question whether a second surgery is always required as a restage procedure is still unanswered. The patient's concern about completeness, morbidity, and financial considerations of a major surgery cannot be overlooked. Moreover, it also puts a strain on the already overburdened healthcare system. To answer this question, whether it is oncologically sound to omit a second resection, the current study evaluated the outcomes of patients undergoing restage TURBT, and analyzed the preoperative factors predicting a change in the staging of this malignancy. The study design was a prospective observational including NMIBC patients from September 2018 to February 2020. A total of 72 patients underwent restage TURBT. Their demographic data, imaging and cystoscopic findings, and histopathological data were recorded. The objective was to study the clinico-pathological correlations and factors predicting recurrence and upstaging of tumor in NMIBC patients undergoing restage TURBT. A total of 101 patients were found eligible for restage TURBT. Eventually, 72 underwent restage TURBT. Twelve (16.7%) patient had recurrence at restage while 3(4.16%) were upstaged to T2. Presence of lower urinary tract symptoms (LUTS) was independently associated with the risk of recurrence of same stage compared to no recurrence (p-0.025, OR-8.793, 95% CI-1.316-98.773). Chemical exposure (p-0.042) was also significantly associated with the same. Presence of lymphadenopathy on CT was independently associated with the risk of upstaging compared to no recurrence (p-0.032, OR-18.25, 95% CI-1.292-257.85). The study concluded that in the presence of a well-performed and adequate initial TURBT, restage TURBT could be skipped for further management. However, in small subgroup of patients with lymphadenopathy on preoperative imaging having a higher risk of tumor recurrence and upstaging, and patients with a history of chemical exposure and previous lower urinary tract symptoms having a high risk of recurrence alone, restage TURBT should still be performed to accurately stage the disease. Further studies with large patient cohort are needed to confirm and reinforce the facts proposed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01516-8.
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Background Lamotrigine (LTG) and subconvulsive doses of pentylenetetrazol (PTZ) as a model mimic drug-resistant epilepsy (DRE), which is a serious unmet medical condition. Previous evidence suggests an imperative role of neuroinflammation in the development of DRE. Various preclinical models of brain injury have reported potent anti-inflammatory and antioxidant properties of ferulic acid (FA). Therefore, its efficacy against intractable epilepsy is worthwhile to study. Materials and methods The present study evaluated the efficacy of FA in LTG and PTZ-induced refractory seizures in mice. On every alternate day for 38 days, LTG (5mg/kg) was injected before PTZ (30-40mg/kg) to establish a murine model of DRE. Animals were treated with two doses of FA (40, 80 mg/kg). All the animals were assessed for seizure score and the latency of seizures every alternate day till the end of the study. Histopathological score and the levels of pro-inflammatory mediators, interleukin-1ßeta (IL-Iß), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were quantified in the brain tissue of these mice. Results Ferulic acid (FA) neither decreases the LTG and PTZ-induced refractory seizures score nor increases the latency to develop seizures. In addition, the injury to hippocampal neurons and the levels of pro-inflammatory cytokines were comparable with two doses of FA in treated mice. Conclusion In the present study, single-dose FA treatment does not show any beneficial effect against the LTG/PTZ model of DRE. Therefore, its single-dose administration might not be beneficial against the DRE model.