BRAF Mutation Heterogeneity Detected Using Circulating Tumor DNA Sequencing in Synchronous Colon Cancer: A Case Report.

Background/Aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer. However, little information is available on heterogeneity among tumor lesions because of difficulty in performing genetic tests in all lesions in clinical practice. Case Report: A 44-year-old man presented with multiple recurrent lung metastases 42 months after the endoscopic resection of early stage synchronous ascending and sigmoid colon cancers. The genetic testing of sigmoid colon cancer tissue samples, their state being more advanced than that of ascending colon cancer, revealed a v-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog mutation (G13C) and BRAF wild type. However, the tumor was refractory to initial chemotherapy and rapidly progressed to new liver metastases. Therefore, we suspected that there may be biological heterogeneity between the primary sigmoid colon lesion and liver metastases. Next, we performed next-generation sequencing on circulating tumor DNA from the patient's plasma (Foundation One Liquid CDx®), which revealed the V600E mutation of BRAF, suggesting that there was genetic heterogeneity among the synchronized primary lesions, one of which was responsible for the chemo-refractory rapid-growing liver metastases. Conclusion: Genetic profiling with liquid biopsy at the time of recurrence and metastasis may be useful in patients with multiple synchronous cancers because there is less heterogeneity between primary and metastatic sites.

Advanced Appendiceal Cancer with Systematic Metastasis without Gastrointestinal Symptoms Found by Subcutaneous Tumor.

An 86-year-old woman with a subcutaneous nodule in her left axilla visited our hospital. She had no gastrointestinal symptoms, but contrast-enhanced computed tomography revealed a cecal mass and systemic metastasis, including cutaneous, bone, peritoneal dissemination and ascites. Colonoscopy revealed a circumferential, elevated cecal lesion. She underwent right hemicolectomy to prevent colon obstruction. The pathological diagnosis was poorly differentiated adenocarcinoma (por1>tub2>muc) arising from the appendix with a BRAFV600E mutation and microsatellite instability-high. Chemotherapy was administered, and she is currently still alive and undergoing chemotherapy. We describe a rare case of advanced appendiceal cancer without gastrointestinal symptoms diagnosed due to cutaneous metastasis.

Correction to: Clinical Impact of Inferior Mesenteric Lymph Node Metastasis in Patients with Cancer of the Sigmoid Colon or Rectum.

[This corrects the article DOI: 10.1007/s13193-021-01389-3.].

Clinical Impact of Inferior Mesenteric Lymph Node Metastasis in Patients with Cancer of the Sigmoid Colon or Rectum.

The aim of this study was to clarify the clinical impact of inferior mesenteric lymph node (IMLN) metastasis from cancer of the sigmoid colon or rectum. A total of 952 patients underwent curative surgery with IMLN dissection for either sigmoid colon cancer or rectal cancer from January 2000 to August 2018. Of these, 26 (2.7%) were pathologically diagnosed with IMLN metastasis. Excluding 1 patient, 25 patients were retrospectively investigated for clinicopathological characteristics and long-term outcomes. Specifically, the clinical course of patients with recurrence was meticulously scrutinised. Of the 25 patients, 14 (56%) had recurrence during the follow-up period. The 5-year recurrence-free survival was 31.2%, and 5-year overall survival was 59.7%. No serious morbidity, such as anastomotic leakage, was observed. Of the 14 patients with recurrence, 6 underwent secondary surgery with curative intent and 5 of the 6 patients remained cancer-free. In contrast, 8 patients were treated with chemotherapy, radiotherapy or best supportive care. Although IMLN metastasis was strongly associated with recurrence, long-term survival could be expected in most cases. Furthermore, there could be a chance for complete cure in patients with recurrence if secondary surgery is successfully carried out.

Congestive ischemic colitis occurring after resection of left colon cancer: 4 case series.

BACKGROUND: Ischemic colitis can occur after colectomy and is sometimes difficult to treat. We report 4 cases of refractory, delayed onset, regional congestive colitis occurring on the anal side of the anastomosis after laparoscopic left hemicolectomy. CASE PRESENTATION: A total of 191 patients underwent surgery for left colon cancer (transverse, descending, and sigmoid colon cancer) at our hospital from January 2012 to December 2017. During the procedures, the left colic artery (LCA) or sigmoid colic artery (SA) was dissected, the superior rectal artery (SRA) was preserved, and the inferior mesenteric vein (IMV) was dissected at the inferior margin of the pancreas. Congestive ischemic colitis due to venous return dysfunction occurred in 4 cases (2.1%), 5 to 34 months postoperatively. The patients had diarrhea and blood in the stool. On computed tomography (CT), the patients exhibited continuous intestinal edema and high-density adipose tissue from the anastomosis site to the rectum. Contrast enhancement showed dilation of the vasa recti and arteries from the inferior mesenteric artery (IMA) to the SRA. Three patients improved with long-term intestinal rest; in 1 case, the stenosis did not improve and required colorectal resection. CONCLUSION: Diagnoses were easy in these cases, but treatment was prolonged and surgery was necessary in 1 case. While this condition is rare, caution is warranted as it is difficult to treat.

[Portal venous stent placement for variceal hemorrhage in the elevated jejunum caused by portal vein stenosis after pancreatoduodenectomy:a case report].

An 86-year-old male underwent pancreatoduodenectomy with resection and reconstruction of portal vein for pancreatic cancer. He was admitted to our hospital because of severe anemia and dyspnea ten months later. Computed tomography showed varices at the biliary-enteric anastomosis in the elevated jejunum caused by portal venous stenosis, which was suspected as the cause of anemia. Therefore, the patient underwent balloon dilatation of the portal vein followed by stent placement and coil embolization of the collaterals using a transileocolic portal vein approach. After the procedure, portal venous flow was improved, and the collaterals disappeared. The patient has been asymptomatic with no recurrence for three years and four months.

Subtelomeres constitute a safeguard for gene expression and chromosome homeostasis.

The subtelomere, a telomere-adjacent chromosomal domain, contains species-specific homologous DNA sequences, in addition to various genes. However, the functions of subtelomeres, particularly subtelomeric homologous (SH) sequences, remain elusive. Here, we report the first comprehensive analyses of the cellular functions of SH sequences in the fission yeast, Schizosaccharomyces pombe. Complete removal of SH sequences from the genome revealed that they are dispensable for mitosis, meiosis and telomere length control. However, when telomeres are lost, SH sequences prevent deleterious inter-chromosomal end fusion by facilitating intra-chromosomal circularization. Surprisingly, SH-deleted cells sometimes survive telomere loss through inter-chromosomal end fusions via homologous loci such as LTRs, accompanied by centromere inactivation of either chromosome. Moreover, SH sequences function as a buffer region against the spreading of subtelomeric heterochromatin into the neighboring gene-rich regions. Furthermore, we found a nucleosome-free region at the subtelomeric border, which may be a second barrier that blocks heterochromatin spreading into the subtelomere-adjacent euchromatin. Thus, our results demonstrate multiple defense functions of subtelomeres in chromosome homeostasis and gene expression.

Telomere-nuclear envelope dissociation promoted by Rap1 phosphorylation ensures faithful chromosome segregation.

Efficient chromosomal movements are important for the fidelity of chromosome segregation during mitosis; however, movements are constrained during interphase by tethering of multiple domains to the nuclear envelope (NE). Higher eukaryotes undergo open mitosis accompanied by NE breakdown, enabling chromosomes to be released from the NE, whereas lower eukaryotes undergo closed mitosis, in which NE breakdown does not occur. Although the chromosomal movements in closed mitosis are thought to be restricted compared to open mitosis, the cells overcome this problem by an unknown mechanism that enables accurate chromosome segregation. Here, we report the spatiotemporal regulation of telomeres in Schizosaccharomyces pombe closed mitosis. We found that the telomeres, tethered to the NE during interphase, are transiently dissociated from the NE during mitosis. This dissociation from the NE is essential for accurate chromosome segregation because forced telomere tethering to the NE causes frequent chromosome loss. The phosphorylation of the telomere protein Rap1 during mitosis, primarily by Cdc2, impedes the interaction between Rap1 and Bqt4, a nuclear membrane protein, thereby inducing telomere dissociation from the NE. We propose that the telomere dissociation from the NE promoted by Rap1 phosphorylation is critical for the fidelity of chromosome segregation in closed mitosis.