Cartilage oligomeric matrix protein (COMP) promotes cell proliferation in early-onset colon cancer tumorigenesis.

BACKGROUND: Colon cancer (CC) is the third most commonly diagnosed cancer in the USA. While the overall incidence is declining, it is rising alarmingly in young patients (EOCC). CC in young patients tends to be more aggressive and often diagnosed at more advanced stages and portend poorer prognosis. Our recently published data showed that EOCC is a distinct disease with unique molecular features compared to late-onset CC (LOCC). The Cartilage Oligomeric Matrix Protein (COMP) was shown to be significantly upregulated in EOCC and correlated with poor survival. However, the role of COMP in CC tumorigenesis, especially in young patients, is not well understood. Thus, the aim of this study was to elucidate the role of COMP in CC tumorigenesis by modulating COMP levels in vitro and test how it affects proliferation. Then, patient samples were evaluated by testing the levels of proliferation marker Ki67. In addition, this study investigates whether higher transcriptional mRNA levels of COMP seen in more aggressive early-onset CC correlate with protein levels compared to late-onset CC. METHODS: COMP mRNA levels in fresh frozen colon tumors (young: n = 5; old: n = 5) were assessed by quantitative PCR (qPCR). Additionally, CC cell lines were profiled for COMP expression to choose an in vitro model to study the role of COMP in CC tumorigenesis. HT-29 (low COMP expression) and CaCo-2 (high COMP expression) cells were used for in vitro proliferation studies. Immunohistochemical (IHC) analysis was conducted to assess COMP and Ki67 protein levels in formalin-fixed paraffin-embedded (FFPE) colon tumors. RESULTS: Significantly higher COMP expression levels were observed in fresh frozen EOCC compared to LOCC tumors. This observation confirmed our previously reported results from NanoString gene expression assay using FFPE samples. Cell proliferation was significantly increased in HT-29 and CaCo-2 cells upon treatment with human recombinant COMP protein after 48 and 72 h (P < 0.05). This increase was more profound in HT-29 cells. Staining for COMP and Ki67 revealed high COMP protein levels in EOCC compared to LOCC patients. CONCLUSION: COMP mRNA and protein levels are significantly higher in EOCC patients. Higher COMP levels correlate with increased proliferation suggesting a role in CC tumorigenesis.

Preoperative anemia and outcomes in patients undergoing surgery for inflammatory bowel disease.

BACKGROUND: Anemia is the most common extraintestinal manifestation in patients with inflammatory bowel disease (IBD), and has been linked to severity of the disease. The aim of the study was to assess the impact of anemia on postoperative outcomes in patients with IBD. METHODS: We retrospectively reviewed patients with IBD from the NSQIP database over an 8-year period. Patients were grouped based on the presence of anemia. The impact of anemia on postoperative morbidity, mortality and length of stay was assessed. RESULTS: A total of 15,761 patients met our criteria. Half of the patients were anemic upon presentation. Anemic patients were more likely to have a history of steroid use, present with sepsis and require an emergency operation. In multivariate analysis, anemia was a significant predictor of overall morbidity, serious morbidity and increased length of stay. CONCLUSIONS: Anemic patients with IBD present more often with sepsis and require emergency surgery compared to their peers. In addition, anemia serves as an independent predictor of overall complications, serious morbidity and increased length of stay following abdominal operations.

Assessing the national trends in colon cancer among Native Americans: A 12 year SEER database study.

INTRODUCTION: Native Americans (NA) form a unique cohort of colon cancer (CC) patients among whom the variability in demographics and cancer characteristics remains unclear. METHODS: We abstracted the national estimates for NA with CC using the Surveillance, Epidemiology, and End Result (SEER) database. Trend analysis of incidence, variation in location and patient demographic analysis were performed. RESULTS: A total number of 26,674 NA with CC were reported during the 12-year study period. While the overall incidence of CC decreased by 12% during the study period, incidence increased by 38% in NA. Incidence of CC was more prevalent and higher increase (42%) seen in NA females than males (p = 0.02; 34%). Stage III tumors represented 29% of all CC, sigmoid colon the most common site location (38%) with 72% of all tumors being moderately differentiated. 55% tumors were localized in left, 36% in right and 9% in transverse colon. 92% of the NA were insured. CONCLUSION: Incidence of CC continues to rise in NA with majority of CC presented at higher stage and moderate differentiation.

Are there differences in outcome after elective sigmoidectomy for diverticular disease and for cancer? A national inpatient study.

AIM: The postoperative outcome after elective sigmoidectomy for diverticulitis has not been compared to that for cancer. The study aimed to evaluate the differences in the postoperative outcome after sigmoidectomy for diverticular disease and cancer. METHOD: The National Inpatient Sample Database was used to identify patients who underwent elective sigmoid resection for diverticular disease or cancer between 2004 and 2011. After excluding patients with metastatic cancer and preoperative weight loss, sigmoid cancer and diverticulitis patients were matched using propensity score, controlling for age, gender, race, type of operation (open vs laparoscopic) and comorbidities. The end-points of interest were infective complications, reoperation, anastomotic leakage, rebleeding, length of hospital stay and in-hospital mortality. RESULTS: After propensity score matching (diverticulitis 11 192 patients, sigmoid cancer 11 192 patients), the mean age was 65 ± 12.5 years, 53.8% were male and 61.5% were Caucasian. Only 18.0% of the operations were done by laparoscopy. The overall complication rate was 17.7% and the in-hospital mortality rate was 0.9%. The diverticulitis group had a higher rate of surgical site infection (3.2% vs 2.6%, P = 0.004), intra-abdominal abscess formation (1.2% vs 0.4%, P < 0.0001) and reoperation (6.1% vs 4.1%, P < 0.0001) compared with the cancer group. The cancer group had a higher incidence of pneumonia (1.9% vs 1.5%, P = 0.01) and anastomotic leakage (9.2% vs 8.3%, P = 0.001). There was no difference in sepsis, deep vein thrombosis, respiratory failure, renal failure, rebleeding, overall complication rate or length of hospital stay. Subgroup analysis showed a higher in-hospital mortality for cancer than for diverticulitis patients whether resected by open or by laparoscopic surgery. CONCLUSION: Although elective sigmoidectomy for diverticular disease has a higher risk of infective complications, elective sigmoidectomy for cancer has a higher risk of anastomotic leakage.

Prognostic significance of lymph node yield in ypN0 rectal cancer.

BACKGROUND: Neoadjuvant radiation therapy for locally advanced rectal adenocarcinoma decreases lymph node yield. This study investigated the association between survival and number of lymph nodes evaluated in patients with pathologically negative nodes after neoadjuvant therapy. METHODS: Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and had pathologically negative lymph nodes were included from the Surveillance, Epidemiology, and End Results (SEER) database over a 7-year interval (January 2004 to December 2010). Systematic dichotomization for optimal cut-off point identification was performed using statistical modelling. RESULTS: A total of 3995 patients met the inclusion criteria. The majority had T3 (66·7 per cent) and moderately differentiated (71·5 per cent) tumours. The median number of lymph nodes retrieved was 12 (i.q.r. 7-16). An optimal cut-off of nine lymph nodes was identified. Increasing age (P < 0·001), increasing T category (T4 versus T1, P < 0·001; T3 versus T1, P = 0·010), response to neoadjuvant therapy (P < 0·001) and number of nodes evaluated (P < 0·001) were significant factors for overall survival in univariable analysis. After adjustment in the multivariable model, the group with nine or more nodes examined had significantly better overall survival (hazard ratio (HR) 0·76, 95 per cent c.i. 0·65 to 0·88, P < 0·001; 5-year survival 83·2 versus 78·0 per cent) and cancer-specific survival (HR 0·76, 0·64 to 0·92, P = 0·004; 5-year survival 87·9 versus 85·1 per cent) than the group with one to eight nodes examined. CONCLUSION: Overall and cancer-specific survival were worse where fewer than nine lymph nodes were identified after neoadjuvant therapy for locally advanced rectal cancer.