Risk factors for emergency surgery for diverticulitis: A retrospective multicentric French study at 41 hospitals.

BACKGROUND: The observed increase in the incidence of complicated diverticulitis may lead to the performance of more emergency surgeries. This study aimed to assess the rate and risk factors of emergency surgery for sigmoid diverticulitis. METHOD: The primary outcomes were the rate of emergency surgery for sigmoid diverticulitis and its associated risk factors. The urgent or elective nature of the surgical intervention was provided by the surgeon and in accordance with the indication for surgical treatment. A mixed logistic regression with a random intercept after multiple imputations by the chained equation was performed to consider the influence of missing data on the results. RESULTS: Between 2010 and 2021, 6,867 patients underwent surgery for sigmoid diverticulitis in the participating centers, of which one-third (n = 2317) were emergency cases. In multivariate regression analysis with multiple imputation by chained equation, increasing age, body mass index <18.5 kg/m2, neurologic and pulmonary comorbidities, use of anticoagulant drugs, immunocompromised status, and first attack of sigmoid diverticulitis were independent risk factors for emergency surgery. The likelihood of emergency surgery was significantly more frequent after national guidelines, which were implemented in 2017, only in patients with a history of sigmoid diverticulitis attacks. CONCLUSION: The present study highlights a high rate (33%) of emergency surgery for sigmoid diverticulitis in France, which was significantly associated with patient features and the first attack of diverticulitis.

Management of adult intestinal stomas: The 2023 French guidelines.

AIM: Digestive stoma are frequently performed. The last French guidelines have been published twenty years ago. Our aim was to update French clinical practice guidelines for the perioperative management of digestive stoma and stoma-related complications. METHODS: A systematic literature review of French and English articles published between January 2000 and May 2022 was performed. Only digestive stoma for fecal evacuation in adults were considered. Stoma in children, urinary stoma, digestive stoma for enteral nutrition, and rare stoma (Koch, perineal) were not included. RESULTS: Guidelines include the surgical landmarks to create digestive stoma (ideal location, mucocutaneous anastomosis, utility of support rods, use of prophylactic mesh), the perioperative clinical practice guidelines (patient education, preoperative ostomy site marking, postoperative equipment, prescriptions, and follow-up), the management of early stoma-related complications (difficulties for nursing, high output, stoma necrosis, retraction, abscess and peristomal skin complications), and the management of late stoma-related complications (stoma prolapse, parastomal hernia, stoma stenosis, late stoma retraction). A level of evidence was assigned to each statement. CONCLUSION: These guidelines will be very useful in clinical practice, and allow to delete some outdated dogma.

Impact of the first wave of COVID-19 epidemy on the surgical management of sigmoid diverticular disease in France: National French retrospective study.

OBJECTIVE: To analyze the surgical management of sigmoid diverticular disease (SDD) before, during, and after the first containment rules (CR) for the first wave of COVID-19. METHODS: From the French Surgical Association multicenter series, this study included all patients operated on between January 2018 and September 2021. Three groups were compared: A (before CR period: 01/01/18-03/16/20), B (CR period: 03/17/20-05/03/20), and C (post CR period: 05/04/20-09/30/21). RESULTS: A total of 1965 patients (A n = 1517, B n = 52, C n = 396) were included. The A group had significantly more previous SDD compared to the two other groups (p = 0.007), especially complicated (p = 0.0004). The rate of peritonitis was significantly higher in the B (46.1%) and C (38.4%) groups compared to the A group (31.7%) (p = 0.034 and p = 0.014). As regards surgical treatment, Hartmann's procedure was more often performed in the B group (44.2%, vs A 25.5% and C 26.8%, p = 0.01). Mortality at 90 days was significantly higher in the B group (9.6%, vs A 4% and C 6.3%, p = 0.034). This difference was also significant between the A and B groups (p = 0.048), as well as between the A and C groups (p = 0.05). There was no significant difference between the three groups in terms of postoperative morbidity. CONCLUSION: This study shows that the management of SDD was impacted by COVID-19 at CR, but also after and until September 2021, both on the initial clinical presentation and on postoperative mortality.

Crossing barriers: the burden of inflammatory bowel disease across Western Europe.

An estimated 2.5-3 million individuals (0.4%) in Europe are affected by inflammatory bowel disease (IBD). Whilst incidence rates for IBD are stabilising across Europe, the prevalence is rising and subsequently resulting in a significant cost to the healthcare system of an estimated 4.6-5.6 billion euros per year. Hospitalisation and surgical resection rates are generally on a downward trend, which is contrary to the rising cost of novel medication. This signifies a large part of healthcare cost and burden. Despite publicly funded healthcare systems in most European countries, there is still wide variation in how patients receive and/or pay for biologic medication. This review will provide an overview and discuss the different healthcare systems within Western Europe and the barriers that affect overall management of a changing IBD landscape, including differences to hospitalisation and surgical rates, access to medication and clinical trial participation and recruitment. This review will also discuss the importance of standardising IBD management to attain high-quality care for all patients with IBD.

Prognostic factors after acute mesenteric ischemia: which patients require specific management?

PURPOSE: Diagnosis and treatment of AMI are a real issue for implicating physicians. In the literature, only one AMI stroke center has reported its results so far, with increasing survival rates. Our aim was to analyze acute mesenteric ischemia (AMI) related mortality and predictive factors, in a single academic center, before creating a dedicated intestinal stroke center. METHODS: All the patients with an AMI, between January 2015 and December 2020, were retrospectively included. They were divided into 2 groups according to the early mortality: death during the first 30 days and alive. The 2 groups were compared. RESULTS: 173 patients (57% of men), were included, with a mean age of 68 ± 16 years. Overall mortality rate was 61%. Mortality occurred within the first 30 days in 78% of dead cases. Dead patients were significantly older, more frequently admitted from intensive care, with more serious clinical, laboratory and radiological characteristics. We have identified 3 protective factors - history of abdominal surgery (Odd Ratio = 0.1; 95%CI = 0.01-0.8, p = 0.03), medical management with curative anticoagulation (OR = 0.09; 95%CI = 0.02-0.5, p = 0.004) and/or antiplatelets (OR = 0.04; 95%CI = 0.006-0.3, p = 0.001)-, and 2 predictive factors of mortality - age > 70 years (OR = 7; 95%CI = 1.4-37, p = 0.02) and previous history of coronaropathy (OR = 13; 95%CI = 1.7-93, p = 0.01). CONCLUSIONS: AMI is a severe disease with high morbidity and mortality rates. Even if its diagnosis is still difficult because of non-specific presentation, its therapeutic management needs to be changed in order to improve survival rates, particularly in patients older than 70 years with history of coronaropathy. Developing a dedicated organization would improve the diagnosis and the management of patients with AMI.

Local excision after neoadjuvant chemoradiotherapy for mid and low rectal cancer: a multicentric French study from the GRECCAR group.

AIM: A complete or subcomplete tumour response (CTR) is observed in 10%-25% of patients with mid/low rectal cancer after neoadjuvant chemoradiotherapy (CRT). The aim of our study was to report a multicentric French experience in local excision (LE) after CRT. METHOD: All patients who underwent LE for mid/low rectal cancer with suspected CTR after CRT, from 2006 to 2019 in seven GRECCAR centres were included. LE was considered adequate if the specimen showed a ypT0/Tis/T1R0 tumour, otherwise, a completion total mesorectal excision (TME) was discussed. Morbi-mortality, functional results and oncological outcomes were studied. RESULTS: A total of 257 patients were included. LE specimens showed 36% ypT0, 4% ypTis and 19% ypT1. Thus, 108 patients (42%) had theoretical indication of completion TME, which was performed in only 42 patients. Overall, 30-day morbidity after LE was 11%, including 2% Clavien-Dindo grade III or IV complications. After completion TME, 47% described major low anterior resection syndrome versus 5% after LE alone (p < 0.001). After a mean follow-up of 4 years (range 2-6 years), the recurrence rate was 11% after LE, 32% after completion TME and 20% in patients for whom completion TME was indicated but not performed (p = 0.021). CONCLUSION: TME remains the gold standard for mid/low rectal cancer after CRT. LE in selected patients is safe for operative and functional, but also oncological, results. However, completion TME was indicated in 42% of patients after LE, highlighting the difficulty of the preoperative diagnosis of CTR after CRT.

Is robotic ventral mesh rectopexy for pelvic floor disorders better than laparoscopic approach at the beginning of the experience? A retrospective single-center study.

PURPOSE: To compare perioperative results of laparoscopic and robotic ventral mesh rectopexy for pelvic floor disorders at the beginning of the surgical experience. METHODS: Between 2017 and 2022, the first 30 laparoscopic ventral mesh rectopexies and the first 30 robotic ventral mesh rectopexies at the beginning of the experience of 2 surgeons were retrospectively analyzed. Perioperative (demographic characteristics, surgical indication, conversion rate, operative time), and postoperative (complications, length of stay, unplanned reintervention) data were compared between groups. RESULTS: Demographic characteristics were similar between groups. Conversion rate was lower (0 vs 17%, p = 0.05), but the operative time was significantly longer (182 [146-290] vs 150 [75-240] minutes, p < 0.0001) during robotic procedure when compared with laparoscopic approach. In terms of learning curve, the number of procedures to obtain the same operative time between the 2 approaches was 15. Postoperative results were similar between groups, in terms of pain (visual analogic scale = 2 [0-8] vs 4 [0-9], p = 0.07), morbidity (17 vs 3%, p = 0.2), and unplanned reintervention (1 vs 0%, p = 0.99). Mean length of stay was significantly reduced after robotic approach when compared with laparoscopic approach (3 [2-10] vs 5 [2-11] days, p < 0.01). Functional results were better after robotic than laparoscopic ventral mesh rectopexy, with higher satisfaction rate (93 vs 75%, p = 0.05), and reduced recurrence rate (0 vs 14%, p = 0.048). CONCLUSION: Despite longer operative time at the beginning of the learning curve, robotic ventral mesh rectopexy was associated with similar or better perioperative results than laparoscopic ventral mesh rectopexy.

Unplanned surgery after colorectal resection: laparoscopy at the index surgery is a protective factor against mortality.

BACKGROUND: The aim of this study was to assess risk factors of mortality after unplanned surgery following colorectal resection. METHODS: All the consecutive patients who underwent colorectal resection between 2011 and 2020 in a French national cohort were retrospectively included. Perioperative data of the index colorectal resection (indication, surgical approach, pathological analysis, postoperative morbidity), and characteristics of unplanned surgery (indication, time to complication, time to surgical redo) were assessed in order to identify predictive factors of mortality. RESULTS: Among 547 included patients, 54 patients died (10%; 32 men; mean age = 68 ± 18 years, range 34-94 years). Patients who died were significantly older (75 ± 11 vs 66 ± 12 years, p = 0.002), frailer (ASA score 3-4 = 65 vs 25%, p = 0.0001), initially operated through open approach (78 vs 41%, p = 0.0001), and without any anastomosis (17 vs 5%, p = 0.003) than those alive. The presence of colorectal cancer, the time to postoperative complication and the time to unplanned surgery were not significantly associated to the postoperative mortality. After multivariate analysis, 5 independent predictive factors of mortality were identified: old age (OR 1.038; IC 95% 1.006-1.072; p = 0.02), ASA score = 3 (OR 5.9, CI95% 1.2-28.5, p = 0.03), ASA score = 4 (OR 9.6; IC95% 1.5-63; p = 0.02), open approach for the index surgery (OR 2.7; IC95% 1.3-5.7; p = 0.01), and delayed management (OR 2.6; IC95% 1.3-5.3; p = 0.009). CONCLUSION: After unplanned surgery following colorectal surgery, one out of 10 patients dies. The laparoscopic approach during the index surgery is associated with a good prognosis in the case of unplanned surgery.

Is Delaying a Coloanal Anastomosis the Ideal Solution for Rectal Surgery?: Analysis of a Multicentric Cohort of 564 Patients From the GRECCAR.

OBJECTIVES: To assess the specific results of delayed coloanal anastomosis (DCAA) in light of its 2 main indications. BACKGROUND: DCAA can be proposed either immediately after a low anterior resection (primary DCAA) or after the failure of a primary pelvic surgery as a salvage procedure (salvage DCAA). METHODS: All patients who underwent DCAA intervention at 30 GRECCAR-affiliated hospitals between 2010 and 2021 were retrospectively included. RESULTS: Five hundred sixty-four patients (male: 63%; median age: 62 years; interquartile range: 53-69) underwent a DCAA: 66% for primary DCAA and 34% for salvage DCAA. Overall morbidity, major morbidity, and mortality were 57%, 30%, and 1.1%, respectively, without any significant differences between primary DCAA and salvage DCAA ( P = 0.933; P = 0.238, and P = 0.410, respectively). Anastomotic leakage was more frequent after salvage DCAA (23%) than after primary DCAA (15%), ( P = 0.016).Fifty-five patients (10%) developed necrosis of the intra-abdominal colon. In multivariate analysis, intra-abdominal colon necrosis was significantly associated with male sex [odds ratio (OR) = 2.67 95% CI: 1.22-6.49; P = 0.020], body mass index >25 (OR = 2.78 95% CI: 1.37-6.00; P = 0.006), and peripheral artery disease (OR = 4.68 95% CI: 1.12-19.1; P = 0.030). The occurrence of this complication was similar between primary DCAA (11%) and salvage DCAA (8%), ( P = 0.289).Preservation of bowel continuity was reached 3 years after DCAA in 74% of the cohort (primary DCAA: 77% vs salvage DCAA: 68%, P = 0.031). Among patients with a DCAA mannered without diverting stoma, 75% (301/403) have never required a stoma at the last follow-up. CONCLUSIONS: DCAA makes it possible to definitively avoid a stoma in 75% of patients when mannered initially without a stoma and to save bowel continuity in 68% of the patients in the setting of failure of primary pelvic surgery.

Iatrogenic ureteral injury during colorectal surgery has a significant impact on patient outcomes: a French multicentric retrospective cohort study.

AIM: The long-term urological sequelae after iatrogenic ureteral injury (IUI) during colorectal surgery are not clearly known. The aims of this work were to report the incidence of IUI and to analyse the long-term consequences of urological late complications and their impact on oncological results of IUI occurring during colorectal surgery through a French multicentric experience (GRECCAR group). METHOD: All the patients who presented with IUI during colorectal surgery between 2010 and 2019 were retrospectively included. Patients with ureteral involvement needing en bloc resection, delayed ureteral stricture or noncolorectal surgery were not considered. RESULTS: A total of 202 patients (93 men, mean age 63 ± 14 years) were identified in 29 centres, corresponding to 0.32% of colorectal surgeries (n = 63 562). Index colorectal surgery was mainly oncological (n = 130, 64%). IUI was diagnosed postoperatively in 112 patients (55%) after a mean delay of 11 ± 9 days. Intraoperative diagnosis of IUI was significantly associated with shorter length of stay (21 ± 22 days vs. 34 ± 22 days, p < 0.0001), lower rates of postoperative hydronephrosis (2% vs. 10%, p = 0.04), anastomotic complication (7% vs. 22.5%, p = 0.002) and thromboembolic event (0% vs. 6%, p = 0.02) than postoperative diagnosis of IUI. Delayed chemotherapy because of IUI was reported in 27% of patients. At the end of the follow-up [3 ± 2.6 years (1 month-13 years)], 72 patients presented with urological sequalae (36%). Six patients (3%) required a nephrectomy. CONCLUSION: IUI during colorectal surgery has few consequences for the patients if recognized early. Long-term urological sequelae can occur in a third of patients. IUI may affect oncological outcomes in colorectal surgery by delaying adjuvant chemotherapy, especially when the ureteral injury is not diagnosed peroperatively.

Supine bottom-up extralevator abdominoperineal excision for anorectal adenocarcinoma is not inferior to standard approach and may be thus safely performed.

BACKGROUND: Extralevator abdominoperineal excision (APE) for rectal carcinoma has been described in order to improve pathological and oncological results compared to standard APE. To obtain the same oncological advantages as extralevator APE, we have previously described a new procedure starting by a perineal approach: the supine bottom-up APE. Our objective is to compare oncological and surgical outcomes between the supine bottom-up APE and the standard APE. METHODS: All patients with low rectal adenocarcinoma requiring APE were retrospectively included and divided into 2 groups: supine bottom-up APE (Group A) and standard APE (Group B). RESULTS: From 2008 to 2016, 61 patients were divided into Groups A (n = 30) and B (n = 31). Postoperative outcomes and median length of stay were similar between groups. Patients from Group A had a significantly longer distal margin (30 [8-120] vs. 20 [1.5-60] mm, p = 0.04) and higher number of harvested lymph nodes (14.5 [0-33] vs. 11 [5-25], p = 0.03) than those from Group B. Circumferential resection margin involvement was similar between groups (28 vs. 22%, p = 0.6), whereas tumors from Group A were significantly larger and more frequently classified as T4 than those from Group B. Operative time was significantly shorter in Group A (437.5 [285-655] minutes) than in Group B (537.5 [361-721] minutes, p = 0.0009). At the end of follow-up, local recurrence occurred in 7 and 16% of patients from Groups A and B (p = 0.68). Three-year overall and disease-free survival rates were similar between groups (87 vs. 90%, p = 0.62 and 61 vs. 63%, p = 0.88, respectively). CONCLUSION: Our findings suggest that supine bottom-up APE doesn't impair surgical outcomes, pathological results, overall and disease-free survivals in comparison with standard APE. This new procedure may be thus safely performed and decrease the operative time. Further randomized multicentric studies are required to confirm these results.

Recurrence of diverticulitis after prophylactic sigmoidectomy: an underestimated problem?

AIM: Several papers have been published about the risk of recurrence after an attack of diverticulitis treated conservatively. However, very few papers have been devoted to the risk of postoperative recurrence of diverticulitis (PRD) after prophylactic sigmoidectomy (PS). The aim of this work was to report the rate of PRD after PS and to assess possible risk factors for recurrence after surgery. METHOD: All consecutive patients who underwent elective laparoscopic PS for diverticulitis between 2005 and 2019 were retrospectively included. PRD was assessed. RESULTS: Three hundred and sixty four patients (199 men, mean age 54 ± 13 years) were included. Among these, 26 (7%) presented with 1.7 ± 1 (range 1-4) episodes of recurrence of diverticulitis after a mean delay of 44 ± 39 months (1 month-11 years) after surgery. Patients who presented with postoperative recurrence of diverticulitis were younger (46 ± 11 vs. 55 ± 13 years, p = 0.002) and more frequently had uncomplicated diverticulitis [15/26 (58%) vs. 97/338 (29%), p = 0.002] and more than two previous episodes before PS [17/26 (65%) vs. 132/338 (39%), p = 0.009] than patients without PRD. After multivariate analysis, two independent risk factors for PRD were identified: patients with more than two episodes before PS (OR = 3.3, 95% CI = 1.2-9, p = 0.005) and age < 50 years (OR = 4.5, 95% CI = 2-11, p = 0.001). If both factors were present, recurrence reached 18% (9/51). CONCLUSION: Postoperative recurrence of diverticulitis is rare (7%) after PS for diverticulitis. Some patients (i.e. those with more than two episodes before PS and/or age <50 years) could be exposed to a higher risk of recurrence (up to 18%), making prophylactic surgery questionable in these patients.

Acute mesenteric ischemia: which predictive factors of delayed diagnosis at emergency unit?

PURPOSE: Acute mesenteric ischemia (AMI) is frequently diagnosed late, leading to a poor prognosis. Our aims were to identify predictive factors of delayed diagnosis and to analyze the outcomes of patients with AMI admitted in emergency units. METHODS: All the patients with AMI (2015-2020), in two Emergency units, were retrospectively included. Two groups were defined according to the time of diagnosis between the arrival at emergency unit and the CT scan: ≤ 6 h (early), > 6 h (delayed). RESULTS: 119 patients (mean age = 71 ± 7 years) were included. The patients with a delayed diagnosis (n = 33, 28%) were significantly associated with atypical presentation, including lower rates of abdominal pain (73 vs 89%, p = 0.003), abdominal tenderness (33 vs 43%, p = 0.03), and plasma lactate (4 ± 2 vs 6 ± 7 mmol/l, p = 0.03) when compared with early diagnosis. After multivariate analysis, the absence of abdominal pain was the only independent predictive factor of delayed diagnosis (Odd Ratio = 0.17; 95% CI = 0.03-0.88, p = 0.03). Patients with delayed diagnosis tended to be associated to lower rates of revascularization (9 vs 17%, p = 0.4), higher rates of major surgical morbidity (90 vs 57%, p = 0.1), longer length of stay (16 ± 23 vs 13 ± 15 days, p = 0.4) and, at the end of follow-up, higher rate of short small bowel syndrome (18 vs 7%, p = 0.095). CONCLUSION: AMI is a challenge for emergency physicians. History of patient, physical exam, biological data are not sufficient to diagnose AMI. New biomarkers, and awareness of emergency physicians should improve and accelerate the diagnosis of AMI.

Rectal Artery Embolization for Hemorrhoidal Disease: Anatomy, Evaluation, and Treatment Techniques.

Chronic hemorrhoidal disease is a common anorectal condition that leads to hemorrhoidal hyperplasia, which affects millions of people worldwide and is a significant medical and socioeconomic issue. Rectal bleeding is one of the main chronic symptoms. Recurrent rectal bleeding can alter an individual's quality of life and, more rarely, cause anemia. Pain is less common, occurring only in the event of complications such as congestive exacerbation, external hemorrhoidal thrombosis, or fissures. The most standard treatment involves dietary and hygiene measures, use of phlebotonic drugs, and nonsurgical treatment such as infrared photocoagulation or elastic band ligation. Excisional treatments such as hemorrhoidectomy and hemorrhoidopexy are the reference standards for treatment of hemorrhoidal disease. Embolization of the rectal arteries (ie, emborrhoid) has recently emerged as an effective treatment option, with few reported adverse effects, minimal blood loss, and a same-day hospital procedure. Hemorrhoid embolization is performed by using femoral or radial access. The inferior mesenteric artery and then the superior rectal arteries are catheterized with a microcatheter. Embolization can be performed by using different agents. Studies have shown improvement in symptoms and high technical success rates after treatment. The basic principles of hemorrhoid embolization that must be understood to achieve effective treatment, including those related to patient evaluation, the arterial anatomy, basic embolization, and published results, are reviewed. An invited commentary by Thompson and Kelley is available online. ©RSNA, 2022.

Morbidity of diverting stoma during colorectal surgery for deep infiltrating endometriosis - an observational study.

PURPOSE: To evaluate stoma-related complications after rectal resection and colorectal anastomosis with diverting stoma for deep infiltrating colorectal endometriosis. METHODS: All the consecutive adult women who underwent colorectal resection with low anastomosis and diverting stoma for deep infiltrating endometriosis in one center between 2013 and 2020 were retrospectively included. Stoma-related complications were retrieved during the stoma period and after stoma reversal. RESULTS: 33 patients (mean age = 32 years (±6, range=24-45 years) were included. After the first surgery, overall and surgical morbidities were observed in 42% and 30% of patients, including stoma-related complications in 3 patients (9%): high output (n = 2) and prolapse (n = 1). One patient presented with rectovaginal fistula, requiring several unplanned surgeries. No anastomotic leakage was observed. All the patients underwent stoma reversal, after mean delay of 3 months (±3, range=1-20 months). Overall morbidity after stoma closure occurred in 9 patients (27%), including 1 major morbidity (digestive bleeding). Long-term results were obtained after a mean follow-up of 21 months (±9, range=14-34 months). Four patients presented with hernia at the stoma site (12%). The cumulative rate of stoma-related complications was 45%. CONCLUSION: There is no consensus about the impact of diverting stoma after rectal resection with colorectal anastomosis for deep infiltrating colorectal endometriosis. Stoma-related complications are frequently observed but there are major in only 12% of patients. High risk patients of rectovaginal fistula and/or anastomotic leakage need to be identified to better indicate the diverting stoma, waiting for randomized trials evaluating the real impact of diverting stoma.

Platelet and Cancer-Cell Interactions Modulate Cancer-Associated Thrombosis Risk in Different Cancer Types.

The first cause of death in cancer patients, after tumoral progression itself, is thrombo-embolic disease. This cancer-associated hypercoagulability state is known as Trousseau's syndrome, and the risk for developing thrombotic events differs according to cancer type and stage, as well as within patients. Massive platelet activation by tumor cells is the key mediator of thrombus formation in Trousseau's syndrome. In this literature review, we aimed to compare the interactions between cancer cells and platelets in three different cancer types, with low, medium and high thrombotic risk. We chose oral squamous cell carcinoma for the low-thrombotic-risk, colorectal adenocarcinoma for the medium-thrombotic-risk, and pancreatic carcinoma for the high-thrombotic-risk cancer type. We showcase that understanding these interactions is of the highest importance to find new biomarkers and therapeutic targets for cancer-associated thrombosis.

Neutrophils, Cancer and Thrombosis: The New Bermuda Triangle in Cancer Research.

Spontaneous venous thrombosis is often the first clinical sign of cancer, and it is linked to a worsened survival rate. Traditionally, tumor-cell induced platelet activation has been the main actor studied in cancer-associated-thrombosis. However, platelet involvement alone does not seem to be sufficient to explain this heightened pro-thrombotic state. Neutrophils are emerging as key players in both thrombus generation and cancer progression. Neutrophils can impact thrombosis through the release of pro-inflammatory cytokines and expression of molecules like P-selectin and Tissue Factor (TF) on their membrane and on neutrophil-derived microvesicles. Their role in cancer progression is evidenced by the fact that patients with high blood-neutrophil counts have a worsened prognosis. Tumors can attract neutrophils to the cancer site via pro-inflammatory cytokine secretions and induce a switch to pro-tumoral (or N2) neutrophils, which support metastatic spread and have an immunosuppressive role. They can also expel their nuclear contents to entrap pathogens forming Neutrophil Extracellular Traps (NETs) and can also capture coagulation factors, enhancing the thrombus formation. These NETs are also known to have pro-tumoral effects by supporting the metastatic process. Here, we strived to do a comprehensive literature review of the role of neutrophils as drivers of both cancer-associated thrombosis (CAT) and cancer progression.