Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Locally advanced squamous cervical carcinoma (M0): management and emerging therapeutic options in the precision radiotherapy era.

Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography-magnetic resonance imaging) PET-MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era.

Management of Patients with Gastric or Gastroesophageal Junction Cancer: From Theory to Integrated Clinical Path- ways Implementation in the Real World.

Introduction: Best care of esophagogastric junction and gastric cancer (EGC) requires a complex, timely interaction between members of a multi-disciplinary team (MDT). An integrated clinical pathway (ICP) is necessary to achieve this goal as well as the implementation of its use in daily practice. The objective of this study was to elaborate on an integrated clinical pathway for the multi-disciplinary management of ECG. Authors also put in act an implementation program to improve adherence to guidelines thought an ICP. Method: This prospective work carried out by a multi-institutional MDT in Italy identified expert panel extracted relevant recommendations and/or statements from published papers and guidelines obtaining a set of crucial interventions employed the Estimate-Talk-Estimate method. A flow-chart diagram was elaborated to elicit the process at a glance. The primary outcome measure was the elaboration of an ICP with a high consensus rate also reported as a snapshot diagram and its implementation in daily clinical practice. An accredited certification body agency validated results, and an implementation process was started in several hospitals known to treat ECG. Results: A methodologist aggregated a multi-disciplinary panel of experts from different institutions. The panel elaborated a flow-chart diagram with crucial intervention highlight and connecting lines, as well as outcome measures. An accredited certification body agency validated the entire process, representing the basis for empowerment and implementation among patients and oncological professionals in various hospitals. Conclusion: The multi-disciplinary and multi-institutional expert panel successfully elaborated on a validated ICP for all stages ECG. An in-hospital implementation program has been programmed.

Biological effect of astaxanthin on alcohol-induced gut damage in Carassius auratus used as experimental model.

Alcohol and its metabolites are responsible for damage both within the gastrointestinal tract and other organs. Alcohol abuse promote intestinal inflammation, that may be the cause of multiple organ dysfunctions and chronic disorders. In this research, the effect of astaxanthin, a powerful antioxidant with several biological effects, on alcohol damage-induced in the intestine of Carassius auratus, was investigated. In the fishes exposed to ethanol, an increase of the intestinal epithelium mucous cells and circulating macrophages, with intestinal mucosa disorganization was observed. In contrast, in the fishes treated with astaxanthin intestinal morphology was restored. By immunohistochemical analysis, using α-Smooth Muscle Actin (α-SMA) and Vasoactive intestinal polypeptide (VIP) antibodies, a reduction of inflammatory states alcohol-induced was evident, with more regular muscularis submucosa and more organized intestinal mucosa without inflammatory cells. The results suggest that astaxanthin treatments can be a good candidate for preventing damage within the gastrointestinal associated with excessive alcohol consumption.

Effect of light on the calretinin and calbindin expression in skin club cells of adult zebrafish.

In the last decade, zebrafish has been used as a model for the study of several human skin diseases. The epidermis of Danio rerio is composed of keratinocytes and two types of secretory cells: mucous cells and club cells. Club cells have multiple biological functions and among them may be important in the protection against ultraviolet damage through the proliferative response or through the increased production of protective substances. Calcium-binding proteins such as calbindin D28K and calretinin are used as markers of nervous and enteric nervous systems, but they are present in numerous other cells. These proteins are involved in a wide variety of cell activities, such as cytoskeletal organization, cell motility and differentiation, cell cycle regulation and neuroprotective function. In this study we demonstrated, for the first time, the presence of calretinin and calbindin D28K in skin club cells of Danio rerio exposed to different wavelengths by immunohistochemistry analysis. Exposure to white-blue light and blue light causes the expression and colocalization of calbindin-D28K and calretinin. These proteins were moderately expressed and no colocalization was observed in the club cells of the control fish. In zebrafish exposed to continuous darkness for 10 days, in the club cells the two antibodies did not detect any proteins specifically. These results demonstrate that calbindin and calretinin could be involved in the pathophysiology of skin injury due to exposure to short-wavelength visible light spectrums.

Expression of Langerin/CD207 in airways, lung and associated lymph nodes of a stranded striped dolphin (Stenella coeruleoalba).

The airways and lungs of vertebrates are an entrance way for several microbial pathogens. Cetaceans present an upper and lower respiratory anatomy that allows the rapid flow of large air volumes, which may lead to high susceptibility to respiratory infections. Mortality and stranding rate of Cetaceans increased dramatically, so wide the knowledge about the immune system and specific antibodies identifying immune cells populations, is of fundamental importance to monitor and document cetacean health. The aim of this study was to identify the localization of dendritic cells marked by Langerin/CD207 in airways, lungs and associated lymph nodes, of the striped dolphin Stenella coeruleoalba. Samples of trachea, bronchi, lungs and lung-associated lymph nodes were obtained from a stranded adult male of Stenella coeruleoalba. Our results showed abundant lymphoid aggregates (LAs) in the lung of S. ceruleoalba. Langerhans-like dendritic cells were well distributed along the epithelium and interstitium of respiratory tract and in associated lymph nodes. The present study deepens the knowledge about the cetacean's immune system and report about the exploitability of a commercial antibody (Langerin/CD207) for cetacean species.

Merkel cells immunohistochemical study in striped dolphin (Stenella coeruleoalba) skin.

Cetacean mechanical senses, such as hearing, echolocation, active touch and the perception of water movements, are essential for their survival. Dolphins skin possesses dense packing of dermal papillae associated with the cutaneous ridges that suggests a sensory function, furthermore they are well innervated and very sensitive to touch. This is mediated by mechanoreceptors, abundant in the region of the head and in the dorsal part of the body. Most odontocetes possess vibrissae (i.e., sensory hair) that have been well described in literature and present a microanatomy similar to that of terrestrial mammals. The aim of this study was to characterize Merkel cell through use of specific antibodies: Substance P, Anti-calbindin DK28, Anti-5HT, Leu- enkephalin, Protein Gene Product 9.5 (PGP9.5) and Anti-Human Neuronal Protein, for the first time. Merkel cells (MCs) in the dolphin skin are specialized skin receptors, characterized by their particular location and close association with nerve terminals. The presence of neuroendocrine markers and different neuropeptides confirms that MCs play also neuroendocrine function and are considered as part of the diffuse neuroendocrine system. Furthermore, the presence of Leu-enkephalin in Merkel cells could involve these cells in inflammatory responses in the skin.

Intestinal immunity of dogfish Scyliorhinus canicula spiral valve: A histochemical, immunohistochemical and confocal study.

The present study describes histochemical and immunohistochemical characteristics of the spiral valve and its associated lymphoid tissue (GALT) in the dogfish Scyliorhinus canicula. The mucosal surface of the spiral valve represents the first line of defense against pathogens coming from the external environment through food. Epithelial, mucus and immune cells play a key role in controlling the inflammatory response. Valve intestine of S. canicula had many folds lined by simple columnar cells and goblet cells, which later reacted positive to PAS, AB and AB-PAS, histochemical stains differentiated the different types of mucins; lectin histochemistry (PNA and WGA), detected neutral and acid mucins secreted that plays an important role in protection against invading pathogens. Integrin α5ß1 was expressed in enterocytes that line the valve's folds with greater marking in the apical part of the cells. Laminin was found on the apical side of the epithelium, in fibrillar and cellular elements of the lamina propria and in the muscularis mucosa. In the spiral valve gut-associated lymphoid tissue (GALT) has been studied. For the first time, massive leucocytes aggregates were identified by confocal immunofluorescence techniques, using the following antibodies: TLR2, S100, Langerin/CD207. Our results expand knowledge about Dogfish valve intestine giving important news in understanding comparative immunology.

Immunohistochemical characterization of epidermal dendritic-like cells in giant mudskipper, Periophthalmodon schlosseri.

Giant Mudskipper, Periophthalmodon schlosseri (Pallas, 1770), is euryhaline, amphibious, and air-breathing fish. These fishes live in close association to mangrove forests and often spend over 90% of time out of water, in adjacent mudflats. They have developed morphological and physiological adaptations to satisfy their unique lifestyles. The skin is the primary interface between the body and the environment, and has a central role in host defence. The initiation of immune responses to antigens in the vertebrate skin has often been attributed to epidermal Langerhans'cells (LC) that are dendritic cells (DC), antigen-presenting cells (APC) which reside in the epidermis. Dendritic cells have been characterized morphologically and functionally in the teleost fish tissues such as rainbow trout, salmonids, medaka, African catfish and zebrafish. However, there is no evidence of the presence of DCs and their role in mudskippers immunity. The aim of this preliminary study was to characterize, through use of specific antibodies: Toll-like receptor 2, S100, serotonin (5-HT), and Vesicular acetylcholine transporter VAChT, a specific DC-like subpopulation in Pn. schlosseri's epidermis.

Opuntia ficus-indica (L.) Miller as a source of bioactivity compounds for health and nutrition.

Plants with beneficial properties are known in traditional medicine. Nowadays, in spite of widespread availability of synthetic compounds, the search goes towards natural compounds to lower cost and few side effects. The increasing interest in preventive medicine encourages use of nutraceuticals, bioactive compounds of vegetable origin with important nutritional values. Among the medicinal plants, Opuntia ficus-indica (L.) Miller (Family Cactaceae, subfamily Opuntiodeae, Genus Opuntia, subgenus Platyopuntia, species Opuntia ficus-indica (L.) Miller) is widely known for its beneficial properties. The aim of the present review is to stress the major classes of Opuntia components and their medical interest through emphasis on some of their biological effects, particularly those having the most promising expected health benefits and therapeutic impacts on fish and mammals.

Immunohistochemical colocalization of G protein alpha subunits and 5-HT in the rectal gland of the cartilaginous fish Scyliorhinus canicula.

Serotonin [5-hydroxytryptamine (5-HT)] is an important neuromodulator involved in a wide range of physiological functions. The effects of serotonin are mediated by an extended family of receptors coupled to multiple heterotrimeric G-proteins, associated with cellular membrane. G proteins connect receptors to effectors and thus trigger intracellular signaling pathways. These cellular processes several regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis. Generally, elasmobranch fish dwell a hypersaline environment and utilize a specialized extrarenal salt secreting organ, the rectal gland, to face ionic homeostasis. In this study in addition to the morphological, histochemical and immunohistochemical description of the Scyliorhinus canicula rectal gland, for the first time, the presence of serotonin (5-HT), and distribution of different types of G protein alpha subunits (Gα o, Gα q/11, and Gα s/olf) has been investigated in the rectal gland epithelium by confocal immunofluorescence techniques. Colocalization G proteins and 5-HT in the secretory epithelium of the gland suggests serotonin acts as a hormone and involves G proteins in an autocrine-paracrine control of rectal gland homeostasis.

Immunohistochemical characterization of Toll-like receptor 2 in gut epithelial cells and macrophages of goldfish Carassius auratus fed with a high-cholesterol diet.

Toll-like receptors (TLRs) are a group of pattern recognition molecules that play a crucial role in innate immunity. The structural conservation of the archaic TLR system suggests that the regulation of the immune response might be similar in fish and mammals. Several TLRs (TLR-1, -2, and -4) are expressed by activated macrophages, "foam cells" in human atherosclerotic lesions. To date, 20 different TLRs were identified in more than a dozen different fish species. In this study we found that feeding goldfish, Carrassius auratus, a high-cholesterol diet (HCD) resulted macrophage foam cell formation in the intestinal tissues. The expression of TLR2 has been found in foam cells and in the cytoplasm of enterocytes, however the staining was more intense at the apical surface of polarized intestinal epithelial cells and in the lamina propria. In the intestinal epithelial cells and in the lamina propria cells of the control fish the TLR2 was expressed at low levels. The intestinal epithelium is directly involved in the mucosal immune response through its expression of proinflammatory genes, release of inflammatory cytokines, and recruitment of inflammatory cells.

Stereotactic body radiotherapy in non-operable lung cancer patients

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Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma.

AIM: To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. MATERIAL AND METHODS: Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland-Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. RESULTS: For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). CONCLUSION: Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late hepatic arterial phase in patients with hepatocellular carcinoma.

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer: Preliminary Results in 26 Patients.

BACKGROUND: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. PATIENTS AND METHODS: Patients with LpC having prostate volume ≤90 cm(3) were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. RESULTS: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. CONCLUSIONS: Our preliminary results of SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.

Immunohistochemical localization of Toll-like receptor 2 in skin Langerhans' cells of striped dolphin (Stenella coeruleoalba).

The skin is the primary interface between the body and the environment, and has a central role in host defence. In the epidermis, Langerhans' cells form an interconnecting network of dendritic cells, that play a central role within inflammatory and immune responses of terrestrial and aquatic mammals, but few studies aimed at their characterization have been carried out in cetaceans, so far. Toll-like receptors are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. The aim of this preliminary study was to describe the expression of Toll-like receptor 2 in a stranded striped dolphin (Stenella coeruleoalba) skin. Immunoreactive cells were predominantly found within the stratified squamous epithelium. Other Toll-like receptor 2 positive cells of varying morphology, were found, and may help to increase the knowledge on the interaction occurring between dolphins and the environment in which they live at their most crucial interface: the skin.

Is there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable? A survey of head and neck surgical/radiation oncologists.

Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (ROs) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of ROs recommended PRT in the case of positive/close margins (R(+)/R(close)) or in the case of initial involvement of thyroid cartilage (pT3(tci)). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in R(close) and with 56-60 Gy (34%) in pT3(tci). In Conclusion, OPL raises new considerations about PRT.