Salivary Diagnosis of Dental Caries: A Systematic Review.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

Diagnostic and Therapeutic Approach to Children and Adolescents with Obstructive Sleep Apnea Syndrome (OSA): Recommendations in Emilia-Romagna Region, Italy.

Obstructive sleep apnoea syndrome (OSA) in paediatrics is a rather frequent pathology caused by pathophysiological alterations leading to partial and prolonged obstruction (hypoventilation) and/or intermittent partial (hypopnoea) or complete (apnoea) obstruction of the upper airways. Paediatric OSA is characterised by daytime and night-time symptoms. Unfortunately, there are few data on shared diagnostic-therapeutic pathways that address OSA with a multidisciplinary approach in paediatric age. This document summarizes recommendations from the Emilia-Romagna Region, Italy, developed in order to provide the most appropriate tools for a multidisciplinary approach in the diagnosis, treatment and care of paediatric patients with OSA. The multidisciplinary group of experts distinguished two different 'step' pathways, depending on the age group considered (i.e., under or over two years). In most cases, these pathways can be carried out by the primary care paediatrician, who represents the first filter for approaching the problem. For this reason, it is essential that the primary care paediatrician receives adequate training on how to formulate the diagnostic suspicion of OSA and on what criteria to use to select patients to be sent to the hospital centre. The relationship between the paediatrician of the patient and her/his parents must see a synergy of behaviour between the various players in order to avoid uncertainty about the diagnostic and therapeutic decisions as well as the follow-up phase. The definition and evaluation of the organizational process and outcome indicators of the developed flow-chart, and the impact of its implementation will remain fundamental.

Recommendations for a safe restart of elective aerosol-generating oral surgery procedures following the COVID-19 pandemic outbreak: An Italian multicenter study.

Among healthcare workers, oral and maxillofacial surgeons are some of the most exposed to coronavirus disease (COVID-19). The aim of this retrospective study was to develop suggestions for continuing the work of oral and maxillofacial surgeons using a safe protocol for elective and urgent aerosol-generating procedures that could prevent the onset of new clusters. Based on the results obtained and a guidelines review of those Asian countries that had promptly managed the current pandemic, the following safety protocol was developed.

Neuroendocrine small cell carcinoma of the cervix: A case report.

Merkel cell polyomavirus (MCPyV) has been found in patients with Merkel cell carcinoma and respiratory tract infections. Merkel cell carcinoma is a primary aggressive neuroendocrine carcinoma of the skin. It has been demonstrated that MCPyV can be transmitted during sexual activity and may be present in the oral and anogenital mucosa. The aim of the present study was to evaluate whether MCPyV coexisted with HPV in three cases of neuroendocrine small cell carcinoma of the cervix using PCR and immunohistochemical analysis Three cases of NSC of the cervix were identified in the pathology archives of Parma University (Italy). Of these, two cases were associated with an adenocarcinomatous component. A set of general primers from the L1 region (forward, L1C1 and reverse, L1C2 or L1C2M) was PCR amplified to detect the broad-spectrum DNA of genital HPV. The presence of MCPyV was investigated via immunohistochemistry using a mouse monoclonal antibody against the MCPyV LT antigen and through PCR analysis to separate viral DNA. HPV DNA was present in all three neuroendocrine carcinomas and in the adenocarcinoma component of the two mixed cases. None of the cases were immunoreactive to CM2B4 and did not contain viral DNA in either their neuroendocrine or adenocarcinomatous component. Whilst it is difficult to draw definitive conclusions from such a small sample size, these data suggested that MCPyV does not coexist with HPV in the cervix. However, in the present study, the absence of detectable MCPyV may have been due to the presence of a genotype that was not detected by the primers used in the PCR analysis or by the antibody used for the immunohistochemical study. MCPyV microRNA may also have been present, inhibiting LT expression. Additional studies with larger cohorts and more advanced molecular biology techniques are required to confirm the hypothesis of the current study.

Italian guidelines for the prevention and management of dental trauma in children.

Dental trauma is a frequent occurrence in children and adolescent and a correct diagnosis and treatment are essential for a favourable long-term prognosis. The present Guidelines aim to formulate evidence-based recommendations to assist dentists, paediatricians, surgeons, teachers, school and sport staff, parents in the prevention and first aid of dental trauma in children and to provide a careful assessment of the medico-legal implications, reviewing the first draft of the guidelines published in 2012. A multidisciplinary panel on the behalf of the Italian Ministry of Health and in collaboration with the WHO Collaborating Centre for Epidemiology and Community Dentistry of Milan, developed this document. The following four queries were postulated: 1) Which kind of precautions the health personnel, parents, sports and educational personnel must activate in order to prevent the dental trauma damage? 2) How an orofacial trauma in paediatric patients should be managed either in the Emergency Care Unit and/or in private dental office? 3) What criteria should be adopted by a dentist private practitioner to fill in a certificate in cases of dental and/or tempomandibular joint trauma occurring in children and adolescents? 4) What are the elements that should lead clinicians to suspect a non-accidental dental trauma? A systematic review and analysis of the scientific literature published in English, Italian and French from 2007 to 2017 regarding dental trauma in children and adolescents aged 0-18 years was performed, and about 100 papers were analysed and included. The following four domains were analysed and discussed: Dental Trauma Prevention Strategies and Health Education, First aid in orofacial and dental trauma, Certificate of the dental trauma, Oral and dental signs of child abuse and neglect. Twenty-eight recommendations were draw up and codified by the panel according to the Methodological handbook, produced by the Istituto Superiore di Sanità, in order to guide physicians in the prevention and first aid of dental trauma in children and adolescents. In addition, a careful assessment of the medico-legal implications is reported in this document.

Validación del índice de comorbilidad para trasplante hematopoyético en una cohorte retrospectiva de niños y adolescentes argentinos receptores de trasplante alogénico / Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina

Introducción. El trasplante hematopoyético es una terapia con riesgo de mortalidad relacionada con el trasplante (MRT), que puede variar según la comorbilidad previa. El índice de comorbilidad para trasplante hematopoyético (ICTH) es un instrumento desarrollado para medir este riesgo. Los reportes sobre su uso en pediatría son escasos. El objetivo de este estudio fue validar el ICTH en una cohorte pediátrica de receptores de trasplante hematopoyético alogénico en Argentina. Población y métodos. Cohorte retrospectiva de 140 pacientes trasplantados en el Hospital J. P. Garrahan entre 2008 y 2012. Se revisaron, de las historias clínicas, sus antecedentes y evolución. Se calculó el ICTH de cada paciente y se clasificaron como de riesgo bajo (puntaje 0), intermedio (puntaje 1-2) o alto (puntaje > 3). Se estimó la supervivencia para cada grupo por el método de Kaplan-Meier y se comparó con la prueba de logaritmos de rangos. En el caso de las enfermedades malignas, la recaída fue considerada un evento competitivo con la MRT. Se consideró significativa una p < 0,05. Resultados. La mediana del ICTH fue 1 (r: 0-6). El 45,7% de los pacientes tuvieron puntaje 0; el 40,7%, 1-2; y el 13,6%, > 3. Las comorbilidades más frecuentes fueron obesidad, infección y compromiso pulmonar y hepático. La MRT de los pacientes con puntaje 0 fue 14,1%; con puntaje 1-2, 43,7%; y con puntaje > 3, 52,6%. Las curvas de supervivencia manifestaron diferencias entre los tres grupos (p 0,01). Conclusión. El ICTH mostró ser una herramienta efectiva para predecir el riesgo de MRT en nuestro medio.

Introduction. Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. Population and methods. Retrospective cohort made up of 140 transplant patients at Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value <0.05 was considered significant. Results. The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). Conclusion. The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting.

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina. / Validación del índice de comorbilidad para trasplante hematopoyético en una cohorte retrospectiva de niños y adolescentes argentinos receptores de trasplante alogénico.

INTRODUCTION: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. POPULATION AND METHODS: Retrospective cohort made up of 140 transplant patients a, Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value 〈 0.05 was considered significant. RESULTS: The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). CONCLUSIONS: The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting. KEY WORDS: comorbidity, hematopoietic stem cell transplantation, non-relapse mortality, pediatrics.

INTRODUCCIÓN: El trasplante hematopoyético es una terapia con riesgo de mortalidad relacionada con el trasplante (MRT), que puede variar según la comorbilidad previa. El índice de comorbilidad para trasplante hematopoyético (ICTH) es un instrumento desarrollado para medir este riesgo. Los reportes sobre su uso en pediatría son escasos. El objetivo de este estudio fue validar el ICTH en una cohorte pediátrica de receptores de trasplante hematopoyético alogénico en Argentina. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva de 140 pacientes trasplantados en e, Hospital J. P. Garrahan entre 2008 y 2012. Se revisaron, de las historias clínicas, sus antecedentes y evolución. Se calculó el ICTH de cada paciente y se clasificaron como de riesgo bajo (puntaje 0), intermedio (puntaje 1-2) o alto (puntaje 〉 3). Se estimó la supervivencia para cada grupo por el método de Kaplan-Meier y se comparó con la prueba de logaritmos de rangos. En el caso de las enfermedades malignas, la recaída fue considerada un evento competitivo con la MRT. Se consideró significativa una p 〈 0,05. RESULTADOS: La mediana del ICTH fue 1 (r: 0-6). El 45,7% de los pacientes tuvieron puntaje 0; el 40,7%, 1-2; y el 13,6%, 〉 3. Las comorbilidades más frecuentes fueron obesidad, infección y compromiso pulmonar y hepático. La MRT de los pacientes con puntaje 0 fue 14,1%; con puntaje 1-2, 43,7%; y con puntaje 〉 3, 52,6%. Las curvas de supervivencia manifestaron diferencias entre los tres grupos (p 0,01). CONCLUSIONES: El ICTH mostró ser una herramienta efectiva para predecir el riesgo de MRT en nuestro medio.

Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (AHSCT) represents the only curative treatment for the majority of pediatric patients with Myelodysplastic Syndrome (MDS). We aimed to evaluate overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM) and relapse incidence in children who underwent AHSCT for MDS in six institutions from Argentina. PROCEDURE: A retrospective analysis of 54 AHSCT was carried out in 52 patients (mean age: 9 years; range: 2-19; 35 males). RESULTS: MDS subtypes were refractory cytopenia of childhood (RCC) (n: 26, 50%), refractory anemia with excess blasts (RAEB) (n: 9, 18%), RAEB in transformation (RAEB-T) (n: 8, 15%) and juvenile myelomonocytic leukemia (JMML) (n: 9, 17%). At time of transplant, seven (13%) patients transformed to acute myeloid leukemia (AML) and two patients with RCC to RAEB. Donors were related in 32 cases (59%) and the stem cells source was: bone marrow (63%), peripheral blood (26%), and umbilical cord blood (11%). Five-year DFS and OS were 50% and 55% respectively; and for patients with JMML, 57% and 67% respectively. Cumulative incidence of NRM and relapse were 27% and 21% respectively. In the multivariate analysis, umbilical cord blood (HR 4.07; P = 0.025) and age ≥ 9 years at transplantation (HR 3.28; P = 0.017) were associated with lower OS; age and graft-versus-host disease (GVHD) had a higher NRM. CONCLUSIONS: In our series, more than half of the patients achieved long term OS with AHSCT. Less toxic conditioning regimens or more intensive GVHD prophylaxis could lead to better results in some children.

Adenomatous polyposis coli gene involvement in ileal enterochromaffin cell neuroendocrine neoplasms.

The adenomatous polyposis coli gene is a key tumor suppressor gene. Alterations in this gene have been found in most sporadic colon cancers; associated with familial adenomatous polyposis; and found in neoplasms of other organs, such as the liver, stomach, lung, breast, and cerebellar medulloblastoma. In the heterogeneous group of neuroendocrine neoplasms of the gastrointestinal tract, the involvement of adenomatous polyposis coli is debated, and only occasional reports found adenomatous polyposis coli alterations in foregut and midgut neuroendocrine neoplasms, with adenomatous polyposis coli mutations only in the latter. To elucidate the penetrance of adenomatous polyposis coli alterations in ileal neuroendocrine neoplasms, we performed DNA fragment analysis (loss of heterozygosity for 5q22-23 and 5q23) and sequencing on the mutation cluster region of the adenomatous polyposis coli gene on 30 ileal enterochromaffin cell neuroendocrine neoplasms. Adenomatous polyposis coli gene mutations were detected in 23% of cases (7/30); in particular, 57% were missense and 14%, nonsense/frameshift, all novel and different from those reported in colorectal or other cancers. Loss of heterozygosity analysis demonstrated a deletion frequency of 15% (4/27). No association was found with features of tumor progression. Our observations support the involvement of somatic adenomatous polyposis coli alterations in tumorigenesis of ileal enterochromaffin cell neuroendocrine neoplasms; the mechanisms of adenomatous polyposis coli gene inactivation appear to be different from those reported in other tumor types.

Primary squamous cell carcinoma of the endometrium unrelated to human papilloma virus: a molecular study.

In this paper we report a molecular study of a case of Primary Endometrial Squamous Carcinoma (PESC), in which a Human Papilloma Virus (HPV) infection had been previously excluded by Polymerase Chain Reaction (PCR). The studies performed in an effort to explain the carcinogenesis included immunohistochemical over-expression of p53 and p16 proteins as previously observed in our own papers, plus microsatellite analysis of D10S1765 at 10q23.3 (PTEN) and TP53 at 17p13.1 (P53) as well as the methylation status of the of BRCA1 and p16 promoters using specific PCRs. In this rare malignancy, we found allelic imbalance (AI) at 17p13.1 (P53). Instead, AI at D10S1765 (PTEN) gene was absent. The genetic alteration of p53, with hyper-expression of p53 protein and an absence of abnormalities in the PTEN gene are consistent with the similarities between Uterine Serous Carcinoma (USC) and our case of PESC. The aberrant methylation of both p16 and BCAR1 promoters was not detected in our case. This finding too could imply that ESC is more similar to Uterine Serous Carcinoma than Uterine Endometrioid Carcinoma (UEC). Moreover, the lack of aberrant methylation of p16, which is in accordance with over-expression of p16 immunoreactivity, in the absence of HPV infection may be related to other unknown genetic alterations. In our opinion, it is hard to reach any definite conclusion concerning the carcinogenesis of PESC, because of its rarity and the very few molecular studies reported in the literature. Further studies with more numerous cases and larger molecular analyses are mandatory for this malignancy, to confirm whether it is more closely related to papillary endometrial cancer than to endometrioid carcinoma.

Therapeutic management for post-traumatic treatment of the anterior dental region: a case report with long-term follow up.

The treatment plan represents the final step in every diagnostic procedure and is the result of a series of assessments based on information gathered from a detailed clinical history. This clinical case reports the replacement of two central incisors that were lost because of a trauma. The advantages and disadvantages of the two treatment options (i.e. implantology or prosthetic restoration) were carefully evaluated in relation to the case in hand. Patient compliance and aesthetic requirements had been also considered. In this case, a conventional prosthetic restoration was performed using a metal-ceramic bridge, utilising full crowns between the right and left maxillary lateral incisors associated with minimal canine preparation. By this strategy, the treatment plan allows for a future implant restoration, should this become necessary.

Cyclic fatigue resistance of Mtwo NiTi rotary instruments used by experienced and novice operators--an in vivo and in vitro study.

BACKGROUND: The aim of the present study was to evaluate the cyclic fatigue resistance of Mtwo NiTi rotary instruments after clinical use by 1 experienced and 1 novice operator. MATERIAL/METHODS: Cyclic fatigue testing of instruments was performed on tapered artificial canals with a 5 mm radius of curvature and 60° angle of curvature. Twenty Mtwo instruments for each size were selected and divided into 2 groups: group A consisted of 10 instruments of each size used for shaping 10 root canals in molar teeth of patients by an experienced operator; group B consisted of 10 instruments of each size used for shaping 10 root canals in molar teeth of patients by a novice operator. Instruments were rotated until fracture occurred and the numbers of cycles to failure (NCF) were recorded. Data obtained were subjected to an independent sample t-test to determine statistical differences. The significance was determined at a 95% confidence level. RESULTS: No statistically significant difference (P<0.05) was noted between the instruments of groups A and B for all sizes. More instruments with visible signs of plastic deformation were identified for the novice operator. CONCLUSIONS: The clinical use of Mtwo NiTi rotary instruments by a novice operator did not significantly affect the cyclic fatigue resistance when compared with the control group of the same instrument sizes used by an experienced operator. It can be concluded that novice operators can use these instruments safely under the recommended technical guidelines.

A new case of primary signet-ring cell carcinoma of the cervix with prominent endometrial and myometrial involvement: Immunohistochemical and molecular studies and review of the literature.

BACKGROUND: As a rule, endocervical tumours with signet-ring cell are classed as metastatic extra-genital neoplasms. In a patient aged 45 years, we describe primary cervical signet-ring cell carcinoma (PCSRCC) characterized by prominent endometrial and myometrial involvement, simulating primary endometrial adenocarcinoma with cervical extension. In addition, a review was made of the literature to identify the clinical and pathological features of this rare malignancy. CASE PRESENTATION: A 45-year-old woman was referred to our Gynaecology Department due to persistent abnormal vaginal bleeding. Transvaginal ultrasonography showed slight endometrial irregularities in the whole uterine cavity suggestive of endometrial neoplasms. Pelvic magnetic resonance imaging revealed diffuse enlargement of the cervix, which had been replaced by a mass. Induration extended to the parametria and sigmoid colon fat.Histological examination of endometrial curettage and a cervical biopsy revealed a neoplasm characterized by neoplastic signet-ring cells and trabecular structures. Immunohistochemical analysis and molecular studies showed certain findings consistent with a cervical neoplasm, such as positivity to CEA, keratin 7, Ca-125 and p16 and the presence of HPV (Human Papilloma Virus) DNA 18.On examination of the hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the lesion replacing the cervix, endometrium and myometrium, revealed the same immunohistochemical findings observed on endometrial curettage and cervical biopsy specimens. Metastases were found in an ovarian cystic lesion and the lymph nodes. CONCLUSION: With this report the authors have demonstrated that the spread of cervical adenocarcinoma to the uterine corpus, although rare, may be observed, and that in this instance immunohistochemical and molecular studies can provide sufficient information for accurate diagnosis even on small biopsy specimens.

Central incisor loss after delayed replantation following avulsion: a contemporary restorative and adjunctive orthodontic management approach.

Delayed replantation of an avulsed tooth may result in rapid root resorption or, more frequently, dental ankylosis with subsequent bone substitution. If this process develop slowly, it is possible to observe that tooth loss is characterized by a well conserved alveolus with regard to bone preservation, particularly in vertical dimension. This clinical case reports a dental trauma of a central incisor in a young boy characterized by tooth avulsion and its delayed replantation. After 10 years, dental ankylosis of the incisor was recorded and the patient underwent a prosthetic-orthodontic rehabilitation using CAD-CAM technology and no-prep veneers.

Metaplastic papillary tumor of the salpinx: report of a case using microsatellite analysis.

Metaplastic papillary tumor (MPT) of the salpinx is a rare lesion found in the lumen of fallopian tubes during the postpartum period. This lesion is very small and is composed microscopically of papillae lined by stratified epithelium. Similar to serous borderline ovarian tumors (BOTs), epithelial elements of MPT show a budding, abundant, dense, and eosinophilic cytoplasm, bland nuclei or with mild atypia. It is not clear whether this lesion is a papillary metaplastic proliferation or a small atypical proliferative (borderline) serous tumor associated with pregnancy. Owing to its rarity, MPT has never been investigated in molecular studies and compared with ovarian serous neoplasms. In this study, a case of tubal MPT was molecularly examined and compared with 4 BOTs and with 2 low-grade ovarian carcinomas, using microsatellite analysis with 13 markers at 8 chromosomal regions involved in ovarian carcinogenesis. The tubal MPT and one of the BOTs showed no alterations in the investigated chromosomal regions. The remaining 3 BOTs showed only single allelic imbalances. Instead, low-grade serous carcinomas showed a higher frequency of alterations, including allelic imbalance at chr10q23, 1p36, 9p22, and 17. In conclusion, this study provides, for the first time, molecular data on an MPT of the fallopian tube, indicating that this entity might share both morphologic and molecular similarities with a subset of minimally altered BOTs, termed atypical proliferative serous tumors, which behave in a benign manner. However, in our opinion, further molecular studies should be conducted on other cases of MPTs to confirm this hypothesis.

Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors.

HER-2/neu overexpression and/or gene amplification occurs in several human malignancies, frequently correlates with tumor aggressiveness, and provides the basis for treatment with trastuzumab. Among neuroendocrine neoplasms (NEN) of the gastroenteropancreatic (GEP) tract, ileal neuroendocrine tumors show peculiar features of malignancy with frequent metastases at the diagnosis. We investigated the overexpression and/or amplification of HER-2/neu and the involvement of the metastasis-related proteins c-Met, MTA-1, and VEGF in 24 primary ileal NEN by immunohistochemistry and fluorescence in situ hybridization (FISH). Data were compared with those of 43 GEP endocrine tumors of other sites. All primary ileal NEN showed an intense membranous and cytoplasmic immunostaining for HER-2/neu. According to the breast cancer scoring system, 17% of ileal carcinoids showed a score of 3+ and 71% with a score of 2+ with a significant difference respect the non-ileal GEP endocrine tumors (p < 0.0000). FISH analysis revealed chromosome 17 polysomy in 33% of 2+/3+ ileal tumors but not HER-2/neu gene amplification. The c-Met and MTA-1 but not VEGF were overexpressed in almost all ileal NEN, whereas VEGF presented more frequently a normal staining. The comparisons with the other GEP NEN demonstrated significant differences for all the three proteins (p < 0.0000, p < 0.0002, and p < 0.001, respectively). These findings suggest that in ileal NEN, HER-2/neu overexpression plays a role in the carcinogenetic process and by triggering the altered expression of c-Met and MTA-1, may activate the molecular pathway(s) promoting tumor progression and metastasis development. Ileal HER-2/neu overexpressing neuroendrocrine tumors may constitute potential candidates for target therapy with specific humanized monoclonal antibodies.

Use of customized fiber posts for the aesthetic treatment of severely compromised teeth: a case report.

The introduction of fiber posts has improved the treatment of endodontically treated teeth, increasing retention, and distributing the stress along the root in order to reduce the risk of fracture. This clinical case describes the use of posts during the prosthetic rehabilitation of severely compromised teeth in the anterior segment.

Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of beta-catenin and chromosomal instability.

The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and beta-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered beta-catenin localization were tested for beta-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (P=0.042) and correlating with aggressive features (high histology grade, P<0.02; tumour death, P=0.026; high fractional allelic loss, P=0.002, in turn correlating with short survival, P=0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (P=0.002) and correlating with histology grade (P=0.012). beta-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (P=0.047) and short survival (P=0.006). APC, but not beta-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormal beta-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas.

Genetic alterations in combined neuroendocrine neoplasms of the lung.

Large-cell neuroendocrine and small-cell lung carcinomas are highly aggressive neuroendocrine tumors that can be associated in a variant of 'small-cell lung carcinoma combined with large-cell neuroendocrine carcinoma'. Little is known about this rare tumor type with biphenotypic neuroendocrine differentiation. The aim of the present study was to genetically characterize each component of a series of combined small-cell/large-cell neuroendocrine carcinomas, to gain information on their histogenesis and to compare the alterations observed with those found in their respective pure forms. To this end, 22 formalin-fixed, paraffin-embedded lung neuroendocrine tumors obtained from surgical resections were investigated: six combined small-cell/large-cell carcinomas, eight pure large-cell carcinomas and eight pure small-cell carcinomas. For the combined neuroendocrine neoplasms, DNA was extracted separately from each of the two cytologically different populations. Allelic imbalance was investigated by PCR amplification of 30 highly polymorphic microsatellite markers located at 11 different chromosomal regions. A common background of genetic alterations, similar in both components of the combined neoplasms, was demonstrated at 17p13.1, 3p14.2-3p21.2, 4q12-4q24, 5q21 and 9p21. In fact, the two components appeared to be more similar to each other than to their respective pure forms. In addition, allelic imbalances preferentially involving one of the two components were found. These alterations often appeared to be specific for this histological variant, as compared with those observed in pure forms or in the literature. In conclusion, this is the first report in which a molecular characterization of the variant of small-cell lung carcinoma combined with large-cell neuroendocrine carcinoma was performed. The finding of common alterations in the two phenotypically different neuroendocrine cell components suggests a close genetic relationship and supports the hypothesis of a monoclonal origin from a common ancestor. The genetic differences observed provide the basis for the divergent differentiation and parallel the morphological differences in the two components of these combined neuroendocrine neoplasms.