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).

High-risk medications in older patients with trauma: a cross-sectional study of risk mitigation

Background: The Beers Criteria for Potentially Inappropriate Medication Use inOlder Adults is a framework that can assess the nature of high-risk medication use. The objective of this study was to use the Beers Criteria to assess the prevalence and nature of polypharmacy, the magnitude of medication changes during the hospital stay and the impact of Beers Criteria medications on outcomes in older patients with trauma. Methods: We used the Alberta Trauma Registry to conduct a retrospective review of patients aged 65 years or older with major trauma (Injury Severity Score ≥ 12) who were admitted to a level 1 trauma centre between January 2013 and December 2014. We analyzed changes in medication prescriptions during the hospital stay using descriptive statistics and assessed the association between Beers Criteria medications and relevant outcomes using multivariable regression analysis. Results: There was no significant change in the number of Beers Criteria medications prescribed before and after admission. The adjusted odds ratio for 30-day mortality for each additional Beers Criteria medication prescribed was 2.02 (95% confidence interval [CI] 1.16­3.51) versus 1.24 (95% CI 1.04­1.59) for each additional medication of any type. The corresponding adjusted incidence rate ratios for length of stay were 1.15 (95% CI 1.03­1.30) versus 1.05 (95% CI 1.01­1.10). Conclusion: Beers Criteria medications were not discontinued during trauma admissions. Using the Beers Criteria as a process indicator for quality improvement in trauma care may provide interdisciplinary trauma teams an opportunity to audit patient medications and stop potentially harmful medications in a vulnerable population.

Contexte: Les critères de Beers sur les médicaments potentiellement inappropriés chez les adultes âgés constituent un cadre qui permet d'évaluer la nature d'une pharmacothérapie à risque élevé. L'objectif de cette étude était d'utiliser les critères de Beers pour évaluer la prévalence et la nature de la polypharmacologie, l'ampleur des changements de prescriptions en cours d'hospitalisation et l'impact des médicaments potentiellement inappropriés sur l'évolution de l'état de personnes âgées victimes de traumatismes. Méthodes: Nous avons utilisé le Registre albertain des traumatismes pour procéder à une revue rétrospective des patients de 65 ans et plus victimes d'un traumatisme grave (indice de gravité des blessures ≥ 12) admis dans un centre de traumatologie entre janvier 2013 et décembre 2014. Nous avons analysé les changements de médicaments prescrits durant le séjour hospitalier au moyen de statistiques descriptives et nous avons évalué le lien entre les médicaments potentiellement inappropriés et les variables pertinentes au moyen d'une analyse de régression multivariée. Résultats: On n'a noté aucun changement significatif entre les médicaments potentiellement inappropriés prescrits avant et après l'admission. Le rapport des cotes ajusté pour la mortalité à 30 jours pour chaque médicament potentiellement inapproprié prescrit a été de 2,02 (intervalle de confiance [IC] à 95 % 1,16­3,51) contre 1,24 (IC à 95 % 1,04­1,59) pour chaque médicament additionnel, de tout type. Les rapports des taux d'incidence ajustés correspondants pour la durée de l'hospitalisation ont été de 1,15 (IC à 95 % 1,03­1,30) contre 1,05 (IC à 95 % 1,01­1,10). Conclusion: Les médicaments potentiellement inappropriés (selon les critères de Beers) n'ont pas été cessés durant les admissions pour traumatisme. L'utilisation des critères de Beers comme indicateur de processus pour l'amélioration de la qualité des soins en traumatologie pourrait fournir aux équipes interdisciplinaires une occasion de vérifier les médicaments prescrits et de cesser ceux qui sont nuisibles à une population vulnérable.

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.

Platelet-derived growth factor receptor-α promotes lymphatic metastases in papillary thyroid cancer.

Lymph node metastases are common in papillary thyroid cancer (PTC) and can be resistant to surgical extirpation or radioiodine ablation. We examined the role of platelet-derived growth factor receptor (PDGFR) in mediating lymph node metastases in PTC. Clinical specimens of PTC (n = 137) were surveyed in a tissue array and by western blots to examine the relationship between expression of the α and ß subunits of PDGFR and lymph node metastases. PDGFR-α was found at high levels in primary tumours with known lymphatic metastases but not in those tumours lacking nodal involvement (p < 0.0001). However, PDGFR-ß expression was not linked to metastatic disease (p = 0.78) as it was found in virtually all PTC specimens. A matching analysis in fresh PTC specimens (n = 13) confirmed that PDGFR-α expression was strongly linked to metastatic spread (p = 0.0047). PDGFR-α and -ß were not found in normal thyroid tissue (p < 0.0001). PTC cell lines selectively expressing PDGFR-α or -ß were assessed for invasive potential and activation of downstream signal transduction pathways. PTC cell lines expressing PDGFR-α responded to PDGF-BB stimulation with increased invasive potential and this process can be blocked by the tyrosine kinase receptor inhibitor sunitinib (p < 0.009). Cell lines with only PDGFR-ß, or no PDGFR, did not show significant changes in invasive potential. Activation of PDGFR-α led to downstream up-regulation of both the MAPK/ERK and PI3K/Akt pathways and disruption of either pathway is sufficient to block PDGFR-mediated increases in invasive potential. Thus, PDGFR-α is associated with lymph node metastases in papillary thyroid carcinoma and PDGFR-α promotes increased invasive potential in PTC cell lines. PDGFR-α is a strong candidate for a diagnostic biomarker to identify patients at risk of nodal metastases. Our results also strengthen the rationale for selection of tyrosine kinase receptor inhibitors that target PDGFR in the treatment of progressive, metastatic PTC.

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.

The Impact of Bariatric Surgery on Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis.

Bariatric surgery has been proven to be a successful management strategy for morbid obesity, but limited studies exist on its effect on polycystic ovary syndrome (PCOS). A comprehensive search of electronic databases was completed. Meta-analysis was performed on PCOS, hirsutism, and menstrual irregularity outcomes following bariatric surgery. Thirteen primary studies involving a total of 2130 female patients were identified. The incidence of PCOS preoperatively was 45.6 %, which significantly decreased to 6.8 % (P < 0.001) and 7.1 % (P < 0.0002) at 12-month follow-up and study endpoint, respectively. The incidences of preoperative menstrual irregularity and hirsutism both significantly decreased at 12-month and at study end follow-up. Bariatric surgery effectively attenuates PCOS and its clinical symptomatology including hirsutism and menstrual irregularity in severely obese women.