Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

Immune checkpoint inhibitor-induced diarrhea: Clinicopathological study of 11 patients

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICI-induced diarrhea aged 46–81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICI-induced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.     

Use of a Web-Based Physical Activity Record System to Analyze Behavior in a Large Population: Cross-Sectional Study

BackgroundThe use of Web-based physical activity systems has been proposed as an easy method for collecting physical activity data. We have developed a system that has exhibited high accuracy as assessed by the doubly labeled water method.ObjectiveThe purpose of this study was to collect behavioral data from a large population using our Web-based physical activity record system and assess the physical activity of the population based on these data. In this paper, we address the difference in physical activity for each urban scale.MethodsIn total, 2046 participants (aged 30-59 years; 1105 men and 941 women) participated in the study. They were asked to complete data entry before bedtime using their personal computer on 1 weekday and 1 weekend day. Their residential information was categorized as urban, urban-rural, or rural. Participant responses expressed the intensity of each activity at 15-minute increments and were recorded on a Web server. Residential areas were compared and multiple regression analysis was performed.ResultsMost participants had a metabolic equivalent (MET) ranging from 1.4 to 1.8, and the mean MET was 1.60 (SD 0.28). The median value of moderate-to-vigorous physical activity (MVPA, ≥3 MET) was 7.92 MET-hours/day. A 1-way ANCOVA showed that total physical activity differed depending on the type of residential area (F_2,2027=5.19, P=.006). The urban areas (n=950) had the lowest MET-hours/day (mean 37.8, SD, 6.0), followed by urban-rural areas (n=432; mean 38.6, SD 6.5; P=.04), and rural areas (n=664; mean 38.8, SD 7.4; P=.002). Two-way ANCOVA showed a significant interaction between sex and area of residence on the urban scale (F_2,2036=4.53, P=.01). Men in urban areas had the lowest MET-hours/day (MVPA, ≥3 MET) at mean 7.9 (SD 8.7); men in rural areas had a MET-hours/day (MVPA, ≥3 MET) of mean 10.8 (SD 12.1, P=.002). No significant difference was noted in women among the 3 residential areas. Multiple regression analysis showed that physical activity consisting of standing while working was the highest contributor to MVPA, regardless of sex.ConclusionsWe were able to compile a detailed comparison of physical activity because our Web-based physical activity record system allowed for the simultaneous evaluation of physical activity from 2046 Japanese people. We found that rural residents had greater total physical activity than urban residents and that working and transportation behaviors differed depending on region type. Multiple regression analysis showed that the behaviors affected MVPA. People are less physically active while working, and sports and active transportation might be effective ways of increasing physical activity levels.     

Robust arterial transit time and cerebral blood flow estimation using combined acquisition of Hadamard‐encoded multi‐delay and long‐labeled long‐delay pseudo‐continuous arterial spin labeling: a simulation and in vivo study

Arterial transit time (ATT) prolongation causes an error of cerebral blood flow (CBF) measurement during arterial spin labeling (ASL). To improve the accuracy of ATT and CBF in patients with prolonged ATT, we propose a robust ATT and CBF estimation method for clinical practice. The proposed method consists of a three‐delay Hadamard‐encoded pseudo‐continuous ASL (H‐pCASL) with an additional‐encoding and single‐delay with long‐labeled long‐delay (1dLLLD) acquisition. The additional‐encoding allows for the reconstruction of a single‐delay image with long‐labeled short‐delay (1dLLSD) in addition to the normal Hadamard sub‐bolus images. Five different images (normal Hadamard 3 delay, 1dLLSD, 1dLLLD) were reconstructed to calculate ATT and CBF. A Monte Carlo simulation and an in vivo study were performed to access the accuracy of the proposed method in comparison to normal 7‐delay (7d) H‐pCASL with equally divided sub‐bolus labeling duration (LD). The simulation showed that the accuracy of CBF is strongly affected by ATT. It was also demonstrated that underestimation of ATT and CBF by 7d H‐pCASL was higher with longer ATT than with the proposed method. Consistent with the simulation, the 7d H‐pCASL significantly underestimated the ATT compared to that of the proposed method. This underestimation was evident in the distal anterior cerebral artery (ACA; P = 0.0394) and the distal posterior cerebral artery (PCA; 2 P = 0.0255). Similar to the ATT, the CBF was underestimated with 7d H‐pCASL in the distal ACA (P = 0.0099), distal middle cerebral artery (P = 0.0109), and distal PCA (P = 0.0319) compared to the proposed method. Improving the SNR of each delay image (even though the number of delays is small) is crucial for ATT estimation. This is opposed to acquiring many delays with short LD. The proposed method confers accurate ATT and CBF estimation within a practical acquisition time in a clinical setting.     

Mixture-based gatekeeping procedures in adaptive clinical trials

ABSTRACT

Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to “multivariate” multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.     

Fate of full‐house immunofluorescence staining in renal allograft: A case report

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.