Spectrum and surgical outcomes of gastrointestinal stromal tumours.

BACKGROUND: Surgery and imatinib are the mainstays of the management of gastrointestinal stromal tumours (GIST). This study aimed to analyse the outcomes in the management of GIST utilising surgery and imatinib. METHODS: Progression-free survival (PFS) and overall survival (OS) were analysed in relation to imatinib therapy, location of tumour, resection margins, type and extent of surgery. Imatinib was administered in the neoadjuvant (maximum 12 months) and adjuvant setting (minimum 36 months) and until disease progression or drug intolerance. Disease response was assessed with the Choi criteria. Survival analysis included calculation of PFS, OS and Kaplan-Meier curves. RESULTS: Sixty-two patients were reviewed and 56 had surgical resection. The median age (range) was 58.5 (8-95) years. The median PFS and OS (IQR) was 24.0 (0-52.0) and 41.0 (15.0-74.0) months, respectively. Thirty-nine (70%) patients were treated with imatinib, with 21 of these in a neoadjuvant setting. In the patients undergoing surgery, surgical margins were R0, R1 and R2 in 41 (75%), eight (15%) and six (11%) respectively. There was an insignificant difference in the overall survival in these three groups. For those having liver metastasectomy and multivisceral resection, the PFS and OS were 32.5 (17.5-60.3) and 28.5 (5.75-49.8) (p = 0.008), and 96.0 (58.5-116) and 80 (50.5-92.3) months (p = 0.033), respectively. CONCLUSION: Whilst the numbers were small, certain trends were observed. Surgery in combination with imatinib offers survival benefit in patients undergoing R0, R1, R2, liver metastases and multivisceral resections.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

In vivo delivery of bovine viral diahorrea virus, E2 protein using hollow mesoporous silica nanoparticles.

Our work focuses on the application of mesoporous silica nanoparticles as a combined delivery vehicle and adjuvant for vaccine applications. Here we present results using the viral protein, E2, from bovine viral diarrhoea virus (BVDV). BVDV infection occurs in the target species of cattle and sheep herds worldwide and is therefore of economic importance. E2 is a major immunogenic determinant of BVDV and is an ideal candidate for the development of a subunit based nanovaccine using mesoporous silica nanoparticles. Hollow type mesoporous silica nanoparticles with surface amino functionalisation (termed HMSA) were characterised and assessed for adsorption and desorption of E2. A codon-optimised version of the E2 protein (termed Opti-E2) was produced in Escherichia coli. HMSA (120 nm) had an adsorption capacity of 80 µg Opti-E2 per mg HMSA and once bound E2 did not dissociate from the HMSA. Immunisation studies in mice with a 20 µg dose of E2 adsorbed to 250 µg HMSA was compared to immunisation with Opti-E2 (50 µg) together with the traditional adjuvant Quillaja saponaria Molina tree saponins (QuilA, 10 µg). The humoral responses with the Opti-E2/HMSA nanovaccine although slightly lower than those obtained for the Opti-E2 + QuilA group demonstrated that HMSA particles are an effective adjuvant that stimulated E2-specific antibody responses. Importantly the cell-mediated immune responses were consistently high in all mice immunised with Opti-E2/HMSA nanovaccine formulation. Therefore we have shown the Opti-E2/HMSA nanoformulation acts as an excellent adjuvant that gives both T-helper 1 and T-helper 2 mediated responses in a small animal model. This study has provided proof-of-concept towards the development of an E2 subunit nanoparticle based vaccine.

Water pollution of Sabarmati River--a harbinger to potential disaster.

River Sabarmati is one of the biggest and major river of Gujarat that runs through two major cities of Gujarat, Gandhinagar and Ahmedabad and finally meets the Gulf of Khambhat (GoK) in the Arabian Sea. A study was conducted to evaluate the water quality of this river, as it could possibly be one of the major sources for filling up Kalpasar, the proposed man-made freshwater reservoir supposed to be the biggest one in the world. A total of nine sampling stations were established covering 163 km stretch of the river from upstream of Gandhinagar city to Vataman near Sabarmati estuary. Physicochemical (temprature, pH, salinity, chloride, total dissolved solids, turbidity, dissolved oxygen, biochemical oxygen demand, phenol, and petroleum hydrocarbons), biological (phytoplankton), and microbiological (total and selective bacterial count) analyses indicated that the river stretch from Ahmedabad-Vasana barriage to Vataman was highly polluted due to perennial waste discharges mainly from municipal drainage and industries. An implementation of sustainable management plan with proper treatment of both municipal and industrial effluents is essential to prevent further deterioration of the water quality of this river.

Blood anticoagulant sulphated polysaccharides of the marine green algae Codium dwarkense (Boergs.) and C. tomentosum (Huds.) Stackh.

Cold water extracts of marine green algae Codium dwarkense and C. tomentosum were precipitated with different molar concentrations of KCl and were subjected to anion exchange and gel filtration chromatography. Both the species yielded sulphated arabinan through bioassay-guided purification and both were chemically identified as a polymer of alpha-L-arabinofuranose. Products were assayed for their blood anticoagulant activity using PT, APFT and TT tests and found that they differed in the potency of activity though they are chemically identical. Bioassay-guided purification of cold water extract of C. tomentosum yielded sulphated arabinan and sulphated arabinogalactan.

Sulphated polysaccharides of Codium dwarkense Boergs. from the west coast of India: chemical composition and blood anticoagulant activity.

Bioassay-guided purification of sulphated polysaccharides from a green marine alga, Codium dwarkense, yielded two products, which contained sulphated arabinan and sulphated arabinogalactan. The product containing arabinan sulphate exhibited stronger blood anticoagulant activity than the one containing sulphated arabinogalactan.

Intraneural mucous cysts of peripheral nerves.

We present three cases of a rare mucous cyst inside the peripheral nerves of the upper extremity; a lateral cutaneous nerve of the forearm, a dorsal sensory branch of the ulnar nerve, and a median nerve at the wrist. All our cases were intraneural, and we excised longitudinal strips of the cyst wall between nerve fascicles in all, preserving nerve function in each case.

Bioactivity of marine organisms: Part VIII--Screening of some marine flora of western coast of India.

Methanolic extracts of 31 botanically identified species of marine flora, collected from Gujarat Coast, have been screened for a wide range of biological activities. Of these, 3 extracts showed anti-implantation, 2 had antiviral, 2 showed hypotensive, 1 had anti-inflammatory while 12 extracts showed diuretic activities. The antiviral activity; against EMCV, was confirmed in one alga. The active principles and results of these studies are reported.

Multiple schwannomas of the ulnar nerve: a case report.

Multiple schwannomas may occur as visible tumors or may occur as tumors in situ. The tumors in situ may be missed when the visible tumors are excised. In time, the schwannomas in situ grow and appear to be recurrent, while in fact, they are multicentric. The prognosis on multicentric schwannomas thus remains guarded.

K23. A low-incidence antigen in the Kell blood group system identified by biochemical characterization.

An antibody in the serum of a gravida 4, para 3 woman reacted with red cells from two of her children, her husband, and his mother, but with none of more than 2100 reference red cell samples and blood samples from donors. The reactive antigen was inactivated by 2-aminoethylisothiouronium bromide or dithiothreitol-papain treatment. The antigen was immunoprecipitated from paternal red cells with maternal antibody and shown to migrate by sodium dodecylsulfate polyacrylamide gel electropheresis as a single protein of approximately 93,000 daltons. After transfer to nitrocellulose paper by Western blotting, the protein reacted with a rabbit antibody specific for Kell protein. The chemical inactivation and electrophoretic findings were characteristic of Kell group antigens. The reaction with the rabbit antibody establishes that the "new" low incidence antigen was an epitope on Kell group protein and must be coded for by the Kell gene. It has been designated K23.

Closed vitrectomy after trauma.

The results of vitrectomy in fifty traumatized eyes were assessed, and six types of pathological change resulting from trauma identified. The anatomical and visual results were good except where surface vitreo-retinal traction was present either at the vitreous base or posteriorly.