Trends and outcome of neoadjuvant treatment for rectal cancer: a retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006e2009; II) 2010e2013; III)2014e2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14,391 patients,8871 (61.6%) received neoadjuvant treatment. Long-course chemo/ radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemo- therapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%,p ¼ 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p ¼ 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p ¼ 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59e0.87, Cochrane-Mantel-Haenszel P ¼ 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, pre- operative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN þ benefited the most. © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgica

Treatment for acute uncomplicated diverticulitis without antibiotherapy: systematic review and meta-analysis of randomized clinical trials

Background: Use of antibiotics in selected cases of acute uncomplicated diverticulitis (AUD) has recently been questioned. Objective: The aim of this study is to examine the safety and efficacy of treatment regimens without antibiotics compared with that of traditional treatments with antibiotics in selected patients with AUD. Data sources: PubMed, Medline, Embase, Web of Science, and the Cochrane Library Methods: A systematic review was performed according to PRISMA and AMSTAR guidelines by searching through Medline, Embase, Web of Science, and the Cochrane Library for randomized clinical trials (RCTs) published before December 2022. The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. Study selection: RCTs on treating AUD without antibiotics published in English before December 2022 were included. Intervention: Treatments without antibiotics were compared with treatments with antibiotics. Main outcome measures: The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. Results: The search yielded 1163 studies. Four RCTs with 1809 patients were included in the review. Among these patients, 50.1% were treated conservatively without antibiotics. The meta-analysis showed no significant differences between nonantibiotic and antibiotic treatment groups with respect to rates of readmission [odds ratio (OR) = 1.39; 95% CI: 0.93-2.06; P = 0.11; I-2 = 0%], change in strategy (OR = 1.03; 95% CI: 0.52-2,02; P = 0.94; I-2 = 44%), emergency surgery (OR = 0.43; 95% CI: 0.12-1.53; P = 0.19; I-2 = 0%), worsening (OR = 0.91; 95% CI: 0.48-1.73; P = 0.78; I-2 = 0%), and persistent diverticulitis (OR = 1.54; 95% CI: 0.63-3.26; P = 0.26; I-2 = 0%). Limitations: Heterogeneity and a limited number of RCTs. Conclusions: Treatment for AUD without antibiotic therapy is safe and effective in selected patients. Further RTCs should confirm the present findings

Quality check: concordance between two monitoring systems for postoperative organ/space-surgical site infections in rectal cancer surgery. Linkage of data from the Catalan Cancer Plan and the VINCat infection surveillance programme

Background The Catalan Cancer Plan (CCP) undertakes periodic audits of cancer treatment outcomes, including organ/space surgical site infections (O/S-SSI) rates, while the Catalan Healthcare-associated Infections Surveillance Programme (VINCat) carries out standardized prospective surveillance of surgical site infections (SSI) in colorectal surgery. This cohort study aimed to assess the concordance between these two monitoring systems for O/S-SSI following primary rectal cancer surgery. Methods The study compared O/S-SSI incidence data from CCP clinical audits versus the VINCat Programme in patients undergoing surgery for primary rectal cancer, in 2011-12 and 2015-16, in publicly funded centres in Spain. The main outcome variable was the incidence of O/S-SSI in the first 30 days after surgery. Concordance between the two registers was analysed using Cohen's kappa. Discordant cases were reviewed by an expert, and the main reasons for discrepancies evaluated. Results Pooling data from both databases generated a sample of 2867 patients. Of these, O/S-SSI was detected in 414 patients-235 were common to both registry systems, with satisfactory concordance (kappa = 0.69, 95% confidence interval 0.65-0.73). The rate of discordance from the CCP (positive cases in VINCat and negative in CCP) was 2.7%, and from VINCat (positive in CCP and negative in VINCat) was 3.6%. External review confirmed O/S-SSI in 66.2% of the cases in the CCP registry and 52.9% in VINCat. Conclusions This type of synergy shows the potential of pooling data from two different information sources with a satisfactory level of agreement as a means to improving O/S-SSI detection. ClinicalTrials.gov Identifier: NCT06104579. Registered 30 November 2023

Identification of a Twelve-microRNA Signature with Prognostic Value in Stage II Microsatellite Stable Colon Cancer

Simple Summary Colorectal cancer (CRC) is one of the most prevalent cancers, and approximately a quarter of patients diagnosed at stage II exhibit a significant risk of recurrence. In this study, we successfully identified a microRNA (miRNA) signature allowing the recognition of patients at high recurrence risk. The validity of these findings has been confirmed through an entirely separate group of patients diagnosed with stage II microsatellite stability (MSS) colon adenocarcinoma (COAD). Most of the miRNAs present in the signature have demonstrated prognostic relevance in various other cancer types. Upon examining their gene targets, we discovered that some of these miRNAs are intricately involved in pivotal pathways of cancer progression. We aimed to identify and validate a set of miRNAs that could serve as a prognostic signature useful to determine the recurrence risk for patients with COAD. Small RNAs from tumors of 100 stage II, untreated, MSS colon cancer patients were sequenced for the discovery step. For this purpose, we built an miRNA score using an elastic net Cox regression model based on the disease-free survival status. Patients were grouped into high or low recurrence risk categories based on the median value of the score. We then validated these results in an independent sample of stage II microsatellite stable tumor tissues, with a hazard ratio of 3.24, (CI95% = 1.05-10.0) and a 10-year area under the receiver operating characteristic curve of 0.67. Functional analysis of the miRNAs present in the signature identified key pathways in cancer progression. In conclusion, the proposed signature of 12 miRNAs can contribute to improving the prediction of disease relapse in patients with stage II MSS colorectal cancer, and might be useful in deciding which patients may benefit from adjuvant chemotherapy

Pelvic exenterations for primary rectal cancer : Analysis from a 10-year national prospective database

To identify short-term and oncologic outcomes of pelvic exenterations (PE) for locally advanced primary rectal cancer (LAPRC) in patients included in a national prospective database. Few studies report on PE in patients with LAPRC. For this study, we included PE for LAPRC performed between 2006 and 2017, as available, from the Rectal Cancer Registry of the Spanish Association of Surgeons [Asociación Española de Cirujanos (AEC)]. Primary endpoints included procedure-associated complications, 5-year local recurrence (LR), disease-free survival (DFS) and overall survival (OS). A propensity-matched comparison with patients who underwent non-exenterative surgery for low rectal cancers was performed as a secondary endpoint. Eight-two patients were included. The mean age was 61.8 ± 11.5 years. More than half of the patients experienced at least one complication. Surgical site infections were the most common complication (abdominal wound 18.3%, perineal closure 19.4%). Thirty-three multivisceral resections were performed, including two hepatectomies and four metastasectomies. The long-term outcomes of the 64 patients operated on before 2013 were assessed. The five-year LR was 15.6%, the distant recurrence rate was 21.9%, and OS was 67.2%, with a mean survival of 43.8 mo. R+ve resection increased LR [hazard ratio (HR) = 5.58, 95%CI: 1.04-30.07, P = 0.04]. The quality of the mesorectum was associated with DFS. Perioperative complications were independent predictors of shorter survival (HR = 3.53, 95%CI: 1.12-10.94, P = 0.03). In the propensity-matched analysis, PE was associated with better quality of the specimen and tended to achieve lower LR with similar OS. PE is an extensive procedure, justified if disease-free margins can be obtained. Further studies should define indications, accreditation policy, and quality of life in LAPRC

From "Breakthrough" to "Episodic" Cancer Pain? A European Association for Palliative Care Research Network Expert Delphi Survey Towards a Common Terminology and Classification of Transient Cancer Pain Exacerbations

Context: Cancer pain can appear with spikes of higher intensity. Breakthrough cancer pain (BTCP) is the most common term for the transient exacerbations of pain, but the ability of the nomenclature to capture relevant pain variations and give treatment guidance is questionable. Objectives: To reach consensus on definitions, terminology, and sub classification of transient cancer pain exacerbations. Methods: The most frequent authors on BTCP literature were identified using the same search strategy as in a systematic review and invited to participate in a two-round Delphi survey. Topics with a low degree of consensus on BTCP classification were refined into twenty statements. The participants rated their degree of agreement with the statements on a numeric rating scale (NRS 0-10). Consensus was defined as a median NRS score of ≥ 7 and an interquartile range of ≤ 3. Results: Fifty-two authors had published three or more papers on BTCP over the past ten years. Twenty-seven responded in the first round and 24 in the second round. Consensus was reached for 13 of 20 statements. Transient cancer pain exacerbations can occur without background pain, when background pain is uncontrolled, and regardless of opioid treatment. There exist cancer pain exacerbations other than BTCP, and the phenomenon could be named “episodic pain”. Patient reported treatment satisfaction is important with respect to assessment. Sub classification according to pain pathophysiology can provide treatment guidance. Conclusion: Significant transient cancer pain exacerbations include more than just BTCP. Patient input and pain classification are important factors for tailoring treatment

The Comprehensive Complication Index (CCI®) is a Novel Cost Assessment Tool for Surgical Procedures

OBJECTIVE The aim of this study was to identify a readily available, reproducible, and internationally applicable cost assessment tool for surgical procedures. SUMMARY OF BACKGROUND DATA Strong economic pressure exists worldwide to slow down the rising of health care costs. Postoperative morbidity significantly impacts on cost in surgical patients. The comprehensive complication index (CCI), reflecting overall postoperative morbidity, may therefore serve as a new marker for cost. METHODS Postoperative complications and total costs from a single tertiary center were prospectively collected (2014 to 2016) up to 3 months after surgery for a variety of abdominal procedures (n = 1388). CCI was used to quantify overall postoperative morbidity. Pearson correlation coefficient (rpears) was calculated for cost and CCI. For cost prediction, a linear regression model based on CCI, age, and type of surgery was developed and validated in an international cohort of patients. RESULTS We found a high correlation between CCI and overall cost (rpears = 0.75) with the strongest correlation for more complex procedures. The prediction model performed very well (R = 0.82); each 10-point increase in CCI corresponded to a 14% increase to the baseline cost. Additional 12% of baseline cost must be added for patients older than 50 years, or 24% for those over 70 years. The validation cohorts showed a good match of predicted and observed cost. CONCLUSION Overall postoperative morbidity correlates highly with cost. The CCI together with the type of surgery and patient age is a novel and reliable predictor of expenses in surgical patients. This finding may enable objective cost comparisons among centers, procedures, or over time obviating the need to look at complex country-specific cost calculations (www.assessurgery.com)

Diagnostic Accuracy of Abdominal CT for Locally Advanced Colon Tumors: Can We Really Entrust Certain Decisions to the Reliability of CT?

Many different options of neoadjuvant treatments for advanced colon cancer are emerging. An accurate preoperative staging is crucial to select the most appropriate treatment option. A retrospective study was carried out on a national series of operated patients with T4 tumors. Considering the anatomo-pathological analysis of the surgical specimen as the gold standard, a diagnostic accuracy study was carried out on the variables T and N staging and the presence of peritoneal metastases (M1c). The parameters calculated were sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, as well as the overall accuracy. A total of 50 centers participated in the study in which 1950 patients were analyzed. The sensitivity of CT for correct staging of T4 colon tumors was 57%. Regarding N staging, the overall accuracy was 63%, with a sensitivity of 64% and a specificity of 62%; however, the positive and negative likelihood ratios were 1.7 and 0.58, respectively. For the diagnosis of peritoneal metastases, the accuracy was 94.8%, with a sensitivity of 40% and specificity of 98%; in the case of peritoneal metastases, the positive and negative likelihood ratios were 24.4 and 0.61, respectively. The diagnostic accuracy of CT in the setting of advanced colon cancer still has some shortcomings for accurate diagnosis of stage T4, correct classification of lymph nodes, and preoperative detection of peritoneal metastases

Surviving rectal cancer at the cost of a colostomy: global survey of long-term health-related quality of life in 10 countries

Background Colorectal cancer management may require an ostomy formation; however, a stoma may negatively impact health-related quality of life (HRQoL). This study aimed to compare generic and stoma-specific HRQoL in patients with a permanent colostomy after rectal cancer across different countries. Method A cross-sectional cohorts of patients with a colostomy after rectal cancer in Denmark, Sweden, Spain, the Netherlands, China, Portugal, Australia, Lithuania, Egypt, and Israel were invited to complete questionnaires regarding demographic and socioeconomic factors along with the Colostomy Impact (CI) score, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and five anchor questions assessing colostomy impact on HRQoL. The background characteristics of the cohorts from each country were compared and generic HRQoL was measured with the EORTC QLQ-C30 presented for the total cohort. Results were compared with normative data of reference European populations. The predictors of reduced HRQoL were investigated by multivariable logistic regression, including demographic and socioeconomic factors and stoma-related problems. Results A total of 2557 patients were included. Response rates varied between 51-93 per cent. Mean time from stoma creation was 2.5-6.2 (range 1.1-39.2) years. A total of 25.8 per cent of patients reported that their colostomy impairs their HRQoL 'some'/'a lot'. This group had significantly unfavourable scores across all EORTC subscales compared with patients reporting 'no'/'a little' impaired HRQoL. Generic HRQoL differed significantly between countries, but resembled the HRQoL of reference populations. Multivariable logistic regression showed that stoma dysfunction, including high CI score (OR 3.32), financial burden from the stoma (OR 1.98), unemployment (OR 2.74), being single/widowed (OR 1.35) and young age (OR 1.01 per year) predicted reduced stoma-related HRQoL. Conclusion Overall HRQoL is preserved in patients with a colostomy after rectal cancer, but a quarter of the patients interviewed reported impaired HRQoL. Differences among several countries were reported and socioeconomic factors correlated with reduced quality of life. In this global survey among 2557 individuals with a colostomy after rectal cancer, generic and stoma-specific HRQoL differed significantly between countries; however, it resembled that of country-specific population norms. The most important predictors of stoma-related reduced HRQoL were stoma dysfunction and being financially burdened by the colostomy