Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

Molecular Basis of Extramural Vascular Invasion (EMVI) in Colorectal Carcinoma.

BACKGROUND: Extramural vascular invasion (EMVI) is a known poor prognostic factor in colorectal carcinoma; however, its molecular basis has not been defined. This study aimed to assess the expression of molecular markers in EMVI positive colorectal carcinoma to understand their tumor microenvironment. METHODS: Immunohistochemistry was performed on tissue microarrays of surgically resected colorectal cancer specimens for immunological markers, and BRAFV600E mutation (and on the tissue blocks for mismatch repair proteins). Automated quantification was used for CD8, LAG3, FOXP3, PU1, and CD163, and manual quantification was used for PDL1, HLA I markers (beta-2 microglobulin, HC10), and HLA II. The Wilcoxon rank-sum test was used to compare EMVI positive and negative tumors. A logistic regression model was fitted to assess the predictive effect of biomarkers on EMVI. RESULTS: There were 340 EMVI positive and 678 EMVI negative chemo naïve tumors. PDL1 was barely expressed on tumor cells (median 0) in the entire cohort. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 cells, PDL1 positive macrophages, and beta-2 microglobulin on tumor cells in the EMVI positive subset (p ≤ 0.001). There was no association of BRAFV600E or deficient mismatch repair proteins (dMMR) with EMVI. PU1 (OR 0.8, 0.7-0.9) and low PDL1 (OR 1.6, 1.1-2.3) independently predicted EMVI on multivariate logistic regression among all biomarkers examined. CONCLUSION: There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

Patient Survival With ypT0N+ Following Neoadjuvant Therapy in Rectal Cancer.

BACKGROUND: After neoadjuvant therapy, pathologic analysis of rectal cancer resected specimens may show a complete response in the primary tissue cancer with residual tumor in the lymph nodes (ypT0N+). OBJECTIVES: The aim of this study was to describe the 5-year overall survival and factors associated with survival of ypT0N+ patients with rectal cancer who had neoadjuvant therapy followed by surgery and to compare these patients' survival with patients in other pathologic categories. DESIGN: We conducted a retrospective analysis. SETTINGS: We used the National Cancer Database. PATIENTS: We identified patients with rectal adenocarcinoma who underwent total neoadjuvant therapy or neoadjuvant chemoradiation followed by surgery between 2006 and 2016. Besides ypT0N+, 5 pathologic categories were identified: ypT0N0, ypT1-2N0, ypT3-4N0, ypT1-2N+, and ypT3-4N+. MAIN OUTCOME MEASURE: The primary outcome measure was 5-year overall survival. RESULTS: We included 30,751 patients with rectal adenocarcinoma. A total of 342 patients developed ypT0N+, of whom 181 (52.9%) received total neoadjuvant therapy. Among patients who received total neoadjuvant therapy, developing ypT0N+ was associated with a lower 5-year overall survival than ypT0N0 and ypT1-2N0. However, ypT0N+ disease was associated with a higher 5-year overall survival than ypT3-4N+. There were no differences in 5-year overall survival between ypT0N+ and ypT3-4N0 or ypT1-2N+. Similar findings were noticed among patients who received neoadjuvant chemoradiation and adjuvant chemotherapy. For patients with ypT0N+, older age, male gender, and higher number of positive lymph nodes were all associated with a decrease in the overall survival. LIMITATIONS: Limitations include the retrospective nature of this study, lack of variables describing the chemotherapy and radiation regimens used, and paucity of data on disease-specific survival or recurrence. CONCLUSIONS: Developing ypT0N+ was associated with a lower 5-year overall survival than ypT0N0 and ypT1-2N0. However, it was associated with a higher 5-year overall survival than ypT3-4N+. See Video Abstract at http://links.lww.com/DCR/B863 . SOBREVIDA DE LOS PACIENTES CON YPTN DESPUS DE LA TERAPIA NEOADYUVANTE EN EL CNCER DE RECTO: ANTECEDENTES:Después del tratamiento neoadyuvante en el cáncer de recto bajo, el análisis patológico de la pieza operatoria resecada, puede mostrar una respuesta patológica completa del tumor primario pero con tumor residual en los ganglios linfáticos (ypT0N+).OBJETIVOS:Describir la sobrevida general a 5 años y los factores asociados con la sobrevida de los pacientes ypT0N+ con cáncer de recto, que recibieron terapia neoadyuvante seguida de cirugía y comparar la sobrevida de estos pacientes con la de pacientes con otros estadios patológicos.DISEÑO:Realizamos un análisis retrospectivo.AJUSTES:Utilizamos la base de datos nacional del cáncer.PACIENTES:Identificamos pacientes con adenocarcinoma de recto que se sometieron a terapia neoadyuvante total, seguida de cirugía entre 2006 y 2016. Además de ypT0N +, se identificaron 5 categorías patológicas: ypT0N0, ypT1-2N0, ypT3-4N0, ypT1-2N+, e ypT3-4N+.PRINCIPAL MEDIDA DE RESULTADO:La medida de resultado principal fue la supervivencia general a 5 años.RESULTADOS:Se incluyeron 30.751 pacientes con adenocarcinoma de recto. Un total de 342 pacientes desarrollaron ypT0N+, de los cuales 181 (52,9%) recibieron terapia neoadyuvante total. Entre los pacientes que recibieron terapia neoadyuvante total, el desarrollo de ypT0N+ se asoció con una supervivencia general a 5 años más baja que ypT0N0 e ypT1-2N0. Sin embargo, la enfermedad ypT0N+ se asoció con una supervivencia general a 5 años más alta que ypT3-4N+. No hubo diferencias en la supervivencia global a 5 años entre ypT0N+ y ypT3-4N0 o ypT1-2N+. Se observaron hallazgos similares entre los pacientes que recibieron terapia neoadyuvante y quimioterapia adyuvante. Para los pacientes con ypT0N+, la edad avanzada, el sexo masculino y un mayor número de ganglios linfáticos positivos se asociaron con una disminución en la supervivencia general.LIMITACIONES:Las limitaciones incluyen la naturaleza retrospectiva del estudio, la falta de variables que describan los regímenes de quimioterapia y radiación utilizados y la escasez de datos sobre la supervivencia o la recurrencia específicas de la enfermedad.CONCLUSIONES:El desarrollo de ypT0N+ se asoció con una supervivencia general a 5 años más baja que ypT0N0 e ypT1-2N0. Sin embargo, se asoció con una supervivencia global a 5 años más alta que ypT3-4N+. Consulte Video Resumen en http://links.lww.com/DCR/B863 . (Traducción-Dr. Rodrigo Azolas ).

Clinical impact of PET/MRI in oligometastatic colorectal cancer.

BACKGROUND: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies. METHODS: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020. RESULTS: Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49-65 years). PET/MR and SCI results were divergent in 19% (95% CI 9-37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412). CONCLUSIONS: These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC.

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.

Ten-year survival after pathologic complete response in rectal adenocarcinoma.

BACKGROUND: Multimodal treatment is the standard of care for rectal adenocarcinoma, with a subset of patients achieving a pathologic complete response (pCR). While pCR is associated with improved overall survival (OS), long-term data on patients with pCR is limited. METHODS: This is a single institution retrospective cohort study of all patients with clinical stages II/III rectal adenocarcinoma who underwent neoadjuvant chemoradiation therapy and operative resection (January 1, 2004-December 31, 2017). PCR was defined as no tumor identified in the rectum or associated lymph nodes by final pathology. RESULTS: Of 370 patients in this cohort, 50 had a pCR (13.5%). For pCR patients, 5-year disease-free survival (DFS) was 92%, 5-year OS was 95%. Twenty-six patients had surgery > 10 years before the study end date, of which 20 had an OS > 10 years (77%) with median OS 12.1 years and 95% alive to date (19/20). Of the 50 pCR patients, there was a single recurrence in the lung at 44.3 months after proctectomy which was surgically resected. CONCLUSION: For patients with rectal adenocarcinoma that undergo neoadjuvant chemoradiation and surgical resection, pCR is associated with excellent long-term DFS and OS. Many patients live greater than 10 years with no evidence of disease recurrence.

The growing trend for no primary surgery in colorectal cancer.

AIM: In colorectal cancer (CRC), surgery of the primary site is commonly curative. Our aim was to determine estimates of 'no surgery' for primary CRC while identifying common reasons for no surgery. METHOD: We identified all patients with a diagnosis of colorectal adenocarcinoma from the National Cancer Database between January 2004 and December 2016. Then, we identified patients who did not undergo surgery on the primary tumour and their demographic, tumour and institutional characteristics. Kaplan-Meier and logistic regression analyses were used to evaluate specific factors associated with overall survival as related to no surgery and recommendations against operative management. RESULTS: A total of 1,208,878 patients with CRC were identified, 14.5% of whom had no surgery of the primary cancer. No surgery was more common in rectal cancer than in colon cancer. Despite a steady incidence of CRC diagnoses, the likelihood of no surgery grew by 170% over the study period. Metastatic disease was noted in 53.7% of the no surgery cohort. Nine per cent of the no surgery patient cohort received a recommendation against surgery despite the absence of metastatic disease, 7.5% refused surgery and only 2% underwent palliative surgery. On multivariable analysis, patients who were not recommended to have surgery were more likely to be older, uninsured, comorbid and receive care at a single hospital. The no surgery patients had significantly lower overall survival. CONCLUSION: A substantial proportion of patients with CRC do not have surgery. Interventions aimed at expanding access and promoting second opinions at other cancer hospitals might reduce the growing rate of no surgery in CRC.

Academic Partnerships in Global Surgery: An Overview American Surgical Association Working Group on Academic Global Surgery.

: Most surgeons from high-income countries who work in global surgery will do so through partnerships between their institutions and institutions in low- and middle-income countries (LMICs). In this article, the American Surgical Association Working Group for Global Surgery lays out recommendations for criteria that contribute to equitable, sustainable, and effective partnerships. These include ethically engaging with the LMIC partner institution by putting its interests first and by proactively seeking to be aware of cultural issues. Formally structuring the partnership with a memorandum of understanding and clearly designating leaders at both institutions are important criteria for assuring long-term sustainability. Needs assessments can be done using existing methods, such as those established for development of national surgical, obstetric, and anesthesia plans. Such assessments help to identify opportunities for partnerships to be most effective in addressing the biggest surgical needs in the LMIC. Examples of successful high-income countries-LMIC partnerships are provided.

Global Surgery: Effective Involvement of US Academic Surgery: Report of the American Surgical Association Working Group on Global Surgery.

: There is an unacceptably high burden of death and disability from conditions that are treatable by surgery, worldwide and especially in low- and middle-income countries (LMICs). The major actions to improve this situation need to be taken by the surgical communities, institutions, and governments of the LMICs. The US surgical community, including the US academic surgical community, has, however, important roles to play in addressing this problem. The American Surgical Association convened a Working Group to address how US academic surgery can most effectively decrease the burden from surgically treatable conditions in LMICs. The Working Group believes that the task will be most successful (1) if the epidemiologic pattern in a given country is taken into account by focusing on those surgically treatable conditions with the highest burdens; (2) if emphasis is placed on those surgical services that are most cost-effective and most feasible to scale up; and (3) if efforts are harmonized with local priorities and with existing global initiatives, such as the World Health Assembly with its 2015 resolution on essential surgery. This consensus statement gives recommendations on how to achieve those goals through the tools of academic surgery: clinical care, training and capacity building, research, and advocacy. Through all of these, the ethical principles of maximally and transparently engaging with and deferring to the interests and needs of local surgeons and their patients are of paramount importance. Notable benefits accrue to US surgeons, trainees, and institutions that engage in global surgical activities.

Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis. METHODS: Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis. Expression of different cathepsins (CTS-B, -D, -F, -G, -K, -L, -O, and -S) was determined by quantitative RT-PCR and immunohistochemistry. The hand-held cathepsin-based fluorescent imaging system was used to detect peritoneal xenografts derived from human colon cancer cells (HT29, LoVo and HCT116) in nu/nu mice. RESULTS: While the expression levels of CTS-B, -D, -L, and -S could be higher in peritoneal tumors than normal peritoneum with a median (range) of 6.1 (2.9-25.8), 2.0 (1.0-15.8), 1.4 (0.8-7.0), and 2.1 (1.6-13.9) folds by quantitative RT-PCR, respectively, CTS-B was consistently the major contributor of the overall cathepsin expression in appendiceal and colonic peritoneal tumors, including adenocarcinomas and low-grade appendiceal mucinous neoplasms. Using peritoneal xenograft mouse models, small barely visible colonic peritoneal tumors (<2.5 mm in maximum diameter) could be detected by the hand-held cathepsin-based fluorescent imaging system. CONCLUSIONS: Because cathepsin expression is higher in peritoneal tumors than underlying peritoneum, the hand-held cathepsin-based fluorescent imaging system could be useful for intraoperative detection of microscopic peritoneal metastasis during CRS-HIPEC and clinical trial is warranted.

Action perception is intact in autism spectrum disorder.

Autistic traits span a wide spectrum of behavioral departures from typical function. Despite the heterogeneous nature of autism spectrum disorder (ASD), there have been attempts at formulating unified theoretical accounts of the associated impairments in social cognition. A class of prominent theories capitalizes on the link between social interaction and visual perception: effective interaction with others often relies on discrimination of subtle nonverbal cues. It has been proposed that individuals with ASD may rely on poorer perceptual representations of other people's actions as returned by dysfunctional visual circuitry and that this, in turn, may lead to less effective interpretation of those actions for social behavior. It remains unclear whether such perceptual deficits exist in ASD: the evidence currently available is limited to specific aspects of action recognition, and the reported deficits are often attributable to cognitive factors that may not be strictly visual (e.g., attention). We present results from an exhaustive set of measurements spanning the entire action processing hierarchy, from motion detection to action interpretation, designed to factor out effects that are not selectively relevant to this function. Our results demonstrate that the ASD perceptual system returns functionally intact signals for interpreting other people's actions adequately; these signals can be accessed effectively when autistic individuals are prompted and motivated to do so under controlled conditions. However, they may fail to exploit them adequately during real-life social interactions.

Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications for the Clinical Surgeon.

Colorectal cancer is a heterogeneous disease with a wide range of long-term outcomes and responses to treatment. Recent advances in the genetic and molecular characterization of tumors has yielded a set of prognostic and predictive biomarkers that aid the identification of patients at higher risk for disease recurrence and progression, and in some cases indicate the likelihood of response to a specific treatment. Increasingly, these biomarkers have become integral to the treatment algorithm for managing patients with colorectal cancer. Prognostic and predictive factors in colorectal cancer can broadly be categorized into treatment impact, clinicopathologic factors, and molecular markers. This review will focus primarily on molecular markers, which are foundational to the paradigmatic shift toward personalized cancer therapy.

Current status of imaging and emerging techniques to evaluate liver metastases from colorectal carcinoma.

Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. Liver is a common site of tumor spread and in approximately 30% of the cases; synchronous liver disease is present at the time of diagnosis. Early detection of liver metastases is crucial to appropriately select patients who may benefit from hepatic resection among those needing chemotherapy, to improve 5-year survival. Advances in imaging techniques have contributed greatly to the management of these patients. Multidetector computed tomography is the most useful test for initial staging and in posttreatment surveillance settings. Magnetic resonance imaging is considered superior to multidetector computed tomography and positron emission tomography for the detection and characterization of small lesions and for liver evaluation in the presence of background fatty liver changes. Positron emission tomography-computed tomography has a problem-solving role in the detection of distant metastasis and in posttreatment evaluation. The advanced imaging methods also serve a role in selecting appropriate patients for radiologically targeted therapies and in monitoring response to conventional and novel therapies.

The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development.

Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.