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.

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.

Role of Magnetic Resonance Imaging in evaluation of tuberculous tubo ovarian mass.

OBJECTIVE: Role of Magnetic Resonance Imaging (MRI) in diagnosis of tuberculous tubo-ovarian (TO) mass. METHODS: MRI was performed on 33 patients of tuberculous TO mass of female genital tuberculosis (FGTB). RESULTS: Mean age, BMI, and parity was 27.5 ± 4.2 years, 22.7 ± 3.6 kg/m2, and 0.27 ± 0.13. All patients (100%) had infertility; primary infertility (72.72%) and secondary infertility (27.23%) with mean 5.8 years. Abdominal/pelvic pain 33 (100%) cases, abdominal lump 4 (12.12%), adnexal mass 33 (100%). MRI findings showed pelvic masses 33 (100%), bilateral TO masses 11 (33.33%), cystic lesion 4 (12.12%), solid cystic lesion 3 (9.09%) with bilateral pyosalpinx 1 (3.3%), homogeneous content with ascites 1 (3.03%), rim enhancing lesion abutting pelvic wall in 1 (3.03%). Right adnexal mass 11 (33.33%), right adnexal cyst 2 (6.06%), right adnexal cystic mass in 1 (3.03%), right sided complex TO mass 1 (3.03%), right sided hydrosalpinx in 1 (3.03%) case, right sided TO mass in 4 (12.12%) cases and right sided para-ovarian cyst in 2 (6.06%). Left sided adnexal mass was seen in 11 (33.33%), cystic lesion in 1 (3.03%), ovarian cyst in 3 (9.09%) cases, left sided hydrosalpinx in 2 (6.06%), left ovarian cyst 2 (6.06%) cases, left sided ovarian cyst with encysted ascites 1 (3.03%) case and with left sided paraovarian cyst 2 (6.06%) case. Miscellaneous finding were generalised ascites (6.06%), encysted ascites (3.03%), pelvic (1; 3.03%) and mesenteric lymphadenopathy 1 (3.03%). Incidental finding were fibroid 3 (9.09%) and adenomyosis 1 (3.03%) case. CONCLUSION: MRI appears to be useful diagnostic modality for tuberculous TO masses where differential diagnosis is malignancy but molecular diagnosis remains the gold standard.

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.

Cancer surgery during COVID increased the patient mortality and the transmission risk to healthcare workers: results from a retrospective cohort study (NCT05240378).

BACKGROUND: India encountered two waves of COVID-19 pandemic with variability in its characteristics and severity. Concerns were raised over the safety of treatment, and higher morbidity was predicted for oncological surgery. The present study was conducted to evaluate and compare the rate of morbidity and mortality in patients undergoing curative surgery for cancer before and during the COVID-19 pandemic. METHOD: The prospectively obtained clinical data of 1576 patients treated between April 2019 and May 2021 was reviewed; of these, 959 patients were operated before COVID-19 and 617 during the pandemic. The data on complications, deaths, confirmed or suspected COVID-19 cases, and COVID-19 infection among health workers (HCW) was extracted. RESULTS: A 35% fall in number of surgeries was seen during the COVID period; significant fall was seen in genital and esophageal cancer. There was no difference in postoperative complication; however, the postoperative mortality was significantly higher. A total of 71 patients had COVID-19, of which 62 were preoperative and 9 postoperative, while 30/38 healthcare workers contracted COVID-19, of which 7 had the infection twice and 3 were infected after two doses of vaccination; there was no mortality in healthcare workers. CONCLUSION: The present study demonstrates higher mortality rates after surgery in cancer patients, with no significant change in morbidity rates. A substantial proportion of HCWs were also infected though there was no mortality among this group. The results suggest higher mortality in cancer patients despite following the guidelines and protocols.

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.

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.

Natural protein-based electrospun nanofibers for advanced healthcare applications: progress and challenges.

Electrospinning is an electrostatic fiber fabrication technique that operates by the application of a strong electric field on polymer solution or melts. It is used to fabricate fibers whose size lies in the range of few microns to the nanometer range. Historic development of electrospinning has evinced attention due to its outstanding attributes such as small diameter, excellent pore inter-connectivity, high porosity, and high surface-to-volume ratio. This review aims to highlight the theory behind electrospinning and the machine setup with a detailed discussion about the processing parameters. It discusses the latest innovations in natural protein-based electrospun nanofibers for health care applications. Various plant- and animal-based proteins have been discussed with detailed sample preparation and corresponding processing parameters. The usage of these electrospun nanofibers in regenerative medicine and drug delivery has also been discussed. Some technical innovations in electrospinning techniques such as emulsion electrospinning and coaxial electrospinning have been highlighted. Coaxial electrospun core-shell nanofibers have the potential to be utilized as an advanced nano-architecture for sustained release targeted delivery as well as for regenerative medicine. Healthcare applications of nanofibers formed via emulsion and coaxial electrospinning have been discussed briefly. Electrospun nanofibers have still much scope for commercialization on large scale. Some of the available wound-dressing materials have been discussed in brief.

Progression of the first stage of labour, in low risk nulliparas in a South Asian population: a prospective observational study.

We compared the labour pattern in the active phase of labour, defined at 4 cm versus 6 cm cervical dilatation, in a South Asian population. This was a prospective observational study where 500 low risk nulliparous women were recruited. Our aim was to study, the average labour pattern curve of all parturients. Mean duration of the active phase from 4 to 10 cm was 5.12 ± 2.10 hours and from 6 to 10 cm was 2.79 ± 1.72 hours. The 95th percentile values suggests that it takes 5-6 hours to progress from 4 to 6 cm and again 5-6 hours from 6 to 10 cm. The minimum labour progression rate can be as low as 0.5 cm/hour with vaginal delivery (VD) still being achieved. The slope of labour curve steepens after 6 cm, suggesting 6 cm as the onset of the active phase. Allowing labour to continue for a longer period before 6 cm of cervical dilation may reduce the rate of unnecessary intrapartum intervention and caesarean section (CS) for labour dystocia.Impact StatementWhat is already known on this subject? Friedman's definitions of normal labour and abnormal labour are widely accepted in current obstetric practises. Friedman's normal dilatation rate of 1 cm/h that is universally accepted is becoming questionable in our current obstetric population because of escalating rates of unnecessary labour interventions like oxytocin augmentation and CS.What the results of this study add? The rule of 1 cm/hour of labour progression cannot be applied to every woman and inappropriate interventions should be withheld until labour progression does falls below 0.5 cm/hour.What the implications are of these findings for clinical practice and/or further research? Six centimetres rather than 4 cm of cervical dilatation is a more appropriate landmark for the start of the active phase. Allowing labour to continue for a longer period before 6 cm of cervical dilation may reduce the rate of unnecessary intrapartum interventions and CS for labour dystocia.

Morphological and Swelling Potential Evaluation of Moringa oleifera Gum/Poly(vinyl alcohol) Hydrogels as a Superabsorbent.

Synergistic use of superabsorbent hydrogels has vital contribution to the daily life. This work gives an account of a facile approach to synthesize superabsorbent hydrogels based on Moringa oleifera gum and polyvinyl alcohol cross-linked with borax. Fourier transform infrared, X-ray diffraction, and scanning electron microscopy were employed to characterize the structure, crystallinity, and surface morphologies of the samples. The cross-link density, swelling ratio, reswelling, water retention properties, and salt sensitivity of hydrogels were investigated. Reaction parameters for the hydrogel synthesis were optimized on the basis of water absorbency, and the reaction condition of greater water absorbency after 12 h at room temperature was taken as an ideal condition. Optimum conditions were obtained as [poly(vinyl alcohol) PVA] = 10% (w/v) and [borax] = 1.05 × 10-3 mol/L. Under the optimized conditions, the maximum swelling ratio of MOG/PVA hydrogel reached 1163 g/g in deionized water and 290 g/g in 0.9 wt % NaCl solution. Furthermore, all hydrogels exhibited salt sensitivity and excellent water retention capacity under the high temperature state and displayed smart swelling behaviors in physiological saline solutions. The water absorbency, reusability, and salt sensitivity of the hydrogels give these smart polymer wide promising applications.

A review on latest innovations in natural gums based hydrogels: Preparations & applications.

The prospective uses of natural gum polysaccharides in various aspects of food, water, energy, biotechnology, environment and medicine industries, have garnered a great deal of attention recently. Natural gums have gained widespread attention due to their availability, low cost, structural diversity and remarkable properties as 'green' bio-based renewable materials. Natural gums are obtainable as natural polysaccharides from various tree genera possessing exceptional properties, including their renewable, biocompatible, biodegradable, and non-toxic nature and their ability to undergo easy chemical modifications. Hydrogels based on natural gums offer several valuable properties when equated to synthetic origin. The fundamental objective of this review is to compile different strategies for the preparation of hydrogels based on several important commercially available gums (arabic, guar, gellan, ghatti, karaya, kondagogu, konjac, locust bean tamarind, tragacanth, tara and xanthan) for the greener synthesis and stabilization of metal/metal oxide NPs, production of electrospun fibers, water purification, drug delivery, tissue engineering, agriculture and for antimicrobial and biomedical applications.

Enhanced potential of biomimetic, silver nanoparticles functionalized Antheraea mylitta (tasar) silk fibroin nanofibrous mats for skin tissue engineering.

In the present study, we have successfully prepared tasar fibroin nanofibrous mats using 1­butyl­3­methylimidazolium acetate for skin tissue engineering. The prepared tasar nanofibrous mat was further coated by silver nanoparticles (AgNPs) in situ using dandelion (Tridax procumbens) leaf extract. The kinetic of silver nanoparticles formation was studied by UV-VIS spectrophotometer. The prepared silver nanoparticles were further confirmed by XRD and TEM. The coating of tasar nanofibrous mat with silver nanoparticles was confirmed by EDX and EDX mapping techniques. The physical, mechanical, antimicrobial and biological properties of these silver nanoparticles coated tasar nanofibrous mat were determined in order to check its suitability for skin tissue engineering and wound dressing applications.

Dextrose modified flexible tasar and muga fibroin films for wound healing applications.

This paper is focused on preparation and characterization of regenerated muga and tasar fibroin flexible films from cocoon using ionic liquid. These flexible muga and tasar fibroin films were prepared by incorporating dextrose (5 to 15% w/w) as plasticizer. The mechanical, thermal, physical, morphological and biological properties of dextrose plasticized muga and tasar fibroin films were characterized. These plasticized films showed higher elongation at break as well as water holding capacity as compared to the un-plasticized films. The surface roughness and water absorbance capacity of the dextrose plasticized films were higher than un-plasticized films, which results in improved adherence and proliferation of L929 fibroblast cells. Gentamicin loaded plasticized muga and tasar fibroin films showed slightly higher rate of release as compared to un-plasticized films. The biodegradability of dextrose plasticized films was significantly higher as compared to their respective counterpart. The regeneration of flexible muga and tasar silk fibroin films pave the way to expand potential use of non-mulberry in the field of biomedical such as wound dressing.

Fabrication of robust Antheraea assama fibroin nanofibrous mat using ionic liquid for skin tissue engineering.

Electrospinning is an emerging technique used for fabrication of nanofibrous mats for skin tissue engineering applications. The aim of this study centered on fabrication of muga fibroin electrospun mats by using ionic liquid and its characterizations. The muga fibroin extracted from cocoon of Antheraea assama is dissolved in 1-butyl, 3-methyl imidazolium acetate (BMIMAc), a green solvent, to prepare a dope solution for electrospinning. The molecular weight, rheology and structural properties of dope solution are characterized. The process parameters of electrospinning machine such as voltage and concentration of dope solution are varied to obtain nanofibrous mats. The nanofibrous mat having average fiber diameter of 160nm are obtained from 10% w/v concentration of muga fibroin in BMIMAc with an applied voltage of 20KV. The mechanical, structural, physical and thermal properties of muga nanofibrous mat (MNF) are analyzed and compare with muga cast film. The cytocompatibility test is performed using L929 fibroblast cells. It is observed that muga nanofibrous mat support higher growth of fibroblast cells (p<0.05) as compared to muga cast film (MCF). Muga nanofibrous mat and cast film are loaded with gentamycin sulphate. The release rate and antimicrobial efficiency of gentamycin sulphate loaded muga nanofibrous mat are found to be significantly higher (p<0.05) as compared to muga cast film. All these results indicate that muga nanofibrous mat would be a promising material for skin tissue engineering.