Is it possible to treat melanoma by intercepting the CXCR4/CXCL12 pathway?

Melanoma is a particularly aggressive type of skin cancer that can spread to distant organs, resulting in poor patient outcomes. C-X-C motif chemokine ligand 12 (CXCL12) interacts to the C-X-C chemokine receptor type 4 (CXCR4). This connection between CXCR4 and its companion ligand CXCL12 is important in melanoma metastasis and progression, encouraging cell proliferation, invasion, and survival via downstream signaling pathways. Furthermore, CXCR4 is implicated in the interaction between melanoma cells and the tumor microenvironment, which promotes malignant cell migration and immune evasion. Given the importance of the CXCR4/CXCL12 axis in melanoma, addressing this axis has the potential to prevent metastasis and improve patient outcomes. We present an overview of the CXCR4/CXCL12 axis in cancer progression and explain its role in the melanoma microenvironment in this paper. Furthermore, we investigate CXCR4's predictive usefulness as a possible biomarker for monitoring melanoma progression. Finally, we discuss the most recent research and clinical trials on CXCR4 inhibitors, emphasizing their efficacy and limits. We hope to improve the quality of life for melanoma patients by better understanding the role of CXCR4 and investigating novel therapeutic options.

Unravelling the mechanism of polarization transfer from spin-1/2 to spin-1 system in solids.

An analytic theory based on the concept of "effective-fields" is proposed to explain the mechanism of polarization transfer from spin I = 1/2 to spin S = 1 in non-rotating (static) solids. Employing an isolated two-spin model system, the matching conditions responsible for polarization transfer in cross-polarization (CP) experiments are identified and described in terms of the single-transition operators. In contrast to other existing treatments, the polarization transfer among spins is quantified through analytic expressions highlighting the individual contributions emerging from all plausible CP matching conditions. The interplay between the CP matching conditions observed in experiments is outlined in both isotropic and anisotropic systems and verified through comparison between simulations based on analytic and exact numerical methods. The predictions emerging from the analytic theory are verified over a wide range of experimentally relevant parameters and could be beneficial in the optimization of the CP experiments.

Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.

BACKGROUND: Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor hypoxia can help us predict response to treatment and survival. METHODS: A review of the literature on the present evidence and potential clinical importance of tumor hypoxia in head and neck cancer was carried out. The data obtained from the literature search is presented as a narrative review. RESULTS: The literature shows possible associations between prognosis and low tumor oxygenation. Intermediate hypoxia biomarkers like HIF-1, GLUT-1, miRNA, and lactate, can help in predicting the response to therapy and survival as their altered expression is related to prognosis. CONCLUSIONS: Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.

Arthropods are not declining but are responsive to disturbance in the Luquillo Experimental Forest, Puerto Rico.

A number of recent studies have documented long-term declines in abundances of important arthropod groups, primarily in Europe and North America. These declines are generally attributed to habitat loss, but a recent study [B.C. Lister, A. Garcia, Proc. Natl. Acad. Sci. USA 115, E10397-E10406 (2018)] from the Luquillo Experimental Forest (LEF) in Puerto Rico attributed declines to global warming. We analyze arthropod data from the LEF to evaluate long-term trends within the context of hurricane-induced disturbance, secondary succession, and temporal variation in temperature. Our analyses demonstrate that responses to hurricane-induced disturbance and ensuing succession were the primary factors that affected total canopy arthropod abundances on host trees, as well as walkingstick abundance on understory shrubs. Ambient and understory temperatures played secondary roles for particular arthropod species, but populations were just as likely to increase as they were to decrease in abundance with increasing temperature. The LEF is a hurricane-mediated system, with major hurricanes effecting changes in temperature that are larger than those induced thus far by global climate change. To persist, arthropods in the LEF must contend with the considerable variation in abiotic conditions associated with repeated, large-scale, and increasingly frequent pulse disturbances. Consequently, they are likely to be well-adapted to the effects of climate change, at least over the short term. Total abundance of canopy arthropods after Hurricane Maria has risen to levels comparable to the peak after Hurricane Hugo. Although the abundances of some taxa have declined over the 29-y period, others have increased, reflecting species turnover in response to disturbance and secondary succession.

The emerging role of non-coding RNAs in the epigenetic regulation of pediatric cancers.

Epigenetics is a process that involves the regulation of gene expression without altering the sequence of DNA. Numerous studies have documented that epigenetic mechanisms play a critical role in cell growth, differentiation, and cancer over the past decade. The well-known epigenetic modifications are either on DNA or at the histone proteins. Although several studies have focused on regulating gene expression by non-coding RNAs, the current understanding of their biological functions in various human diseases, particularly in cancers, is inadequate. Only about two percent of DNA is involved in coding the protein-coding genes, and leaving the rest 98 percent is non-coding and the scientific community regarded as junk or noise with no known purpose. Most non-coding RNAs are derived from such junk DNA and are known to be involved in various signaling pathways involving cancer initiation, progression, and the development of therapy resistance in many human cancer types. Recent studies have suggested that non-coding RNAs, especially microRNAs, piwi-interactingRNAs, and long non-coding RNAs, play a significant role in controlling epigenetic mechanism(s), indicating the potential effect of epigenetic modulation of non-coding RNAs on cancer progression. In this review article, we briefly presented epigenetic marks' characteristics, crosstalk between epigenetic modifications and microRNAs, piwi-interactingRNAs, and long non-coding RNAs to uncover the effect on the phenotype of pediatric cancers. Further, current knowledge on understanding the RNA epigenetics will help design novel therapeutics that target epigenetic regulatory networks to benefit cancer patients in the clinic.

Evaluation of the model malaria elimination strategy in Mandla district along with its neighbouring districts: a time series analysis from 2008 to 2020.

BACKGROUND: Compared to 2017, India achieved a significant reduction in malaria cases in 2020. Madhya Pradesh (MP) is a tribal dominated state of India with history of high malaria burden in some districts. District Mandla of MP state showed a considerable decline in malaria cases between 2000 and 2013, except in 2007. Subsequently, a resurgence of malaria cases was observed during 2014 and 2015. The Malaria Elimination Demonstration Project (MEDP) was launched in 2017 in Mandla with the goal to achieve zero indigenous malaria cases. This project used: (1) active surveillance and case management using T4 (Track fever, Test fever, Treat patient, and Track patient); (2) vector control using indoor residual sprays and long-lasting insecticidal nets; (3) information education communication and behaviour change communication; and (4) regular monitoring and evaluation with an emphasis on operational and management accountability. This study has investigated malaria prevalence trends from 2008 to 2020, and has predicted trends for the next 5 years for Mandla and its bordering districts. METHODS: The malaria prevalence data of the district Mandla for the period of January 2008 to August 2017 was obtained from District Malaria Office (DMO) Mandla and data for the period of September 2017 to December 2020 was taken from MEDP data repository. Further, the malaria prevalence data for the period of January 2008 to December 2020 was collected from DMOs of the neighbouring districts of Mandla. A univariate time series and forecast analysis was performed using seasonal autoregressive integrated moving average model. FINDINGS: Malaria prevalence in Mandla showed a sharp decline [- 87% (95% CI - 90%, - 84%)] from 2017 to 2020. The malaria forecast for Mandla predicts zero cases in the next 5 years (2021-2025), provided current interventions are sustained. By contrast, the model has forecasted a risk of resurgence of malaria in other districts in MP (Balaghat, Dindori, Jabalpur, Seoni, and Kawardha) that were not the part of MEDP. CONCLUSION: The interventions deployed as part of MEDP have resulted in a sustainable zero indigenous malaria cases in Mandla. Use of similar strategies in neighbouring and other malaria-endemic districts in India could achieve similar results. However, without adding extra cost to the existing intervention, sincere efforts are needed to sustain these interventions and their impact using accountability framework, data transparency, and programme ownership from state to district level.

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

Determination of the mutual orientation between proton CSA tensors mediated through band-selective 1H-1H recoupling under fast MAS.

The mutual orientation of nuclear spin interaction tensors provides critical information on the conformation and arrangement of molecules in chemicals, materials, and biological systems at an atomic level. Proton is a ubiquitous and important element in a variety of substances, and its NMR is highly sensitive due to their virtually 100% natural abundance and large gyromagnetic ratio. Nevertheless, the measurement of mutual orientation between the 1H CSA tensors has remained largely untouched in the past due to strong 1H-1H homonuclear interactions in a dense network of protons. In this study, we have developed a proton-detected 3D 1H CSA/1H CSA/1H CS correlation method that utilizes three techniques to manage homonuclear interactions, namely fast magic-angle spinning, windowless C-symmetry-based CSA recoupling (windowless-ROCSA), and a band-selective 1H-1H polarization transfer. The asymmetric 1H CSA/1H CSA correlated powder patterns produced by the C-symmetry-based methods are highly sensitive to the sign and asymmetry parameter of the 1H CSA, and the Euler angle ß as compared to the symmetric pattern obtained by the existing γ-encoded R-symmetry-based CSA/CSA correlation methods and allows a larger spectral area for data fitting. These features are beneficial for determining the mutual orientation between the nuclear spin interaction tensors with improved accuracy.

A unique case of rectal cancer with coexistence of multiple pathways of carcinogenesis.

BACKGROUND: Colorectal cancer with a global incidence of 10% has multiple pathways implicated in its carcinogenesis. WNT signaling is the principal underlying pathway via APC gene, while defective mismatch repair genes and epigenetic changes also are known to contribute. CASE PRESENTATION: Here, we present an unusual case of rectal adenocarcinoma in a woman, with germline MSH6 and PMS1 mutations, and simultaneous somatic APC and TP53 mutations treated with surgery and adjuvant capecitabine. CONCLUSIONS: The case is unique suggesting a possible interaction between the two pathways and contributing to carcinogenesis in this patient. This also suggests need for a thorough germline and somatic mutation evaluation in select colorectal cancer patients to direct a tailored therapy.

Role of PARP inhibitors beyond BRCA mutation and platinum sensitivity in epithelial ovarian cancer: a meta-analysis of hazard ratios from randomized clinical trials.

BACKGROUND: PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear. METHODS: A meta-analysis of hazard ratios (HR) of randomized control trials (RCTs) was conducted to study the role of PARPi. The published RCTs comparing the efficacy of PARP inhibitors alone or in combination with chemotherapy and/or target therapies versus placebo/chemotherapy alone/target therapy alone in primary or recurrent ovarian cancer settings were selected. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. RESULTS: A total of 14 primary studies and 5 updated studies are considered, consisting of 5363 patients. Overall, HR for PFS was 0.50 [95% CI 0.40-0.62]. HR of PFS was 0.94 [95% CI 0.76-1.15] in the PROC group, 0.41 [95% CI 0.29-0.60] was in HRD with BRCA unknown (BRCAuk), 0.38 [95% CI 0.26-0.57] in HRD with BRCAm, and 0.52 [95% CI 0.38-0.71] in HRD with BRCAwt. In the HRP group, overall HR for PFS was 0.67 [95% CI 0.56-0.80], 0.61 [95% CI 0.38-0.99] in HRD unknown with BRCA wt, and 0.40 [95% CI 0.29-0.55] in BRCAm HR for PFS. Overall, HR for OS was 0.86 [95% CI 0.73-1.031]. CONCLUSIONS: The results suggest that PARPi have a meaningful clinical benefit in PSOC, HRD, BRACm, and also in HRP and PROC; however, the evidence is not sufficient to recommend their routine use and further studies are needed to expand their role in the HRP and PROC groups.

Novel mutations in a second primary gastric cancer in a patient treated for primary colon cancer.

A 60-year-old man presented with complaints of abdominal pain and melena. Patient had a history of colon cancer 16 years back and had undergone right hemi colectomy for microsatellite instability (MSI) negative, mismatch repair (MMR) stable, T2N0 disease with no mutations on next-generation sequencing (NGS). Investigations revealed a second primary in stomach (intestinal type of adenocarcinoma) with no recurrent lesions in colon or distant metastasis. He was started on CapOx with Bevacizumab and developed gastric outlet obstruction. Total gastrectomy with D2 lymphadenectomy and Roux-en-Y oesophageao-jejunal pouch anastomosis was done. The histopathology showed intestinal type of adenocarcinoma with pT3N2 disease. NGS showed 3 novel mutations in KMT2A, LTK, and MST1R gene. The pathway enrichment analysis and Gene Ontology were carried out, followed by the construction of protein-protein interaction network to discover associations among the genes. The results suggested that these mutations have not been reported in gastric cancer earlier and despite not having a direct pathway of carcinogenesis they probably act through modulation of host of miRNA's. Further studies are needed to investigate the role of KMT2A, LTK, and MST1R gene in gastric carcinogenesis.

Uncovering the Lipid Web: Discovering the Multifaceted Roles of Lipids in Human Diseases and Therapeutic Opportunities.

Lipids, characterized by their hydrophobic nature, encompass a wide range of molecules with distinct properties and functions [...].

How men with alcohol use disorder perceive communication, couple satisfaction, relational boredom, and quality of life compared to wives: Findings from a hospital-based study.

In India, use of alcohol between 10 and 70 years is increasing significantly as per the Government of India, Ministry of Social Justice & Empowerment. Chronic alcohol use in men can potentially disrupt their relationships with their wives in several ways, leading to poor communication, trust issues, emotional disconnection, physical abuse, financial strain, and neglecting responsibilities. These factors may reduce the quality of life of the couple and negatively impact the couple's overall well-being. This cross-sectional study assesses the communication, couple satisfaction, relational boredom, and quality of life of wives with alcoholic husbands admitted to inpatient psychiatry services (patients: n = 30; wives: n = 30). A social demographic data sheet, self-perceived communication in couples, couple satisfaction, relational boredom scale, and the World Health Organization's quality of life scales were used to collect data. All participants were chronic alcohol users and had used alcohol for over 10 years. The mean scores of couple satisfaction (p < .001) and quality of life were greater among husbands. In contrast, wives scored significantly higher in communication (p < .001) and relational boredom (p < .001) compared to husbands with alcohol use disorder. Furthermore, communication, couple satisfaction, relational boredom, and quality of life domains were negatively correlated (p < .001). In contrast, communication and relational boredom were positively correlated (p < .001). Men with alcohol use disorder perceived a satisfactory relationship and higher quality of life than did their wives.

Old drugs, new uses: Drug repurposing in hematological malignancies.

Discovery and development of novel anti-cancer drugs are expensive and time consuming. Systems biology approaches have revealed that a drug being developed for a non-cancer indication can hit other targets as well, which play critical roles in cancer progression. Since drugs for non-cancer indications would have already gone through the preclinical and partial or full clinical development, repurposing such drugs for hematological malignancies would cost much less, and drastically reduce the development time, which is evident in case of thalidomide. Here, we have reviewed some of the drugs for their potential to repurpose for treating the hematological malignancies. We have also enlisted resources that can be helpful in drug repurposing.

Unravelling of the comparative Transcriptomic Profile of Gallbladder Cancer using mRNA sequencing.

BACKGROUND: Gallbladder cancer (GBC) represents a wide geographical diversity as well as heterogeneity in clinical and genomic landscape. There seems to be little progress in the development of diagnostic biomarkers, targeted therapies or individualized approaches to GBC management. In this study, we investigated the whole transcriptome profile of GBC patients using RNA sequencing and identified key genes and pathways associated with gallbladder cancer using bioinformatics. METHODOLOGY: A total of 10 cases of GBC were collected and sequenced. The raw reads of the gallbladder sample was compared with the gallbladder normal control (SRA Database ID: ERX288537: HPA RNA-seq normal tissues gallbladder). Using Gene ontology analysis the differentially expressed genes were categorized into the biological pathway, cellular component, and molecular function. Pathway enrichment analyses, protein-protein interaction, transcription factor and miRNA interaction that regulate the expression of hub genes were conducted using bioinformatics tool. RESULTS: A total of 954 differentially expressed mRNA transcripts were identified, including overexpression of REG4, TMEM238, S100A2, LYPD2, and KRT17, as well as underexpressed genes like CCKAR, IGSF10, CHRM2, CRISP3, and FGF19. Enrichment analysis showed the metabolic pathways to be the top five cancer pathways in gallbladder carcinogenesis besides PI3k-Akt signalling pathway, cAMP signalling pathway, miRNAs in cancer, and cell adhesion profile of GBC. CONCLUSIONS: CCKAR, CDKN2A and LRRK2 were found to be most involved genes in its progression and development through different regulatory pathways. Further, most of the genes were significantly involved in PI3k-Akt, Wnt and hedgehog signaling pathways which have a key role in gallbladder cancer development.

MAP kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: results from bioinformatic analysis of next generation sequencing data from a hospital-based cohort (NCT05404347).

BACKGROUND: Gallbladder Cancer (GBC) is one of the most common cancers of the biliary tract and the third commonest gastrointestinal (GI) malignancy worldwide. The disease is characterized by the late presentation and poor outcome despite treatment, and hence, newer therapies and targets need to be identified. METHODS: The current study investigated various functionally enriched pathways in GBC pathogenesis involving the genes identified through Next Generation Sequencing (NGS) in a hospital-based cohort. The Pathway enrichment analysis and Gene Ontology (GO) were carried out after NGS, followed by the construction of the protein-protein interaction (PPI) network to discover associations among the genes. RESULTS: Of the thirty-three patients with GBC who were screened through next-generation sequencing (NGS), 27somatic mutations were identified. These mutations involved a total of 14 genes. The p53 and KRAS were commonly found to be mutated, while mutations in other genes were seen in one case each, the mean number of mutations were 1.2, and maximum mutation in a single case (eight) was seen in one case. The bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR, and Focal Adhesion PI3K-AKT-mTOR signaling pathways and cross-talk between these. CONCLUSION: The results suggest that the complex crosstalk between the mTOR, MAPK, and multiple interacting cell signaling cascades can promote GBC progression, and hence, mTOR-MAPK targeted treatment will be an attractive option.

An unexpected player in Gaucher disease: The multiple roles of complement in disease development.

The complement system is well appreciated for its role as an important effector of innate immunity that is activated by the classical, lectin or alternative pathway. C5a is one important mediator of the system that is generated in response to canonical and non-canonical C5 cleavage by circulating or cell-derived proteases. In addition to its function as a chemoattractant for neutrophils and other myeloid effectors, C5a and its sister molecule C3a have concerted roles in cell homeostasis and surveillance. Through activation of their cognate G protein coupled receptors, C3a and C5a regulate multiple intracellular pathways within the mitochondria and the lysosomal compartments that harbor multiple enzymes critical for protein, carbohydrate and lipid metabolism. Genetic mutations of such lysosomal enzymes or their receptors can result in the compartmental accumulation of specific classes of substrates in this organelle summarized as lysosomal storage diseases (LSD). A frequent LSD is Gaucher disease (GD), caused by autosomal recessively inherited mutations in GBA1, resulting in functional defects of the encoded enzyme, acid ß-glucosidase (glucocerebrosidase, GCase). Such mutations promote excessive accumulation of ß-glucosylceramide (GC or GL1) in innate and adaptive immune cells frequently associated with chronic inflammation. Recently, we uncovered an unexpected link between the C5a and C5a receptor 1 (C5aR1) axis and the accumulation of GL1 in experimental and clinical GD. Here, we will review the pathways of complement activation in GD, its role as a mediator of the inflammatory response, and its impact on glucosphingolipid metabolism. Further, we will discuss the potential role of the C5a/C5aR1 axis in GL1-specific autoantibody formation and as a novel therapeutic target in GD.

Tubo-ovarian mass with raised CA-125 in a 21-year-old female.

INTRODUCTION: Peritonitis associated with fungal species Curvularia lunata seldom occurs with only five cases reported in the literature, all in middle-age patients with comorbidities undergoing dialysis. CASE REPORT: A 21-year-old female who was referred to surgical oncology OPD with a diagnosis of ovarian malignancy, based on raised cancer antigen 125 (CA 125) and suspected tubo-ovarian mass (TOM) on magnetic resonance imaging (MRI). A review of the MRI showed a pelvic collection with TOM, suggestive of infective pathology. Fungal culture and mass spectroscopy of the cystic collection identified the presence of Curvularia lunata. She was treated with oral itraconazole which showed symptomatic improvement and radiological response. In the follow-up period, the patient developed chest wall swelling, aspiration and geneXpert® revealed multidrug-resistant (MDR) tuberculosis, and treatment was started. CONCLUSIONS: Unusual causes of TOM and raised CA 125 should be kept in mind when dealing with young patients, as the possibility of epithelial ovarian cancer in this age is very low.

TFE3-associated perivascular epithelioid cell tumor with complete response to mTOR inhibitor therapy: report of first case and literature review.

BACKGROUND: Perivascular epitheloid cell tumor (PEComas) are characterized by expression of both muscles, most often smooth muscle actin (in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3-associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby, we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. CASE PRESENTATION: A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving the uterus, cervix, and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with the presence of cells in sheets with granular eosinophillic cytoplasm; IHC showed positivity for TFE-3, H Caldesmon, GATA-3, and Melan A- and HMB-45; and Ki 67 index was 35%. The basis of above diagnosis of PEComa was made and she was started on Everolimus; repeat imaging after 3 months of therapy showed complete response. CONCLUSION: We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behavior then their conventional PEComa.

Lymphadenectomy in ovarian cancers: a meta-analysis of hazard ratios from randomized clinical trials.

BACKGROUND: The debate surrounding systematic lymphadenectomy in the epithelial cancers of the ovary (EOC) was temporarily put to rest by the LION trial. However, there was a glaring disparity between the number of patients registered and the number of patients randomized suggesting inadvertent selection. A subsequent meta-analysis after this trial included all types of studies in the literature (randomized, non-randomized, case series, and, retrospective cohort), thus diluting the results. METHODS: We conducted a meta-analysis of hazard ratios of randomized controlled trials, to study the role of systematic para-aortic and pelvic lymph node dissection in the EOC. A detailed search of MEDLINE, Cochrane, and Embase databases was done to look for the published randomized controlled trials (RCT) comparing lymphadenectomy versus no lymphadenectomy in EOC. A meta-analysis of hazard ratios (HR) was performed for overall survival (OS) and progression-free survival (PFS) using fixed and random effect models. The quality of the RCTs was evaluated on Jadad's score, and the risk of bias was estimated by the Cochrane tool. RESULTS: A total of 1342 patients with EOC were included for quantitative analysis. On meta-analysis, HR for PFS was 0.9 (95% CI 0.79-1.04) favoring lymphadenectomy. HR for OS was 1 (95% CI 0.84-1.18) signifying no benefit of systematic lymphadenectomy. CONCLUSION: The results show a trend towards increased PFS which did not reach statistical significance nor translate into any meaningful benefit in OS. There is still a need for a greater number of well-conducted, suitably powered trials to convincingly answer this question.