The long and winding road to biomarkers for immunotherapy: a retrospective analysis of samples from patients with triple-negative breast cancer treated with pembrolizumab.

BACKGROUND: Immune checkpoint blockade (ICB) in combination with chemotherapy improves outcome of patients with triple-negative breast cancer (TNBC) in metastatic and early settings. The identification of predictive biomarkers able to guide treatment decisions is challenging and currently limited to programmed death-ligand 1 (PD-L1) expression and high tumor mutational burden (TMB) in the advanced setting, with several limitations. MATERIALS AND METHODS: We carried out a retrospective analysis of clinical-pathological and molecular characteristics of tumor samples from 11 patients with advanced TNBC treated with single-agent pembrolizumab participating in two early-phase clinical trials: KEYNOTE-012 and KEYNOTE-086. Clinical, imaging, pathological [i.e. tumor-infiltrating lymphocytes (TILs), PD-L1 status], RNA sequencing, and whole-exome sequencing data were analyzed. We compared our results with publicly available transcriptomic data from TNBC cohorts from TCGA and METABRIC. RESULTS: Response to pembrolizumab was heterogeneous: two patients experienced exceptional long-lasting responses, six rapid progressions, and three relatively slower disease progression. Neither PD-L1 nor stromal TILs were significantly associated with response to treatment. Increased TMB values were observed in tumor samples from exceptional responders compared to the rest of the cohort (P = 3.4 × 10-4). Tumors from exceptional responders were enriched in adaptive and innate immune cell signatures. Expression of regulatory T-cell markers (FOXP3, CCR4, CCR8, TIGIT) was mainly observed in tumors from responders except for glycoprotein-A repetitions predominant (GARP), which was overexpressed in tumors from rapid progressors. GARP RNA expression in primary breast tumors from the public dataset was significantly associated with a worse prognosis. CONCLUSIONS: The wide spectrum of clinical responses to ICB supports that TNBC is a heterogeneous disease. Tumors with high TMB respond better to ICB. However, the optimal cut-off of 10 mutations (mut)/megabase (Mb) may not reflect the complexity of all tumor subtypes, despite its approval as a tumor-agnostic biomarker. Further studies are required to better elucidate the relevance of the tumor microenvironment and its components as potential predictive biomarkers in the context of ICB.

Reduction of red blood cell transfusion with a patient blood management protocol in urological and visceral surgery: a before-after study.

BACKGROUND: Although Patient Blood Management (PBM) is recommended by international guidelines, little evidence of its effectiveness exists in abdominal surgery. The aim of this study was to evaluate the benefits of the implementation of a PBM protocol on transfusion incidence and anaemia-related outcomes in major urological and visceral surgery. METHODS: In this before-after study, a three-pillar PBM protocol was implemented in 2020-2021 in a tertiary care centre, including preoperative correction of iron-deficiency anaemia, intraoperative tranexamic acid administration, and postoperative restrictive transfusion. A historical cohort (2019) was compared to a prospective cohort (2022) after the implementation of the PBM protocol. The primary outcome was the incidence of red blood cell transfusion intraoperatively or within 7 days after surgery. RESULTS: Data from 488 patients in the historical cohort were compared to 499 patients in the prospective cohort. Between 2019 and 2022, screening for iron deficiency increased from 13.9% to 69.8% (p < 0.01), tranexamic acid administration increased from 9.5% to 84.6% (p < 0.01), and median haemoglobin concentration before transfusion decreased from 77 g.L-1 to 71 g.L-1 (p = 0.02). The incidence of red blood cell transfusion decreased from 11.5% in 2019 to 6.6% in 2022 (relative risk 0.58, 95% CI 0.38-0.87, p = 0.01). The incidence of haemoglobin concentration lower than 100 g.L-1 at discharge was 24.2% in 2019 and 21.8% in 2022 (p = 0.41). The incidence of medical complications was comparable between the groups. CONCLUSION: The implementation of a PBM protocol over a two-year period was associated with a reduction of transfusion in major urological and visceral surgery.

Impact of obesity on morbidity and oncologic outcomes after total mesorectal excision for mid and low rectal cancer.

BACKGROUND: A recent meta-analysis showed that obesity increased the conversion rate and postoperative morbidity of rectal cancer surgery, but did not influence pathological results. However, this meta-analysis included patients with cancer of the upper rectum and had many biases. The aim of the present retrospective study was to investigate the impact of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, on postoperative morbidity and short- and long-term oncologic outcomes of total mesorectal excision for mid and low rectal cancer in consecutive patients. METHODS: This study included all eligible patients who were operated on for mid and lower rectal cancer between 1999 and 2018 in our hospital. We compared 90-day postoperative morbidity and mortality, and short- and long-term oncologic outcomes between obese and non-obese patients. RESULTS: Three hundred and ninety patients [280 males, mean age 65.7 ± 11.3 years, 59 obese individuals (15.1%)] were included. There was no difference in the 90-day mortality rate between obese and non-obese groups (p = 0.068). There was a difference in the overall 90-day morbidity rate between the obese and non-obese groups that disappeared after propensity score matching of the patients. There was no difference in short-term oncological parameters, with a median follow-up of 43 (20-84) months, and there were no significant differences in disease-free and overall survival between obese and non-obese patients (p = 0.42 and p = 0.11, respectively). CONCLUSIONS: Obesity does not affect the 90-day morbidity rate, or short- and long-term oncologic results in patients operated on for mid and lower rectal cancer.

Experimental characterisation and modelling of breast Cooper's ligaments.

The aim of this study was to characterise the mechanical behaviour of Cooper's ligaments. Such ligaments are collagenous breast tissue that create a three-dimensional structure over the entire breast volume. Ten ligaments were extracted from a human cadaver, from which 28 samples were cut and used to perform uniaxial tensile tests. Histological analysis showed that the main direction of the fibres visible to the naked eye corresponds to the orientation of the fibres on a microscopic scale. The specimens were cut according to this orientation, which allowed the sample to be stretched in the main fibre direction. From these experimental stretch/stress curves, an original anisotropic hyperelastic constitutive law is proposed to model the behaviour of Cooper's ligaments and the material parameter validity is discussed.

Tumor BRCA testing can reveal a high tumor mutational burden related to POLE pathogenic variants.

OBJECTIVE: Tumors harboring a POLE pathogenic variant, associated with high tumor mutational burden, are good candidates for immunotherapy. However, POLE pathogenic variants are not currently screened in routine clinical practice. Can these tumors be identified by means of an already available test? METHODS: We describe seven tumors harboring a POLE pathogenic variant, among eight patients with tumors harboring multiple BRCA1/2 variants (from 4 to 20). All patients were managed at Institut Curie, Paris. Five patients were selected because of unexpected tumor BRCA testing results with multiple variants and another three patients were selected because of a POLE pathogenic variant detected by large tumor testing. We looked for other tumor variants by Next-Generation Sequencing in tumors harboring multiple BRCA1/2 variants, and for multiple BRCA1/2 variants in tumors harboring a POLE pathogenic variant. RESULTS: Four of the five tumors selected because of multiple BRCA1/2 variants exhibited a POLE pathogenic variant, and all three tumors selected for POLE pathogenic variants exhibited multiple BRCA1/2 variants. CONCLUSIONS: Tumor BRCA testing could be a way to detect tumors harboring a highly mutagenic POLE pathogenic variant.

Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery.

BACKGROUND: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. PATIENTS AND METHODS: One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. RESULTS: Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-ß pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis. CONCLUSION: Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.

Laparoscopic segmental left colectomy for splenic flexure carcinoma: a single institution experience.

BACKGROUND: There is ongoing debate regarding surgical treatment of splenic flexure cancer. The main points of controversy include the appropriate extent of colon resection, either to the right or to the left, and the appropriate extent of lymph-node dissection. The aim of this study was to review our experience in laparoscopic treatment of splenic flexure cancer cases and to compare our data to the recent literature. METHODS: Consecutive patients, operated on for splenic flexure colon carcinoma at a single institution between April 2005 and January 2013, were included in the study. Exclusion criteria were a previous history of colorectal cancer, recurrent colonic cancer, emergency cases with an obstructive tumor or a perforated tumor with peritonitis, synchronous cancer, palliative surgery, and a past history of colorectal resection. Patients underwent laparoscopic segmental left colectomy with ligation of the left branch of the middle colic and of the left colic artery. Patient characteristics, operative and postoperative outcomes, and long-term technical, functional, and oncological results from a prospectively maintained database were retrospectively analyzed. After hospital discharge, standardized follow-up was performed at 1 month postoperatively, then every 3 months during the first 2 years, and every 6 months thereafter, for a total of 5 years. RESULTS: A total of 28 consecutive patients (16 males) with a median age of 71.8 years (range 42.5-88.8 years) were included. Ninety-day mortality was 3.5% and surgical morbidity was 21.5% with anastomotic leak rate of 10.7%. All survivors experienced good or very good functional results. During a median follow-up period of 50.9 months, eight patients (28.5%) presented with a recurrence. The 5-year overall and disease-free survival rates were 46.3% and 39.2%, respectively. CONCLUSIONS: Segmental left colectomy for splenic flexure carcinoma is associated with reasonably low morbidity and very good functional results. However, survival rates are low.

Prospective evaluation of functional outcomes after laparoscopic sigmoidectomy with high tie of the inferior mesenteric artery for diverticular disease in consecutive male patients.

BACKGROUND: To date, there has been no consensus concerning the vascular approach during sigmoid colectomy for diverticular disease. The aim of this study was to determine the functional impact of elective laparoscopic sigmoidectomy performed with high ligation of the inferior mesenteric artery for diverticulitis in consecutive male patients. METHODS: Twenty-five consecutive patients of median age 53 years were enrolled in a prospective single-centre pilot study at a tertiary teaching hospital. Main outcome measures were functional results. Patients were asked to complete standardized, validated questionnaires to evaluate preoperative and 6 months postoperative bowel symptomatology (Jorge-Wexner Incontinence Score and KESS score), urinary function (IPSS), and sexual function (IIEF). Secondary outcomes were surgical data, morbidity, and quality of life (SF-36). RESULTS: There were no significant differences between preoperative and 6 months postoperative total scores for bowel symptomatology, urinary function, and sexual function. There were no perioperative deaths. The morbidity rate was 12% including three minor and no major events. Quality of life demonstrated statistically better general health (p < 0.01) and better medical status over the prior 4 weeks at 6 months after surgery, compared to baseline. This single-centre prospective study has a limited number of patients, relatively short follow-up time, and includes only male patients. CONCLUSION: Laparoscopic sigmoidectomy with high tie of the inferior mesenteric artery for diverticular disease does not induce functional disorders at 6 months after surgery. The benefit of the operation for quality of life is even greater for general health and medical status.

Biomechanical behaviour of human bile duct wall and impact of cadaveric preservation processes.

Biliary diseases are the third most common cause of surgical digestive disease. There is a close relationship between the mechanical performance of the bile duct and its physiological function. Data of biomechanical properties of human main bile duct are scarce in literature. Furthermore, mechanical properties of soft tissues are affected by these preservation procedures. The aim of the present work was, on the one hand, to observe the microstructure of the human bile duct by means of histological analysis, on the other hand, to characterize the mechanical behavior and describe the impact of different preservation processes. A mechanical study in a controlled environment consisting of cyclic tests was made. The results of the mechanical tests are discussed and explained using the micro-structural observations. The results show an influence of the loading direction, which is representative of an anisotropic behavior. A strong hysteresis due to the viscoelastic properties of soft tissues was also observed. Embalming and freezing preservation methods had an impact on the biomechanical properties of human main bile duct, with fiber network deterioration. That may further provide a useful quantitative baseline for anatomical and surgical training using embalming and freezing.

Level of inferior mesenteric artery ligation in low rectal cancer surgery: high tie preferred over low tie.

BACKGROUND: There is no demonstrated benefit of high-tie versus low-tie vascular transections in low rectal cancer surgery. The aim of this study was to compare the effects of high tie and low tie of the inferior mesenteric artery on colonic length. METHODS: This study was conducted in a surgical anatomy research laboratory. Anatomical dissections were performed on 11 human cadavers. We performed full left colonic mobilization, section of the descending-sigmoid junction, and high and low ligation of the inferior mesenteric artery. Distance from the proximal colon limb to the lower edge of the pubis symphysis was recorded after each step of vascular division. Three measurements were successively performed: before vascular section, after inferior mesenteric artery ligation, and after inferior mesenteric artery and vein section. RESULTS: Before vascular section, the mean distance between colonic end and lower edge of the symphysis pubis was - 1.9 ± 3.5 cm. After combined artery and vein section, the mean distance was + 10.7 ± 4.6 cm for high tie and + 1.5 ± 3 cm for low tie. A limitation of this study is the use of embalmed anatomical specimens, rather than live patients, and the small number of specimens. This study also does not evaluate colon limb vascularization or the impact of proximal lymph node dissection on survival rates. CONCLUSIONS: High tie of the inferior mesenteric artery at its aortic origin allows a gain of extra length of about 9 cm over low tie.

Preventable deaths in a French regional trauma system: A six-year analysis of severe trauma mortality.

BACKGROUND: Analyzing mortality in a mature trauma system is useful to improve quality of care of severe trauma patients. Standardization of error reporting can be done using the classification of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO). The aim of our study was to describe preventable deaths in our trauma system and to classify errors according to the JCAHO taxonomy. METHODS: We performed a six-year retrospective study using the registry of the Northern French Alps trauma network (TRENAU). Consecutive patients who died in the prehospital field or within their stay at hospital were included. An adjudication committee analyzed deaths to identify preventable or potentially preventable deaths from 2009 to 2014. All errors were classified using the JCAHO taxonomy. RESULTS: Within the study period, 503 deaths were reported among 7484 consecutive severe trauma patients (overall mortality equal to 6.7%). Seventy-two (14%) deaths were judged as potentially preventable and 36 (7%) deaths as preventable. Using the JACHO taxonomy, 170 errors were reported. These errors were detected both in the prehospital setting and in the hospital phase. Most were related to clinical performance of physicians and consisted of rule-based or knowledge based failures. Prevention or mitigation of errors required an improvement of communication among caregivers. CONCLUSIONS: Standardization of error reporting is the first step to improve the efficiency of trauma systems. Preventable deaths are frequently related to clinical performance in the early phase of trauma management. Universal strategies are necessary to prevent or mitigate these errors.

Laparoscopic delayed coloanal anastomosis without diverting ileostomy for low rectal cancer surgery: 85 consecutive patients from a single institution.

BACKGROUND: Surgical treatment for low rectal cancer septic complications often requires an ileostomy for fecal diversion. Delayed coloanal anastomosis (CAA) has been performed for several years to reduce septic complications and to avoid ileostomy. The aim of this study was to report the technical, functional and oncological results of delayed CAA in patients operated on for low rectal cancer focusing on pelvic septic complications. METHODS: All consecutive patients operated on for low rectal cancer suitable for total mesorectal excision and two-step delayed CAA at a single institution between May 2000 and September 2013 were included in the study. Patients' characteristics, operative and postoperative outcomes, long-term technical, functional and oncological results from a prospectively maintained database, were retrospectively analyzed. RESULTS: A total of 85 consecutive patients (69 men), of median age 63 years (range 42-83 years) were included. Median delay between the first and the second step of the operation was 6 days (range 2-13 days). Twenty-one patients (25%) developed pelvic sepsis, nine of them (10.6%) developed an anastomotic leak. Twenty-three patients had a definitive stoma at the end of follow-up. Seventeen patients (29%) experienced a poor functional result. Thirty-three patients (38%) presented with recurrence at a median follow-up of 59 months (range 12-135 months). Seven (8.2%) developed a local recurrence, 18 a distant metastasis (21.1%) and 8 (9.4%) both a local and distant recurrence. CONCLUSIONS: In our series, laparoscopic total mesorectal excision with delayed coloanal anastomosis was associated with septic complications and oncologic results similar to those reported after total mesorectal excision with conventional anastomosis and ileostomy, nearly one-third of patients experience a poor functional result. A randomized trial comparing these two options for low rectal cancer is under way.

Experimental characterization and constitutive modeling of the biomechanical behavior of male human urethral tissues validated by histological observations.

This work aims at observing the mechanical behavior of the membranous and spongy portions of urethrae sampled on male cadavers in compliance with French regulations on postmortem testing, in accordance with the Scientific Council of body donation center of Grenoble. In this perspective, a thermostatic water tank was designed to conduct ex vivo planar tension tests in a physiological environment, i.e., in a saline solution at a temperature of [Formula: see text] [Formula: see text]. In order to observe the anisotropy of the tissues, the samples were tested in two directions. Tests consisting of a series of load-unload cycles of increasing amplitudes were performed to highlight their viscous behavior. The results were then discussed according to the microstructure of tissue, which was investigated using different staining methods and histological analysis. The observed behaviors were then fitted using an anisotropic hyperelastic or a visco-hyperelastic matrix-fiber model.

Management of splenic and pancreatic trauma.

The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non-operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early.

Management of pancreatic trauma.

INTRODUCTION: Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. MATERIAL AND METHODS: Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. RESULTS: Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. CONCLUSION: In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions.

Mechanical behaviour׳s evolution of a PLA-b-PEG-b-PLA triblock copolymer during hydrolytic degradation.

PLA-b-PEG-b-PLA is a biodegradable triblock copolymer that presents both the mechanical properties of PLA and the hydrophilicity of PEG. In this paper, physical and mechanical properties of PLA-b-PEG-b-PLA are studied during in vitro degradation. The degradation process leads to a mass loss, a decrease of number average molecular weight and an increase of dispersity index. Mechanical experiments are made in a specific experimental set-up designed to create an environment close to in vivo conditions. The viscoelastic behaviour of the material is studied during the degradation. Finally, the mechanical behaviour is modelled with a linear viscoelastic model. A degradation variable is defined and included in the model to describe the hydrolytic degradation. This variable is linked to physical parameters of the macromolecular polymer network. The model allows us to describe weak deformations but become less accurate for larger deformations. The abilities and limits of the model are discussed.

TET peptidases: A family of tetrahedral complexes conserved in prokaryotes.

The TET peptidases are large polypeptide destruction machines present among prokaryotes. They form 12-subunits hollow tetrahedral particles, and belong to the family of M42 metallo-peptidases. Structural characterization of various archaeal and bacterial complexes has revealed a unique mechanism of internal compartmentalization and peptide trafficking that distinguishes them from the other oligomeric peptidases. Different versions of the TET complex often co-exist in the cytosol of microorganisms. In depth enzymatic studies have revealed that they are non-processive cobalt-activated aminopeptidases and display contrasting substrate specificities based on the properties of the catalytic chambers. Recent studies have shed light on the assembly mechanism of homo and hetero-dodecameric TET complexes and shown that the activity of TET aminopeptidase towards polypeptides is coupled with its assembly process. These findings suggested a functional regulation based on oligomerization control in vivo. This review describes a current knowledge on M42 TET peptidases biochemistry and discuss their possible physiological roles. This article is a part of the Special Issue entitled: «A potpourri of proteases and inhibitors: from molecular toolboxes to signalling scissors¼.

Anastomotic leakage after gastrointestinal surgery: diagnosis and management.

Anastomotic leakage represents a major complication of gastrointestinal surgery, leading to increased postoperative morbidity; it the foremost cause of mortality after intestinal resection. Identification of risk factors is essential for the prevention of AL. AL can present with various clinical pictures, ranging from the absence of symptoms to life-threatening septic shock. Contrast-enhanced CT scan is the most complete investigation to define AL and its consequences. Early and optimal multidisciplinary management is based on three options: medical management, radiologic or endoscopic intervention, or surgical re-intervention. Prompt treatment should help decrease postoperative morbidity and mortality, with the choice depending on the septic status of the patient. If the patient is asymptomatic, treatment can be medical only, coupled with close surveillance. Interventional management is indicated when the fistula is symptomatic but not life-threatening. On the other hand, when the vital prognosis is engaged, surgery is indicated, emergently, associated with intensive care. Even more than their prevention, early and appropriate management counts most to decrease their consequences.