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Background/aim: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin that is frequently associated with anorectal carcinoma. Rectal canal carcinoma with Pagetoid spread (PS) is a relatively rare disease, and few reports on its outcomes are available. The relatively rare nature of this disease makes the development of treatment recommendations difficult. This study aimed to clarify the characteristics of the disease and factors related to prognosis. We present a case report and review of 89 cases, including those from the existing literature and our own experience., Case Report: The patient was an 81-year-old man who was referred to our hospital for surgery after endoscopic examination of the lower gastrointestinal tract revealed cancer of the anal canal with PS. Physical examination revealed erythema and erosions around the anus. Lower gastrointestinal endoscopy revealed an erythematous area and a continuous raised lesion in the anal canal. We diagnosed the patient with anal canal carcinoma with PS, and robot-assisted abdominoperineal resection was performed., Conclusion: Our findings indicate that the five-year survival rate for PPD patients was 63%, comparable to that of anal canal cancer without PS. The histological type and presence of lymph node metastasis may be related to the prognosis. The study suggests that early-stage patients with favorable histological types and no lymph node involvement may benefit from less invasive treatment options, such as endoscopic submucosal dissection., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

The therapeutic benefit of recently developed mutant KRAS (mKRAS) inhibitors has been limited by the rapid onset of resistance. Here, we aimed to delineate the mechanisms underlying acquired resistance to mKRAS inhibition and identify actionable targets for overcoming this clinical challenge. Previously, we identified Syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by mKRAS. By leveraging both pancreatic and colorectal cancer models, we found that surface SDC1 expression was initially diminished upon mKRAS inhibition, but recovered in tumor cells that bypass mKRAS dependency. Functional studies showed that these tumors depended on SDC1 for survival, further establishing SDC1 as a driver for the acquired resistance to mKRAS inhibition. Mechanistically, we revealed that the YAP1-SDC1 axis was the major driving force for bypassing mKRAS dependency to sustain nutrient salvage machinery and tumor maintenance. Specifically, YAP1 activation mediated the recovery of SDC1 localization on cell surface that sustained macropinocytosis and enhanced the activation of multiple RTKs, promoting resistance to KRAS-targeted therapy. Overall, our study has provided the rationale for targeting the YAP-SDC1 axis to overcome resistance to mKRAS inhibition, thereby revealing new therapeutic opportunities for improving the clinical outcome of patients with KRAS-mutated cancers.

We experienced a case of laparoscopic left hemicolectomy for advanced descending colon cancer in patient with idiopathic pulmonary arterial hypertension(IPAH). The patient was a 39-year-old woman. She visited her family doctor in November 201X because of bowel movement disturbance and melena. She was diagnosed as advanced descending colon cancer. Although intraoperative management for hemodynamic stability was expected to be difficult due to IPAH, hemodynamic stability was achieved under 10 mmHg pneumoperitoneum. During the operation noradrenaline and phenylephrine were used for hemodynamic management. Laparoscopic left hemicolectomy was performed safely. Postoperative histopathological findings were as follows; Type 2, tub1>tub2, pT4a(SE), pN1a(1/65), int, INF b, ly1, v1, Pn1b, pPM0, pDM0, pStage Ⅲb(the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th edition). The patient was discharged from the hospital on the 18th day after surgery without any complications except for Grade 2 diarrhea, which was considered a side effect of PGI2 preparation.

Objective: To evaluate the efficacy and safety of CAPOX plus bevacizumab as second-line chemotherapy for metastatic colorectal cancer., Methods: In this multicenter phase Ⅱ study, the planned number of patients was 48, but owing to poor case accumulation, registration was discontinued for 20 patients. The primary endpoint was the response rate(RR). Secondary endpoints were progression-free survival(PFS), overall survival(OS), disease control rate(DCR), and safety., Results: First-line treatment was combined with irinotecan in 14 cases and bevacizumab in 12 cases. The median number of second- line treatment courses was 7, and the median treatment period was 203 days. The reason for discontinuation of treatment was disease progression in 13 cases, adverse events in 4 cases, and other reasons in 3 cases. The best response was PR in 5 cases, SD in 8 cases, and NE in 4 cases. The RR was 25%, and the DCR was 65%. The median PFS was 7.2 months, and the median OS was 18.6 months. Grade≥3 adverse events were neutropenia in 3 cases and diarrhea and peripheral neuropathy in 2 cases each. There were no treatment-related deaths., Conclusion: CAPOX plus bevacizumab was a safe and effective second-line treatment option for metastatic colorectal cancer.