Impact of intramural and extramural vascular invasion on stage II-III colon cancer outcomes.

BACKGROUND AND OBJECTIVES: Vascular invasion, in particular extramural venous invasion (EMVI), is a pathologic characteristic that has been extensively studied in rectal cancer but rarely in colon cancer. This study aims to evaluate its prognostic role in stage II-III colon cancer. METHODS: All stage II-III colon cancer patients who underwent surgery between 2004 and 2015 were reviewed. We compared patients without invasion, with intramural invasion only (IMVI), EMVI only, and both IMVI/EMVI (n = 923). RESULTS: EMVI was associated with other high-risk features, including T4, N+ disease, lymphatic, and perineural invasion (P < 0.001). EMVI+ patients had higher rates of locoregional and distant recurrence and subsequently disease-specific mortality (stage-II, odds ratio [OR] 3.64; P = 0.001; stage-III OR, 1.94; P = 0.009), whereas outcomes were comparable between IMVI and no vascular invasion (OR, 1.21; P = 0.764; OR, 1.28, P = 0.607, respectively). The adjusted HRs for EMVI+ patients on disease-free survival, and disease-specific survival were 2.07 ( P < 0.001) and 1.67 ( P = 0.027), respectively. Moreover, EMVI+ stage-II patients fared worse than EMVI- stage-III patients, even after adjusting for adjuvant chemotherapy. CONCLUSION: EMVI is a strong predictor for worse oncologic outcomes in stage II-III colon cancer patients, whereas IMVI is not. It is also associated with worse outcomes compared in patients with higher stage disease who are EMVI negative.

A Transverse Colectomy is as Safe as an Extended Right or Left Colectomy for Mid-Transverse Colon Cancer.

BACKGROUND: Although extended colectomy is often chosen for patients with transverse colon cancer, the optimal surgical approach for mid-transverse colon cancer has not been established. METHODS: We identified patients who underwent a transverse (TC) or an extended colectomy (EC) for mid-transverse colon cancer between 2004 and 2014. To adjust for potential selection bias between the groups, a propensity score matching analysis was performed. RESULTS: A total of 103 patients were included, of whom 63% underwent EC (right 47%, left 17%) and 37% TC. EC patients tend to have worse short-term outcomes. Although fewer lymph nodes were harvested after TC, 5-year overall (OS) ad disease-free survival (DFS) was comparable between the groups. When comparing long-term outcomes stage-by-stage, worse OS and DFS were seen in stage-II. All stage-II patients died of a non-cancer-related cause and recurrence occurred in pT4 TC patients who did not receive adjuvant therapy. The propensity-matched cohort demonstrated similar postoperative morbidity, but more laparoscopic procedures in EC. Additionally, TC tumors were correlated with poorer histopathological features and disease recurrence was only seen after TC. CONCLUSION: Our study underlines the oncological safety of a transverse colectomy for mid-transverse colon cancer. Although TC tumors were associated with poorer histopathological features, survival rates were comparable.

Risk Stratification in Patients with Stage II Colon Cancer.

BACKGROUND: The decision to receive adjuvant chemotherapy is far from evident and remains controversial in patients with American Joint Committee on Cancer stage II colon cancer. This study analyzes several pathological characteristics in order to assess their (combined) predictive value for outcomes in stage II colon cancer. METHODS: All stage II patients treated surgically for colon cancer at our tertiary care center (2004-2011) were extracted from a prospectively maintained, Institutional Review Board-approved data repository (n = 313). Mortality and metastasis were compared, including multivariable Cox regression adjusted for stage subdivisions (IIA/IIB/IIC) and potential confounders. RESULTS: Colon cancer-specific mortality was substage independently increased in patients with baseline carcinoembryonic antigen (CEA) >5 ng/L [hazard ratio (HR) 2.88; p = 0.022], large vessel invasion (LVI; HR 4.59; p < 0.001), perineural invasion (HR 3.08; p = 0.006), and extramural vascular invasion (EMVI; HR 4.96; p < 0.001). Overall mortality adjusted for substage, age, and comorbidity was also significantly higher in patients with high-grade disease (HR 2.54; p < 0.001), LVI (HR 1.74; p = 0.015), perineural (HR 2.42; p < 0.001), and EMVI (HR 2.79; p < 0.001). Metastatic recurrence adjusted for adjuvant chemotherapy status had substage-independent associations with baseline CEA >5 ng/L (HR 2.37; p = 0.046), LVI (HR 3.07; p = 0.001), perineural invasion (HR 2.57; p = 0.010), and EMVI (HR 2.83; p = 0.002). The number of high-risk features (0, 1, 2-3, 4+) was associated with a clear incremental increase in overall and disease-specific mortality and recurrence (p ≤ 0.001). The major inflection point is at two high-risk characteristics or more, whereas 5-year survival is almost halved from 77.4 % to 31.7 % (p < 0.001). CONCLUSIONS: The risk score introduced provides a prognostic tool based on readily available data extracted from baseline pathology and preoperative CEA, which provides an easy method to stratify risks of mortality and recurrence and may therefore help in treatment decisions after surgery in stage II patients.

Effect of High-Grade Disease on Outcomes of Surgically Treated Colon Cancer.

INTRODUCTION: Tumor grade is one of the cardinal pathological characteristics of colon cancer. Despite a large body of evidence on disease grade in general, the exact impact of high-grade disease in the context of the simplified high/low-grade dichotomy that is based on glandular formation rate has yet to be quantified. METHODS: Patients with sporadic colon cancer treated surgically at our center (2004-2011) were included in an institutional review board-approved database. We measured the rates of distant and nodal disease spread in baseline pathology and the multivariable hazard radio (mHR) of recurrence and overall- and disease-specific mortality. RESULTS: Among 922 patients with specified tumor grade in baseline surgical pathology, 175 (19.0 %) had high-grade disease. These patients were at far higher risk of lymph node metastasis (63.8 vs. 39.6 %; P < 0.001) and metastatic presentation (31.4 vs. 15.8 %; P < 0.001). These baseline differences also led to significantly worse outcomes, including disease recurrence (17.1 vs. 10.6 %; mHR = 1.83; P = 0.026), overall mortality (57.7 vs. 33.3 %; mHR = 1.65; P < 0.001), and colon cancer-specific mortality (39.4 vs. 16.9 %; mHR = 1.57; P = 0.004). Most significantly, in stage II patients (n = 294), those with high-grade disease (16.0 %) had an mHR of 2.84 (P < 0.001) for mortality. CONCLUSIONS: High-grade disease on baseline surgical pathology is associated with a considerably higher rate of nodal and distant metastasis in colon cancer. As a result, the colon cancer-related mortality doubles for patients with high-grade disease. These findings were independent of baseline staging and confirm that the high-/low-grade tumor dichotomy is an important prognostic factor greatly influencing colon cancer outcomes across stages.

Renewed assessment of the stapled anastomosis with the increasing role of laparoscopic colectomy for colon cancer.

INTRODUCTION: Stapled gastrointestinal anastomosis has gained wide adoption among the surgical community for its ease, speed, and its applicability in laparoscopic surgery. Over the last decade, with the increase in laparoscopic techniques in colon surgery, anastomotic stapling has become the technique of choice for colon cancer surgery at our center. This abstract assesses whether the increasing adoption of anastomotic stapling affected the rate of anastomotic leaks and duration of surgery. METHODS: All patients surgically treated for colon cancer with a primary bowel anastomosis from 2004 through 2011 were included (n = 998). Duration of stay, surgery, and postoperative complication rates was compared between hand-sewn and stapled anastomosis. RESULTS: The number of stapled anastomoses grew significantly from 45.8% in 2004-2007 to 80.3% in 2008-2011 (p < 0.001), and an increasing portion of those is performed in laparoscopic procedures (29.8 to 43.3%; p = 0.01). Surgeries using stapled anastomosis initially took longer, but a decreasing trend (2004-2007: 147.5 min to 2007-2011: 124 min; p < 0.001) along with an increasing duration in hand-sewn surgeries (94-118.5 min; p < 0.01) meant stapled procedures became shorter than hand-sewn procedures by 2009. Complication rates did not differ significantly between groups, with stapled anastomoses having lower percentages of anastomotic leaks (1.6 vs. 2.4%; p = 0.38). By the second half of our research period, the median admission for patients with stapled anastomoses was two days shorter (4 vs. 6 days; p < 0.001), independently of the chosen approach. CONCLUSION: Stapled anastomoses did not increase anastomotic leak rates. If anything, leak rates appeared slightly lower. In addition, stapled anastomoses significantly shortened operation duration. With the benefit of being a tool that facilitates minimally invasive surgery, it is a safe way to improve efficiency, reduce costs, and promote faster and better recovery.

Treatment delay in surgically-treated colon cancer: does it affect outcomes?

BACKGROUND: Treatment delay, or the time lapse between diagnosis and surgery, may have a detrimental effect on cancer outcomes. This study assesses the effect of treatment delay on cancer-related outcomes in a large, continuous series of surgically treated colon cancer patients. METHODS: All surgical colon cancer cases at our center from 2004 through 2011 were reviewed. Patients who underwent preoperative chemotherapy, emergency admissions, palliative cases, and incidental and postoperative diagnoses were excluded. Treatment delay was correlated with outcomes in univariate and multivariate regression and proportional hazards models. RESULTS: In 769 included patients, for every treatment-delay quartile increase, odds of death decreased by an odds ratio (OR) of 0.78 (p = 0.001), and metastatic recurrence by OR 0.78 (p = 0.013). Shorter survival duration had a hazard ratio (HR) of 0.81 (p = 0.001) and shorter disease-free survival HR 0.72 (p < 0.001). Multivariate regression adjusting for baseline staging greatly reduces these ratios, and makes them non-significant. Similar patterns were shown in high-risk subsets, including stage III disease, ethnic minorities, patients with positive margins, and extramural vascular invasion. CONCLUSIONS: The inverse relation between treatment delay and survival and recurrence reflected adequate prioritization of advanced and high-risk cases and concurrently showed that, matched for stage and risk categories, treatment delay was not associated with worse cancer outcomes for patients with colon cancer. A reasonable delay between diagnosis and subsequent surgery is not detrimental to patient outcomes and permits more flexibility in scheduling and justifies allowing time to complete proper preoperative evaluation and staging, improving the quality and safety of resection and treatment.

Gender and ethnic disparities in colon cancer presentation and outcomes in a US universal health care setting.

OBJECTIVE: Access to care is a pillar of U.S. healthcare reform and could potentially challenge existing ethnic and gender disparities in care. We present a snapshot of these disparities in surgical colon cancer patients in the largest public hospital in Massachusetts, a state leading in providing universal healthcare, to indicate potential changes that might result from universal care access. METHODS: All surgical colon cancer patients at Massachusetts General Hospital (2004-2011) were included. Baseline characteristics, perioperative, and long-term outcomes were compared. RESULTS: Among 1,071 patients, the 110 (10.3%) minority patients presented with more comorbid (mean Charlson score 0.84 vs. 0.71; P = 0.039), metastatic (21.8% vs. 14%; P = 0.026), and node-positive disease (50% vs. 38.8%; P = 0.014). Women (n = 521; 48.6%) had less screening diagnoses (overall: 17.8% vs. 22.6%; P = 0.049, screening age: 26.4% vs. 32.7%; P = 0.036) with subsequently higher rates of metastatic disease on pathology (11.3% vs. 7.1%, P = 0.02). Multivariate adjustment for baseline staging makes outcome disparities no longer statistically significant. CONCLUSIONS: Significant gender and ethnic disparities subsist at baseline despite long-standing low-threshold healthcare access, although seemingly mitigated by enrollment into high-level care, empowering equal chances for underprivileged groups. The outcomes are also a reminder that universal healthcare will not be a panacea for the deeply rooted and dynamic causes of presentation inequalities.

Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer.

OBJECTIVE: Several reports have shown that certain pre-operative CEA intervals can be predictive of long-term outcomes and have subsequently implied that preoperative CEA may be useful to assess the risk of recurrence or death as a continuous number for individual cases. This analysis assesses if this hypothesis is valid after correction for confounders. METHODS: All colon cancer patients operated on at Massachusetts General Hospital from 2004 through 2011 were considered for retrospective review. Association between outcomes and preoperative CEA was measured in intervals and as a linear relationship. RESULTS: Of the 1,071 patients operated for colon adenocarcinoma, 621 (57.9%) had a preoperative CEA drawn and were included in the analysis. In models using intervals, preoperative CEA did show association with (disease-free) survival, but this was shown to be chiefly a surrogate for metastatic presentation. In linear approaches adjusted for metastatic presentation, CEA loses all correlations with metastatic disease (P = 0.84), survival (P = 0.11), survival duration (P = 0.42) and disease-free interval (P = 0.94). CONCLUSIONS: Extrapolating the predictive value of certain preoperative CEA intervals to a continuous approach for use in a case-for-case basis is unjustified. Preoperative CEA may be a useful risk estimator but has limited significance for predictions of long-term outcomes in individual cases.

Surgical treatment of gastrinomas: a single-centre experience.

BACKGROUND: Gastrinomas are rare neuroendocrine tumours, and responsible for Zollinger-Ellison syndrome (ZES). Surgery is the only treatment that can cure gastrinomas. The success of surgical treatment of gastrinomas in a single centre was evaluated. METHODS: A retrospective review of all patients who underwent resection for a gastrinoma between 1992 and 2011 at a single institution was performed. Presentation, diagnostics, operative management and outcome were analysed. RESULTS: Eleven patients with a median age of 46 years were included. All patients had fasting hypergastrinaemia and a primary tumour was localized using imaging studies in all patients. A pylorus-preserving pancreaticoduodenectomy was performed in three patients: two patients underwent duodenectomy and one patient central pancreatectomy. The remaining five patients underwent enucleation. A primary tumour was removed in nine patients: five tumours were situated in the pancreas, three in the duodenum and one patient was considered to have a primary lymph node gastrinoma. The median follow-up was 3 years (range 1-15) after which 7 patients were disease-free and 3 patients had (suspected) metastatic disease. One patient died 13 years after initial surgery. CONCLUSION: The success of surgical treatment of a gastrinoma in this series was 7/11 with a median follow-up of 3 years; comparable to recent published studies.

Outcomes of persistent lymph node involvement after neoadjuvant therapy for stage III rectal cancer.

INTRODUCTION: Lymph node involvement is a well-known predictor of recurrent rectal cancer in patient who did not undergo neoadjuvant therapy patients. The role of persistent lymph node disease after neoadjuvant treatment, however, is debatable. This study compares outcomes of patients with clinical, stage III rectal cancer who had nodal disease on surgical pathology after neoadjuvant treatment to patients with negative nodes. METHODS: We reviewed retrospectively a consecutive cohort of all clinical, American Joint Committee on Cancer stage III rectal cancer patients who received neoadjuvant chemoradiotherapy and had an R0 resection at the Massachusetts General Hospital between 2004 and 2015. RESULTS: A total of 166 patients met the inclusion criteria, of whom 53 had persistent nodal disease on pathologic examination. This group had a greater rate of local and distant disease recurrence and a shorter median recurrent disease-free survival than patients with a complete nodal response. In multivariable analyses for disease recurrence, disease free survival was greater for patients without positive results in lymph nodes on pathologic examination. CONCLUSION: Persistent nodal involvement after neoadjuvant therapy is associated with an increased risk of distant metastases and a shorter disease-free survival. Identifying patients with treatment-resistant lymph nodes preoperatively and adjusting neoadjuvant treatment might result in better outcomes.

Prone positioning reduces perineal infections when performing the miles procedure.

BACKGROUND: Abdominoperineal resection (APR) remains the cornerstone treatment for rectal cancers less than 5 cm from the anal verge. The perineal portion of an APR can be done with the patient in lithotomy or repositioned to prone jack-knife position, which influences accessibility, visualization and ability to close the wound. This paper analyses the effect of patient positioning on perineal wound dehiscence and infections. METHODS: A retrospective review of all rectal cancer patients who underwent an APR at Massachusetts General Hospital between 2004 and 2014 (n = 149). Patients were divided into supine (n = 91) or prone (n = 58) positioning as documented in operative reports. RESULTS: Twenty-two percent of supine positioned patients developed a perineal wound infection, versus 3.4% of the prone patients (P = 0.002). Perineal wound dehiscence rate was also higher in the supine positioned group (14.3% vs. prone 3.4%; P = 0.032). Multivariable analysis showed OR = 9.2 of developing a perineal wound infection for supine positioned patients, compared to prone, corrected for obesity and smoking history. CONCLUSION: Repositioning patients into prone position for the perineal portion of an APR was associated with significantly lower perineal wound infection and dehiscence rates compared to supine positioned patients.

Risk Stratification for Surgical Site Infections in Colon Cancer.

Importance: Surgical site infections (SSIs) feature prominently in surgical quality improvement and pay-for-performance measures. Multiple approaches are used to prevent or reduce SSIs, prompted by the heavy toll they take on patients and health care budgets. Surgery for colon cancer is not an exception. Objective: To identify a risk stratification score based on baseline and operative characteristics. Design, Setting, and Participants: This retrospective cohort study included all patients treated surgically for colon cancer at Massachusetts General Hospital from 2004 through 2014 (n = 1481). Main Outcomes and Measures: The incidence of SSI stratified over baseline and perioperative factors was compared and compounded in a risk score. Results: Among the 1481 participants, 90 (6.1%) had SSI. Median (IQR) age was 66.9 (55.9-78.1) years. Surgical site infection rates were significantly higher among people who smoked (7.4% vs 4.8%; P = .04), people who abused alcohol (10.6% vs 5.7%; P = .04), people with type 2 diabetics (8.8% vs 5.5%; P = .046), and obese patients (11.7% vs 4.0%; P < .001). Surgical site infection rates were also higher among patients with an operation duration longer than 140 minutes (7.5% vs 5.0%; P = .05) and in nonlaparoscopic approaches (clinically significant only, 6.7% vs 4.1%; P = .07). These risk factors were also associated with an increase in SSI rates as a compounded score (P < .001). Patients with 1 or fewer risk factors (n = 427) had an SSI rate of 2.3%, equivalent to a relative risk of 0.4 (95% CI, 0.16-0.57; P < .001); patients with 2 risk factors (n = 445) had a 5.2% SSI rate (relative risk, 0.78; 95% CI, 0.49-1.22; P = .27); patients with 3 factors (n = 384) had a 7.8% SSI rate (relative risk, 1.38; 95% CI, 0.91-2.11; P = .13); and patients with 4 or more risk factors (n = 198) had a 13.6% SSI rate (relative risk, 2.71; 95% CI, 1.77-4.12; P < .001). Conclusions and Relevance: This SSI risk assessment factor provides a simple tool using readily available characteristics to stratify patients by SSI risk and identify patients at risk during their postoperative admission. Thereby, it can be used to potentially focus frequent monitoring and more aggressive preventive efforts on high-risk patients.

Do packed red blood cell transfusions really worsen oncologic outcomes in colon cancer?

BACKGROUND: Data from small retrospective studies have argued that perioperative packed red blood cell transfusions may increase the risk of developing metastatic recurrence in cancer patients. This study tests this assumption in a large cohort spanning a decade of operatively treated colon cancer patients. METHODS: All patients undergoing primary resection of a colon cancer at a tertiary care center between 2004-2014 (n = 1,423) were included in a retrospective review of a prospectively maintained data repository. Survival and disease-free survival were compared and also adjusted in multivariable Cox regression standardized for follow-up, American Society of Anesthesiologists score, age, sex, postoperative chemotherapy, baseline staging, and tumor grade. RESULTS: Of the 1,423 patients, 305 (21.4%) received a perioperative packed red blood cell transfusion during their index admission. During follow-up, overall mortality was greater in patients who received perioperative packed red blood cell (53.1% vs 30.9%; P < .001); however, there were no appreciable differences in rates of long-term distant recurrence (in patients without baseline metastasis 11.1% vs 13.9%; P = .25), or disease-specific mortality (21.3% vs 17.3%; P = .104; without baseline metastasis: 8.6% vs 8.9%; P = .89). Similarly, multivariable Cox regression showed no statistical difference in recurrence (hazard ratio: 0.83, 95% confidence interval, 0.83-1.26; P = .38) or disease-specific mortality (hazard ratio: 1.12, 95% confidence interval, 0.83-1.51; P = .47). CONCLUSION: Mortality rates were significantly greater in patients with perioperative packed red blood cell transfusions, a finding that is backed by a body of evidence that associates perioperative packed red blood cell transfusion with comorbidity and serious illness, but contrary to earlier evidence, findings in our cohort do not support a hypothesis that perioperative perioperative packed red blood cell transfusions have a detrimental effect on recurrence rates of operatively treated colon cancer patients.

Diverse repetitive element RNA expression defines epigenetic and immunologic features of colon cancer.

There is tremendous excitement for the potential of epigenetic therapies in cancer, but the ability to predict and monitor response to these drugs remains elusive. This is in part due to the inability to differentiate the direct cytotoxic and the immunomodulatory effects of these drugs. The DNA-hypomethylating agent 5-azacitidine (AZA) has shown these distinct effects in colon cancer and appears to be linked to the derepression of repeat RNAs. LINE and HERV are two of the largest classes of repeats in the genome, and despite many commonalities, we found that there is heterogeneity in behavior among repeat subtypes. Specifically, the LINE-1 and HERV-H subtypes detected by RNA sequencing and RNA in situ hybridization in colon cancers had distinct expression patterns, which suggested that these repeats are correlated to transcriptional programs marking different biological states. We found that low LINE-1 expression correlates with global DNA hypermethylation, wild-type TP53 status, and responsiveness to AZA. HERV-H repeats were not concordant with LINE-1 expression but were found to be linked with differences in FOXP3+ Treg tumor infiltrates. Together, distinct repeat RNA expression patterns define new molecular classifications of colon cancer and provide biomarkers that better distinguish cytotoxic from immunomodulatory effects by epigenetic drugs.

The prognostic value of lymph node ratio in colon cancer is independent of resection length.

BACKGROUND: Lymph node ratio (LNR), the ratio of tumor-positive lymph nodes (+LN) to the total number of resected lymph nodes (rLN), predicts recurrence and survival in colon cancer. Variations in colonic resection length (RL) may influence rLN, +LN, or both, thereby potentially impacting LNR and its prognostic value in colon cancer. METHODS: All colon cancer patients treated surgically at our center from 2004 to 2011 were included in an institutional review board-approved data repository (n = 1,039). RESULTS: Larger RL was associated with increased rLN (ρ = .22; P < .001) but not with +LN (P = .21). In node-positive patients (n = 411), RL-adjusted LNR had weaker correlations with death (ρ = .338 vs .373, both P < .001) or metastatic disease (ρ = .303 vs .345; both P < .001) and a smaller area under the curve (death: .695 vs .715, metastasis: .675 vs .699). Findings were similar in segmental, extended segmental, and total colectomy subgroups. CONCLUSIONS: Provided that resections are performed following standard oncologic principles, our analysis shows that RL does not significantly impact the prognostic value of LNR in colon cancer. Correcting LNR for RL seems redundant and may even act as noise distorting LNR values.

The conundrum of the young colon cancer patient.

BACKGROUND: Colonoscopy has had a major impact on the incidence and survival of colon cancer for patients who are screened, usually beginning at the age of 50. Meanwhile, the incidence rate of colon cancer is actually increasing in the patients younger than 50 while no routine screening is implemented for this age group. METHODS: All patients surgically treated for colon cancer (2004-2011) without preexisting high-risk characteristics (hereditary nonpolyposis colorectal cancer, inflammatory bowel disease) were included (n = 1,015). Age-related disparities in baseline disease and outcomes were reviewed. RESULTS: Patients younger than 50 years of age (n = 108; 10.6%) had the greatest baseline rates of metastatic (20.4% vs 8.0%; P < .001), node-positive disease (54.6% vs 39.4%; P = .002), and greater rates of extramural vascular invasion (38.9 vs 29.4%; P = .043). Cancer-related mortality also was greatest in this group (28.7 vs 18.4%; P = .011). Multivariable Cox regression shows that patients younger than 50 are still at significantly greater risk of mortality after adjustment for effects of age, baseline AJCC staging, smoking, and comorbidity (hazard ratio: 1.57, 95% confidence interval 1.01-2.45; P = .049). DISCUSSION: Patients younger than 50 present with the most advanced and aggressive disease, giving them the worst stage-independent prognosis of all age groups. Potential causes include age-related differences in tumor biology and underdetection by current screening efforts. This raises the question of how to address the conundrum of the young colon cancer patient, who often is the proverbial needle in a haystack of young patients, with nonspecific gastrointestinal symptoms but who would benefit considerably from early detection.

Colon cancer surgery following emergency presentation: effects on admission and stage-adjusted outcomes.

BACKGROUND: Emergency presentation with colon cancer is intuitively related to advanced disease. We measured its effect on outcomes of surgically treated colon cancer. METHODS: A retrospective cohort of 1,071 surgical colon cancer patients (2004 to 2011), with 102 emergency cases requiring surgery within the index admission, was analyzed. RESULTS: Emergency patients required longer surgeries (median 141 vs 124 minutes; P = .04), longer median admissions (8% vs 5%; P < .001), more readmissions (12.7% vs 7.1%; P = .040), and perioperative mortality (7.8% vs .8%; P < .001). Surgical pathology displayed higher rates of node-positive disease (56.6% vs 38.6%; P < .001), extramural vascular invasion (39.6% vs 29.1%; P = .021), and metastatic disease (19.6% vs 8%; P < .001). Consequently, adjusting for staging, emergency presentations had considerably higher mortality (odds ratio = 2.07; P = .003) and shorter disease-free survival (hazard ratio = 1.39; P = .042). CONCLUSIONS: Emergency presentation is a stage-independent poor prognostic factor associated with aggressive tumor biology, resulting in longer surgeries and admissions, frequent readmissions, worsening outcomes, and increasing healthcare costs.

Variations in Metastasis Site by Primary Location in Colon Cancer.

OBJECTIVE: The purpose of this paper is to determine whether sites of distant recurrence are associated with specific locations of primary disease in colon cancer. METHODS: A cohort including all patients (n = 947) undergoing a segmental colonic resection for colon cancer at our center (2004-2011) comparing site-specific metastatic presentation and recurrence rates, as well as their respective multivariable American Joint Committee on Cancer (AJCC) stage-adjusted hazard ratios (mHR). RESULTS: Right-sided colectomies (n = 557) had a lower overall metastasis rate (24.8% vs. 31.8%; P = 0.017; mHR = 1.24 [95% CI: 0.96-1.60]; P = 0.011) due to significantly lower pulmonary metastasis in follow-up (2.7% vs. 9%; P < 0.001; mHR = 0.32 [95% CI: 0.17-0.58]; P = 0.001) and lower overall liver metastasis rate (15.6 vs. 22.1%; P = 0.012; mHR = 0.74 [95% CI: 0.55-0.99];P = 0.050). Left colectomies (n = 127) had higher rates of liver metastasis during follow-up (9.4% vs. 4.8%; P = 0.029; mHR = 1.64 [95% CI: 0.86-3.15]; P = 0.134). Sigmoid resections (n = 238) had higher baseline rates of liver metastasis (17.1% vs. 11.3%; P = 0.015) and higher cumulative rates of lung (12.2% vs. 5.4%; P < 0.001; mHR = 2.26 [95% CI: 1.41-3.63]; P = 0.001) and brain metastases (2.3% vs. 0.6%; P = 0.033; mHR = 4.03 [95% CI: 1.14-14.3]; P = 0.031). Other sites of metastasis, including the (retro) peritoneum, omentum, ovary, and bone, did not yield significant differences. CONCLUSIONS: Important variations in site-specific rates of metastatic disease exist within major resection regions of colon cancer. These variations may be important to consider when evaluating options for adjuvant treatment and surveillance after resection of the primary disease.

Does active smoking induce hematogenous metastatic spread in colon cancer?

BACKGROUND: No consensus exists on the influence of active smoking on the baseline staging of colon cancer patients. METHODS: A cohort of colon cancer patients treated surgically at Massachusetts General Hospital (2004 to 2011) was reviewed. RESULTS: Of 1,071 patients, 563 reported ever smoking, among which 128 (12%) patients were current smokers. Ex-smokers and never smokers had similar rates of nodal (relative risk [RR] .9, P = .19) and metastatic disease (RR .96, P = .72), leading to comparable colon cancer-related mortality (RR 1.01, P = .95). Current smokers had similar rates of lymph node disease (RR 1.01, P = .88), but had significantly higher stage-adjusted odds of metastatic disease at presentation (odds ratio 2.57, 95% confidence interval 1.36 to 4.98, P = .005), in addition to higher stage-adjusted all-cause mortality (hazard ratio 1.44, P = .017). CONCLUSIONS: Active smoking was a stage-independent risk factor for baseline hematogenous metastasis and mortality. As this link was not present in former smokers, a potential healthcare benefit may be achieved in terms of baseline colon cancer presentation and outcomes through smoking cessation.

Association of Radial Margin Positivity With Colon Cancer.

IMPORTANCE: In colon cancer, radial margin positivity (RMP) is defined as primary disease involvement at the cut edge of the mesentery or nonserosalized portions of the colon. Although extensively studied for rectal malignancies, RMP has unclear prognostic implications for tumors of the colon. OBJECTIVE: To determine the effect of RMP on perioperative outcomes as well as survival and disease-free survival in colon cancer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study including all patients with surgically treated colon cancer at a tertiary care center from January 1, 2004, through December 31, 2011. The cohort was retrospectively extracted from an institutional patient data repository and included in a data repository maintained prospectively starting June 1, 2011, to April 1, 2014. Participants included 984 patients with surgical colon cancer in the given period, excluding patients with intramucosal tumors (n = 47), palliative resections (n = 24), and patients where radial margin status was not assessable (n = 16). MAIN OUTCOMES AND MEASURES: Surgical characteristics, postoperative staging, and long-term outcomes, including recurrence and disease-free survival. RESULTS: Of the 984 included cases, 52 (5.3%) had an involved radial margin. Patients with RMP had much higher rates of multivisceral resection (40.4% vs 12.8%; relative risk, 3.16 [95% CI, 2.18-4.58]; P < .001) and conversion (50.0% vs 13.7%; relative risk, 3.78 [95% CI, 1.56-9.18]; P = .01). All patients with RMP had American Joint Committee on Cancer stage II cancer or higher, with higher rates of node positivity (86.5% vs 38.8%; relative risk, 2.23 [95% CI, 1.95-2.55]; P < .001), metastasis (34.6% vs 6.7%; relative risk, 5.20 [95% CI, 3.34-8.11]; P < .001), extramural vascular invasion (76.9% vs 28.4%; relative risk, 2.71 [95% CI, 2.26-3.24]; P < .001), and high-grade tumor (45.1% vs 18.2%; relative risk, 3.01 [95% CI, 2.44-3.88]; P < .001). In patients without baseline metastasis, metastatic disease in follow-up was considerably higher in patients with RMP (37.5% vs 12.5%; relative risk, 3.32 [95% CI, 2.79-3.95]; P < .001), especially peritoneal (18.8% vs 2.6%; relative risk, 7.24 [95% CI, 2.40-21.8]; P < .001) and liver (18.8% vs 6%; relative risk, 3.10 [95% CI, 1.08-8.92]; P = .04) metastasis. In multivariable Cox regression, the hazard ratio for survival adjusted for baseline staging, age, comorbidity, smoking, and neoadjuvant chemotherapy was higher (hazard ratio, 3.39; 95% CI, 2.41-4.77; P < .001) compared with metastasis adjusted for baseline staging, smoking, and neoadjuvant chemotherapy (hazard ratio, 2.03; 95% CI, 1.43-2.89; P < .001). The median follow-up duration for patients alive on April 1, 2014, was 51 months (interquartile range, 33-76 months). CONCLUSIONS AND RELEVANCE: An involved radial margin leads to high rates of conversion and multivisceral resection. Although occurring infrequently, RMP is an important stage-independent outcome predictor strongly associated with recurrence, risk of death, and shorter survival. Preoperative assessment, especially imaging, could play a key role in the timely identification of potential patients with RMP to take adequate preparatory surgical and therapeutic measures.