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1.
Oncologist ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823035

RESUMO

BACKGROUND: No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget's disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD. METHODS: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period. RESULTS: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated. CONCLUSION: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).

2.
Gan To Kagaku Ryoho ; 50(13): 1479-1481, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303314

RESUMO

We report the rare case of an 89-year-old female with axillary lymph node recurrence after curative surgery for transverse colon cancer who had undergone right hemicolectomy with D3 lymphadenectomy with an uneventful postoperative course. Pathological examination confirmed the tumor's status as tub2>sig, T4aN3M0, and pStage Ⅲc, and signet-ring cell carcinoma was remarkably found in the metastatic lymph node. Genetic testing revealed wild-type RAS, a BRAF mutation, and a high MSI. After 9 months of follow-up without adjuvant chemotherapy, CEA increased sharply to 41.3 ng/mL by 9 months postoperatively, and CT showed nodules in the right axilla, adrenal gland, and retroperitoneum. PET-CT showed abnormal fluorodeoxyglucose uptake in the same regions. A core needle biopsy of the axillary lymph node revealed signet-ring cell carcinoma, which was diagnosed as a recurrence of transverse colon cancer. Although we suggested chemotherapy due to the unresectable recurrence of colorectal cancer, she preferred to receive supportive care instead. Three months after the recurrence was diagnosed, CEA increased to 248.4 ng/mL, and CT showed enlargement of the axillary lesion and a new lesion in the hilum of the lung.


Assuntos
Carcinoma de Células em Anel de Sinete , Colo Transverso , Neoplasias do Colo , Feminino , Humanos , Idoso de 80 Anos ou mais , Colo Transverso/cirurgia , Colo Transverso/patologia , Axila/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Metástase Linfática/patologia , Linfonodos/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Excisão de Linfonodo , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Carcinoma de Células em Anel de Sinete/cirurgia
3.
Clin Exp Dermatol ; 47(12): 2277-2280, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35875892

RESUMO

Here we present a patient with cutaneous eyelid melanoma patient with lacrimal sac metastasis. Clinicopathological findings in this case support the theory that lacrimal fluid can be a metastatic pathway for tumour cells. Dermatologists should be aware of the possibility that cutaneous eyelid melanoma may involve the nasolacrimal system and should examine it during the perioperative period and in postoperative follow-up.


Assuntos
Neoplasias Palpebrais , Doenças do Aparelho Lacrimal , Melanoma , Ducto Nasolacrimal , Neoplasias Cutâneas , Humanos , Ducto Nasolacrimal/patologia , Ducto Nasolacrimal/cirurgia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Pálpebras , Neoplasias Palpebrais/patologia , Doenças do Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/cirurgia , Melanoma Maligno Cutâneo
4.
Endocr J ; 69(2): 139-154, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34526426

RESUMO

The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December 2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japanese pathologists and translated into English to introduce the Japanese diagnostic standard to foreign countries. In this edition of the GRDTC, the histopathological classification and descriptions differ in some respects from those of the fourth edition of the World Health Organization (WHO) classification as revised in 2017. For example, the GRDTC does not adopt the concept of borderline lesions (FT-UMP, WDT-UMP, and NIFTP) of the WHO, taking into consideration the popular histological criteria accepted by Japanese pathologists. The cytological reporting system of the GRDTC was partly modified from the Bethesda system in 2015. It has an additional cyst fluid category separated from the unsatisfactory category that has been demonstrated to be useful in Japan. This translated edition makes it easy to submit Japanese clinicopathological studies of thyroid tumors in an international journal. We also wish to contribute to the improvement, standardization, and globalization of the pathological diagnosis of thyroid tumors.


Assuntos
Adenocarcinoma Folicular , Procedimentos Cirúrgicos Endócrinos , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/patologia , Humanos , Japão , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
5.
BMC Surg ; 21(1): 13, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407379

RESUMO

BACKGROUND: Pheochromocytoma is a catecholamine-secreting tumour that leads to various symptoms. Haemoptysis is rarely caused by a pheochromocytoma occurring outside the bronchus or thoracic cavity. Here, we report the case of an extra-adrenal abdominal pheochromocytoma initially manifesting as haemoptysis/dyspnoea during exercise without classic symptoms. CASE PRESENTATION: A 22-year-old man with a history of severe dyspnoea experienced difficulties in breathing following a marathon owing to haemoptysis that required ventilator management 1 year before presentation. His father had undergone surgery for ectopic pheochromocytoma. Computed tomography (CT) revealed a 30-mm tumour between the inferior vena cava and pancreatic head while urinalysis revealed abnormally high noradrenaline levels. He was clinically diagnosed with an extra-adrenal abdominal ectopic pheochromocytoma. After controlling blood pressure, surgery was performed, and the tumour was successfully removed. Histopathology revealed chromogranin A (+), synaptophysin (+), S100 protein (+), and MIB-1 index of 1%. Therefore, the patient was finally diagnosed with extra-adrenal abdominal ectopic pheochromocytoma. CONCLUSIONS: Haemoptysis is a rare manifestation of abdominal ectopic paraganglioma. Prompt consideration of pheochromocytoma/paraganglioma when patients experience haemoptysis without any other possible aetiology may prevent inappropriate diagnosis and treatment and ultimately fatalities.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hemoptise , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Hemoptise/etiologia , Humanos , Masculino , Recidiva Local de Neoplasia , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
Gastric Cancer ; 23(3): 418-425, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31667687

RESUMO

BACKGROUND: To safely perform minimized gastrectomy based on sentinel node (SN) concept for early gastric cancer patients, intraoperative diagnostic accuracy is indispensable. This study aimed to evaluate the clinical utility of the one-step nucleic acid amplification (OSNA) assay in the intraoperative diagnosis of SN metastasis in early gastric cancer patients compared with that of histopathological examination. METHODS: We conducted a prospective study using the OSNA assay for 43 patients with cT1N0M0 gastric cancer undergoing gastrectomy with SN mapping. All the SNs and selected non-SNs were examined by routine histopathological diagnosis, and the OSNA assay. RESULTS: We performed permanent histopathology (PH) in 1732 lymph nodes (LNs) (286 SNs and 1446 non-SNs) obtained from 43 patients. We also evaluated 439 LNs (286 SNs and 153 non-SNs) with the OSNA assay in addition to PH. Intraoperative histopathology (IH) was performed in 214 LNs (213 SNs and 1 non-SN). PH revealed LN metastasis in 6 patients (14%), all of whom showed positive SNs by PH. The diagnostic accuracy to predict the LN status based on the SN concept by histological examination was 100%. The concordance rate between the OSNA assay and the PH and IH were 0.970 and 0.981 respectively. Discordant results between PH and OSNA assay were observed in 13 LNs. The sensitivity and specificity of the OSNA assay compared with those of PH were 0.636, and 0.988, and compared with those of IH were 0.800, and 0.995. CONCLUSION: Our results suggest that the OSNA assay is a useful and convenient tool for the intraoperative detection of SN metastasis in early gastric cancer patients.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Técnicas de Amplificação de Ácido Nucleico/métodos , Linfonodo Sentinela/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
7.
Rinsho Ketsueki ; 61(10): 1502-1507, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33162448

RESUMO

An 18-year-old woman presented with fever and liver dysfunction. Computed tomography showed lymphadenopathy, hepatosplenomegaly, and vascular lesions such as aneurysms and irregularities at multiple arteries, including coronary arteries. Based on the high copy number of Epstein-Barr virus (EBV)-DNA in the peripheral blood, EBV-infected CD4+T cells, and the proliferation of EBER-positive cells in the bone marrow, chronic active EBV infection (CAEBV) was diagnosed. Although the fever and liver dysfunction improved as a result of the initial immunosuppressive therapy and multiagent chemotherapy, EBV-DNA remained high. Moreover, she experienced repeated episodes of angina pectoris due to coronary arterial lesions. Therefore, cord blood transplantation was performed after reduced-intensity conditioning. EBV-DNA decreased quickly after initiating the conditioning and became undetectable at day 7 after the transplant. Vascular lesions did not progress after the transplant, and the patient's angina pectoris resolved. At 2.5 years after the transplant, she is alive without disease recurrence. The prognosis of CAEBV with vascular lesions is especially poor. Although the indication for allogeneic hematopoietic stem cell transplantation (HSCT) is difficult to determine in such cases, the clinical course of our case suggests that allogenic HSCT could be safely performed under appropriate management and could successfully control not only CAEBV but also vascular lesions.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Adolescente , Doença Crônica , Infecções por Vírus Epstein-Barr/complicações , Feminino , Humanos , Condicionamento Pré-Transplante
8.
Ann Surg Oncol ; 26(9): 2874-2881, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31209674

RESUMO

BACKGROUND: Recent advances in endoscopic examinations have resulted in the detection of a larger number of early esophageal cancers; however, there have been many cases with clinically negative but pathologically positive lymph node metastasis (LNM). In this study, we aimed to evaluate the discrepancy between the clinical and pathological diagnoses of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer, and assess LNM size in these patients to clarify the presence of LNM that cannot be detected with current modalities. METHODS: This study included 50 patients who underwent surgery for cT1a-MM/cT1b N0M0 thoracic esophageal squamous cell carcinoma between January 2012 and November 2016 at our institution. The maximum size of involved LNs and metastatic nests were measured, and the distribution of LNM was investigated. RESULTS: Of the 50 patients, 13 (26%) had LNM on pathological examination. Lymphatic invasion was significantly more frequent in the LNM-positive group than in the LNM-negative group (p = 0.005). The median sizes of 28 involved LNs and metastatic nests were 3 and 1.6 mm, respectively. Of these LNs, 20 (71%) were classified as micrometastases (≤ 2 mm). The involved nodes were distributed across three fields. CONCLUSIONS: There was a discrepancy between the clinical and final pathological findings of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer. The detection of involved nodes with current modalities in these patients was difficult because of the small size of LNM. Therefore, continued strong consideration for extended LN dissection is necessary in these patients to ensure appropriate diagnosis and treatment.


Assuntos
Adenocarcinoma/secundário , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Linfonodos/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Idoso , Diagnóstico Diferencial , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Ultrassonografia
9.
Breast J ; 25(1): 9-15, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29687661

RESUMO

The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P < .001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P < .001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P = .0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Povo Asiático , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
10.
BMC Nephrol ; 20(1): 120, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943904

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) in transplant recipients are very rare and only a handful of cases have been reported to date. Here we present the first known case of a huge GIST in a kidney transplant recipient with perforation of small intestine. CASE PRESENTATION: A 64-year-old male presented at our hospital with right colic pain; he had received an ABO incompatible kidney transplant 6 years earlier and was treated with cyclosporine, mycophenolate mofetil, and methylprednisolone. Radiological evaluation revealed a huge (11 cm in diameter) solitary tumor at the small intestine without distant metastasis. The small intestinal wall at the tumor location was perforated one week after diagnosis and the patient underwent emergency surgery. The pathological findings were compatible with GIST and the tumor consisted of spindle cells with positive staining for KIT, CD34, and DOG1 and negative or weak staining for desmin and S-100 protein. A mutation in exon 11 of the c-kit gene was also detected. Cyclosporine was withdrawn and imatinib mesylate (400 mg daily) was introduced. However, thereafter, we needed to decrease the dose at 300 mg daily due to severe hyponatremia. Reduced imatinib treatment was well tolerated and recurrence was not observed for 18 months after surgery. CONCLUSIONS: The occurrence of GISTs in transplant patients is rare, and huge GISTs should be resected immediately after diagnosis because gastrointestinal tract at the tumor site could be perforated. Imatinib treatment is feasible in transplant recipients under immunosuppression, although immunosuppressive drugs metabolized by CYP3A4 should be used at a reduced dosage or withdrawn.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Perfuração Intestinal , Transplante de Rim , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Hospedeiro Imunocomprometido , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Resultado do Tratamento , Carga Tumoral
11.
World J Surg Oncol ; 17(1): 32, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760272

RESUMO

BACKGROUND: Endoscopic resection (ER) has come to be recognized as a standard treatment for early gastric cancer (EGC). While its adoption is expanding, ER remains restricted to cases of EGC without lymph node metastasis for the treatment of local resection. On the other hand, histopathological analyses of surgically resected specimens of EGC have revealed the presence of lymph node (LN) metastasis in some cases of mucosal gastric cancer (MGC) and undifferentiated MGC (UD-MGC) is considered to have higher risk of nodal metastases than differentiated MGC (D-MGC). To evaluate the risk factors for LN metastasis in MGC, we investigated the characteristics of UD-MGC associated with LN metastasis. METHODS: Among all UD-MGC patients who underwent surgery as initial treatment, between January 2000 and March 2016, we reviewed the clinicopathological data, including the preoperative endoscopic findings and histopathological findings in the resected specimens, of the 11 UD-MGC patients who were identified as having lymph node metastasis. Furthermore, in comparison with cases without lymph node metastasis, we examined the possibility of expansion of the indication for local treatment. RESULTS: In most of the cases of UD-MGC with LN metastasis, the lesions were relatively large (> 20 mm in diameter) and of the clearly depressed type with faded color and apparent border, and histopathology revealed a high percentage of cases with lymphatic invasion and a predominance of signet ring cell carcinomas. No cases with LN metastasis without depressed macroscopic type nor signet ring cell carcinoma component existed. A degree of invasion of lamina propria (LP) or muscularis mucosae (MM) had same relation to the risk of LN metastasis. CONCLUSIONS: In this study, none of the cases of undifferentiated-type mucosal cancer (UD-MGC) with LN metastasis satisfied the current adoption criteria for ER. We suggested significant risk factors for LN metastasis in UD-MGC cases as depressed tumor type, presence of a signet ring cell carcinoma component, presence of lymphatic tumor invasion, and a large tumor size. More detailed analyses of the endoscopic and histopathological findings may allow further risk classification for LN metastasis in cases of UD-MGC.


Assuntos
Carcinoma de Células em Anel de Sinete/patologia , Ressecção Endoscópica de Mucosa/métodos , Gastrectomia/métodos , Gastroscopia/métodos , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/cirurgia , Diferenciação Celular , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia
12.
Dig Endosc ; 31(6): 706-711, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31278777

RESUMO

Despite the rarity of colorectal poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig), they are more frequent in patients with ulcerative colitis (UC). However, little is known about these components of early colitis-associated cancer due to the difficulty of detection at an early stage. Here, we reviewed colitis-associated high-grade dysplasia/cancer with Por/Sig components within the submucosa among 103 lesions of 79 UC patients who presented between 1997 and 2017. In total, one Sig in situ, three intramucosal and two submucosal carcinomas (8.7%) were identified among 69 lesions within the submucosa. Depressed appearance, loss of crypt architecture and amorphous surface pattern suggested the presence of Por/Sig, rather than submucosal infiltration. All lesions were located in the rectosigmoid colon and included high-grade dysplasia. While the surrounding noncancerous mucosa expressed E-cadherin and MUC5AC, the expression of E-cadherin was reduced and the expression of MUC5AC was negative in all of the carcinomas except for the Sig in situ. The gastric type metaplasia associated with altered MUC5AC profiles may be a sign of the stepwise accumulation of molecular alterations, including TP53 defects and a reduced expression level of E-cadherin.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Colite Ulcerativa/complicações , Colo/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Estadiamento de Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/etiologia , Colite Ulcerativa/diagnóstico , Neoplasias Colorretais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Biochem Biophys Res Commun ; 497(2): 783-789, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29470983

RESUMO

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.


Assuntos
Técnicas de Cultura de Órgãos/métodos , Organoides/citologia , Glândula Tireoide/citologia , Animais , Feminino , GTP Fosfo-Hidrolases/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Organoides/patologia , Organoides/fisiologia , Mutação Puntual , Glândula Tireoide/patologia , Glândula Tireoide/fisiologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Proteína Supressora de Tumor p53/genética
14.
Gastrointest Endosc ; 87(2): 450-456, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28890117

RESUMO

BACKGROUND AND AIMS: During endoscopic full-thickness resection (EFTR) for cancers, whether exposure of the lumen to the abdominal cavity during the procedure is acceptable is controversial because of the potential risk of tumor cell seeding. To assess the possibility of transplantation as a result of contact with tumor cells during the procedure, we prospectively investigated the ability of cancer cells to be detached by touching the tumor surface. METHODS: In 48 patients with a single early gastric cancer resected by endoscopic submucosal dissection, stamp cytology was performed by touching the surface of the specimens to glass slides. Samples were obtained from cancerous and noncancerous areas, constituting the study and control groups, respectively. The detection rate of malignant class IV or V (C-IV/C-V) samples was investigated with Papanicolaou staining. The rate of CD44v9-positive cases, a cancer stem cell marker, was assessed in C-IV/C-V samples with immunohistochemical staining. RESULTS: Detection rates of C-IV/C-V samples in the cancerous group (53/192 slides, 27.6%) differed significantly from those of the C-IV/C-V samples in the noncancerous group (0/96 slides, 0%). Among the 53 slides of C-IV/C-V samples in the cancerous group, CD44v9 cells were expressed in 18 slides (34.0%). CONCLUSIONS: These data suggest that cancer cells, including cancer stem cells, in early gastric cancers are easily detached via contact with the tumor surface. In EFTR, a nonexposure approach is recommended to avoid the risk of iatrogenic cancer cell seeding via contact with and transplantation of cancer cells.


Assuntos
Gastroscopia/efeitos adversos , Inoculação de Neoplasia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Peritoneais/etiologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Teste de Papanicolaou , Neoplasias Gástricas/metabolismo
16.
Hepatol Res ; 48(3): E360-E366, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28626871

RESUMO

Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

17.
Jpn J Clin Oncol ; 47(4): 334-341, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28064204

RESUMO

OBJECTIVE: Myxofibrosarcoma has high frequency of local recurrence after surgery. To determine an optimal treatment for recurrent tumors, clinical features of recurrent cases should be characterized. METHODS: We performed a retrospective analysis of 30 patients with recurrent myxofibrosarcoma who underwent surgery between 1999 and 2008. RESULTS: A negative margin after surgery was achieved in only 12 patients (40.0%). The 5-year re-recurrence free-survival rate was 31.7%. The 5-year re-recurrence free survival for those with positive histological margin and those with negative margin were 9.8% and 62.3%, respectively, which indicated that a positive margin was the significant predictor of poor prognosis (P = 0.006). In 21 patients with recurrent myxofibrosarcoma in the extremities, 10 patients (47.6%) ultimately underwent amputation in the follow-up period and the 5-year amputation-free survival rate was 62.5%. The 5-year metastasis-free survival rates and the 5-year overall survival rates were 84.8% and 83.6%, respectively. CONCLUSIONS: In this study, the majority of recurrent cases could not achieve negative margins; notably, a positive margin is a significant poor prognostic indicator of local re-recurrence in patients with recurrent myxofibrosarcoma. To control local recurrence of myxofibrosarcoma was extremely difficult and amputation is often needed in the extremity cases.


Assuntos
Fibroma/cirurgia , Salvamento de Membro/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibroma/mortalidade , Fibroma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Int J Gynecol Cancer ; 27(7): 1517-1524, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28562470

RESUMO

OBJECTIVE: Sentinel nodes (SNs) have been observed in several reports from Japan and overseas in cases with endometrial cancer; however, no consensus has been reached regarding the types of tracers or the method of their injection. A combination of the radioisotope (RI) and dye method is considered to be desirable. We assessed SN mapping using either dye or near-infrared fluorescence imaging to clarify a suitable method in cases of endometrial cancer. METHODS: Patients were enrolled from 92 patients diagnosed with endometrial cancer and having no extrauterine metastasis by the preoperative imaging between 2009 and 2014 at our institution. To identify the SNs, we performed 3 methods using either dye or fluorescence solutions in conjunction with a RI method. In the dye method, we injected indocyanine green in the uterine subserosa, visually identifying SNs as stained green. In the fluorescence method, a dilute indocyanine green solution (0.5 mg, fluorescence A or 0.25 mg, fluorescence B, each per 10 mL of solvent) was injected and the SN identified by the HyperEye Medical System. RESULTS: The SN detection rates were 100%, 100%, and 96% using dye and fluorescence A or B solution, respectively. Pelvic SNs were detected by the 3 methods in 98%, 100%, and 96% of cases and para-aortic SNs in 65%, 88%, and 74%, respectively. Fluorescence A solution was somewhat better than dye in detecting para-aortic SNs, although not significantly so (P = 0.07). The sensitivity and negative predictive values for detecting SNs with metastases with the dye method were 92% and 98% compared with 100% and 100%, respectively, for both fluorescence solutions. CONCLUSIONS: Although both dye and fluorescence methods performed well, no method perfectly identified para-aortic SNs. The concomitant use of the RI method is required to detect para-aortic SNs.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Imagem Óptica/métodos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
19.
Endocr J ; 64(11): 1087-1097, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-28867693

RESUMO

Thyroid peroxidase (TPO) deficiency, caused by biallelic TPO mutations, is a well-established genetic form of congenital hypothyroidism (CH). More than 100 patients have been published, and the patients have been diagnosed mostly in the frame of newborn screening (NBS) programs. Correlation between clinical phenotypes and TPO activity remains unclear. Here, we report clinical and molecular findings of two unrelated TPO mutation-carrying mildly hypothyroid patients. The two patients were born at term after an uneventful pregnancy and delivery, and were NBS negative. They sought medical attention due to goiter at age 8 years. Evaluation of the thyroid showed mild elevation of serum TSH levels, normal or slightly low serum T4 levels, high serum T3 to T4 molar ratio, high serum thyroglobulin levels, and high thyroidal 123I uptake. We performed next-generation sequencing-based genetic screening, and found that one patient was compound heterozygous for two novel TPO mutations (p.Asp224del; c.820-2A>G), and the other was homozygous for a previously known mutation (p.Trp527Cys). In vitro functional analyses using HEK293 cells showed that the two amino acid-altering mutations (p.Asp224del and p.Trp527Cys) caused partial loss of the enzymatic activity. In conclusion, we report that TPO mutations with residual activity are associated with mild TPO deficiency, which is clinically characterized by marked goiter, mild TSH elevation, high serum T3 to T4 molar ratio, and high serum thyroglobulin levels. Our findings illuminate the hitherto under-recognized correlation between clinical phenotypes and residual enzymatic activity among patients with TPO deficiency.


Assuntos
Autoantígenos/genética , Autoantígenos/metabolismo , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/metabolismo , Iodeto Peroxidase/deficiência , Proteínas de Ligação ao Ferro/genética , Proteínas de Ligação ao Ferro/metabolismo , Mutação , Criança , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/patologia , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Testes Genéticos , Células HEK293 , Humanos , Recém-Nascido , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Masculino , Triagem Neonatal , Linhagem , Fenótipo , Índice de Gravidade de Doença
20.
J Obstet Gynaecol Res ; 43(2): 416-420, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27928858

RESUMO

Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46-year-old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer history met the revised Bethesda criteria, we examined microsatellite instability and the result was negative, but loss of the MSH6 expression was detected by immunohistochemistry. Genetic testing revealed deleterious germline mutation of MSH6, which was compatible with Lynch syndrome. To our knowledge, this is the first case of endometrial carcinoma of the LUS with MSH6 germline mutation.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Neoplasias Uterinas/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade
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