Desmoid tumors describe a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Although histologically benign, desmoids are locally ...invasive and associated with a high local recurrence rate, but lack metastatic potential. On the molecular level, desmoids are characterized by mutations in the β‐catenin gene, CTNNB1, or the adenomatous polyposis coli gene, APC. Proof of a CTNNB1 mutation may be useful when the pathological differential diagnosis is difficult and location might be predictive for disease recurrence.
Many issues regarding the optimal treatment of patients with desmoids remain controversial; however, surgery is the therapeutic mainstay, except if mutilating and associated with considerable function loss. Postoperative radiotherapy reduces the local recurrence rate, in cases of involved surgical margins. Because of the heterogeneity of the biological behavior of desmoids, including long periods of stable disease or even spontaneous regression, treatment needs to be individualized to optimize local tumor control and preserve patients' quality of life. Therefore, the application of a multidisciplinary assessment with multimodality treatment forms the basis of care for these patients. Watchful waiting may be the most appropriate management in selected asymptomatic patients. Patients with desmoids located at the mesentery or in the head and neck region could present with life‐threatening complications and often need more aggressive treatment. This review describes treatment options and management strategies for patients with desmoid tumors with a focus on advanced disease.
摘要
硬纤维瘤是一种罕见的单克隆纤维母细胞增生性疾病，其特征为临床病程多变，常难以预测。虽然硬纤维瘤的组织学为良性，仍有局部浸润表现，且局部复发率高，但缺乏转移潜力。分子水平上，硬纤维瘤的特征为β连环蛋白基因、CTNNB1或腺瘤性结肠息肉病（APC）基因突变。病理鉴别诊断存在困难时，CTNNB1突变的证据有助于诊断，肿瘤所在部位可能是疾病复发的预测因素。
硬纤维瘤患者治疗选择相关的许多话题仍存在争议，然而外科手术是治疗主流，除非手术为致残性，可能导致相当的功能丧失。手术切缘受累时，术后放疗可降低局部复发率。由于硬纤维瘤生物学行为的异质性（疾病长期保持稳定甚或自发性消退），需行个体化治疗以获得最佳局部肿瘤控制，并维持患者的生活质量。因此，多学科联合评估和多模式治疗的应用是硬纤维瘤患者临床治疗的基础。对某些无症状患者而言，观察等待可能最为恰当。肠系膜或头颈部区域硬纤维瘤可能导致威胁生命的并发症，常需更具侵袭性的治疗。本综述旨在探讨进展期硬纤维瘤患者的治疗选择和处理策略。
This review describes treatment options and management strategies for patients with desmoid tumors with a focus on advanced disease.
Neuroendocrine tumors of the thymus (TNET) are exceedingly rare neoplasms. Their histomorphology is identical to neuroendocrine tumors elsewhere in the body (in particular the lungs) and bears no ...similarity with thymomas and thymic carcinomas. Recent molecular findings have profoundly changed our perception of these tumors and may impact future histological classification systems.
The history of thymoma (TH) research begins in the early 20th century, when Bell first recognized the epithelial nature of these tumors and their association with myasthenia gravis (MG) ....
Thymus and autoimmunity Marx, Alexander; Yamada, Yosuke; Simon-Keller, Katja ...
Seminars in immunopathology,
02/2021, Letnik:
43, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The thymus prevents autoimmune diseases through mechanisms that operate in the cortex and medulla, comprising positive and negative selection and the generation of regulatory T-cells (Tregs). Egress ...from the thymus through the perivascular space (PVS) to the blood is another possible checkpoint, as shown by some autoimmune/immunodeficiency syndromes. In polygenic autoimmune diseases, subtle thymic dysfunctions may compound genetic, hormonal and environmental cues. Here, we cover (a) tolerance-inducing cell types, whether thymic epithelial or tuft cells, or dendritic, B- or thymic myoid cells; (b) tolerance-inducing mechanisms and their failure in relation to thymic anatomic compartments, and with special emphasis on human monogenic and polygenic autoimmune diseases and the related thymic pathologies, if known; (c) polymorphisms and mutations of tolerance-related genes with an impact on positive selection (e.g. the gene encoding the thymoproteasome-specific subunit,
PSMB11
), promiscuous gene expression (e.g.
AIRE
,
PRKDC
,
FEZF2
,
CHD4
), Treg development (e.g.
SATB1
,
FOXP3
), T-cell migration (e.g.
TAGAP
) and egress from the thymus (e.g.
MTS1
,
CORO1A
); (d) myasthenia gravis as the prototypic outcome of an inflamed or disordered neoplastic ‘sick thymus’.
This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and ...variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.
The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted ...(EC) colonoscopy and standard colonoscopy (SC).
This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany.
500 patients (235 males, median age 64IQR 54-73) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).
The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%95% confidence interval{CI} 29-41% vs. 20.7%95%CI 15-26%, p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio OR 1.03; 95%CI 1.01-1.05), male sex (OR 1.74; 95%CI 1.10-2.73), withdrawal time (OR 1.16; 95%CI 1.05-1.30), procedure time (OR 1.07; 95%CI 1.04-1.10), colon cleanliness (OR 0.60; 95%CI 0.39-0.94) and use of Endocuff (OR 2.09; 95%CI 1.34-3.27) were independent predictors of adenoma detection rates.
EC increases the adenoma detection rate by 14.7%(95%CI 6.9-22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.
ClinicalTrials.gov NCT02034929.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients whose tumors showed methylation and decreased expression of the gene
TFAP2E
were more than five times as likely as patients with normal
TFAP2E
gene expression to have resistance to ...fluorouracil.
The treatment options and prognosis for patients with advanced colorectal cancer have improved through the development of novel drugs.
1
,
2
However, studies of the molecular biology of cancer initiation and progression have so far provided scant knowledge of the molecular mechanisms contributing to chemotherapy resistance.
2
Epigenetic alterations underlying the pathogenesis of colorectal cancer have been reported by several groups.
3
These alterations include hypomethylation and hypermethylation of DNA as well as histone modifications, all of which have a profound effect on transcriptional gene regulation. The role of these molecular alterations in response prediction and treatment resistance are far less well known. . . .
Acute kidney injury (AKI) is a common and severe complication of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) causing progressive chronic kidney disease (CKD), end-stage ...renal disease (ESRD) or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in pauci-immune necrotizing and crescentic glomerulonephritis (GN), a common manifestation of glomerular injury in AAV. However, there is growing evidence that activation of the complement pathway contributes to the pathogenesis and progression of AAV. We here aimed to compare glomerular and tubulointerstitial lesions in ANCA GN and extrarenal manifestation of AAV in association with levels of circulating complement components C3c and C4. Methods: Plasma levels of C3c and C4 in a total number of 53 kidney biopsies with ANCA GN were retrospectively included between 2015 and 2020. Glomerular and tubulointerstitial lesions were evaluated according to established scoring systems for ANCA GN and analogous to the Banff classification. Results: We here show that circulating levels of C3c and C4 in ANCA GN were comparable to the majority of other renal pathologies. Furthermore, hypocomplementemia was only detectable in a minor subset of ANCA GN and not correlated with renal or extrarenal AAV manifestations. However, low levels of circulating C3c correlated with AKI severity in ANCA GN independent of systemic disease activity or extrarenal AAV manifestation. By systematic scoring of glomerular and tubulointerstitial lesions, we provide evidence that low levels of circulating C3c and C4 correlated with vasculitis manifestations to distinct renal compartments in ANCA GN. Conclusions: We here expand our current knowledge about distinct complement components in association with vasculitis manifestations to different renal compartments in ANCA GN. While low levels of C4 correlated with glomerulitis, our observation that low levels of circulating complement component C3c is associated with interstitial vasculitis manifestation reflected by intimal arteritis implicates that C3c contributes to tubulointerstitial injury in ANCA GN.
We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische ...Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial.
TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided.
With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4.
Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.
Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody ...(ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN. Furthermore, we compared this scoring with established classification systems in renal AAV including histopathological findings.
We here directly compare the scoring system with retrospective data about PLEX treatment in our own clinical practice and according to current recommendations in a cohort of 53 patients with severe AAV presenting with RPGN confirmed by kidney biopsy.
We here confirm that PLEX scoring is capable to identify patients at risk for short-term poor outcome in severe AAV presenting with RPGN (
). Furthermore, multiple stepwise regression analysis revealed that the PLEX score with renal biopsy performed best to predict poor outcome in this patient population (
).
Our observations underscore the relevance of performing a kidney biopsy in this patient population that is often challenged in the setting of intensive care treatment, requirement of KRT with need for anticoagulation and bleeding risk. Therefore, validation of our observations and this recent scoring system for treatment response to PLEX in independent cohorts would be of great clinical relevance in the treatment of patients with severe AAV presenting with RPGN.
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