Browsing by Author "Tewari, Mallika"
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Publication A comparative study of transdiscal versus transaortic celiac plexus neurolytic block for upper gastrointestinal cancer patients. A prospective, randomized control study(BeSARPP, 2021) Rath, Amrita; Reena; Paswan, Anil Kumar; Tewari, MallikaAim: To compare transdiscal and transaortic techniques of neurolytic celiac plexus block for upper gastrointestinal cancer patients. Methods: In this prospective randomized study 60 patients with upper gastrointestinal malignancies were included and randomly divided into two groups, group TD and group TA, receiving neurolytic celiac plexus blocks via transdiscal and transaortic techniques, respectively. The primary outcome was quality of life (QoL) as assessed by WHOQOL BREF questionnaire and secondary outcomes were pain relief using visual analogue scale (VAS), and occurrence of complications like hypotension, loose motion, bleeding and discitis. Result: QoL and VAS score were significantly improved in both groups post procedure. Transdiscal approach is more effective in improving VAS score than transaortic approach (1 vs 3) after 1 week and the relief of pain was better in TD group (3 vs 6) at the end of 2 months. Transdiscal approach was found to be more effective in improving QoL (227.00�28.85 vs 191.17�35.78) as compared to transaortic approach. However, postprocedural QoL improved in both groups when compared to pre-procedural QoL (p<0.05). Hypotension, diarrhea and bleeding from aorta were higher in TA group; however, no serious complications were seen in any of the groups. Conclusion: Transdiscal technique is better in terms of adequate pain relief and improving QoL as compared to transaortic technique of NCPB in patients of upper GI malignancies and is associated with lesser incidences of complications. � Acta An�sthesiologica Belgica, 2021.Publication Centralization of Complex Cancer Surgeries in India: a Difficult Road(Springer, 2022) Tewari, Mallika[No abstract available]Publication Clinical Significance of Overexpression of Oct4 in Advanced Stage Gallbladder Carcinoma(Springer, 2023) Singh, Deepika; Biswas, Dipanjan; Tewari, Mallika; Kar, Amrita Ghosh; Ansari, Mumtaz Ahmad; Singh, Sunita; Narayan, GopeshwarBackground: Oct4 has critical role in maintaining pluripotency, proliferative potential, and self-renewal capacity in embryonic stem and germ cells. Although Oct4 has been shown to be upregulated in many cancers, its clinical significance in gallbladder carcinoma is poorly understood. Methods: We studied the expression profile of Oct4 in 61 GBC and 30 chronic cholecystitis (as control) using real time RT-PCR, western blotting, and immunohistochemistry. The expression data was correlated with clinico-pathological parameters. The diagnostic utility was assessed through ROC curve, and prognostic value was analyzed by Kaplan�Meier method. Results: Oct4 was significantly upregulated at mRNA as well as protein levels. The higher mRNA expression shows significant association with late stage, late T stage, and higher grade of tumor. A significant positive correlation was also observed with stage, T stage, and tumor grade. Sum score analysis of protein expression shows positive correlation with stage and the presence or absence of gallstone in tumor samples. The ROC curve analysis revealed the moderate diagnostic potential of Oct4. Kaplan�Meier analysis showed that patients having higher expression of Oct4 were having low mean survival compared with the patients with lower Oct4 expression. Conclusion: In conclusion, our data suggests that higher expression of Oct4 may serve as potential biological indicator for tumor aggressiveness and poor prognosis of GBC. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Publication Design, synthesis and evaluation of 4,7-disubstituted 8-methoxyquinazoline derivatives as potential cytotoxic agents targeting ?-catenin/TCF4 signaling pathway(Neoplasia Press, Inc., 2022) Neogi, Kaushik; Murumkar, Prashant R.; Sharma, Priyanshu; Yadav, Poonam; Tewari, Mallika; Karunagaran, Devarajan; Nayak, Prasanta Kumar; Yadav, Mange RamOveractivation of Wnt/?-catenin signaling by accumulated ?-catenin in the nucleus has been shown to play a crucial role in the etiology of cancer. Interaction of ?-catenin with Transcription factor 4 (TCF4) is a key step for the activation of Wnt genes in response to upstream signals of the Wnt/?-catenin pathway. Hence, down regulation of Wnt/?-catenin signaling or targeting downstream events by selective ?-catenin/TCF4 protein�protein interaction inhibitors could be a potential therapeutic strategy against such cancers. In this study structure-based drug design approach was followed to design novel 4,7-disubstituted 8-methoxyquinazoline-based derivatives which could act as potential cytotoxic agents inhibiting the ?-catenin/TCF4 protein�protein interactions. Fifteen compounds possessing 4,7-disubstituted 8-methoxyquinazoline scaffold were synthesized. Cytotoxic potential of the synthesised derivatives were determined against constitutively activated ?-catenin/TCF4 signaling pathway cancer cells (HCT116 and HepG2) using the sulforhodamine B assay. The most potent compound (18B) was selected for detailed biological evaluation. Cell morphology, Hoechst 33342 and Annexin V/PI staining were used to detect apoptosis, while inhibition of cell migration was assessed by in vitro wound healing assay against HCT116 and HepG2 cells. Effect on ?-catenin/TCF mediated transcriptional activity was assessed by TOPFlash/FOPFlash assay, TCF4 and ?-catenin protein expression by immunocytofluorescence, and Wnt target genes (like c-MYC and Cyclin D1) mRNA levels by RT-PCR against HCT116 cells. Cytotoxic potency of the most potential compound (18B) against primary human gallbladder cancer cells was also evaluated. The derivatives showed interactions with active site residues of ?-catenin and were capable of hindering the TCF4 binding, thereby disrupting ?-catenin/TCF4 interactions. Cytotoxic potencies (IC50) of these derivatives ranged from 5.64 � 0.68 to 23.18 � 0.45 ?M against HCT116 and HepG2 cells respectively. Compound (18B), the most potent compound among the series, induced apoptosis and inhibited cell migration against HCT116 and HepG2 cells. Mechanistic studies indicated that compound (18B) downregulated ?-catenin/TCF4 signaling pathway, ?-catenin and TCF4 protein expression, and mRNA levels of c-MYC andCyclin D1 in HCT116 cells and showed cytotoxicity against primary human gallbladder cancer cells with IC50 value of 8.50 � 1.44 ?M. Thus, novel 4,7-disubstituted 8-methoxyquinazoline derivatives were identified as potential cytotoxic agents with potencies comparable to that of imatinib mesylate. Compound (18B) represents a promising lead molecule as anticancer agent against colon, hepatocellular and gallbladder cancers targeting ?-catenin/TCF4 signaling pathway. � 2022Publication Epigenetic Silencing of p16INK4a gene in Sporadic Breast Cancer(Springer, 2023) Singh, Satya P.; Tewari, Mallika; Singh, Alok K.; Mishra, Raghvendra R.; Shukla, Hari S.Epigenetic alterations of tumor suppressor genes (TSG) involved in the onset and progression of Breast Cancer (BC) may serve as biomarkers for early detection and prediction of disease prognosis. We have herein tried to determine the methylation status of TSG, p16INK4a, in our 50 BC patients and their association with clinicopathological parameters. The methylation status of the p16INK4a gene in fresh tissue samples from 50 patients with BC was assessed by methylation-specific polymerase chain reaction (MS-PCR). The mean age of BC patients was 49.30 � 9.75�years. Of 50 BC samples tested, 21 (42%) had methylated p16INK4a gene. p16INK4a gene hypermethylation was significantly associated with age ? 50�years, premenopausal status and advanced BC stage. Multivariate analysis revealed a strong association between advanced BC stage (Stage III and Stage IV) and p16INK4a hypermethylation (P = 0.008, RR = 5.996, 95% CI = 1.581�22.739). p16INK4a methylation was significantly associated with Triple Negative BC (TNBC) (P = 0.045, OR = 4.181, 95% CI = 1.030�16.981). These findings indicate that p16INK4a hypermethylation frequently occurs in BC. Hypermethylation of p16INK4a in young, premenopausal, TNBC and with advance stage in BC patients suggests its association with aggressive BC. � 2023, The Author(s), under exclusive licence to Indian Association of Surgical Oncology.Publication Publication Frequent Downregulation and Promoter Hypermethylation of DLC1: Relationship with Clinical Outcome in Gallbladder Cancer(Springer, 2022) Singh, Deepika; Bharti, Amisha; Biswas, Dipanjan; Tewari, Mallika; Kar, Amrita Ghosh; Ansari, Mumtaz Ahmed; Singh, Sunita; Narayan, GopeshwarIntroduction: Down regulation of DLC1 is associated with poor prognosis in many cancers, however, its role in gallbladder cancer (GBC) is still unclear. In present study, we investigated the expression profile and promoter methylation status of DLC1. Methods: Expression profiles of DLC1 in 55 GBC and their paired adjacent control samples were analyzed through real time RT-PCR and immunohistochemistry. The mRNA data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through MSP. Results: DLC1 shows downregulation in 76.4%, upregulation in 10.9% whereas no change in 12.7% of GBC samples. Its underexpression shows significant correlation with tumor grade and nodal spread. IHC shows cytoplasmic expression of DLC1 in normal as well as tumor samples. IHC result was concordant to mRNA result. Samples having downregulated DLC1 expression show heterozygous methylation in 83.3% of samples and homozygous methylation in 9.5% of samples whereas 7% of samples have no methylation. Kaplan�Meier analysis shows patient with decreased mRNA of DLC1 have significant low mean survival compared to patients with higher mRNA expression of DLC1. Conclusion: Our findings suggested that dysregulated expression of DLC1 and its hypermethylation may be one of the events playing roles in tumorigenesis of GBC and may serve as a potential target for development of future GBC gene therapy. � 2021, Springer Science+Business Media, LLC, part of Springer Nature.Publication Frequent promoter hypermethylation and down regulation of BNIP3: An early event during gallbladder cancer progression(Elsevier B.V., 2022) Bharti, Amisha; Kar, Amrita Ghosh; Singh, Deepika; Ansari, Mumtaz Ahmad; Tewari, Mallika; Narayan, Gopeshwar; Singh, SunitaBackground: Epigenetic alterations have been reported as one of the risk factors of gallbladder cancer. Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. Aims: Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. Methods: The expression analysis and methylation status of BNIP3 was performed by semi-quantitative reverse transcription polymerase chain reaction and Methylation-specific polymerase chain reaction respectively in 84 GBC patients and 29 gallstone tissues (used as normal controls). Results: We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. Conclusion: Our results suggest that promoter hypermethylation is an early event and can be a frequent mechanism for downregulation of BNIP3 in GBC. � 2022Publication Publication Hepato-pancreato-biliary (HPB) Surgery: Pushing the Boundaries with Technology(Springer, 2022) Tewari, Mallika[No abstract available]Publication Influence of adjuvant therapy on pattern of failure and survival in curatively resected gallbladder carcinoma(Wolters Kluwer Medknow Publications, 2021) Choudhary, Sunil; Gupta, Neha; Verma, Chandra Prakash; Das, Avipsa; Aggarwal, Lalit Mohan; Tewari, Mallika; Mandal, Abhijit; Asthana, Anupam KumarPurpose: The study was done to evaluate the role of adjuvant therapy in curatively resected Stage II and III gallbladder carcinoma (GBC). Materials and Methods: This was a retrospective analysis of patients of GBC registered between 2008 and 2017 in outpatient department of a tertiary cancer hospital in India. Patients who had any of the following adjuvant treatment after radical surgery: (a) external beam radiotherapy (RT) alone, (b) chemotherapy (CT) alone, and (c) RT with CT (CRT) were considered for the study. Results: A total of fifty patients could meet the selection criteria. It was seen that seven patients were treated with RT, 20 with CT, and 23 with CRT. Median follow-up for patients who were alive was 26.7 months. Nineteen patients had locoregional failure while eight had distant failure. Patients treated with CRT had a significantly better mean overall survival compared to those treated with RT or CT (44.0 months, 12.5 months, and 15.1 months, respectively; P = 0.003). Similarly, mean disease-free survival was superior in CRT arm compared to RT and CT arms (43.6 months, 9.6 months, and 12.4 months, respectively; P = 0.002). Conclusions: Adjuvant CRT had better survival outcome compared to patients treated with either RT or CT with Stage II and III disease after curative cholecystectomy. � 2020 Journal of Cancer Research and Therapeutics.Publication Inspirational Women in Surgery: Professor Vijayalakshmi Deshmane, MS (Surgical Oncologist, India)(Springer Science and Business Media Deutschland GmbH, 2022) Tewari, Mallika; Barreto, Savio George[No abstract available]Publication Invasive Cancer in Accessory Axillary Breast: a Rare Presentation(Springer, 2023) Rateria, Nisha; Naidu, Palia Gowri; Tewari, MallikaAccessory breast tissue has an incidence of 0.3�6% and primary cancer arising in it is even rarer 0.2�0.6%. It may have aggressive course with tendency for early metastasis. Due to its rarity, variety of differentials, and lack of clinical awareness, treatment is usually delayed. We present here an interesting case of a 65-year-old lady with a 8 � 7-cm hard lump in right axillary region for 3 years with fungation for 3 months and with no concomitant breast lesion or axillary lymphadenopathy. Biopsy revealed invasive ductal carcinoma with no systemic metastasis. Management of accessory breast cancer follows same guidelines with primary treatment being wide excision and lymphadenectomy. Adjuvant therapies include radiotherapy and hormonal therapy. � 2022, The Author(s), under exclusive licence to Indian Association of Surgical Oncology.Publication Mediating role of affective experiences in the relationship between perceived social support and life satisfaction among breast cancer patients(Wolters Kluwer Medknow Publications, 2021) Srivastava, Jyoti; Kaushik, Sandhya; Tewari, Mallika; Shukla, HariAim: The role of social support network in managing psychological symptoms in cancer patients is widely acknowledged. The purpose of this study was to investigate the potential mediating role of Affective experiences in the relationship between perceived social support (PSS) and life satisfaction (LS) among breast cancer patients in India. Methods: A total of 100 breast cancer patients from S. S. Hospital, Banaras Hindu University participated in the study. They were tested using the PGI Social Support questionnaire, Satisfaction with Life Scale and Scale of Positive and Negative Experiences. Results: Co-relational results indicated that PSS was positively associated with positive affect and LS, while inversely related to negative affect. Affect was also associated with LS. Results showed that the mediation of affective experiences in the relationship between PSS and LS was significant (P <.01 level). Conclusion: Both PSS played a big role in LS among breast cancer patients. Besides focusing on improvement of the social support network, the psychologists and counsellors should adopt an integrated approach for evidence-based intervention strategies to enhance their ability to effectively balance their positive and negative emotions to promote LS among cancer patients. � 2021 Wolters Kluwer Medknow Publications. All rights reserved.Publication Octreotide and postoperative pancreatic fistula after pancreaticoduodenectomy: What we know so far- A narrative review(Wolters Kluwer Medknow Publications, 2023) Tilak, Mandar; Tewari, Mallika; Shukla, H.S.Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords 'somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula' was made. Further filters were applied in the search 'Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021,' and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate. � 2023 Copyright:Publication Pancreatic exocrine insufficiency occurs in most patients following pancreaticoduodenectomy(Wolters Kluwer Medknow Publications, 2021) Kumar, Thogari K.; Tewari, Mallika; Shukla, S.K.; Mishra, S.P.Background: Pancreatic exocrine insufficiency (PEI) is a well-defined complication of malignant diseases and pancreatic resection; however, study results of PEI are less consistent. Assessment of PEI by estimation of fecal elastase (FE)-1 in stool by enzyme-linked immunosorbent essay (ELISA) is a relatively inexpensive, noninvasive, and simple test. This study assessed exocrine function of pancreas following pancreaticoduodenectomy (PD) by estimating FE-1. Methods: This prospective hospital-based study involved 30 patients who had undergone PD for malignancy. All 30 patients had an uneventful postoperative period under the unit's enhanced recovery after surgery (ERAS) protocol with no Grade B, C postoperative pancreatic fistula/postpancreatectomy hemorrhage as per the International Study Group of Pancreatic Surgery (ISGPS) definitions. Stool samples were collected postoperatively 3 months after surgery from all patients irrespective of clinical symptoms. The analysis was based on a solid phase ELISA used for the quantitative determination of human elastase 1 in feces. Fecal elastase was considered normal if >200 ?g/gm stool, moderately reduced if 100-200 ?g/gm stool, and severely reduced if <100 ?g/gm stool. Results: Among 30 patients included, fecal elastase levels were moderately reduced in 10 (33.33%) and severely reduced in 20 (66.67%) patients (P <0.0001). Mean (� standard deviation) of fecal elastase was 87.12 � 38.76 with median of 74.6 ?g/gm stool. There was no significant difference in the fecal elastase levels between men and women (P = 0.057), age (P = 0.48), pancreatic duct diameter (P = 0.609), pancreatic texture (P = 0.286), and presence or absence of clinical symptoms (P = 0.181). Conclusions: PD was frequently associated with PEI. Unfortunately PEI is an under recognized and under treated long-term sequel of PD. Fecal elastase 1 should be performed routinely in both symptomatic and asymptomatic patients. Pancreatic enzyme replacement therapy should be considered in every patient after PD. � 2021 Indian Journal of Cancer | Published by Wolters Kluwer-Medknow.Publication Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy(Future Medicine Ltd., 2021) Singh, Deepika; Tewari, Mallika; Singh, Sunita; Narayan, GopeshwarTNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers. � 2021 Future Medicine LtdPublication Sporadic Peutz-Jeghers Syndrome with Recurrent Intussusception and Malignant Change in Hamartomatous Polyps(Springer, 2023) Kumar, Sandeep; Gaba, Shivam; Tewari, Mallika; Jain, GauravPeutz-Jeghers syndrome (PJS) is a rare inherited autosomal dominant disease characterised by mucocutaneous pigmentation and multiple polyps in the gastrointestinal tract. In up to 25% of cases, there is no family history of PJS (sporadic cases). Acute intestinal intussusception due to multiple polyps is the most common complication of PJS. PJS is associated with cancers of the gastrointestinal tract and in other organs. Adenocarcinoma arising in hamartomatous polyps is heavily debated. A 23-year-old gentleman presented with sporadic PJS with recurrent ileal intussusceptions and multifocal well-differentiated adenocarcinomas arising in the background of hamartomatous polyps following hamartoma-dysplasia-carcinoma sequence, which is herein discussed. The hamartoma-dysplasia-carcinoma sequence is one of the pathways of carcinogenesis within hamartomatous polyps in PJS. � 2022, Association of Surgeons of India.Publication Surgical Fire: Where, Why, and What to Do(Springer, 2023) Tewari, MallikaA surgical fire is a fire that occurs on or in a patient. It is an emergency for it can result in devastating consequences. The operating room (OR) team needs to be aware of the possibility of the same and of the protocol to be followed if an unfortunate incident does occur. The present review discusses the constituents of the fire triad/triangle that are constantly present in any OR, namely the oxidizer, ignition source and the fuel, and their role in the causation of a surgical fire. Furthermore, safeguards to mitigate the risk of a surgical fire are elaborated on along with the fire algorithms on the topic. Some case examples of actual published incidents are also presented. Surgical fire is totally preventable if due care is taken and everyone in the OR team is abreast with the fire protocols. � 2022, Association of Surgeons of India.Publication Transcription factor 4 expression and correlation with tumor progression in gallbladder cancer(Wolters Kluwer Medknow Publications, 2022) Neogi, Kaushik; Tewari, Mallika; Singh, Ashish Kumar; Sharma, Kavyanjali; Tej, Gullanki Naga Venkata Charan; Verma, Sumit Singh; Gupta, Subash Chandra; Nayak, Prasanta KumarBackground: Dysregulation in Wnt/?-catenin signaling has been associated with the initiation and metastasis of cancer cells. Transcription factor 4 (TCF4) (also named as transcription factor 7-like 2) is a key transcriptional factor of the Wnt signaling pathway, which, when interact with ?-catenin activates Wnt genes which plays an essential role in tumor development. The expression pattern and clinical significance of TCF4 in gallbladder cancer (GBC) are not yet established. Aims: This study was performed to assess the expression pattern of TCF4 in GBC tissue and attempted to correlate its expression with different clinicopathological parameters. Materials and Methods: The study was conducted on 33 surgically resected specimens of gallbladder carcinoma (GBC) and 12 cases of chronic cholecystitis (CC) as control, which had been confirmed from histology. The expression of TCF4 was performed by the reverse transcription polymerase chain reaction and immunohistochemistry. Results: Relative mRNA expression levels of ?-catenin and TCF4 in GBC tissues were significantly (P < 0.05) higher than in CC samples. TCF4 protein expression was observed in 81.82% (27/33) GBC cases. Specifically, among GBC samples, 21.21% (7/33) was graded as strongly positive, 60.61% (20/33) graded as moderately positive, whereas 18.18% (6/33) graded as negative. All 12 CC samples graded as negative. Overall, TCF4 expression in GBC tissues was statistically significant over CC samples (P < 0.05). Moreover, we observed that TCF4 expression was significantly higher (P < 0.05) in high tumor grades than low grade, higher (P < 0.05) in Stage 2 and Stage 3 than Stage 1. Conclusion: The present study suggests that TCF4 may exert an oncogenic role in the progression of GBC and may serve as a new potential candidate biomarker for tumor progression, and it might be a potential therapeutic target against GBC. � 2022 Journal of Cancer Research and Therapeutics.
