Positive Circumferential Resection Margin in Rectal Cancer Is a Robust Predictor of Poor Long-term Prognosis With Clinicopathological Bias Between Groups Compensated by Propensity-score Matching Analysis.

BACKGROUND/AIM: Circumferential resection margin (CRM) is the most reliable predictor of local and distant recurrence in locally-advanced rectal cancer (LARC). The present study was conducted to compare the long-term outcomes between CRM (+) and (-) groups using propensity-score (PS) matching analysis to compensate for bias between groups. PATIENTS AND METHODS: Of 563 consecutive patients with Stage II/III rectal cancer who were treated surgically with curative-intent at Juntendo University Hospital between Jan 1989 and Mar 2018, 412 patients were enrolled retrospectively in the study. The patients were divided into a CRM (+) group (n=21; 5.1%) and a CRM (-) group (n=391; 94.9%). RESULTS: In the entire cohort, recurrence-free survival (RFS), local recurrence-free survival (LRFS), non-local recurrence-free survival (NLRFS), and cancer-specific survival (CSS) were significantly worse among patients in the CRM (+) group compared with those in the CRM (-) group. Univariate analysis demonstrated patients in the CRM (+) group had significantly larger primary tumors (p=0.02), more frequently had open surgery (p=0.009), had an abdominoperineal resection (APR) procedure (p=0.01) and a T4 primary tumor (p<0.0001). After PS matching analysis, in the propensity-matched cohort, RFS, LRFS, NLRFS and CSS were significantly worse among patients in the CRM (+) group compared with those in the CRM (-) group. CONCLUSION: PS matching analysis demonstrated that RFS, LRFS, NLRFS, and CSS were significantly worse among patients in the CRM (+) group compared with those in the CRM (-) group. The present results indicate that CRM (+) is a robust predictor of long-term outcome of LARC, independent of tumor size.

The methylation level of a single cancer risk marker gene reflects methylation burden in gastric mucosa.

BACKGROUND: Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori (H. pylori) infection, and thus cancer risk. METHODS: Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person's gastric mucosa and those in an entirely healthy mucosa. RESULTS: The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3). The average methylation levels of nine driver genes tended to increase according to the risk levels (P = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups. CONCLUSIONS: The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk.

[A Case of Cecum Cancer with Lymph Node Metastasis and Invasion in the Superior Mesenteric Vein Treated with Combined SMV Resection and Reconstruction].

The patient was a 77-year-old woman. She visited her family doctor with a complaint of bloody stools, and was pointed out a Type 3 colon cancer in the cecum with a colonoscopy. In addition, an enlarged lymph node(#203)was found on the right side of the superior mesenteric vein(SMV). Laparoscopic surgery was initiated, and when the patient was moved to vascular processing, a firm adhesion of the lymph node(#203)was observed on the right side of the SMV. A small laparotomy was added, and a partial combined resection of the SMV was performed en bloc to complete the ileal resection. Histopathological findings showed T4b(transverse colon)N3M0, pStage Ⅲc, and metastatic lymph node(#203)showed evidence of invasion to the SMV. Adjuvant chemotherapy was administered, but lung metastases appeared 4 months and liver metastasis appeared 29 months after surgery. The patient was transferred to a different hospital for best supportive care(BSC)at 34 months after surgery.

Local recurrence of submucosal invasive colorectal cancer after endoscopic submucosal dissection revealed by copy number variation.

We report a case in which analysis of copy number variation revealed local recurrence of submucosal invasive colorectal cancer after curative endoscopic submucosal dissection (ESD). An 86-year-old man with a history of abdominoperineal resection of the rectum for rectal cancer underwent resection with ESD for early-stage sigmoid cancer 5 cm away from the stoma opening. At the same time, ileocecal resection was performed for advanced cecal cancer. Twelve months after ESD, advanced cancer occurred in the area of the ESD lesion. It was unclear if the cancer was a local recurrence after ESD, implantation of cecal cancer, or a new lesion. Copy number variation analysis performed for the three lesions revealed that the new lesion originated from residual tumor cells from ESD and was unlikely to be cecal cancer.

[A Case Report for Peritoneal Recurrences by Laparoscopic Surgery after Colorectal Cancer Resection].

We report a cases report of colorectal cancer who underwent repeated resection for peritoneal recurrences by laparoscopic surgery. In 2013, a 70-year-old woman diagnosed with an ascending colon cancer underwent laparoscopic right hemicolectomy. The pathological diagnosis was tub2, pT4aN1M0, Stage Ⅲb. Postoperative adjuvant chemotherapy(uracil and tegafur/Leucovorin)was administered. PET-CT performed at 25 months after the surgery because of CEA elevation. It revealed a peritoneal recurrence in the pouch of Douglas. The following peritoneal recurrences were removed by laparoscopic Hartmann's procedure. Chemotherapy(5-fluorouracil/levofolinate/oxaliplatin/bevacizumab)was administered 11 courses and after that chemotherapy(5-fluorouracil/levofolinate/bevacizumab)was administered 6 courses. PET-CT performed 37 months after the second surgery revealed a peritoneal recurrence near the right ovary in the pouch of Douglas. The following peritoneal recurrences was removed. Chemotherapy(tegafur/gimeracil/oteracil/bevacizumab)was administered 11 courses. The long-term survival has been continued for 7 years and 7 months after first operation. It was considered that laparoscopic surgery for peritoneal recurrence in colorectal cancer is contributed to one of the surgical procedures in selected patients.

CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer.

BACKGROUND/AIM: We investigated whether promoter methylation of the checkpoint-with-forkhead-and-ring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients. MATERIALS AND METHODS: CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectal-cancer tissues from 44 CRC patients. CHFR promoter-methylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients. RESULTS: CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort. CONCLUSION: Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.

[A Case Report of a Giant GIST Markedly Responsive to Neoadjuvant Chemotherapy with Imatinib Mesylate].

Male in his 50s complaining of abdominal pain was referred to our hospital. Abdominal CT scan showed a giant tumor which had diameter of approximately 50 mm in lower rectum. A biopsy specimen was positive for CD34 and c-kit. Based on these findings, it was diagnosed as gastrointestinal stromal tumor(GIST). We treated the patient with neoadjuvant therapy using imatinib mesylate(IM)to reduce the tumor size and to avoid the extensive surgery. The patient started to take IM at a daily dose of 400 mg. After 3 months, CT and MRI revealed that the tumor size decreased(40% reduction). We performed the robot assisted intersphincteric resection(ISR). Although it has been 28 months since the surgery, there are no obvious signs of recurrence. A patient diagnosed with giant GIST could avoid an extensive surgery due to neoadjuvant therapy with IM.

[A Case of Recurrence in the Abdominal Wall and Perineal Region of Rectal Cancer Successfully Treated with Minimally Invasive Surgery and Radiation Therapy].

Local recurrence after rectal cancer surgery is often difficult to treat because there are few effective treatments. In this study, we report a case of parastomal and perineal recurrence after Miles' surgery in an elderly patient who had a favorable outcome after laparoscopic surgery and radiation therapy. Our results suggest that a combination of minimally invasive treatment may be effective in elderly patients and after polysurgery.

Laparoscopic Surgery Is Acceptable for Elderly Patients With Colorectal Cancer: A Propensity Score-matched Study.

BACKGROUND/AIM: The study was performed to examine the suitability of laparoscopic surgery for elderly patients with colorectal cancer. PATIENTS AND METHODS: The subjects were 242 patients aged ≥80 years who underwent primary tumor resection of colorectal cancer using laparoscopic assisted colectomy (LAC, n=145) or open colectomy (OC, n=97). Propensity score matching used to balance the characteristics of the groups resulted in 76 patients being assigned to each group. RESULTS: Before matching, Glasgow Prognostic Score (GPS), American Society of Anesthesiologists physical status (ASA-PS), and previous abdominal surgery differed significantly between the groups (p<0.05), but after matching, all covariates were balanced (p≥0.05). Short-term outcomes were better after LAC (p<0.05), including fewer postoperative complications and less delirium. Regarding long-term outcomes, 5-year overall survival did not differ significantly between the groups (p=0.91). CONCLUSION: In elderly patients with colorectal cancer, short-term results are better after LAC than OC and long-term results are similar. These findings indicate that LAC is acceptable in this patient population.

[A Case of Metastatic Colorectal Cancer with Hyperammonemic Encephalopathy Induced by mFOLFOX6 and SOX Therapy].

A 77-year-old man was given a diagnosis of pT4aN0M1a(PUL2), stage Ⅳ, RAS mutant type, after the operation for advanced ascending colon cancer. He was administered mFOLFOX6 plus Bmab as first-line chemotherapy. He showed consciousness disturbance on the 2nd day during the 6 cycles. Because of head computed tomography and magnetic resonance imaging showing no abnormal findings, we diagnosed convulsive seizure. His consciousness level gradually improved after intravenous infusion. He showed consciousness disturbance on the 2nd day during the 7 cycles again. Because blood ammonia level were high at 400µg/dL, he was diagnosed as hyperammonemic encephalopathy. His consciousness level rapidly recovered after branched chain amino acid(BCAA)infusion. SOX plus Bmab therapy was started as a post-treatment, he developed hyperammonemia(NH3 288µg/dL)again, on the 4th day during the 3 cycles. After taking of oral administration of BCAA and lactulose, the recurrence of hyperammonemic encephalopathy was not found. Therefore, 3 cycles of SOX plus Bmab therapy and 12 cycles of IRIS plus Bmab therapy were administered.