Human Granzyme K Is a Feature of Innate T Cells in Blood, Tissues, and Tumors, Responding to Cytokines Rather than TCR Stimulation.

NK cells and CD8 T cells use cytotoxic molecules to kill virally infected and tumor cell targets. While perforin and granzyme B (GzmB) are the most commonly studied lytic molecules, less is known about granzyme K (GzmK). However, this granzyme has been recently associated with improved prognosis in solid tumors. In this study, we show that, in humans, GzmK is predominantly expressed by innate-like lymphocytes, as well as a newly identified population of GzmK+CD8+ non- mucosal-associated invariant T cells with innate-like characteristics. We found that GzmK+ T cells are KLRG1+EOMES+IL-7R+CD62L-Tcf7int, suggesting that they are central memory T and effector memory T cells. Furthermore, GzmK+ cells are absent/low in cord blood, suggesting that GzmK is upregulated with immune experience. Surprisingly, GzmK+ cells respond to cytokine stimuli alone, whereas TCR stimulation downregulates GzmK expression, coinciding with GzmB upregulation. GzmK+ cells have reduced IFN-γ production compared with GzmB+ cells in each T cell lineage. Collectively, this suggests that GzmK+ cells are not naive, and they may be an intermediate memory-like or preterminally differentiated population. GzmK+ cells are enriched in nonlymphoid tissues such as the liver and adipose. In colorectal cancer, GzmK+ cells are enriched in the tumor and can produce IFN-γ, but GzmK+ expression is mutually exclusive with IL-17a production. Thus, in humans, GzmK+ cells are innate memory-like cells that respond to cytokine stimulation alone and may be important effector cells in the tumor.

Prophylactic onlay mesh placement techniques for optimal abdominal wall closure: randomized controlled trial in an ex vivo biomechanical model.

BACKGROUND: Incisional hernias occur after up to 40 per cent of laparotomies. Recent RCTs have demonstrated the role of prophylactic mesh placement in reducing the risk of developing an incisional hernia. An onlay approach is relatively straightforward; however, a variety of techniques have been described for mesh fixation. The biomechanical properties have not been interrogated extensively to date. METHODS: This ex vivo randomized controlled trial using porcine abdominal wall investigated the biomechanical properties of three techniques for prophylactic onlay mesh placement at laparotomy closure. A classical onlay, anchoring onlay, and novel bifid onlay approach were compared with small-bite primary closure. A biomechanical abdominal wall model and ball burst test were used to assess transverse stretch, bursting force, and loading characteristics. RESULTS: Mesh placement took an additional 7-15 min compared with standard primary closure. All techniques performed similarly, with no clearly superior approach. The minimum burst force was 493 N, and the maximum 1053 N. The classical approach had the highest mean burst force (mean(s.d.) 853(152) N). Failure patterns fell into either suture-line or tissue failures. Classical and anchoring techniques provided a second line of defence in the event of primary suture failure, whereas the bifid method demonstrated a more compliant loading curve. All mesh approaches held up at extreme quasistatic loads. CONCLUSION: Subtle differences in biomechanical properties highlight the strengths of each closure type and suggest possible uses. The failure mechanisms seen here support the known hypotheses for early fascial dehiscence. The influence of dynamic loading needs to be investigated further in future studies.

Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

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.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

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 incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review.

Colorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.

The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo.

Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 µM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1ß, IL-8 and TNFα). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo.

Anastomotic leak risk in complete responders to neoadjuvant therapy for rectal cancer: a systematic review.

PURPOSE: The oncological benefits of achieving a complete pathological response following neoadjuvant chemoradiotherapy for rectal cancer are well defined. How a pathological response affects anastomotic healing or leak rates is not clear. The aim of this systematic review was to compare anastomotic leak rates among patients who did and did not achieve a complete pathological response. METHODS: Three major databases (PubMed, Embase, and Scopus) were searched. Predetermined inclusion criteria included prospective and retrospective articles published in English reporting complete pathological response and anastomotic leak rates following total mesorectal excision in ≥ 30 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and total mesorectal excision. The primary outcomes measured included complete pathological response and 30-day postoperative morbidity. RESULTS: From a total of 8919 patients with rectal cancer in 7 studies, 4165 fulfilled the criteria for inclusion. The majority (> 80%) of patients had clinical stage II or III disease. A defunctioning loop ileostomy was formed in 76.5%. A total of 589 (14.1%) patients achieved a pCR of whom 63 (10.7%) developed an anastomotic leak compared to 272/3576 (7.6%) patients without a pCR (p = 0.02). CONCLUSION: Patients with complete pathological response following neoadjuvant chemoradiotherapy and total mesorectal excision may be at higher risk of anastomotic leak than incomplete responders. This may need to be taken into account when counseling patients about the relative risks of organ preservation versus anterior resection.

Evidence-based treatment strategies for acute diverticulitis.

PURPOSE: Diverticular disease is a common acquired condition of the lower gastrointestinal tract that may be associated with significant morbidity. The term encompasses a spectrum of pathological processes with varying clinical manifestations. The purpose of this review was to update the reader on modern evidence-based treatment strategies for acute diverticulitis. METHODS: A literature search of the PUBMED database was performed using the keywords 'diverticulosis', 'diverticular disease' and 'diverticulitis'. Only articles published in the English language were included. RESULTS: Evidence-based treatment strategies for acute diverticulitis have evolved over time. Data have questioned the need for antibiotic therapy for Hinchey I disease and the role of percutaneous abscess drainage for Hinchey II. Clinical trials have demonstrated laparoscopic lavage is an appropriate option for select patients with Hinchey III disease and primary resection with anastomosis and defunctioning stoma may be considered in some cases of Hinchey IV disease. CONCLUSION: Risk-adapted treatment strategies and operative decision-making for acute diverticulitis are increasingly based on a combination of patient and disease factors.

The role of intraoperative radiotherapy in advanced rectal cancer: a meta-analysis.

AIM: Patients with locally advanced and locally recurrent rectal cancer (LARC/LRRC) experience higher rates of local recurrence (LR) and poorer overall survival than patients with primary rectal cancer restricted to the mesorectum despite improved neoadjuvant treatment regimens and radical surgical procedures. Intraoperative radiotherapy (IORT) has been suggested as an adjunctive tool in the surgical management of these challenging cases. However, clear evidence regarding the oncological benefit of IORT is sparse. The aim of this review was to update this evidence in the era of standardized neoadjuvant radiotherapy administration. METHOD: A systematic review of patients who received IORT as part of multimodal treatment for advanced rectal cancer from 2000 to 2020 and an analysis of IORT and surgery/external beam radiotherapy (EBRT) groups was performed. The primary endpoint was the rate of LR between the two groups. RESULTS: Seven papers met the predefined criteria. LR was reduced by the addition of IORT when compared with the surgery/EBRT alone group (14.7% vs. 21.4%; OR 0.55, 95% CI 0.27-1.14; p = 0.11). There was no increase in reported genitourinary morbidity, wound issues, pelvic collections or anastomotic leak in those patients who received IORT. Notably, there was no survival difference between the two groups. CONCLUSION: The addition of IORT to current treatment strategies in the management of patients with LARC/LRRC is associated with a lower rate of locoregional recurrence without increased morbidity. However, this marks a highly selective group of patients, with heterogeneity regarding indications, prior neoadjuvant treatments and/or IORT dosing.

Extended right colectomy, left colectomy, or segmental left colectomy for splenic flexure carcinomas: a European multicenter propensity score matching analysis.

BACKGROUND: The surgical resection of the splenic flexure carcinoma (SFC) is challenging and the optimal surgical procedure for SFCs remains a matter of debate. The present study aimed to compare in a multicenter European sample of patients the short- and long-term outcomes of extended right (ERC) vs. left (LC) vs. segmental left colectomy (SLC) for SFCs. METHODS: This retrospective multicenter study analyzed the surgical and oncological outcomes of SFC patients undergoing elective curative intent surgery between 2000 and 2018. Descriptive and exploratory analyses were first conducted on the whole sample. Outcomes of the different procedures (ERC vs. LC vs. SLC) were then compared using propensity score matching for multilevel treatment. Overall (OS) and disease-free survival (DFS) were evaluated by Kaplan-Meier method. RESULTS: From a total of 399 SFC patients, 143 (35.8%) underwent ERC, 131 (32.8%) underwent LC, and 125 (31.4%) underwent SLC. Overall, 297 (74.4%) were laparoscopic procedures. An increase in operative time, time to flatus, time to regular diet, and hospital stay was observed with the progressive extension of SFC resection. ERC was associated with significantly increased risk of postoperative ileus compared to both LC and SLC. A significantly greater number of lymph nodes were retrieved by ERC, but the objective of at least 12 retrieved lymph nodes was achieved in 85% of patients, without procedure-related differences. No differences were observed in OS or DFS between ERC, LC, and SLC. CONCLUSION: The present study supports the resection of SFCs by colon-sparing surgical techniques, such as SLC.

Evidence-based Reviews in Surgery Long-term Outcome of Surgery Versus Conservative Management for Recurrent and Ongoing Complaints After an Episode of Diverticulitis: Five-year Follow-up Results of a Multicenter Randomized Controlled Trial (DIRECT-Trial).

QUESTION: Does surgery or conservative management of recurring diverticulitis/ongoing symptoms results in a higher quality of life (QoL) at 5-year follow-up. DESIGN: Randomized controlled trial. SETTING: Multicenter trial in the Netherlands. PATIENTS: Patients aged 18 to 75 years, who presented with either ongoing abdominal complaints (for >3 months) and/or frequently recurring left-sided diverticulitis (>2 episodes in 2 years) after an objectified (via Computed Tomography, Ultrasound or Endoscopy) episode of diverticulitis were included in this study. INTERVENTION: Elective Sigmoid Resection within 6 weeks vs. Conservative Management MAIN OUTCOME:: QoL at 5-year follow-up, as measured by the Gastrointestinal Quality of Life Index (GIQLI). Secondary outcomes included additional QoL assessments (including the EuroQoL-5D-3L, Visual Analogue Score for pain, and the short form 36 health survey) RESULTS:: The intention to treat analysis showed the surgical group had a higher quality of life (GIQLI) score than the conservative group (mean difference 9.7, 95% confidence interval 1.7-17.7, P = 0.018), which approached but did not meet the minimum important difference of 10. This difference was achieved in 67% of those in the operative group versus 57% in the conservative group (many of who eventually underwent surgery). CONCLUSIONS: The study results demonstrate that HRQOL at 5-year follow-up may be improved in patients undergoing surgical resection, although this difference did not meet the MID for the GIQLI.

A meta-analysis of carbon dioxide versus room air insufflation on patient comfort and key performance indicators at colonoscopy.

BACKGROUND: Carbon dioxide (CO2) has been used as an alternative to air insufflation at endoscopy with good results; however, uptake of the technique has been poor, possibly due to perceived lack of outcome equivalency. This meta-analysis evaluates the effectiveness of CO2 versus air in reducing pain post-colonoscopy and furthermore examines other key performance indicators (KPIs) such as sedative use, procedure times and polyp detection rates. METHODS: This meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pubmed, Pubmed Central, Embase and Cochrane Library were searched for randomized studies from 2004 to 2019, reporting outcomes for patients undergoing colonoscopy with air or CO2 insufflation, who reported pain on a numerical or visual analogue scale (VAS). Results were reported as mean differences (MD) or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Of 3586 citations, 23 studies comprising 3217 patients were analysed. Patients undergoing colonoscopy with air insufflation had 30% higher intraprocedural pain scores than those receiving CO2 (VAS 3.4 versus 2.6, MD -0.7, 95% CI - 1.4-0.0, p = 0.05), with a sustained beneficial effect amongst those in the CO2 group at 30 min, 1-2-h and 6-h post procedure (MD - 0.8, - 0.6 and - 0.2, respectively, p < 0.001 for all), as well as less distension, bloating and flatulence (p < 0.01 for all). There were no differences between the two groups in KPIs such as the sedation required, procedure time, caecal intubation or polyp detection rates. CONCLUSIONS: CO2 insufflation improves patient comfort without compromising colonoscopic performance.

Meta-analysis of early bowel resection versus initial medical therapy in patient's with ileocolonic Crohn's disease.

BACKGROUND: Early bowel resection (EBR) in ileocolonic Crohn's disease (CD) may be associated with more durable remission compared with initial medical therapy (IMT) even when biologic therapy is included. AIM: To compare the efficacy of EBR versus IMT for ileocolonic CD METHODS: A systematic search was performed to identify studies that compared EBR (performed < 1 year from initial diagnosis) or IMT for the management of ileocolonic CD. Log hazard ratios (InHR) for relapse-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (OR). Quality assessment of the included studies was performed using the Newcastle-Ottawa (NOS) and Jadad scales. RESULTS: A total of 7 studies with 1863 CD patients (EBR n = 581, 31.2%; IMT n = 1282, 68.8%) were eligible for inclusion. There was a moderate-to-high risk of bias. The median NOS was 8 (range 7-9). There was a reduced likelihood of overall (OR, 0.53; 95% confidence interval (95% CI), 0.34, 0.83; p = 0.005) and surgical (OR, 0.47; 95% CI, 0.24, 0.91; p = 0.03) relapse with EBR. There was also a less requirement for maintenance biologic therapy (OR, 0.24; 95% CI, 0.14, 0.42; p < 0.0001). Patients who underwent EBR had a significantly improved RFS than those who underwent IMT (HR, 0.62; 95% CI, 0.52, 0.73; p < 0.001). There was no difference in morbidity (OR, 1.67; 95% CI, 0.44, 6.36; p = 0.45) between the groups. CONCLUSION: EBR may be associated with less relapse and need for maintenance biologic therapy than IMT. 'Upfront' or early resection may represent a reasonable and cost-effective alternative to biologic therapy, especially in biologic-resistant subpopulations.

Systemic inflammatory response predicts oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient colorectal cancer.

INTRODUCTION: A variety of inflammatory scoring systems and their prognostic value have been reported in many solid organ cancers. This study aimed to examine the association between the systemic and local inflammatory responses, and oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient (dMMR) phenotype colorectal cancer (CRC). MATERIALS AND METHODS: Consecutive patients undergoing resection for dMMR CRC were identified from a prospectively maintained database and compared with a cohort of patients with proficient mismatch repair system tumours. Systemic inflammatory response was assessed by the modified Glasgow prognostic score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, lymphocyte-monocyte ratio, C-reactive protein/albumin ratio, prognostic index and prognostic nutritional index. Local inflammatory response was defined by the presence of tumour infiltrating lymphocytes, tumour infiltrating neutrophils, plasma cells or macrophages at the invasive front. The inflammatory infiltrate was assessed using the Klintrup-Mäkinen (KM) score. RESULTS: On univariable analysis, preoperative NLR ≥ 5 (hazard ratio [HR] 2.5; 95% confidence interval [CI] 1.25-5.19; p = 0.007) and mGPS (HR 1.6; 95% CI 1.1-2.6; p = 0.03) predicted worse overall survival, but only NLR was associated with greater recurrence (HR 3.6; 95% CI 1.5-8.8; p = 0.004). Increased local inflammatory response, as measured by KM score (HR 0.31; 95% CI 0.1-0.7; p = 0.009) and the presence of macrophages in the peritumoral infiltrate (HR 0.17; 95% CI 0.07-0.3; p < 0.001), was associated with better outcomes. NLR was the only independent prognostic factor of overall and disease-free survival. CONCLUSION: Systemic inflammatory response predicts oncological outcomes in CRC patients, but only NLR has prognostic value in the dMMR group.

The sentinel stent? A systematic review of the role of prophylactic ureteric stenting prior to colorectal resections.

PURPOSE: 'Prophylactic' ureteric stents potentially reduce rates, and facilitate intraoperative recognition, of iatrogenic ureteric injury (IUI) during colorectal resections. A lack of consensus surrounds the risk-benefit equation of this practice, and we aimed to assess the evidence base. METHODS: A systematic review was performed according to PRISMA guidelines. MEDLINE, Scopus, EMBASE and Cochrane databases were searched using terms 'ureteric/ureteral/JJ/Double J stent' or 'ureteric/ureteral catheter' and 'colorectal/prophylactic/resection/diverticular disease/diverticulitis/iatrogenic injury'. Primary outcomes were rates of ureteric injuries and their intraoperative identification. Secondary outcomes included stent complication rates. RESULTS: We identified 987 publications; 22 papers met the inclusion criteria. No randomised controlled trials were found. The total number of patients pooled for evaluation was 869,603 (102,370 with ureteric stents/catheters, 767,233 controls). The most frequent indications for prophylactic stents were diverticular disease (45.38%), neoplasia (33.45%) and inflammatory bowel disease (9.37%). Pooled results saw IUI in 1521/102,370 (1.49%) with, and in 1333/767,233 (0.17%) without, prophylactic ureteric stents. Intraoperative recognition of IUIs occurred in 10/16 injuries (62.5%) with prophylactic stents, versus 9/17 (52.94%) without stents (p = 0.579). The most serious complications of prophylactic stent use were ureteric injury (2/1716, 0.12%) and transient ureteric obstruction following stent removal (13/666, 1.95%). CONCLUSIONS: Placement of prophylactic ureteric stents has a low complication rate. There is insufficient evidence to conclude that stents decrease ureteric injury or increase intraoperative detection of IUIs. Apparently higher rates of IUI in stented patients likely reflect use in higher risk resections. A prospective registry with harmonised data collection points and stratification of intraoperative risk is needed.