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摘要： Although adjuvant radiotherapy has been used for cutaneous squamous cell carcinoma, its outcome benefits, especially for patients with clear surgical margins, have not been statistically estimated, and the characteristics that can indicate patients who require adjuvant therapy need to be validated with more evidence. We conducted a systematic review and meta-analysis of literature on the survival outcomes and prognostic factors in patients with cSCC treated by surgery with or without adjuvant radiotherapy. Twenty related studies involving 2605 patients met our inclusion criteria. The significant survival outcomes of adjuvant radiotherapy included lower recurrence (OR, 0.56;95% CI, 0.36-0.85), longer disease-free survival (OR, 2.17;95% CI, 1.23-3.83) and longer overall survival (OR, 2.94;95% CI, 1.75-4.91). Significant prognostic factors for poor outcomes were perineural invasion (HR, 1.61;95% CI, 1.24-2.09), involved surgical margins (HR, 2.34;95% CI, 1.42-3.83) and immunosuppression (HR, 3.02;95% CI, 2.14-4.25) while adjuvant radiotherapy significantly contributed to better overall survival (HR, 0.47;95% CI, 0.34-0.65). In conclusion, this systematic review suggests that in cutaneous squamous cell carcinoma patients with risk factors, including metastasis to the parotid gland, perineural invasion and immunosuppression, the use of adjuvant radiotherapy may be beneficial irrespective of surgical margin status.

关键词： Antibiotics   Carp   Cell line   Cytotoxicity   Ecotoxicity   Mussel  

摘要： The ubiquitous use of antibiotics leads exposure of these chemicals on non-target aquatic species, while the toxicity assays for these chemicals are time/labor consuming and expensive. Alternative approaches using primary cell cultures which retain the tissue functionality at its highest form have received global attention compared to cell lines. In the current study, the cytotoxic effects of two commonly used antibiotics from amphenicol (florfenicol) and macrolide (erythromycin) groups were evaluated on primary cell cultures of Unio crassus (mantle, digestive gland, gill, and gonad) and Cyprinus carpio (gill and liver) using MTT and Neutral Red assays. The highest cytotoxic effects were found on the mussel digestive gland and carp liver cells for florfenicol and erythromycin, while the lowest cytotoxic effects were found in mussel mantle cells for both drugs in the MTT test. In the NR test, the highest cytotoxic effects of erythromycin and florfenicol were found in the mussel gill, mantle, gonad, and carp gill cells;the lowest cytotoxic effect of erythromycin was found in the mussel digestive gland, while the lowest effect of florfenicol was found in the carp liver cells. The cytotoxicity of florfenicol was quite low for the carp liver, while the cytotoxicity of erythromycin was quite low in the mussel digestive tract. Thus, it was concluded that cells made from mussel tissues could be used in ecotoxicity tests, and sensitivity may vary according to the tissue.

关键词： Phenotype   Clustering   Cell tracking   Cell morphology   Cell motility  

摘要： In vitro cell culture model systems often employ monocultures, despite the fact that cells generally exist in a diverse, heterogeneous microenvironment in vivo. In response, heterogeneous cultures are increasingly being used to study how cell phenotypes interact. However, the ability to accurately identify and characterize distinct phenotypic subpopulations within heterogeneous systems remains a major challenge. Here, we present the use of a computational, image analysis-based approach-comprising automated contour-based cell tracking for feature identification, principal component analysis for feature reduction, and partitioning around medoids for subpopulation characterization-to non-destructively and non-invasively identify functionally distinct cell phenotypic subpopulations from live-cell microscopy image data. Using a heterogeneous model system of endothelial and smooth muscle cells, we demonstrate that this approach can be applied to both mono and co-culture nuclear morphometric and motility data to discern cell phenotypic subpopulations. Morphometric clustering identified minimal difference in mono- versus co-culture, while motility clustering revealed that a portion of endothelial cells and smooth muscle cells adopt increased motility rates in co-culture that are not observed in monoculture. We anticipate that this approach using non-destructive and non-invasive imaging can be applied broadly to heterogeneous cell culture model systems to advance understanding of how heterogeneity alters cell phenotype.

关键词： convolutional neural networks (CNN)   unet   machine learning   semantic segmentation   demosponge behavior   classification   time series   deep learning   image analysis  

摘要： Biological data sets are increasingly becoming information-dense, making it effective to use a computer science-based analysis. We used convolution neural networks (CNN) and the specific CNN architecture Unet to study sponge behavior over time. We analyzed a large time series of hourly high-resolution still images of a marine sponge, Suberites concinnus (Demospongiae, Suberitidae) captured between 2012 and 2015 using the NEPTUNE seafloor cabled observatory, off the west coast of Vancouver Island, Canada. We applied semantic segmentation with the Unet architecture with some modifications, including adapting parts of the architecture to be more applicable to three-channel images (RGB). Some alterations that made this model successful were the use of a dice-loss coefficient, Adam optimizer and a dropout function after each convolutional layer which provided losses, accuracies and dice scores of up to 0.03, 0.98 and 0.97, respectively. The model was tested with five-fold cross-validation. This study is a first step towards analyzing trends in the behavior of a demosponge in an environment that experiences severe seasonal and inter-annual changes in climate. The end objective is to correlate changes in sponge size (activity) over seasons and years with environmental variables collected from the same observatory platform. Our work provides a roadmap for others who seek to cross the interdisciplinary boundaries between biology and computer science.

关键词： Head and neck cancer   Human papillomavirus   Squamous cell carcinoma   Squamous cell carcinoma of unknown primary  

摘要： Purpose: To examine the potential benefit of reevaluation of original slides and p16 immunohistochemistry (IHC) of tonsillectomy specimens for primary tumor identification in cases of human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck of unknown primary. Materials and methods: Through a retrospective review, we identified all patients 18 or older who presented at our institution from 2003 to 2015 with histologically confirmed HPV-positive SCC in a cervical lymph node with unidentified primary tumor after initial workup. For patients for whom specimens were available, an expert head and neck pathologist re-reviewed original hematoxylin and eosin (H&E) slides to confirm absence of tumor and performed p16 IHC and deep sectioning of tissue blocks to identify potential tumor foci. Results: Among 735 patient records assessed, 80 were HPV-positive SCC with unknown primary, 28 of which did not have a primary tumor identified, and 20 with original specimens available. Upon re-review of 103 original H&E slides, invasive SCC was identified for 2 patients. Deep sectioning and p16 IHC did not identify additional primary tumors. Conclusion: Re-review of original slides by an expert head and neck pathologist, but not p16 staining or deeper H&E sections, was able to identify additional tumors.

关键词： Primary renal tumour   Renal cell carcinoma   Nivolumab   Cytoreductive nephrectomy   Immune checkpoint inhibitors  

摘要： Primary tumour response may impact therapeutic strategies in metastatic renal cell carcinoma (mRCC) but remains unknown in the era of immune checkpoint inhibitors. We aimed to describe the response of the primary tumour in patients who did not undergo upfront cytoreductive nephrectomy (uCN) and were treated with nivolumab in the GETUG-AFU-26 NIVOREN phase 2 trial. Primary tumour response was prospectively assessed, as well as the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Among 720 patients, 111 did not undergo uCN, mainly patients with intermediate (45%) and poor (49%) International mRCC Database Consortium (IMDC) risk. In the 111 patients, nivolumab was used in the second line for 63% of patients and the third line or more for 37%, with an ORR of 16% (95% confidence interval ICI] 1025%);with a median follow-up of 24.5 mo (95% CI 21.6-27.1), median PFS was 2.7 mo (95% CI 2.5-4.0) and median OS was 15.9 mo (95% CI 9.5-19.8). A total of 67 patients had an evaluable primary renal lesion, four of whom (6%) experienced shrinkage of more than 30%. Overall, patients who did not undergo uCN had adverse baseline characteristics and nivolumab activity against the primary tumour was limited. Patient summary: In this report, we observed that nivolumab was associated with a limited response of the primary tumour in previously treated patients with metastatic kidney cancer. (c) 2021 Published by Elsevier B.V. on behalf of European Association of Urology.

关键词： Thyroid gland   T lymphocytes   Lymphoproliferative disorders   Hashimoto disease   Tertiary lymphoid structures  

摘要： Thyroid lymphoproliferative disorder is known to be associated with Hashimoto thyroiditis. The major histological types of thyroid lymphoproliferative disorders are malignant lymphoma, such as diffuse large B cell lymphoma, extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT), and follicular lymphoma. All of these are B cell lymphomas;however, T cell lymphoproliferative disorders represent only a minority of cases. Since T cell lymphoproliferative disorder rarely develops and T cell lymphoma is a heterogeneous entity, it is difficult to concisely summarize this complex topic. Here, we present a case of primary thyroid T cell lymphoproliferative disorder reminiscent of indolent T cell lymphoproliferative disorder of the gastrointestinal tract: the pathological findings from this case also were similar to those of MALT lymphoma such as small lymphoid cells, lymphoepithelial lesions, and a low Ki-67 labeling index. T cell lymphoproliferative disorders with these pathological features have been reported in the thyroid gland, lymph nodes, palate, spleen, and gastrointestinal tract. Furthermore, we reviewed and summarized the studies on thyroid T cell lymphoproliferative disorders and compared the cases and their clinicopathological characteristics.

关键词： PET   PET/CT   Rituximab   CHOP   Large B-cell lymphoma   Primary mediastinal   Radiotherapy  

摘要： End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%;44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

关键词： Ectopic   Primary hyperparathyroidism   Giant parathyroid adenoma   Water clear cell adenoma   Case report  

摘要： Background: Ectopic parathyroid gland is not uncommon, and is associated with primary hyperparathymidism. Giant parathyroid adenoma (PA) and concurrent presence of enlarged thyroid nodule increases the probability of ectopic location. The combination of a giant PA that is ectopic (within the strap muscle) in the neck is very rare, especially in cases with no previous surgery. The rare histopathological findings of the current case, water clear cell parathyroid adenoma (WCCPA), could explain the patient's presentation, since it has low endocrine function. Case presentation: A 56-year-old Qatari female on routine visit to primary health care physician for hypertension, was incidentally discovered to be hypercalcemic and was referred to the emergency department of our institution. Neck ultrasound showed a thyroid nodule on the left side, but Tc-99m-sestamibi scintigraphy identified a left PA. FNAC of the thyroid nodule showed that it was a colloid nodule. She underwent left hemithyroidectomy and excision of left PA. Intraoperatively, the PA was giant and in the sternohyoid muscle. Intraoperative monitoring of intact PTH (IOiPTH) confirmed successful excision. Discussion: Ectopic giant parathyroid adenoma is rare especially with the intramuscular location in sternohyoid muscle in the neck without previous neck surgeries. The presence of thyroid nodule could be a precipitating factor for migration of the PA. Preoperative assessment with the radiological image is crucial for diagnosis but sometimes fail to localized the PA. Conclusion: Giant asymptomatic PA with long standing low function before hyperfunctioning should raise the suspicion of WCCPA. If diagnosis is confirmed, metastasis from a clear cell renal cell carcinoma should be ruled out.

关键词： incidence   nomogram   prognosis   pulmonary acinar cell carcinoma   SEER  

摘要： Purpose The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). Methods PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. Results A total of 2918 patients were identified with PACC. The mean age was 65.2 +/- 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. Conclusion PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.