The BRAF V600E mutation occurs in approximately 10% of patients with metastatic colorectal cancer (CRC) and constitutes a distinct subtype of the disease with extremely poor prognosis. To address this refractory disease, we investigated the unique metabolic gene profile of BRAF V600E‐mutated tumors via in silico analysis using a large‐scale clinical database. We found that BRAF V600E‐mutated tumors exhibited a specific metabolic gene expression signature, including some genes that are associated with poor prognosis in CRC. We discovered that BRAF V600E‐mutated tumors expressed high levels of glycolytic enzyme enolase 2 (ENO2), which is mainly expressed in neuronal tissues under physiological conditions. In vitro experiments using CRC cells demonstrated that BRAF V600E‐mutated cells exhibited enhanced dependency on ENO2 compared to BRAF wild‐type cancer cells and that knockdown of ENO2 led to the inhibition of proliferation and migration of BRAF V600E‐mutated cancer cells. Moreover, inhibition of ENO2 resulted in enhanced sensitivity to vemurafenib, a selective inhibitor of BRAF V600E. We identified AP‐1 transcription factor subunit (FOSL1) as being involved in the transcription of ENO2 in CRC cells. In addition, both MAPK and PI3K/Akt signaling were suppressed upon inhibition of ENO2, implying an additional oncogenic role of ENO2. These results suggest the crucial role of ENO2 in the progression of BRAF V600E‐mutated CRC and indicate the therapeutic implications of targeting this gene.

Background The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis. Methods Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination. Results Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity. Conclusions The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

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Highlights Pain in the anus or presented with red, flat, elevated lesions in the anus needs to suspecte anal canal cancer. To differentiate between extramammary Paget’s disease (EMPD) and Anorectal cancer with pagetoid spread (PS) is difficult. A two-stage operation, a local excision followed by pathological diagnosis and an additional excision,can be useful in PS.

Background Endoscopic and transanal local resection without lymph node dissection are treatment options for patients with a low risk of lymph node metastasis; however, some patients might have undiagnosed lymph node metastases before surgery. This retrospective study aimed to evaluate the efficacy of preoperative PET/CT for diagnosing regional lymph node metastasis. Methods Patients who underwent curative resection with lymph node dissection for colorectal cancer at Osaka University between January 2012 and December 2015 were included. The cut-off values appropriate for diagnosing lymph node metastasis were calculated by way of a receiver operating characteristic (ROC) curves from maximum standard unit value (SUVmax) of main tumour, and lymph node short axis, and SUVmax of lymph node. The cut-off values of primary tumour SUVmax: 7, short-axis diameter of the lymph node at 7 mm, and lymph node SUVmax at 1.5 were set. Result A total of 541 patients were included. Regional lymph node metastases were confirmed in resected specimens from 187 patients (35 per cent). With a primary tumour SUVmax of 7 used as a cut-off value, the sensitivity and specificity of regional lymph node metastasis were 70.1 per cent and 45.5 per cent respectively. With a cut-off short-axis diameter of the regional lymph node of 7 mm, the sensitivity and specificity of regional lymph node metastasis were 75.2 per cent and 82.6 per cent respectively, and with a cut-off regional lymph node SUVmax of 1.5, the sensitivity and specificity of regional lymph node metastasis were 78.6 per cent and 96.8 per cent respectively. When the diagnostic criteria were defined by a lymph node short-axis diameter of 7 mm or SUVmax of 1.5, the sensitivity and specificity were 87.4 per cent and 81.8 per cent respectively. Conclusion Preoperative PET/CT is a useful modality for evaluating regional lymph node metastasis in patients with colorectal cancer.