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Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.
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Objective To identify the potential long non-coding RNA (lncRNA) expressed in rheumatoid arthritis (RA) synovium key to RA onset and investigate its association with immune cell infiltration. Methods RA synovium data were downloaded from the GEO database and normalized. The lncRNAs key to RA onset were identified using multiple machine learning methods. Infiltration of 22 immune cell populations in RA synovium was measured by cell-type identification by estimating relative subsets of RNA transcripts (CIBER-SORT). The relationship between the key lncRNA and infiltrating immune cells was analyzed. Finally, real-time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells. Results lncRNA human leukocyte antigen complex P5(HCP5) was identified as the key lncRNA associated with RA onset. Infiltration analysis revealed increased abundance of CD8+ T cells, γδ T cells, and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue. Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8+ T cells, γδ T cells, and M1 macrophages in RA synovial tissue. Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up-regulated. Conclusion lncRNA HCP5 expression is up-regulated in RA synovial tissue and potentially associated with immune cells infiltration.
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Humanos , Artrite Reumatoide , Linfócitos T CD8-Positivos , Antígenos HLA/metabolismo , RNA Longo não Codificante/metabolismo , Membrana Sinovial/metabolismoRESUMO
Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.
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Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Cutâneas/patologia , Prognóstico , Estudos Retrospectivos , Hibridização in Situ Fluorescente , China , Melanoma/diagnóstico , Doenças da Unha/patologia , Antígenos de NeoplasiasRESUMO
Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4%(56/1 035).The positive rate of ALK(1A4)was 7.2%(75/1 035),and that of ALK(D5F3)was 5.7%(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100%and 98.2%,and the specifici-ties were 98.1%and 99.6%,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.
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OBJECTIVE@#To measure and compare medial proximal tibial angle (MPTA) of lower limbs under different axial rotation angles(neutral position, 30° internal rotation, 30° external rotation) on the load position radiographs, and explore changes and significance of MPTA measured within and between groups of tibia at different axial rotation positions.@*METHODS@#From January 2018 to December 2018, 40 patients with knee osteoarthritis (KOA) were selected, with a total of 80 limbs, including 12 males and 28 females, aged from 29 to 73 years old with an average of (59.6±12.7) years old. Full length radiographs of the lower limbs were taken on neutral tibia position, 30° internal rotation and 30° external rotation, respectively. MPTA was measured and the results were compared between groups and within groups.@*RESULTS@#MPTA measured on the left lower extremity of neutral tibia, 30° internal rotation and 30° external rotation were (86.08±2.48) °, (88.62±2.94) ° and (83.47±3.10) °, respectively. MPTA measured on the right lower limb were (86.87±1.97) °, (89.02±2.39) ° and (83.80±2.77) °, respectively, and there were no significant difference in MPTA measured between rotation angle group (P>0.05). While there were statistical difference in MPTA on the same limb between groups (P<0.05). On 30° internal rotation, MPTA of left and right lower limbs increased by (2.54±1.74) ° and (2.15±1.78) ° compared with tibia neutral position. On 30° external rotation, MPTA of left and right lower limbs decreased (2.61±2.03) ° and (3.07±1.75) ° compared with tibial neutral position.@*CONCLUSION@#When a full-length X-ray film is taken on the weight-bearing position of both lower limbs, if there is axial rotation or external rotation of tibia, MPTA will increase or decrease compared with neutral position, which may cause a certain degree of deviation in clinical operation based on the accurate measurement of MPTA. However, the extent to which this bias affects the clinical operation effect remains to be verified. In addition, limited by the total number of samples and the number of measurement groups, whether there is a linear relationship between MPTA deviation and tibial axial rotation needs to be further studied.
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Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Tíbia/cirurgia , Extremidade Inferior , Osteoartrite do Joelho/cirurgia , Radiografia , Osteotomia/métodos , Articulação do Joelho/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE@#To investigate whether the anteversion angle of acetabular prosthesis can be evaluated on the anteroposterior X-ray film of common double hip joint.@*METHODS@#Total 32 patients(41 hips) after total hip arthroplasty were selected, including 18 males and 14 females, aged(66.2±4.1) years. All patients completed the positive X-ray film of both hips and plain CT scan of pelvis after operation. Acetabular anteversion was measured by plain CT scan of pelvis, and measured by Saka and other measurement formulas on X-ray film.@*RESULTS@#The acetabular anteversion measured by X-ray film was(16.2±5.0)° and that measured by CT was (31.8±9.7)°(P=0.00). In addition, there was a significant linear correlation between X-ray film and CT(Pearson correlation coefficient (r=0.84, P=0.00).@*CONCLUSION@#CT can accurately measure the acetabular anteversion, but it has obvious disadvantages, such as large radiation, high cost, phantom CT artifact and so on. Although Saka measurement formula can not directly obtain the accurate acetabular anteversion as CT measurement, it has a high correlation with the acetabular anteversion measured by CT. Therefore, the method proposed in this study can also preliminarily evaluate the acetabular anteversion.
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Feminino , Humanos , Masculino , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Articulação do Quadril/cirurgia , Prótese de Quadril , PelveRESUMO
The use of tourniquets in total knee arthroplasty (TKA) helps to obtain a blood-free operating space and clear anatomical landmarks, reduce the operation time and intraoperative bleeding and facilitate bone cement fixation. Arterial calcification is relatively common in the elderly people. There is still no consensus on whether it is safe to use tourniquets in patients with arterial calcification in total knee arthroplasty. Some studies showed that the use of tourniquets in patients with vascular calcification does not increase postoperative complications. Other studies showed that the use of tourniquets in patients with calcification will increase postoperative vascular complications. This article reviews the use of tourniquets in patients with vascular calcification. It is recommended that patients with vascular calcification should undergo detailed lower extremity vascular and cardiovascular assessments before surgery. The consult to a vascular surgeon is important. For patients with extensive vascular calcification, It's better to avoid the use of tourniquets during TKA to reduce possible complications.
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Objective:To identify the key genes related to rheumatoid arthritis (RA) by to the weighted gene co-expression network analysis (WGCNA) and experimental verification to find key genes related to RA.Methods:The microarray data of RA were downloaded from the Gene Expression Omnibus (GEO) database. Gene network was constructed, and the genes were classified into different modules using WGCNA. HUB genes in modules related to RA clinical symptoms were analyzed by gene ontology. Subsequently, different data sets of GEO were used to verify the expression profile and diagnostic capacity of the HUB gene [receiver operating characteristic curve (ROC)]. In addition, the expression of HUB gene in RA was verified by real time polymerase chain reaction (RT-PCR) and Western blot, and the relationship between key genes and disease activity score 28 joints (DAS28) was analyzed. Paired-sample t-test and Pearson's correlation analysis was used for statistical analysis. Results:A total of 5 413 differentially expressed genes were filtered. Weighted gene coexpression network was constructed and genes were classified into 23 modules. Among them, the black module is closely related to the clinical symptoms of RA, which contained 346 genes. Enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signal pathway analysis showed that it was to be enriched in the positive regulation of interleukin 6, interleukin 1 beta secretion, osteoclast differentiation, NOD-like receptor signaling pathway, T helper cell 17 (Th17) cell differentiation and many other pathways closely related to RA. Motile sperm domain-containing protein 2 (MOSPD2) was significantly correlated with clinical symptoms. It was highly expressed in blood monocytes and bone marrow monocytes ( t=2.238, P=0.032; t=3.153, P=0.006), and positively correlated with blood expression in RA joint synovial fluid ( r=0.683, P=0.03). ROC curve analysis determined that MOSPD2 could distinguish RA from the control group (the area under the curve was 0.855 and 0.726) respectively. RT-PCR and Western blotting results showed that MOSPD2 was up-regulated in RA patients ( t=-3.96, P=0.02). MOSPD2 expression levels in blood were positively correlated with DAS28 in RA patients ( r=0.884 6, P=0.046 2). Conclusion:MOSDP2 is closely related to the clinical symptoms of RA patients, and may be one of the targets for the diagnosis and treatment of RA.
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Objective To analyze the correlation between tortuosity and stenosis in patients with myocardial bridge(MB)on the left anterior descending artery(LAD). Methods Data of patients with MB on the LAD,which was discovered by coronary computed tomography angiography(CCTA),in the Affiliated Hospital of North China University of Science and Technology from October 2015 to December 2018 were retrospectively analyzed.Among them 278 patients with tortuosity on LAD and 278 patients without tortuosity were selected.The clinical charateristics(age,gender,hypertension,hyperlipidemia,diabetes,smoking history,and family history)as well as the incidence and severity of stenosis of LAD were recorded and compared. Results The incidence of coronary artery stenosis in the non-tortuosity group(57.6%)was significantly lower than that in the tortuosity group(71.9%)($\bar{χ}$=12.608,
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Humanos , China , Constrição Patológica , Angiografia Coronária , Estenose Coronária/epidemiologia , Vasos Coronários/diagnóstico por imagem , Ponte Miocárdica/patologia , Estudos RetrospectivosRESUMO
A case report of periprosthetic hip clostridium perfringens infection 13 years after total hip arthroplasty, the patient had hip pain with fever for one week. Physical examination and imaging examination confirmed the periprosthetic joint infection. The pathogenic bacterium was clostridium perfringens according to bacterial culture, and the pathogenic bacterium of clostridium perfringens was suspected relating to the gallbladder disease in this patient. Considering such periprosthetic joint infection was early stage hematogenous periprosthetic joint infection, treatment of debridement, retention of the prosthesis, irrigating, and indwelling drainage tube were conducted. By reviewing literature about periprosthetic clostridium perfringens infection, only seven reports of periprosthetic joint infection were caused by clostridium perfringens, which were all case reports. From the previous case reports and our case, we found that the infection around the prosthesis caused by clostridium perfringens was limited to the area around the joint, and prognosis of such cases may not be as severe as the natural gas gangrene which developed very rapidly, but great attention should be paid to. The hematogenous periprosthetic joint infection caused by clostridium perfringens who had gastrointestinal symptoms in the early stage should be highly suspicious of gallbladder lesions and thorough debridement, retention of the prosthesis, irrigating and indwelling drainage tube maybe a treatment method.
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Objective@#To review the clinical data of patients who underwent maxillary and mandibular reconstruction with vascularized fibula osteomycutaneous flap, using virtual surgery planning.@*Methods@#From January 2012 to December 2016, 23 patients with mandibular defect and 2 patients with maxillary defect were treated in our department. In virtual surgery planning, the optimal osteotomy line and angle were designed. Segmental maxillectomy and mandibulectomy, as well as mandibular reconstruction were performed using guided templates to practice the virtual planning.Actual reconstruction results were compared with those of virtual surgery.@*Results@#Among the 25 patients, 2 patients were repaired with the ipsilateral fibula myocutaneous flap, 22 patients were lateral fibula myocutaneous flap. One case of maxillary type Ⅱd defect was repaired with left fibular muscle flap. All patients were followed up for 12 to 48 months. Satisfied bony unions and occlusion were observed in 25 patients.All patients reported excellent or good facial appearance. One of them received dental implants at 1 year postoperatively.@*Conclusions@#An ideal contour of maxilla and mandible can be obtained using vascularized fibula osteomycutaneous flap in virtual surgery.
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Objective@#To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features.@*Methods@#Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed.@*Results@#BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033).@*Conclusion@#BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.
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A case report of periprosthetic hip clostridium perfringens infection 13 years after total hip arthroplasty, the pa?tient had hip pain with fever for one week. Physical examination and imaging examination confirmed the periprosthetic joint infec?tion. The pathogenic bacterium was clostridium perfringens according to bacterial culture, and the pathogenic bacterium of clos?tridium perfringens was suspected relating to the gallbladder disease in this patient. Considering such periprosthetic joint infection was early stage hematogenous periprosthetic joint infection, treatment of debridement, retention of the prosthesis, irrigating, and in?dwelling drainage tube were conducted. By reviewing literature about periprosthetic clostridium perfringens infection, only seven reports of periprosthetic joint infection were caused by clostridium perfringens, which were all case reports. From the previous case reports and our case, we found that the infection around the prosthesis caused by clostridium perfringens was limited to the ar?ea around the joint, and prognosis of such cases may not be as severe as the natural gas gangrene which developed very rapidly, but great attention should be paid to. The hematogenous periprosthetic joint infection caused by clostridium perfringens who had gastrointestinal symptoms in the early stage should be highly suspicious of gallbladder lesions and thorough debridement, retention of the prosthesis, irrigating and indwelling drainage tube maybe a treatment method.
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Objective@#To investigate the clinicopathologic features and prognosis of ALK-positive Spitz tumors.@*Methods@#Thirteen patients with ALK-positive Spitz tumors diagnosed at Shanghai Cancer Center, Fudan University from October 2016 to December 2017 were collected. All cases were routinely evaluated histopathological features in HE staining and detected ALK protein expression by immunohistochemistry. The ALK fusions of 7 cases were confirmed by fluorescence in situ hybridization (FISH).Follow-up data was collected.@*Results@#The age of patients including 2 males and 11 females ranged from 4 to 47 years (mean 25 years). 12 patients were diagnosed with atypical Spitz tumors and 1 patient was diagnosed with Spitz nevus. Clinically, most lesions presented as papules or nodules, while a few lesions presented as plaques. Histologically, most tumors were exophytic (9/13). More than half of the tumors were amelanotic and the junctional component was mainly composed of melanocytic nests. Kamino bodies were not found. The bases of the tumors were mainly wedge-shaped (5/13) and flat (7/13). Eight tumors displayed mixed cell types, while 5 tumors were composed of only spindle cells. All the tumors showed a plexiform and/or intersecting fascicular growth pattern, and perineural extension was observed in 3 tumors. ALK immunohistochemistry showed diffuse and intense cytoplasmic staining in 13 cases, and 7 of them were detected by FISH to confirm the presence of ALK fusions. All patients were followed up for 7 to 21 months (median=12), with no recurrence or lymph node dissemination.@*Conclusions@#Spitz tumors with ALK fusions have their special histopathologic features.ALK fusions mainly occur in Spitz nevi and atypical Spitz tumors. The follow-up data of the existing literatures and our research indicates that the prognosis of ALK-positive Spitz tumors may be good.
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Objective@#To evaluate the effect of vascular localization using computerized tomography angiography (CTA) combined with refined three dimensional (3D) printing in guiding the resection and reconstruction of complex oral cancer.@*Methods@#From December 2013 to July 2017, the clinical data of 30 patients with complex oral cancer enrolled in the Hunan Cancer Hospital were retrospectively analyzed. 15 patients received CTA+ 3D assisted surgery, while the other 15 patients underwent traditional surgery. In CTA+ 3D assisted surgery group, CT and Magnetic Resonance Imaging (MRI) data were combined with CTA to print refined solid 3D model and surgical guide plate. The preoperative and intraoperative virtual surgical system and the operative experience were combined for preoperative evaluation and surgery. In traditional surgery group, preoperative evaluation and surgery were performed according to imaging data and surgeons′ clinical experience. Operative time, intraoperative blood loss, hospital stay and local recurrence rate were compared between the two groups.@*Results@#In CTA+ 3D assisted surgery group, one patient gave up surgical treatment after intuitively watching the lesion through the 3D model, and the remaining 14 patients underwent surgery as planned. All the 15 patients in traditional surgery group received surgery. But the preoperative plans of three patients were temporarily and passively modified due to insufficient preoperative evaluation. The average intraoperative blood loss was(320.1±27.2)ml in CTA+ 3D assisted surgery group and(430.2±30.3)ml in traditional surgery group. Mean operation time was(440.3±19.2)min and(552.2±23.3)min, respectively. Mean hospitalization time was (20.4±3.2)d and (25.1±3.7)d, respectively. The differences were all statistically significant (all P<0.05). 1 year and 3 years local recurrence rates were 9.1% and 28.6% in CTA+ 3D assisted surgery group, as well as 14.3% and 50.4% in traditional surgery group with statistical significance (P<0.05).@*Conclusion@#For complex oral cancer patients with difficulty in opening the mouth or postoperative recurrence, CTA vascular localization combined with fine 3D printing technology has significant advantages in the surgical process, surgical effect and postoperative evaluation index compared with traditional method using imaging data and clinical experience.
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Aim To explore the anti-psoriatic effects of honokiol on the mouse model induced by imiquimod and the underlying mechanism. Methods The mice were randomly divided into control group, model group, liposome solvent control group, dexamethasone positive group and honokiol high, medium, low dose groups. The progress of the disease was observed by the psoriasis area and severity index (PASI). The morphological changes of the skin cells were observed by HE staining, and epidermis thickness was meas-ured. The expression of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB was semi-quantitively analyzed by immunohistochemistry. Results Compared to model group, the scaling and thickness of honokiol treated groups were alleviated. Inflammatory infiltration and micro abscess were reduced. The expressions of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB in model group were higher than those in honokiol-high and honokiol-medium group in a dose-dependent manner. Conclusion Honokiol can inhibit imiquimod-induced psoriasis-like lesions in mice by inhibiting the IL-17/IL-23 inflammatory axis.
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PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.
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Humanos , Povo Asiático , Neoplasias da Mama , Mama , Quinase do Ponto de Checagem 2 , Citoplasma , Dano ao DNA , Reparo do DNA , DNA , Estrogênios , Genes BRCA1 , Genes BRCA2 , Imuno-Histoquímica , Fosfotransferases , Rad51 Recombinase , Receptores ErbBRESUMO
Objective@#To study the clinicopathologic features, differential diagnosis and prognosis of lentigo maligna (LM) and lentigo maligna melanoma (LMM).@*Methods@#Histopathologic evaluation and immunohistochemical study by HRP multimer method were carried out in 24 cases of LM and LMM from 2012 to 2017 at Fudan University Shanghai Cancer Center. The clinical information and follow-up data were analyzed.@*Results@#Of total 24 cases, there were 7 cases of LM and 17 cases of LMM; 10 males and 14 females. The age of patients ranged from 32 to 88 years (mean 67 years). The male-to-female ratio was 1.0∶1.4. Tumors were all located on head and face. Clinically, all patients presented with mottled light brown or sepia macule located on head and face for a long time, and some of them followed by nodules or ulceration within the lesion. The diameter of lesions ranged from 0.5 to 3.0 cm. Microscopically, LM and in-situ component of LMM were all characterized by a predominantly junctional proliferation of atypical melanocytes with marked pleomorphism, frequently extending down the walls of hair follicles and sweat ducts. Multinucleate cells were frequently present. The invasive components of LMM mainly consisted of atypical melanocytic spindle cells (13 cases, 76.5%), and the mean Breslow thickness was 1.2 mm (0.1-2.7 mm). The lesions of LM/LMM were generally associated with severe actinic damage, scattered infiltration of lymphocytes and melanophages. Statistically, the number of cases whose diameter of lesion ≥0.6 cm, mitotic rates ≥4/mm2 and nests of melanocytes within epidermis in group of LMM were significantly more than those in group of LM. Immunohistochemically, atypical melanocytes in LM and LMM were generally positive for S-100, HMB45, PNL2, Melan A and SOX-10. Follow-up was available in all cases, ranging from 1 to 64 months. Only one out of 23 patients with wide surgical excision had local recurrence, and the remaining 22 patients were all alive with no evidence of disease. One LM patient who was merely treated with biopsy was alive with disease progression after 20 months follow-up.@*Conclusions@#LM/LMM is a special subtype of melanoma predominantly located on the sun-exposed skin of elderly people. Recognition of its specific histologic features can help distinguish with sun-damaged diseases and other subtypes of melanoma. The prognosis of LM/LMM patients treated with surgical excision is considered relatively favorable. However, long term follow-up should be recommended in patients with LM/LMM because of high recurrence rates indicated by previous studies.
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Objective@#To investigate the difference between routine hematoxylin-eosin (HE) staining and immunohistochemistry in diagnosing metastatic melanoma in sentinel lymph node (SLN) metastases, and to evaluate the association of SLN tumor burden with the status of non-sentinel lymph nodes (NSLN).@*Methods@#126 melanoma patients were treated with SLN biopsy and further examined with immunohistochemistry at Fudan University Shanghai Cancer Center between 2010 and 2016, and the status of SLN was respectively estimated by HE stain and immunohistochemistry (S-100 protein, HMB45, Melan A and SOX10). In 39 patients who were treated with complete lymph node dissection, characteristics of SLN tumor burden (maximum diameter of the tumor deposit, tumor penetrative depth and the microanatomic location of the metastasis) and the associations of SLN tumor burden with the involvement of NSLN were all evaluated.@*Results@#Of the total 126 cases, 33 (26.2%) were positive by HE staining and 49 (38.3%) were positive by immunohistochemistry. S-100 protein was positive in 48 out of 49 cases (98.0%). HMB45 was positive in 46 out of 49 cases (93.9%). Melan A was positive in 47 out of 49 cases (96.0%). SOX10 was positive in 8 out of 8 cases. The outcome indicated that the application of immunohistochemistry identified positive SLN missed by HE stain in about 12.1% of cases. Of the 39 patients who were treated with complete lymph node dissection, six showed metastases in NSLN. The frequency of metastases in NSLN was 15.4% (6/39) when SLN was positive. Additionally, the frequency of metastases in NSLN in cases with SLN metastatic deposits ≤2 mm was significantly lower than that in cases with SLN metastatic deposits >2 mm; eight cases with SLN metastatic deposits <0.2 mm had no additional positive NSLN.@*Conclusions@#The findings suggest that immunohistochemistry could effectively improve the detection of positive SLN in melanoma. Cases with SLN metastatic deposits ≤2 mm are less likely to have further metastases in NSLN. There is a need for prospective large-population based studies to identify a subgroup of SLN positive patients who can safely be spared complete lymph node dissection.
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<p><b>OBJECTIVE</b>To observe the therapeutic effects of arthroscopic treatment for recurrent patellar dislocation by anatomical reconstruction of medial patellarfemoral ligament.</p><p><b>METHODS</b>From June 2009 to December 2014, 25 patients with recurrent patellar dislocation were treated with anatomical reconstruction of medial patellarfemoral ligament surgery under arthroscopy. There were 10 males and 15 females, with an average age of 18.4 years old (ranged, 15 to 25 years old ). There were 15 patients who had a medical history of sports injury, 7 patients had a chronic impairment history, and the other 3 patients had the symptoms without obvious predisposing causes. Fourteen patients had injuries on the right knee and 11 patients had injuries on the left knee. All the patients suffered from patellar dislocation 3 to 10 times. After operation, the exercise of knee joint were performed postoperatively. The knee range of motion, Lysholm score, Kujala score, Insall criteria, Patellar apprehension test and patellar grinding test were observed to evaluate the clinical effects.</p><p><b>RESULTS</b>All the patients were followed up, and the duration ranged from 12 to 48 months, with an average of 24.8 months. After surgery, all the wounds were healed excellent and there were no complications like surgical incision infection or patellar redislocation. The ranges of motion was increased from preoperative (105.40±5.93)° to postoperative(122.60±5.42)°. At the latest follow-up, the Lysholm scores were increased from preoperative 64.12±7.49 to postoperative 91.44±5.53, the Kujala scores were increased from preoperative 57.88±5.10 to postoperative 92.44±2.69. According to the Insall criteria, 19 patients got an excellent result, 5 good and 1 fair.</p><p><b>CONCLUSIONS</b>It has a satisfactory clinical therapeutic effect on anatomical reconstruction of medial patellarfemoral ligament under arthroscopy for the treatment of recurrent patellar dislocation. It is helpful for the relief of clinical symptoms and improvement of knee joint function.</p>