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Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. Results: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p >.05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p =.004; RFS: 68.8% vs. 77.3%, p =.005) and multivariable analysis (OS: HR: 1.52, p =.019; RFS: HR: 1.32, p =.05). Conclusions: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

After the development of EGFR tyrosine kinase inhibitors (TKIs), genetic testing of EGFR became required for effective treatment of lung cancer. Initially, the testing was conducted separately for each mutated region. However, many EGFR mutations have since been identified that determine the efficacy of EGFR-TKIs. Therefore, genetic testing of EGFR by next generation sequencing (NGS) may be a suitable strategy for lung cancer. Here we examined the applicability of the NGS method in regard to sensitivity, time and cost. A total of 939 specimens were obtained from 686 lung cancer patients at our hospital. DNA and RNA were simultaneously extracted from specimens derived from surgery, bronchoscopy, and fluid aspiration. Specimens included cerebrospinal fluid, pleural effusion, abdominal fluid, and pericardial effusion. From RNA, target regions (EGFR, KRAS, ALK fusion and RET fusion) were enriched by RT-PCR and sequenced with MiSeq. From DNA, PCR or PCR-RFLP conventional methods were performed. NGS and conventional methods were carried out routinely per week. Among the total 939 specimens, 38 specimens could not be examined with NGS. Among these, 34 specimens were analyzed by conventional testing with simultaneously extracted DNA. The remaining four specimens could not be tested with either method. Compared with the conventional method, the concordance rate of mutations was 99% (892/901), excluding specimens with NGS failure. The time period required from processing of specimens to results was 4 days, and the cost per sample was sufficiently low. In conclusion, the genetic testing with NGS method was useful for lung cancer treatment. The cost, sensitivity and time were able to tolerate routine examinations.

Genetic testing is needed for the treatment of colorectal cancer (CRC), especially molecular-targeted therapy. The effects of anti-EGFR therapy and prognosis are affected by the presence of KRAS mutations. However, whether primary CRC or metastatic tissues are appropriate in the analysis is still unclear. In the present study, we assessed the concordance of KRAS/BRAF mutation status and microsatellite instability (MSI) in primary CRC and corresponding metastases. This study enrolled 457 patients with surgically resected primary and corresponding metastatic CRC (499 synchronous metastases and 57 metachronous metastases) and seven local recurrences, and KRAS/BRAF mutation and MSI status were analysed for these tumours. The concordance rates of KRAS mutation, BRAF mutation, wild-type, MSI-H and MSS between primary CRC and corresponding metastases were 93.9% (214/228), 100% (30/30), 99.3% (304/306), 87.5% (21/24) and 100% (137/137), respectively. These high concordance rates were not different between synchronous and metachronous metastases. In conclusion, a high concordance of KRAS/BRAF mutation status and MSI status was observed between primary CRC and corresponding metastases in this study. Either primary CRC or metastatic tissues can be used for testing KRAS/BRAF mutation status and MSI status.

Background DKC1 (dyskerin pseudouridine synthase 1) is a causative gene for X-linked dyskeratosis congenita. Approximately 8% of patients with dyskeratosis congenita have malignancy, but information about the development of malignancy in patients with dyskeratosis congenita is limited. Case presentation A young Japanese patient with bone marrow failure developed metachronous rectal adenocarcinomas at the ages of 16 and 18 years. He had no family history of cancer. Microsatellite instability testing with rectal tumor tissue demonstrated low-level microsatellite instability. To clarify whether any cancer susceptibility genes were involved in the development of rectal cancer, RNA sequencing was performed. Cancer-related genes were assessed, and a c.361A>G (p.Ser121Gly) germline variant was detected in DKC1. The same missense variant was previously reported in two patients with dyskeratosis congenita as a pathogenic variant, but those patients did not develop malignancies. Conclusions Our patient developed rectal cancer at an early age of onset compared with the previously reported typical onset age of patients with dyskeratosis congenita. DKC1 might be involved in predisposition to colorectal cancer in young adulthood; therefore, appropriate surveillance may be considered.

Background The clinical relevance of combined microsatellite instability (MSI) and BRAF status for adjuvant treatment in stage III colorectal cancer (CRC) remains elusive. Methods In 405 patients with curatively resected stage III CRC, the prognostic value of combined MSI and BRAF status was assessed in four groups, as follows: high-levels of microsatellite instability (MSI-H) and BRAF-wild type, MSI-H and BRAF-mutation, microsatellite stable (MSS) and BRAF-wild type, and MSS and BRAF-mutation. Results Combined MSI and BRAF status provided significant prognostic stratification of disease-free survival (DFS), and was independently associated with worse DFS. The MSI-H and BRAF-wild type group had similar outcomes to stage II CRC patients, despite no benefit from 5-FU monotherapy. Further, patients in the MSS and BRAF-wild type group with stage IIIA CRC had favorable outcomes to 5-FU monotherapy, similar to those with stage II CRC. In contrast, 5-FU monotherapy was insufficient among patients in the MSS and BRAF-wild type group with stage IIIB or IIIC CRC or patients in the MSS and BRAF-mutation group with stage III CRC. Conclusions The combination of MSI and BRAF status serves as both a prognostic and predictive marker and may provide much-needed guidance during the planning of therapeutic strategies. J. Surg. Oncol. 2014; 110:982–988. © 2014 Wiley Periodicals, Inc.

Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high‐frequency MSI (MSI‐H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI‐H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI‐H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver‐operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790–0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut‐off score of 4 points. The receiver‐operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806–0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5‐FU‐based adjuvant chemotherapy and cancer immunotherapy.

Background: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. Patients and Methods: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated. Results: There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006). Conclusion: Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.

Purpose/objectives To examine the relationship between quality of life (QOL) as an index of adaptation status and concepts related to self-care skills of patients who have been diagnosed with and undergone surgery for digestive system cancer: sense of coherence (SOC), social support, demands of illness, and the thought "Why me?" Design Cross-sectional survey. Setting General hospitals in Japan. Sample 60 patients who had been newly diagnosed with digestive system cancer and had undergone surgery. Methods Questionnaires were distributed to participants whose discharge date had been determined. The questionnaires were returned through the mail within two weeks of the discharge date. Main research variables QOL, SOC, social support, demands of illness, and the thought "Why me?" Findings QOL was strongly correlated with SOC and the demands of illness and was moderately correlated with social support. The only variable that was negatively correlated with SOC was the question, "Why me?" SOC and demands of illness accounted for 54% of the variance in QOL; social support was not a significant factor. Conclusions This study suggests that SOC is positively correlated with QOL and the demands of illness are negatively correlated with QOL among study participants. Implications for nursing Nursing interventions focusing on SOC and illness demands may have a significant effect on QOL of patients following cancer surgery.

PURPOSE/OBJECTIVES To document the domains and properties of the self-reported needs of ambulatory patients with cancer. DESIGN Descriptive. SETTING Outpatient units in three general hospitals in Japan. SAMPLE 139 ambulatory patients with cancer. METHODS The data were collected using questionnaires. Five theoretical groups, which were composed of 30 items, were extracted empirically as domains. Alpha coefficients for each domain ranged from 0.70-0.89. Relationships between each domain and other variables and among the domains themselves were examined. MAIN RESEARCH VARIABLES Expressed needs of ambulatory patients with cancer, their backgrounds, medical and treatment characteristics, and physical functioning. FINDINGS All domains for patient needs, except for healthcare needs, were negatively correlated with the level of their physical function. Emotional, physical, and functional needs were positively correlated with the frequency of visiting an outpatient unit. Compared with other needs, adaptation needs were greater for patients who were employed or within three months of discharge. Among patients with one of three cancer sites (i.e., breast, stomach, and colorectal cancers), the needs for individualized care were the lowest for patients with colorectal cancer and highest for patients with breast cancer. CONCLUSIONS From the needs that ambulatory patients with cancer expressed, five domains were derived. Those domains had relationships with other variables. IMPLICATIONS FOR NURSING The findings shed light on a segment of ambulatory cancer nursing and may be useful when developing and testing programs needed in the future.

PURPOSE/OBJECTIVES: To investigate the dynamic experience of patients who recently experienced the stressful situation of being diagnosed with colorectal cancer and undergoing surgery. RESEARCH APPROACH: A qualitative and inductive inquiry. SETTING: General hospitals in Japan. PARTICIPANTS: 12 patients who had undergone colorectal cancer surgery and had been discharged in the previous six months. METHODOLOGIC APPROACH: To inductively elicit the findings from patients' real experiences, interviews and qualitative analysis were used. MAIN RESEARCH VARIABLES: Experience of patients with colorectal cancer. FINDINGS: Three domains that symbolized experiences of patients with colorectal cancer during the first six months after surgery emerged: types of burdens, steps in accepting the cancer diagnosis, and way of living a normal life. Burdens included vulnerability, lack of control, asking for assistance or support, and a "why has this happened to me?" attitude. Way of living a normal life included resisting vulnerability, constructing a daily living routine, and asking for help. CONCLUSIONS: Although patients faced many and varied burdens, they were able to take several actions to gradually accept their cancer diagnoses and resume normal lives. INTERPRETATION: Some of the patients were sincere and skillful in asking for help to live normal lives, but others found that difficult. The present findings are significant in helping nurses provide interventions to enable patients to make use of assistance or support.

476 Background: KRAS gene mutation in colorectal tumors is predictive of nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (CRC). The F-PHFA has been developed as a simple and accurate mutation detection assay especially for somatic mutations. In this study, we evaluated KRAS mutation detection by F-PHFA which detects 7 common mutations in codon 12 and 13. This study was a multicenter, clinical evaluation trial designed to evaluate the efficacy of the F-PHFA method forKRAS testing in patients with CRC. Primary endpoint was the concordance rate of KRAS mutation between F-PHFA and direct sequencing with manual micro-dissection (MMD) to enrich the tumor concentration. Secondary endpoints included the concordance rate between F-PHFA and direct sequencing without MMD. Methods: The key eligibility criteria included histologically confirmed colorectal adenocarcinoma with adequate tumor samples. The materials were formalin-fixed paraffin-embedded (FFPE) 8 unstained slides at 10 um and 2 matching hematoxylin-eosin (HE)-stained slide, which were sent to the central pathology review to confirm the tumor content and to mark the tumor area. Genomic DNA was extracted using QIAamp DNA FFPE Tissue from both whole tissue of slide and tissue with MMD. F-PHFA and direct sequencing were conducted independently in two laboratories. Results: FFPE specimens from 165 patients with colorectal adenocaricinoma were registered. Success rates on KRAS tests of F-PHFA both of with or without MMD were 100% (165/165). However, those of direct sequencing were 99.4% (164/165). The concordance rate between F-PHFA and direct sequencing were 99.4% (163/164) for both of with MMD and without MMD. Only one discordant sample had a rare mutation other than the 7 common mutations. Total assay time was about 3.5 hrs. Also 20 ng of DNA was enough to examine 7 types of KRAS mutations. Conclusions: We confirmed that F-PHFA and direct sequencing shows high concordance rate regardless of MMD. F-PHFA for KRAS mutation detection method is very suitable for clinical use in terms of easiness and accuracy.