Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.

No abstract

Background Persistent descending mesocolon (PDM) is a congenital anomaly associated with the failure of fixation of the descending colon to the lateral abdominal wall. In the laparoscopic colectomy for colorectal cancer, it has been noticed that there are extensive adhesions and a distinctive anatomy of colonic vessels in cases with PDM. Therefore, it is necessary to have sufficient knowledge about PDM so that it can be appropriately treated during surgery. Case presentation Case 1—a 79-year-old man underwent laparoscopic intersphincteric resection for rectal cancer. Preoperative barium enema (BE) revealed that the sigmoid colon was located at the right side of the abdomen. An enhanced computed tomography (CT) showed that the common trunk of the left colic artery (LCA) and the first sigmoid colonic artery (S1) branched from the inferior mesenteric artery (IMA). Case 2—a 68-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer and laparoscopic distal gastrectomy for gastric cancer synchronously. BE showed that the descending colon ran from the splenic flexure to medial caudal side. An enhanced CT showed that the distance from the LCA to the marginal artery was 1.0 cm. Case 3—a 68-year-old man underwent laparoscopic low anterior resection for rectal cancer. BE showed that the descending colon ran to the medial caudal side. An enhanced CT showed that the mesentery of the descending colon was comparatively shortened. Case 4—a 60-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. An enhanced CT showed that the descending colon ran to the medial caudal side and predicted that the LCA and S1 formed a common trunk and branched radially from the IMA. We reported four cases with PDM recognized preoperatively as above. Three cases had a shortening of the mesocolon. While dissecting the vessels, although special attention was required to maintain the blood flow to the intestine, none of these cases developed any complications during the postoperative course. Conclusions We considered that it is important to have positional awareness of the LCA and the marginal artery to perform the laparoscopic surgery safely when a colorectal cancer with PDM is diagnosed preoperatively using imaging methods.

The recent development of next-generation sequencing technology for extensive mutation analysis, and beadarray technology for genome-wide DNA methylation analysis has made it possible to obtain integrated pictures of genetic and epigenetic alterations, using the same cancer samples. In this study, we aimed to characterize such a picture in esophageal squamous cell carcinomas (ESCCs). Base substitutions of 55 cancer-related genes and copy number alterations (CNAs) of 28 cancer-related genes were analyzed by targeted sequencing. Forty-four of 57 ESCCs (77%) had 64 non-synonymous somatic mutations, and 24 ESCCs (42%) had 35 CNAs. A genome-wide DNA methylation analysis using an Infinium HumanMethylation450 BeadChip array showed that the CpG island methylator phenotype was unlikely to be present in ESCCs, a different situation from gastric and colon cancers. Regarding individual pathways affected in ESCCs, the WNT pathway was activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). The p53 pathway was inactivated by TP53 mutations (70%), and potentially by aberrant methylation of its downstream genes. The cell cycle was deregulated by mutations of CDKN2A (9%), deletions of CDKN2A and RB1 (32%), and by aberrant methylation of CDKN2A and CHFR (9%). In conclusion, ESCCs had unique methylation profiles different from gastric and colon cancers. The genes involved in the WNT pathway were affected mainly by epigenetic alterations, and those involved in the p53 pathway and cell cycle regulation were affected mainly by genetic alterations. © 2016 Wiley Periodicals, Inc.

Salvage indications of recurrence, earlier disease, and complete tumor resection are related to longer survival. The total area of mediastinal dissection with a sufficient number of dissected mediastinal lymph nodes improves survival. Additional neck dissection does not add benefit. The optimal procedure for lymph node dissection in salvage esophagectomy should be established in future studies.