Salivary duct carcinoma (SDC), an aggressive subtype of salivary gland cancer, is androgen receptor (AR)–positive in 67–96% of cases. In patients with locally recurrent and metastatic (R/M) ...AR-positive SDC, androgen deprivation therapy (ADT) has an overall response rate of 18–64.7%. In this study, we describe the efficacy of adjuvant ADT in patients with poor-risk (stage 4a) AR-positive SDC.
This is a retrospective cohort study in which patients with stage 4a AR-positive SDC were offered adjuvant ADT, i.e. bicalutamide, luteinizing hormone-releasing hormone (LHRH) analogue or a combination of these after tumour resection. In the control group, data were collected on patients with stage 4a SDC who underwent a tumour resection but did not receive adjuvant ADT.
Twenty-two AR-positive SDC patients were treated with adjuvant ADT for a median duration of 12 months. The control group consisted of 111 SDC patients. After a median follow-up of 20 months in the ADT-treated patients and 26 months in the control group, the 3-year disease-free survival (DFS) was estimated as 48.2% (95% confidence interval CI 14.0–82.4%) and 27.7% (95% CI 18.5–36.9%) (P = 0.037). Multivariable Cox regression analysis showed a hazard ratio of 0.138 (95% CI 0.025–0.751, P = 0.022) for DFS and 0.064 (95% CI 0.005–0.764, P = 0.030) for overall survival (OS) in favour of the ADT-treated patients.
Poor-risk, AR-positive SDC patients who received adjuvant ADT have a significantly longer DFS compared with patients in the control group, who did not receive adjuvant ADT. For OS, this was just below and above the significance level, in case there was or was no correction for confounders.
•Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer.•Palliative androgen deprivation therapy (ADT) has a response rate of 18–64.7%.•In this retrospective cohort study, we describe the efficacy of adjuvant ADT in poor-risk SDC.•Adjuvant ADT showed a significantly longer disease-free survival.•Overall survival was significantly longer after correction for confounders.
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs ...such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications. Both physicians and patients should be educated to recognize drug-related toxicities in order to manage them in an early phase. Tools (e.g. toxicities summary booklet) for physicians and patients could be considered to improve the knowledge on side effects management. Guidelines, whenever available, should be followed.
Aim
To determine the protective capacity against Salmonella infection in mice of the cell‐free fraction (postbiotic) of fermented milk, produced at laboratory and industrial level.
Methods and ...Results
The proteolytic activity (PA) of 5 commercial cultures and 11 autochthonous Lactobacillus strains was evaluated. The DSM‐100H culture displayed the highest PA and it was selected for further studies. The capacity of the postbiotics produced by pH‐controlled fermentation to stimulate the production of secretory IgA in faeces and to protect mice against Salmonella infection was evaluated. A significant increase in secretory IgA in faeces of mice fed 14 days the postbiotic obtained at the laboratory (F36) was detected compared to control animals. A significantly higher survival was observed in mice fed the F36 and the FiSD (industrial product) compared to controls.
Conclusion
The postbiotics obtained showed immunomodulatory and protective capacity against Salmonella infection in mice.
Significance and Impact of the Study
The pH‐controlled milk fermentation by the proteolytic DSM‐100H culture could be a suitable strategy to obtain a food ingredient to be added to a given food matrix, not adequate to host viable cells of probiotics, to confer it enhanced functionality and thus expand the functional food market.
Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory ...Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval CI, 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively.
Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
•Patients with metastatic differentiated thyroid cancer (DTC) have poor survival rate.•Lenvatinib improved clinical outcomes in patient with metastatic radioactive iodine-refractory DTC.•Lenvatinib is active and safe, even in a real-life patient population.•Older patients show survival benefit from lenvatinib, without safety concern.
The ability of the adjunct culture Lacticaseibacillus paracasei 90 (L90) to prevent undesired eye formation by heterofermentative bacteria was assessed in soft cheeses, ripened either in normal ...conditions or with interruptions in the cold chain. Leuconostoc mesenteroides D11 isolated from defective cheeses with undesired eye production were added to control (C) and experimental (E) Cremoso soft cheeses to simulate the occurrence of high levels of adventitious heterofermentative bacteria; the adjunct culture L90 was added only to E cheeses. The presence of high levels of L90 affected the carbohydrates fermentation, and the levels of hippuric and benzoic acids. These changes produced an adverse environment for the undesirable activity of the strain D11. In effect, the incorporation of L90 decreased the metabolic activity of the D11 strain and consequently avoided the unwanted eye formation. The maintenance of an adequate cold chain was also an important factor to obtain cheese without eye defects.
Background
Transanal irrigation(TAI) has been reported to be an inexpensive and effective treatment for low anterior resection syndrome(LARS). The aim of the present prospective study was to evaluate ...the use of TAI in patients with significant LARS symptoms at a single medical center.
Methods
Patients who had low anterior resection for rectal cancer between April 2015 and May 2016 at the Careggi University Hospital were assessed for LARS using the LARS and the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI) questionnaires 30–40 days after surgery or ileostomy closure (if this was done). Quality of life was evaluated using a visual analog scale and the Short Form-36 Health Survey. All patients with LARS score of 30 or higher were included (early LARS) as were all patients with a LARS score of 30 or higher referred 6 months or longer after surgery performed elsewhere (chronic LARS) in the same study period. Study participants were trained to perform TAI using the Peristeen™ System for 6 months, followed by 3 months of enema therapy following a similar protocol.
Results
Thirty-three patients were enrolled in the study. Six patients stopped the treatment. The 27 patients (19 early LARS and 8 chronic LARS) who completed the study had a significant decrease in the number of median daily bowel movements baseline 7 (range 0–14); 6 months 1 (range 0–4); 9 months 4 (range 0–13). The median LARS Score fell from 35.1 (range 30–42) (baseline) to 12.2 (range 0–21) after 6 months (
p
< 0.0001) and then rose to 27 (range 5–39) after 3 months of enema therapy. There was no difference in LARS score decrease at 6 months between the patients with early and chronic LARS (22.5 and 23.9 respectively; p=0.7) and there were no predictors of score decrease. Four components of the SF-36 significantly improved during the TAI period. The MSKCC BFI score significantly improved in several domains. Twenty-three patients (85%) asked to continue the treatment with TAI after the study ended.
Conclusions
TAI appears to be an effective treatment for LARS and results in a marked improvement of continence and quality of life. Patients may be assessed and treated for LARS early after surgery since the treatment benefit is similar to that observed in patients with LARS diagnosed 6 months or longer after surgery. The potential rehabilitative role of TAI for LARS is promising and should be further investigated.
Twenty-seven aromatic herbs, 28 spices and 48 herbal infusions and med plants were analysed for estimation of aflatoxins by high-performance liquid chromatography (HPLC) using a post-column ...derivatisation procedure (Kobra cell) and a fluorescence detection. Samples were randomly collected, from 2000 to 2005, from markets, shops and bonded warehouse in Emilia Romagna Region, Italy. Of the 103 samples analysed only 7 spices resulted positives: 5 chilli-peppers, 1 nut meg and 1 cinnamon. Two samples contained the toxin at non-permissible levels. It’s interesting to note that none of the aromatic herb, herb-tea and medicinal-plant samples analysed was contaminated, even if they are from tropical countries.
The contribution to flavor generation and secondary proteolysis of 2 strains of mesophilic lactobacilli isolated from cheese was studied. Miniature soft cheeses (200g) were produced with or without ...the inclusion of a culture of Lactobacillus plantarum I91 or Lactobacillus casei I90 in the starter composed of Streptococcus thermophilus. During ripening, cheeses containing the added lactobacilli showed an increased content of total free amino acids, but this increase was only significant in cheeses with Lb. plantarum I91. In addition, free amino acid profiles were modified by selective increases of some amino acids, such as Asp, Ser, Arg, Leu, and Phe. Cheeses inoculated with Lb. plantarum I91 or Lb. casei I90 were also characterized by a significantly higher concentration of diacetyl, a key flavor compound, and an increased content of acetoin. Results suggest an increase in the catabolism of either citrate or aspartate, with the production of the derived aroma compounds. Overall, aspartate content increased in both lactobacilli-added cheeses, whereas citrate was more or less constant, suggesting that aspartate could be the source of increased diacetyl and acetoin. A triangle aroma test showed that the addition of the lactobacilli strains significantly changed the sensory attributes of cheeses. At least 11 of 12 panelists commented that the aroma of cheeses with adjuncts was more buttery than that of control cheeses, which is desirable in most soft cheeses. Both Lb. plantarum I91 and Lb. casei I90 performed well as adjunct cultures by influencing cheese aroma development and cheese proteolysis.
Summary EGFR overexpression in salivary gland carcinomas provides the rational for the investigation of anti-EGFR treatments in recurrent and/or metastatic salivary gland cancers (RMSGCs). The ...activity of cetuximab in terms of clinical benefit rate (CBR) defined as the occurrence of objective response (CR or PR) or stable disease (SD) for ⩾6 months was investigated. From April to December 2005, 30 patients 23 adenoid cystic carcinoma (ACC) and 7 non-ACC were treated with cetuximab at 400 mg/m2 /week followed by 250 mg/m2 /week until progression, major toxicity or voluntary discontinuation. EGFR expression and gene status were retrospectively analyzed by immunocytochemistry and fluorescence in situ hybridization, respectively. A median of 14 courses of cetuximab (range 5–54) were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene amplification and an increased EGFR copy number was observed in 12% of samples, all ACC. Skin rash ⩾G2, EGFR overexpression and EGFR copy number were not statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting agents are advisable and should take place by appropriate tumor biological selection, differentiating ACC from non-ACC.
Two probiotic strains,
Lactobacillus acidophilus and
Lactobacillus paracasei subsp.
paracasei, were used as adjunct cultures in semi-hard cheesemaking experiments, in order to study their influence ...on proteolysis during ripening. Cheeses with and without probiotic bacteria were manufactured. The population of probiotics remained above 10
7
cfu
g
−1 during all ripening, and they did not influence primary proteolysis. However,
L. acidophilus produced a significant increase in the level of low molecular weight nitrogen compounds and individual free amino acids; the amino acid profiles were also different. Multivariate analysis of peptide profiles showed that samples were grouped mainly by ripening time, although the impact of probiotics was also noticeable.
L. acidophilus showed a clear influence on secondary proteolysis, while a minor effect of
L. paracasei was evidenced at the end of the ripening. These results showed that the tested strains influenced distinctly proteolysis of cheeses, probably as a consequence of their different proteolytic systems and their activity via the alimentary matrix (cheese).
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