BackgroundThe presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer.MethodsThis retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses.ResultsClassification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001).ConclusionsThe LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 IHC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment.

Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.

Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutanttype were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., rightsided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/ frameshift mutation compared with left-sided RNF43 mutanttype. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.

ObjectivesAnti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.Materials and methodsA total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as “all wild-type”, while remaining patients were defined as “mutant-type”.ResultsFifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were “all wild-type” compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and “mutant-type” RCRC showed significantly worse PFS compared with “all wild-type” LCRC (P = 0.004).ConclusionsRCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

AIMTo assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage IV low rectal cancer.METHODSWe selected 71 consecutive stage IV low rectal cancer patients who underwent primary tumor resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis. The patients had distant metastasis such as liver, lung, peritoneum, and paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan. All patients underwent primary tumor resection, 27 patients underwent total mesorectal excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME group). Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group. R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients. We evaluated possible prognostic factors for 5-year overall survival (OS), and compared 5-year cumulative local recurrence between the LPLND and TME groups.RESULTSFor OS, univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor. Regarding cumulative local recurrence, the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833).CONCLUSIONProphylactic LPLND shows no oncological benefits in patients with Stage IV low rectal cancer without clinical LPLN metastasis.

A 26-year-old woman with ulcerative colitis was transferred to our hospital with left hemiparesis due to cerebral infarction. Cervical ultrasonography and magnetic resonance imaging angiography revealed thrombosis at the right common carotid artery and the right internal carotid artery. Antithrombotic and anticoagulant therapies were commenced. After about 2 wk of the treatment, the frequency of her diarrhea increased. She underwent emergency subtotal colectomy, but 10 d later an abundant hemorrhage from the remnant rectum occurred, so the remnant rectum was resected and an ileal pouch anal anastomosis was performed. Antithrombotic and anticoagulant therapies were continued, but neither her neurological status nor magnetic resonance imaging angiography findings showed subsequent changes. She was discharged 3 mon after operation. This is a rare case of common carotid arterial thrombosis occurring as a complication of ulcerative colitis, in which antithrombotic and anticoagulant therapies are considered to provoke a deterioration of the patient's bowel disease.

We herein report the case of a rapidly progressive sporadic mesenteric desmoid tumor (DT). A 62-year-old woman presented with a 4-cm-diameter palpable mass in the left supraumbilical area. The mass showed an ill-defined margin with heterogeneous delayed enhancement on computed tomography and heterogeneous high intensity on T2-weighted magnetic resonance imaging. Sixteen months after the initial observation, the mass had grown in size, reaching 13 cm in diameter. The resected mass was histologically confirmed as a DT of the mesentery. Since DT often has an unpredictable clinical course, clinicians should bear in mind the need for imaging follow-up.