Combined High-Throughput Proteomics and Random Forest Machine-Learning Approach Differentiates and Classifies Metabolic, Immune, Signaling and ECM Intra-Tumor Heterogeneity of Colorectal Cancer.

Colorectal cancer (CRC) is a frequent, worldwide tumor described for its huge complexity, including inter-/intra-heterogeneity and tumor microenvironment (TME) variability. Intra-tumor heterogeneity and its connections with metabolic reprogramming and epithelial-mesenchymal transition (EMT) were investigated with explorative shotgun proteomics complemented by a Random Forest (RF) machine-learning approach. Deep and superficial tumor regions and distant-site non-tumor samples from the same patients (n = 16) were analyzed. Among the 2009 proteins analyzed, 91 proteins, including 23 novel potential CRC hallmarks, showed significant quantitative changes. In addition, a 98.4% accurate classification of the three analyzed tissues was obtained by RF using a set of 21 proteins. Subunit E1 of 2-oxoglutarate dehydrogenase (OGDH-E1) was the best classifying factor for the superficial tumor region, while sorting nexin-18 and coatomer-beta protein (beta-COP), implicated in protein trafficking, classified the deep region. Down- and up-regulations of metabolic checkpoints involved different proteins in superficial and deep tumors. Analogously to immune checkpoints affecting the TME, cytoskeleton and extracellular matrix (ECM) dynamics were crucial for EMT. Galectin-3, basigin, S100A9, and fibronectin involved in TME-CRC-ECM crosstalk were found to be differently variated in both tumor regions. Different metabolic strategies appeared to be adopted by the two CRC regions to uncouple the Krebs cycle and cytosolic glucose metabolism, promote lipogenesis, promote amino acid synthesis, down-regulate bioenergetics in mitochondria, and up-regulate oxidative stress. Finally, correlations with the Dukes stage and budding supported the finding of novel potential CRC hallmarks and therapeutic targets.

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging.

Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes.

Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy.

BACKGROUND: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). RESULTS: One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. CONCLUSION: Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.

The MIS-COVID-AGICT Study: Trend of Minimally Invasive Surgery for Gastrointestinal Cancer Treatment During the First Waves of the COVID-19 Pandemic in Italy. Subgroup Analysis from the COVID-AGICT Study: COVID-19 and Advanced Gastrointestinal Cancer Surgical Treatment.

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 (P = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P = .01). Major postoperative complications were similar in both years (11% versus 11%, P = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).

Right Colectomy with Intracorporeal Anastomosis: A European Multicenter Propensity Score Matching Retrospective Study of Robotic Versus Laparoscopic Procedures.

BACKGROUND: This study aimed to compare the short- and long-term outcomes of robotic (RRC-IA) versus laparoscopic (LRC-IA) right colectomy with intracorporeal anastomosis using a propensity score matching (PSM) analysis based on a large European multicentric cohort of patients with nonmetastatic right colon cancer. METHODS: Elective curative-intent RRC-IA and LRC-IA performed between 2014 and 2020 were selected from the MERCY Study Group database. The two PSM-groups were compared for operative and postoperative outcomes, and survival rates. RESULTS: Initially, 596 patients were selected, including 194 RRC-IA and 402 LRC-IA patients. After PSM, 298 patients (149 per group) were compared. There was no statistically significant difference between RRC-IA and LRC-IA in terms of operative time, intraoperative complication rate, conversion to open surgery, postoperative morbidity (19.5% in RRC-IA vs. 26.8% in LRC-IA; p = 0.17), or 5-yr survival (80.5% for RRC-IA and 74.7% for LRC-IA; p = 0.94). R0 resection was obtained in all patients, and > 12 lymph nodes were harvested in 92.3% of patients, without group-related differences. RRC-IA procedures were associated with a significantly higher use of indocyanine green fluorescence than LRC-IA (36.9% vs. 14.1%; OR: 3.56; 95%CI 2.02-6.29; p < 0.0001). CONCLUSION: Within the limitation of the present analyses, there is no statistically significant difference between RRC-IA and LRC-IA performed for right colon cancer in terms of short- and long-term outcomes.

The paradox of Zeno in bariatric surgery weight loss: Superobese patients run faster than morbidly obese patients, but can't overtake them.

Introduction: Superobesity (SO) is defined as a BMI > 50 Kg/m2, and represents the extreme severity of the disease, resulting in a challenge for the surgeons. Methods: In this retrospective study we aimed to compare the outcomes of SO patients compared to morbidly obese (MO) patients. Results: We included in this study 154 MO patients, with a median preoperative BMI of 40.8 kg/m2, and 19 SO patients with median preoperative BMI of 54.9 kg/m2. The MO patients underwent sleeve gastrectomy (SG) in 62 (40.3%) cases, laparoscopic Roux-and-Y gastric bypass (LRYGBP) in 85 (55.2%) cases and One-Anastomosis Gastric Bypass (OAGB) in 7 (4.5%) cases. underwent OAGB. The patients in the SO group were submitted to SG in 11 (57.9%) cases, LRYGBP in 5 (26.3%) cases, and OAGB in 3 (15.8%). At 24-month follow-up, an excess weight loss (EWL) >50% was achieved in 129 (83.8%) patients in the MO group and in 15 (78.9%) in the SO group (p = 0.53). A BMI < 35 kg/m2 was achieved in 137 (89%) patients in the MO group and from 8 (42.2%) patients in the SO group (p < 0.001). The total weight loss was significantly directly related to the initial BMI. Superobesity was identified as independent risk factor for surgical failure when considering the outcome of BMI < 35 kg/m2. Discussion: Our study confirms that, although SO patients tend to gain a greater weight loss than MO patients, they less frequently achieve the desired BMI target. In this setting, it should be necessary to re-consider malabsorptive procedures as first choice.

Conversion to Open Surgery During Minimally Invasive Right Colectomy for Cancer: Results from a Large Multinational European Study.

Background: The risk of conversion to open surgery is inevitably present during any minimally invasive colorectal surgical procedure. Conversions have been associated with adverse postoperative and oncologic outcomes. No previous study has evaluated the specific causes and consequences of conversion during a minimally invasive right colectomy (MIS-RC). Materials and Methods: We analyzed the Minimally invasivE surgery for oncologic Right ColectomY (MERCY) study database including patients who underwent laparoscopic or robotic RC because of colon cancer between 2014 and 2020. Descriptive analyses were performed to determine the different reasons for conversion. Uni- and multivariate logistic regressions were run to identify potential variables associated with this outcome. Cox regression analyses were used to evaluate the impact of conversion on tumor recurrence. Results: Over a total of 1574 MIS-RC, 120 (7.6%) were converted to open surgery. The main reasons for conversion were procedural difficulties related to adherences from previous abdominal surgical procedures (39.2%), or owing to large tumor size or infiltration of adjacent structures (26.7%). Only 16.7% of the conversions were caused by intraoperative medical or surgical complications. Converted patients required longer operative times and developed more postoperative complications, both overall (39.2% versus 27.5%; P = .006) and severe ones (13.3% versus 8.3%; P = .061). Male gender (odds ratio [OR] = 1.89 [95% confidence interval: 1.31-2.71]), obesity (OR = 1.99 [1.4-2.83]), prior abdominal surgery (OR = 1.68 [1.19-2.37]), and pT4 cancers (OR = 4.04 [2.86-5.69]) were independently associated with conversion. Conversion to open surgery was not significantly associated with tumor recurrence (hazard ratios = 1.395 [0.724-2.687]). Conclusions: Although conversion to open surgery during MIS-RC for cancer is associated with worsened postoperative outcomes, it seems not to impact on the oncologic prognosis.

Limits of Clinical Restaging in Detecting Responders After Neoadjuvant Therapies for Rectal Cancer.

BACKGROUND: Accurate clinical restaging is required to select patients who respond to neoadjuvant chemoradiotherapy for locally advanced rectal cancer and who may benefit from an organ preservation strategy. OBJECTIVE: The purpose of this study was to review our experience with the clinical restaging of rectal cancer after neoadjuvant therapy to assess its accuracy in detecting major and pathological complete response to treatment. DESIGN: This was a retrospective cohort study. SETTING: This study was conducted at 2 high-volume Italian centers for Colorectal Surgery. PATIENTS: Data were included from all consecutive patients who underwent neoadjuvant therapy and surgery for locally advanced rectal cancer from January 2012 to July 2020. Criteria to define clinical response were no palpable mass, a superficial ulcer <2 cm (major response), or no mucosal abnormality (complete response) at endoscopy and no metastatic nodes at MRI. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, positive predictive values, and negative predictive values of clinical restaging in detecting pathological complete response (ypT0) or major pathological response (ypT0-1) after neoadjuvant therapy. RESULTS: A total of 333 patients were included; 81 (24.3%) had a complete response whereas 115 (34.5%) had a pathological major response. Accuracy for clinical complete response was 80.8% and for major clinical response was 72.9%. Sensitivity was low for both clinical complete response (37.5%) in detecting ypT0 and clinical major response (59.3%) in detecting ypT0-1. Positive predictive value was 68.2% for ypT0 and 60.4% for ypT0-1. LIMITATIONS: The main limitation of the study its retrospective nature. CONCLUSION: Accuracy of actual clinical criteria to define pathological complete response or pathological major response is poor. Failure to achieve good sensitivity and precision is a major limiting factor in the clinical setting. Current clinical assessments need to be revised to account for indications for rectal preservation after neoadjuvant chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/C63 . LMITES DE LA REESTADIFICACIN CLNICA EN LA DETECCIN DE RESPONDEDORES DESPUS DE TERAPIAS NEOADYUVANTES PARA EL CNCER DE RECTO: ANTECEDENTES:Se requiere una nueva reestadificación clínica precisa para seleccionar pacientes que respondan a la quimiorradioterapia neoadyuvante para el cáncer de recto localmente avanzado y que puedan beneficiarse de una estrategia de preservación de órganos.OBJETIVO:El propósito de este estudio fue revisar nuestra experiencia con la reestadificación clínica del cáncer de recto después de la terapia neoadyuvante para evaluar su precisión en la detección de una respuesta patológica importante y completa al tratamiento.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Este estudio se realizó en dos centros italianos de alto volumen para cirugía colorrectal.PACIENTES:Incluimos datos de todos los pacientes consecutivos que se sometieron a terapia neoadyuvante y cirugía por cáncer de recto localmente avanzado desde enero de 2012 hasta julio de 2020. Los criterios para definir la respuesta clínica fueron ausencia de masa palpable, úlcera superficial <2 cm (respuesta mayor) o ausencia de anomalías en la mucosa. (respuesta completa) en la endoscopia, y sin ganglios metastásicos en la resonancia magnética.PRINCIPALES MEDIDAS DE RESULTADO:Exploramos la sensibilidad, la especificidad, los valores predictivos positivos y negativos de la reestadificación clínica para detectar una respuesta patológica completa (ypT0) o mayor (ypT0-1) después de la terapia neoadyuvante.RESULTADOS:Se incluyeron 333 pacientes; 81 (24,3%) tuvieron una respuesta completa mientras que 115 (34,5%) tuvieron una respuesta patológica mayor. La precisión de la respuesta clínica completa y la respuesta clínica importante fue del 80,8 % y el 72,9 %, respectivamente. La sensibilidad fue baja tanto para la respuesta clínica completa (37,5 %) en la detección de ypT0 como para la respuesta clínica mayor (59,3 %) en la detección de ypT0-1. El valor predictivo positivo fue del 68,2 % para ypT0 y del 60,4 % para ypT0-1.LIMITACIONES:Nuestro estudio tiene como principal limitación su carácter retrospectivo.CONCLUSIÓNES:La precisión de los criterios clínicos reales para definir una respuesta patológica completa o mayor es pobre. El hecho de no lograr una buena sensibilidad y precisión es un factor limitante importante en el entorno clínico. La indicación para la preservación rectal después de la quimiorradioterapia neoadyuvante necesita una mejora de la evaluación clínica actual. Consulte Video Resumen en http://links.lww.com/DCR/C63 . (Traducción-Dr. Mauricio Santamaria ).

COVID-19 free pathways decrease postoperative complications in patients undergoing elective colorectal surgery.

Background: To reduce the exposition risk to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in surgical patients more prone to develop serious forms of Coronavirus disease 2019, a reorganization that previewed the creation "COVID-19-free" hospitals or units was pursued. The aim of this study was to quantify the effect of clear pathways to reduce the risk of SARS-Cov-2 transmission, on postoperative complications. Methods: Data of all consecutive patients undergoing surgical procedure for colorectal diseases, between November 2019 and July 2020 in two Italian referral centers, were retrospectively analyzed. Patients were divided into two groups: the ones underwent surgical procedures during the period before the pandemic from November 2019 to March 2020 (Group 1) (before-COVID), and those who underwent surgical procedure from April to July 2020 during the pandemic (Group 2) (during-COVID pandemic). Results: Overall, 264 patients were collected, 168 (63.4%) in Group 1 and 96 (36.4%) Group 2. Preoperative characteristics were similar between groups; during the pandemic there was a higher proportion of patients who underwent surgical procedures for malignancy compared with the period before the pandemic (92.7% vs 72%; p = 0.001). Patients in Group 2 had a lower rate of postoperative general complications (21.9% vs 34.5%; p = 0.03) and a lower rate of surgical complications (14.6% vs 25%; p = 0.05). No difference in term of medical complications, infections, and intraoperative complications were found. Minimally invasive approach (OR 0.46; 95% CI 0.04-0.83; p = 0.01) and isolation of patients (OR, 0.18; 95% CI, 0.04-0.83; p = 0.03) were independently associated with lower risk of postoperative complications. Conclusion: In this cohort study COVID-19-free pathways were significantly associated with low rate of postoperative morbidity in patients undergoing colorectal elective surgery.

Impact of operation duration on postoperative outcomes of minimally-invasive right colectomy.

AIM: Operation time (OT) is a key operational factor influencing surgical outcomes. The present study aimed to analyse whether OT impacts on short-term outcomes of minimally-invasive right colectomies by assessing the role of surgical approach (robotic [RRC] or laparoscopic right colectomy [LRC]), and type of ileocolic anastomosis (i.e., intracorporal [IA] or extra-corporal anastomosis [EA]). METHODS: This was a retrospective analysis of the Minimally-invasivE surgery for oncological Right ColectomY (MERCY) Study Group database, which included adult patients with nonmetastatic right colon adenocarcinoma operated on by oncological RRC or LRC between January 2014 and December 2020. Univariate and multivariate analyses were used. RESULTS: The study sample was composed of 1549 patients who were divided into three groups according to the OT quartiles: (1) First quartile, <135 min (n = 386); (2) Second and third quartiles, 135-199 min (n = 731); and (3) Fourth quartile ≥200 min (n = 432). The majority (62.7%) were LRC-EA, followed by LRC-IA (24.3%), RRC-IA (11.1%), and RRC-EA (1.9%). Independent predictors of an OT ≥ 200 min included male gender, age, obesity, diabetes, use of indocyanine green fluorescence, and IA confection. An OT ≥ 200 min was significantly associated with an increased risk of postoperative noninfective complications (AOR: 1.56; 95% CI: 1.15-2.13; p = 0.004), whereas the surgical approach and the type of anastomosis had no impact on postoperative morbidity. CONCLUSION: Prolonged OT is independently associated with increased odds of postoperative noninfective complications in oncological minimally-invasive right colectomy.

Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue.

DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology.

Association of Delayed Surgery With Oncologic Long-term Outcomes in Patients With Locally Advanced Rectal Cancer Not Responding to Preoperative Chemoradiation.

Importance: Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking. Objective: To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes. Design, Setting, and Participants: This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020. Exposures: Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored. Main Outcomes and Measures: The primary outcomes were overall and disease-free survival between the 2 groups. Results: Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P < .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P < .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P < .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P < .001). Conclusions and Relevance: In this cohort study, a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.

The COVID-19 incidence in Italian regions correlates with low temperature, mobility and PM10 pollution but lethality only with low temperature.

BACKGROUND: The aim was to verify whether the density of particulate matter (PM10), the climate, and the mobility of people can influence the pandemic in the 19 regions and in the two autonomous Italian provinces as incidence rate and lethality. DESIGN AND METHODS: The incidence rates per 100,000 inhabitants and the case fatality ratio (CFR) (dependent variables) in all Italian regions were calculated in January 2021 at John Hopkins University Coronavirus Center. The independent variables were: Minimum average temperatures in the same month (January) of 2020; average pollution of PM10 in the air in each region in the last year available reported on a 0-10 scale to 0 = total absence of PM10 to 10 maximum pollutions; number of places in hotels occupied per inhabitants in 2020. Linear regression and Multiple Regression Analysis were carried out. RESULTS: The spread of the COVID-19 in the Italian regions seems to be related to pollution of PM10, the number of beds occupied in hotels (as an index of mobility and temperature (indirect correlation). On the contrary, the CFR correlates inversely with temperature but not with pollution. Measuring the concomitant effect of two independent variables by means of Multiple Regression Analysis, temperature and pollution show a synergistic effect on COVID-19 incidence. CONCLUSIONS: The study seems to confirm the literature on the influence of temperature on the lethality of COVID-19 but adds the new results of an inverse relationship between the spread of the virus and low temperature in regions between the Mediterranean area (which includes southern Italy and Sicily and Sardinia islands) and the cold European temperate zone which includes the northern regions under the Alps. A new date also concerns the summation effect of the risk between cold weather and PM10 air pollution was found. Due to several methodic weaknesses, the study has an exploratory than conclusive relevance.

C reactive protein to albumin ratio (CAR) as predictor of anastomotic leakage in colorectal surgery.

BACKGROUND: Anastomotic leakage (AL) is one of the most severe complications in colorectal surgery. Currently, no predictive biomarkers of AL are available. The aim of this study was to investigate the role of C reactive protein (CRP) to albumin ratio (CAR) as a predictor of AL in patients undergoing elective surgery for colorectal cancer. MATERIALS AND METHODS: Data on 1183 consecutive patients surgically treated for histologically proven colorectal cancer in the surgical units involved in the study were collected. Data included sex, age, BMI, ASA score, Charlson comorbidity index, localization, histology and stage of the disease, as well as blood tests including albumin and CRP at the 4th postoperative day. Differences in CAR between patients who developed AL and those who did not were analyzed, and the ability of CAR to predict AL was investigated with ROC analysis. RESULTS: CAR was significantly higher in patients with AL in comparison to those without, at the 4th postoperative day. In ROC analysis CAR showed a good ability in detecting AL (AUC 0.825, 95%CI: 0,786-0,859), greater than those of CRP and albumin alone. CAR also showed a high ability in detecting postoperative deaths (AUC 0.750, 95% CI 0,956-0,987). These findings were confirmed in multivariate analysis including the most relevant risk factors for AL. CONCLUSION: Our study evidenced that CAR, an inexpensive and widely available laboratory biomarker, adequately predicts AL and death in patients who underwent elective surgery for colorectal cancer.

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study.

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD.

Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management.

INTRODUCTION: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common. AREA COVERED: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission. EXPERT OPINION: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.

Colonic J-Pouch or Straight Colorectal Reconstruction After Low Anterior Resection For Rectal Cancer: Impact on Quality of Life and Bowel Function: A Multicenter Prospective Randomized Study.

BACKGROUND: Patient-reported outcomes associated with different bowel reconstruction techniques following anterior resection for rectal cancer are still a matter of debate. OBJECTIVE: This study aimed to assess quality of life and bowel function in patients who underwent colonic J-pouch or straight colorectal anastomosis reconstruction after low anterior resection. DESIGN: Bowel function and quality of life were assessed within a multicenter randomized trial. Questionnaires were administered before the surgery (baseline) and at 6, 12, and 24 months after surgery. SETTINGS: Patients were enrolled by 19 centers. The enrollment started in October 2009 and was stopped in February 2016. The study was registered at www.clinicaltrials.gov (Identifier: NCT01110798). PATIENTS: Patients who underwent low anterior resection for primary mid-low rectal cancer and who were randomly assigned in a 1:1 ratio to receive either stapled colonic J-pouch or straight colorectal anastomosis were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and bowel function. RESULTS: Of the 379 patients who were evaluable, 312 (82.3%) completed the baseline, 259 (68.3%) the 6-month, 242 (63.9%) the 12-month, and 199 (52.5%) the 24-month assessment. Bowel functioning and quality of life did not significantly differ between arms for almost all domains. The total bowel function score, the urgency, and the stool fractionation scores significantly worsened after surgery and remained impaired over time in both arms (p < 0.0032), whereas constipation improved after surgery but recovered to baseline levels from 1 year onward (p < 0.0036). All patients showed a significant and continuous improvement in emotional functioning (p < 0.0013) and future perspective (p < 0.0001) from baseline to the end of the study. LIMITATIONS: Limitations of the study include missing data, which increased over time; the possibility that some treatments have slightly changed since the study was conducted; and investigators not blind to treatment allocation. CONCLUSION: The findings of this study do not support the routine use of colonic J-pouch reconstruction in patients with rectal cancer who undergo a low anterior resection. See Video Abstract at http://links.lww.com/DCR/B328. BOLSA J COLÓNICA O RECONSTRUCCIÓN COLORRECTAL RECTA DESPUÉS DE RESECCIÓN ANTERIOR BAJA PARA CÁNCER RECTAL: IMPACTO EN LA CALIDAD DE VIDA Y LA FUNCIÓN INTESTINAL: UN ESTUDIO ALEATORIZADO PROSPECTIVO MULTICÉNTRICO: Los resultados informados por el paciente asociados con diferentes técnicas de reconstrucción intestinal después de la resección anterior para el cáncer de recto aún son tema de debate.Evaluar la calidad de vida y la función intestinal en pacientes que se sometieron a una bolsa en J colónica o reconstrucción de anastomosis colorrectal recta después de una resección anterior baja.La función intestinal y la calidad de vida se evaluaron en un ensayo aleatorizado multicéntrico. Los cuestionarios se administraron antes de la cirugía (basal) y a los 6, 12 y 24 meses después de la cirugía.Los pacientes fueron incluidos en 19 centros. La inscripción comenzó en Octubre de 2009 y se detuvo en Febrero de 2016. El estudio se registró en www.clinicaltrials.gov (Identificador: NCT01110798).Pacientes que se sometieron a resección anterior baja por cáncer rectal primario medio-bajo y que fueron aleatorizados en una proporción de 1: 1 para recibir bolsa J colónica con grapas o anastomosis colorrectal recta.calidad de vida y función intestinal.De los 379 pacientes que fueron evaluables, 312 (82.3%) completaron la evaluación inicial, 259 (68.3%) a los 6 meses, 242 (63.9%) a los 12 meses y 199 (52.5%) a los 24 meses. . El funcionamiento intestinal y la calidad de vida no difirieron significativamente entre los dos grupos en casi todos los dominios. La puntuación total de la función intestinal, la urgencia y las puntuaciones de fraccionamiento de las heces empeoraron significativamente después de la cirugía y continuaron con el tiempo extra en ambos grupos (p <0.0032), mientras que el estreñimiento mejoró después de la cirugía pero se recuperó a los niveles basales a partir de 1 año en adelante (p <0.0036). Todos los pacientes mostraron una mejora significativa y continua en el funcionamiento emocional (p <0.0013) y la perspectiva futura (<0.0001) desde el inicio hasta el final del estudio.Datos faltantes, que aumentaron con el tiempo; la posibilidad de que algunos tratamientos hayan cambiado ligeramente desde que se realizó el estudio; investigadores no cegados a la asignación del tratamiento.Los hallazgos de este estudio no respaldan el uso rutinario de la reconstrucción de la bolsa J colónica en pacientes con cáncer rectal que se someten a una resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B328. (Traducción-Dr. Yesenia Rojas-Khalil).

Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression.

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.

Blood cell count indexes as predictors of anastomotic leakage in elective colorectal surgery: a multicenter study on 1432 patients.

BACKGROUND: The aim of this study was to evaluate a series of blood count inflammation indexes in predicting anastomotic leakage (AL) in elective colorectal surgery. METHODS: Demographic, pathologic, and clinical data of 1432 consecutive patients submitted to colorectal surgery in eight surgical centers were retrospectively evaluated. The neutrophil to lymphocyte (NLR), derived neutrophil to lymphocyte (dNLR), lymphocyte to monocyte (LMR), and platelet to lymphocyte (PLR) ratios were calculated before surgery and on the 1st and 4th postoperative days, in patients with or without AL. RESULTS: There were 106 patients with AL (65 males, mean age 67.4 years). The NLR, dNLR, and PLR were significantly higher in patients with AL in comparison to those without, on both the 1st and 4th postoperative days, but significance was greater on the 4th postoperative day. An NLR cutoff value of 7.1 on this day showed the best area under the curve (AUC 0.744; 95% CI 0.719-0.768) in predicting AL. CONCLUSIONS: Among the blood cell indexes of inflammation evaluated, NLR on the 4th postoperative day showed the best ability to predict AL. NLR is a low cost, easy to perform, and widely available index, which might be potentially used in clinical practice as a predictor of AL in patients undergoing elective colorectal surgery.