ERAS Protocol Applied to Oncological Colorectal Mini-invasive Surgery Reduces the Surgical Stress Response and Improves Long-term Cancer-specific Survival

Background: Enhanced recovery after surgery (ERAS) protocols are known to reduce postoperative complications and improve short-term outcomes by minimizing the surgical stress response (SSR). Retrospective reviews of large cohorts suggest that they may also have an impact on long-term oncological outcomes. In 2016, Mari et al published a randomized trial on ERAS protocol and the impact on the SSR; they found that IL-6 was less expressed in patients who undergo laparoscopic colorectal surgery within an ERAS protocol compared with controls. The aim of the present study is to report the long-term oncological outcomes of patients enrolled 5 years after the conclusion of the study. Methods: Patients enrolled had received the indication for major colorectal surgery, aged between 18 and 80 years, with American Society of Anesthesiologists (ASA) grades I to III, autonomous for mobilization and walking, eligible for laparoscopic technique. In total, 140 patients were enrolled and randomized into 2 groups of 70 patients each. Among these patients, 52 in the ERAS group (EG) and 53 in the Standard group (SG) had colorectal cancer. For them, a 5-year oncological follow-up according to the NCCN 16 guidelines was planned. IL-6, C-reactive protein, prolactine, white blood cell count, albumin, and prealbumin were compared between oncological patients in the EG and in the SG. Results: EG showed lower IL-6 on postoperative day 1 (21.2±9.1 vs. 40.3 ±11.3; P <0.05) and on day 5 (14.9±6.2 vs. 38.7±8.9; P <0.05), lower C-reactive protein on day 1 (48.3±15.7 vs. 89.4±20.3; P <0.05) and on day 5 (38.3±11.4 vs. 74.3±19.7; P <0.05), and lower pre-albumine on day 5 (18.9±7.2 vs. 12.3±6.9; P <0.05) compared with SG. Median oncological follow-up was 57 months [46.5 to 60]. There was no statistically significant difference in overall survival (log rank=0.195) and disease-free survival (Log rank=0.089) between groups. Cancer-specific survival was significantly better (log rank=0.038) in the EG compared with patients in the SG. Conclusions: ERAS protocol applied to colorectal laparoscopic surgery for cancer is able to minimize the SSR. As a possible result, cancer-specific survival seems to be improved in patients within enhanced protocols. However, even though there may be an association between an excess of SSR and worse oncological outcomes, the favorable effect of ERAS protocols toward better overall and disease-free survival is yet to be demonstrated

Colorectal Cancer Outcomes of Robotic Surgery Using the HugoTM RAS System: The First Worldwide Comparative Study of Robotic Surgery and Laparoscopy

Background/Objectives: The aim of the study was to compare the perioperative and oncologic outcomes of patients who underwent surgery for colorectal cancer (CRC) performed using laparoscopy or using the Medtronic HugoTM Robotic-Assisted Surgery (RAS) system. Methods: This is a retrospective comparative single-center study of consecutive minimally invasive surgeries for CRC performed by two colorectal surgeons with extensive laparoscopic experience at the beginning of their robotic expertise. Patients were not selected for the surgical approach, but waiting lists and operating room availability determined whether the patients were in the robotic group or the laparoscopic group. The primary outcome was to compare 30-day postoperative complications according to the Clavien–Dindo classification and the Complication Comprehensive Index (CCI). The secondary outcomes included operating times, conversion rates, intraoperative complications, length of hospital stays (LOS), readmission rates, and short-term oncologic outcomes, such as the R0 resection, the number of lymph nodes harvested, the total mesorectal excision (TME) quality, and the circumferential resection margin (CRM). Results: Of the 109 patients, 52 underwent robotic and 57 laparoscopic CRC surgery. Patient demographic and clinical characteristics were similar in the two groups. There was no significant difference between the robotic and the laparoscopic groups regarding postoperative complications, the Clavien–Dindo classification, and the CCI. They also had similar operating times, conversion rates, intraoperative complications, LOSs, readmission rates, and short-term oncologic outcomes (the lymph nodes harvested, the R0 resection, TME quality, and CRM status). Conclusions: This study reports the largest cohort of CRC surgery performed using the Medtronic HugoTM RAS system and is the first comparative study with laparoscopy. The perioperative and oncologic outcomes were similar, demonstrating that the Medtronic HugoTM RAS system is safe and feasible for CRC as compared to laparoscopic surgery, even at the beginning of the robotic experience

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P < 0.001) and MEDIUM-volume (OR 0.72, 95% c.i. 0.62-0.83, P < 0.001) centres was lower than in VERY HIGH-volume centres. Of the 4676 rectal cancer patients, the rate of >= 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes

Patterns of opioid use after surgical discharge: a multicentre, prospective cohort study in 25 countries

Background Excessive opioid prescribing following surgery contributes to the growing opioid crisis. Prescribing practices are modifiable, yet data to guide appropriate prescription of opioids at surgical discharge remain sparse. This study aimed to evaluate factors associated with opioid consumption following discharge from surgery. Methods An international prospective multicentre cohort study was performed recruiting adult patients undergoing common general, orthopaedic, gynaecological and urological surgery, with follow-up 7 days after discharge. The primary outcome measures were the quantities of prescribed and consumed opioids in oral morphine milligram equivalents. Descriptive and multivariable analyses were performed to investigate factors associated with the primary outcome measures. Results This analysis included 4273 patients from 144 hospitals in 25 countries. Overall, 1311 (30.7%) patients were prescribed opioids at discharge. For those patients prescribed opioids, mean (SD) 179 (240) oral morphine milligram equivalents were prescribed, yet only 81 (145) oral morphine milligram equivalents were consumed within the first 7 days after discharge. An increased dose of opioids prescribed at discharge was associated with an increased dose of opioids consumed during the follow-up period (β = 0.33 (95%CI 0.31–0.34), p < 0.001). The risk of prescribing more opioids than patients consumed increased as quantities of opioids prescribed at discharge exceeded 100 oral morphine milligram equivalents, independent of patient comorbidity, procedure and pain. Patients were prescribed more than twice the quantity of opioids they consumed in the first 7 days following discharge from surgery. Conclusions Our data suggest that the current quantities of opioids provided at discharge exceed patient needs and may contribute to increasing community opioid use and circulation

The Diverticular Disease Registry (DDR Trial) by the Advanced International Mini-Invasive Surgery Academy Clinical Research Network: Protocol for a Multicenter, Prospective Observational Study

Diverticular disease is an increasingly common issue, with a variety of clinical presentations and treatment options. However, very few prospective cohort studies explore outcomes between the different presentations and treatments. The Diverticular Disease Registry (DDR Trial) is a multicenter, prospective, observational cohort study on behalf of the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network. The DDR Trial aims to investigate the short-term postoperative and long-term quality of life outcomes in patients undergoing surgery or medical treatments for diverticular disease. DDR Trial is open to participation by all tertiary-care hospitals. DDR Trial has been registered at ClinicalTriats.gou (NCT 04907383). Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on June 1 , 2021 and will end after 5 years of recruitment. All adult patients with imaging-proven colonic diverticular disease (i.e., symptomatic colonic diverticulosis including diverticular bleeding, diverticulitis, and Symptomatic Uncomplicated Diverticular Disease) will be included. The primary outcome of DDR Trial is quality of life assessment at 12-month according to the Gastrointestinal Quality of Life Index (GIQLI). The secondary outcome is 30-day postoperative outcomes according to the Clavien-Dindo classification. DDR Trial will significantly advance in identifying the optimal care for patients with diverticular disease by exploring outcomes of different presentations and treatments

30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE):A Prospective, International Collaborative Cohort Study

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications.SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level.METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes.RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications.CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.</p

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&nbsp;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

National variations in perioperative assessment and surgical management of Crohn's disease: a multicentre study

Aim: Crohn's disease (CD) requires a multidisciplinary approach and surgery should be undertaken by dedicated colorectal surgeons with audited outcomes. We present a national, multicentre study, with the aim to collect benchmark data on key performance indicators in CD surgery, to highlight areas where standards of CD surgery excel and to facilitate targeted quality improvement where indicated. Methods: All patients undergoing ileocaecal or redo ileocolic resection in the participating centres for primary and recurrent CD from June 2018 to May 2019 were included. The main objective was to collect national data on hospital volume and practice variations. Postoperative morbidity was the primary outcome. Laparoscopic surgery and stoma rate were the secondary outcomes. Results: In all, 715 patients were included: 457 primary CD and 258 recurrent CD with a postoperative morbidity of 21.6% and 34.7%, respectively. Laparoscopy was used in 83.8% of primary CD compared to 31% of recurrent CD. Twenty-five hospitals participated and the total number of patients per hospital ranged from 2 to 169. Hospitals performing more than 10 primary CD procedures per year showed a higher adoption of laparoscopy and bowel sparing surgery. Conclusions: There is significant heterogeneity in the number of CD surgeries performed per year nationally in Italy. Our data suggest that high-volume hospitals perform more complex procedures, with a higher adoption of bowel sparing surgery. The rate of laparoscopy in high-volume hospitals is higher for primary CD but not for recurrent CD compared with low-volume hospitals

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins