Supplementary Data from Three DNA Methylation Epigenotypes in Human Colorectal Cancer

Colorectal cancer metastasis to the retroperitoneum, especially solitary metastasis allowing curative resection, is rare. We report a case of complete resection of retroperitoneal metachronous solitary metastasis from caecal cancer without distant metastasis. An 80-year-old woman with caecal cancer underwent laparoscopic ileocaecal resection with regional lymph node dissection. According to the eighth edition of the TNM classification, the pathological diagnosis was stage IIA (T3N0M0). Six months following the surgery, computed tomography revealed a solitary mass of 2cm diameter, dorsal to the right kidney. A second procedure for the removal of the tumour was performed. The lesion was pathologically diagnosed as a metachronous solitary retroperitoneal metastasis from caecal cancer. The patient is surviving and free from recurrence 17 months following the second procedure.

3515 Background: The no-touch isolation technique (NTIT) aims to reduce cancer cells flowing from the primary tumor site to the liver and other organs by first ligation of blood vessels that feed the primary tumor. The efficacy of NTIT has not been proved in previous studies. To acquire the answer of an unsolved problem more than 60 years, we conducted a phase III trial to confirm the superiority of NTIT in patients with cT3/T4 colon cancer. This is the primary analysis of the disease-free survival (DFS) as the primary endpoint. Methods: Eligibility criteria included histologically proven colon cancer; tumor located in the cecum, ascending, transverse, descending, sigmoid or rectosigmoid colon; clinical T3 or T4, N0-2, M0; patients age 20-80 years. Patients were randomized preoperatively to either conventional technique (CoT) arm or NTIT arm. Operation was performed in open surgery. Patients with pathological stage III received adjuvant chemotherapy with capecitabine. The primary endpoint was DFS. Planned sample size was 850 to detect a hazard ratio (HR) of 0.732 in DFS with one-sided alpha of 5% and power of 80%. Results: A total of 853 patients were randomized (CoT: 427, NTIT: 426) between January 2011 and November 2015. The 3-year DFS were 77.3% and 76.2% in the CoT arm and NTIT arm,respectively. The HR was 1.029(95% CI 0.800-1.324); thus the superiority of NTIT was not confirmed (p = 0.59). The 3-year overall survival (OS), 3-year recurrence-free survival (RFS) and 3-year liver-recurrence-free survival (LRFS) are shown in the Table. Conclusions: The superiority of NTIT to CoT was not confirmed. NTIT does not improve the DFS or OS, RFS, LRFS in the patents with stage II and III colon cancer. Clinical trial information: UMIN000004957. [Table: see text]

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on F-18-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.

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.

above the anal canal. Aspiration biopsy was positive for c-kit and CD34, and the tumor was diag-nosed as a gastrointestinal stromal tumor of the rectum. Computed tomography revealed a tumor measuring 10 cm in diameter between the vagina and the lower rectum. There was no evidence of either lymph node or distant metastasis. Although preoperative imatinib mesylate therapy was considered, surgical resection was selected, because immunohistochemical examination of a biopsy specimen revealed an Exon-9 KIT mutation. Therefore, abdominoperineal resection with resection of the posterior wall of the vagina was performed. The defect in the vaginal wall was reconstructed using a gluteal fold flap by plas-tic surgeons. The patient did not receive adjuvant therapy, but remains alive 18 months after the opera-tion with no evidence of recurrence.

症例は66歳の男性で，S状結腸癌腹壁浸潤の診断にて手術予定となったが，入院数日前より腹部膨満および左下腹部の発赤・緊満が出現し，入院時にはS状結腸腹壁浸潤部を中心に腹壁膿瘍を形成し，広範な皮下気腫を認め，さらに閉塞性イレウスを来していた．まず人工肛門造設術および切開排膿術を施行した．全身状態の改善を待って，初回手術から42日目に腹壁合併切除を伴うS状結腸切除を施行した．腹壁の欠損部は13×17 cmとなり，有茎大腿筋膜張筋皮弁を用いて腹壁を再建した．腹壁膿瘍を伴う大腸癌症例では，局所の浸潤傾向に比べて遠隔転移は比較的少ないという報告もあり，切除可能であれば必ずしも予後不良ではないと考えられる．広範な腹壁合併切除を要しても，筋皮弁による腹壁再建を行うことで切除可能となるならば，切除を行う意義は十分にあると考えられた．

Few cases of recurrent colorectal carcinomas were treated non-surgically and cured. Here, we report 3 such cases. Case No. 1 was of a 66-year-old woman, who underwent ISR for very low rectal cancer. Her disease Stage was tub2, T2N0M0. Two years and 6 months later, she developed intrapelvic recurrence involving sacral bones(S1-S3). Radiotherapy of 50 Gy followed by mFOLFOX6 with bevacizumab was administered for a year. She has been cancer-free for 6 years. Case No. 2 was of a 47-year-old man who underwent preoperative CRT of 40 Gy with 5-FU plus Leucovorin, and LAR was performed for very low rectal cancer. The disease Stage was tub2, T3N2M0. One year later, he was diagnosed with recurrent aortic lymph node metastasis. After 7 months of mFOLFOX6 with bevacizumab, he developed an anastomotic fistula. His chemotherapy was discontinued; he was cancer-free for 6 years. Case No. 3 was of a 56-year-old man who underwent TPE for low rectal cancer. The disease Stage was muc, T4b(urinary bladder)N0M1a(perianal skin). One year and 6 months later, he developed ileus and was diagnosed with intrapelvic recurrence. He underwent intestinal bypass operation, and CRT of 46 Gy with capecitabine was administered. He attained CR quickly, and was cancer-free for 5 years. Collecting similar cases to analyze the key to successful treatment is important.

症例は30歳，女性，Lynch症候群の未発症変異保有者であり，サーベイランスの下部内視鏡が施行された．盲腸に0-IIa病変を認め，後日ESDが予定されたが内視鏡挿入困難で外科切除の方針となった．注腸検査で上行結腸の固定不全，造影CTでSMV rotation sign，3D-CT angiographyでSMA右側に小腸枝を認め，腸回転異常症を伴う盲腸癌と診断した．手術は腹腔鏡下回盲部切除を施行した．盲腸・上行結腸の後腹膜との固定は認められず，Ladd靭帯を介して右腹壁と連続していた．小腸は右側腹部に偏在し，小腸間膜は後腹膜と軽度の癒着を認めるのみであった．通常通りの内側アプローチで手術を開始，回結腸静脈を腹側に展開した際にSMVも腹側に吊り上がるため，腹膜切開ラインの決定に注意を要した．術後経過良好で第9病日に退院，腸回転異常症を伴う症例に対しても腹腔鏡手術は安全に施行できると考えられた．

We experienced 3 impressive colorectal cancer patients who developed peritoneal recurrences and underwent surgery several times and survived for more than 5 years. Case No. 1 was of a 44-year-old woman who underwent right hemicolectomy for her stage II A ascending colon cancer. She developed left ovarian metastasis, which was resected 3 years later. Five years later, she developed a pelvic peritoneal recurrence, which was resected successfully. Thirteen years later, she is doing well. Case No. 2 was of a 61-year-old man who underwent transverse colectomy for his stage II B colon cancer. He developed ileus 2 years 9 months later due to peritoneal recurrence, which was removed successfully. He underwent another resection for peritoneal metastasis 2 years 6 months later. He was administered 15 courses of FOLFOX6. He has remained cancer-free since 2009. Case No. 3 was of a 62-year-old man who underwent sigmoidectomy for his stage II A colon cancer. One year 8 months later, he underwent resection for a painful abdominal wall metastasis. Eight months later, he developed another abdominal wall recurrence, which was resected successfully. He underwent thoracoscopic resection 4 times for lung metastases and was given 16 courses of FOLFOX6. In 2009, he developed pelvic peritoneal nodules, which were resected. He later needed lymphadenectomy twice. He has remained cancer-free for the last 5 years and 6 months. Curative resection must be performed for a patient with peritoneal recurrence of colorectal cancer when surgery is indicated.

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.

BACKGROUND: Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic lateral lymph node dissection remain to be determined.OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.DESIGN: This was a retrospective cohort study using an exact matching method.SETTING: We conducted a multicenter study of 69 specialized centers in Japan.PATIENTS: Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.MAIN OUTCOME MEASURES: Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.RESULTS: Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).LIMITATIONS: The study was limited by its retrospective design and potential selection bias.CONCLUSIONS: Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.

Although several markers, including the lymph node ratio (LNR), have been proposed as a clinically prognostic tool for colorectal cancer (CRC), it remains unclear which markers have the most relevance in determining recurrence following adjuvant chemotherapy for stage III CRC.

Sphincter-preserving procedures (SPPs) for surgical treatment of low-lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II-III rectal cancer between 2010 and 2011. Patients with tumors 2-5 cm from the anal verge and clinical stage T3-4 were eligible. Primary outcome was 3-year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77-1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3-year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42-1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

We conducted a randomized phase III trial comparing tegafur/uracil (UFT) and Polysaccharide-K (PSK) to surgery alone in curatively resected stage II rectal cancer patients.

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.

大腸癌の腹膜播種再発症例は，一般的に切除が敬遠されることが多い．われわれは大腸癌は，再発例でも播種個数が少数であることが多いことを経験し，積極的切除を施行している．今回，その長期成績を検討した．【対象】2000年1月から2014年12月までの腹膜再発を切除してR0/R1にできた再発例80症例，101回手術を検討対象とした．同期間で腹膜再発切除R2となった45例を対照とした．【結果】R0/R1症例は平均61.6歳で男女比46：34，播種個数は1個から70個に及び，中央値で3個であった．術後5年生存率はR0/R1症例全体では26.5％で，そのうち腹膜播種単独群では34.2％であった．R2群では最長生存が34.0ヵ月でMSTは12ヵ月であった．【結論】大腸癌の腹膜播種は他臓器原発癌の腹膜播種とは違い，R0/R1切除が可能ならば，積極的切除の意義はあると思われた．