Pulpal neuropeptidergic fibers

A study was carried out on Met- and Leu-enkephalin, Gastrin / CCK-, SP-, CGRP-, NPY- immunoreactive fibers using paraffin sections of dental pulp taken from 8 apparently normal teeth (wisdom teeth or teeth extracted for orthodontic reasons).Within the limitations of the samples studied, dental pulp is characterized by the presence of sensory (Enkephalin-, Gastrin/CCK- immunoreactive) and pain fibers (SP-immunoreactive) and of fibers with a potent vasodilatory action (CGRP-immunoreactive) and by the absence of fibers with a vasoconstrictor action (NPY-immunoreactive).Notre étude a porté sur la mise en évidence sur des coupes après inclusion à la paraffine des fibres Met- et Leu-enképhaline, Gastrine / CCK-, SP-, CGRP- et NPY-immunoréactives, dans la pulpe de huit dents normales (dents de sagesse ou dents extraites pour des raisons orthodontiques).Dans la limite des échantillons utilisés, la pulpe dentaire est caractérisée par la présence de fibres sensitives (Enképhalin-, Gastrin/CCK-immunoréactives), des fibres de la douleur (SP-immunoréactives) et de fibre à action vasodilatatrice (CGRP-immunoréactives) et par l’absence de fibres à action vasoconstrictive (NPY-immunoréactives)

Deep inside of gastric signet-ring cell carcinoma

The histology of signet-ring cell carcinoma (SRC) of the stomach has been revisited with the support of current immunohistochemical techniques in order to explain particular features of this tumor; its great capacity of local diffusion and lymph node metastasis, also through a neo-lymphoangiogenesis. An observational retrospective study on 50 cases of SRC in stage II and III has been performed with the addition of histochemical (Alcian Blue, DDD-Fast Blue B, Mercury Orange) and immunohistochemical (cytocheratin, CD3, CD4, CD8, CD10, CD56, CD68, perforin, granzyme B, podoplanin, collagen type IV) investigations for each case. The signet ring cells, typical for this tumor, show abundant content of electro-negative sialomucins and demonstrate a great capacity of diffusion through the gastric wall. They evoke production and deposition of collagen type IV in the sub-mucosa layer through the local action of fibroblasts. The immunological response to this tumor in the gastric wall and in the metastatic lymph nodes is represented by an increase of B and T-helper lymphocytes, but not of T-killers or natural killers. The neoplastic cells are curiously able to avoid these newly formed ‘lymph nodules’. An extended neo-lymphangiogenesis has been observed around the primary tumor and in metastatic lymph nodes. A careful immunohistochemical characterization has allowed a better knowledge of SRC, regarding especially the peculiar behavior of local diffusion of its cells, the associated neo-lymph angiogenesis, and poor immunological reaction

Continuing medical education and evidence-based clinical pathways. Training emergency health workers in Latium, Italy

Background: In recent decades, studies that evaluate training programmes have shown that continuing education for physicians is not very effective in improving performance and behavioural changes. One of our goals was to create a Continuing Medical Education Programme (CMEP) that would result in changing the behaviour of health professionals. In early 2005, a new CMEP was offered to emergency medical services and emergency room professionals to introduce an Emergency Critical Pathway (ECP) for the management of acute stroke patients. This paper illustrates the main characteristics of the educational model and the strategies and activities adopted to realize it. Methods: The training programme was planned and organized applying the concepts and tools of experiential learning, It was organised in three successive phases: 1.) interviews with health professionals to identify their learning ne-eds; 2) training the ECP coordinators/facilitators in a residential setting; and 3) on-site training in small groups of health professionals (6-8), led by a coordinator/facilitator. Results: The CME involved 324 emergency health professionals, Participants positively evaluated both the educational programme and the clinical indications of the protocols. Over six months of the ECP training, health professionals treated 657 stroke patients: 153 (23.3%) were transferred to the stroke unit where 15 (9.8%) were thrombolysed. In the same period of the previous year, the professionals treated 638 patients: 99 (15.5%) were transferred to the stroke unit and no patients were thrombolysed. Conclusion: The application of the new educational methodology has contributed to improved management of stroke patients in Latium.</p

Continuing medical education and evidence-based clinical pathways. Training emergency health workers in Latium, Italy

Background: In recent decades, studies that evaluate training programmes have shown that continuing education for physicians is not very effective in improving performance and behavioural changes. One of our goals was to create a Continuing Medical Education Programme (CMEP) that would result in changing the behaviour of health professionals. In early 2005, a new CMEP was offered to emergency medical services and emergency room professionals to introduce an Emergency Critical Pathway (ECP) for the management of acute stroke patients. This paper illustrates the main characteristics of the educational model and the strategies and activities adopted to realize it. Methods: The training programme was planned and organized applying the concepts and tools of experiential learning, It was organised in three successive phases: 1.) interviews with health professionals to identify their learning ne-eds; 2) training the ECP coordinators/facilitators in a residential setting; and 3) on-site training in small groups of health professionals (6-8), led by a coordinator/facilitator. Results: The CME involved 324 emergency health professionals, Participants positively evaluated both the educational programme and the clinical indications of the protocols. Over six months of the ECP training, health professionals treated 657 stroke patients: 153 (23.3%) were transferred to the stroke unit where 15 (9.8%) were thrombolysed. In the same period of the previous year, the professionals treated 638 patients: 99 (15.5%) were transferred to the stroke unit and no patients were thrombolysed. Conclusion: The application of the new educational methodology has contributed to improved management of stroke patients in Latium.</p

Primary and secondary prevention to effectively reduce the risk of bisphosphonate-related osteonecrosis of the jaw in patients with bone metastases .

Background Bone is one of the most frequent sites of metastasis in patients with advanced cancer. Nearly all patients with myeloma, 65–75% of patients with prostate or breast cancer, and 30–40% of patients with lung cancer or other solid tumors, eventually develop bone metastases. Bisphosphonates (BP), particularly zoledronic acid and denosumab, were demonstrated to effectively reduce skeletal complications in patients with bone metastases. However, bisphosphonate-related osteonecrosis of the jaw (BRONJ) can occur spontaneously, favored by dental extraction, dental implant surgery, or denture wearing. The purpose of this study was to underline the role of dental prevention as an effective tool to reduce the risk of BRONJ. Material and methods BRONJ was identified with the standardized query “osteonecrosis” among all data from patients treated at Modena Cancer Center from 2005 to 2016. For each case, demographic and medical information were analyzed, as well as data about notification (year of occurrence, outcome), type and duration of BP exposure, and associated risk factors (dento-alveolar surgery, chemotherapy, antiangiogenics). Data were differently analyzed taking into account the implementation of a Dental Prevention Service in patients who are candidates for BP therapy.Results Among 1663 patients treated with BP, 63 cases of BRONJ were identified (3.8%). 44 female and 19 men with a median age of 69 years (range 47-90 years), have been treated with BP for bone metastases from breast cancer (54%), hematologic malignancy (21%), prostate cancer (13%), renal cancer (5%), lung cancer (2%) and other tumors (5%). 15 maxillae and 48 mandibles were involved. The trigger event was a dental extraction in 29% of the cases, being spontaneously the other 71%. The median time to BRONJ was 28 months (range 1-89.1 months) from the first dose of BP, and 25 was the mean number of BP doses administered before BRONJ. Overall, a preliminary odontoiatric evaluation was performed in only 14 cases (22%). All but one of these dentistry opinions were obtained after 2010 when the Dental Prevention Service was created, which is a drop out of the risk of BRONJ from 4.1 to 1.9%. Conclusions. Prevention of the BRONJ is critical in in bone metastatic patients. The incidence of BRONJ over time can drop to 1.9% when primary and secondary prevention measures are implemented in routine clinical practice

Predictive Role Of Body Composition Parameters In Operable Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND: Fat tissue is strongly involved in BC tumorigenesis inducing insulin resistance, chronic inflammation and hormonal changes. Computed tomography (CT) imaging instead of body mass index (BMI) gives a reliable measure of skeletal muscle mass and body fat distribution. The impact of body composition parameters (BCPs) on chemosensitivity is still debated. We examined the associations between BCPs and tumor response to neoadjuvant chemotherapy (NC) in patients treated for operable breast cancer (BC). METHODS: A retrospective review of BC patients treated with NC in Modena Cancer Center between 2005 and 2017 was performed. BCPs, such as subcutaneous fat area (SFA), visceral fat area (VFA), lumbar skeletal muscle index (LSMI) and liver-to-spleen (L/S) ratio were calculated by Advance workstation (General Electric), software ADW server 3.2 or 4.7. BMI and BCPs were correlated with pathological complete response (pCR) and survival outcomes. RESULTS: 407 patients were included in the study: 55% with BMI &lt; 25 and 45% with BMI 65 25. 137 of them had pre-treatment CT scan imagines. Overweight was significantly associated with postmenopausal status and older age. Hormonal receptor positive BC was more frequent in overweight patients (p&lt;0.05). Postmenopausal women had higher VFA, fatty liver disease and obesity compared to premenopausal patients. No association between BMI classes and tumor response was detected. High VFA and liver steatosis were negative predictive factors for pCR (pCR rate: 36% normal VFA vs 20% high VFA, p= 0.048; no steatosis 32% vs steatosis 13%, p=0.056). Neither BMI classes nor BCPs significantly influenced overall survival and relapse-free survival. CONCLUSION: Visceral adiposity as well as steatosis were closely involved in chemosensitivity in BC patients treated with NC. Their measures from clinically acquired CT scans provide significant predictive information that outperform BMI value. More research is required to evaluate the relationship among adiposity site and survival outcomes

Predictive factors for relapse in triple-negative breast cancer patients without pathological complete response after neoadjuvant chemotherapy

IntroductionTriple-negative breast cancer (TNBC) patients who do not obtain pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify the predictive factors for relapse in TNBC patients without pCR after NACT. MethodsWomen with TNBC treated with NACT from January 2008 to May 2020 at the Modena Cancer Center were included in the analysis. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of relapse. ResultsWe identified 142 patients with a median follow-up of 55 months. After NACT, 62 patients obtained pCR (43.9%). Young age at diagnosis (&lt;50 years) and high Ki-67 (20%) were signi!cantly associated with pCR. Lack of pCR after NACT resulted in worse 5-year event-free survival (EFS) and overall survival (OS). Factors independently predicting EFS in patients without pCR were the presence of multifocal disease [hazard ratio (HR), 3.77; 95% CI, 1.45-9.61; p=0.005] and residual cancer burden (RCB) III (HR, 3.04; 95% CI, 1.09-9.9; p=0.04). Neither germline BRCA status nor HER2-low expression were associated with relapse. DiscussionThese data can be used to stratify patients and potentially guide treatment decision-making, identifying appropriate candidates for treatment intensi!cation especially in neo-/adjuvant setting

Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients

Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical-pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the PIK3CA (47%), FGFR (19%) and ERBB2 genes (12%), and to a lesser extent in other genes. Of the 61 patients with pathogenic mutations, 46 (75%) had at least one actionable mutation. Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. Median PFS for these patients was 3.8 months. The study results show that using the NGS test on cancer tissue of metastatic breast cancer could influence the therapeutic choices, considering the small sample size and limited follow-up. About 9% of the study population had their therapy modified based on the results of NGS. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical–pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the PIK3CA (47%), FGFR (19%) and ERBB2 genes (12%), and to a lesser extent in other genes. Of the 61 patients with pathogenic mutations, 46 (75%) had at least one actionable mutation. Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. Median PFS for these patients was 3.8 months. The study results show that using the NGS test on cancer tissue of metastatic breast cancer could influence the therapeutic choices, considering the small sample size and limited follow-up. About 9% of the study population had their therapy modified based on the results of NGS. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active