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The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Paraneoplastic syndromes are rare but possible manifestations of colorectal cancer. We present THE CASE of a 51-year-old female diagnosed with cT3N2 rectal adenocarcinoma who developed back pain and progressive muscle weakness during preoperative treatment. She had a rapid worsening in mobility and was ultimately ambulating with a wheelchair, despite physical therapy and conservative treatments. Extensive laboratory workup including onconeural antibodies was negative and her lower extremity electromyogram was suggestive of a subacute demyelinating lumbosacral plexopathy. After multidisciplinary discussion, the decision was made to proceed with curative resection. She had significant improvement in her weakness following resection, suggesting a paraneoplastic etiology. One year after resection, she remains free of disease and is ambulating comfortably. Onconeural antibodies can be a helpful diagnostic tool, but their absence does not rule out paraneoplastic disease. A high index of suspicion is necessary when assessing patients with atypical symptoms, particularly with the rise of colorectal cancer in young adults., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Background and Objectives: Area of residence may adversely affect survival and outcomes in many cancers. The objective of this study was to evaluate the impact of geographical and demographic disparities on survival of patients with colorectal cancer., Materials and Methods: Data were obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal datasets. Patients were categorized by area of residence, namely, metropolitan (MA), urban (UA), or rural (RA). Sociodemographic and tumor-related data were collected and analyzed to evaluate variables affecting overall survival (OS)., Results: In total, 973,139 patients between 2004 and 2013 were included in the study, of which 83%, 15%, and 2% were MA, UA, and RA residents, respectively. RA and UA patients were mostly white male with low income and no comorbidities. In univariate analysis, OS was worse for RA (hazard ratio [HR] 1.10) and UA (HR 1.06) colorectal cancer patients than that for MA colorectal cancer patients. In multivariate analysis revealed significant association between OS and geographic residence, with worse OS for RA (HR 1.02, p = 0.04) and UA (HR 1.01, p = 0.003) patients. Black (HR 1.14) and Native American (HR 1.17) patients had worse outcomes, while Asians (HR 0.8), women (HR 0.88), and patients with higher income had improved OS (HR 0.88)., Conclusion: The differences in the OS for RA and UA patients with colorectal cancer were significantly driven by economic disparity. Area of residence represents an important factor independently limiting access to care, particularly in geographically isolated individuals.

Importance: Changes in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients., Objective: To investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use., Design, Setting, and Participants: In this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019., Main Outcomes and Measures: Main outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured., Results: A total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P < .001). The ROPP implementation led to a 45% decrease in prescribed opioids after surgery (mean [SD], 157.22 [338.06] mean morphine milligram equivalents [MME] before ROPP vs 83.54 [395.70] MME after ROPP; P < .001). Patients in the post-ROPP cohort requested fewer refills (367 of 2051 [17.9%] vs 422 of 2017 [20.9%] in the pre-ROPP cohort; P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P < .001) and those without cancer (6.1% [19 of 310] to 2.7% [16 of 600]; P = .02)., Conclusions and Relevance: In this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Background: Controversy exists regarding the ability of neoadjuvant chemoradiation (nCR) to diminish lymph node yield (LNY) and how that relationship is influenced by tumor response in patients undergoing proctectomy for locally advanced rectal cancer., Materials and Methods: The National Cancer Database was used to identify patients with rectal adenocarcinomas from 2004 to 2014. Patients that received nCR were compared with those that underwent surgery alone. LNY was stratified into <12 and ≥12 groups to determine their differences in stage specific overall survival., Results: Of 56,812 patients 46.5% underwent surgery alone and 53.5% were administered nCR. There were more patients with LNY<12 in the nCR group compared to surgery alone, across all stages (44.1% versus 36.5%, P < 0.001). nCR improved OS regardless of LNY (P < 0.001). Although patients with LNY≥12 had improved overall survival, patients who had a pathologic complete response (pCR) achieved the greatest survival. In patients that did not achieve a pCR, LNY≥12 was a marker of improved OS but LNY did not impact OS in patients that attained pCR (P < 0.001)., Conclusions: Although nCR diminished LNY, LNY≥12 improved OS demonstrating the importance of quality total mesorectal excision. However, LNY did not impact patients that achieved pCR. These patients, who achieved the best OS, demonstrated that tumors' biologic response to nCR had the greatest impact on patient outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

Background: Previous studies have shown that variability in molecular markers correlates with poorer survival outcomes in patients with right-sided colon cancer (RCC) compared with left-sided colon cancer (LCC). However, several studies have shown conflicting results when examined stage for stage. We examined RCC and LCC to assess for differences in histopathologic features and overall survival (OS)., Materials and Methods: The National Cancer Database was used to identify patients with RCC and LCC from 2004 to 2013. A propensity-adjusted analysis evaluating the association between the primary site and OS was performed., Results: Of the 422,443 patients identified, 54.7% had RCC and 45.3% had LCC. For all stages, the patients with RCC were older, had more poorly differentiated tumors, and had a greater degree of microsatellite instability compared with those with LCC. Patients with RCC also had more KRAS mutations than did those with LCC. RCC patients had poorer 3- and 5-year OS at all stages, especially stage 3 (62% vs. 73% and 50% vs. 62%, respectively; P < .001). The median OS was 77.5 months for LCC and 62.3 months for RCC (P < .001)., Conclusion: The present study is one of the largest studies demonstrating that RCC and LCC are different biologic entities. Patients with RCC had significantly greater rates of microsatellite instability for all stages, which has been previously shown to be prognostically advantageous. However, the results of the present study showed poorer OS at every disease stage for RCC compared with LCC. These factors have important implications for the further use of targeted therapies in the treatment of advanced colon cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Individualized postoperative survival calculators for patients with cancer can be an aid for predicting prognosis and clinical decision making, such as the use of adjuvant chemotherapy. The aim of this study was to compare existing survival calculators for colon cancer and determine their performance using an independent cohort of patients., Methods: A retrospective analysis of a multi-site institutional experience was performed on patients diagnosed with stage II-III colon cancer between January 2012 and March 2013. Patient survival rates were estimated using Roswell Park Comprehensive Cancer Center (RPCCC), Memorial Sloan Kettering Cancer Center (MSKCC), and MD Anderson Cancer Center (MDACC) calculators. These calculators vary in the number and breadth of variables that are included. The agreement between selected models was obtained through a scatter plot matrix and related intra-class correlation coefficient (ICC). Calculators' performances were compared using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC) values., Results: After the application of inclusion and exclusion criteria, a total of 97 patients were included in the analysis. Survival data were available for all patients. Median follow-up was 57.6 months, and the overall 5-year survival rate was 0.74 (95% CI: 0.64-0.82). Overall, the different calculators tended to predict survival similarly (ICC =0.017). However, there was variation among calculator performance with the RPCCC calculator showing the highest performance (AUC =0.913), followed by the MSKCC calculator (AUC =0.803), and the MDACC calculator (AUC =0.644)., Conclusions: Prognostic models incorporating a more comprehensive amount of patient and tumor specific variables may provide a more accurate estimate of individual patient survival rates. These tools can be an actual aid in the clinical practice, allowing physicians to personalize treatment and follow-up for patients with colon cancer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

The NCCN Guidelines for Anal Carcinoma provide recommendations for the management of patients with squamous cell carcinoma of the anal canal or perianal region. Primary treatment of anal cancer usually includes chemoradiation, although certain lesions can be treated with margin-negative local excision alone. Disease surveillance is recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is essential for optimal patient care., (Copyright © 2018 by the National Comprehensive Cancer Network.)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: The purpose of this study was to characterize disparities among centers performing major surgery for esophageal or gastric cancer stratified by case volume., Methods: The National Cancer Data Base (NCDB) was queried for cases of esophagectomy or total gastrectomy. Centers were compared based on number of cases during 2004-2013: low volume [1-99], middle [100-200], and high [>200]., Results: For esophagectomy, 17,547 patients were included; 73.5% were treated in low volume centers, 14.6% in middle, and 11.9% in high. For gastrectomy, 20,059 patients were included, with 87.5%, 8.3%, and 4.3%, respectively. Patients treated at low volume centers were more likely to be of racial/ethnic minorities, uninsured, and have lower socioeconomic status. Overall survival (OS) was superior for patients treated at high volume centers. On multivariable analysis for either procedure, a higher number of disparate factors was identified in the low and middle volume centers compared to the high volume centers, which were associated with poorer OS., Conclusions: This study identified higher numbers of disparate patient factors associated with low/middle volume centers compared to high volume centers, which were associated with worse OS, and further makes the case for performance of esophagectomy and total gastrectomy at high volume centers., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Importance: Failure to rescue (FTR), or death after a potentially preventable complication, is a nationally endorsed, publicly reported quality measure. However, little is known about the impact of frailty on FTR, in particular after low-risk surgical procedures., Objective: To assess the association of frailty with FTR in patients undergoing inpatient surgery., Design, Setting, and Participants: This study assessed a cohort of 984 550 patients undergoing inpatient general, vascular, thoracic, cardiac, and orthopedic surgery in the National Surgical Quality Improvement Program between January 1, 2005, and December 31, 2012. Frailty was assessed using the Risk Analysis Index (RAI), and patients were stratified into 5 groups (RAI score, ≤10, 11-20, 21-30, 31-40, and >40). Procedures were categorized as low mortality risk (≤1%) or high mortality risk (>1%). The association between RAI scores, the number of postoperative complications (0, 1, 2, or 3 or more), and FTR was evaluated using hierarchical modeling., Main Outcomes and Measures: The number of postoperative complications and inpatient FTR., Results: A total of 984 550 patients were included, with a mean (SD) age of 58.2 (17.1) years; women were 549 281 (55.8%) of the cohort. For patients with RAI scores of 10 or less, major complication rates after low-risk surgery were 3.2%; rates of those with RAI scores of 11 to 20, 21 to 30, 31 to 40, and more than 40 were 8.6%, 13.5%, 23.8%, and 36.4%, respectively. After high-risk surgery, these rates were 13.5% for those with scores of 10 or less, 23.7% for those with scores of 11 to 20, 31.1% for those with scores of 21 to 30, 42.5% for those with scores of 31 to 40, and 54.4% for those with scores of more than 40. Stratifying by the number of complications, significant increases in FTR were observed across RAI categories after both low-risk and high-risk procedures. After a low-risk procedure, odds of FTR after 1 major complication for patients with RAI scores of 11 to 20 increased 5-fold over those with RAI scores of 10 or less (odds ratio [OR], 5.3; 95% CI, 3.9-7.1). Odds ratios were 8.1 (95% CI, 5.6-11.7) for patients with RAI scores of 21 to 30; 22.3 (95% CI, 13.9-35.6) for patients with scores of 31 to 40; and 43.9 (95% CI, 19-101.1) for patients with scores of more than 40. For patients undergoing a high-risk procedure, the corresponding ORs were likewise consistently elevated (RAI score 11-20: OR, 2.5; 95% CI, 2.3-2.7; vs RAI score 21-30: 5.1; 95% CI, 4.6-5.5; vs RAI score 31-40: 8.9; 95% CI, 8.1-9.9; vs RAI score >40: 18.4; 95% CI, 15.7-21.4)., Conclusions and Relevance: Frailty has a dose-response association with complications and FTR, which is apparent after low-risk and high-risk inpatient surgery. Systematic assessment of frailty in preoperative patients may help refine estimates of surgical risk that could identify patients who might benefit from perioperative interventions designed to enhance physiologic reserve and potentially mitigate aspects of procedural risk, and would provide a framework for shared decision-making regarding the value of a given surgical procedure.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma., Study Design: We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S)., Results: Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC., Conclusion: Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to identify differences in both demographic and pathologic factors associated with the age-related rates of colorectal cancer (CRC) and overall survival (OS)., Methods: The National Cancer Data Base (NCDB), 2004-2013, was queried for patients with CRC. Patients were stratified by age (≤50 vs. ≥60 years). Multivariable analysis was performed to identify factors associated with OS., Results: A total of 670,030 patients were included; 488,121 with colon, and 181,909 with rectal or rectosigmoid cancer. For colon cancer, patients ≤50 years had higher proportions of pathologic stage III and IV disease than patients ≥60 (III: 33.7% vs. 28.6%, IV: 25.5% vs. 14.3%, respectively; P≤0.001). Similar differences were found for patients with rectal cancer (III: 35.8% vs. 28.6%, IV: 16.5% vs. 11.6%, respectively for age ≤50 and ≥60 years; P≤0.001). More aggressive pathologic factors were identified in the ≤50 cohort and were associated with worse OS, including higher tumor grade, lymphovascular invasion (LVI), perineural invasion (PNI), and elevated serum carcinoembryonic antigen (CEA). Disparities associated with OS were also identified for both colon and rectal cancer. For patients ≤50 with CRC, African-American and Hispanic race, lower income and lower education were associated with increased risk of mortality compared to the ≥60 cohort., Conclusions: There are clear differences in biological factors and in racial and socioeconomic disparities of patients with early onset CRC. Earlier screening should be seriously considered in patients under 50 years who are African-American and Hispanic, as these populations present with more aggressive and advanced disease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures., Background: ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols., Methods: A systematic review was performed using "enhanced recovery after surgery" or "fast track" as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs., Results: A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI: $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis., Conclusions: ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.

Background: In locally advanced rectal adenocarcinoma, 15% to 20% of patients treated with neoadjuvant chemoradiation (nCRT) achieve a pathologic complete response (pCR). The benefit of adjuvant chemotherapy is controversial in rectal cancer. Our objective was to evaluate the effect of clinical risk factors and adjuvant chemotherapy usage on the outcomes of the pCR patient population., Patients and Methods: We performed a retrospective study using the National Cancer Data Base from 2006 to 2013. The primary outcome was overall survival (OS). The association between OS and patient characteristics (demographics, tumor variables, and treatment) was examined using multivariable Cox regression modelling., Results: A total of 2891 patients were identified who had achieved a pCR. Of these 2891 patients, 2102 received nCRT and 789 received nCRT followed by adjuvant chemotherapy. The median follow-up duration was 43.2 months. The factors significantly associated with OS included age (P < .001), gender (P = .011), Charlson-Deyo comorbidity score (P < .001), grade (P = .029), clinical T stage (P = .030), carcinoembryonic antigen negativity (P = .002), and receipt of adjuvant chemotherapy (P < .001). Nodal status was not significantly associated with survival. The 5-year OS rate was 94% in the nCRT plus adjuvant group compared with 84% in the nCRT-alone group. Adjuvant chemotherapy was more likely to be given to younger patients (aged < 60 years), higher grade, lower Charlson-Deyo comorbidity score, elevated carcinoembryonic antigen level, higher clinical T stage, and higher clinical N stage., Conclusion: Our findings showed a significant improvement in OS for patients who received nCRT plus adjuvant chemotherapy compared with those who received nCRT alone. The nCRT plus adjuvant patients were more likely to be younger, have a lower comorbidity score, have clinical ≥ T3 disease, and have clinical node-positive disease. Thus, a selection bias could have been present. Nonetheless, even in the setting of already excellent outcomes, for patients with locally advanced rectal adenocarcinoma who achieve a pCR, the additional benefit of adjuvant chemotherapy should be weighed against the potential for toxicity., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The incidence of colorectal cancer (CRC) among Americans under the age of 50 years is increasing. The purpose of this study was to identify racial and socioeconomic disparities associated with this trend. The National Cancer Data Base was used to identify patients with CRC from 1998 to 2011. Patients were stratified by age (<50 versus >60 years), with ages 50 to 60 years omitted from the analysis to minimize overlapping trends between the two age groups. Relative frequencies (RFs) by year were plotted against demographic variables. Changes in RF over time and intervals from diagnosis to treatment (including surgery and chemotherapy) were compared. A total of 1,213,192 patients were studied; 885,510 patients with colon cancer and 327,682 with rectal or rectosigmoid cancer. Patients <50 years had higher RF for stage III/IV CRC compared with >60 years, with the highest rate of increase in stage III colon cancer (0.198% per year). Patients <50 years had higher RF for CRC if they were African-American or Hispanic. Hispanic patients <50 years had the highest rates of increase for both colon (RF = 0.300% per year) and rectal cancer (RF = 0.248% per year). Compared with race, other variables including education and income were not found to have as strong an association on age-related rates of CRC. No clinically significant differences were observed for time from diagnosis to treatment in either age group. Important racial disparities are associated with differences in age-related CRC rates, warranting further investigation to develop improved strategies for the earlier detection of CRC in these populations.

Background: Our group reported that patients with clinically node-negative esophageal adenocarcinoma do not derive overall survival (OS) benefit from neoadjuvant chemoradiation (nCRT) compared with clinically node-positive patients. The aim of this study was to develop a calculator that could more easily identify which patients derive OS benefit from nCRT., Study Design: Using the National Cancer Data Base (2006 to 2012), patients with clinical status T1b to T4a, N-/+, M0 adenocarcinoma of the esophagus who underwent resection were selected. Of this cohort, 80% were randomly selected to develop and test the prediction model using Cox regression. The remaining 20% were used to internally validate the model, and performance was evaluated using receiver operating characteristic curves and area under the curves., Results: A total of 8,974 patients met study criteria. Using the model testing cohort (7,179 patients), variables that were independently associated with OS in multivariable analysis were included in the model. These variables included Charlson-Deyo comorbidity score, tumor grade, clinical T and N status, and nCRT before surgery. Factors associated with increased risk of death were higher grade and higher T or N status. Receipt of nCRT was associated with improved OS. After validation, model performance showed an area under the curve of 0.630 and 0.682 for 1-year and 3-year OS, respectively., Conclusions: A novel OS calculator was developed for esophageal adenocarcinoma that reasonably predicts which patients are expected to derive OS benefit from nCRT. This tool can be helpful in determining OS benefit from nCRT to assist with treatment decision making., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Background: Prediction calculators estimate postoperative survival and assist the decision-making process for adjuvant treatment. The objective of this study was to create a postoperative overall survival (OS) calculator for patients with stage II/III colon cancer. Factors that influence OS, including comorbidity and postoperative variables, were included., Study Design: The National Cancer Data Base was queried for patients with stage II/III colon cancer, diagnosed between 2004 and 2006, who had surgical resection. Patients were randomly divided to a testing (nt) cohort comprising 80% of the dataset and a validation (nv) cohort comprising 20%. Multivariable Cox proportional hazards regression of nt was performed to identify factors associated with 5-year OS. These were used to build a prediction model. The performance was assessed using the nv cohort and translated into mobile software., Results: A total of 129,040 patients had surgery. After exclusion of patients with carcinoma in situ, nonadenocarcinoma histology, more than 1 malignancy, stage I or IV disease, or missing data, 34,176 patients were used in the development of the calculator. Independent predictors of OS included patient-specific characteristics, pathologic factors, and treatment options, including type of surgery and adjuvant therapy. Length of postoperative stay and unplanned readmission rates were also incorporated as surrogates for postoperative complications (1-day increase in postoperative stay, hazard ratio [HR] 1.019, 95% CI 1.018 to 1.021, p < 0.001; unplanned readmission vs no readmission HR 1.35, 95% CI 1.25 to 1.45, p < 0.001). Predicted and actual 5-year OS rates were compared in the nv cohort with 5-year area under the curve of 0.77., Conclusions: An individualized, postoperative OS calculator application was developed for patients with stage II/III colon cancer. This prediction model uses nationwide data, culminating in a highly comprehensive, clinically useful tool., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS)., Objective: To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status., Design, Setting, and Participants: A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed., Main Outcome and Measures: The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality., Results: A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22)., Conclusions and Relevance: Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Background: With improvement in survival, elective surgical procedures are being increasingly performed on patients with metastatic disease. We aimed to study the association of pre-operative unintentional weight loss (UWL) with operative outcomes in this patient population., Methods: We extracted data on all patients with disseminated cancer undergoing elective surgeries between 2005 and 2011 from the National Surgical Quality Improvement Program (NSQIP), along with the Current Procedure Terminology (CPT) codes. Based on the presence of unintentional weight loss of >10% body weight in the 6-month period preceding surgery, patients were divided into 2 cohorts - (1) patients with UWL ('UWL' cohort) and (2) patients without UWL ('No UWL') cohort. Differences in patient characteristics, co-morbid conditions and outcomes were compared., Results: There were 30,669 surgeries recorded under 1,638 CPT codes, with 8,436 surgeries involving the eight most common CPT codes. UWL was present in 11.5% of all patients. UWL patients were more commonly (P < 0.05) male, African-American, of higher ASA (American Society of Anesthesiology) class, and had multiple associated comorbidities. Nearly all complications, including wound infections, prolonged ventilator requirement, unplanned intubation, cardiac arrest, DVT, sepsis and mortality were more common in UWL patients. Multivariate analysis demonstrated that UWL was independently associated with 21%, 22% and 49% higher risk of overall morbidity, serious morbidity and 30-day mortality, respectively., Conclusion: UWL is an independent risk factor associated with increased morbidity and mortality following elective surgeries in patients with disseminated cancer., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Surgery alone is often inadequate for advanced-stage gastric cancer. Surgical complications may delay adjuvant therapy. Understanding these complications is needed for multidisciplinary planning., Material and Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients who underwent gastrectomy for malignancy (ICD-9 code 151.x) from 2005 to 2010. Thirty-day mortality and morbidity were evaluated., Results: Overall, 2,580 patients underwent gastrectomy for malignancy, divided as total gastrectomy 999 (38.7 %) and partial gastrectomy 1,581 (61.3 %). Overall, serious morbidity occurred in 23.6 %, and the 30-day mortality was 4.1 %. Patients receiving a total gastrectomy were younger and healthier than those receiving a partial gastrectomy for the following measured criteria: age, diabetes, chronic obstructive pulmonary disease and hypertension. Serious morbidity and mortality were significantly higher in the total gastrectomy group than the partial gastrectomy group (29.3 vs. 19.9 %, p < 0.001; and 5.4 vs. 3.4 %, p < 0.015, respectively). The inclusion of additional procedures increased the risk of mortality for the following: splenectomy (odds ratio [OR] 2.8; p < 0.001), pancreatectomy (OR 3.5; p = 0.001), colectomy (OR 3.6; p < 0.001), enterectomy (OR 2.7; p = 0.030), esophagectomy (OR 3.5; p = 0.035). Abdominal lymphadenectomy was not associated with increased morbidity (OR 1.1; p = 0.41); rather, it was associated with decreased mortality (OR 0.468; p = 0.028)., Conclusions: Gastrectomy for cancer as currently practiced carries significant morbidity and mortality. Inclusion of additional major procedures increases these risks. The addition of lymphadenectomy was not associated with increased morbidity or mortality. Strategies are needed to optimize surgical outcomes to ensure delivery of multimodality therapy for advanced-stage disease.

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference., (Copyright © 2014 by the National Comprehensive Cancer Network.)

Endoscopic techniques are gaining popularity in the management of colorectal polyps and occasionally superficial cancers. While their use is in many times palliative, they have proven to be curative in carefully selected patients with polyps or malignancies, with less morbidity than radical resection. However, one should note that data supporting local and ablative therapies for colorectal cancer is scarce and may be subject to publication bias. Therefore, for curative intent, these techniques should only be considered in highly select cases as higher rates of local recurrences have also been reported. The aim of this review is to explain the different modalities of local and ablative therapies specific to colorectal neoplasia and explain the indications and circumstances where they have been most successful.

Changes in pulmonary microhemodynamics are important variables in a large variety of pathological processes. We used in vivo fluorescent videomicroscopy of the subpleural microvasculature in mechanically ventilated rats to directly monitor microvascular flow velocity (FV) and shear rate in pulmonary arterioles, capillaries, and venules in healthy rats and in septic rats 20 h after cecal ligation and puncture (CLP). Observations were made through a small thoracotomy after injection of fluorescent microspheres (D = 1 microm) into the systemic circulation. The FVs were calculated off-line by frame-by-frame measurements of the distance covered by individual microspheres per unit of time. In healthy rats, inspiratory FV were 1322 +/- 142 microm/s in subpleural arterioles and 599 +/- 25 microm/s in capillaries. The highest FV was found in venules (1552 +/- 132 microm/s). The calculated shear rates were 547 +/- 62/s in arterioles and 619 +/- 19/s in capillaries. The highest shear rates were detected in venules (677 +/- 59/s). No significant changes in FV and shear rates were observed throughout the 1-h observation period in any of the microvascular compartments. Pulmonary microvascular FV and shear rates found in sham-operated rats in the CLP experiments were not significantly different from values of healthy rats. The CLP caused a significant increase in leukocyte sequestration in the lungs and a mean of 27% to 34% decrease in FV in all sections of the pulmonary microvasculature (P < 0.001 in capillaries and P < 0.05 in venules). Also, CLP caused a 23% decrease in capillary shear rate that reached only borderline statistical significance (P < 0.06) and a significant 35% decrease in mean shear rate in venules (P < 0.05). Fluorescent videomicroscopy is offered as a stable and reproducible method for in vivo determinations of pulmonary microhemodynamics in clinically relevant models of sepsis.

Background: The co-morbidity of human immunodeficiency virus and other sexually transmitted diseases in Israel has not been established., Objectives: To compare the prevalence of STDs among HIV-positive patients to HIV-negative patients visiting an STD clinic in northern Israel., Methods: Between December 2000 and December 2001, 176 HIV-positive individuals (53% males) were screened and compared to 200 HIV-seronegative individuals (76% males). Demographics, symptomatology and risk factors were obtained via questionnaire. First-void urine samples were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis B and syphilis., Results: Relative to the seronegative STD patients, HIV-positive patients exhibited significantly greater risk-reducing sexual behaviors such as consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001]. Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative patients (79.5% vs 37.5%, P < 0.001). HSV-2, syphilis and HBV were more common among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%), P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200 (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more common in HIV-negative patients than HIV-positive patients [3/176 (1.7%) vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively., Conclusion: Despite the low risk sexual behavior of Israeli HIV patients, they had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be attributed to routine antibiotic prophylaxis against opportunistic infections. Nevertheless, as advocated by international health organizations, it appears prudent to recommend the routine screening of these asymptomatic HIV-positive patients for STD pathogens.