Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells.

BACKGROUND: Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples. RESULTS: In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens. CONCLUSIONS: Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.

Comparative accuracy of cervical cancer screening strategies in healthy asymptomatic women: a systematic review and network meta-analysis.

To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.

Muscle mass evaluation using psoas muscle mass index by computed tomography imaging in hemodialysis patients.

BACKGROUND AND AIMS: The use of the psoas muscle mass index (PMI) using computed tomography (CT) has become a marker of interest to evaluate whole body muscle mass. However, in hemodialysis (HD) patients, reports about the clinical significance of psoas muscle evaluation are limited. We aimed to clarify the association between PMI and skeletal muscle mass index (SMI) using bioelectrical impedance analysis (BIA), and to investigate factors affecting PMI in HD patients. METHODS: In this prospective observational study, to evaluate muscle mass, SMI was measured using BIA after HD, and PMI was measured by the manual trace method on routinely available CT scans. PMI measurement was assessed twice by two physicians to compute intra-rater and inter-rater reliability. The correlations between PMI and the clinical factors were evaluated using Pearson's correlation coefficient and a linear regression analysis. Variables with a p-value < 0.05 in the simple linear regression analysis were included in the multivariable linear regression analysis to identify the factors that affected PMI of the HD patients. RESULTS: Fifty HD patients were recruited (31 males and 19 females; HD duration, 9.0 ± 8.8 years). The SMI was 6.10 ± 1.20 kg/m2, and the PMI was 4.79 ± 1.61 cm2/m2. Regarding the reliability of PMI measurements, intra-rater reliability [intra-class correlation (ICC) = 0.999] and inter-rater reliability (ICC = 0.998) were high in this study. The mean PMI of male patients was 5.40 ± 1.62 cm2/m2, while that of female patients was significantly lower (3.78 ± 0.98 cm2/m2; p < 0.001). The PMI was significantly and positively correlated with SMI (r = 0.630, p < 0.001), in addition to HD duration, body mass index (BMI), serum phosphate and serum creatinine (Cr). In the multivariate linear regression analysis by two models using SMI or BMI, they were respectively extracted as an independent factor associating with PMI, in addition to serum Cr and the difference of sex. CONCLUSIONS: PMI assessed with CT positively correlated with SMI measured using BIA. PMI might be one of the methods for evaluating the muscle mass in HD patients, when CT scans are taken as part of routine care.

Skeletal Muscle Mass Index Is Positively Associated With Bone Mineral Density in Hemodialysis Patients.

Background: Patients with chronic kidney disease (CKD) are at risk for bone loss and sarcopenia because of associated mineral and bone disorders (MBD), malnutrition, and chronic inflammation. Both osteoporosis and sarcopenia are associated with a poor prognosis; however, few studies have evaluated the relationship between muscle mass and bone mineral density (BMD) in hemodialysis (HD) patients. The present study examined the association between skeletal muscle mass index (SMI) and BMD in the lumbar spine and femoral neck in HD patients. Methods: Fifty HD patients (mean age, 69 ± 10 years; mean HD duration, 9.0 ± 8.8 years) in Minami-Uonuma City Hospital were evaluated. BMD was measured by dual-energy X-ray absorptiometry, and SMI was measured by bioelectrical impedance analysis (InBodyTM) after HD. The factors affecting lumbar spine and femoral neck BMD were investigated, and multivariate analysis was performed. Results: In simple linear regression analysis, the factors that significantly affected the lumbar spine BMD were sex, presence of hypertension, presence of diabetes mellitus, body mass index, triglyceride level, grip strength, and SMI; the factors that significantly affected the femoral neck BMD were sex, HD duration, serum creatinine level, tartrate-resistant acid phosphatase 5b level, undercarboxylated osteocalcin (ucOC) level, N-terminal propeptide of type I procollagen level, grip strength, and SMI. In multivariate analysis, SMI (standardized coefficient: 0.578) was the only independent factor that affected the lumbar spine BMD; the independent factors that affected the femoral neck BMD were SMI (standardized coefficient: 0.468), ucOC (standardized coefficient: -0.366) and sex (standardized coefficient: 0.231). Conclusion: SMI was independently associated with the BMD in the lumbar spine and femoral neck in HD patients. The preservation of skeletal muscle mass could be important to prevent BMD decrease in HD patients, in addition to the management of CKD-MBD.

Clinicopathological Features of 15 Occult and 178 Clinical Pancreatic Ductal Adenocarcinomas in 8339 Autopsied Elderly Patients.

OBJECTIVE: The aim of the study was to investigate the clinicopathological features of pancreatic cancer at different stages using autopsy results. METHODS: We retrospectively evaluated 8399 consecutive cases of autopsy performed between 1972 and 2013 at our geriatric hospital. RESULTS: Macroscopic pancreatic lesions were detected in 6.13% of the cases. Primary and secondary pancreatic tumors were observed in 2.88% and 2.10% of the cases, respectively. Most primary tumors were invasive ductal adenocarcinomas (193 cases [2.31%]; mean patient age, 78.09 years) with a peak incidence at 50 to 59 years. Occult invasive ductal adenocarcinoma was discovered incidentally in 15 cases, with distant metastasis present in 26.67% of those. Microscopically, occult and advanced tumors exhibited similar characteristics such as hyalinized fibrous stroma, necrosis, invasion into vessels, peripancreatic fat tissues, and extrapancreatic nerve plexus. Mucin 1 and 2 immunohistochemical expression levels were also similar. Occult cancer incidence increased with age. Patients aged 85 years or older had shorter survival, a small tumor size, and a low incidence of lymph node metastasis. Approximately 8% of pancreatic invasive ductal adenocarcinomas progressed asymptomatically and were discovered incidentally at autopsy. CONCLUSIONS: Pancreatic cancers in elderly patients tend to progress asymptomatically, but once symptoms develop, they are more often fatal than those in younger patients.