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1.
BMC Med Genet ; 21(1): 161, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807118

RESUMO

BACKGROUND: Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant. CASE PRESENTATION: The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed. CONCLUSIONS: This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.


Assuntos
Adenoma/genética , Proteína Axina/genética , Estesioneuroblastoma Olfatório/genética , Células Germinativas/metabolismo , Neoplasias Gástricas/genética , Estesioneuroblastoma Olfatório/diagnóstico por imagem , Estesioneuroblastoma Olfatório/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Radiografia Panorâmica , Neoplasias Gástricas/diagnóstico por imagem
2.
BMC Gastroenterol ; 19(1): 36, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30813906

RESUMO

BACKGROUND: Cronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown. CASE PRESENTATION: We present the case of a man who at the age of 66.0 years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0 kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000 mg t.i.d.) was added to prednisolone (10.0 mg/d). This therapy led to a remission within 6.0 months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5 mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0 years after the initial diagnosis the patient is still in complete remission without any treatment. CONCLUSION: The optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glucocorticoides/uso terapêutico , Polipose Intestinal/tratamento farmacológico , Mesalamina/uso terapêutico , Prednisolona/uso terapêutico , Idoso , Alopecia/etiologia , Diagnóstico Diferencial , Diarreia/etiologia , Esquema de Medicação , Disgeusia/etiologia , Humanos , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Masculino , Desnutrição/etiologia , Desnutrição/terapia , Doenças da Unha/etiologia , Indução de Remissão , Redução de Peso
4.
ACG Case Rep J ; 11(9): e01514, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39267621

RESUMO

Patients with hereditary polyposis syndromes (HPS) are among the highest risk of multiple types of cancer. This risk is further magnified by comorbid obesity; however, HPS present unique risks for bariatric surgery. The advent of endoscopic bariatric and metabolic therapies along with advancements in the realm of antiobesity medications provides potential weight loss alternatives in this vulnerable population. We present 2 cases of patients with obesity and HPS successfully treated with intragastric balloons in combination with antiobesity medications.

5.
World J Gastrointest Surg ; 15(1): 1-8, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36741069

RESUMO

In this editorial we present an overview and insights of the management of hereditary polyposis syndromes. The primary focus was on familial adenomatous polyposis, juvenile polyposis syndrome and Peutz-Jegher syndrome. Genetic testing has become increasingly available and is easier than ever to integrate into clinical practice. Furthermore, several genes have been added to the expanding list of genes associated with hereditary polyposis syndromes, allowing for precise diagnostics and tailored follow-up. Endoscopic evaluation of patients with hereditary polyposis syndromes is paramount in the surveillance strategies. Current endoscopic procedures include both diagnostic procedures and surveillance as well as therapeutic interventions. Recommendations for endoscopic procedures in the upper and lower gastrointestinal canal were described. Surgery is still a key component in the management of patients with hereditary polyposis syndromes. The increased cancer risk in these patients often render prophylactic procedures or intended curative procedures in the case of cancer development. Surgical interventions in the upper and lower gastrointestinal canal were described with relevant considerations. Development of chemopreventive medications is ongoing. Few drugs have been investigated, including nonsteroidal anti-inflammatory drugs. It has been demonstrated that cyclooxygenase-2 inhibitors may lower the number of polyps. Other medications are currently under investigation, but none have, to date, consistently been able to prevent development of disease.

6.
World J Gastrointest Endosc ; 15(10): 623-628, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37900118

RESUMO

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene. It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults. Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up. CASE SUMMARY: We report on the case of a 56-year-old female diagnosed with JPS after genetic testing revealed a rare variant of the BMPR1A gene BMPR1A c.1409T>C (p.Met470Thr). She was initially referred for colonoscopy by her general practitioner after testing positive on a screening faecal immunochemical test and subsequently found to have polyposis throughout the entire colorectum on her index screening colonoscopy. The patient was asymptomatic with a normal physical examination and no related medical or family history. Blood tests revealed only mild iron deficiency without anemia. To date, there has only been one other reported case of JPS with the same genetic variant. Subsequent colonoscopies were organised for complete polyp clearance and the patient was returned for surveillance follow-up. CONCLUSION: JPS patients can present with no prior symptoms or family history. Genetic testing plays an important diagnostic role guiding management.

7.
Pathology ; 54(2): 157-166, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34763900

RESUMO

Cutaneous findings are commonly associated with underlying gastrointestinal disorders and, in many instances, may be the first manifestation. Many such syndromes have incomplete penetrance and variable expressivity, making them difficult to recognise. Skin manifestations may be an easily recognised feature of the underlying disorder. Most of these syndromes are hereditary but not all are associated with malignancies; either benign or premalignant extraintestinal lesions can be the initial manifestation. Some involve a single organ system, while others involve multiple organs of the gastrointestinal tract. In this review, we have focused on Lynch syndrome (hereditary nonpolyposis colon cancer and Muir-Torre syndrome), familial adenomatous polyposis, the hamartomatous polyposis syndromes that include Peutz-Jeghers syndrome and the PTEN hamartoma syndromes, which include Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome and, lastly, Cronkhite-Canada syndrome, which is not heritable. Some of these are associated with colorectal cancer, of which 15% are heritable. The majority are inherited in an autosomal dominant fashion. These syndromes are uncommon. However, because of the strong association with the cutaneous findings, early detection and screening may be possible and are key to decreasing the morbidity and mortality associated with them, for both the patient and family members. The clinical findings, epidemiological findings, underlying genetic alterations and pathological findings are reviewed.


Assuntos
Neoplasias Gastrointestinais/patologia , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Cutâneas/patologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética
8.
Clin Case Rep ; 8(1): 92-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31998494

RESUMO

Juvenile polyposis syndrome (JPS) patients can have a significantly high burden of polyposis. Patient who undergoes prophylactic colectomy for polyps not amenable to endoscopic treatments requires close clinical surveillance to negate risk of malignancy from interval polyposis.

9.
Clin Transl Oncol ; 21(2): 220-231, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29956073

RESUMO

PURPOSE: The aim of this study is to explore the roles of ß-catenin, decorin, septin-7, and S100A10 expression in colorectal cancer development. METHODS: Twenty-five BALB/c mice were divided into five groups; four groups were administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group was administrated normal saline for 20 weeks. The colons were collected for histopathological analysis. Protein samples prepared from the frozen colon tissues of mice treated with N,N-dimethylhydrazine for the different time points were evaluated using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled with the 2D liquid chromatography-tandem mass spectrometry analysis. Based on the proteomic analysis results, immunohistochemical staining of ß-catenin, decorin, septin-7, and S100A10 was performed in paraffin-embedded mice colorectal tissue, and 53 cases of human hereditary polyposis colorectal cancer samples. RESULTS: Colorectal cancer was observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two differentially expressed proteins were involved in the development of cancer as per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2 = 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P = 0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the normal epithelium, which was confirmed via immunohistochemical staining. CONCLUSIONS: The subcellular localization of ß-catenin and decorin, septin-7, and S100A10 expressions are associated with the development of colorectal cancer in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis colorectal cancers.


Assuntos
Polipose Adenomatosa do Colo/patologia , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Adulto , Animais , Anexina A2/análise , Anexina A2/biossíntese , Carcinógenos/toxicidade , Neoplasias Colorretais/induzido quimicamente , Decorina/análise , Decorina/biossíntese , Dimetilidrazinas/toxicidade , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteômica/métodos , Proteínas S100/análise , Proteínas S100/biossíntese , Septinas/análise , Septinas/biossíntese , beta Catenina/análise , beta Catenina/biossíntese
10.
Clin Case Rep ; 7(1): 202-205, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30656042

RESUMO

Even in well-described genetic syndromes, such as neurofibromatosis type 1, expansion of the phenotype should be considered as a possible explanation for atypical presentations. However, it is critical to complete the evaluation for a potential dual diagnosis, as there could be significant prognostic and management implications.

11.
Pathology ; 50(1): 49-59, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29169633

RESUMO

Colorectal cancer (CRC) accounts for over 8% of all deaths annually worldwide. Between 2 and 5% of all CRCs occur due to inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis and Cowden/PTEN hamartoma syndrome. In addition, serrated polyposis is a clinically defined condition characterised by multiple colorectal serrated polyps and an increased risk of CRC but the genetics are not known. In most hereditary CRC syndromes, polyps undergo carcinogenesis, but the exact route to carcinoma seems to differ between the conditions. Discovery of the key germline mutations in these syndromes has been instrumental to our understanding of the underlying molecular mechanisms of colorectal carcinogenesis. This review summarises the genetic and pathological alterations in hereditary CRC syndromes.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/genética , Síndrome de Peutz-Jeghers/genética , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Mutação em Linhagem Germinativa , Humanos , Polipose Intestinal/genética , Polipose Intestinal/patologia , Síndromes Neoplásicas Hereditárias/patologia , Síndrome de Peutz-Jeghers/patologia
12.
J Gastrointest Oncol ; 7(Suppl 1): S44-54, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27034812

RESUMO

The gastrointestinal (GI) and cutaneous systems are closely linked in origin. Skin manifestations are frequently seen as a part of different GI syndromes. Gastroenterologists play an important role in recognizing the symptoms, patient workup and arriving at appropriate diagnoses, often in consultation with dermatologists. This review discusses the diseases with both cutaneous and intestinal involvement. Hereditary polyposis GI cancers, hereditary nonpolyposis colorectal cancers (CRCs), hamartomatous disorders, and inflammatory bowel disease (IBD) are reviewed with emphasis on the genetic basis, diagnostic, histologic findings, screening modalities, and therapeutic options.

13.
Clin Colon Rectal Surg ; 21(4): 263-72, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20011437

RESUMO

Familial colorectal adenocarcinoma (CRC) accounts for approximately 15 to 20% of CRC. Of these, hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) represent the most common hereditary syndromes associated with CRC, followed by other less common diseases including juvenile polyposis (JP) and Peutz-Jeghers syndrome (PJS). Extracolonic manifestations are common in each of these syndromes having significant implications for surveillance and management in at-risk individuals. The authors review the most common and clinically relevant extracolonic manifestations for each of these syndromes focusing on incidence, presentation, genotype/phenotype correlations, and management (including surveillance) strategies.

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