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2021 ◽  
Vol 11 ◽  
Zhiyang Zhang ◽  
Penglian Gao ◽  
Zhengqi Bao ◽  
Linggong Zeng ◽  
Junyi Yao ◽  

ObjectiveClear cell carcinoma (CCC) of the endometrium is an uncommon yet aggressive tumor. Few cohort studies are reporting the overall survival time of CCC patients. This study aimed to retrospectively analyze the clinicopathologic features, molecular characteristics and survival data of 27 endometrial CCC patients to improve the understanding of CCC.MethodsThe clinicopathologic features, molecular characteristics and survival data total of 27 CCC patients admitted to the BBMU affiliated hospital (Anhui, China) between January 2005 and December 2018 were retrospectively analyzed. Kaplan-Meier method was used to analyze the prognosis-related factors.ResultsThe median age of the patients was 60 years (range; 39 to 81 years). The average tumor size was 3.8 cm (range; 0.8 to 13.0cm). Myometrial infiltration greater than 50% was reported in 55.6% of the patients, while the Ki-67 index greater than 50% was reported in 70.4% of the patients. The patients’ FIGO (2009) surgical stages were as follows: 18 I, 3 II, 4 III, and 2 IV. Besides, 7 (25.6%) patients had lymphovascular invasion, 3 (11.1%) patients with distant metastasis, including 1 patient with bone metastasis, and 2 with liver metastasis. Adjuvant treatment included 7 with chemotherapy alone, 9 with radiotherapy alone, and 9 with both radiotherapy and chemotherapy. The median overall survival time from the time of CCC diagnosis was 56 months. ER and PR showed negative expression and P16 showed patchy immunostaining. 18 (63%) cases showed Napsin A positive expression. Loss of MSH2, MSH6 and PTEN were seen in 5, 4 and 7 cases respectively. All cases showed HER-2/nue negative expression.ConclusionCCC is a rare and invasive tumor. Age of diagnosis, FIGO stage, tumor size, myometrial infiltration, lymphovascular invasion, distant metastasis, Ki-67 index and P53 expression are important indicators to evaluate patient’s prognosis (P = 0.048, P < 0.001, P = 0.016, P = 0.043, P = 0.001, P < 0.001, P = 0.026, and P = 0.007, respectively). CCC has a worse prognosis than endometrioid carcinoma (P = 0.002), and there is no significant difference when compared with uterine papillary serous carcinoma (P = 0.155).

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Raed Aldahash

Anaplastic large-cell lymphoma is a rare type of aggressive non-Hodgkin’s lymphoma, and arriving at a final diagnosis for this tumor is a challenge for the healthcare providers. Usually, it involves the lymph nodes and extranodal tissues such as the lungs, skin, and other soft tissues. Its presentation by extending into different organs such as the liver, lungs, bones, spleen, and thyroid is rare. Thus, involvement of other organs is very rare as we found in a 54-year-old male patient, a known case of hypertension and end-stage renal disease who was on hemodialysis, who presented to the emergency department with a history of generalized weakness and weight loss of about 20 kg for two months. The tumor cells are positive for CD45, CD30, CD15, MUMi, and Ki-67 (80%) and negative for CD20, PAX-5, CD79a, CD3, CD5, CD10, BCL6, BCL2, EMA, ALK-1, and CD138. The patient was hypoglycemic and hypercalcemic and was managed accordingly. The patient was evaluated, and the third assessment showed that hypoglycemia was resolved due to dexamethasone. The patient’s glucose storage was depleted most likely due to liver involvement plus poor general condition. It was asserted that the patient’s hypoglycemia could be related to his underlying malignancy. Also, the patient was advised to start tablet diazoxide 45 mg three times a day (3 mg/kg/day TID) in addition to levothyroxine tablet 50 mcg once a day. Tablet diazoxide was stopped, and nutritional support was recommended. This case reveals a rare systematic ALK-1-negative anaplastic large-cell lymphoma that involves multiple organs. The main learning point from this report is that these tumors can present atypically even in adults and can be ALK-1 negative, which is contrary to the typical systematic anaplastic large-cell lymphomas that are positive for ALK.

2021 ◽  
Wei-liang Chen ◽  
Yan Wang ◽  
Bin Zhou ◽  
Juan-kun Liao ◽  
Rui Chen

Abstract Background: This study evaluated the clinical outcomes of the patients with adenoid cystic carcinoma (ACC) of the minor salivary glands of the palate. Methods: Forty-four patients with stage I–II disease and 14 patients with stage III–IV disease underwent radical excision and reconstruction with a facial-submental artery island flap (FSAIF) and titanium mesh plus a free anterolateral thigh flap (ALTF) and radiotherapy respectively. Patients with stage III–IV disease subsequently received cobalt Co 60 adjuvant radiotherapy. Ki-67 expression was determined semiquantitatively in 52 patients with ACC by based on the cytoplasm staining intensity and percentage of positively stained tumor cells.Results: The median (range) follow-up was 32.9 (14–58) months. Forty-one (71.7%) patients survived without disease recurrence. Nine patients (15.5%) survived with recurrent tumors (four with local recurrence, three with regional recurrence requiring salvage surgery, and two with distant metastasis); among these patients, five had overlapping recurrence. Eight patients (13.8%) died of regional, distant, or multiorgan metastasis (range: 22–42 months). The overall median (95% CI) survival time was 32.5 (25.0–39.5) months, and the median (95% CI) progression-free survival time was 32.9 (28.5–36.9) months. Rates of survival and recurrence differed significantly between patients with low- and high-grade tumors, patients with clinical stage I–II disease and those with stage III–IV disease, patients with and without lymph node metastasis, patients who underwent radical excision with versus without radiotherapy, and patients with low and high Ki-67 expression. Conclusion: Radical resection and reconstruction with FSAIF is the most suitable treatment for stage I–II ACC of the minor salivary glands of the palate. Stage III–IV tumors require radical resection, reconstruction with titanium mesh and free ALTF, and radiotherapy.

2021 ◽  
Vol 66 (4) ◽  
pp. 499-511
E. V. Batorov ◽  
V. V. Sergeevicheva ◽  
T. A. Aristova ◽  
S. A. Sizikova ◽  
G. Y. Ushakova ◽  

Introduction. High-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of treatment for multiple myeloma (MM) patients. The post-transplant period appears to be promising for targeted anti-checkpoint therapy in MM.Aim — to study the dynamics and functional properties of T-cells expressing inhibitory checkpoint molecules PD-1 and TIM-3 in patients with MM under conditions of lymphopenia after HDC with auto-HSCT.Methods. The study included 40 patients with MM who underwent HDC with auto-HSCT. The counts of PD-1- and TIM3-positive CD8+ and CD4+ T-cells and their functional activity on the intracellular expression of Ki-67, production of granzyme B, and interferon-γ were assessed by fl ow cytometry.Results. Relative counts of patient PD-1+ and TIM-3+ subsets of CD8+ and CD4+ T-cells obtained from bone marrow samples were higher compared to peripheral blood. CD8+ PD-1+ and CD4+ PD-1+ T-cells of MM patients had a pronounced cytotoxic and cytokine-producing potential. The functional activity of CD8+ TIM-3+ and CD4+ TIM-3+ T-cells was signifi cantly reduced compared with TIM-3-negative subsets. Low functional activity was also detected in populations of CD8+ and CD4+ T-lympho cytes, co-expressing PD-1 and TIM-3. The frequencies of T-cells expressing PD-1 and TIM-3 increased signifi cantly on the engraftment day after auto-HSCT. The proliferative activity of PD-1+ and TIM-3+ CD4+ and CD8+ T-cells and the cytotoxic potential of PD-1+ and TIM-3+ CD8+ T-cells were also signifi cantly increased compared to the data prior auto-HSCT.Conclusions. PD-1-positive T-cells in MM patients are related to activated or “early dysfunctional” but not exhausted subsets, while T-cells exhaustion is more analogous with CD8+ TIM-3+ and CD4+ TIM-3+ T-cells, as well as with subsets co-expressing PD-1 and TIM-3. To identify the state of T-cells exhaustion, it is necessary to evaluate T-cells subsets co-expressing PD-1, TIM-3, and other ICMs, and/or to study their functional properties. In the early post-transplant period, the proportion of Tcells expressing PD-1 and TIM-3 increases due to an increase in their proliferative potential.

2021 ◽  
Kun-kai Su ◽  
Xue-hua Zheng ◽  
Christian Bréchot ◽  
Xiao-ping Zheng ◽  
Dan-hua Zhu ◽  

Abstract Background: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer. However, the lipid pro-inflammatory mediators have only been seldom investigated in HCC pathogenesis. Activation of NF-κB and expression of c-Myc are negatively regulated by cylindromatosis (CYLD) in hepatocarcinogenesis. But it remains largely unknown whether lipid pro-inflammatory mediators are involved in CYLD suppression. Here, we aimed to evaluate the significance of hepatic lipid pro-inflammatory metabolites of arachidonate affected CYLD expression via 5-lipoxygenase (5-LO)-pathway.Methods: Resection liver tissues from HCC patients or donors were evaluated for the correlation of 5-LO/cysteinyl leukotrienes (CysLTs)-signaling to expression of CYLD. The impact of functional components in 5-LO/CysLTs cascade on survival of HCC patients was subsequently assessed. Both livers from canines, a routine animal for drug safety evaluation, and genetic-modified human HCC cells treated with hepatocarcinogen aristolochic acid I (AAI) were further used to reveal the possible relevance between 5-LO pathway activation and CYLD depression. Results: 5-LO-activating protein (FLAP), an essential partner of 5-LO, significantly overexpressed and was parallel to CYLD depression, CD34 neovascular localization, and high Ki-67 expression in the resection tissues from HCC patients. Importantly, high hepatic FLAP transcription markedly shortened the median survival time of HCC patients after surgical resection. In the livers of AAI-treated canines, FLAP overexpression was parallel to enhanced CysLTs contents, simultaneous attenuated CYLD expression. Moreover, knock-in FLAP significantly diminished the expression of CYLD in AAI-treated human HCC cells.Conclusions: Hepatic FLAP/CysLTs axis is a crucial suppressor of CYLD in HCC pathogenesis, which highlights a novel mechanism in hepatocarcinogenesis and development. FLAP therefore can be explored for the early HCC detection and a target of anti-HCC therapy.

2021 ◽  
Yong Chen ◽  
Baojiang Wang ◽  
Yanjuan Chen ◽  
Qunyan Wu ◽  
Kutty Selva Nandakumar ◽  

Abstract Background To investigate HAPLN1 contribution to the viability of RA-FLSs and identify its potential role in RA pathogenesis. Methods Plasma levels and synovial expression of HAPLN1 were compared between healthy controls, and osteoarthritis (OA) and RA patients. Proliferation and migration of RA-FLSs transfected with siHAPLN1, HAPLN1OE (over-expression vector) and respective controls or treated with rHAPLN1 were measured by MTT and CCK8 assays as well as wound healing and transwell assays. RT-qPCR and automated WB analysis were used to compare the expression of AMPK-ɑ, TNF-ɑ, TGF-β, ACAN, MMPs, Cyclin-D1 and Ki-67 after siHAPLN1 or HAPLN1OE transfection. Proteomics and mRNA-seq analysis was done to study the differentially expressed proteins/genes after siHAPLN1 or rHAPLN1 treatment. Results Expression of HAPLN1 was increased in the plasma samples and synovium tissues of RA patients. HAPLN1OE transfected or rHAPLN1 treated RA-FLSs showed an increased proliferation capacity. However, Si-HAPLN1 has failed to affect the viability of RA-FLSs, though it decreased the migration ability of these cells. On the other hand, HAPLN1OE or rHAPLN1 had inhibitory effect on migration. Both si-HAPLN1 and HAPLN1OE treated RA-FLSs had down-regulated AMPK-ɑ gene expression, while protein level was found to be up-regulated. Furthermore, si-HAPLN1 has down-regulated TNF-ɑ, MMPs, IL-6, TGF-β, fibronectin and ACAN levels, while HAPLN1OE has up-regulated the levels of TNF-ɑ, MMPs, IL-6 and ACAN. Proteomics and mRNA-Seq analysis demonstrated HAPLN1 function in the activation of inflammation, proliferation, increased cell adhesion and strengthening of ECM function. Conclusons: HAPLN1 accelerated the proliferation of RA-FLSs but inhibited its migration ability. HAPLN1 network was found to be mainly involved in the activation of inflammation, cell proliferation and increased cell adhesion.

Gamze Akkus ◽  
Fulya Odabaş ◽  
Sinan Sözütok ◽  
Murat Sert ◽  
Numan Emre Ak ◽  

AbstractAccording to the recent studies, immunohistochemical subtypes of growth hormone (GH) secreting adenomas have been considered as a predictive factor in determining the clinical outcomes including biochemical, radiologic, and endocrine remission. In a 20 year-of time period, acromegaly patients who were treated and followed at the Endocrinology Department of our University Hospital were screened for the study. Of total 98 patients, 65 patients who had been operated by transsphenoidal surgery and having postoperative specimens were included. Postoperative specimens of the surgery of the patients were classified into 3 groups based on the histochemical characteristics (densely, sparsely, and mixed). Parasellar extensions of pituitary tumors were classified into the five grades according to Knosp classification. The patients were investigated and evaluated for postoperative clinical progress, remission rates, comorbidities regarding with the histopathological patterns. Of total 65 patients, 31 were classified as densely granulated (group 1), 32 were classified as sparsely granulated (group 2), and 2 patients were assessed as mixed granulated (group 3). There was no difference between groups for age and gender. Pre-treatment of adenoma size in all groups was correlated with each other and the frequency of macroadenoma (1 vs. 2, 77.4 vs. 84.3%) was higher in two groups. Although mean initial GH levels in group 1 was higher than the other groups (p=0.03), IGF1 levels (age and gender matched) were similar in each group. Adenomas in all groups demonstrated noninvasive radiological characteristics (Knosp grade 0–1–2). Ki-67 proliferation index of both groups (64.5 vs. 50%) was predominantly 1%. With a similar follow-up period, the endocrine remission rates (GH<1 μg/l) in groups were 64 vs. 69%, respectively. In conclusion, classification according to immunohistochemical subtypes of growth hormone secreting adenomas may not be a qualified parameter to evaluate patients with patterns of aggressiveness, clinical outcomes, or treatment response.

2021 ◽  
Vol 14 (12) ◽  
pp. 1852-1857
Rui Liu ◽  
Hong Zhang ◽  
Xin Ge ◽  
Jian-Min Ma ◽  

AIM: To monitor the prognosis of patients with lacrimal gland pleomorphic adenoma (LGPA) following surgical resection within the past 10y. The factors affecting patient prognosis are analyzed and the experience of surgical treatment is summarized. METHODS: In this retrospective, comparative case series, clinical records from 109 cases of LGPA treated chiefly at the same institution between November 2009 and May 2019 were reviewed. All 109 patients underwent surgery, histopathological examination, and imaging examination. For patients who underwent surgery for the first time, LGPA could be resected completely, including tumor and capsule tissues, using a surgical approach via the eyebrow arch or double eyelid crease. RESULTS: The ratio of males to females was 1:1.60, the ages ranged from 19 to 74 years old with a mean age of 43.64±13.07 years old, and the ratio of left to right eyes was 1:1.37. A total of 109 patients underwent surgical excision and five of these received radiotherapy after malignant transformation. Of these patients, 15 were lost to follow up within the April 1, 2020 deadline and 1 was diagnosed as a recurring pathology. The 5-year recurrence rate for 86 patients who underwent initial surgery was 7.27%. Single factor analysis revealed that the course of disease, bone destruction, invasion of surrounding tissues, tumor size, capsule integrity, and expression of Ki-67 were statistically significant (P<0.05). Binomial Logistic regression analysis showed that capsule integrity was a risk factor influencing recurrence (P=0.008). CONCLUSION: LGPA has a risk of recurrence and potential for malignant transformation. Complete removal of the tumor and capsule in the initial surgery is a key factor in preventing recurrence.

2021 ◽  
Vol 10 (23) ◽  
pp. 5571
Hans-Jonas Meyer ◽  
Jakob Leonhardi ◽  
Anne Kathrin Höhn ◽  
Johanna Pappisch ◽  
Hubert Wirtz ◽  

Texture analysis derived from computed tomography (CT) might be able to provide clinically relevant imaging biomarkers and might be associated with histopathological features in tumors. The present study sought to elucidate the possible associations between texture features derived from CT images with proliferation index Ki-67 and grading in pulmonary neuroendocrine tumors. Overall, 38 patients (n = 22 females, 58%) with a mean age of 60.8 ± 15.2 years were included into this retrospective study. The texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. In discrimination analysis, “S(1,1)SumEntrp” was significantly different between typical and atypical carcinoids (mean 1.74 ± 0.11 versus 1.79 ± 0.14, p = 0.007). The correlation analysis revealed a moderate positive association between Ki-67 index with the first order parameter kurtosis (r = 0.66, p = 0.001). Several other texture features were associated with the Ki-67 index, the highest correlation coefficient showed “S(4,4)InvDfMom” (r = 0.59, p = 0.004). Several texture features derived from CT were associated with the proliferation index Ki-67 and might therefore be a valuable novel biomarker in pulmonary neuroendocrine tumors. “Sumentrp” might be a promising parameter to aid in the discrimination between typical and atypical carcinoids.

2021 ◽  
Vol 12 ◽  
Nara Vasconcelos Cavalcanti ◽  
Patrícia Palmeira ◽  
Marcelo Biscegli Jatene ◽  
Mayra de Barros Dorna ◽  
Magda Carneiro-Sampaio

Background and AimsCongenital heart diseases (CHDs) are diagnosed in approximately 9 in 1,000 newborns, and early cardiac corrective surgery often requires partial or complete thymectomy. As the long-term effect of early thymectomy on the subsequent development of the immune system in humans has not been completely elucidated, the present study aimed to evaluate the effects of thymus removal on the functional capacity of the immune system after different periods.MethodsA systematic review of the literature was performed using MEDLINE, EMBASE, LILACS and Scopus. The inclusion criteria were original studies that analyzed any component of the immune system in patients with CHD who had undergone thymectomy during cardiac surgery in the first years of life. The results were evaluated for the quality of evidence.ResultsTwenty-three studies were selected and showed that patients who underwent a thymectomy in the first years of life tended to exhibit important alterations in the T cell compartment, such as fewer total T cells, CD4+, CD8+, naïve and CD31+ T cells, lower TRECs, decreased diversity of the TCR repertoire and higher peripheral proliferation (increased Ki-67 expression) than controls. However, the numbers of memory T cells and Treg cells differed across the selected studies.ConclusionsEarly thymectomy, either partial or complete, may be associated with a reduction in many T cell subpopulations and TCR diversity, and these alterations may persist during long-term follow-up. Alternative solutions should be studied, either in the operative technique with partial preservation of the thymus or through the autograft of fragments of the gland.Systematic Review RegistrationProspero [157188].

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