Clinicopathological Profile and Survival Outcomes in Patients with Localised Extremity Synovial Sarcomas.

AIMS: Synovial sarcoma is a rare but aggressive variant of soft-tissue sarcoma. Literature is sparse and reported mostly from the West. We analysed the clinical profiles and prognostic factors of extremity synovial sarcoma patients in order to study their clinical journey. MATERIALS AND METHODS: This was a retrospective analysis. All patients with extremity synovial sarcoma treated between 1992 and 2020 were included. Patients with metastases at presentation were excluded. A descriptive analysis of demographic and clinicopathological features of patients undergoing limb salvage surgery (LSS) or amputation was carried out. Overall survival and disease-free survival were calculated for the entire cohort as well as for the LSS and amputation groups. Factors prognostic for survival were identified. RESULTS: In total, 157 patients had localised extremity synovial sarcoma. Predominantly, young adults (median 31 years) and males (61%) were affected. Over 70% of patients presented after recurrence or unplanned surgeries. Sixty-seven per cent of tumours were >5 cm, 69% were deep and 23% involved bone. The limb salvage rate was 64%. In the LSS group, adjuvant radiotherapy and chemotherapy were given to 72% and 68% of patients, respectively. In the amputation group, 72% of patients received adjuvant chemotherapy. In a median follow-up of 59 months, 39.4% of patients had recurrences, the majority (61.2%) were systemic. Five-year overall survival and disease-free survival were 53.4% and 49.8%, respectively. Overall survival was 63.9% and 29.7% in the LSS and amputation groups, respectively. On multivariate analysis, tumour size, depth, omission of radiotherapy and bone invasion were found to be the adverse prognostic factors. CONCLUSION: This is one of the largest studies on extremity synovial sarcoma. Mostly males and young adults were affected. The limb salvage rate was 64%, despite most being referred after unplanned surgery. Almost 70% of patients received radiotherapy and chemotherapy. Overall survival was inferior in the amputation group. Tumour size >5 cm, depth and bone invasion were negative, whereas adjuvant radiotherapy was a positive prognostic factor for survival. Chemotherapy had no impact on survival.

Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - an Analysis of Critical Perioperative and Surgical Outcomes among 155 Peritoneal Surface Malignancy Patients Treated at a Tertiary Care Cancer Centre.

AIMS: Various factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients. MATERIALS AND METHODS: Patients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups. RESULTS: The clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3-4 complications (25.4% versus 36.9%). CONCLUSIONS: The results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.

Dose-dense Paclitaxel and Carboplatin as Neoadjuvant Chemotherapy for Stage IIB/IIIA Non-small Cell Lung Cancer - A Phase II trial.

AIMS: The approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial. MATERIALS AND METHODS: Paclitaxel at 80 mg/m2 on days 1, 8 and 15 with AUC-6 carboplatin on day 1, 3 weekly for four cycles was evaluated as NACT. Patients with Eastern Cooperative Oncology Group performance status 0-2, stage IIB and IIIA (with only non-bulky N2 nodes) were included. The primary end point was the objective response rate. Secondary end points included toxicity, progression-free survival, recurrence-free survival, complete resection rate and overall survival. The relative dose intensity (RDI) was calculated to define tolerability (CTRI/2016/05/006916). RESULTS: In total, 37 patients were enrolled (median age 55 years). Most (78.8%) were smokers. Most patients had adenocarcinoma (57.6%) and stage IIIA disease (81.0%) according to the seventh American Joint Committee on Cancer staging system. Seventy-eight per cent of patients completed four cycles. The objective response rate was 75.6% with a complete response in 10.8%. The mean RDI of paclitaxel was 88.61%, with 68.0% of patients able to maintain an RDI ≥85.0%. In total, 187 toxicity events were recorded (120 grade 1, 64 grade 2 and three grade 3 events). Common toxicities were peripheral neuropathy (20.3%), myalgia (19.8%), nausea (15.7%) and neutropenia (10.2%). There were no treatment-related deaths. Seventeen patients underwent surgery (lobectomy 82.4%). After a median follow-up of 47 months (95% confidence interval 27-50.7 months), the median progression-free survival was 9.6 months (7.4-17.4) and overall survival was 29.2 months (16.0-37.2). CONCLUSION: Dose-dense paclitaxel-carboplatin is feasible, safe and efficacious and should be evaluated further in potentially resectable NSCLC.

Gestational trophoblastic neoplasia: A 6 year retrospective study.

AIMS AND OBJECTIVES: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. MATERIALS AND METHODS: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score /=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. RESULTS: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). CONCLUSION: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Colloidal silver nanoparticles/rhamnolipid (SNPRL) composite as novel chemotactic antibacterial agent.

The antibacterial activity of silver nanoparticles and rhamnolipid are well known individually. In the present research, antibacterial and chemotactic activity due to colloidal silver nanoparticles (SNP), rhamnolipid (RL) and silver nanoparticles/rhamnolipid composite (SNPRL) were evaluated using Staphylococcus aureus (MTCC3160), Escherichia coli (MTCC40), Pseudomonas aeruginosa (MTCC8163) and Bacillus subtilis (MTCC441) as test strains. Further, the SNPRL nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The observation clearly indicates that SNPRL shows prominent antibacterial and chemotactic activity in comparison to all of its individual precursor components.

Rhamnolipid (RL) from Pseudomonas aeruginosa OBP1: a novel chemotaxis and antibacterial agent.

In the present study, the interaction of rhamnolipid produced by Pseudomonas aeruginosa OBP1 with the cell surfaces of Staphylococcus aureus (MTCC 3160) and Klebsiella pneumoniae (MTCC 618) were studied. Rhamnolipid concentration below critical micelle concentration (CMC) did not exhibit significant antibacterial activity. However, on increasing rhamnolipid concentration beyond CMC a prominent antibacterial activity was observed. The results demonstrated different degree of rhamnolipid interaction with both the bacteria. This might be due to the changes in their cell wall composition. The antibacterial activity determined by minimum inhibitory concentration (MIC). The antibacterial activity is prominent within 30 min of incubation. The antibacterial property of rhamnolipid was effective in all tested pH levels (5-9). The rhamnolipid was effective in almost all tested pH levels and showed better chemoattractant property against both the tested bacteria in comparison to glucose. The increase in the membrane permeability was evidenced by increase in the release of protein, enhancement in cell surface hydrophobicity and raises in the retention of crystal violet dye. Further, leakage of 260 nm absorbing intracellular materials, fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis confirmed the disruptive action of rhamnolipid. The above evidences support the idea that rhamnolipid significantly alters the cell membrane/envelop that leads to cell damage and enhances membrane permeability. Such activity of rhamnolipid could be used as an additive in the formulation of antibiotic and other antimicrobial agents for enhancing the effectiveness of chemotherapeutics.

Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice.

Fibroblast growth factor-2 (FGF2) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of FGF2 in mice are equivocal. In this study, we used transgenic mice with increased expression of FGF2 in photoreceptors (rhodopsin promoter/FGF2 transgenics) to investigate the effects of sustained increased expression of FGF2 in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase beta subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/FGF2 transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to FGF2 transgenic mice (P = 0.0001). These data indicate that increased expression of FGF2 in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that FGF2 protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.

Arecoline-induced changes of poly-ADP-ribosylation of cellular proteins and its influence on chromatin organization.

Arecoline, the major alkaloid of betel nut (Areca catechu L.) and a suspected carcinogen, has been implicated in human cancers of various sites. A considerable portion of the world's population is constantly exposed to arecoline due to the habit of masticating betel nuts. The present work relates to the study of early molecular events following chronic arecoline exposure at a dose of 10 microg/ml to Swiss albino mice. Poly-ADP-ribosylation of all cellular proteins, histones and poly-ADP-ribose polymerase were studied in bone marrow and spleen cells and correlated with the organizational status of the chromatin. While most proteins showed lowering of their poly-ADP-ribosylation following arecoline treatment, only histone protein H1 in spleen cells and H2B in bone marrow cells exhibited an increase. The chromatin of both the tissues was progressively relaxed upon arecoline exposure. The implications of these changes have been discussed regarding the process of initiation of arecoline-induced carcinogenesis.

Poly-ADP-ribosylation of histone proteins of human kidney T1-cells in vitro following gamma-irradiation.

Poly-ADP-ribosylation of cellular proteins is involved with radiation induced damage and its repair. It has been observed that suspension of human kidney T1-cells in vitro attained elevated levels of poly-ADP-ribosylation due to experimental manipulations necessary for preparation of single cell suspension from monolayer cell cultures. These cells in suspension were exposed to various doses of gamma-rays with or without subsequent repair incubation. The PADPR of histones H3, H1 and H2B increased with increasing dose of radiation and decreased after 90 min or repair incubation. Concomitant with these changes, the affinity of histones to DNA in chromatin reduced immediately after irradiation. Normal affinity was reestablished after post-irradiation repair incubation. The results indicate that induction of poly-ADP-ribosylation of histone proteins by radiation and by manipulations to prepare single cell suspension involved different cellular components.

2-Mercaptopropionylglycine affords enhanced radioprotection after a liposome encapsulation.

Use of radioprotective drugs in radiotherapy is desirable to protect normal tissues. 2-mercaptopropionylglycine (MPG) has shown promising results in experimental radioprotection. In this report, a liposome drug delivery system for MPG has been used in Swiss albino mice exposed to 1 to 8 Gy whole body Gamma-irradiation to test whether or not this modality enhances the MPG afforded radioprotection. A statistically significant, dose dependent enhancement of protection by liposome encapsulated MPG (LEM) was observed. LEM, as compared to free MPG, improved the viabilities of spleen and bone marrow cells by factors between 1.11 and 2.23 for different doses of radiation.

Steady-state serum concentrations after cis (Z)-flupentixol decanoate in viscoleo.

Serum concentrations of cis(Z)-flupentixol have been measured in patients on cis(Z)-flupentixol decanoate injections during successive dosage intervals of 2-4 weeks. The calculation of the fluctuation of the serum concentration in the dosage interval indicates that each individual patient should have his own dosage interval. For the 2-week group a significant correlation was found between weekly dose and preinjection concentration (r = 0.79) although an interindividual variability of X 4 was found. For this group the relative within-patient variation in the pre-injections concentration was calculated to be 9.6%, showing that a constant dosage regimen in the individual patient leads to an almost constant drug load.