Dilemmas in the Clinical Management of pT1 Colorectal Cancer

Colonoscopy; Colorectal Neoplasms; Colorectal SurgeryColonoscopia; Neoplasias colorrectales; Cirugía colorrectalColonoscòpia; Neoplàsies colorrectals; Cirurgia colorrectalImplementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2-10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment

Transcranial Doppler monitoring during laparoscopic anterior lumbar interbody fusion

We studied the consequences on cerebral hemodynamics of lengthy laparoscopic procedures requiring pneumoperitoneum and head-down positioning. From October 1995 to April 1999, 17 ASA status I or II patients (16 women and 1 man; mean age, 38 yr) were treated with laparoscopic anterior lumbar fusion. Besides standard perioperative monitoring for laparoscopic surgery, the mean blood-flow velocity of both middle cerebral arteries and the pulsatility index were determined by transcranial Doppler ultrasound. Adequate acoustic windows were encountered in 11 of the 17 patients, and the remaining 6 were excluded from the analysis. PaCO(2) and end-tidal CO(2) were maintained within normal limits (<40 mm Hg); ventilation was optimized in all cases. There was a significant increase (P < 0.05) in heart rate and central venous pressure with the change from supine to head-down position in all patients. Transcranial Doppler results for mean middle cerebral artery blood-flow velocity and pulsatility index showed no significant variations at any of the four time points studied during the procedure. There were no technique-related complications, except for moderate postoperative headache in eight patients that resolved with rest and oxygen therapy. We conclude that lengthy laparoscopic procedures in the head-down position performed in otherwise healthy patients do not significantly affect intracranial circulation

Cardiac tamponade associated with a peripheral vein central venous catheter

We present a case of cardiac tamponade associated with placement of a central venous catheter (CVC) via a peripheral vein in a 14-year-old girl with idiopathic scoliosis undergoing corrective surgery. A number of complications have been described in association with CVC misplacement. Sporadic cases of cardiac tamponade from this have been reported, but the actual incidence is unknown. Death from cardiac tamponade attributed to CVCs ranges from 65 to 100%. In our patient, cannulation of the pericardiophrenic vein was probably the cause of cardiac tamponade, based on radiological evidence that the initial location of the catheter was near the right atrium and possibly at the outlet of the pericardiophrenic vein. The catheter could have advanced into the vein and then to the pericardial sac with postural changes. The acute clinical course of cardiac tamponade in our patient had potentially lethal hemodynamic repercussions. The main diagnostic test for this condition is echocardiography and the only effective treatment is drainage of the pericardial effusion. Echocardiography should be performed before pericardiocentesis except in life-threatening situations or high clinical suspicion. Although they are rare, it is important to be aware of the potential for CVC complications

Antifibrinolytic therapy in complex spine surgery: a case-control study comparing aprotinin and tranexamic acid

Abstract: A case-control study was performed to determine the impact of aprotinin or tranexamic acid use on reducing intraoperative blood loss and transfusion needs in complex spine surgery. Sixty-nine patients undergoing complex spine surgery received aprotinin or tranexamic acid. The aprotinin group contained 30 patients (8 men and 22 women) and the tranexamic acid group 39 patients (11 men and 28 women). The following variables were recorded: duration of surgery, number of levels fused, intraoperative and total blood loss, and number of blood units transfused (autologous and allogenic). In addition, various parameters related to blood loss in this type of surgery were calculated. The groups differed with regard to duration of surgery (aprotinin 662 min vs tranexamic acid 448 min, P<.001) and number of levels fused (aprotinin 11.2 vs tranexamic acid 7.6, P=.004). There were no significant differences in intraoperative blood loss (aprotinin 2118 mL vs tranexamic acid 1608 mL, P=.066) or total blood loss (aprotinin 3312 mL vs tranexamic acid 2627 mL, P=.056). Statistical differences were found for the number of autologous blood units transfused (aprotinin 2.2 vs tranexamic acid 1.3 P=.047) and total units transfused (aprotinin 4.1 vs tranexamic acid 2.6, P=.008). Blood loss per hour of surgery, transfused units per level fused, and transfused units per hour of surgery were similar in the 2 groups. Significant differences were found for intraoperative blood loss per fusion level (aprotinin 228 mL vs tranexamic acid 428, P=.025) and total blood loss per fusion level (aprotinin 360 mL vs tranexamic acid 638 mL, P=.01). Analysis of the applied geometric mean showed that aprotinin reduced total blood loss by 16.4% and total number of blood units transfused by 12.4% as compared to tranexamic acid, although statistical significance was not reached. The type of antifibrinolytic used did not have a significant impact on the main outcome variables of the study

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis.

INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.This work was funded by grants from the Instituto de Salud Carlos III (PI12/01481; PI19/01050). Project PI19/ 01050 is funded by Instituto de Salud Carlos III (ISCIII) and co funded by the European Union. CIBEREHD is funded by the Insti tuto de Salud Carlos III and Beca Marató de TV3 (201932-30). Parts of this work were also supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC) and by the Hospital Clínics Premi Fi de Residència (G.J). None of the funding parties has been involved in collection, analysis, and interpretation of the data

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias. A Randomized Trial.

Background: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. Objective: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Design: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136) Setting: Spanish colorectal cancer screening program. Participants: 3213 persons with a positive fecal immunochemical test. Intervention: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Measurements: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. Results: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. Limitations: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Conclusion: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Primary Funding Source: Medtronic

Rectal Aberrant Crypt Foci in Humans Are Not Surrogate Markers for Colorectal Cancer Risk

NTRODUCTION: Over the past 20 years, aberrant crypt foci (ACF) have emerged as potential precursors and biomarkers for colorectal cancer (CRC). However, data regarding their molecular pathogenesis, as well as their endoscopic and histological identification, remain inconsistent. METHODS: A wide cohort of ACF from 100 control subjects and 100 case patients, including patients with adenoma and CRC, were characterized for endoscopic, morphologic, and molecular features. RESULTS: We observed that among all the endoscopic features evaluated, only the number of large ACF correlated with CRC risk (P = 0.003), whereas the histological classification, as assessed by 2 different pathologists, was inconsistent and did not differ between control and case patients. Moreover, only a few APC and BRAF mutations and no microsatellite instability were detected in our samples. KRAS mutations were detected in 16.3% of ACF samples, which also exhibited increased MGMT hypermethylation. However, none of those events were found to be predictive of CRC risk. DISCUSSION: Although ACF might be preneoplastic lesions of the colon, they are not suitable biomarkers for assessing CRC progression

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis

Introduction: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. Methods: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). Results: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). Discussion: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression

Variation in Colonoscopy Performance Measures According to Procedure Indication

BACKGROUND & AIMS: Most fulfillment and benchmarking information for colonoscopy quality indicators has been obtained from studies of primary screening colonoscopies. We analyzed differences in the fulfillment of colonoscopy quality indicators based on the indication for endoscopy. METHODS: We performed an observational, multicenter, cross-sectional study of 14,867 patients who underwent endoscopy procedures for gastrointestinal symptoms (40.3%), a positive result from a fecal immunochemical test (36.0%), postpolypectomy surveillance (15.3%), or primary screening (8.4%), from February 2016 through December 2017 at 14 centers in Spain. We evaluated rates of adequate colon cleansing, cecal intubation, adenoma detection, and colorectal cancer detection, among others. We used findings from primary screening colonoscopies as the reference standard. RESULTS: Fewer than 90% of patients had adequate bowel preparation; 83.1% of patients with gastrointestinal symptoms had adequate bowel preparation (odds ratio [OR] compared with patients with primary screening colonoscopies, 0.62; 95% CI, 0.49–0.78) and 85.3% of patients receiving postpolypectomy surveillance had adequate bowel preparation (OR, 0.71; 95% CI, 0.55–0.91). The cecal intubation rate was also lower in patients with gastrointestinal symptoms (93.1%) (OR, 0.34; 95% CI, 0.22–0.52). The adenoma detection rate was higher in patients with a positive result from a fecal immunochemical test (46.4%) (OR, 2.01; 95% CI, 1.71–2.35) and in patients undergoing postpolypectomy surveillance (48.2%) (OR, 1.41; 95% CI, 1.20–1.67). The highest proportion of patients with colorectal cancer was in the gastrointestinal symptom group (5.1%) (OR, 5.24; 95% CI, 2.30–11.93) and the lowest was in patients undergoing surveillance (0.8%) (OR, 0.83; 95% CI, 0.32–2.14). CONCLUSIONS: Fulfillment of colonoscopy performance measures varies substantially by indication. Policies addressing performance measures beyond colonoscopy screening procedures should be developed. Benchmarking recommendations could be adjusted according to colonoscopy indication

Factors associated with lesion detection in colonoscopy among different indications

Background and objective: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. Methods: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. Results: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). Conclusions: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications