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1.
Cytopathology ; 34(2): 106-112, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336883

RESUMO

OBJECTIVE: The Paris System for Reporting Urinary Cytology (TPS) is a well-known urinary diagnostic model; however, occasional false-positives are a problem. To address this issue, we developed an improved algorithm (IA), based on additional cytological features, for TPS diagnosis. METHODS: Cytological features were evaluated in 29 hard-to-classify cases, including 22 malignant cases and seven benign cases, using image analysis. The optimal IA was determined using the area under the receiver operating characteristic curve as an index. Re-evaluation was performed by applying measured values to the TPS and IA algorithms. RESULTS: Using TPS, 12 of the 22 malignant cases were reassigned to a more appropriate category, and the remaining 10 malignant cases remained hard-to-classify. Two of the seven benign cases were classified as suspicious for high-grade urothelial carcinoma, and the remaining five benign cases remained in the original category. The IA, which included nuclear area as a parameter, showed the same diagnostic sensitivity as TPS, and three of the seven benign cases were reassessed as negative. Thus, the positive and negative predictive values of the IA were higher than those of TPS (84.6% and 100% vs 75.9% and 0%). CONCLUSIONS: The newly developed IA is a practical algorithm with which to address the limitations of TPS and thus may contribute to improved diagnostic accuracy.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Citologia , Urotélio/patologia , Citodiagnóstico/métodos , Urina
2.
Acta Med Okayama ; 77(1): 57-64, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36849146

RESUMO

Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years.


Assuntos
Melanose , Caracteres Sexuais , Feminino , Humanos , Masculino , Melanose/diagnóstico , Colonoscopia , Antraquinonas , Progressão da Doença
3.
Gan To Kagaku Ryoho ; 50(6): 727-729, 2023 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-37317609

RESUMO

Appendiceal goblet cell adenocarcinoma(AGCA)is a newly designated pathological term adopted in the 5th edition of the WHO classification. It is synonymous with goblet cell carcinoid, which was previously categorized as a part of appendiceal carcinoid. However, since 2018, it has been classified as a subtype of adenocarcinoma. We have experienced 3 cases of this relatively rare tumor, of which 2 were initially diagnosed with acute appendicitis and were diagnosed with AGCA by pathological examination after an emergency appendectomy. Each of them underwent additional ileocolic resection with lymph node dissection as the second surgery. In the 3rd case, an appendiceal tumor was detected during preoperative examinations for an ovarian tumor. Staging laparoscopy revealed comorbid peritoneal dissemination, and only the appendix and right ovary were removed in the consecutive surgery. The ovarian tumor was pathologically diagnosed as a metastasis of AGCA. In this case, the introduction of oxaliplatin-based systemic chemotherapy after surgery achieved a complete response after more than 2 years. Although no recurrence has been observed in all 3 cases to date, AGCA is considered highly malignant compared to conventional appendiceal carcinoids. Therefore, it is crucial to practice multidisciplinary treatments, including sufficient radical surgery based on a precise diagnosis of AGCA, as is performed for advanced colorectal cancer.


Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Tumor Carcinoide , Neoplasias Ovarianas , Feminino , Humanos , Células Caliciformes , Tumor Carcinoide/cirurgia , Adenocarcinoma/cirurgia , Neoplasias do Apêndice/cirurgia
4.
BMC Gastroenterol ; 22(1): 319, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35764928

RESUMO

BACKGROUND: To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis. METHODS: We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared. RESULTS: Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004-3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438-12.63; p < 0.001), and subjective symptoms (HR 1.986; 95% CI 1.037-3.803; p = 0.0386) as independent risk factors for overall survival. In the symptomatic group, the mean time from symptom onset to diagnosis was 2.4 ± 4.3 months. The incidence of subjective symptoms differed by clinical stage, and the prognosis of patients with swallowing-related symptoms was significantly worse than that of patients with other symptoms. CONCLUSION: The results of this study suggest that screening by upper gastrointestinal endoscopy, independent of subjective symptoms (especially swallowing-related symptoms), may play an important role in the early detection and improvement of prognosis of ESCC, although further validation in a large prospective study is needed.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Humanos , Prognóstico , Estudos Retrospectivos
5.
Tohoku J Exp Med ; 258(2): 121-128, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35922907

RESUMO

Vasohibin-2 (VASH2) is a gene that promotes local angiogenesis. The tubulin carboxypeptidase activity of vasohibin causes detyrosination of alpha-tubulin and may play an important role in the regulation of various phenomena. Pathological and therapeutic angiogenesis are involved in atherosclerotic lesions. This study aimed to investigate whether the expression of VASH2 is associated with peripheral artery disease (PAD) in relation to angiogenesis, tubulin detyrosination, and severity of atherosclerotic lesions. An analysis of femoral and tibial arteries obtained from 86 patients with PAD or abdominal aortic aneurysm (AAA) was performed. The expressions of cluster of differentiation 31, VASH1, VASH2, and detyrosinated alpha-tubulin (DT-tubulin) were examined by immunohistochemistry, and their association with PAD was analyzed. The counts of VASH2 in the tunica media and adventitia in the tibial artery were significantly higher than those in the femoral artery in the PAD (P = 0.005 and P = 0.008, respectively) and AAA (P = 0.002 and P < 0.001, respectively) groups. In the tunica media and adventitia, VASH2 was significantly correlated with DT-tubulin. There was no significant difference in the expression of VASH2 and DT-tubulin in medial smooth muscle cells (McNemar test, P > 0.999). This study revealed the possible involvements of VASH2 in atherosclerosis by two methods-one maybe related to the progression of atherosclerosis by inducing angiogenesis and the second may be related to the decrease in arterial elasticity by increasing DT-tubulin in medial smooth muscle cells.


Assuntos
Proteínas Angiogênicas , Doença Arterial Periférica , Tubulina (Proteína) , Proteínas Angiogênicas/genética , Proteínas Angiogênicas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Humanos , Tubulina (Proteína)/metabolismo
6.
Dig Endosc ; 34(4): 700-713, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34674318

RESUMO

Autoimmune gastritis (AIG) is a special type of chronic gastritis characterized by autoimmune disorders caused by cellular immunity, resulting in the destruction of parietal cells and production of antiparietal cell antibodies. Endoscopic findings of AIG are mainly characterized by corpus-dominant advanced atrophy. The antral area is generally considered to have no or mild atrophy; however, there are cases wherein the gastric mucosa is red or faded due to past infection with Helicobacter pylori or bile reflux. Currently, there are no diagnostic criteria for AIG in Japan, and it is important to make a diagnosis based on the presence of gastric autoantibodies and characteristic endoscopic and histological findings. AIG is associated with gastric cancer, neuroendocrine tumors (NETs), and other autoimmune diseases, such as thyroid diseases, anemia, and neurological symptoms due to impaired absorption of iron and vitamin B12 , and thus requires systemic treatment. The significance of diagnosing AIG is to include patients as a high-risk group for the development of gastric cancer and gastric NETs, provide an opportunity to detect autoimmune endocrine diseases, and initiate therapeutic intervention before anemia and neurological symptoms develop. It is important to pay close attention to the occurrence of AIG comorbidities not only at the time of AIG diagnosis but also during follow-up after detection.


Assuntos
Doenças Autoimunes , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Atrofia/complicações , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Gastrite/diagnóstico , Gastrite/patologia , Infecções por Helicobacter/patologia , Humanos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico
7.
J Clin Biochem Nutr ; 71(2): 165-171, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36213792

RESUMO

The severity and distribution of melanosis coli differ among individuals, and the related factors remain unknown. Additionally, their clinical implications have not been sufficiently demon-strated. Thus, we aimed to detect clinical factors related to the severity and range of melanosis coli and elucidate the associations between the grade, location, and detection rate of colorectal neoplasms. Colonoscopy cases performed at our institution from January 2011 to February 2021 were included. Melanosis coli was classified into mild and severe grades. Clinical characteristics and neoplasm detection rates were compared between the mild and severe MC groups and between the right-sided and whole-colon melanosis coli groups. Overall, 236 MC (mild, n = 143; severe, n = 93) cases, of which 50 were right-sided, 5 were left-sided, and 181 were whole-colon melanosis coli cases, were enrolled. The proportion of anthranoid users was higher in the severe melanosis coli group than in the mild melanosis coli group. The adenoma detection rate was higher in the severe melanosis coli and whole-colon melanosis coli groups. The prevalence of neoplasms measuring 5-9 mm and >9 mm was higher in the severe melanosis coli group (p<0.01 and p = 0.04). Severe melanosis coli due to anthranoid usage is associated with colorectal adenoma development.

8.
Int J Colorectal Dis ; 36(10): 2177-2188, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34156546

RESUMO

PURPOSE: The association between melanosis coli (MC) and colorectal neoplasms remains unclear. Thus, we primarily aimed to clarify the epidemiology of MC in the Japanese population, identify the relationship between the use of anthranoids and MC, and determine the prevalence of detected intestinal lesions in patients with MC. We subsequently conducted a meta-analysis of published data, including our results, to summarize the influence of MC on the prevalence of colonic neoplasms. METHODS: We conducted a retrospective survey in Japan to investigate the effects of MC on intestinal disorders. The prevalence of colorectal neoplasms and ileal ulcers was evaluated by colonoscopy, and the clinical characteristics of the participants were investigated using an electronic database. Odds ratios for colorectal neoplasms were calculated. We also performed a meta-analysis using Review Manager to reveal the comprehensive relationship between MC and colorectal neoplasms. RESULTS: We enrolled 690 Japanese participants in the primary study. The prevalence of regular anthranoid use was significantly higher in the MC group than in the control group (50.9% vs. 6.5%, p < 0.01). Hyperplastic/inflammatory polyps and adenomas were more frequently detected in the MC group than in the control group. In a meta-analysis of five studies, a significantly higher prevalence of hyperplastic/inflammatory polyps and adenomas was reported in the MC group than in the control group, while the incidence of adenocarcinoma was not significantly different between the two groups. CONCLUSION: Although hyperplastic polyps and adenomas were more frequently detected in MC patients, MC was not associated with an elevated risk of colorectal cancer.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Melanose , Neoplasias Colorretais/epidemiologia , Humanos , Japão/epidemiologia , Melanose/epidemiologia , Estudos Retrospectivos
9.
Gan To Kagaku Ryoho ; 48(7): 967-969, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267038

RESUMO

Medullary carcinoma of the colorectum is a relatively new histological subtype that was first described in the eighth edition of the Japanese classification of colorectal, appendiceal, and anal carcinoma. In our institution, only 3 cases of medullary carcinoma have been diagnosed since 2013. Case #1 was a 93-year-old woman with type 1 ascending colon cancer; she received a right hemicolectomy. The tumor invaded the subserosal layer, but no lymph nodal metastasis was observed. Case #2 was a 91-year-old woman with obstructive ascending colon cancer. After intracolonic decompression using the transnasal ileus tube, she received a right hemicolectomy. This tumor also extended into the subserosal layer without lymph nodal metastasis. Case #3 was a 65-year-old woman with a family history of cancers; she received a right hemicolectomy for cecal cancer with an aberrant elevation of serum tumor markers such as CEA and CA19-9. The tumor invaded the subserosal layer with regional lymph nodal metastases. Notably, these 3 cases were females who had right-sided tumors and all showed diminished expressions of MLH1 and PMS2 mismatch repair-associated genes, together with epidemiological characteristics of medullary carcinoma. Herein, we report their pathological features along with the corresponding literature review.


Assuntos
Adenocarcinoma , Carcinoma Medular , Neoplasias do Colo , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/cirurgia , Reparo de Erro de Pareamento de DNA , Feminino , Humanos
10.
BMC Endocr Disord ; 20(1): 120, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758269

RESUMO

BACKGROUND: Basedow's disease and Hashimoto's thyroiditis are autoimmune thyroid disorders and usually diagnosed with elevation of serum autoimmune antibodies. Thyrotropin receptor antibodies (TRAb) and/or thyroid-stimulating antibody (TSAb) are usually used for diagnosis of Basedow's disease, and thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb) are for diagnosis of Hashimoto's thyroiditis. However, it is difficult to diagnose a subject as Basedow's disease with associated features of Hashimoto's thyroiditis only with elevation of such autoimmune antibodies. CASE PRESENTATION: A 44-year-old woman with 5-year history of Basedow's disease underwent a total thyroidectomy. She did not have a goiter. TRAb, TSAb, TPOAg and TgAb were all positive before a total thyroidectomy. In histopathological macroscopic examination, diffuse hyperplasia of the thyroid gland was observed. Furthermore, in histopathological microscopic examination, both characteristics of Basedow's disease and Hashimoto's thyroiditis were observed. After a total thyroidectomy, titers of all thyroid-associated autoimmune antibodies were markedly reduced. CONCLUSION: Herein, we report a subject with Basedow's disease without a goiter whose TPOAb and TgAb were relatively high at the onset of Basedow's disease. In addition, interestingly, the histopathological findings of this subject showed direct signs of Basedow's disease and Hashimoto's thyroiditis in the same thyroid gland. Considering from such findings, she seemed to have Basedow's disease with associated features of Hashimoto's thyroiditis. In conclusion, we should bear in mind the possibility of Basedow's disease with associated features of Hashimoto's thyroiditis in subjects with Basedow's disease, particularly when TPOAb and TgAb as well as TRAb and TSAb are positive.


Assuntos
Doença de Graves/sangue , Doença de Graves/diagnóstico , Doença de Hashimoto/sangue , Adulto , Autoanticorpos/sangue , Biópsia , Diagnóstico Diferencial , Feminino , Doença de Graves/patologia , Doença de Graves/cirurgia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/patologia , Doença de Hashimoto/cirurgia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Tireoidectomia
11.
World J Surg Oncol ; 13: 273, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26376726

RESUMO

An 85-year-old Japanese man with a complaint of exertional dyspnea was admitted to our hospital. Sixty-three years prior to admission at our hospital, he handled asbestos for 2 years in a factory. His chest computed tomography showed a massive pericardial effusion leading to cardiac tamponade and right pleural plaque. After a pericardiocentesis was performed, he recovered from cardiac failure caused by the cardiac tamponade. Pathological examination of the pericardial effusion revealed malignant mesothelial cells. Therefore, he was diagnosed with primary pericardial mesothelioma (PPM) related to asbestos exposure. Although his disease slowly progressed over 18 months, he remained active without any adjuvant treatments such as chemotherapy. Long-term palliation in an aged patient with PPM is rarely obtained using supportive care alone because the prognosis of PPM has been consistently reported to be very poor and almost fatal within a year. Clinical oncologists and thoracic surgeons should be aware of this disease because the accumulation of knowledge on PPM may lead to successful treatment even in aged patients.


Assuntos
Amianto/efeitos adversos , Tamponamento Cardíaco/terapia , Neoplasias Cardíacas/complicações , Mesotelioma/complicações , Cuidados Paliativos , Derrame Pericárdico/terapia , Neoplasias Pleurais/complicações , Idoso de 80 Anos ou mais , Carcinógenos/farmacologia , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/patologia , Neoplasias Cardíacas/patologia , Humanos , Masculino , Mesotelioma/patologia , Derrame Pericárdico/etiologia , Derrame Pericárdico/patologia , Pericardiocentese , Neoplasias Pleurais/patologia , Prognóstico
13.
Hum Cell ; 37(4): 1132-1140, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38829559

RESUMO

Approximately 3-5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months). In this study, we established tumoroids (PDT-LUAD#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALK v3 mutation. PDT-LUAD#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1). Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDT-LUAD#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.


Assuntos
Quinase do Linfoma Anaplásico , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Proteínas de Fusão Oncogênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Transformação Celular Neoplásica/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Crizotinibe/farmacologia , Linhagem Celular Tumoral , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia
14.
Hum Cell ; 37(4): 1194-1204, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38632190

RESUMO

Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production. The tumoroids were derived from the malignant pleural effusion of a patient with lung cancer and have been successfully developed for long-term culture (> 11 months). Karyotyping by fluorescence in situ hybridization using an alpha-satellite probe showed that tumoroids harbored aneuploid karyotypes. Subcutaneous inoculation of PDT-LUAD#99 lung tumoroids into immunodeficient mice resulted in tumor formation, suggesting that the tumoroids were derived from cancer. Xenografts from PDT-LUAD#99 lung tumoroids reproduced the solid adenocarcinoma with mucin production that was observed in the patient's metastatic lymph nodes. Immunoblot analysis showed MUC5AC secretion into the culture supernatant of PDT-LUAD#99 lung tumoroids, which in contradistinction was barely detected in the culture supernatants of NCI-A549 and NCI-H2122 pulmonary adenocarcinoma cells known for their mucin-producing abilities. Here, we established a novel high-mucus-producing lung tumoroids from a solid adenocarcinoma. This preclinical model may be useful for elucidating the pathogenesis of mucus-producing lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Mucina-5AC , Muco , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Muco/metabolismo , Animais , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mucina-5AC/metabolismo , Mucina-5AC/genética , Camundongos , Linhagem Celular Tumoral , Células Tumorais Cultivadas , Masculino , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo
15.
Cancer Lett ; 588: 216816, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38499265

RESUMO

Pulmonary large-cell neuroendocrine carcinoma (LCNEC), a disease with poor prognosis, is classified as pulmonary high-grade neuroendocrine carcinoma, along with small-cell lung cancer. However, given its infrequent occurrence, only a limited number of preclinical models have been established. Here, we established three LCNEC tumoroids for long-term culture. Whole-exome sequencing revealed that these tumoroids inherited genetic mutations from their parental tumors; two were classified as small-cell carcinoma (S-LCNEC) and one as non-small cell carcinoma (N-LCNEC). Xenografts from these tumoroids in immunodeficient mice mimicked the pathology of the parent LCNEC, and one reproduced the mixed-tissue types of combined LCNEC with a component of adenocarcinoma. Drug sensitivity tests using these LCNEC tumoroids enabled the evaluation of therapeutic agent efficacy. Based on translational research, we found that a CDK4/6 inhibitor might be effective for N-LCNEC and that Aurora A kinase inhibitors might be suitable for S-LCNEC or LCNEC with MYC amplification. These results highlight the value of preclinical tumoroid models in understanding the pathogenesis of rare cancers and developing treatments. LCNEC showed a high success rate in tumoroid establishment, indicating its potential application in personalized medicine.


Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Animais , Camundongos , Medicina de Precisão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia
16.
Intern Med ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569909

RESUMO

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

17.
Radiol Case Rep ; 19(3): 1166-1170, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38259698

RESUMO

We report a patient with a mucocele with diffuse wall thickening diagnosed by transabdominal ultrasonography and contrast-enhanced ultrasonography. Transabdominal ultrasonography showed diffuse thickening of the entire appendix wall and an anechoic area that appeared to be fluid collected throughout the appendix lumen. However, the "onion skin sign" was not detected. Contrast-enhanced ultrasonography combined with superb microvascular imaging revealed abundant mucosal blood flow and no abnormal vascular network within the mucosa of the appendix wall. We preoperatively diagnosed a mucocele complicated by acute and chronic appendicitis, and ileocecal resection was performed. Macroscopic and microscopic findings of the resected specimens demonstrated that the appendiceal wall was diffusely thickened, with fibrosis and inflammatory cell infiltration, and that the appendiceal root rumen was narrowed with epithelial hyperplasia. No neoplastic changes were observed. The cause of the appendiceal mucocele was likely fibrosis and stenosis at the root of the appendix due to initial acute appendicitis.

18.
J Cutan Pathol ; 40(3): 317-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23241021

RESUMO

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20-year-old Japanese woman presented with a 10-year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small- to medium-sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band-like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T-cell intracellular antigen (TIA)-1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein-Barr virus (EBV) latent membrane protein 1. An EBV-encoded small non-polyadenylated RNA-1 (EBER-1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígeno CD56/metabolismo , Antígenos CD8/metabolismo , Micose Fungoide , Proteínas de Neoplasias/metabolismo , Neoplasias Cutâneas , Adulto , Feminino , Humanos , Micose Fungoide/metabolismo , Micose Fungoide/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
19.
Breast Cancer ; 30(6): 1041-1053, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37642903

RESUMO

BACKGROUND: B7 homolog 4 (B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes. METHODS: Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor-stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression. RESULTS: B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8; p = 0.021), inflamed TIL pattern (p = 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = - 0.509, p < 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (ρ = - 0.354, p < 0.001). CONCLUSIONS: These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Receptores Androgênicos/metabolismo , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Prognóstico
20.
Thorac Cancer ; 14(21): 2085-2089, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37308179

RESUMO

A 52-year-old female never-smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast-enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video-assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review.


Assuntos
Adenocarcinoma de Pulmão , Fístula , Pneumopatias , Neoplasias Pulmonares , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Artéria Pulmonar/patologia , Pneumonectomia/métodos , Pulmão/patologia , Adenocarcinoma de Pulmão/patologia , Pneumopatias/cirurgia , Neoplasias Pulmonares/patologia , Fístula/patologia
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