Tumour genotypes account for survival differences in right- and left-sided colon cancers.

AIM: We sought to identify genetic differences between right- and left-sided colon cancers and using these differences explain lower survival in right-sided cancers. METHOD: A retrospective review of patients diagnosed with colon cancer was performed using The Cancer Genome Atlas, a cancer genetics registry with patient and tumour data from 20 North American institutions. The primary outcome was 5-year overall survival. Predictors for survival were identified using directed acyclic graphs and Cox proportional hazards models. RESULTS: A total of 206 right- and 214 left-sided colon cancer patients with 84 recorded deaths were identified. The frequency of mutated alleles differed significantly in 12 of 25 genes between right- and left-sided tumours. Right-sided tumours had worse survival with a hazard ratio of 1.71 (95% confidence interval 1.10-2.64, P = 0.017). The total effect of the genetic loci on survival showed five genes had a sizeable effect on survival: DNAH5, MUC16, NEB, SMAD4, and USH2A. Lasso-penalized Cox regression selected 13 variables for the highest-performing model, which included cancer stage, positive resection margin, and mutated alleles at nine genes: MUC16, USH2A, SMAD4, SYNE1, FLG, NEB, TTN, OBSCN, and DNAH5. Post-selection inference demonstrated that mutations in MUC16 (P = 0.01) and DNAH5 (P = 0.02) were particularly predictive of 5-year overall survival. CONCLUSIONS: Our study showed that genetic mutations may explain survival differences between tumour sites. Further studies on larger patient populations may identify other genes, which could form the foundation for more precise prognostication and treatment decisions beyond current rudimentary TNM staging.

Infiltrating Tumor Border Configuration is a Poor Prognostic Factor in Stage II and III Colon Adenocarcinoma.

INTRODUCTION: Tumor border configuration (TBC) is a prognostic factor in colorectal adenocarcinoma; however, the significance of TBC is not well-documented in colon adenocarcinoma alone. OBJECTIVE: Our aim was to study the effect of TBC on overall and disease-free survival in stage II and III colon adenocarcinoma. METHODS: We included patients with stage II and III colon adenocarcinoma who were surgically treated at a tertiary medical center between 2004 and 2015, to ensure long-term follow-up. Patients were stratified into four groups based on stage and TBC. A Cox regression was used to model the relationship of groups while accounting for relevant confounders. RESULTS: The cohort consisted of 700 patients (371 stage II and 329 stage III). Infiltrating TBC was statistically significantly associated with stage (p < 0.001) and extramural vascular invasion (p < 0.001), but not histologic grade (p = 0.7). Compared with pushing TBC, infiltrating TBC increased the hazard of death by a factor of 1.8 [95% confidence interval (CI) 1.4-2.4; p < 0.001] and 1.7 (95% CI 1.3-2.2; p < 0.001). The hazard of death in patients with stage II disease (infiltrating TBC) or stage III disease (pushing TBC) was not significantly different (adjusted hazard ratio 1.1, 95% CI 0.7-1.7; p = 0.8). CONCLUSION: Infiltrating TBC is a high-risk feature in patients with stage II and III colon adenocarcinoma. Stage II disease patients with infiltrating TBC and who are node-negative should be considered for adjuvant chemotherapy.

Are There Variations in Mortality From Diverticular Disease By Sex?

BACKGROUND: Previous data reveal that females account for a disproportionate majority of all patients diagnosed with diverticulitis. OBJECTIVE: This study analyzed the variation in mortality from diverticular disease by sex. DESIGN: This was a nationwide retrospective cohort study. SETTINGS: Data were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research national registry. PATIENTS: All citizens of the United States who died from an underlying cause of death of diverticulitis between January 1999 and December 2016 were included. MAIN OUTCOME MEASURES: The primary outcome addressed was overall mortality rate of diverticulitis by sex. Secondary outcomes included pattern variances in demographics and secondary causes of death. RESULTS: During the study period, 55,096 patients (0.12%) died with an underlying cause of death of diverticulitis from a total of 44,915,066 deaths. Compared with other causes, females were disproportionally more likely to die from diverticulitis than males (0.17% females vs 0.08% males; p < 0.001). Age-adjusted incidence of death was higher for females compared with males. Female patients were less likely to die within the hospital compared with males (OR = 0.72 (95% CI, 0.69-0.75); p < 0.001). Conversely, female patients were more likely to die either at nursing homes or hospice facilities (OR = 1.64 (95% CI, 1.55-1.73); p < 0.001). In addition, females with an underlying cause of death of diverticulitis were less likely to have a surgical complication as their secondary cause of death (OR = 0.72 (95% CI, 0.66-0.78); p < 0.001) but more likely to have nonsurgical complications related to diverticulitis such as sepsis (OR = 1.04 (95% CI, 1.01-1.05); p < 0.03), nonsurgical GI disorders such as obstruction (OR = 1.16 (95% CI, 1.09-1.24); p < 0.001), or chronic pelvic fistulizing disease (OR = 1.43 (95% CI, 1.23-1.66); p < 0.001). LIMITATIONS: The study was limited by a lack of more specific clinical data. CONCLUSIONS: Females have a higher incidence of diverticular disease mortality. Their deaths are more commonly secondary to nonsurgical infections, obstruction, or pelvic fistulae. Female patients represent a particularly vulnerable population that may benefit from more intensive diverticulitis evaluation. See Video Abstract at http://links.lww.com/DCR/B257. ¿EXISTEN VARIACIONES EN LA MORTALIDAD POR ENFERMEDAD DIVERTICULAR POR GÉNERO?: Los datos anteriores revelan que las mujeres representan una mayoría desproporcionada de todos los pacientes diagnosticados con diverticulitis.Este estudio analizó la variación en la mortalidad por enfermedad diverticular por género.Estudio de cohorte retrospectivo a nivel nacional.Los datos se obtuvieron del registro nacional WONDER del Centro de Control de Enfermedades.Se incluyeron todos los ciudadanos de los Estados Unidos que murieron por una causa subyacente de muerte (UCOD por sus siglas en inglés) de diverticulitis del 1 / 1999-12 / 2016.El resultado primario abordado fue la tasa de mortalidad general de la diverticulitis por género. Los resultados secundarios incluyeron variaciones de patrones en la demografía y causas secundarias de muerte.Falta de datos clínicos más específicos.Durante el período de estudio, 55.096 pacientes (0,12%) murieron con un UCOD de diverticulitis de un total de 44.915.066 muertes. En comparación con otras causas, las mujeres tenían una probabilidad desproporcionadamente mayor de morir de diverticulitis que los hombres (0.17% F vs. 0.08% M, p <0.001). La incidencia de muerte ajustada por edad fue mayor para las mujeres que para los hombres. Las pacientes femeninas tenían menos probabilidades de morir en el hospital en comparación con los hombres (OR 0.72, IC 0.69-0.75, p <0.001). Por el contrario, las pacientes femeninas tenían más probabilidades de morir en asilos de ancianos o en centros de cuidados paliativos (OR 1.64, IC 1.55-1.73, p <0.001). Además, las mujeres con una UCOD de diverticulitis tenían menos probabilidades de tener una complicación quirúrgica como causa secundaria de muerte (OR 0.72, CI 0.66-0.78, p <0.001) pero más probabilidades de tener complicaciones no quirúrgicas relacionadas con la diverticulitis, como sepsis (OR 1.04, CI 1.01-1.05, p <0.03), trastornos gastrointestinales no quirúrgicos como obstrucción (OR 1.16, CI 1.09-1.24, p <0.001), o enfermedad fistulizante pélvica crónica (OR 1.43, CI 1.23-1.66, p <0,001).Las mujeres tienen una mayor incidencia de mortalidad por enfermedad diverticular. Sus muertes son más comúnmente secundarias a infecciones no quirúrgicas, obstrucción o fístulas pélvicas. Las pacientes femeninas representan una población particularmente vulnerable que puede beneficiarse de una evaluación más intensiva de diverticulitis. Consulte Video Resumen en http://links.lww.com/DCR/B257.

What Is the Risk of Anal Carcinoma in Patients With Anal Intraepithelial Neoplasia III?

BACKGROUND: The risk of anal carcinoma after previous diagnosis of anal intraepithelial neoplasia III is unclear. OBJECTIVE: The purpose of this study was to estimate the risk of anal carcinoma in patients with anal intraepithelial neoplasia III and to identify predictors for subsequent malignancy. DESIGN: This was a retrospective review using the Surveillance, Epidemiology, and End Results registry (1973-2014). SETTING: The study was composed of population-based cancer registries from the United States. PATIENTS: Patients who were diagnosed with anal intraepithelial neoplasia III were included. MAIN OUTCOME MEASURES: The primary outcome was rate of subsequent anal squamous cell carcinoma. Predictors for anal cancer were identified using logistic regression and Cox proportional hazard models. RESULTS: A total of 2074 patients with anal intraepithelial neoplasia III were identified and followed for a median time of 4.0 years (interquartile range, 1.8-6.7 y). Of the cohort, 171 patients (8.2%) subsequently developed anal cancer. Median time from anal intraepithelial neoplasia III diagnosis to anal cancer diagnosis was 2.7 years (interquartile range, 1.1-4.5 y). Fifty-two patients (30.4%) who developed anal carcinoma were staged T2 or higher. Ablative therapies for initial anal intraepithelial neoplasia III were associated with a reduction in the risk of anal cancer (OR = 0.3 (95% CI, 0.1-0.7); p = 0.004). Time-to-event analysis revealed that the 5-year incidence of anal carcinoma after anal intraepithelial neoplasia III was 9.5% or ≈1.9% per year. LIMITATIONS: The registry did not record HIV status, surveillance schedule, use of high-resolution anoscopy, or provider specialty. CONCLUSIONS: In the largest published cohort of patients with anal intraepithelial neoplasia III, ≈10% of patients were projected to develop anal cancer within 5 years. Nearly one third of anal cancers were diagnosed at stage T2 or higher despite a previous diagnosis of anal intraepithelial neoplasia III. Ablative procedures were associated with a decreased risk of cancer. This study highlights the considerable rate of malignancy in patients with anal intraepithelial neoplasia III and the need for effective therapies and surveillance. See Video Abstract at http://links.lww.com/DCR/A764.

The time Interval Between the End of Radiotherapy and Surgery Does Not Affect Outcomes in Rectal Cancer.

INTRODUCTION: The ideal time interval between the completion of chemoradiotherapy and subsequent surgical resection of advanced stage rectal tumors is highly debated. Our aim is to study the effect of the time interval between the completion of chemoradiotherapy and surgical resection on postoperative and oncologic outcomes in rectal cancer. METHODS: Patients who underwent neoadjuvant chemoradiotherapy for resected locally advanced rectal tumors between 2004 and 2015 were included in this analysis. The time interval was calculated from the date of radiation completion to date of surgery. Patients were split into 2 groups based on the time interval (<8 weeks and >8 weeks). Postoperative outcomes (anastomotic leak, pathologic complete response (pCR), and readmission) and survival were assessed with multivariable logistic regression and Cox regression models while adjusting for relevant confounders. RESULTS: 200 patients (62% male) underwent resection with a median time interval of 8 weeks from completion of radiotherapy. On multivariable logistic regression, there was no significant increase in odds between time interval to surgery and anastomotic leak (aOR = .8 [.27-2.7], P = .8), pCR (aOR = 1.2[.58-2.6] P = .6), or readmission (aOR = 1.02, 95% CI:0.49-2.24, P = .9). Time interval to surgery was not an independent prognostic factor for overall (HR = 1.04 CI = .4-2.65, P = .9) and disease-free survival (HR = 1.2 CI = .5-2.9, P = .6). CONCLUSION: The time interval between neoadjuvant radiotherapy completion and surgical resection does not affect anastomotic leak rate, achievement of pCR, or overall and disease-free survival in patients with rectal cancer. Extended periods of time to surgical resection are relatively safe.

Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. METHODS: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. RESULTS: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. CONCLUSIONS: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.

Zip Code-Related Income Disparities in Patients With Colorectal Cancer.

INTRODUCTION: Screening and early detection reduce morbidity and mortality in colorectal cancer. Our aim is to study the effect of income disparities on the clinical characteristics of patients with colorectal cancer in Massachusetts. METHODS: Patients were extracted from a database containing all surgically treated colorectal cancers between 2004 and 2015 at a tertiary hospital in Massachusetts. We split patients into 2 groups: "above-median income" and "below-median income" according to the median income of Massachusetts ($74,167). RESULTS: The analysis included 817 patients. The above-median income group consisted of 528 patients (65%) and the below-median income group consisted of 289 patients (35%). The mean age of presentation was 64 ± 15 years for the above-median income group and 67 ± 15 years for the below-median income group (P = .04). Patients with below-median income were screened less often (P < .001) and presented more frequently with metastatic disease (P = .02). Patients with above-median income survived an estimated 15 months longer than those with below-median income (P < .001). The survival distribution was statistically significantly different between the groups for stage III disease (P = .004), but not stages I, II, or IV (P = 1, 1, and .2, respectively). For stage III disease, a lower proportion of below-median income patients received chemotherapy (61% vs. 79%, P = .002) and a higher proportion underwent nonelective surgery (5% vs. 2%, P = .007). CONCLUSIONS: In Massachusetts, patients with colorectal cancer residing in lower income areas are screened less, received adjuvant chemotherapy less, and have worse outcomes, especially when analyzing those who present with stage III disease.

Delay to Intervention for Complicated Diverticulitis is Associated with Higher Inpatient Mortality.

BACKGROUND: Patients with diverticular disease complicated by abscess and/or perforation represent the most severely afflicted with the highest mortality and poorest outcomes. This study investigated patient and operative factors associated with poor outcomes from diverticulitis complicated by abscess or perforation. METHODS: We analyzed the National Inpatient Sample to identify inpatient discharges for colonic diverticulitis in the United States from 1/1988 to 9/2015. We identified patients with perforation and/or intestinal abscess based on ICD-9 codes. The primary outcome was inpatient mortality. RESULTS: During the study period, a total of 993,220 patients were discharged with diverticulitis from sampled U.S. hospitals. From this group, 10.7% had an abscess and 1.0% had a perforation associated with diverticular disease. Inpatient mortality of diverticulitis patients with a perforation was 5.4% compared to 1.5% in those without a perforation (p<0.001). Patients with a perforation who underwent surgery had an inpatient mortality of 6.3% vs. 3.0% mortality amongst patients with a perforation who did not undergo an operation (p<0.001). Patients with a perforation that underwent surgery had a 31% increased mortality risk for each day after admission that a procedure was delayed (OR 1.31, CI 1.05-1.78; p=0.03). Mortality risk was increased for patients with either abscess or perforation who underwent surgery if they were female, age ≥65, higher comorbidity, were admitted urgently, underwent peritoneal lavage, or had a post-procedural complication. CONCLUSIONS: Patients with perforated diverticular disease had substantial associated inpatient mortality compared to those with uncomplicated diverticulitis. This increased risk may be associated with performance of peritoneal lavage or because of a delay to procedural intervention.

Adjuvant Chemotherapy Benefits on Patients with Extramural Vascular Invasion in Stages II and III Colon Cancer.

INTRODUCTION: Extramural vascular invasion (EMVI) is a poor prognostic factor in colon cancer. However, the benefit of adjuvant chemotherapy in patients with EMVI is not well defined. The objective of this study is to determine if there is a survival benefit for using adjuvant chemotherapy in patients with EMVI-positive colon cancers. METHODS: We performed a retrospective review of all patients with stages II and III colon adenocarcinoma who underwent surgical resection between 2004 and 2015. Cox regression was used to determine the effect of chemotherapy on EMVI-positive patients while adjusting for the extent of invasion, regional lymph node metastasis, histologic grade, age, site of tumor, and ASA score. RESULTS: A total of 750 patients were included in this study. Extramural vascular invasion was present in 93 out of 387 stage II patients (24%) and 187 out of 363 stage III patients (52%). The Cox regression model showed that in patients with EMVI, those who did not receive adjuvant chemotherapy had a 1.6-fold (1.1-2.3) increase in the hazard of death compared with those who received chemotherapy. CONCLUSIONS: Patients who were EMVI-negative fared better than those who were EMVI-positive. In patients who were EMVI-positive, adjuvant chemotherapy improved overall survival.

Octogenarians present with a less aggressive phenotype of colon adenocarcinoma.

BACKGROUND: Octogenarians constitute a growing percentage of patients diagnosed with colon malignancies. This study aims to determine if the clinical and pathologic presentation of octogenarians with colon cancer differs from that of patients diagnosed at a younger age. METHODS: Data were collected retrospectively for all patients diagnosed with colon cancer who underwent resection at a single institution between January 1, 2004 and December 31, 2017; patients with rectal cancer were excluded. Patients were categorized by age at diagnosis: either 50 to 79 years of age or ≥80 years of age; those <50 years of age were excluded because of the greater risk of a hereditary etiology. The primary outcome was the correlation between patient age and pathologic features of the tumor, including tumor size, lymph node metastases, perineural invasion, and extramural venous invasion. RESULTS: Of 1,301 patients, 329 (25%) were ≥80. Female patients predominated the octogenarian cohort (61% vs 39%; P < .001). Octogenarians presented with larger tumors when compared to patients age 50 to 79 (5.2 cm vs 4.5 cm; P < .001). More patients ≥80 had tumors which were >8 cm (17.3% vs 8.9%; P < .001). Tumors in younger patients were more often detected on screening colonoscopy (23.1% vs 7.3%; P < .001). Regardless of tumor size, octogenarians were less likely to have positive lymph nodes than younger patients (P = .02). In addition, octogenarians were less likely to exhibit extramural venous invasion compared to younger patients across all tumor sizes (P < .001). Younger patients had greater median overall survival (6.4 years vs 4.4 years; P < .001), yet 3-year disease-free survival was comparable between age groups (P = .12). CONCLUSION: Octogenarians with colon cancer present with larger tumors but appear to have less aggressive disease, as reflected in a lower pathologic stage, less extramural venous invasion, and less lymph node metastases, than younger patients with similar size tumors. Three-year disease-free survival is comparable between octogenarians and patients aged 50 to 79.