Fine needle aspiration biopsy indications for thyroid nodules: compare a point-based risk stratification system with a pattern-based risk stratification system.

OBJECTIVES: We aim to compare the diagnostic performance to assess thyroid nodules and reliability for recommending fine needle aspiration biopsy (FNAB) between American College of Radiology thyroid image reporting and data system (ACR TI-RADS) and American Thyroid Association (ATA) guidelines. METHODS: In total, this retrospective study included 1001 consecutive thyroid nodules in 918 patients from May 2016 to December 2017. US features of the thyroid nodules, including composition, echogenicity, shape, margins, echogenic foci, and size, were reviewed and were classified according to ACR TI-RADS and ATA guidelines, respectively. The diagnostic performance to assess thyroid nodules and reliability for recommending fine needle aspiration biopsy were compared between ACR TI-RADS and ATA guidelines. RESULTS: Of the 1001 thyroid nodules, 609 (60.8%) were benign and 392 (39.2%) were malignant. The sensitivity, specificity, PPV, NPV, and accuracy were 96.7%, 77.3%, 73.3%, 97.3%, and 84.9%, respectively, for ACR TI-RADS and 99.2%, 16.1%, 43.2%, 97.0%, and 48.7%, respectively, for ATA guidelines. AUC of ACR TI-RADS was significantly greater than ATA guidelines (0.935 (0.918, 0.949) vs 0.884 (0.862, 0.903), p < 0.001). Biopsy yield of malignancy, biopsy rate of malignancy, and unnecessary FNAB rate were 59.5%, 91.3%, and 40.5%, respectively, for ACR TI-RDS and 38.5%, 97.4%, and 61.5%, respectively, for ATA guidelines. CONCLUSIONS: ACR TI-RADS was more accurate than ATA guidelines for differentiating malignant thyroid nodules from benign nodules and more reliable than ATA guidelines for recommending thyroid nodules for FNAB. KEY POINTS: • Malignant risk of thyroid nodules can be stratified by ultrasound. • American College of Radiology guidelines were more accurate for differentiating malignant thyroid nodules from benign nodules. • American College of Radiology guidelines were more reliable for recommending thyroid nodules for biopsy.

Computer-Aided Diagnosis of Solid Breast Lesions With Ultrasound: Factors Associated With False-negative and False-positive Results.

OBJECTIVES: To investigate factors that may lead to false-positive or false-negative results in a computer-aided diagnostic system (S-Detect; Samsung Medison Co, Ltd, Seoul, Korea) for ultrasound (US) examinations of solid breast lesions. METHODS: This prospective study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital. All patients signed and provided written informed consent before biopsy or surgery. From September 2017 to May 2018, 269 consecutive women with 338 solid breast lesions were included. All lesions were examined with US and S-Detect before biopsy or surgical excision. The final US assessments made by radiologists and S-Detect were matched to the pathologic results. Patient and lesion factors in the "true" and "false" S-Detect groups were compared, and multivariate logistic regression analyses were used to identify the factors associated with false S-Detect results. RESULTS: The mean age of the patients ± SD was 42.6 ± 12.9 years (range, 18-77 years). Of the 338 lesions, 209 (61.8%) were benign, and 129 (38.2%) were malignant. Larger lesions, the presence of lesion calcifications detected by B-mode US, and grades of 2 and 3 according to Adler et al (Ultrasound Med Biol 1990; 16:553-559) were significantly associated with false-positive S-Detect results (odds ratio [OR], 1.071; P = .006; OR, 5.851; P = .001; OR, 1.726; P = .009, respectively). Smaller lesions and the absence of calcifications detected by B-mode US in malignant solid breast lesions were significantly associated with false-negative S-Detect results (OR, 1.141; P = .015; OR, 7.434; P = .016). CONCLUSIONS: Larger benign lesions, the presence of lesion calcifications, and high degrees of vascularity are likely to show false-positive S-Detect results. Smaller malignant lesions and the absence of calcifications are likely to show false-negative S-Detect results.

Post-marketing safety of anti-IL-5 monoclonal antibodies (mAbs): an analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS). METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically. RESULTS: There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days). CONCLUSION: Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.

Safety and Efficacy of Combined Imbrication Axle Reconstruction and Z-Type Titanium Plate Fixation for Hinge Fracture Displacement During Open-Door Laminoplasty.

BACKGROUND: Open-door laminoplasty is a classical decompression method used to treat cervical spondylotic myelopathy. However, hinge fracture displacement (HFD) is a common occurrence during this procedure. The current study aimed to investigate the safety and efficacy of a combined imbrication axle reconstruction and Z-type titanium plate fixation method for HFD during open-door laminoplasty. METHODS: In total, 617 patients with cervical spondylotic myelopathy who underwent C3-C7 open-door laminoplasty from March 2015 to October 2018 were included in this retrospective study. Overall, 73 patients developed HFD during surgery. Of these, 43 underwent combined imbrication axle reconstruction and Z-type titanium plate fixation (IRZF group) and 30 underwent traditional titanium plate fixation (TF group). Data such as the operative time, intraoperative blood loss volume, and distribution of fractured hinges were recorded. Both groups were compared in terms of improvement in neurologic function, cervical curvature index, hinge fusion rate, incidence of C5 palsy, severity of axial symptoms, and development of complications. RESULTS: The operative time and intraoperative blood loss were slightly higher in the IRZF group than in the TF group; however, the differences were not significant (p > 0.05). Furthermore, there was no significant difference between the groups in terms of the number of fractured segments and the distribution of fractured hinges (p > 0.05). The cervical curvature index did not decline in the two groups (p > 0.05). The IRZF group had a higher hinge fusion rate than the TF group at 3 (79.6 vs. 57.1%) and 12 (93.9 vs. 74.3%) months postoperatively (p < 0.05). There was no significant difference in the incidence of C5 palsy between the two groups (9.3 vs. 6.7%; p > 0.05). However, the TF group had more severe axial symptoms than the IRZF group (p < 0.05). The neurologic function of the two groups increased postoperatively as per the Japanese Orthopaedic Association scoring system (p < 0.05). Nevertheless, there was no significant difference in terms of neurologic function at any observational time point (p > 0.05). One patient in the TF group with hinge nonunion underwent laminectomy due to lamina displacement into the spinal canal and nerve root compression. CONCLUSION: In patients with HFD, IRZF facilitates a more intimate contact between the lamina and the lateral mass and, therefore, achieves fractured hinge fusion without additional surgical trauma. This technical improvement can significantly promote neurologic recovery, decrease the severity of axial symptoms, and prevent the development of spinal cord or nerve root recompression.

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present. METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs. RESULTS: From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC025 (information component). The potential strong signals (IC025 > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy. CONCLUSION: Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.

Post-traumatic cauda equina nerve calcification: A case report.

BACKGROUND: Post-traumatic cauda equina nerve calcification is extremely rare in clinical practice, and its etiology, pathogenesis, treatment and prognosis are unclear. There are few studies and reports on Post-traumatic cauda equina nerve calcification, and this review reports a case of Post-traumatic cauda equina nerve calcification for reference. CASE SUMMARY: A 52-year-old patient presented to our hospital with a history of lumbar spinal stenosis and a lumbar vertebral fracture caused by trauma. The patient's right lower limb had weakness in hip flexion, knee extension and plantarflexion with muscle strength grade 3, right ankle dorsiflexion and thumb dorsiflexion with muscle strength grade 0. The patient's skin sensation below the right knee plane disappeared. The patient's Computed tomography (CT) data showed signs of cauda equina nerve calcification and the terminal filaments in the plane of the third to fifth lumbar vertebrae. After treatment the patient's symptoms were slightly relieved. CONCLUSION: We provide an extremely rare case of Post-traumatic cauda equina nerve calcification and offer a conservative treatment plan. However, the etiology, mechanism and treatment of Post-traumatic cauda equina nerve calcification are still unclear. This requires scholars to conduct more research and exploration in this area.

Combination of Body Mass Index and Fasting Blood Glucose Improved Predictive Value of New-Onset Prediabetes or Diabetes After Acute Pancreatitis: A Retrospective Cohort Study.

OBJECTIVES: We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP). METHODS: In this retrospective cohort study, we used Kaplan-Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above. RESULTS: In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408-3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748-3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group ( P = 0.018) or the low-risk group ( P < 0.001). CONCLUSIONS: Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.

ACR TI-RADS classification combined with number of nodules, halo features optimizes diagnosis and prediction of follicular thyroid cancer.

OBJECTIVES: To investigate the application value of The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category combined with other ultrasound features of nodules in distinguishing follicular thyroid carcinoma (FTC) from thyroid follicular adenoma (FTA). METHODS: We collected and retrospectively analyzed clinical and ultrasound data for 118 and 459 patients with FTCs and FTAs, respectively, at our hospital. Next, we used ACR TI-RADS classification combined with other ultrasound features of nodules to distinguish FTC from FTA. Multivariate Logistic regression was used to screen independent risk factors for FTC, which were subsequently used to construct a nomogram for predicting FTC. RESULTS: ACR TI-RADS categories 4 and 5, unilateral multiple nodules, and halo thickness≥2 mm were independent risk factors for FTC. ACR TI-RADS category combined with number of nodules, halo features of the nodule was a significantly better prediction model for FTC diagnosis (AUC = 0.869) than that of ACR TI-RADS classification alone (AUC = 0.756). CONCLUTIONS: Clinicians need to pay attention to the halo of nodules when distinguishing FTA from FTC. Notably, ACR TI-RADS combined with other nodule ultrasound features has superior predictive performance in diagnosis of FTC compared to ACR TI-RADS classification alone, thus can provide an important reference value for preoperative diagnosis of FTC.

A New Posterior Extensor Attachment-Point Reconstruction Technique for Cervical Spondylotic Myelopathy Involving C2 Segment: Clinical Outcome and Safety.

BACKGROUND AND STUDY AIM: Cervical spondylotic myelopathy (CSM) is a common degenerative disease that mainly occurs in elder patients, leading to different degrees of neurological dysfunction. Spinal cord involvement is mainly distributed at the C3-C7 segments, but it may also involve up to the C2 level. This study aimed to assess the clinical efficacy and safety of open-door laminoplasty using a new extensor attachment-point reconstruction technique for treating CSM involving the C2 segment. PATIENTS AND METHODS: Fifty-nine patients with CSM involving the C2 segment and undergoing open-door laminoplasty were included in this retrospective study. Based on the titanium plate used in the operation, patients were divided into two groups, a reconstructed titanium plate fixation (RPF) group (n = 28) and a conventional titanium plate fixation (CPF) group (n = 31). Improvements in neurological function, cervical range of motion (ROM), cervical curvature index (CCI), preservation of posterior cervical muscle mass, and axial symptoms were compared between the two groups. RESULTS: There were no significant differences in operative time and intraoperative blood loss between the groups (p > 0.05). The Japanese Orthopaedic Association (JOA) score significantly increased in both groups postsurgery (p < 0.05); the neurological recovery rate was similar between the two groups (64.1 ± 13.3% vs. 65.9 ± 14.7%, p > 0.05). There was no significant loss of cervical ROM in either group (p > 0.05). The anteroposterior dural sac diameter at the C2 level was significantly enlarged in both groups (p < 0.05). Alternatively, CCI was significantly reduced in the CRP group (p < 0.05) but unchanged in the RPF group (p > 0.05). The cross-sectional area of the posterior cervical muscles was also significantly reduced in the CPF group (p < 0.05) but maintained in the RPF group (p > 0.05). Finally, axial symptoms were more severe in the CPF group than in the RPF group (p < 0.05). CONCLUSION: Laminoplasty is an effective surgical procedure for CSM involving the C2 segment. The reconstructed titanium plate achieved superior maintenance of cervical curvature and reduced both muscle atrophy and severity of axial symptoms compared with titanium conventional plates.

Comparison studies of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in the treatment of neurogenic cricopharyngeal muscle dysfunction.

BACKGROUND: Cricopharyngeal muscle dysfunction (CPD) management has been challenging in clinical practice. OBJECTIVE: To compare the efficacy and safety of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in treating CPD. METHODS: Forty patients with CPD were randomly divided into two groups, namely the botulinum toxin injection group (BTX group) and balloon dilatation group (BD group). Patients in the BTX group received a single ultrasound-guided injection of 50 units of botulinum toxin type A, while the BD group received dilatation therapy five times per week, consecutively for two weeks. Relative opening percentage of the upper esophageal sphincter (UES), the penetration-aspiration scale (PAS), and the Dysphagia Outcome Severity Scale (DOSS) were evaluated by a videofluoroscopic swallowing study (VFSS) at baseline, 1-month, and 3-months posttreatment. The Functional Oral Intake Scale (FOIS) and Standardized Swallowing Assessment (SSA) were also used to evaluate participants' swallowing function at baseline and the 1-week, 2-week, 1-month, and 3-month follow-ups. RESULTS: A generalized estimating equation (GEE) model revealed the significant main effect for time in UES, PAS, DOSS, FOIS, and SSA compared to baseline (P <0.05), while no group-by-time interactions (except for the PAS assessment) or main effect for treatment was detected among the above multiple variances. No systematic complications or severe adverse effects were noted. CONCLUSION: Both ultrasound-guided botulinum toxin type A injections and balloon dilatation therapy have been proven as safe and effective treatments for CPD patients. Future clinical trials with longer follow-up periods and more participants are warranted.

[Acupoint puncture combined with Ilizarov technique for the treatment of elderly paitents with knee osteoarthritis].

OBJECTIVE: To explore the clinical effect of acupoint puncture combined with Ilizarov technique in the treatment of knee osteoarthritis in the elderly. METHODS: From March 2015 to February 2016, 76 patients with primary knee osteoarthritis were treated with tibial osteotomy acupoint puncture grouop and Ilizarov technique anatomical puncture group, including 24 males and 52 females, aged 56 to 75 years old with an average of 61.4 years old, and a course of 3 to 17 years with an average of 5.2 years. Among them, 38 cases were treated with external fixation of acupoint puncture needle and 38 cases were treated with external fixation of anatomical puncture needle. Preoperative full-length X-ray of both lower limbs showed tibial varus deformity, narrowing of medial knee joint space and enlargement of lateral knee joint space. The force line of the affected knee and lower limb was moved inward by body surface measurement, and the KSS knee function score was decreased. Symptoms included medial knee pain, flexion and extension, and conservative treatment for more than 2 years. RESULTS: The lower limb force lines of both groups were corrected and the osteotomy ends healed well. No nonunion of osteotomy, inadequate correction of lower limbs or recurrence of deformity were found. Seventy-five patients were followed up for 3, 6, 12 and 24 months after operation. There was no significant difference in knee joint mobility between the two groups before operation and on 6, 12, 24 months after operation(F=1.346, P>0.05). There were significant difference in KSS pain and total score between the two groups at 3 months after operation, acupoint puncture group was better than anatomical puncture group(P<0.05); there was no significant difference in KSS score at 12 months after operation(P>0.05). CONCLUSIONS: The acupoint puncture group formed a potential acupuncture effect in the acupoint area by continuously tightening the steel needle on Ilizarov ring external fixator during the post-operative adjustment. Within three months after wearing external fixator, the knee pain symptoms of knee osteoarthritis were relieved rapidly, continuously and effectively, which was significantly better than that of the anatomical puncture group.

[The effect of immunofecal occult blood test on colorectal cancer screening].

OBJECTIVE: To discuss the clinical value of immunofecal occult blood test in screening of colorectal cancer and its precancerous lesions in a large series of health checkup population. METHODS: Colorectal cancer and its precancerous lesions in 5919 subjects undergoing health checkup in our hospital were screened out by using immunofecal occult blood test from July 2006 to June 2007; positive cases with the test were subjected to colorectal endoscopy or X-ray barium enema examination. Relevant results were analyzed in combination with clinical and pathological data. RESULTS: Positive result was obtained in 314 out of the 5919 subjects undergoing health checkup with immunofecal occult blood test; the positive rate was 5.30%. 241 cases (76.75%) of them accepted colorectal endoscopic examination and 23 cases (7.32%) accepted X-ray barium enema examination. The total follow up rate was 84.08% with 50 cases out of contact. After excluding the cases out of contact, 16 cases of colorectal cancer were found morbidity 2.37 per thousand including 8 (50.00%) cases of Dukes A, 7 cases (43.75%) of Dukes B and 1 case of Dukes C (6.25%). The detection rate of colorectal cancer with positive immunofecal occult blood test was 6.06% (16/264). 94 cases (16.01 per thousand) of adenomatous polyps were found including 55 cases (58.51%) of tubular adenoma, 23 cases (24.47%) of villiform-tubular adenoma and 16 cases (17.02%) of villiform adenoma. Among these cases 55 (58.51%) were solitary and 39 (41.49%) multiple. In addition, 6 cases of ulcerative colitis in active phase were found. Altogether 116 (43.94%) of the 264 cases with positive immunofecal blood test and not out of contact were found to have colorectal cancer or its precancerous lesions. CONCLUSION: Immunofecal occult blood test is suitable for screening of colorectal cancer and its precancerous lesions in large series of population. Colorectal cancer and its precancerous lesions may be found in relatively early phase and be eradicated in curable stage, thus to reduce the morbidity and mortality.

[Case-control study on Pi needle for the treatment of the cutaneous nerve entrapment low back pain].

OBJECTIVE: To explore a safe and effective method for the treatment of low back pain in the cutaneous nerve, and to clarify the indication of Pi needle to treat it. METHODS: From January 2003 to December 2004, 278 patients with cutaneous nerve entrapment low back pain were divided into two groups: Pi needle group and electrical stimulation group. In the Pi needle group, there were 68 males and 70 females, ranging in age from 20 to 60 years old, with an average of(41.92±10.88)years old. In the electrical stimulation group, there were 68 males and 72 females, ranging in age from 18 to 60 years old, with an average of(41.44±10.47) years old. The pain, tenderness and soft tissue tension of the two groups were measured and compared before and after treatment. RESULTS: All of the selected cases were qualified. No suspension, culling and shedding cases occurred in either group. In Pi needle group, visual analog scale(VAS) of pain decreased from 8.78±1.52 before treatment to 1.33±1.33 after treatment;and in electrical stimulation group, VASof pain decreased from 8.59±1.76 before treatment to 5.20±2.64 after treatment;and the VAS of pain of the Pi needle group was lower than that of the electrical stimulation group. In Pi needle group, VAS of tenderness decreased from 9.12±1.24 before treatment to 1.60±1.36 after treatment;and in electrical stimulation group, VAS of pain decreased from 8.79±1.60 before treatment to 5.34±2.60 after treatment;and the VAS of pain of the Pi needle group was lower than that of the electrical stimulation group. CONCLUSIONS: Once tissue texture changes to pain point, cord, nodules, Pi needle is the first line treatment for the cutaneous nerve entrapment low back pain.

[Expression of circadian gene NPAS2 in colorectal cancer and its prognostic significance].

OBJECTIVE: To study the expression of NPAS2 in colorectal cancer (CRC) and analyze its relationship with the clinicopathological parameters and prognosis of the patients. METHODS: Real-time q-PCR was used to detect the expression of NPAS2 mRNA in 40 fresh CRC tissues and paired adjacent tissues; immunohistochemistry was used to detect the expression of NPAS2 protein in 120 paraffin-embedded tumor and adjacent tissues. The relationship between NPAS2 expression level and the 5-year survival rate of 78 CRC patients with follow-up data were analyzed with Kaplan-Meier survival analysis. RESULTS: Compared with the adjacent tissues, fresh CRC tissue expressed significantly lower NPAS2 mRNA levels (P<0.01). Among the paraffin-embedded CRC tissues, 19.2% were positive for NPAS2 expression, as compared to a much higher rate of 62.5% in the adjacent tissues (P<0.05). The expression of NPAS2 was correlated with the tumor size, lymph node metastasis and TNM stages (P<0.05) but not with the patients' gender, age, distant tumor metastasis, differentiation, or invasion. Patients with high NPAS2 expression levels had a significantly higher 5-year survival rate than those with low NPAS2 expressions (P=0.0001). CONCLUSION: NPAS2 is down-regulated in CRC and closely correlated with the malignant biological behavior of the tumor and 5-year survival of the patients, suggesting its value in predicting the prognosis of the CRC patients.

Percutaneous ethanol injection, radiofrequency and their combination in treatment of hepatocellular carcinoma.

AIM: To evaluate the therapeutic effect and the indication of percutaneous ethanol injection (PEI), radiofrequency ablation (RFA) and their combination in treatment of hepatocellular carcinoma (HCC). METHODS: Two hundred and fifty-five patients with HCC received treatment of PEI, RFA or their combination. Group 1 (< 3 cm in diameter, n=85) was treated with PEI, group 2 (< 3 cm in diameter, n=153) with RFA. Group 3 (> 3 cm in diameter, n=86) was divided into two groups. Group 3a (n=34) was treated with RFA, while group 3b (n=52) was treated with RFA for 2 wk after transcatheter arterial chemoembolization or PEI. Contrast-enhanced sonography was performed for 61 patients before and after RFA. Liver function and serum alpha-fetoprotein (AFP) were measured for all patients. Changes of the lesions on ultrasound and contrast-enhanced CT/MRI were evaluated for assessing the therapeutic responses. The 1-, 2-, 3- and 5-year survival rates were recorded after treatment. RESULTS: In group 1, the complete necrosis rate of lesions after 1 mo was 77.6% (66/85). The level of AFP declined conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 80.0% (52/65), 60.4% (32/53), 52.5% (21/40) and 33.3% (7/21), respectively. In group 2, the complete necrosis rate of lesions after 1 moh was 92.2% (141/153). The level of AFP decreased conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 94.6% (88/93), 73.2% (52/71), 63.5% (33/52) and 46.4% (13/28), respectively. In group 3a, the complete necrosis rate of lesions after 1 mo was 23.5% (8/34). AFP dropped down to the normal level in only one patient after 1 mo. The 1-, 2- and 3-year survival rate after treatment was 47.6% (10/21), 42.9% (6/14) and 27.3% (3/11), respectively. Only one patient was still alive after 5 years. In group 3b, the complete necrosis rate of lesions after 1 mo was 57.7% (30/52). The level of AFP decreased after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 68.6% (24/35), 46.2% (12/26), 36.8% (7/19) and 27.3% (3/11), respectively. CONCLUSION: The therapeutic effect of RFA on small HCC is better than that of PEI. Small HCC is the optimal indication of RFA. For recurrent HCC (diameter > 3 cm), the combined treatment of RFA and PEI/ACE should be used.

Differentiation between malignant and benign nodules in the liver: use of contrast C3-MODE technology.

AIM: To investigate the value of contrast-enhanced C3-MODE technology in differentiating malignant nodules of liver from the benign ones. METHODS: Forty-six nodules in 36 patients (29 men and 7 women) were studied by contrast-enhanced C3-MODE technology and contrast-enhanced CT in 1 wk before the biopsy or operation. A low MI monitor and a high MI flash imaging were intermittently performed. After the injection of contrast agent, the period from 10 to 30 s and the time later than 100 s were respectively defined as early arterial phase and the late phase. The vascularities of the liver nodules in the two phases were combined for differential diagnosis. Corresponding to the pathological diagnosis, the accuracy, sensitivity and specificity of contrast-enhanced C3-MODE technology were compared to those of contrast-enhanced CT. RESULTS: By C3-MODE technology, 33 of the 46 liver nodules were demonstrated as defected area in the late phase and were diagnosed as malignant tumors. Of them, 28 with hypervascularity in the early arterial phase were assessed as hepatocellular carcinoma, the other five nodules with rim-like enhancement in the early arterial phase were diagnosed as metastatic tumors. Thirteen nodules were shown as iso or hypervascularity in the late phase as well as centripetal filling in the early arterial phase and we made a diagnosis of hemangioma. Corresponding to the pathological results, the sensitivity, specificity and accuracy of contrast-enhanced C3-MODE technology in differentiating malignant and benign nodules in the liver were 97.0%, 92.3% and 95.7%, respectively. With comparison to those of contrast CT (sensitivity, 94.1%; specificity, 91.7%; accuracy, 93.5%), the difference was not significant. CONCLUSION: Contrast-enhanced C3-MODE technology can effectively differentiate malignant liver tumors from the benign nodules. It highly agrees diagnostically with the pathology. We suggest that it provides a new approach for differential diagnosis of liver nodules in addition to contrast-enhanced CT.

Hydroxyapatite nanoparticles modified by branched polyethylenimine are effective non-viral vectors for siRNA transfection of hepatoma cells in vitro.

Small interfering RNA (siRNA) technology is a powerful tool in biomedical research and holds great potential for RNA interference-based therapies for HIV, hepatitis and cancer. However, the absence of a safe and efficient method for the delivery of siRNA has become a bottleneck for their development. Nanocrystallized hydroxyapatite (nHAP) appears to be an optimal candidate non-viral gene vector for several reasons, including its good biocompatibility and ease of production, however, nHAP microemulsions cannot remain monodispersed for long periods of time. Due to their high surface energy, nHAP particles gradually aggregate into large ones that are difficult for the cell to take up. To overcome this we modified nHAP with polyethylenimine (PEI) to generate a compound (MnHAP) with a tight size-distribution of <200 nm. The positive surface potential of MnHAP inhibited particle aggregation and thus made it easier to conjugate more siRNA. The transfection efficiency of MnHAP/fluorescent FAM-labeled siRNA complex was tested using flow cytometry, and the transfected cells were observed using fluorescence microscopy. The cytotoxicity of MnHAP/siRNA complexes to the human liver cancer cell line BEL-7402 was assessed in vitro by a formazan dye assay. Our results show that the in vitro transfection efficiency of MnHAP/siRNA was equivalent to that of the commercially available transfection agent Lipofectamine® 2000, but with decreased cytotoxicity. The MnHAP nanoparticles were also able to deliver siRNA for silencing of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in BEL-7402 cells, which supports that MnHAP might be a promising non-viral vector for biomedical research and gene delivery.

Ultrasonic elastography features of phyllodes tumors of the breast: a clinical research.

The purpose of this study was to analyze the ultrasonic elastography features of phyllodes tumors of the breast comparing with fibroadenomas. A retrospective database was queried for the patients diagnosed as phyllodes tumors and fibroadenomas at Sun Yat-sen Memorial Hospital from January 2008 to August 2012. Three hundred and fifty lesions from 323 consecutive patients were included in the study. All the cases were examined by conventional ultrasonography and ultrasound elastography. Ultrasound elastography was used to calculate strain ratio of the lesions with bilateral breast tissue at the same depth as reference. There were 36 phyllodes tumors (27 benign, 8 borderline, 1 malignant) and 314 fibroadenomas (158 the pericanalicular type, 103 the intracanalicular type, 53 other special types). The strain ratio for phyllodes tumors (3.19 ± 2.33) was significantly higher than for fibroadenomas (1.69 ± 0.88) (p<0.05). The Spearman(.)s correlation coefficient between strain ratio of ultrasound elastography and pathological groups was significant, with a value of 0.17 (p<0.05). Ultrasound elastography could provide additional information to differentiate phyllodes tumors from fibroadenoma in breast.

Could ultrasonic elastography help the diagnosis of small (≤2 cm) breast cancer with the usage of sonographic BI-RADS classification?

OBJECTIVES: To evaluate the additive value of ultrasound strain elastography (USE) to BI-RADS for the differentiation of benign and malignant breast small lesions. METHODS: Breast masses (≤2 cm) with histological diagnosis examined by ultrasonography and USE in our department from April 2004 to December 2009 were reviewed. Conventional B-mode ultrasound findings were classified according to the BI-RADS classification. USE findings were classified according to the 5-point scale. Histological diagnosis was used as the reference standard. RESULTS: 401 (246 benign (61.3%), 155 malignant (38.7%)) from 370 consecutive patients were included in the study. Sensitivity and specificity were 90.3%, 68.3% for BI-RADS; 72.3%, 91.9% for USE. The sensitivity of BI-RADS was better than that of USE (P<0.05), while the specificity of USE was better than that of BI-RADS (P<0.05). A revised BI-RADS combined with USE results was proposed in this study. Sensitivity and specificity were 83.9% and 87.8% for revised BI-RADS. The diagnostic performance of revised BI-RADS was better than BI-RADS (P<0.05). CONCLUSIONS: USE could give BI-RADS some help in the differentiation of benign and malignant breast small lesions. The addition of elastography to BI-RADS could improve the diagnostic performance in <2 cm lesions.