Progress in Retroperitoneal Sarcoma Management: Surgical and Radiotherapy Approaches.

Surgical resection is the cornerstone of curative treatment for retroperitoneal sarcomas (RPS), aiming for complete excision, yet the complexity of RPS with its proximity to vital structures continues to lead to high local recurrence rates after surgery alone. Thus, the role of radiotherapy (RT) continues to be refined to improve local control, which remains an important goal to prevent RPS recurrence. The recently completed global randomized trial to evaluate the role of surgery with and without preoperative RT - STRASS1, did not demonstrate a significant overall benefit for neoadjuvant RT based on the pre-specified definition of abdominal recurrence-free survival, however, sensitivity analysis using a standard definition of local recurrence and analysis of outcomes by compliance to the RT protocol suggests histology-specific benefit in well- and some de-differentiated liposarcomas. Ultimately, multidisciplinary collaboration and personalized approaches that consider histological sarcoma types and patient-specific factors are imperative for optimizing the therapeutic strategy in the management of RPS.

Palliative Care as a Component of High-Value and Cost-Saving Care During Hospitalization for Metastatic Cancer.

PURPOSE: Randomized controlled trials have demonstrated that palliative care (PC) can improve quality of life and survival for outpatients with advanced cancer, but there are limited population-based data on the value of inpatient PC. We assessed PC as a component of high-value care among a nationally representative sample of inpatients with metastatic cancer and identified hospitalization characteristics significantly associated with high costs. METHODS: Hospitalizations of patients 18 years and older with a primary diagnosis of metastatic cancer from the National Inpatient Sample from 2010 to 2019 were analyzed. We used multivariable mixed-effects logistic regression to assess medical services, patient demographics, and hospital characteristics associated with higher charges billed to insurance and hospital costs. Generalized linear mixed-effects models were used to determine cost savings associated with provision of PC. RESULTS: Among 397,691 hospitalizations from 2010 to 2019, the median charge per admission increased by 24.9%, from $44,904 in US dollars (USD) to $56,098 USD, whereas the median hospital cost remained stable at $14,300 USD. Receipt of inpatient PC was associated with significantly lower charges (odds ratio [OR], 0.62 [95% CI, 0.61 to 0.64]; P < .001) and costs (OR, 0.59 [95% CI, 0.58 to 0.61]; P < .001). Factors associated with high charges were receipt of invasive medical ventilation (P < .001) or systemic therapy (P < .001), Hispanic patients (P < .001), young age (18-49 years, P < .001), and for-profit hospitals (P < .001). PC provision was associated with a $1,310 USD (-13.6%, P < .001) reduction in costs per hospitalization compared with no PC, independent of the receipt of invasive care and age. CONCLUSION: Inpatient PC is associated with reduced hospital costs for patients with metastatic cancer, irrespective of age and receipt of aggressive interventions. Integration of inpatient PC may de-escalate costs incurred through low-value inpatient interventions.

Effects of polycyclic aromatic hydrocarbons on marine and freshwater microalgae - A review.

The first synthetic review of the PAHs effects on microalgae in experimental studies and aquatic ecosystems is provided. Phytoplankton and phytobenthos from marine and freshwaters show a wide range of sensitivities to PAHs, and can accumulate, transfer and degrade PAHs. Different toxicological endpoints including growth, chlorophyll a, in vivo fluorescence yield, membrane integrity, lipid content, anti-oxidant responses and gene expression are reported for both freshwater and marine microalgal species exposed to PAHs in culture and in natural assemblages. Photosynthesis, the key process carried out by microalgae appears to be the most impacted by PAH exposure. The effect of PAHs is both dose- and species-dependent and influenced by environmental factors such as UV radiation, temperature, and salinity. Under natural conditions, PAHs are typically present in mixtures and the toxic effects induced by single PAHs are not necessarily extrapolated to mixtures. Natural microalgal communities appear more sensitive to PAH contamination than microalgae in monospecific culture. To further refine the ecological risks linked to PAH exposure, species-sensitivity distributions (SSD) were analyzed based on published EC50s (half-maximal effective concentrations during exposure). HC5 (harmful concentration for 5% of the species assessed) was derived from SSD to provide a toxicity ranking for each of nine PAHs. The most water-soluble PAHs naphthalene (HC5 = 650 µg/L), acenaphthene (HC5 = 274 µg/L), and fluorene (HC5 = 76.8 µg/L) are the least toxic to microalgae, whereas benzo[a]pyrene (HC5 = 0.834 µg/L) appeared as the more toxic. No relationship between EC50 and cell biovolume was established, which does not support assumptions that larger microalgal cells are less sensitive to PAHs, and calls for further experimental evidence. The global PAHs HC5 for marine species was on average higher than for freshwater species (26.3 and 1.09 µg/L, respectively), suggesting a greater tolerance of marine phytoplankton towards PAHs. Nevertheless, an important number of experimental exposure concentrations and reported toxicity thresholds are above known PAHs solubility in water. The precise and accurate assessment of PAHs toxicity to microalgae will continue to benefit from more rigorously designed experimental studies, including control of exposure duration and biometric data on test microalgae.

Capacity of the potentially toxic diatoms Pseudo-nitzschia mannii and Pseudo-nitzschia hasleana to tolerate polycyclic aromatic hydrocarbons.

This study investigates the effects of polycyclic aromatic hydrocarbons (PAHs) on two potentially toxic Pseudo-nitzschia hasleana and P. mannii, isolated from a PAH contaminated marine environment. Both species, maintained in non-axenic cultures, have been exposed during 144 h to increasing concentrations of a 15 PAHs mixture. Analysis of the domoic acid, showed very low concentrations. Dose-response curves for growth and photosynthesis inhibition were determined. Both species have maintained their growth until the end of incubation even at the highest concentration tested (120 µg l-1), Nevertheless, P mannii showed faster growth and seemed to be more tolerant than P. hasleana. To reduce PAH toxicity, both species have enhanced their biovolume, with a higher increase for P. mannii relative to P hasleana. Both species were also capable of bio-concentrating PAHs and were able to degrade them probably in synergy with their associated bacteria. The highest biodegradation was observed for P. mannii, which could harbored more efficient hydrocarbon-degrading bacteria. This study provides the first evidence that PAHs can control the growth and physiology of potentially toxic diatoms. Future studies should investigate the bacterial community associated with Pseudo-nitzschia species, as responses to pollutants or to other environmental stressors could be strongly influence by associated bacteria.

GC-MS analysis of polycyclic aromatic hydrocarbons in bottled olive oil marketed in Lebanon.

Lebanon has witnessed elevated levels of pollution over the last few years due to increased waste incineration, emissions from vehicles and electricity generators, and mass demonstrations involving the burning of tires. The resultant generation of polycyclic aromatic hydrocarbons (PAHs) from the incomplete combustion of organic materials present in these sources may contaminate various foods including olive oil. Lebanon has a sizeable olive oil industry that is a main pillar of its agricultural sector. In this study, we investigated the occurrence of 16 semi-volatile lipophilic organic pollutants in 25 bottled olive oil brands, marketed in Lebanon, using a solid phase extraction (SPE) method followed by gas chromatography mass spectrometry (GC-MS). PAHs were detected in 60% of brands (41% of samples) where 12% of brands contained traces of probably carcinogenic (Class 2A) compounds and 56% of brands contained traces of possibly carcinogenic (Class 2B) compounds. One brand revealed levels of benzo[a]pyrene of 9.45 µg/kg and 11.9 µg/kg in batches collected over two production dates which are higher than the limit set by the European Commission for benzo[a]pyrene in food (2 µg/kg). The same batches contained a total of 19.3 µg/kg and 26.7 µg/kg of the four PAHs: benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, and chrysene which also exceeded the limit set by the EC for the combination of these four PAHs in olive oil (10 µg/kg). This study is the first-of-its-kind in Lebanon and emphasizes the need to perform adequate cleanup steps in the manufacturing process in order to reduce the content of carcinogenic PAHs in olive oil.

Structural and functional responses of coastal marine phytoplankton communities to PAH mixtures.

The toxicity of polycyclic aromatic hydrocarbons (PAHs) mixtures was evaluated on natural phytoplankton communities sampled from lagoons of Bizerte (South-western Mediterranean Sea) and Thau (North-western Mediterranean Sea). PAHs induced short-term dose and ecosystem-dependant decreases in photosynthetic potential. Chlorophyll a was negatively affected by increasing PAHs concentrations, together with dramatic changes in phytoplankton community composition. Size classes were strongly affected in the Bizerte compare to the Thau lagoon, with a decrease in nano- and microphytoplankton densities compare to picophytoplankton. In both locations, the diatom Entomoneis paludosa appeared favoured under PAH exposure as evidenced by increase in cell density, whereas autotrophic flagellates and dinophytes were strongly reduced. Smaller cells were more tolerant to exposure to highest PAHs concentrations, with persistent picophytoplankton carbon biomass at the end of the incubations. Apparent recovery of photosynthetic potential, accompanied with a regrowth of chlorophyll a under the lowest PAH doses, coincided with a significantly altered community composition in both lagoons. Furthermore, sensitivity to PAHs was not related to the phytoplankton cell size, and toxicity-induced modification of top-down control by grazers during the experiment cannot be excluded.

Toxicity of benz(a)anthracene and fluoranthene to marine phytoplankton in culture: does cell size really matter?

The toxicity of benz(a)anthracene and fluoranthene (polycyclic aromatic hydrocarbons, PAHs) was evaluated on seven species of marine algae in culture belonging to pico-, nano-, and microphytoplankton, exposed to increasing concentrations of up to 2 mg L(-1). The short-term (24h) toxicity was assessed using chlorophyll a fluorescence transients, linked to photosynthetic parameters. The maximum quantum yield Fv/Fm was lower at the highest concentrations tested and the toxicity thresholds were species-dependent. For acute effects, fluoranthene was more toxic than benz(a)anthracene, with LOECs of 50.6 and 186 µg L(-1), respectively. After 72 h exposure, there was a dose-dependent decrease in cell density, fluoranthene being more toxic than benz(a)anthracene. The population endpoint at 72 h was affected to a greater extent than the photosynthetic endpoint at 24h. EC50 was evaluated using the Hill model, and species sensitivity was negatively correlated to cell biovolume. The largest species tested, the dinoflagellate Alexandrium catenella, was almost insensitive to either PAH. The population endpoint EC50s for fluoranthene varied from 54 µg L(-1) for the picophytoplankton Picochlorum sp. to 418 µg L(-1) for the larger diatom Chaetoceros muelleri. The size/sensitivity relationship is proposed as a useful model when there is a lack of ecotoxicological data on hazardous chemicals, especially in marine microorganisms.