Publications by authors named "Silvia Pizzi"

29 Publications

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

Ital J Pediatr 2019 Dec 4;45(1):157. Epub 2019 Dec 4.

Department of Pediatrics, Pugliese-Ciaccio Hospital of Catanzaro, Viale Papa Pio X, 83, 88100, Catanzaro, Italy.

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.
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http://dx.doi.org/10.1186/s13052-019-0734-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894327PMC
December 2019

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina.

Arch Argent Pediatr 2016 Aug 30;114(4):337-42. Epub 2016 Jun 30.

Servicio de Trasplante de Médula Ósea, Hospital Garrahan, Ciudad Autónoma de Buenos Aires, Argentina.

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.
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http://dx.doi.org/10.5546/aap.2016.eng.337DOI Listing
August 2016

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

Pediatr Blood Cancer 2015 Jan 27;62(1):153-7. Epub 2014 Sep 27.

Hospital Privado Centro Médico de Córdoba, Córdoba, Argentina; Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, 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.
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http://dx.doi.org/10.1002/pbc.25238DOI Listing
January 2015

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

Hum Pathol 2013 Dec 16;44(12):2736-42. Epub 2013 Oct 16.

Centre for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy University and University Hospital of Parma, 43126 Parma, Italy.

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.
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http://dx.doi.org/10.1016/j.humpath.2013.06.019DOI Listing
December 2013

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

Pathol Oncol Res 2013 Jul 21;19(3):495-9. Epub 2013 Feb 21.

Department of Biomedical, Biotechnological & Translational Sciences, Pathological Anatomy & Histology Unit, University of Parma, Faculty of Medicine, Via Antonio Gramsci 14, 43126 Parma, Italy.

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.
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http://dx.doi.org/10.1007/s12253-013-9607-3DOI Listing
July 2013

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

Med Sci Monit 2012 Jun;18(6):MT41-5

Department of Endodontics, Sapienza University of Rome, Rome, Italy.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560727PMC
http://dx.doi.org/10.12659/msm.882887DOI Listing
June 2012

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.

World J Surg Oncol 2012 Jan 11;10. Epub 2012 Jan 11.

Department of Pathology and Medicine of Laboratory, Section of Pathology, Parma University.

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.
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http://dx.doi.org/10.1186/1477-7819-10-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320546PMC
January 2012

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

Int J Gynecol Pathol 2011 Nov;30(6):532-5

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Via Gramsci 14, Parma, Italy.

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.
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http://dx.doi.org/10.1097/PGP.0b013e31821713d2DOI Listing
November 2011

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

Dent Traumatol 2013 Jun 4;29(3):234-7. Epub 2011 Oct 4.

Dental Practicioner Brescia and Parma Dental Technician Brescia Sezione di Odontostomatologia, Università di Parma, Italy.

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.
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http://dx.doi.org/10.1111/j.1600-9657.2011.01065.xDOI Listing
June 2013

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

Dent Traumatol 2012 Apr 14;28(2):161-5. Epub 2011 Jul 14.

Dental Practitioner, Brescia and Parma, Brescia, Italy.

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.
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http://dx.doi.org/10.1111/j.1600-9657.2011.01036.xDOI Listing
April 2012

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

Virchows Arch 2011 May 29;458(5):525-36. Epub 2011 Mar 29.

Department of Pathology, Section of Anatomic Pathology, University of Parma, Parma, Italy.

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.
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http://dx.doi.org/10.1007/s00428-011-1069-yDOI Listing
May 2011

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

Dent Traumatol 2008 Dec;24(6):671-5

Sezione ed Unità Operativa di Odontostomatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.

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.
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http://dx.doi.org/10.1111/j.1600-9657.2008.00594.xDOI Listing
December 2008

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

Endocr Relat Cancer 2008 Dec 16;15(4):1013-24. Epub 2008 Jul 16.

Section of Pathological Anatomy, Department of Pathology and Laboratory Medicine, University of Parma, via Gramsci, 14, I-43100 Parma, Italy.

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.
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http://dx.doi.org/10.1677/ERC-07-0230DOI Listing
December 2008

Genetic alterations in combined neuroendocrine neoplasms of the lung.

Mod Pathol 2008 Apr 18;21(4):414-22. Epub 2008 Jan 18.

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.

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.
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http://dx.doi.org/10.1038/modpathol.3801014DOI Listing
April 2008

Legionella contamination in the water system of hospital dental settings.

Acta Biomed 2007 Aug;78(2):117-22

Public Health Department, University of Parma, Italy.

Background And Aim Of The Work: Among hospital facilities the dental unit is an environment that is at major risk of Legionella due to equipment such as the air/water syringe, the turbine, the micromotor and the scaler which generate potentially harmful aerosols that may to be a source of exposure to Legionella spp. particularly in immunodeficient patients, and those affected by chronic diseases, and also in dental personnel. Therefore, an examination of the extent of Legionella spp. contamination in the dental chairs waterlines and the incoming water supply of some public dental units is the subject of the present study.

Methods: From February 2002 to March 2004, a total of 208 water samples were collected: 160 samples from the water supply of 4 dental chair and 48 samples from the cold incoming tap water of 2 units.

Results: Legionella spp. was detected in 46 samples (22.1% ): 19 of them (41.3% of Legionella spp.; 9.1% of the total) were Legionella pneumophila; Pseudomonas aeruginosa was detected in 86 samples (41.4%) and both microorganisms were detected in 2 samples (0.96%).

Conclusions: Our results show a microbiological condition in dental settings, that is not at all satisfactory due to the presence of Legionella in concentrations that are considered to be a health hazard (> or = 10(3)) in certain cases. Given the extent of the health risk in these surroundings, the difficulty in its assessment, and also considering the wide diffusion of general dental care, our investigation has confirmed the need to regularly monitor the microbiological condition of water in dental units.
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August 2007

Sex chromosome alterations associate with tumor progression in sporadic colorectal carcinomas.

Clin Cancer Res 2007 Aug;13(15 Pt 1):4365-70

Department of Pathology and Laboratory Medicine, Medical School, Parma University, Parma, Italy.

Purpose: The X and Y chromosomes have been associated with malignancy in different types of human tumors. This study attempts to determine the involvement of X chromosome and pseudoautosomal regions (PAR) in sporadic colorectal carcinogenesis.

Experimental Design: An allelotyping of X chromosome in 20 premalignant and 22 malignant sporadic colorectal tumors (CRC) from female patients and an analysis of losses [loss of heterozygosity (LOH)] on PARs from 44 CRCs and 12 adenomas of male patients were carried out. In male tumors, a fluorescence in situ hybridization analysis was done to identify which sex chromosome was possibly lost.

Results: The LOH frequency in female CRCs was 46% with higher incidence in patients with tumor recurrence than in those who were disease-free (P < 0.01) and with a significant difference from adenomas (11%; P < 0.0001). The LOH rate of PARs in male CRCs was 37% with a frequency significantly higher in patients with recurrence (P < 0.03). These results were maintained also when data from PARs of all 66 male and female patients were cumulated (P < 0.05). LOH in PARs was significantly correlated with LOH at 5q (P < 0.01) and 18q (P < 0.01), early and late events, respectively, in colorectal carcinogenesis. Fluorescence in situ hybridization analysis in male patients with extensive PAR LOH revealed a preferential loss of the Y chromosome.

Conclusions: Our data suggest a role for sex chromosome deletions in the malignant progression of sporadic CRCs and support the presence in the PARs of putative tumor suppressor genes involved in the progression of human sporadic CRCs.
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http://dx.doi.org/10.1158/1078-0432.CCR-06-2736DOI Listing
August 2007

Criteria for malignancy in gastrointestinal endocrine tumors.

Endocr Pathol 2006 ;17(2):119-29

Department of Pathology and Laboratory Medicine, Section of Anatomic Pathology, University of Parma, Parma, Italy.

In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.
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http://dx.doi.org/10.1385/ep:17:2:119DOI Listing
February 2007

Inferior alveolar nerve injury related to surgery for an erupted third molar.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007 Feb 7;103(2):e7-9. Epub 2006 Nov 7.

Unità Operativa di Odontostomatologia, Azienda Ospedaliero, Parma, Italy.

Removal of third molars is one of the most common operations performed in oral surgery. A well recognized serious complication of mandibular third molar extraction is injury to the inferior alveolar nerve (IAN). We describe a case of an unusual nerve passage discovered after the extraction of a completely erupted third molar. The likelihood of direct damage to the IAN can be predicted with more specific information obtained by the use of a preoperative computerized tomography scan when conventional radiography does not clearly show the nerve canal.
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http://dx.doi.org/10.1016/j.tripleo.2006.09.002DOI Listing
February 2007

Xq25 and Xq26 identify the common minimal deletion region in malignant gastroenteropancreatic endocrine carcinomas.

Virchows Arch 2006 Feb 22;448(2):119-26. Epub 2005 Oct 22.

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Via Gramsci 14, 43100 Parma, Italy.

Loss of heterozygosity (LOH) for markers on X chromosome are associated with malignancy in endocrine tumors of the stomach and pancreas. The aim of this work is to investigate low-grade, well-differentiated endocrine carcinomas (WDEC) vs high-grade, poorly differentiated endocrine carcinomas (PDEC) of the gastroenteropancreatic (GEP) tract for common deletion regions on X chromosome. We performed a comparative allelotyping analysis with 24 highly polymorphic markers for the X chromosome in 12 WDECs and 5 PDECs. Overall, the LOH frequency in all informative loci investigated was 59% in primary and 61% in metastasis, with a significantly higher rate in PDECs than in WDECs (p<0.015 for primary and p<0.00005 for metastasis). In both WDECs and PDECs, the small Xq25 region as defined by DXS8059, DXS8098, and DXS8009 markers showed higher LOH rate as compared to the rest of the chromosome markers (p<0.04). In addition, LOH was very frequently elevated also in DXS294 and in DXS102 loci mapping the chromosomal region Xq26. In no instances differences were found between primary tumors and metastases. Methylation analysis revealed that Xq25 loss preferentially occurred on the inactive X chromosome, a feature in agreement with findings from other human cancers suggesting escape of tumor suppressor genes to X chromosome inactivation at this region. Overall, our data indicate that the two chromosomal regions, Xq25 and Xq26, may participate to the malignant progression of GEP endocrine carcinomas.
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http://dx.doi.org/10.1007/s00428-005-0058-4DOI Listing
February 2006

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors.

Mod Pathol 2005 Jun;18(6):795-805

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.

Association of X chromosome allelic losses with tumor malignancy has been identified in foregut but not in midgut endocrine neoplasms. The aim of this study was to investigate the association of deletions on X chromosome with malignancy in lung neuroendocrine tumors, another family of foregut neoplasms comprising four categories with increased malignancy: typical and atypical carcinoids, large cell neuroendocrine and small cell lung carcinomas. To evaluate loss of heterozygosity, DNA extracted from nine typical carcinoids, 17 atypical carcinoids, six large cell neuroendocrine carcinomas and five small cell lung carcinomas was PCR-amplified for 18 microsatellite markers spanning the whole X chromosome. All tissue samples were formalin-fixed and paraffin-embedded. X chromosome losses were absent in typical carcinoids, whereas they were found in nine out of 17 atypical carcinoids and in five out of six large cell neuroendocrine carcinomas (involving 28 and 70% of informative loci, respectively). On the contrary, deletions on X chromosome were an extremely rare event in small cell lung carcinomas. In atypical carcinoids, the presence of losses was associated with larger tumor size, higher pT status and advanced stage. No death occurred in atypical carcinoid patients without deletions on X chromosome, whereas all atypical carcinoid patients who had died from disease showed allelic losses. In conclusion, X chromosome allelic losses, absent in benign 'typical' carcinoids, progressively increased in frequency from intermediate-grade 'atypical' carcinoids to high-grade large cell neuroendocrine carcinomas. These results extend the association of deletions on X chromosome with malignancy, already demonstrated in other foregut endocrine neoplasms, to lung neuroendocrine tumors. The absence of X chromosome allelic losses in small cell lung carcinomas underlines a striking difference from large cell neuroendocrine carcinomas, possibly linked to different pathogenetic mechanisms of these two highly aggressive neuroendocrine lung tumors.
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http://dx.doi.org/10.1038/modpathol.3800353DOI Listing
June 2005

Association between recurrence of sporadic colorectal cancer, high level of microsatellite instability, and loss of heterozygosity at chromosome 18q.

Dis Colon Rectum 2004 Sep 12;47(9):1467-82. Epub 2004 Aug 12.

Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University Medical School, Parma, Italy.

Purpose: Microsatellite instability and loss of heterozygosity of chromosomes 18q, 8p, and 4p are genetic alterations commonly found in colorectal cancer. We investigated whether these genetic markers allow for the stratification of patients with Stage II to III colorectal cancer into groups with different recurrence risks, and with different prognoses.

Methods: Tumors of 113 patients were evaluated for loss of heterozygosity of chromosomes 18q, 8p, and 4p and for microsatellite instability by use of six microsatellite markers. Genetic alterations involving each of these genetic markers were examined for association with disease recurrences and survival.

Results: Loss of heterozygosity of chromosomes 18q, informative in 96 percent of cases, in Stage III tumors was associated with higher risk of overall recurrence ( P< 0.001), local recurrence ( P< 0.001), distant metastases ( P< 0.001), decreased overall survival ( P= 0.002), and disease-free survival ( P< 0.001). The recurrence rates and survival rates among patients with Stage II colorectal cancer were independent of loss of heterozygosity of chromosome 18q. Stage III and loss of heterozygosity of chromosome 8p also were associated with a higher risk of recurrences when these factors were considered individually. In multivariate analysis, only loss of heterozygosity of chromosome 18q was independently associated with risk of recurrences ( P < 0.001) and with disease-free survival ( P= 0.001). No correlation was observed between microsatellite instability and recurrence rates. However, microsatellite instability was associated with improved overall survival ( P= 0.04) and with a longer disease-free interval ( P= 0.002). Only in five cases (16.7 percent) was it possible to perform resection of recurrences; two of these patients had microsatellite instability tumor. In no cases was it possible to resect recurrence of tumors with loss of heterozygosity of chromosome 18q.

Conclusions: Loss of heterozygosity of chromosome 18q is an informative genetic marker, which in resected Stage III colorectal cancer can be used to predict recurrences and survival. Microsatellite instability identified cases that, even in the case of recurrence, have a more favorable prognosis.
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http://dx.doi.org/10.1007/s10350-004-0628-6DOI Listing
September 2004

Health hazard evaluation in private dental practices: a survey in a province of northen Italy.

Acta Biomed 2004 Apr;75(1):50-5

Dipartimento di Sanita Pubblica, Sezione di Igiene, Università degli Studi di Parma, Italy.

The purpose of this questionnaire survey was to evaluate the knowledge and attitudes of private dental health care workers about cross-infection hazards through examination of practising behaviour in respect of infection control. A questionnaire was sent by mail to the private dentists operating in Parma province. The survey concerned 7 groups of questions about demographic data, personal protective equipment, immunization, sterilization and disinfection, waste disposal and occupationally acquired injuries, behaviour. Four hundred questionnaires were sent to the members of the Medical and Dentist College of Parma: 122 were returned and analysed (30.5%). Among the infectious diseases 45% of the interviewed think that the most dangerous diseases are Hepatitis B and C, followed by HIV infection (21.5%). The most used personal protective equipments are gloves (98%), masks (95%) and protective eyewear (94%). Sixty eighth per cent of the dentists treat HBV, HCV, HIV, TB, HSV suffering patients at the end of the working day. Twenty nine point 7% of them claim to have written protocols to follow in case of accident. Altogether the results show a good knowledge of the most important risks related to dentistry activity and of the main procedures for the infection control and management.
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April 2004

Abnormal Fhit protein expression and high frequency of microsatellite instability in sporadic colorectal cancer.

Eur J Cancer 2004 Jul;40(10):1581-8

Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University, Medical School, Via Gramsci 14, 43100 Parma, Italy.

The role of Fhit protein in the oncogenesis of colorectal cancer is still in debate. Recent studies have revealed that reduced Fhit protein expression is associated with a deficiency of the mismatch repair protein. One hundred and twenty unselected patients who underwent curative resection for sporadic colorectal cancer in a three-year period were evaluated for microsatellite instability (MSI) using six microsatellite markers, and for the presence of Fhit and mismatch repair (MMR) proteins (Mlh1 and Msh2) by means of immunostaining. The relations between these markers were analysed. Reduced or absent Fhit expression was noted in 18 out of 118 patients. This altered expression was significantly higher in right-sided cancer (P = 0.005), mucinous tumours (P = 0.005) and in poorly differentiated histological types (P = 0.0001). MSI was found in 22 out of 109 patients, more so in right-sided cancer (P = 0.0001), poorly differentiated histology (P = 0.0001), and mucinous tumours (P = 0.0001). No association was found with TNM stage. MSI was present in 66.7% of tumours with altered Fhit expression and in only 10% of tumours with preserved or intermediate Fhit expression (P = 0.0001). Of the tumours with reduced or absent Fhit expression, 72.2% had loss of nuclear Mlh1 or Msh2 expression compared with only 14% of the preserved or intermediate Fhit expression tumours (P = 0.0001). These results support the hypothesis that deficiency in a MMR gene could be a cause of the high frequency of alterations in Fhit expression, and they permit the suggestion that FHIT gene alteration may be part of the genetic pathway involving MSI through which some colorectal cancers arise.
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http://dx.doi.org/10.1016/j.ejca.2004.02.021DOI Listing
July 2004

[Prognostic significance of chromosome and microsatellite instability in colorectal cancer].

Chir Ital 2003 Nov-Dec;55(6):821-8

Dipartimento di Scienze Chirurgiche, Sezione di Clinica Chirurgica Generale e Terapia Chirurgica, Università degli Studi di Parma.

The prediction of recurrence and the prognosis of colorectal cancer have always been related to the stage of the disease. Clinical pathological classifications are unable to predict the individual risk of recurrence and the prognosis which would also appear to be linked to additional factors, which have yet to be properly assessed, such as the genetic endowment of the tumour. In this study we assessed how microsatellite and chromosomal instability may help us to stratify two classes of risk of recurrence in patients at the same stage. From July 1996 to June 1999 we prospectively collected data on 112 patients (59 male, 53 female) affected by colorectal cancer and undergoing surgery with a radical intent. Biopsies of normal and tumor tissue were submitted to DNA extraction and amplification to evaluate the presence of chromosomal instability (loss of heterozygosity) and microsatellite instability. Analysis of the data revealed that loss of heterozygosity in the long arm of chromosome 18 is associated, in patients with stage III colorectal cancer, with a higher risk of recurrence and therefore with a worse prognosis. Microsatellite instability proved to be associated with a better prognosis even in cases of recurrence.
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February 2004

Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract.

Cancer 2003 Sep;98(6):1273-82

Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy.

Background: The molecular pathogenesis of poorly differentiated endocrine carcinomas of the gastrointestinal tract (GI PDECs) remains unclear. It has been suggested that these lesions either originate from multipotent stem cells that also can serve as the origin of nonendocrine adenocarcinomas or arise due to the dedifferentiation of well-differentiated endocrine carcinomas (WDECs).

Methods: Ten gastric and 9 colorectal PDECs, 9 gastric WDECs, and 12 colorectal carcinomas (CRCs) were analyzed for loss of heterozygosity (LOH) at 11q13 (MEN1), 17p13.1 (p53), 3p14.2 (FHIT), 3p21.3 (RASSF1A), and 18q23 (DCC/DPC4/Smad2), and for immunohistochemical expression of p53, FHIT, Rb, and p16.

Results: PDECs exhibited high fractional allelic loss (FAL; 0.49), with frequent (> 40%) alterations in p53, Rb, MEN1, FHIT, and 18q. No significant differences were found between gastric and colorectal PDECs. Gastric WDECs also exhibited high FAL (0.44), with frequent alterations in Rb and/or p16, MEN1, and 3p21. CRCs exhibited a low level of FAL (0.23), with frequent (> 50%) p16 and p53 alterations. When gastric PDECs and WDECs were compared, substantial similarities were found with respect to FAL (0.42 vs. 0.44) and with respect to individual gene alterations, except in p53, which was consistently altered only in PDECs. CRCs, which were characterized by a lower FAL (0.56 vs. 0.23) and which lacked alterations in both 3p and Rb, were found to be significantly different from colorectal PDECs.

Conclusions: GI PDECs demonstrated a high level of chromosomal instability; consistent inactivation of both the p53 and p16/Rb pathways; and frequent LOH at 3p (possibly involving FHIT), the MEN1 locus, and 18q. The profile of genetic alterations in PDECs was more consistent with the profile in WDECs than with the profile in CRCs.
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http://dx.doi.org/10.1002/cncr.11621DOI Listing
September 2003

Pleomorph poorly differentiated endocrine carcinoma of the rectum.

Virchows Arch 2003 Jun 7;442(6):605-10. Epub 2003 May 7.

Department of Pathology and Laboratory Medicine, Section of Anatomic Pathology, University of Parma, 43100, Parma, Italy.

We present a case of poorly differentiated endocrine carcinoma (PDEC) of the rectum identified immunohistochemically and characterized by a high degree of cellular pleomorphism, including bizarre giant cells. This case indicates that gastrointestinal PDECs are not restricted to small cell carcinomas. Among the multiple genes investigated, loss of heterozygosity (LOH) of the p53 locus without p53 immohistochemical accumulation, overexpression of c-kit and absent expression of p16 were seen.
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http://dx.doi.org/10.1007/s00428-003-0807-1DOI Listing
June 2003

Different patterns of 11q allelic losses in digestive endocrine tumors.

Hum Pathol 2002 Mar;33(3):322-9

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.

Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors.
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http://dx.doi.org/10.1053/hupa.2002.32219DOI Listing
March 2002

Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours.

J Pathol 2002 Apr;196(4):401-7

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.

Information on genetic changes involved in the progression of gastroenteropancreatic (GEP) endocrine tumours is scanty. On the other hand, the identification of molecular markers of malignancy could be crucial for the prognostic evaluation of these neoplasms, which is hardly predictable on the basis of conventional histological criteria. An association of X-chromosome deletions with malignancy has already been found in gastric endocrine tumours. To investigate this further, a comparative loss of heterozygosity (LOH) analysis was performed on 17 pancreatic endocrine tumours (PETs) and 17 intestinal (ten ileal, six appendiceal, and one rectal) carcinoids from female patients. The relationship of X-chromosome LOH with the ploidy status of the neoplasms was also investigated. LOH was found in six of eight malignant PETs (60% of the informative markers), but was infrequent in the nine benign ones (4.5%). In contrast, although retention of heterozygosity was consistently observed in benign midgut tumours, LOH was infrequent in malignant carcinoids (15%). No correlation was found between LOH and the ploidy status. These results indicate an association between X-chromosome LOH and malignancy in foregut endocrine tumours. The lack of such an association in midgut carcinoids suggests that different molecular mechanisms are involved in the progression of these two categories of endocrine neoplasms, which are otherwise considered to be closely related. These findings emphasize the need for further molecular studies on GEP endocrine tumours, carefully subdivided according to their anatomical site of origin.
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http://dx.doi.org/10.1002/path.1075DOI Listing
April 2002

Pancreatic polypeptide-related tumors.

Peptides 2002 Feb;23(2):339-48

From the Department of Pathology and Laboratory Medicine, Section of Anatomic Pathology, University of Parma, Parma, Italy.

PP-producing tumors are mostly located in the pancreas and may present as three pathologic lesions: pure PP-omas, mixed tumors with minor PP cell population, and PP-cell hyperplasia. These tumors are among the most common multiple adenomas frequently found in patients with multiple endocrine neoplasia type 1. Hypersecretion and high circulating levels of PP are frequently found. They are symptomless but may be useful for the identification of the pancreatic tumors. Numerous types of extrapancreatic endocrine tumors are able to synthesize and secrete PP. They occur mostly but not exclusively in the gastrointestinal tract, particularly in the rectum. The inactivation of the MEN 1 gene at 11q13 appears to be involved in the development of pancreatic but not of rectal PP-producing tumors.
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http://dx.doi.org/10.1016/s0196-9781(01)00606-4DOI Listing
February 2002