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2021 ◽  
Vol 11 ◽  
Mohammad Al-Shinnag ◽  
Helen Marfan ◽  
Rachel Susman ◽  
Jan Wakeling ◽  
Sonja Gustafson ◽  

AimWe aimed to describe and analyse clinical features, characteristics, and adherence to surveillance guidelines in an Australian Birt-Hogg-Dubé syndrome (BHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC) cohort.MethodsAll identified patients with a diagnosis of BHD or HLRCC at RBWH 01/01/2014-01/09/2019 were included (HREC/17/QRBW/276). All patients were initially assessed and counselled by a clinical geneticist and then referred to an adult nephrologist. Baseline and incidental clinical variables were extracted and analysed.ResultsFifty-seven patients were identified (28 BHD, 29 HLRCC) with a median age of 47 years. The median and cumulative follow-up were 1 and 99 years, respectively. Baseline renal MRI occurred in 40/57 patients, and 33/57 had regular MRI as per the national guidelines (eviQ). Of 18/57 without baseline imaging, nine were yet to have imaging, seven were lost follow-up, and two patients had logistic difficulties. RCC was diagnosed in 11/57 patients: two of 28 with BHD were diagnosed with RCC aged 73 and 77, both prior to commencement of surveillance. Nine of 29 patients with HLRCC were diagnosed with RCC (one of 29 during surveillance at 47 years of age) and eight of 29 prior to commencement of surveillance (11–55 years). Amongst BHD patients, cutaneous fibrofolliculomas were noted in 15 patients, lung cysts were detected in seven patients, spontaneous pneumothoraces in five patients, and parotid oncocytoma in two of 28. Amongst those with HLRCC, cutaneous leiomyomas were noted in 19/29, cutaneous leiomyosarcoma diagnosed in one of 29, and uterine fibroids in 13 female patients.ConclusionEvidence-based RCC screening in BHD and HLRCC cohort is feasible and able to identify incidental renal lesions. Multidisciplinary patient management enables expedited genetic counselling, diagnosis, longitudinal screening, and RCC management. The success of this clinical model warrants consideration of undertaking longitudinal screening of BHD and HLRCC patients by nephrologists.

Naveena A. N. Kumar ◽  
Anmi Jose ◽  
Nawaz Usman ◽  
Keshava Rajan ◽  
Murali Munisamy ◽  

Abstract Purpose There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. Methods A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. Results This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. Conclusion Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

Stefanie D. Krens ◽  
Wim Boxtel ◽  
Maike J.M. Uijen ◽  
Frank G.A. Jansman ◽  
Ingrid M.E. Desar ◽  

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2333
Sabrina Adorisio ◽  
Lorenza Cannarile ◽  
Domenico V. Delfino ◽  
Emira Ayroldi

Programmed cell death protein 1 (PD-1) and its ligands, PD-L1/2, control T cell activation and tolerance. While PD-1 expression is induced upon T cell receptor (TCR) activation or cytokine signaling, PD-L1 is expressed on B cells, antigen presenting cells, and on non-immune tissues, including cancer cells. Importantly, PD-L1 binding inhibits T cell activation. Therefore, the modulation of PD-1/PD-L1 expression on immune cells, both circulating or in a tumor microenvironment and/or on the tumor cell surface, is one mechanism of cancer immune evasion. Therapies that target PD-1/PD-L1, blocking the T cell-cancer cell interaction, have been successful in patients with various types of cancer. Glucocorticoids (GCs) are often administered to manage the side effects of chemo- or immuno-therapy, exerting a wide range of immunosuppressive and anti-inflammatory effects. However, GCs may also have tumor-promoting effects, interfering with therapy. In this review, we examine GC signaling and how it intersects with PD-1/PD-L1 pathways, including a discussion on the potential for GC- and PD-1/PD-L1-targeted therapies to “confuse” the immune system, leading to a cancer cell advantage that counteracts anti-cancer immunotherapy. Therefore, combination therapies should be utilized with an awareness of the potential for opposing effects on the immune system.

2021 ◽  
Vol 34 (Supplement_1) ◽  
Xiufeng Wei ◽  
Yin Li ◽  
Jianjun Qin ◽  
Ruixiang Zhang ◽  
Xiankai Chen ◽  

Abstract   99mTc bone scintigraphy(BS) is still the most widely used method to evaluate bone metastasis in China. The aim of this study was to investigate the necessity of the 99mTc bone scintigraphy in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer (ESCC,cT1-4aN0–3). Methods This was a prospective cross-section clinical trial (ChiCTR1800020304). There were a total of 471 patients who were diagnosed ESCC in Thoracic Surgery Clinic from October 2018 to September 2020. Of these 471 patients, 385 patients with cT1-4aN0–3 who were potentially candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The treatment strategy could be changed if the bone metastasis was confirmed. The primary endpoint was the incidence rate of the treatment regimen being changed because of bone metastasis. The secondary endpoint was the rate of positive BS findings. Results In all 385 patients, there are only 2(0.5%) patients changed their treatment regimen because of bone metastasis proved by BS. The rate of positive BS findings is 1%. The number of patients with false positive and false negative was 2(0.5%) and 2 (0.5%), respectively. The BS diagnostic performance for bone metastasis was as follows: sensitivity, 50%; specificity, 99.5%; positive predictive value, 50%; negative predictive value, 99.5% and accuracy, 99.0%. There were no significant difference of bone metastasis among the Age, Sex, Tumor location and Clinical stage. Conclusion 99mTc bone scintigraphy is unnecessary in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer.

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