Different oncological features of colorectal cancer codon-specific KRAS mutations:Not codon 13 but codon 12 have prognostic value

BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.

Colonic J-pouch anal anastomosis after ultralow anterior resection with upper sphincter excision for low-lying rectal cancer

AIM: There is some evidence of functional superiority of colonic J-pouch over straight coloanal anastomosis (CAA)in ultralow anterior resection (ULAR) or intersphincteric resection. On the assumption that colonic J-pouch anal anastomosis is superior to straight CAA in ULAR with upper sphincter excision (USE: excision of the upper part of the internal sphincter) for low-lying rectal cancer, we compare functional outcome of colonic J-pouch vs the straight CAA.METHODS: Fifty patients of one hundred and thirty-three rectal cancer patients in whom lower margin of the tumors were located between 3 and 5 cm from the anal verge received ULAR including USE from September 1998 to January 2002. Patients were randomized for reconstruction using either a straight (n = 26) or a colonic J-pouch anastomosis (n = 24) with a temporary diverting-loop ileostomy. All patients were followed-up prospectively by a standardized questionnaire [Fecal Inco-ntinence Severity Index (FISI) scores and Fecal Incontinence Quality of Life (FIQL) scales].RESULTS: We found that, compared to straight anastomosis patients, the frequency of defecation was significantly lower in J-pouch anastomosis patients for 10 mo afterileostomy takedown. The FISI scores and FIQL scales were significantly better in J-pouch patients than in straight patients at both 3 and 12 mo after ileostomy takedown.Furthermore, we found that FISI scores highly correlated with FIQL scales.CONCLUSION: This study indicates that colonic J-pouch anal anastomosis decreases the severity of fecal incontinence and improves the quality of life for 10 mo after ileostomy takedown in patients undergoing ULAR with USE forlow-lying rectal cancer.

Early rehabilitation programs after laparoscopic colorectal surgery:Evidence and criticism

During the past several decades,early rehabilitation programs for the care of patients with colorectal surgery have gained popularity.Several randomized controlled trials and meta-analyses have confirmed that the implementation of these evidence-based detailed perioperative care protocols is useful for early recovery of patients after colorectal resection.Patients cared for based on these protocols had a rapid recovery of bowel movement,shortened length of hospital stay,and fewer complications compared with traditional care programs.However,most of the previous evidence was obtained from studies of early rehabilitation programs adapted to open colonic resection.Currently,limited evidence exists on the effects of early rehabilitation after laparoscopic rectal resection,although this procedure seems to be associated with a higher morbidity than that reported with traditional care.In this article,we review previous studies and guidelines on early rehabilitation programs in patients undergoing rectal surgery.We investigated the status of early rehabilitation programs in rectal surgery and analyzed the limitations of these studies.We also summarized indications and detailed protocol components of current early rehabilitation programs after rectal surgery,focusing on laparoscopic resection.

Iatrogenic colorectal perforation induced by anorectal manometry:Report of two cases after restorative proctectomy for distal rectal cancer

There are no reports regarding perforation of the colorectum induced by anorectal manometry. We report two cases of colorectal perforation that occurred during manometry in the patients undergoing restorative proctectomy for distal rectal cancer. In the fi rst patient, computed tomography showed an extraperitoneal perforation in the pelvic cavity and a rupture of the rectal wall. A localized perforation into the retroperitoneum was managed conservatively. In the second patient, a 3 cm linear colon rupture was detected above the anastomotic site. A primary closure of the perforated colon and proximal ileostomy were conducted, but the patient died 2 wk later. We hypothesize that the perforation induced by anorectal manometry may be associated with the relative weakening of the proximal bowel wall due to anastomosis, decreased compliance, and abnormal rectal sensation. We suggest that measurement of the maximum tolerable volume should not be routinely performed after restorative proctectomy for distal rectal cancer.