Recommendations related to the analytical equivalence assessment of gene panel testing

Advances in cancer genome care over the past few years have included the development of gene panel testing for various biomarkers. This article summarizes issues and provides recommendations related to analytical performance evaluations for new oncology gene panels. The scope of these recommendations includes comprehensive genomic profiling assays related to gene panel testing that uses histological or serum specimens to detect gene mutations. As a research project of the Japan Agency for Medical Research and Development Research on Regulatory Science of Pharmaceuticals and Medical Devices, we convened the working group committee that consisted of more than 30 experts from academia, industry, and government. We have discussed the points that should be considered to allow maximal simplification of assessments using clinical specimens in evaluating accuracy and limit of detection in equivalence and analytical performance for three years. We provide recommendations specific to each type of gene mutation as well as to reference standards or specimens used for evaluations. In addition, in order to facilitate the discussion on the analytical performance of gene panel tests by multidisciplinary tumor boards of hospitals, the present recommendations also describe the items that companies are expected to provide information on in their packaging inserts and reports, and the items that are expected to be discussed by multidisciplinary tumor boards. Our working group document will be important for participants in multidisciplinary tumor boards including medical oncologists and genome scientists, and developers of gene panels not only in Japan but also in other countries

Environmental contamination by arsenic and lead in some rural villages in India

This investigation focuses on the arsenic contamination problems in tube well groundwater systems and the different forms of arsenic and other toxic elements accumulated in human hair samples taken in a rural area of Allahabad, Uttar Pradesh, India. The local residents at the study site depend on groundwater as their major source of household water. The oxidation reduction potential (ORP) and pH of groundwater samples were measured directly after the sampling of groundwater. Arsenic concentrations were measured directly in water samples by a colorimetric arsenic analysis kit after the water was pumped from a tube well and/or at a nearby laboratory. Human hair samples from the residents of the villages in the study site were analyzed by PIXE to measure a wide range of elements. An atomic absorption spectrometer was also used to measure arsenic concentrations. The results indicated that the concentrations of arsenic in groundwater and human hair were significantly higher in the village of Bada Kanjasa than in the villages of Kanua and Chota Kanjasa (P< 0.05), clearly indicating that the higher arsenic concentration in groundwater reflected the accumulation of arsenic in human hair in the residents of Bada Kanjasa. The PIXE analysis also revealed an unusually high concentration of lead in human hair samples from Chota Kanjasa. Although the actual health effects and the detailed exposure mechanisms remain to be investigated, lead pollution is suspected to be the source of the exposure

Histological Evaluation of Therapeutic Effect and RCB (Residual Cancer Burden) Index in Primary Breast Cancer Operated after Neoadjuvant Chemotherapy: Retrospective Study of the Clinicopathological Findings and Prognosis

The therapeutic effect found histologically after surgery following neoadjuvant chemotherapy (NAC) correlates with patient prognosis. Such correlations must consider the remaining invasive lesions as well as intra-ductal components and lymph node metastasis. To this end, we compared the residual cancer burden (RCB) index with the conventional method of judging the histopathological therapeutic effect. We also took into account the clinicopathological features of patients related to recurrence and prognosis by the RCB index. We studied 244 cases of primary breast cancer in 238 patients who had undergone surgery after NAC in Showa University Hospital from 2005 to 2014. We classified the cases into groups based on the Japanese Breast Cancer Society\u27s criteria for evaluating the histological therapeutic effect and the RCB index. The cases were also analyzed in regard to various clinicopathological factors. The prognosis was evaluated by drawing recurrence-free survival curves using the Kaplan-Meier method, and the log rank test was used to test statistical significance. The RCB index was evaluated for cases of Grade 0–1b that had a certain degree of residual tumor tissue. Comparison of the recurrence-free survival rates in each of the RCB index groups indicated a significant correlation, although only for patients with some degree of residual malignancy even after chemotherapy. We conclude that the RCB index can be used for providing a more precise prediction of recurrence

Clinicopathological Study of Mass-forming Gallbladder Cancer Focusing on the Grade of Cellular Dysplasia

The relationship between the clinicopathological features and the grade of cellular dysplasia of the neoplastic glands in mass-forming gallbladder cancer was investigated. In this retrospective study, 41 mass-forming （≧1cm） gallbladder cancer specimens from 83 resected cases were examined. Tumors were classified into three groups: Group A had intraluminal masses consisting of neoplastic glands with only low-grade dysplasia; Group B had mixed low- and high-grade dysplasia, and Group C had only high-grade dysplasia. Of the 41 tumors, 13 were classified as Group A, 11 as Group B, and 17 as Group C. For Group A, B, and C, respectively, the mean tumor diameter was 1.6, 3.7 and 3.4cm; macroscopic type （pedunculated/semi-pedunculated/sessile） was 7/5/1, 4/6/1 and 0/10/7; frequency of an invasive component inside the mass was 0％, 9％ and 82％; and cell lineage （biliary/metaplastic/mixed） was 2/1/10, 8/1/2 and 14/1/2. In addition, invasion depth （Tis＋T1/T2/T3） was 13/0/0, 7/4/0 and 3/10/4; lymph node metastases were present in 0％, 9％ and 24％ of patients; 3-year survival rate was 100％, 100％ and 82％; and 5-year survival rate was 100％, 100％ and 69％, for A, B and C, respectively. Significant intergroup differences were seen for positive lymph node metastasis rate and 5-year survival rate. The present study indicates that the clinicopathological features of mass-forming gallbladder cancer are different depending on the grade of cellular dysplasia of the mass lesion. The tumors in Groups A and B were of lower malignancy than those in Group C and the prognosis of patients in the former groups was excellent. Group A and B tumors may be intracholecystic papillary-tubular neoplasms, a recently proposed new disease concept

Small Intestinal Obstruction Caused by Anisakiasis

Small intestinal anisakiasis is a rare disease that is very difficult to diagnose, and its initial diagnosis is often surgical. However, it is typically a benign disease that resolves with conservative treatment, and unnecessary surgery can be avoided if it is appropriately diagnosed. This case report is an example of small intestinal obstruction caused by anisakiasis that resolved with conservative treatment. A 63-year-old man admitted to our department with acute abdominal pain. A history of raw fish (sushi) ingestion was recorded. Abdominal CT demonstrated small intestinal dilatation with wall thickening and contrast enhancement. Ascitic fluid was found on the liver surface and in the Douglas pouch. His IgE (RIST) was elevated, and he tested positive for the anti-Anisakis antibodies IgG and IgA. Small intestinal obstruction by anisakiasis was highly suspected and conservative treatment was performed, ileus tube, fasting, and fluid replacement. Symptoms quickly resolved, and he was discharged on the seventh day of admission. Small intestinal anisakiasis is a relatively uncommon disease, the diagnosis of which may be difficult. Because it is a self-limiting disease that usually resolves in 1-2 weeks, a conservative approach is advisable to avoid unnecessary surgery