Is the ileocolic artery crossing pattern related to oncological outcomes of right-sided colon cancer?

BACKGROUND: Complete mesocolic excision + D3 lymphadenectomy for right-sided colon cancer is standard procedure in Japan. A postmortem study has shown that in patients with the ileocolic artery (ICA) crossing posterior to the superior mesenteric vein (SMV), D3 lymphadenectomy may be potentially inadequate due to anatomical difficulties in lymphadenectomy of the ventral and lateral areas of the ICA. However, whether the ICA crossing pattern is associated with oncologic outcomes of right-sided colon cancer remains unclear. This study aimed to clarify whether differences in ICA crossing patterns are associated with disease-free survival and overall survival. METHODS: In this retrospective study, we searched a prospectively maintained database to identify medical records of patients with right-sided colon cancer who underwent right hemicolectomy and D3 lymphadenectomy. We classified patients into two groups based on the ICA crossing pattern: ICA crossing anterior to the SMV (group A) and ICA crossing posterior to the SMV (group P). We compared oncologic outcomes between the two groups. RESULTS: A total of 336 patients were included in the final analytic cohort: 175 in group A and 161 in group P. There was no significant difference in the number of harvested lymph nodes between the two groups. The two groups did not differ in 5-year overall survival within any disease stage. Similarly, the 5-year disease-free survival rates did not differ significantly between the two groups within any disease stage. We performed univariate and multivariate analyses, which showed the ICA crossing pattern had no clinical relevance. CONCLUSION: Our study did not show an association between the ICA crossing pattern and oncologic outcomes in patients with right-sided colon cancer who underwent right hemicolectomy with D3 lymphadenectomy.

[Laparoscopic Abdominoperineal Resection after Preoperative Chemoradiotherapy for Adenocarcinoma Associated with Anal Fistula].

A 72-year-old man had a chief complaint of anal pain and difficulty in defecation. He was diagnosed with adenocarcinoma by biopsy from a tumor of the anal canal. A computed tomography scan revealed neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa anal canal cancer. Preoperative capecitabine- based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. Digital rectal examination and imaging evaluation 8 weeks after preoperative CRT revealed that the tumor had shrunk. Fifteen weeks after preoperative CRT, laparoscopic abdominoperineal resection was performed. The pathological findings showed mucinous adenocarcinoma associated with anal fistula. At present, 12 months after the operation, no local recurrence and distant metastasis has been detected under follow-up evaluations.

Verification of the Japanese staging system for rectal cancer, focusing on differences with the TNM classification.

PURPOSE: The 9th Japanese Classification of Colorectal Cancer (9th JSCCR) has two main differences from the TNM classification (8th AJCC): first, main or lateral lymph node metastasis is classified as jN3; second, tumor nodules (ND) are treated as lymph node metastasis. In this study, we verified the 9th JSCCR for rectal cancer, focusing on the differences with the 8th AJCC. METHODS: This retrospective analysis involved 212 patients with stage I-III rectal cancer. ND was evaluated using whole-mount sections. We evaluated the relapse-free survival of each staging system, and compared the prognostic significance of the different staging systems using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Main or lateral lymph node metastasis was detected in nine of 212 (4%) patients. ND was detected in 79 of 212 (37%) patients. The best risk stratification power was observed in the 9th JSCCR (AIC, 759; c-index, 0.708) compared with the 7th JSCCR (AIC, 771; c-index, 0.681), 8th JSCCR (AIC, 768; c-index, 0.696), and the 8th AJCC (AIC, 766; c-index, 0.691). CONCLUSIONS: The 9th JSCCR, which includes the concepts of jN3 and ND, is useful for the risk stratification of rectal cancer, and the contributes to precise decision-making for follow-up management and adjuvant therapy.

The clinical significance of distal spread differs according to the primary tumor location in rectal cancer.

PURPOSE: Treatment strategies of rectal cancer differ between tumors located above (RS/Ra) and below (Rb) the peritoneal reflection. Based on the extent of distal spread (DS), the Japanese Society for Cancer of Colon and Rectum proposed an optimal distal margin in RS/Ra and Rb tumors. In this study, we investigated the clinical significance of DS between RS/Ra and Rb tumors. METHODS: We analyzed 287 stage I-III rectal cancer patients who underwent curative intent resection without preoperative therapy. DS and other pathological factors were evaluated using whole-mount sections. To investigate the clinical significance of DS in RS/Ra and Rb tumors, clinicopathological variables, including DS, were analyzed for the survival outcome according to the tumor group. RESULTS: DS was detected in 20 out of 185 (11%) patients with RS/Ra tumors and 8 out of 102 (8%) patients with Rb tumors. DS was not significantly associated with the overall survival (OS) or relapse-free survival (RFS) in RS/Ra tumors, but was an independent prognostic factor for the OS and RFS in Rb tumors (P = 0.002 and 0.007, respectively). CONCLUSIONS: The clinical significance of DS differs between RS/Ra and Rb tumors. DS is associated with a worse survival in Rb tumors, but not in RS/Ra tumors.

[A Case of a"Watch and Wait Therapy"Approach after Preoperative Chemoradiotherapy for Rectal Cancer Accompanied by Severe Emphysema].

A 72-year-old man was referred to our hospital for treatment for rectal cancer. Digital rectal examination and colonoscopy revealed a 4 cm tumor located at the anterior rectal wall 5 cm away from the anal verge, and pathological examination confirmed that the tumor was adenocarcinoma. A computed tomography scan detected neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa rectal cancer. The preoperative general examination revealed bradyarrhythmia and severe emphysema, and he was considered to be high risk for general anesthesia. After placement of a pacemaker, preoperative capecitabine-based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. The digital rectal examination and imaging evaluation 4 weeks after preoperative CRT revealed that the tumor disappeared, and pathological examination showed no malignant findings. Considering the risks of general anesthesia, the"watch and wait therapy"approach was adopted with sufficient informed consent. At present, 15 months after preoperative CRT, no evidence of regrowth or distant metastasis has been detected under rigorous follow- up evaluations.

[A Case of High-Frequency Microsatellite Instability in Colorectal Cancer with MSH2 Mutation Detected Using Gene Panel Testing with a Next-Generation Sequencer].

Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.

SMAD4 alteration associates with invasive-front pathological markers and poor prognosis in colorectal cancer.

AIMS: SMAD4 acts as a tumour suppressor, and the loss of SMAD4 is associated with poor prognosis in colorectal cancer (CRC) patients. Although next-generation sequencing (NGS) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC. METHODS AND RESULTS: We retrospectively investigated 201 patients with stage I-IV CRC, by using a 415-gene panel. To analyse the relationship between SMAD4 alteration and other clinicopathological characteristics, we evaluated clinicopathological variables, including invasive-front pathological markers: tumour budding, poorly differentiated cluster, and Crohn-like lymphoid reaction. Fifty-six patients (28%) had SMAD4 alteration: 24 and 32 patients had SMAD4 mutation and deletion, respectively. SMAD4 alteration was significantly associated with T category (P = 0.027), N category (P = 0.037), M category (P = 0.028), and invasive-front pathological markers, such as poorly differentiated cluster grade 3 (P = 0.020) and absence of Crohn-like lymphoid reaction (P = 0.004). Immunohistochemistry revealed that SMAD4 alteration was significantly associated with loss of SMAD4 (P = 0.023). In 90 patients with stage I-III disease, SMAD4 alteration was significantly associated with poor prognosis for relapse-free and overall survival (P = 0.047; P = 0.022, respectively). Conversely, in 111 patients with stage IV disease, SMAD4 alteration was not significantly associated with overall survival. CONCLUSION: SMAD4 alteration is associated with invasive-front pathological markers and poor prognosis in stage I-III CRC patients.

[Digestive Surgery Intervention for Gynecological Malignant Tumor].

AIM: This study aimed to determine surgical outcomes in patients with gynecological cancers for whom surgery was performed by gynecologists and digestive surgeons. METHODS: Seventy-three patients who underwent surgery for a gynecological malignant tumor from January 2010 to December 2014 were included in this retrospective study. Data on the definitive diagnosis, operative procedures, postoperative complications, stoma settings, length of hospital stay, and prognosis was collected for each patient. RESULTS: The median age of this female-only cohort was 60 years. Emergency surgery was performed in 8(11.0%)patients. Ovarian cancer was diagnosed in 56(76.7%)patients, and among these patients, the clinical disease Stage was Ⅰ, Ⅱ, Ⅲ, and Ⅳ in 4, 4, 20, and 11 patients, respectively. Moreover, 17 patients had recurrent ovarian cancer. Intestinal resection with anastomosis was performed in 25(34.2%)patients. Stoma formation was performed in 22 (30.1%)patients, however no patient underwent stoma closure surgery in the current study. The median operative time was 252 minutes, and the median blood loss was 1,190 mL. Regarding postoperative complications, ileus, pelvic abscess, and anastomotic leakage developed in 6(8.2%), 4(5.5%), and 2(2.7%)patients, respectively. The postoperative median survival time in patients with ovarian cancer was 1,399 days. CONCLUSION: These results suggest that tumor debulking, including intestinal tract resection, may contribute to the prolonged prognosis of gynecological tumors, although stoma closure is difficult to perform.

[A Case of Long-Term Survival after Resection for Metachronous Liver and Lung Metastases of Rectal Cancer Associated with Familial Adenomatous Polyposis].

A 37-year-old man was admitted to our hospital for the treatment of familial adenomatous polyposis and rectal carcinoma. He underwent total colectomy with ileoanal anastomosis(pT3N1M0, pStage Ⅲa)followed by adjuvant therapy with S-1. Three months after primary surgery, CT and MRIrevealed liver metastases(S5, S6). Laparoscopic partial hepatectomy was performed. Two years after primary surgery, new liver metastases(S2, S8)were found and we performed open partial hepatectomy and administered mFOLFOX6. Three years and 5 months after primary surgery, right lung metastases(S6, S9) were detected and the patient underwent a thoracoscopic-assisted right lung wedge resection. Repeated resection of metastases might have contributed to the long-survival in our case.

[A Case of Long-Term Survival in a Patient with Advanced Rectal Cancer and Paraaortic and Lateral Lymph Node Metastases].

A 65-year-old woman was referred for further examination following positive results on a fecal occult blood test. Colonoscopy revealed type 0-Ⅱa cancer, with a lesion measuring 2 cm in diameter in the rectosigmoid colon, and type 5 cancer, with a lesion measuring 6 cm in diameter in the upper rectum. Computed tomography(CT)and positron emission tomography (PET)-CT revealed mesorectal lymph node metastases. Therefore, she was diagnosed with rectosigmoid colon cancer(Stage Ⅰ)and upper rectal cancer(Stage Ⅲa). However, PET-CT also revealed slight fluorodeoxyglucose uptake in the paraaortic and lateral lymph node lesions; hence, the possibility ofmetastasis could not be ruled out. Given that chemotherapy was restricted due to renal dysfunction, low anterior resection was performed as the first choice. Analysis of intraoperative frozen sections showed paraaortic and lateral lymph node metastases; thus, we performed lymph node dissection of these lesions. Pathological examination ofthe resected lymph nodes revealed that 21 of 37 lesions were cancer metastases. S-1 was administered as adjuvant chemotherapy for 5 months. Mediastinal lymph node metastases was suspected on chest CT 5 months and 3 years post-surgery; thus, panitumumab was administrated. These lymph nodes decreased in size immediately. Six years after the first surgery, the patient was well without any signs of recurrence.

[A Case of Pathological Complete Response with Neoadjuvant Chemotherapy for Advanced Rectal Cancer].

A 62-year-old man was admitted with complaints of bloody stool. Colonoscopy revealed a 5 cm diameter type 2 tumor in the lower rectum close to the anal canal. Tumor biopsy indicated a well-differentiated tubular adenocarcinoma. Computed tomography revealed locally advanced rectal cancer with mesorectal lymph node metastases(cT3N1P0M0, Stage Ⅲa, JSCCR 8th). The patient was treated with neoadjuvant chemotherapy(NAC)after transverse colostomy as an anus-preserving procedure. For the NAC, 12 courses of capecitabine plus oxaliplatin(CapeOX)and bevacizumab(BV)were administered. Colonoscopy after NAC revealed that the main tumor had considerably shrunk. No malignant tissues were found on biopsy. However, rectal wall thickness remained unchanged. Therefore, response evaluation for chemotherapy indicated partial response. Intersphincteric resection(ISR)with diverting loop ileostomy was performed as an anus-preserving surgical procedure. No remnant tumor in the rectum or lymph node metastases were found upon the pathological examination of resected specimens. Ileostomy closure was performed at 6 months post-ISR. At 12 months post-ISR, the patient was well and showed no signs of recurrence. This case demonstrated that NAC with CapeOX and BV can be a promising option for treating locally advanced lower rectal cancer and preserving the anus.

Clinical Significance of BRAF Non-V600E Mutations in Colorectal Cancer: A Retrospective Study of Two Institutions.

BACKGROUND: Recent advances in next-generation sequencing have enabled the detection of BRAF V600E mutations as well as BRAF non-V600E mutations in a single assay. The present work aimed to describe the clinicopathological characteristics and clinical outcome of the BRAF non-V600E mutant-type in colorectal cancer (CRC). PATIENTS AND METHODS: CRC samples from 111 Stage IV patients were analyzed for somatic mutations using a 415-gene comprehensive genomic sequencing panel. Patients were classified according to BRAF status as wild-type, V600E mutant-type, or non-V600E mutant-type. Differences between clinicopathological characteristics and genetic alterations were analyzed among the three groups. Overall survival (OS) and the response to anti-EGFR therapy were also analyzed. RESULTS: Comprehensive genomic sequencing revealed that 98 patients (88%), 7 patients (6%), and 6 patients (6%) were wild-type, V600E mutant-type, and non-V600E mutant-type, respectively. Non-V600E mutant-type tumors were frequently left-sided (83%), while V600E mutant-type tumors were frequently right-sided (86%; P = 0.025). Non-V600E mutant-type showed better OS than V600E mutant-type (P = 0.038), with no significant difference compared with wild-type tumors. The two patients with non-V600E mutations who underwent repeated metastasectomies showed no evidence of disease at final follow-up. Regarding the efficacy of anti-EGFR therapy, the patient with an I326V mutation had progressive disease (+115%) despite no genetic alterations detected in the EGFR pathway that could drive resistance, suggesting an alternate resistance mechanism. CONCLUSIONS: Non-V600E mutant-type is more likely to be left-sided and demonstrates better OS than V600E mutant-type. Further preclinical and clinical investigations are needed to clarify the role of non-V600E mutations in CRC.

[Staged Laparoscopy-Assisted Surgery Including Hand-Assisted Laparoscopic Surgery for Rectal Cancer with Synchronous Liver Metastases-A Case Report].

Here, we reported a case of a 39-year-old woman having rectal cancer with multiple liver metastases who underwent staged laparoscopic resection. She was diagnosed with low rectal cancer and multiple liver metastases; thus, she underwent low anterior resection and diverting colostomy. Following the neoadjuvant chemotherapy, she underwent colostomy closure and subsequent hand-assisted laparoscopic partial hepatectomy using the operative site during the colostomy closure. The postoperative course was uneventful, and adjuvant chemotherapy with CapeOX was performed 3 weeks post-surgery. Minimally invasive surgery was performed using hand-assisted laparoscopy.

[Two Cases of Colorectal Cancer with SRC Amplification].

Carcinoma with elevated SRC expression is associated with distant metastasis and drug resistance. We report 2 cases of SRC amplification observed after retrospective comprehensive genomic sequencing. Case 1 was a 62-year-old man who had RAS wild-type stage IV carcinoma of the sigmoid colon with multiple liver metastases in both lobes. He underwent low anterior resection and systemic chemotherapy was initiated to treat the unresectable multiple liver metastases. Case 2 was a 73-yearold man who had RAS wild-type stage IV carcinoma of the descending colon with metastasis in the lateral segment of the liver. He underwent left hemicolectomy and lateral segmentectomy. He subsequently underwent open radiofrequency ablation and systemic chemotherapy to treat a hepatic recurrence. Several previous studies have found that molecular targeted therapy with tyrosine kinase inhibitors is effective against colorectal cancer with elevated SRC expression. This suggests that the results of comprehensive genomic sequencing may support the implementation of new treatments.

[Three cases of esophageal carcinoma achieved a pathological complete response after neoadjuvant chemotherapy with cisplatin and 5-fluorouracil].

We report three cases of esophageal carcinoma all of which achieved a pathological complete response after neoadjuvant chemotherapy (NAC) with cisplatin and 5-fluorouracil (CF). All three patients were men with clinical stage II squamous cell carcinoma of the middle thoracic esophagus. We administered 2 courses of CF treatment as NAC and then performed radical esophagectomy. Pathologic examination revealed no viable tumor cells in the resected esophagus. The patients are currently alive with no evidence of disease.

[A case of long-term survival in a patient with rectal cancer with virchow lymph node metastasis, liver metastases, and lung metastases].

A 69-year-old man with advanced rectal cancer and liver metastases was treated with 2 courses of chemotherapy with irinotecan and S-1 followed by low anterior resection and partial hepatectomy. Chemotherapy with S-1 was then administered for 22 months. However, lung metastases developed, for which partial pneumonectomy was performed. Seven months later, computed tomography (CT) revealed swelling of the left supraclavicular lymph node. Despite chemotherapy with 5- fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6); 5-fluorouracil, Leucovorin and irinotecan (FOLFIRI); and capecitabine plus bevacizumab, the lung metastases recurred and Virchow lymph node swelling was noted again. Accordingly, palliative therapy was administered. The patient died 3 years 1 month after Virchow lymph node resection. Herein, we describe a case of advanced rectal cancer, in which lung and Virchow lymph node metastases developed after liver metastasis. Surgical excision of the metastases resulted in long-term survival of 6 years following the first operation.

Prognosis for Metastatic Colorectal Cancer Patients Achieving Complete Response After Systemic Chemotherapy.

PURPOSE: Despite marked recent advances in chemotherapy, few reports have focused on the prognosis for patients with metastatic colorectal cancer (mCRC) achieving complete response (CR) after systemic chemotherapy. This study investigated the clinical course of mCRC patients achieving CR and evaluated the role of chemotherapy in CR. METHODS: This retrospective study searched a prospectively maintained database at the author's institute to identify medical records for mCRC patients achieving CR after systematic chemotherapy from January 2007 to March 2020. RESULTS: The search yielded 23 patients with confirmed CR to systemic chemotherapy. Median time to CR from treatment initiation was 6.8 months. Maintenance chemotherapy was continued for 22 of 23 patients. Median duration of maintenance chemotherapy was 11.1 months. Disease progression occurred for 17 (73.9%) patients at a median 48.1-month follow-up. Median progression-free survival was 26.6 months. Median overall survival was 91.7 months. CONCLUSIONS: Patients with CR to chemotherapy had a high probability of disease progression, but a relatively long-term prognosis. Treatment strategies after achievement of CR should be based an understanding of the high potential that tumor cells will remain. Use of maintenance chemotherapy after achievement of CR is still unclear, and the recent data do not demonstrate a negative impact for continuing maintenance chemotherapy after CR.

Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia.

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

Timing of Surgery to Treat Ulcerative Colitis: An Investigation Focused on Japanese Adults.

INTRODUCTION: There are no specific standards for the timing of surgery to treat ulcerative colitis, so reaching a decision on timing is often difficult. OBJECTIVE: The aim of this study was to evaluate the timing of surgery from the patients' perspective. METHODS: From among 203 patients who underwent restorative proctocolectomy with ileal pouch anal anastomosis to treat ulcerative colitis at our hospital from 1985 to 2013, we mailed a questionnaire to 101 of those who are currently attending periodic follow-up at our hospital. RESULTS: We analyzed 72 valid responses (71.2%). Overall, 65 patients (90.3%) responded that they were happy that they underwent surgery, 38 patients (52.8%) responded that the timing of surgery was appropriate, and 32 patients (44.4%) responded that they would have preferred to have had surgery earlier. The group of patients who would have preferred to have had surgery earlier included 23 patients (71.9%) who had undergone emergency surgery; the incidence of emergency surgery was significantly higher than in the group of 13 patients (34.2%) who had responded that the timing of surgery was appropriate (p = 0.002). Scores on the Medical Outcomes Study 36-Item Short-Form Health Survey (SF36), which reflect postoperative quality of life, were maintained at the same level as the Japanese standard values in our Japanese patients. CONCLUSION: The degree of satisfaction of patients who underwent surgery for ulcerative colitis was favorable, although it is important to consider surgery at an earlier stage in patients who may need emergency surgery.

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided 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 mutant-type were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., right-sided 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 mutant-type. 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.