Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

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.

Surgery for synchronous and metachronous colorectal cancer: segmental or extensive colectomy?

PURPOSE: To assess the impact of surgical approach on morbidity, mortality, and the oncological outcomes of synchronous (SC) and metachronous (MC) colorectal cancer (CRC). METHODS: All patients undergoing resection for double location CRC (SC or MC) between 2006 and 2020 were included. The exclusion criteria were polyposis or SC located on the same side. RESULTS: Sixty-seven patients (age, 64.8 years; male, 78%) with SC (n = 41; 61%) or MC (n = 26; 39%) were included. SC was treated with segmental colectomy (right and left colectomy/proctectomy; n = 19) or extensive colectomy (subtotal/total colectomy or restorative proctocolectomy with pouch; n = 22). Segmental colectomy was associated with a higher incidence of anastomotic leakage (47.4 vs. 13.6%; p = 0.04) and a higher rate of medical morbidity (47.4 vs. 16.6%; p = 0.04). The mean number of lymph nodes harvested was similar. For MC, the second cancer was treated by iterative colectomy (n = 12) or extensive colectomy (n = 14) and there was no significant difference in postoperative outcomes between the two surgical approaches. The median follow-up period was 42.4 ± 29.1 months. The 5-year overall and disease-free survival of the SC and MC groups did not differ to a statistically significant extent. CONCLUSIONS: Extensive colectomy should be preferred for SC to reduce morbidity and improve the prognosis. In contrast, iterative colectomy can be performed safely for patients with MC.

Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis.

Germline BRCA1/2 mutations lead to malfunction of DNA damage repair pathways and predispose to pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to synthesise the available research on this topic. Four studies reporting risk ratio (RR) were included in the final meta-analysis to minimise misrepresenting our results by combining separate risk estimates. Our meta-analysis revealed a statistically significant increased risk of PDAC in BRCA carriers overall (RR: 2.65, 95% confidence interval: 1.43-4.91, p = 0.002).

The role of bariatric surgery in liver transplantation: timing and type.

INTRODUCTION: The rise in obesity worldwide has shifted the indications for liver transplantation (LT), with non-alcoholic steatohepatitis (NASH) being the second most common indication for transplantation. There remains an underestimation of cirrhosis being attributed to NASH. Bariatric surgery (BS) is a reliable solution to overcome obesity and its associated comorbidities. The role of BS in LT has been investigated by different studies; however, the type of BS and timing of LT need further investigation. METHODS: A systemic review examining the role of BS in LT patients was performed. After selection of the studies based on inclusion and exclusion criteria, data extraction was performed by two independent reviewers. Primary outcomes included patient and graft survival. RESULTS: From a total of 2374 articles, five met the prefined criteria. One hundred sixty-two patients had both BS + LT and 1426 underwent LT alone. The percentage of female patients in the BS + LT and LT cohorts was 75% and 35% respectively. The average age in BS + LT and LT cohorts was 43.05 vs. 56.22 years respectively. Patients undergoing BS had comparable outcomes in terms of overall patient survival, graft survival and post-operative morbidity compared to LT alone. When comparing BMI change in patients with prior versus simultaneous BS + LT, no significant difference was found. CONCLUSION: BS and LT patients achieve comparable outcomes to general LT populations. Further studies examining simultaneous BS + LT are needed to answer questions concerning patient selection and timing of surgery.

Laparoscopic rectal dissection preserves erectile function after ileal pouch-anal anastomosis: a two-centre study.

AIM: Few studies have been published on erectile function after ileal pouch-anal anastomosis (IPAA) and, unlike in women, male fertility after IPAA has never been assessed. The primary objective was to assess the impact of IPAA on erectile function. The secondary objective was to assess the impact of IPAA on male fertility. METHODS: All of the male patients who underwent IPAA in two university care centres between 2003 and 2017, aged 70 years or less at the time of operation, were included. Forty-eight per cent of the patients responded to the international index of erectile function, the Jorge-Wexner score and a fertility questionnaire. All demographic and perioperative data were prospectively collected. Fertility results were compared with those of a control group undergoing appendectomy, matched for age at the time of operation, desire for paternity and length of follow-up. RESULTS: One hundred and thirty-nine patients were included, among which 46 (33%) presented with erectile dysfunction and 14 (10%) with severe erectile dysfunction. Age older than 50 years (OR 0.27, 95% CI 0.12-0.62, P = 0.002) and rectal dissection performed by open surgery (OR 4.16, 95% CI 1.62-10.65, P = 0.003) were independent risk factors for erectile dysfunction. There was no infertility after IPAA compared with controls: indeed, 23 (16%) IPAA patients presented with pregnancy in their couple versus 27 (22%) controls (P = 0.29), whereas 36 (26%) IPAA patients and 34 (28%) controls (P = 0.80) expressed paternity desire. CONCLUSION: A total laparoscopic approach, including rectal dissection, should be preferred to preserve erectile function. Male fertility is not impaired after IPAA.

Can a Local Drainage Salvage a Failed Colorectal or Coloanal Anastomosis? A Prospective Cohort of 54 Patients.

BACKGROUND: Local drainages can be used to manage leakage in select patients without peritonitis. OBJECTIVE: The aim of this study was to evaluate the efficacy of drainage procedures in maintaining a primary low anastomosis after anastomotic leakage. DESIGN: A retrospective observational study was performed on a prospectively maintained database. SETTINGS: The study was performed between 2014 and 2017 in a tertiary referral center. PATIENTS: Patients undergoing rectal resections with either a colorectal or coloanal anastomosis with diverting stoma were identified. Anastomotic leakages requiring a radiological or transanal drainage without peritonitis were included. MAIN OUTCOME MEASURES: The primary outcome was the maintenance of the primary anastomosis after local drainage of an anastomotic leakage and stoma reversal. RESULTS: A low anastomosis for rectal cancer with diverting stoma was performed in 326 patients. A total of 77 anastomotic leakages (24%) occurred, of which, 6 (8%) required abdominal surgery, 17 (22%) were treated conservatively (medical management), and 54 (70%) were managed by drainage. Surgical transanal drainage was performed in 21 patients (39%), with radiologic drainage procedures performed in 33 patients (61%). The median interval between surgery and drainage was 13 days (range, 9-21 d). Five patients (9%) required emergency abdominal surgery. Twenty-seven patients (50%) did not require any additional intervention after drainage procedure, whereas 21 patients (39%) underwent redo anastomotic surgery. Forty-three patients (80%) had no stoma at the end of follow-up. Failure to maintain the primary anastomosis after local drainage was associated with increased age (p = 0.04), a pelvic per-operative drainage (p = 0.05), a drainage duration >10 days (p = 0.002), the time between surgery and drainage >15 days (p = 0.03), a side-to-end or J-pouch anastomosis (p = 0.04), and surgical transanal drainage (p = 0.03). LIMITATIONS: The small sample size of the study was the main limitation. CONCLUSIONS: Local drainage procedures maintained primary anastomosis in 50% of cases after an anastomotic leakage. See Video Abstract at http://links.lww.com/DCR/B57. ¿PUEDE UN DRENAJE LOCAL SALVAR UNA ANASTOMOSIS COLORRECTAL O COLOANAL FALLIDA? UNA COHORTE PROSPECTIVO DE 54 PACIENTES: Los drenajes locales se pueden utilizar para controlar las fugas en pacientes seleccionados sin peritonitis.El objetivo de este estudio fue evaluar la eficacia de los procedimientos de drenaje, para mantener una anastomosis primaria baja, después de una fuga anastomótica.Se realizó un estudio observacional retrospectivo en una base de datos mantenida prospectivamente.El estudio se realizó entre 2014-2017, en un centro de referencia terciaria.Se identificaron pacientes sometidos a resecciones rectales con anastomosis colorrectal o coloanal y estoma de derivación. Se incluyeron fugas anastomóticas sin peritonitis, que requirieron drenaje radiológico o transanal.El resultado primario fue el mantenimiento de la anastomosis primaria, después del drenaje local de una fuga anastomótica y la reversión del estoma.Se realizó una anastomosis baja para cáncer rectal con estoma derivativo en 326 pacientes. Se produjeron 77 (24%) fugas anastomóticas, de las cuales 6 (8%) requirieron cirugía abdominal, 17 (22%) fueron tratadas de forma conservadora (tratamiento médico) y 54 (70%) fueron manejadas por drenaje. Se realizó drenaje transanal en 21 pacientes (39%) y procedimientos de drenaje radiológico en 33 pacientes (61%). La mediana del intervalo entre la cirugía y el drenaje fue de 13 días [9-21]. 5 (9%) pacientes requirieron cirugía abdominal de emergencia. Veintisiete (50%) pacientes no requirieron ninguna intervención adicional después del procedimiento de drenaje, mientras que 21 pacientes (39%) se sometieron a una reparación quirúrgica anastomótica. 43 pacientes (80%) no tuvieron estoma al final del seguimiento. El fracaso para mantener la anastomosis primaria después del drenaje local, se asoció con un aumento de la edad (p = 0.04), un drenaje pélvico preoperatorio (p = 0.05), una duración del drenaje >10 días (p = 0.002), el tiempo entre la cirugía y el drenaje >15 días (p = 0.03), anastomosis termino lateral o bolsa en J (p = 0.04) y drenaje quirúrgico transanal (p = 0.03).El pequeño tamaño de la muestra del estudio fue la principal limitación.Después de la fuga anastomótica, los procedimientos del drenaje local conservaron la anastomosis primaria en el 50% de los casos. Vea el Resumen del Video en http://links.lww.com/DCR/B57.

Prognostic value of tumor deposits in rectal cancer: A monocentric series of 505 patients.

BACKGROUND AND OBJECTIVES: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer. METHODS: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis. RESULTS: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001). CONCLUSION: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

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.

Does A Longer Waiting Period After Neoadjuvant Radio-chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years' Follow-up Results of the Greccar-6 Randomized Multicenter Trial.

OBJECTIVE: The aim of this study was to report the 3-year survival results of the GRECCAR-6 trial. SUMMARY BACKGROUND DATA: Current data on the effect of an extended interval between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0) is controversial. Furthermore, its effect on oncological outcomes is unknown. METHODS: The GRECCAR-6 trial was a phase III, multicenter, randomized, open-label, parallel-group, controlled trial. Patients with cT3/T4 or TxN+ tumors of the mid or lower rectum who had received RCT (45-50 Gy with 5-fluorouracil or capecitabine) were included and randomized into a 7- or 11-week waiting period. Primary endpoint was the pCR rate. Secondary endpoints were 3-year overall (OS), disease-free survival (DFS), and recurrence rates. RESULTS: A total of 265 patients from 24 participating centers were enrolled. A total of 253 patients underwent a mesorectal excision. Overall pCR rate was 17% (43/253). Mean follow-up from surgical resection was 32 ±â€Š8 months. Twenty-four deaths occurred with an 89% OS at 3 years. DFS was 68.7% at 3 years (75 recurrences). Three-year local and distant recurrences were 7.9% and 23.8%, respectively. The randomization group had no impact on the 3-year OS (P = 0.8868) or DFS (P = 0.9409). Distant (P = 0.7432) and local (P = 0.3944) recurrences were also not influenced by the waiting period. DFS was independently influenced by 3 factors: circumferential radial margin (CRM) ≤1 mm [hazard ratio (HR) = 2.03; 95% confidence interval (CI), 1.17-3.51], ypT3-T4 (HR = 2.69; 95% CI, 1.19-6.08) and positive lymph nodes (HR = 3.62; 95% CI, 1.89-6.91). CONCLUSION: Extending the waiting period by 4 weeks following RCT has no influence on the oncological outcomes of T3/T4 rectal cancers.

C-Reactive Protein Values After Colorectal Resection: Can We Discharge a Patient With a C-Reactive Protein Value >100? A Retrospective Cohort Study.

BACKGROUND: C-reactive protein is a useful negative predictive test for the development of anastomotic leakage following colorectal surgery. Evolution of procedures (laparoscopy, enhanced recovery program, early discharge, complex redo surgery) may influence C-reactive protein values; however, this is poorly studied to date. OBJECTIVE: The aim of this study is to evaluate C-reactive protein as an indicator of postoperative complication and as a predictor for discharge. DESIGN: This is retrospective study of a consecutive monocentric cohort. SETTINGS: All patients undergoing a colorectal resection with anastomosis (2014-2015) were included. MAIN OUTCOMES MEASURES: C-reactive protein, leukocytosis, type of resection, and postoperative course were the primary outcomes measured. RESULTS: A total of 522 patients were included. The majority had either a colorectal (n = 159, 31%) or coloanal anastomosis (n = 150, 29%). Overall morbidity was 29.3%. C-reactive protein was significantly higher among patient having intra-abdominal complications at an early stage (day 1-2) (164.6 vs 136.2; p = 0.0028) and late stage (day 3-4) (209.4 vs 132.1; p < 0.0001). In multivariate analysis, early C-reactive protein was associated with BMI (coefficient, 4.9; 95% CI, 3.2-6.5; p < 0.0001) and open surgical procedures (coefficient, 43.1; 95% CI, 27-59.1; p < 0.0001), while late C-reactive protein value was influenced by BMI (coefficient, 4.8; 95% CI, 2.5-7.0; p = 0.0024) and associated extracolonic procedures (coefficient, 34.2; 95% CI, 2.7-65.6; p = 0.033). Sensitivity, specificity, negative predictive values, and positive predictive values for intra-abdominal complication were 85.9%, 33.6%, 89.3%, and 27.1% for an early C-reactive protein <100 mg/L and 72.7%, 75.4%, 89.4%, and 49.2% for a late C-reactive protein <100 mg/L. Four hundred seven patients with an uneventful postoperative course were discharged at day 8 ± 6.4 with a mean discharge C-reactive protein of 83.5 ± 67.4. Thirty-eight patients (9.3%) were readmitted and had a significantly higher discharge C-reactive protein (138.6 ± 94.1 vs 77.8 ± 61.2, p = 0.0004). Readmission rate was 16.5% for patients with a discharge C-reactive protein >100 mg/L vs 6% with C-reactive protein <100 mg/L (p = 0.0008). For patients included in an enhanced recovery program (discharge at day 4 ± 2.4), the threshold should be higher because discharge is around day 3 or 4. With a C-reactive protein <140, readmission rate was 2% vs 19%, (p = 0.056). LIMITATIONS: This study includes retrospective data. CONCLUSION: C-reactive protein <100 mg/L is associated with a lower risk of intra-abdominal complication and readmission rates. See Video Abstract at http://links.lww.com/DCR/A749.

The prevalence of venous thromboembolism in rectal surgery: a systematic review and meta-analysis.

PURPOSE: Venous thromboembolism (VTE) following rectal surgery is a significant and preventable cause of morbidity and mortality, yet the true prevalence is not well established. This systematic review and meta-analysis assessed the available literature and determined its prevalence following rectal surgery. METHODS: A systematic review assessed the prevalence of VTE following rectal surgery. In addition, we evaluated whether subgroups (open vs. minimally invasive or benign vs. malignant resections) impacted on its prevalence or rate of deep venous thrombosis (DVT) or pulmonary embolism (PE). RESULT: Thirty-eight studies met the predefined inclusion criteria. The aggregate prevalence of VTE following rectal surgery was 1.25% (95% CI 0.86-1.63), with DVT and PE occurring in 0.68% (95% CI 0.48-0.89) and 0.57% (95% CI 0.47-0.68) of patients. VTE following cancer and benign resection was 1.59% (95% CI 0.60-1.23 and 1.5% (95% CI 0.89-2.12) respectively. The prevalence of VTE in patients having minimally invasive resection was lower than those having open surgery [0.58% (16/2770) vs. 2.22% (250/11278); RR 0.54, 95% CI 0.33-0.86]. CONCLUSION: This review observed that there is sparse evidence on prevalence of VTE following rectal surgery. It provides aggregated data and analysis of available literature, showing overall prevalence is low, especially in those having minimally invasive procedures.

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.

Metachronous colorectal cancer risk in Lynch syndrome patients-should the endoscopic surveillance be more intensive?

PURPOSE: Regular follow-up for patients with Lynch syndrome (LS) is vital due to the increased risk of colorectal (50-80%), endometrial (40-60%), and other cancers. However, there is an ongoing debate concerning the best interval between colonoscopies. Currently, no specific endoscopic follow-up has been decided for LS patients who already have an index colorectal cancer (CRC). The aim of this study was to evaluate the risk of metachronous cancers (MC) after primary CRC in a LS population and to determinate if endoscopic surveillance should be more intensive. METHODS: A prospective cohort of patients with a confirmed diagnosis of hereditary CRC since 2009 was included. Patients with LS and a primary CRC were the cohort of choice. RESULTS: One hundred twenty-one patients were included with a median age of 44 years(16-70). At least one MC occurred in 39 patients (32.2%), with a median interval of 67 months (6-300) from index cancer. Fifteen (38.5%) developed two or more MCs during follow-up, with a median number of two (2-6) tumors occurring. Metachronous CRC were diagnosed after a median interval of 24 (6-57) months since last colonoscopy and were more commonly seen in MSH2 mutation carriers (58 vs. 35%, p = 0.001). After a median follow-up of 52.9 (3-72) months, no cancer-related deaths were recorded. CONCLUSION: Patients with LS have an increased risk of MC, especially CRCs. With a median time period of 24 months between colonoscopy and metachronous CRC, the interval between surveillance colonoscopies following primary CRC should not exceed 18 months, especially in patients with MSH2 mutation.

Postoperative Peritonitis After Digestive Tract Surgery: Surgical Management and Risk Factors for Morbidity and Mortality, a Cohort of 191 Patients.

BACKGROUND: Postoperative peritonitis (POP) following gastrointestinal surgery is associated with significant morbidity and mortality, with no clear management option proposed. The aim of this study was to report our surgical management of POP and identify pre- and perioperative risk factors for morbidity and mortality. METHODS: All patients with POP undergoing relaparotomy in our department between January 2004 and December 2013 were included. Pre- and perioperative data were analyzed to identify predictors of morbidity and mortality. RESULTS: A total of 191 patients required relaparotomy for POP, of which 16.8% required >1 reinterventions. The commonest cause of POP was anastomotic leakage (66.5%) followed by perforation (20.9%). POP was mostly treated by anastomotic takedown (51.8%), suture with derivative stoma (11.5%), enteral resection and stoma (12%), drainage of the leak (8.9%), stoma on perforation (8.4%), duodenal intubation (7.3%) or intubation of the leak (3.1%). The overall mortality rate was 14%, of which 40% died within the first 48 h. Major complications (Dindo-Clavien > 2) were seen in 47% of the cohort. Stoma formation occurred in 81.6% of patients following relaparotomy. Independent risk factors for mortality were: ASA > 2 (OR = 2.75, 95% CI = 1.07-7.62, p = 0.037), multiorgan failure (MOF) (OR = 5.22, 95% CI = 2.11-13.5, p = 0.0037), perioperative transfusion (OR = 2.7, 95% CI = 1.05-7.47, p = 0.04) and upper GI origin (OR = 3.55, 95% CI = 1.32-9.56, p = 0.013). Independent risk factors for morbidity were: MOF (OR = 2.74, 95% CI = 1.26-6.19, p = 0.013), upper GI origin (OR = 3.74, 95% CI = 1.59-9.44, p = 0.0034) and delayed extubation (OR = 0.27, 95% CI = 0.14-0.55, p = 0.0027). CONCLUSION: Mortality following POP remains a significant issue; however, it is decreasing due to effective and aggressive surgical intervention. Predictors of poor outcomes will help tailor management options.

Surgical management of abdominal desmoids: a systematic review and meta-analysis.

BACKGROUND: Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically but more commonly are associated with genetic syndromes such as familial adenomatous polyposis (Sakorafas et al. in Surg Oncol 16(2):131-142, 2007) (FAP). Mutations in either the Wnt, ß-catenin or APC genes are 'key' triggers for the development of these tumours (Howard and Pollock in Oncol Ther 4(1):57-72, 2016). Classically, these tumours do not metastasise; however, they are associated with significant morbidity and mortality due to their infiltrative pattern and/or local invasion. Historically, surgical resection was the cornerstone of treatment. There remains paucity of data regarding outcomes following the surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity. OBJECTIVES: The aim of this review was to assess the current evidence for surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity. METHODS: A systematic search of articles in PubMed, EMBASE and The Cochrane Library databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the period from January 2000 to November 2020. RESULTS: Twenty-three studies were included, of which, 749 patients had surgical resection (696 for primary and 53 for recurrent desmoids), 243 patients (18.8%) were medically managed and 353 patients (27.3%) underwent surveillance. Median follow-up was 51.4 months (range 1-372). Six-hundred and ninety-six of the 749 resections (92.9%) underwent primary desmoid resection, with the remaining 53 (7.1%) undergoing resection for recurrence. One-hundred and two surgically managed patients (19%) developed a (re)recurrence, with mesenteric involvement the commonest site for recurrence (55%). When comparing recurrence post-surgery to progression following medical therapy, there was a trend towards better outcomes with surgery, with 25% of surgical patients having a recurrence versus 50.5% having progression with medical therapy [OR 0.40 (95% CI 0.06-2.70), p = 0.35]. Major morbidity following surgery was 4.4% (n = 33) with 2% (n = 14) mortality within 30 days of resection. CONCLUSION: The management of desmoids has considerable heterogeneity. Surgical resection for abdominal desmoids remains a valid treatment option in highly selective cases where negative margins can be obtained, with low major morbidity and/or mortality.

Mechanical bowel preparation and antibiotics in elective colorectal surgery: network meta-analysis.

BACKGROUND: The use of intravenous antibiotics at anaesthetic induction in colorectal surgery is the standard of care. However, the role of mechanical bowel preparation, enemas, and oral antibiotics in surgical site infection, anastomotic leak, and other perioperative outcomes remains controversial. The aim of this study was to determine the optimal preoperative bowel preparation strategy in elective colorectal surgery. METHODS: A systematic review and network meta-analysis of RCTs was performed with searches from PubMed/MEDLINE, Scopus, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 2022. Primary outcomes included surgical site infection and anastomotic leak. Secondary outcomes included 30-day mortality rate, ileus, length of stay, return to theatre, other infections, and side effects of antibiotic therapy or bowel preparation. RESULTS: Sixty RCTs involving 16 314 patients were included in the final analysis: 3465 (21.2 per cent) had intravenous antibiotics alone, 5268 (32.3 per cent) had intravenous antibiotics + mechanical bowel preparation, 1710 (10.5 per cent) had intravenous antibiotics + oral antibiotics, 4183 (25.6 per cent) had intravenous antibiotics + oral antibiotics + mechanical bowel preparation, 262 (1.6 per cent) had intravenous antibiotics + enemas, and 1426 (8.7 per cent) had oral antibiotics + mechanical bowel preparation. With intravenous antibiotics as a baseline comparator, network meta-analysis demonstrated a significant reduction in total surgical site infection risk with intravenous antibiotics + oral antibiotics (OR 0.47 (95 per cent c.i. 0.32 to 0.68)) and intravenous antibiotics + oral antibiotics + mechanical bowel preparation (OR 0.55 (95 per cent c.i. 0.40 to 0.76)), whereas oral antibiotics + mechanical bowel preparation resulted in a higher surgical site infection rate compared with intravenous antibiotics alone (OR 1.84 (95 per cent c.i. 1.20 to 2.81)). Anastomotic leak rates were lower with intravenous antibiotics + oral antibiotics (OR 0.63 (95 per cent c.i. 0.44 to 0.90)) and intravenous antibiotics + oral antibiotics + mechanical bowel preparation (OR 0.62 (95 per cent c.i. 0.41 to 0.94)) compared with intravenous antibiotics alone. There was no significant difference in outcomes with mechanical bowel preparation in the absence of intravenous antibiotics and oral antibiotics in the main analysis. CONCLUSION: A bowel preparation strategy with intravenous antibiotics + oral antibiotics, with or without mechanical bowel preparation, should represent the standard of care for patients undergoing elective colorectal surgery.

Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis.

INTRODUCTION: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. RESULTS: 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. CONCLUSION: MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.