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International Surgery Jun 2015In this article, we aimed to review the literature on the clinics and management of intraductal papillary mucinous neoplasm (IPMN). Intraductal papillary mucinous... (Review)
Review
In this article, we aimed to review the literature on the clinics and management of intraductal papillary mucinous neoplasm (IPMN). Intraductal papillary mucinous neoplasm of the pancreas is a mucin-producing cystic mass originating from the pancreatic ductal system. Approximately 25% of the pancreatic neoplasms resected surgically and 50% of pancreatic cysts detected incidentally are IPMNs. They can be benign or malignant in character, while malignant transformation of benign forms can be encountered. It is important to determine IPMNs in the early stages, implementation of appropriate treatment approaches, and follow-up to provide better prognosis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the IPMN. Due to the recent advances and widespread implementation of radiological imaging techniques, the incidental detection rate of IPMNs has increased significantly. The effective treatment of the disease is possible via the detailed diagnosis of the disease, determination of the prognostic factors, and a multidisciplinary approach. Recent literature also emphasized the molecular profile determination approaches for assessment of prognosis of patients with IPMN. Current knowledge on IPMN, a clinically important epidemiologic problem, shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Diagnostic Imaging; Humans; Prognosis
PubMed: 26414828
DOI: 10.9738/INTSURG-D-14-00220.1 -
Frontiers in Endocrinology 2020Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory... (Review)
Review
Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory PAs lie between benign adenomas and true malignant PC and are defined as aggressive-invasive PAs characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments, including temozolomide. It is notoriously difficult to manage refractory PAs and PC because of the limited therapeutic options. As a promising therapeutic approach, cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The purpose of this review is to report the progress of immunotherapy in pituitary tumors, including refractory PAs and PCs. The tumor immune microenvironment has been recognized as a key contributor to tumorigenesis, progression, and prognosis. One study indicated that the number of CD68+ macrophages was positively correlated with tumor size and Knosp classification grade for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but pituitary growth hormone (GH) adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in pituitary tumor size and invasiveness. Another study suggested that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogs in acromegaly patients, highlighting a potential role of the tumor immune microenvironment in determining the prognosis of somatotroph pituitary tumors. Preclinical studies have indicated that widely varying degrees of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are found among different subtypes. Functional PAs and aggressive PAs express significantly higher levels of PD-L1 and TILs than other subtypes, indicating that PD-1 blockade might be a promising alternative therapy for patients with aggressive PAs. PD-L1 transcript and protein levels were found to be significantly increased in functioning (GH and prolactin-expressing) pituitary tumors compared to nonfunctioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary tumors harbored higher levels of PD-L1 mRNA than recurrent tumors. These findings suggest the possibility of considering checkpoint blockade immunotherapy for functioning pituitary tumors refractory to conventional management. Animal models of Cushing's disease also demonstrated PD-L1 and TIL expression in cultured tumors and murine models, as well as the effectiveness of checkpoint blockade therapy in reducing the tumor mass, decreasing hormone secretion, and increasing the survival rate. Clinical studies show that immunotherapy may be an effective treatment in patients with pituitary tumors. One corticotroph carcinoma patient showed a significant reduction in hormone levels and shrinkage of the tumor size of primary and metastatic lesions immediately after investigational treatment with ipilimumab and nivolumab. However, another patient with corticotroph adenoma progressed rapidly after four cycles of anti-PD-1 (pembrolizumab) treatment. To date, there are two registered clinical trials of immunotherapy for pituitary tumors. One of them is the phase II clinical trial of nivolumab combined with ipilimumab for patients with aggressive pituitary tumors (NCT04042753). The other one is also a phase II clinical trial of the combination of nivolumab and ipilimumab for rare tumors, including pituitary tumors (NCT02834013). Both clinical trials are in the stage of recruiting patients and have not been completed. In summary, the results from preclinical research and clinical studies indicated that immunotherapy might be a promising alternative therapy for PCs and refractory PAs resistant to conventional treatments. The combination of immunotherapy and radiotherapy or temozolomide may have synergistic effects compared to a single treatment. More preclinical and clinical studies are needed to further indicate the exact efficacy of immunotherapy in pituitary tumors.
Topics: Adenoma; Animals; Carcinoma; Humans; Immunotherapy; Pituitary Neoplasms
PubMed: 33362722
DOI: 10.3389/fendo.2020.608422 -
Ugeskrift For Laeger Nov 2014Incidental cystic lesions of the pancreas are often detected due to the increased use of cross-sectional imaging. Since mucinous cysts have a malignant potential,... (Review)
Review
Incidental cystic lesions of the pancreas are often detected due to the increased use of cross-sectional imaging. Since mucinous cysts have a malignant potential, whereas pseudocysts and serous cystadenomas are benign, the distinction is of key clinical importance. Current recommendations advocate the use of multiple imaging modalities (CT/MRI/endoscopic US/endoscopic US & fine-needle aspiration) during evaluation and follow-up. This review describes the most frequent cystic lesions of the pancreas and suggests a simple investigation and treatment algorithm.
Topics: Algorithms; Carcinoma, Pancreatic Ductal; Cystadenocarcinoma, Mucinous; Cystadenoma, Serous; Humans; Pancreatic Cyst; Pancreatic Pseudocyst
PubMed: 25394925
DOI: No ID Found -
Endocrine Journal 2009Differentiated thyroid carcinoma originates from thyroid follicular cells and is the most prominent malignancy of the endocrine organs. There are two histological types... (Review)
Review
Differentiated thyroid carcinoma originates from thyroid follicular cells and is the most prominent malignancy of the endocrine organs. There are two histological types of differentiated carcinoma, namely, papillary and follicular carcinoma. According to reports from Western countries, papillary carcinoma comprises 85.3% of thyroid malignancies in whites, and 72.3% in blacks. In Japan, a previous study showed that the prevalence of papillary carcinoma was 78.4% based on material registered between 1977 and 1986, but according to recent findings reported in 2004 by Japanese Society of Thyroid Surgeons (JSTS), papillary carcinoma accounted for as much as 93% of all thyroid carcinomas. Papillary carcinoma frequently metastasizes to the regional lymph node and shows multicentricity in the thyroid gland. It usually shows a typical ultrasonographic appearance and can be rather easily diagnosed by fine needle aspiration biopsy (FNAB). Follicular carcinoma accounts for 10.9-20.5% of the patients in the United States. In Japan, the prevalence of follicular carcinoma was reported to be 17.2%, but it decreased to 5% in a report by JSTS in 2004. This carcinoma is only occasionally diagnosed preoperatively, because it is hard to discriminate follicular carcinoma from benign adenoma on imaging studies and cytologic findings. In contrast to papillary carcinoma, follicular carcinoma more often metastasizes to distant organs than regional lymph nodes. In Japan, the prevalence of papillary carcinoma increased and that of follicular carcinoma decreased between reports from 1977 to 1986 and that in 2004, which may be because follicular variant of papillary carcinoma was classified into follicular carcinoma in the previous results. Generally, these carcinomas show an indolent character, but when the lesion dedifferentiates and becomes undifferentiated carcinoma, it displays very rapid growth with an adverse prognosis and is regarded even as the most aggressive malignancy among human solid carcinomas. Furthermore, cases showing certain characteristics are likely to be constantly progressive and even become life-threatening. Such cases should be regarded as "high-risk" requiring careful and extensive surgical treatment and postoperative follow-up. Indeed, it is most important for physicians to correctly distinguish high-risk cases from those with an indolent character, although how to evaluate the biological characteristics of thyroid carcinoma and how to identify high-risk cases remains highly controversial. In this review, the methods of distinguishing high-risk cases and the appropriate therapeutic strategies for papillary and follicular carcinomas predominantly based on our experience are emphasized and our proposals for therapies including surgical treatment are demonstrated.
Topics: Adenocarcinoma, Follicular; Carcinoma, Papillary; Humans; Japan; Lymphatic Metastasis; Prognosis; Thyroid Neoplasms; Thyroidectomy
PubMed: 18703852
DOI: 10.1507/endocrj.k08e-166 -
Scientific Reports Apr 2016Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and...
Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Dendritic Cells; Female; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Male; Middle Aged; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Patient Outcome Assessment; Prognosis; Survival Analysis; Thymus Gland; Thymus Neoplasms; Tumor Microenvironment; Young Adult
PubMed: 27097982
DOI: 10.1038/srep24267 -
The International Journal of Biological... Dec 2023Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in...
The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions.
INTRODUCTION
Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in patients with biologically aggressive features, additional prognostic and predictive data may aid disease management. Dysregulation of the endocannabinoid system including the cannabinoid receptors 1 and 2 (CB-1R and CB-2R) during carcinogenesis has been extensively studied over the last few decades. The aim of this study was to evaluate immunohistochemically the expression levels of both receptors in patients with papillary thyroid carcinoma and benign diseases, and to compare these rates and the histopathologically and clinically prognostic features.
METHODS
The pathological materials and clinical data of 100 patients with papillary thyroid carcinoma and 40 with benign diseases were retrospectively re-evaluated. All tissues were immunohistochemically stained for CB-1R and CB-2R. The expression levels of CB-1R and CB-2R in papillary thyroid carcinomas, and benign lesions were recorded and compared with the pathological and clinical features.
RESULTS
The expression levels of both receptors were significantly higher in papillary thyroid carcinoma patients than in those with benign conditions (= 0.001). CB-1R expression correlated with both extrathyroidal extension (= 0.022) and capsular invasion (= 0.001). CB-2R expression was associated with the risk group of the American Thyroid Association stratification system (= 0.004).
CONCLUSION
Our study suggests that increased cannabinoid receptor expression contributes to thyroid carcinogenesis. The CB-2R expression level could provide additional information aiding risk management. Furthermore, the CB-1R and CB-2R antibodies might increase the accuracy of papillary thyroid carcinoma diagnosis when combined with the papillary thyroid carcinoma biomarkers assayed after fine-needle aspiration of neoplastic cells.
Topics: Humans; Carcinogenesis; Carcinoma, Papillary; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 37700679
DOI: 10.1177/03936155231200285 -
Current Treatment Options in Oncology Oct 2020With the widespread use of esophagogastroduodenoscopy in recent years, the detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) is... (Review)
Review
With the widespread use of esophagogastroduodenoscopy in recent years, the detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) is increasing. Most SNADETs are early-stage adenocarcinoma or benign conditions, including adenoma. Therefore, endoscopic resection is desirable from the perspective of quality of life. However, endoscopic resection for SNADETs has not yet been established. Endoscopic submucosal dissection (ESD) is the most promising method for the treatment of SNADETs, because ESD provides a high rate of en bloc resection and a low rate of recurrence regardless of the tumor size. However, the difficulty of the procedure and a high rate of severe adverse events including perforation and bleeding have become major problems. Various preventive countermeasures for adverse events, such as use of specific devices, endoscope stabilization methods, and endoscopic closure of the post-ESD ulcer using clips, are reported to reduce the risk of the adverse events of ESD for SNADETs. This article reviews and highlights the current state of ESD for SNADETs and new challenges towards safe and effective ESD.
Topics: Adenocarcinoma; Carcinoma; Duodenal Neoplasms; Endoscopic Mucosal Resection; Humans; Neoplasm Recurrence, Local
PubMed: 33104938
DOI: 10.1007/s11864-020-00796-y -
Modern Pathology : An Official Journal... Jan 2016The current 2014 World Health Organization (WHO) Classification of mixed epithelial and mesenchymal tumours of the uterus includes categories of carcinosarcoma,... (Review)
Review
The current 2014 World Health Organization (WHO) Classification of mixed epithelial and mesenchymal tumours of the uterus includes categories of carcinosarcoma, adenosarcoma, adenofibroma, adenomyoma and atypical polypoid adenomyoma, the last two lesions being composed of an admixture of benign epithelial and mesenchymal elements with a prominent smooth muscle component. In this review, each of these categories of uterine neoplasm is covered with an emphasis on practical tips for the surgical pathologist and new developments. In particular, helpful clues in the distinction between carcinosarcoma and dedifferentiated endometrial carcinoma will be discussed. In addition, salient features to help distinguish between adenofibroma, adenosarcoma, embryonal rhabdomyosarcoma and other mesenchymal neoplasms in the differential diagnosis will be outlined. Finally, a discussion of adenomyoma and its main differential diagnostic considerations will be covered.
Topics: Female; Humans; Neoplasms, Complex and Mixed; Neoplasms, Connective and Soft Tissue; Neoplasms, Glandular and Epithelial; Uterine Neoplasms
PubMed: 26715175
DOI: 10.1038/modpathol.2015.137 -
British Medical Journal Apr 1951
Topics: Carcinoma; Humans; Neoplasms, Glandular and Epithelial
PubMed: 14830810
DOI: 10.1136/bmj.1.4712.920 -
Oncology Reports May 2023The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and...
The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and associated clinicopathological features have been linked to various cancers; however, its role in epithelial ovarian cancer (EOC) has remained to be explored. The present study aimed to unveil the function, molecular mechanisms and clinical significance of ATP6V1B1 in EOC. The mRNA levels of ATP6V1 subunits A, B1 and B2 in EOC tissues were determined using data from the Gene Expression Profiling Interactive Analysis database and RNA sequencing. Protein levels of ATP6V1B1 were evaluated through immunohistochemistry staining of EOC, borderline, benign and normal epithelial tissues. The association between ATP6V1B1 expression and clinicopathological features and prognosis of patients with EOC was analyzed. Furthermore, the biological role of ATP6V1B1 in ovarian cancer cell lines was also assessed. RNA sequencing and public dataset analyses revealed elevated ATP6V1B1 mRNA levels in EOCs. High ATP6V1B1 protein levels were also observed in EOC compared with those of borderline and benign tumors and nonadjacent normal epithelial tissues. High ATP6V1B1 expression was associated with the serous cell type, advanced International Federation of Gynecology and Obstetrics stage, high/advanced tumor grade, elevated serum cancer antigen 125 levels and platinum resistance (P<0.001, P<0.001, P=0.035, P=0.029 and P=0.011, respectively). High expression levels of ATP6V1B1 were also associated with poor overall and disease‑free survival (P<0.001). Knockdown of ATP6V1B1 decreased cancer cell proliferation and colony‑forming abilities (P<0.001) by inducing cell cycle arrest in G0/G1 phase. Significant upregulation of ATP6V1B1 was observed in EOC and the prognostic significance and association with chemotherapy resistance of ATP6V1B1 in EOC was demonstrated, rendering it an EOC‑related biomarker for prognostic evaluation and chemotherapy resistance, as well as a potential therapeutic target for patients with EOC.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Biomarkers, Tumor; Ovarian Neoplasms; Prognosis; RNA, Messenger; Neoplasms, Glandular and Epithelial; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Vacuolar Proton-Translocating ATPases
PubMed: 36999629
DOI: 10.3892/or.2023.8539