Classic and Novel Histopathologic Risk Factors for Lymph Node Metastasis in T1 Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment of endoscopically resected T1 colorectal cancers is based on the risk of lymph node metastasis. Risk is based on histopathologic features, although there is lack of consensus as to what constitutes high-risk features. OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis of histopathologic risk factors for lymph node metastasis. DATA SOURCES: A search of MEDLINE, Embase, Scopus, and Cochrane controlled register of trials for risk factors for lymph node metastasis was performed from inception until August 2018. STUDY SELECTION: Included patients must have had an oncologic resection to confirm lymph node status and reported at least 1 histopathologic risk factor. INTERVENTION: Rates of lymph node positivity were compared between patients with and without risk factors. MAIN OUTCOME MEASURES: We report the results of the meta-analysis as ORs. RESULTS: Of 8592 citations, 60 met inclusion criteria. Pooled analyses found that lymphovascular invasion, vascular invasion, neural invasion, and poorly differentiated histology were significantly associated with lymph node metastasis, as were depths of 1000 µm (OR = 2.76), 1500 µm (OR = 4.37), 2000 µm (OR = 2.37), submucosal level 3 depth (OR = 3.08), and submucosal level 2/3 (OR = 3.08) depth. Depth of 3000 µm, Haggitt level 4, and widths of 3000 µm and 4000 µm were not significantly associated with lymph node metastasis. Tumor budding (OR = 4.99) and poorly differentiated clusters (OR = 14.61) were also significantly associated with lymph node metastasis. LIMITATIONS: Included studies reported risk factors independently, making it impossible to examine the additive metastasis risk in patients with numerous risk factors. CONCLUSIONS: We identified 1500 µm as the depth most significantly associated with lymph node metastasis. Novel factors tumor budding and poorly differentiated clusters were also significantly associated with lymph node metastasis. These findings should help inform guidelines regarding risk stratification of T1 tumors and prompt additional investigation into the exact contribution of poorly differentiated clusters to lymph node metastasis.

Malignant Colorectal Polyp Pathology: Are We Getting Sufficient Information to Make Decisions?

BACKGROUND: The College of American Pathologists has published guidelines for malignant colorectal polyp pathology reports that list histopathological features that are "core elements" and "optional." Lack of element reporting may result in inaccurate tumor risk stratification.This study aimed to perform a population-based assessment of pathology reporting for T1 colorectal cancers and determine the completeness of reporting for core and optional histopathological elements.This is a retrospective cohort study.This study reviews the pathology reports of endoscopically resected malignant colorectal polyps in Alberta, Canada between 2014 and 2016.Individuals aged 18 years or older with T1 colorectal polyps were selected.Histopathological elements were dichotomized into core and optional. Malignant polyps were classified as high risk or low risk for lymph node metastases and local intraluminal recurrence. Addendum reports were compared with first reports.After applying exclusion criteria, 431 polyps were analyzed. The mean age of patients was 65.5 years; 59.4% were male. Histological grade, deep margin, and lymphovascular invasion were reported in 82.4%, 86.8% and 75.6%; all 3 were reported in only 66.4%. Tumor budding (not in the 2016 guidelines) was reported in 14.4%. One hundred ninety polyps (44.1%) were high risk. Thirty-seven polyps (8.3%) had an addendum report. Following the addendum, 1 polyp was downgraded to low risk, and 9 polyps were upgraded to high risk.The main limitation of the study is its retrospective nature. The decision making surrounding treatment for T1 cancers is complex, and factors other than histopathological tumor features may have been part of treatment decisions.There is a high rate of incomplete reporting of core and optional elements for malignant colorectal polyp pathology reports in Alberta. Several variables used by colorectal surgeons for decision making, such as tumor budding and depth of submucosal invasion, are not considered core elements and are infrequently reported. A pathology review by a second pathologist often results in a change in risk stratification. See Video Abstract at http://links.lww.com/DCR/B98. PATOLOGÍA DEL PÓLIPO COLORRECTAL MALIGNO: ¿ESTAMOS OBTENIENDO INFORMACIÓN SUFICIENTE PARA TOMAR DECISIONES?: El Colegio de Patólogos Americanos publico pautas para informes de patología de pólipos colorrectales malignos que enumeran características histopatológicas como "elementos centrales" y "opcionales". La falta de información elemental puede resultar en una estratificación de riesgo tumoral imprecisa.Valoración basada en una población de los informes de patología para los cánceres colorrectales T1 y determinar la precisión de los informes en cuanto los elementos histopatológicos centrales y opcionales.Estudio de cohorte retrospectivo.Este estudio revisa los informes de patología de pólipos colorrectales malignos resecados endoscópicamente en Alberta, Canadá, entre 2014 y 2016.personas mayores de 18 años con pólipos colorrectales T1.Los elementos histopatológicos se dicotomizaron entre elementales y opcionales. Pólipos malignos se clasificaron como de alto riesgo o bajo riesgo de metástasis en los ganglios linfáticos y recurrencia intraluminal local. Los informes enmendados se compararon con los informes originales.Después de aplicar los criterios de exclusión, se analizaron 431 pólipos. La edad media fue 65.5 años, con 59.4% masculinos. El grado histológico, el margen profundo y la invasión linfovascular se informaron confirmaron en 82.4%, 86.8% y 75.6% respectivamente; las tres características se demostraron en solo 66.4%. Un patrón tumoral en ciernes se reporto en 14.4-una característica que no se usaba en las guías de 2016. Ciento noventa pólipos (44.1%) eran de alto riesgo. Treinta y siete pólipos (8.3%) requirieron de un informe enmendado. Aplicación de los nuevos criterios resulto en que 1 pólipo se redujo a bajo riesgo y 9 pólipos se actualizaron como a alto riesgo.La principal limitación del estudio es el diseño retrospectivo. La toma de decisiones en torno al tratamiento de los cánceres T1 es compleja y otros factores además de las características histopatológicas del tumor pueden haber sido parte de las decisiones terapéuticas.Hay una alta tasa de informes incompletos de elementos centrales y opcionales para informes de patología de pólipos colorrectales malignos en Alberta. Algunas variables utilizadas por los cirujanos colorrectales para la toma de decisiones, como el patrón tumoral en ciernes y la profundidad de la invasión submucosa, no se consideran elementos centrales y se informan con poca frecuencia. Una revisión de patología realizada por un segundo patólogo a menudo resulta en un cambio en la estratificación del riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B98. (Traducción-Dr. Adrian E. Ortega).

Urine metabolomics as a predictor of patient tolerance and response to adjuvant chemotherapy in colorectal cancer.

Colorectal cancer is the third leading cause of cancer-associated mortality in the western world. The ability to predict a patient's response to chemotherapy may be of great value for clinicians and patients when planning cancer treatment. The aim of the current study was to develop a urine metabolomics-based biomarker panel to predict adverse events and response to chemotherapy in patients with colorectal cancer. A retrospective chart review of patients diagnosed with stage III or IV colorectal cancer between 2008 and 2012 was performed. The exclusion criteria included chemotherapy for palliation and patients living outside of Alberta. Data was collected concerning the chemotherapy regimen, adverse events associated with chemotherapy, disease progression and recurrence and 5-year survival. Adverse events were subdivided as follows: Delays in treatment, dose reductions, hospitalizations and chemotherapy regime changes. Patients provided urine samples for analysis prior to any intervention. Nuclear magnetic resonance (NMR) spectra of urine samples were acquired. The 1H NMR spectrum of each urine sample was analyzed using Chenomx NMRSuite v7.0. Using machine learning, predictors were generated and evaluated using 10-fold cross-validation. Urine spectra were obtained for 62 patients. The best predictors resulted in area under the receiver operating characteristic curve values of: 0.542 for chemotherapy dose reduction, 0.612 for 5-year survival, 0.650 for cancer recurrence and 0.750 for treatment delay. Therefore, predictors were developed for response to and adverse events from chemotherapy for patients with colorectal cancer patients. The predictor for treatment delay has the most promise, and further studies will aid its refinement and improvement of its accuracy.

Endoscopic versus open component separation: systematic review and meta-analysis.

BACKGROUND: The component separation technique (CST) was developed to improve the integrity of abdominal wall reconstruction for large, complex hernias. Open CST necessitates large subcutaneous skin flaps and, therefore, is associated with significant ischemic wound complications. The minimally invasive or endoscopic component separation technique (MICST) has been suggested in preliminary studies to reduce wound complication rates post-operatively. In this study, we systematically reviewed the literature comparing open versus endoscopic component separation and performed a meta-analysis of controlled studies. METHODS: A comprehensive search of electronic databases was completed. All English, randomized controlled trials, non-randomized comparison study, and case series were included. All comparison studies included in the meta-analysis were assessed independently by two reviewers for methodological quality using the Cochrane Risk of Bias tools. RESULTS: 63 primary studies (3,055 patients) were identified; 7 controlled studies and 56 case series. The total wound complication rate was lower for MICST (20.6 %) compared to Open CST (34.6 %). MICST compared to open CST was shown to have lower rates of superficial infections (3.5 vs 8.9 %), skin dehiscence (5.3 vs 8.2 %), necrosis (2.1 vs 6.8 %), hematoma/seroma formation (4.6 vs 7.4 %), fistula tract formation (0.4 vs 1.0 %), fascial dehiscence (0.0 vs 0.4 %), and mortality (0.4 vs 0.6 %.) The open component CST did have lower rates of intra-abdominal abscess formation (3.8 vs 4.6 %) and recurrence rates (11.1 vs 15.1 %). The meta-analysis included 7 non-randomized controlled studies (387 patients). A similar suggestive overall trend was found favoring MICST, although most types of wound complications did not show to significance. MICST was associated with a significantly decreased rate of fascial dehiscence and was shown to be significantly shorter procedure. CONCLUSION: This systematic review and meta-analysis comparing MICST to open CST suggests MICST is associated with decreased overall post-operative wound complication rates. Further prospective studies are needed to verify these findings.