The life expectancy for pancreatic cancer patients has seen no substantial changes in the last 40 years as very few and mostly just palliative treatments are available. As the five years survival ...rate remains around 5%, the identification of novel pharmacological targets and development of new therapeutic strategies are urgently needed. Here we demonstrate that inhibition of the G protein-coupled receptor GPR55, using genetic and pharmacological approaches, reduces pancreatic cancer cell growth in vitro and in vivo and we propose that this may represent a novel strategy to inhibit pancreatic ductal adenocarcinoma (PDAC) progression. Specifically, we show that genetic ablation of Gpr55 in the KRAS
/TP53
/Pdx1-Cre
(KPC) mouse model of PDAC significantly prolonged survival. Importantly, KPC mice treated with a combination of the GPR55 antagonist Cannabidiol (CBD) and gemcitabine (GEM, one of the most used drugs to treat PDAC), survived nearly three times longer compared to mice treated with vehicle or GEM alone. Mechanistically, knockdown or pharmacologic inhibition of GPR55 reduced anchorage-dependent and independent growth, cell cycle progression, activation of mitogen-activated protein kinase (MAPK) signalling and protein levels of ribonucleotide reductases in PDAC cells. Consistent with this, genetic ablation of Gpr55 reduced proliferation of tumour cells, MAPK signalling and ribonucleotide reductase M1 levels in KPC mice. Combination of CBD and GEM inhibited tumour cell proliferation in KPC mice and it opposed mechanisms involved in development of resistance to GEM in vitro and in vivo. Finally, we demonstrate that the tumour suppressor p53 regulates GPR55 protein expression through modulation of the microRNA miR34b-3p. Our results demonstrate the important role played by GPR55 downstream of p53 in PDAC progression. Moreover our data indicate that combination of CBD and GEM, both currently approved for medical use, might be tested in clinical trials as a novel promising treatment to improve PDAC patients' outcome.
We analysed trends in incidence for in situ and invasive melanoma in some European countries during the period 1995–2012, stratifying for lesion thickness.
Individual anonymised data from ...population-based European cancer registries (CRs) were collected and combined in a common database, including information on age, sex, year of diagnosis, histological type, tumour location, behaviour (invasive, in situ) and lesion thickness. Mortality data were retrieved from the publicly available World Health Organization database.
Our database covered a population of over 117 million inhabitants and included about 415,000 skin lesions, recorded by 18 European CRs (7 of them with national coverage). During the 1995–2012 period, we observed a statistically significant increase in incidence for both invasive (average annual percent change (AAPC) 4.0% men; 3.0% women) and in situ (AAPC 7.7% men; 6.2% women) cases.
The increase in invasive lesions seemed mainly driven by thin melanomas (AAPC 10% men; 8.3% women). The incidence of thick melanomas also increased, although more slowly in recent years. Correction for lesions of unknown thickness enhanced the differences between thin and thick cases and flattened the trends. Incidence trends varied considerably across registries, but only Netherlands presented a marked increase above the boundaries of a funnel plot that weighted estimates by their precision. Mortality from invasive melanoma has continued to increase in Norway, Iceland (but only for elder people), the Netherlands and Slovenia.
•This study is the most recent analysis of melanoma trends in Europe by lesion thickness.•We analysed about 415,000 cases incident between 1995 and 2012 from 13 European countries.•Results showed that the incidence of invasive melanoma continues to increase, mainly due to thin lesions.•There was a large variation in trends among countries, with the greatest increase in the Netherlands.•Mortality from invasive melanoma continued to increase in some countries.
Purpose
Otosclerosis is a common ear disease causing ankylosis of the stapedio-vestibular joint and conductive hearing loss. Stapedoplasty is the most advisable surgical solution. The restoration of ...hearing depends on the condition of the patient and the surgery itself. The aim of our work was to compare the surgical and audiological results of stapedoplasty performed with endoscopic versus microscopic technique.
Methods
This is a retrospective study of 254 patients treated with stapedoplasty with a microscopic approach (91/254) or with an endoscopic approach (163/254) between 2014 and 2021 at our tertiary referral center. Statistical significance of differences between the two methods was determined using the Mann–Whitney test for quantitative variables and the Wilcoxon matched-pairs signed-rank test for repeated measures. Categorical variables were assessed with Fisher’s exact test.
Results
Both techniques improved the hearing status of patients, with no statistically significant difference between them. There was also no statistically significant difference in reported complications between the two techniques. There is a statistical difference (
p
< 0.001) in operating time between the two techniques: the endoscopic technique had a mean operating time of 39 min versus 45 min for the microscopic technique.
Conclusions
The two techniques are comparable in terms of results and the choice depends on the surgeon’s preferences and experience.
The availability of population-based cancer registry (CR) data is paramount in the development of modern oncology. Major contributions consisted in accurately measuring cancer burden (incidence, ...survival and prevalence, beside mortality), identifying and quantifying risk factors (case control and cohort studies that, in the last two decades, included gene variant assessment) and evaluating outcomes of treatments and preventive interventions, including mass screening. Cancer registration coverage of European populations progressed slowly since 1940 and is now almost 50%. Areas lacking high-quality national population-based cancer registration still exist within large countries such as France, Italy, Romania and Spain, Germany and Poland having national plans and legislation to reach complete coverage. Depending on programme ownership, history and institutional organisation, European CRs showed huge variations in the scope (research domain), size, available resources and finally exploitation of collected data. This reflects their heterogeneous origins stemming from different professional backgrounds and healthcare systems. This review discusses not only the potential for contributing to acceleration of prevention but also the coverage expansion by and innovation of CR organizations. The latter can be attained not only by more standardisation in institutional organisation and operative methodologies but also by intensification of scientific production and risk communication. The CR's agenda should focus on cancers caused by identifiable risk factor(s) that are amenable to preventive actions, including early detection; short-term priorities usually are with tobacco, and medium-term priorities are with alcohol, occupational exposures, infection-related cancers and ultraviolet-related skin cancers, while obesity-related cancers are likely to increase gradually further in the long term.
Abstract Cancer registries must provide complete and reliable incidence information with the shortest possible delay for use in studies such as comparability, clustering, cancer in the elderly and ...adequacy of cancer surveillance. Methods of varying complexity are available to registries for monitoring completeness and timeliness. We wished to know which methods are currently in use among cancer registries, and to compare the results of our findings to those of a survey carried out in 2006. Methods In the framework of the EUROCOURSE project, and to prepare cancer registries for participation in the ERA-net scheme, we launched a survey on the methods used to assess completeness, and also on the timeliness and methods of dissemination of results by registries. We sent the questionnaire to all general registries (GCRs) and specialised registries (SCRs) active in Europe and within the European Network of Cancer Registries (ENCR). Results With a response rate of 66% among GCRs and 59% among SCRs, we obtained data for analysis from 116 registries with a population coverage of ∼280 million. The most common methods used were comparison of trends (79%) and mortality/incidence ratios (more than 60%). More complex methods were used less commonly: capture–recapture by 30%, flow method by 18% and death certificate notification (DCN) methods with the Ajiki formula by 9%. The median latency for completion of ascertainment of incidence was 18 months. Additional time required for dissemination was of the order of 3–6 months, depending on the method: print or electronic. One fifth (21%) did not publish results for their own registry but only as a contribution to larger national or international data repositories and publications; this introduced a further delay in the availability of data. Conclusions Cancer registries should improve the practice of measuring their completeness regularly and should move from traditional to more quantitative methods. This could also have implications in the timeliness of data publication.
Hearing threshold identification in very young children is always problematic and challenging. Electrophysiological testing such as auditory brainstem responses (ABR) is still considered the most ...reliable technique for defining the hearing threshold. However, over recent years there has been increasing evidence to support the role of auditory steady-state response (ASSR). Retrospective study. Forty-two children, age range 3-189 months, were evaluated for a total of 83 ears. All patients were affected by sensorineural hearing loss (thresholds ≥ 40 dB HL according to a click-ABR assessment). All patients underwent ABRs, ASSR and pure tone audiometry (PTA), with the latter performed according to the child's mental and physical development. Subjects were divided into two groups: A and B. The latter performed all hearing investigations at the same time as they were older than subjects in group A, and it was then possible to achieve electrophysiological and PTA tests in close temporal sequence. There was no significant difference between the threshold levels identified at the frequencies tested (0.25, 0.5, 1, 2 and 4 kHz), by PTA, ABR and ASSR between the two groups (Mann Whitney U test, p < 0.05). Moreover, for group A, there was no significant difference between the ASSR and ABR thresholds when the children were very young and the PTA thresholds subsequently identified at a later stage. Our results show that ASSR can be considered an effective procedure and a reliable test, particularly when predicting hearing threshold in very young children at lower frequencies (including 0.5 kHz).
Paranasal sinus cholesteatoma is a rare occurrence for which only a few cases have been reported in the literature, particularly in the frontal and maxillary sinuses. The clinical features are ...non-specific, and thus a broad differential diagnosis should be considered. In most cases, diagnostic imaging is carried out through CT and/or MRI scans, and the treatment goal is complete eradication regardless of the approach. In our review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and Egger et al.’s approach for Systematic Reviews in Health Care. The papers included were in English or Italian, with an available and congruous full text. Out of the 140 selected articles, we included only 22 papers, ranging from 1958 to 2020 and accounting for 24 patients. Eleven had cholesteatoma in the frontal, 9 in the maxillary sinus, and 4 in other sites. Most patients underwent CT scans or combined CT and MRI, and an open approach was the most selected procedure. Only 2 patients showed postoperative complications, and 5 patients had a recurrence over an average follow-up period of 25 months. In this first systematic review on this subject, we provide an overview of the diagnostic procedures, the proper surgical approach and the postoperative follow-up found in the literature without precise and shared guidelines.
The pharyngocutaneous fistula (PCF) is one of the most common post-operative complications in patients undergoing laryngectomy. Up till now, there is no universally accepted algorithm for managing of ...PCFs and several treatment modalities are used for wound healing. The English language literature was searched using PUBMED databases with the keywords "laryngectomy", "pharyngocutaneous", "fistula", "treatment", and "management" from January 1, 1999 to June 1, 2019; we selected 35 studies according to inclusion criteria and we conducted a systematic review of the articles. The analysis of the international literature shows a high variability of treatment approaches; there is no consensus about conservative treatment and waiting time, and neither about the indication for surgical treatment or the ideal surgical technique. A first attempt of a conservative measure is mandatory in all cases of PCR In case of failure of conservative measures surgical treatment should be considered: direct closure and local flap are suitable for small defects, pedicled or free flaps showed good to excellent results in closure of large and complex cervical defects. Other non-invasive treatment such as hyperbaric oxygen therapy (HBOT) and negative pressure wound therapy (NPWT) showed promising results but in limited case series. Keywords: laryngectomy, pharyngo-cutaneous fistula, reconstructive surgery, hyperbaric oxygen therapy, negative pressure wound therapy, laryngeal cancer
Temporary tracheal balloons have been shown to improve lung growth in fetuses with severe congenital diaphragmatic hernia. Fetoscopic Endoluminal Tracheal Occlusion (FETO) is performed at 26-28 weeks ...gestation, and then is removed in utero at 34 weeks gestation at highly specialized centers. In case of preterm labor at a hospital without a specialized team, a number of techniques have been used to remove the balloon, sometimes with death of the newborn. We have successfully performed an ultrasound-guided approach to puncture and remove the tracheal balloon in a premature infant in an emergency setting at birth. After that she was treated for congenital diaphragmatic hernia at our Newborn Intensive Care Unit.
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