Search

Background: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions: We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates. [ABSTRACT FROM AUTHOR]

Background: To explore the maximum tolerated dose (MTD) and evaluate the safety of dose escalation using hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) concurrent with chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC).Methods: Four escalating radiation dose levels were used. This study included 25 patients with previously untreated NSCLC who received six concurrent weekly chemotherapy cycles comprising cisplatin and docetaxel. Dose-limiting toxicity (DLT) was defined as any acute toxicity that interrupted radiotherapy for more than 1 week. MTD was defined as the highest dose level that didn't induce DLT or grade 5 toxicity in two patients.Results: All 25 patients received the prescribed escalating radiation dose from the start dose up to LEVEL 4. Two patients experienced DLT at dose LEVEL 4. One patient died because of upper gastrointestinal hemorrhage within 6 months after radiotherapy, whereas another patient among the additional five patients died because of grade 5 radiation pneumonitis within 2 months after radiotherapy. Dose LEVEL 3 was defined as MTD. The 1- and 2-year local controls were 82.8 and 67.8%, respectively. The median progression-free survival was 15.4 months, whereas the median overall survival was 27.3 months.Conclusions: Dose escalation was safely achieved up to LEVEL 3 [the planning gross target volume (PTVG) 60.5 Gy/22 Fx, 2.75 Gy/Fx; the planning clinical target volume (PTVC) 49.5 Gy/22 Fx] using SIB-IMRT concurrently with chemotherapy for unresectable stage III NSCLC, and the acute toxicities were generally well tolerated. Further prospective studies on long-term outcomes and late toxicities are warranted.Trial Registration: Retrospective registration, ChiCTR1900027290 (08/11/2019). [ABSTRACT FROM AUTHOR]

Purpose: Neuroendocrine cervical carcinoma (NECC) is an uncommon malignancy of the female reproductive system. This study aimed to evaluate cancer-specific mortality and to construct prognostic nomograms for predicting the survival of patients with NECC.Methods: we assembled the patients with NECC diagnosed between 2004 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, we identified other patients with NECC from the Wenling Maternal and Child Health Care Hospital between 2002 to 2017. Fine and Gray's test and Kaplan-Meier methods were used to evaluate cancer-specific mortality and overall survival (OS) rates, respectively. Nomograms were constructed for predicting cancer-specific survival (CSS) and OS for patients with NECC. The developed nomograms were validated both internally and externally.Results: a total of 894 patients with NECC were extracted from the SEER database, then classified into the training cohort (n = 628) and the internal validation cohort (n = 266). Besides, 106 patients from the Wenling Maternal and Child Health Care Hospital served as an external validation cohort. Nomograms for predicting CSS and OS were constructed on clinical predictors. The validation of nomograms was calculated by calibration curves and concordance indexes (C-indexes). Furthermore, the developed nomograms presented higher areas under the receiver operating characteristic (ROC) curves when compared to the FIGO staging system.Conclusions: we established the first competing risk nomograms to predict the survival of patients with NECC. Such a model with high predictive accuracy could be a practical tool for clinicians. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the biomechanical characteristics of grafts from three different anterior cruciate ligament (ACL) reconstructive surgeries and to determine which method is better at restoring knee joint stability. Methods: A 31-year-old female volunteer was enrolled in the study. According to the magnetic resonance imaging of her left knee, a three-dimensional model consisting of the distal femur, proximal tibia and fibula, ACL, posterior cruciate ligament, medial collateral ligament and lateral collateral ligament was established. Then, the ACL was removed from the original model to simulate the knee joint after ACL rupture. Based on the knee joint model without the ACL, single-bundle ACL reconstruction, double-bundle ACL reconstruction, and flat-tunnel ACL reconstruction were performed. The cross-sectional diameters of the grafts were equally set as 6 mm in the three groups. The bone tissues had a Young's modulus of 17 GPa and a Poisson's ratio of 0.36. The ligaments and grafts had a Young's modulus of 390 MPa and a Poisson's ratio of 0.4. Six probes were placed in an ACL or a graft to obtain the values of the equivalent stress, maximum principal stress, and maximum shear stress. After pulling the proximal tibia with a forward force of 134 N, the distance that the tibia moved and the stress distribution in the ACL or the graft, reflected by 30 mechanical values, were measured. Results: The anterior tibial translation values were similar among the three groups, with the double-bundle ACL reconstruction group performing the best, followed closely by the patellar tendon ACL reconstruction group. In terms of stress distribution, 13 out of 30 mechanical values indicated that the grafts reconstructed by flat bone tunnels had better performance than the grafts in the other groups, while 12 out of 30 showed comparable outcomes, and 5 out of 30 had worse outcomes. Conclusion: Compared with traditional single-bundle and double-bundle ACL reconstructions, flat-tunnel ACL reconstruction has advantages in terms of stress dispersion. Additionally, flat-tunnel ACL reconstruction falls between traditional double-bundle and single-bundle ACL reconstructions in terms of restoring knee joint stability and is superior to single-bundle ACL reconstruction. [ABSTRACT FROM AUTHOR]

Objective: The study aims to evaluate the accuracy of an MRI-based artificial intelligence (AI) segmentation cartilage model by comparing it to the natural tibial plateau cartilage. Methods: This study included 33 patients (41 knees) with severe knee osteoarthritis scheduled to undergo total knee arthroplasty (TKA). All patients had a thin-section MRI before TKA. Our study is mainly divided into two parts: (i) In order to evaluate the MRI-based AI segmentation cartilage model's 2D accuracy, the natural tibial plateau was used as gold standard. The MRI-based AI segmentation cartilage model and the natural tibial plateau were represented in binary visualization (black and white) simulated photographed images by the application of Simulation Photography Technology. Both simulated photographed images were compared to evaluate the 2D Dice similarity coefficients (DSC). (ii) In order to evaluate the MRI-based AI segmentation cartilage model's 3D accuracy. Hand-crafted cartilage model based on knee CT was established. We used these hand-crafted CT-based knee cartilage model as gold standard to evaluate 2D and 3D consistency of between the MRI-based AI segmentation cartilage model and hand-crafted CT-based cartilage model. 3D registration technology was used for both models. Correlations between the MRI-based AI knee cartilage model and CT-based knee cartilage model were also assessed with the Pearson correlation coefficient. Results: The AI segmentation cartilage model produced reasonably high two-dimensional DSC. The average 2D DSC between MRI-based AI cartilage model and the tibial plateau cartilage is 0.83. The average 2D DSC between the AI segmentation cartilage model and the CT-based cartilage model is 0.82. As for 3D consistency, the average 3D DSC between MRI-based AI cartilage model and CT-based cartilage model is 0.52. However, the quantification of cartilage segmentation with the AI and CT-based models showed excellent correlation (r = 0.725; P values < 0.05). Conclusion: Our study demonstrated that our MRI-based AI cartilage model can reliably extract morphologic features such as cartilage shape and defect location of the tibial plateau cartilage. This approach could potentially benefit clinical practices such as diagnosing osteoarthritis. However, in terms of cartilage thickness and three-dimensional accuracy, MRI-based AI cartilage model underestimate the actual cartilage volume. The previous AI verification methods may not be completely accurate and should be verified with natural cartilage images. Combining multiple verification methods will improve the accuracy of the AI model. [ABSTRACT FROM AUTHOR]

Aims: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. Methods: MNDA expression in a cohort of 1293 cases of B-NHLs and 338 cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. Results: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). Conclusions: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated. [ABSTRACT FROM AUTHOR]

Background: The positioning of implant components for total hip arthroplasty (THA) is essential for joint stability, polyethylene liner wear, and range of motion. One potential benefit of the direct anterior approach (DAA) for THA is the ability to use intraoperative fluoroscopy for acetabular cup positioning and limb-length evaluation. Previous studies comparing intraoperative fluoroscopy with no fluoroscopy during DAA have reported conflicting results. This meta-analysis aimed to evaluate whether intraoperative fluoroscopy improves component positioning compared to no fluoroscopy during direct anterior total hip arthroplasty. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched Web of Science, EMBASE, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in May 2023 to identify studies involving intraoperative fluoroscopy versus no fluoroscopy during direct anterior total hip arthroplasty. Finally, we identified 1262 hips assessed in seven studies. Results: There were no significant differences in terms of acetabular cup inclination angle (ACIA, P = 0.21), ACIA within safe zone rate (P = 0.97), acetabular cup anteversion angle (ACAA, P = 0.26); ACAA within safe zone rate (P = 0.07), combined safe zone rate (P = 0.33), and limb-length discrepancy (LLD, P = 0.21) between two groups. Conclusion: Even though intraoperative fluoroscopy was not related to an improvement in cup location or LDD. With fewer experienced surgeons, the benefit of intraoperative fluoroscopy might become more evident. More adequately powered and well-designed long-term follow-up studies were required to determine whether the application of the intraoperative fluoroscopy for direct anterior total hip arthroplasty will have clinical benefits and improve the survival of prostheses. [ABSTRACT FROM AUTHOR]

Background: The positioning of implant components for total hip arthroplasty (THA) is essential for joint stability, polyethylene liner wear, and range of motion. One potential benefit of the direct anterior approach (DAA) for THA is the ability to use intraoperative fluoroscopy for acetabular cup positioning and limb-length evaluation. Previous studies comparing intraoperative fluoroscopy with no fluoroscopy during DAA have reported conflicting results. This meta-analysis aimed to evaluate whether intraoperative fluoroscopy improves component positioning compared to no fluoroscopy during direct anterior total hip arthroplasty. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched Web of Science, EMBASE, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in May 2023 to identify studies involving intraoperative fluoroscopy versus no fluoroscopy during direct anterior total hip arthroplasty. Finally, we identified 1262 hips assessed in seven studies. Results: There were no significant differences in terms of acetabular cup inclination angle (ACIA, P = 0.21), ACIA within safe zone rate (P = 0.97), acetabular cup anteversion angle (ACAA, P = 0.26); ACAA within safe zone rate (P = 0.07), combined safe zone rate (P = 0.33), and limb-length discrepancy (LLD, P = 0.21) between two groups. Conclusion: Even though intraoperative fluoroscopy was not related to an improvement in cup location or LDD. With fewer experienced surgeons, the benefit of intraoperative fluoroscopy might become more evident. More adequately powered and well-designed long-term follow-up studies were required to determine whether the application of the intraoperative fluoroscopy for direct anterior total hip arthroplasty will have clinical benefits and improve the survival of prostheses. [ABSTRACT FROM AUTHOR]

Background: Morphological markers presenting the lateral extension of acromion and the greater tuberosity of humerus were proposed to diagnose and predict rotator cuff tears (RCTs) in recent years, but few studies have addressed the combined performance when using two predictors together. As a presence of a RCT may be associated with the impingement caused by both acromion and the greater tuberosity, we believe a combined utilization of predictors could result in a better diagnostic and predictive performance than using a single predictor. The aim of this study is to (i) explore whether the combination is more efficient to predict and diagnose RCTs; (ii) find out which combination is the most superior screening approach for RCTs.Methods: This was a retrospective study and patients who visited our hospital and were diagnosed with or without partial-thickness or full-thickness RCTs via magnetic resonance imaging from January 2018 to April 2022 were enrolled and classified into two groups respectively. Four predictors, the critical shoulder angle (CSA), the acromion index (AI), the greater tuberosity angle (GTA) and the double-circle radius ratio (DRR) were picked to participate in the present study. Quantitative variables were compared by independent samples t tests and qualitative variables were compared by chi-square tests. Binary logistic regression analysis was used to construct discriminating combined models to further diagnose and predict RCTs. Receiver operating characteristic (ROC) curves were pictured to determine the overall diagnostic performance of the involved predictors and the combined models.Results: One hundred and thirty-nine shoulders with RCTs and 57 shoulders without RCTs were included. The mean values of CSA (35.36 ± 4.57 versus 31.41 ± 4.09°, P < 0.001), AI (0.69 ± 0.08 versus 0.63 ± 0.08, P < 0.001), DRR (1.43 ± 0.10 versus 1.31 ± 0.08, P < 0.001) and GTA (70.15 ± 7.38 versus 64.75 ± 7.91°, P < 0.001) were significantly higher in the RCT group than for controls. Via ROC curves, we found the combined model always showed a better diagnostic performance than either of its contributors. Via logistic regression analysis, we found the values of both predictors over their cutoff values resulted in an increasement (20.169-161.214 folds) in the risk of having a RCT, which is more than that by using a single predictor only (2.815 -11.191 folds).Conclusion: The combined utilization of predictors is a better approach to diagnose and predict RCTs than using a single predictor, and CSA together with DRR present the strongest detectability for a presence of RCTs. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features.Methods: Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 was performed on whole section slides, and the results were correlated with clinicopathologic variables.Results: A total of 108 cases were included in the present study with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3 and 69.6%, respectively, of the total cases. Overall, the estimated 5-year overall survival was 70.3 and 20.7% in patients with early- and late-stage tumors, respectively. Deficient MMR was identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n = 4) and MLH1/PMS2 (n = 2). The average age of the six patients with deficient MMR was 45.6 years, and the rate of MMR-deficient tumors in women ≤50 years was relatively higher than that in women over 50 years (10.0% vs. 2.9%; P = 0.266). Half of the patients with deficient MMR were diagnosed with synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, which was significantly more than their intact counterparts (P = 0.002). All six patients with deficient MMR had early-stage tumors, and the majority (83.3%) were platinum sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than in their intact counterparts (30 months vs. 27 months), but significance was not achieved (P = 0.471).Conclusions: Young ovarian CCC patients with concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors, thereby warranting additional studies to determine whether patients harboring MMR abnormalities have a favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: Despite Vast improvements in technology and surgical technique in total knee arthroplasty (TKA), approximately 15–25% TKAs, have suboptimal subjective clinical outcomes. Our study sought to evaluate if sensor-guided balancing improves postoperative clinical outcomes compared to a conventional gap balancing technique. Methods: We searched Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in March 2022 to identify studies involving sensor-guided balancing versus conventional gap balancing technique in TKA. Finally, we identified 2147 knees assessed in nine studies. Results: Compared with manual gap balancing, Sensor-guided gap balancing resulted in less rate of Manipulation under anesthesia (MUA) (P = 0.02), however more rate of intraoperative additional procedures (P = 0.0003). There were no significant differences in terms of KSS (P = 0.21), KSS Function score (P = 0.36), OKS (P = 0.61), KOOS (P = 0.78), operative time (P = 0.17), Mechanical axis (P = 0.69) and rate of reoperation between two groups. Conclusion: Compared with conventional manual gap balancing techniques, sensors have more balancing procedures being performed. However, it did result in a reduction in the rate of MUA. More extensive, high-quality RCTs are required to verify our findings further. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of tourniquet use during primary total knee arthroplasty (TKA) is thought to reduce intraoperative blood loss, improve surgical exposure, and optimize cement fixation. Tranexamic acid (TXA) use can decrease postsurgical blood loss and transfusion requirements. This review aimed to appraise the effects of tourniquet use in TKA for patients with tranexamic acid use. Methods: A meta-analysis was conducted to identify relevant randomized controlled trials involving TXA plus a tourniquet (TXA-T group) and use of TXA plus no tourniquet (TXA-NT group) in TKA. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through October 2021. Results: We identified 1720 TKAs (1690 patients) assessed in 14 randomized controlled trials. Compared with the TXA-NT group, the TXA-T group resulted in less intra-operative blood loss (P < 0.00001) and decreased duration of surgery (P < 0.00001), however more hidden blood loss (P = 0.0004) and less knee range of motion (P < 0.00001). No significant differences were found between two groups in terms of decrease in hemoglobin (P = 0.84), total blood loss (P = 0.79), transfusion rate (P = 0.18), drainage volume (P = 0.06), Visual Analogue Scale (VAS) at either the day of surgery (P = 0.2), 1 day (P = 0.25), 2 day (P = 0.39), 3 day (P = 0.21), 5 day (P = 0.21), 7 day (P = 0.06) or 1 month after surgery (P = 0.16), Hospital for Special Surgery (HSS) score at either 7 day (P = 0.10), 1 month (P = 0.08), 3 month (P = 0.22) or 6 month after the surgery (P = 0.92), Knee circumference (P = 0.28), length of hospital (P = 0.12), and complications such as intramuscular venous thrombosis (P = 0.81), deep venous thrombosis (P = 0.10), superficial infection (P = 0.45), deep wound infection (P = 0.64), and delayed wound healing (P = 0.65). Conclusion: No big differences could be found by using or not tourniquet when use the TXA, though some benefits are related to operation time and less intra-operative blood loss by using tourniquet and TXA, Using the tourniquet was related to more hidden blood loss and less knee range of motion. More adequately powered and better-designed randomized controlled trials (RCTs) studies with long-term follow-up are required to validate this study. [ABSTRACT FROM AUTHOR]