低酸素環境が大腸癌細胞の抗癌剤感受性に及ぼす影響に関する検討

学位の種別:課程博士University of Tokyo(東京大学

LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360-0.380) vs. 0.332 (0.325-0.339), P \u3c 0.0001; stage III/IV: 0.372 (0.365-0.388) vs. 0.332 (0.325-0.339), P \u3c 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection

Essential anatomy for lateral lymph node dissection

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential

Smoking and tumor obstruction are risk factors for anastomotic leakage after laparoscopic anterior resection during rectal cancer treatment

Objectives: To clarify the surgical outcomes and risk factors for anastomotic leakage (AL) following laparoscopic anterior resection (Lap-AR) for the treatment of rectal cancer. Methods: We retrospectively reviewed the records of 175 consecutive primary rectal cancer patients who had undergone Lap-AR at our institution between April 2012 and November 2015. Patient, tumor, and surgical variables were analyzed using univariate analyses. Results: Of 175 patients, 116 were men (66.3%). All four patients who had AL (2.3%) were men and current smokers with heavy smoking histories. In three of the AL cases, preoperative total colonoscopy was impossible owing to tumor obstruction, and the other case had concomitant obstructive colitis after oral bowel preparation. Univariate analysis identified tumor size, tumor obstruction, and smoking history as factors significantly associated with AL development. Conclusions: Tumor size, tumor obstruction, and smoking history were risk factors for AL following Lap-AR for the treatment of primary rectal cancer

Colorectal cancer with venous tumor thrombosis

Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological type of more than half of the cases was moderately differentiated adenocarcinoma, which is known to be aggressive. Among 41 cases with available data on liver metastasis, eight patients had synchronous liver metastasis, and liver metastatic recurrence after surgical resection was indicated in 10 patients. This liver metastatic rate was high compared to general colorectal cancer. However, 11 of 43 patients with venous tumor thrombosis could survive for more than 2 years after the diagnosis, although five of the 11 patients had liver metastasis. A long survival can be anticipated for patients following complete tumor resection and adjuvant chemotherapy. A greater accumulation of cases will help elucidate the characteristics of colorectal cancer with venous tumor thrombosis and improve the treatment strategy. Keywords: colorectal cancer, liver metastasis, tumor thrombosi

Benefits of a laparoscopic approach for second colorectal resection after colectomy or proctectomy –a retrospective study-

Abstract Background A laparoscopic approach generally provides several benefits in patients who undergo colon or rectal surgery without jeopardizing oncological outcomes. However, there is a paucity of studies on comparative outcomes of laparoscopic versus open approaches for second primary colorectal lesions after colectomy or proctectomy. Methods From patients with colorectal disease who underwent surgery between 2008 and 2022 at our hospital, we collected 69 consecutive patients who had previous colorectal surgery for this retrospective study. Based on the second surgery approach (laparoscopic or open), patients were classified into the Lap (n = 37) or Op group (n = 32). Patients’ baseline data and perioperative and postoperative outcomes were compared between the two groups. Results Four patients (11%) of the Lap group needed conversion to laparotomy. The intraoperative blood loss was lower in the Lap group than the Op group (median: 45 ml vs. 205 ml, p = 0.001). The time to first bowel movement was shorter in the Lap group than the Op group (median: 2.8 days vs. 3.6 days, p = 0.007). The operative time, frequencies of postoperative morbidities, and overall survival did not differ between the two groups. Conclusion Laparoscopic surgery appeared feasible and beneficial for selected patients undergoing second colorectal resection after colectomy or proctectomy regarding blood loss and bowel function recovery without affecting other outcomes