Bowel preparation for elective colorectal resection: multi-treatment machine learning analysis on 6241 cases from a prospective Italian cohort.

BACKGROUND: Current evidence concerning bowel preparation before elective colorectal surgery is still controversial. This study aimed to compare the incidence of anastomotic leakage (AL), surgical site infections (SSIs), and overall morbidity (any adverse event, OM) after elective colorectal surgery using four different types of bowel preparation. METHODS: A prospective database gathered among 78 Italian surgical centers in two prospective studies, including 6241 patients who underwent elective colorectal resection with anastomosis for malignant or benign disease, was re-analyzed through a multi-treatment machine-learning model considering no bowel preparation (NBP; No. = 3742; 60.0%) as the reference treatment arm, compared to oral antibiotics alone (oA; No. = 406; 6.5%), mechanical bowel preparation alone (MBP; No. = 1486; 23.8%), or in combination with oAB (MoABP; No. = 607; 9.7%). Twenty covariates related to biometric data, surgical procedures, perioperative management, and hospital/center data potentially affecting outcomes were included and balanced into the model. The primary endpoints were AL, SSIs, and OM. All the results were reported as odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Compared to NBP, MBP showed significantly higher AL risk (OR 1.82; 95% CI 1.23-2.71; p = .003) and OM risk (OR 1.38; 95% CI 1.10-1.72; p = .005), no significant differences for all the endpoints were recorded in the oA group, whereas MoABP showed a significantly reduced SSI risk (OR 0.45; 95% CI 0.25-0.79; p = .008). CONCLUSIONS: MoABP significantly reduced the SSI risk after elective colorectal surgery, therefore representing a valid alternative to NBP.

Abdominal drainage after elective colorectal surgery: propensity score-matched retrospective analysis of an Italian cohort.

BACKGROUND: In Italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. The aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery. METHODS: A database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. The primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. The results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i. RESULTS: A total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). Group A versus group B showed a significantly lower risk of postoperative duration of stay >6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P < 0.001). A mean postoperative duration of stay difference of 0.86 days was detected between groups. No difference was recorded between the two groups for all the other endpoints. CONCLUSION: This study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery.

Mechanical bowel preparation in elective colorectal surgery: a propensity score-matched analysis of the Italian colorectal anastomotic leakage (iCral) study group prospective cohorts.

Retrospective evaluation of the effects of mechanical bowel preparation (MBP) on data derived from two prospective open-label observational multicenter studies in Italy regarding elective colorectal surgery. MBP for elective colorectal surgery remains a controversial issue with contrasting recommendations in current guidelines. The Italian ColoRectal Anastomotic Leakage (iCral) study group, therefore, decided to estimate the effects of no MBP (treatment variable) versus MBP for elective colorectal surgery. A total of 8359 patients who underwent colorectal resection with anastomosis were enrolled in two consecutive prospective studies in 78 surgical centers in Italy from January 2019 to September 2021. A retrospective PSMA was performed on 5455 (65.3%) cases after the application of explicit exclusion criteria to eliminate confounders. The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSI) rates; the secondary endpoints included SSI subgroups, overall and major morbidity, reoperation, and mortality rates. Overall length of postoperative hospital stay (LOS) was also considered. Two well-balanced groups of 1125 patients each were generated: group A (No MBP, true population of interest), and group B (MBP, control population), performing a PSMA considering 21 covariates. Group A vs. group B resulted significantly associated with a lower risk of AL [42 (3.5%) vs. 73 (6.0%) events; OR 0.57; 95% CI 0.38-0.84; p = 0.005]. No difference was recorded between the two groups for SSI [73 (6.0%) vs. 85 (7.0%) events; OR 0.88; 95% CI 0.63-1.22; p = 0.441]. Regarding the secondary endpoints, no MBP resulted significantly associated with a lower risk of reoperation and LOS > 6 days. This study confirms that no MBP before elective colorectal surgery is significantly associated with a lower risk of AL, reoperation rate, and LOS < 6 days when compared with MBP.

End-to-end invaginated pancreaticojejunostomy during minimally invasive pancreatoduodenectomy: technical description and single center experience.

BACKGROUND: Remarkable progress has been made in pancreatic surgery over the last decades with the introduction of minimally invasive techniques. Minimally invasive pancreatoduodenectomy (MIPD) remains one of the most challenging operations in abdominal surgery and it is performed in a few centers worldwide. The treatment of the pancreatic stump is a crucial step of this operation; however, the best strategy to perform pancreatic anastomosis is still debated. In this article, we describe the technical details of our original technique of modified minimally invasive end-to-end invaginated pancreaticojejunostomy (EIPJ) using video footage. METHODS: In the current study, we retrospectively analyzed a pilot series of 67 consecutive cases of minimally invasive (7 robotic/60 fully laparoscopic) MIPD operated on at the General Surgery Department of the Panico Hospital, Tricase (Italy) between March 2017 and October 2022.The reconstruction phase involved an EIPJ, tailored using an intra-ductal anastomotic plastic stent. The aim of this study was to describe the technique and evaluate the short-term outcomes of patients undergoing MIPD with EIPJ. RESULTS: The mean operative time to perform the EIPJ was 21.57 ± 3.32 min. Seven patients (10.5%) developed biochemical leaks and 13 (19.4%) developed clinically relevant pancreatic fistulas (grade B or C according to the definition of the International Study Group on Pancreatic Surgery). CONCLUSION: The early results confirm that this anastomosis is safe, easy to perform, and effective in the hands of hepatobiliopancreatic (HBP) surgeons with experience in minimally invasive surgery.

Inframesocolic main pancreatic vessels-first approach for minimally invasive radical antegrade modular pancreaticosplenectomy (RAMPS): technical description and first experience.

Radical modular antegrade pancreaticosplenectomy (RAMPS) improves posterior tumor-free margins during resections of pancreatic neoplasia involving the body or tail. However, minimally invasive RAMPS is technically challenging and has been reported seldom. We present for the first time a minimally invasive RAMPS technique with an innovative approach providing early dissection and control of the main peripancreatic vessels from an inframesocolic embryonal window, suitable for laparoscopy and robotics. Minimally invasive RAMPS with inframesocolic main pancreatic vessels-first approach was performed at the Tricase Hospital (Italy) from May 2017 to April 2022 in 11 consecutive patients with neoplastic lesions of the pancreas (8 laparoscopic RAMPS and 3 robotic RAMPS). Among the laparoscopic cases, 1 included a portal vein tangential resection and 1 a celiac artery resection (modified Appleby procedure). There were no conversions, no Clavien-Dindo complications > 2, all resections' margins were tumor free, and no 90-day mortality.

Impact of Oocyte Extract Supplement on Quality of Life after Hepatectomy for Liver Tumours: A Prospective, Multicentre, Double-Blind Randomized Clinical Trial.

BACKGROUND: Previous studies on oocyte extract supplementation showed benefits in patients with liver tumours. In this trial, we hypothesized that the oocyte extract supplement impacted the QoL after hepatectomy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: This was a multicentre, double-blind, randomized clinical trial designed to assess the QoL of patients receiving a supplement of oocyte extract or placebo postoperatively. QoL was assessed using the Short Form-36 questionnaire in participants randomly assigned to treatment (Synchrolevels) or placebo. All study personnel and participants were masked to treatment assignment. The endpoint was the change in the QoL score. RESULTS: Between June 2018 and September 2022, 66 of 128 expected patients were considered as per interim analysis, of which 33 were assigned to the treatment and 33 to the placebo group. Baseline and clinicopathological characteristics were similar between the two groups. In the treatment group, the health, mental and psychological status improved for many of the items considered, reaching statistical significance, while in the placebo group, those items either did not change or were impaired in comparison with the corresponding baseline. CONCLUSIONS: Supplementation with oocyte extract modifies QoL after liver surgery by enhancing functional recovery. Further in-depth studies are required to confirm this evidence.

Outcomes and Complications of Duodenopancreatectomy in Octogenarian Patients: a Review.

Background: Duodenopancreatectomy is a surgical procedure that involves the removal of part of the pancreas, duodenum, and bile ducts. This procedure is commonly performed in patients with pancreatic cancer or other gastrointestinal disorders. However, the safety and efficacy of duodenopancreatectomy in older adults (octogenarians) remain unclear. Objectives:The goal of this review is to assess the outcomes and complications of duodenopancreatectomy in octogenarian patients. Methods:A systematic search of relevant literature was conducted using PubMed, Embase and the Cochrane Library databases. Studies reporting the outcomes and complications of duodenopancreatectomy in octogenarian patients were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Egger's test was used to evaluate publication bias. Results:A total of 14 studies were included in this review. The outcomes of duodenopancreatectomy in octogenarian patients were generally favorable, with a median 30-day mortality rate of 3.5% (range 0-16.7%). The most common complications were pancreatic fistula (12.2%), delayed gastric emptying (6.3%) and wound infection (5.5%). The overall long-term survival rate of octogenarian patients after duodenopancreatectomy was 21.2%. Conclusions:Duodenopancreatectomy can be safely performed in carefully selected octogenarian patients with good outcomes. However, this procedure is associated with a high risk of complications, particularly pancreatic fistula, in this age group.

Image-guided techniques for localization of pulmonary nodules during video-assisted thoracoscopic surgery lobectomy.

In the modern era when screening and early surveillance of pulmonary nodules are increasing in importance, the management of the pulmonary nodule represents a different challenge to thoracic surgeons. The difficulty lies in the merging of sound surgical and oncological principles with more minimally invasive and appropriate lung-sparing surgery. The success rates of video-assisted thoracoscopic surgery (VATS) resection for smaller as well as subsolid nodules have increased as a result of radiologists' preoperative localization tools. Fast tracking in thoracic surgery is promoted by proper postoperative care for patients having lobectomies in combination with the VATS technique. Image-guided surgery refers to the application of a real-time correlation of the surgical field to preoperative imaging data collection that reflects the precise placement of a chosen surgical instrument in the adjacent anatomic structures. Among the cross-sectional digital imaging techniques the most widely utilized imaging modalities for image-guided therapy are computed tomography and magnetic resonance imaging. Additionally, surgical navigation devices, tracking tools, integration software, ultrasound, and angiography are used to support these procedures. For people who are thinking about implementing or optimizing a nodule localization program in view of workflow patterns, surgeon preferences, and institutional resources in a certain facility, this review provides in-depth, unbiased evaluation and offers useful information.

One-stage approach to cholecystocholedocholithiasis treatment: a feasible surgical strategy for emergency settings and frail patients.

BACKGROUND: Cholecystocholedocholithiasis (CCL) occurs in up to 18% of patients undergoing laparoscopic cholecystectomy (LC). The two-stage treatment using endoscopic retrograde cholangiopancreatography (ERCP) followed by LC is the treatment of choice for CCL. However, only 10 to 60% of patients have common bile duct (CBD) stones at the time of ERCP, thus exposing patients to unnecessary ERCPs, causing 3 to 15% of post-interventional pancreatitis. One-stage laparoscopic-endoscopic rendezvous (LERV) is an alternative for the treatment of CCL. Given the selective top-to-bottom CBD cannulation, LERV reduces the risk of pancreatitis and failed CBD cannulation. Additionally, LERV is performed exclusively in patients presenting CBD stones at intraoperative cholangiography, avoiding unnecessary ERCPs. Despite its advantages, considering the logistical burden of coordinating different specialties, LERV is performed in few centers. Here, we present the largest retrospective series of LERVs performed at our department, analyzing elective and emergency procedures. METHODS: All consecutive patients undergoing LERV for CCL between January 2014 and December 2021 were included. LERV success rate, operative time, biliary outflow restoration rate, postoperative complications (POC), length of hospital stay (LOS), and recurrences were analyzed. RESULTS: 181 patients were included (61 elective LERVs, 120 emergency LERVs). We reported a 100% LERV success rate, a 97.79% biliary outflow restoration rate, a 0% conversion rate, a mean intraoperative time of 120.17 ± 31.35 min, and LOS of 4.00 ± 2.82 days. POC included 7 Clavien-Dindo type 1, 11 type 2, and 3 type 3 cases. Seven patients presented with CBD stone recurrence: 2 within 30 days after discharge, 3 within 6 months after discharge, and 2 patients at 1 year. No statistically significant difference was found between elective and emergency patients. CONCLUSION: LERV is safe, representing a valid option even in emergency settings, thus enabling the management of CCL within a single procedure, consequently sparing additional anesthesia and decreasing post-ERCP complications.

Automatic optical biopsy for colorectal cancer using hyperspectral imaging and artificial neural networks.

BACKGROUND: Intraoperative identification of cancerous tissue is fundamental during oncological surgical or endoscopic procedures. This relies on visual assessment supported by histopathological evaluation, implying a longer operative time. Hyperspectral imaging (HSI), a contrast-free and contactless imaging technology, provides spatially resolved spectroscopic analysis, with the potential to differentiate tissue at a cellular level. However, HSI produces "big data", which is impossible to directly interpret by clinicians. We hypothesize that advanced machine learning algorithms (convolutional neural networks-CNNs) can accurately detect colorectal cancer in HSI data. METHODS: In 34 patients undergoing colorectal resections for cancer, immediately after extraction, the specimen was opened, the tumor-bearing section was exposed and imaged using HSI. Cancer and normal mucosa were categorized from histopathology. A state-of-the-art CNN was developed to automatically detect regions of colorectal cancer in a hyperspectral image. Accuracy was validated with three levels of cross-validation (twofold, fivefold, and 15-fold). RESULTS: 32 patients had colorectal adenocarcinomas confirmed by histopathology (9 left, 11 right, 4 transverse colon, and 9 rectum). 6 patients had a local initial stage (T1-2) and 26 had a local advanced stage (T3-4). The cancer detection performance of the CNN using 15-fold cross-validation showed high sensitivity and specificity (87% and 90%, respectively) and a ROC-AUC score of 0.95 (considered outstanding). In the T1-2 group, the sensitivity and specificity were 89% and 90%, respectively, and in the T3-4 group, the sensitivity and specificity were 81% and 93%, respectively. CONCLUSIONS: Automatic colorectal cancer detection on fresh specimens using HSI, using a properly trained CNN is feasible and accurate, even with small datasets, regardless of the local tumor extension. In the near future, this approach may become a useful intraoperative tool during oncological endoscopic and surgical procedures, and may result in precise and non-destructive optical biopsies to support objective and consistent tumor-free resection margins.

Intraoperative bowel perfusion quantification with hyperspectral imaging: a guidance tool for precision colorectal surgery.

BACKGROUND: Poor anastomotic perfusion can cause anastomotic leaks (AL). Hyperspectral imaging (HSI), previously validated experimentally, provides accurate, real-time, contrast-free intestinal perfusion quantification. Clinical experience with HSI is limited. In this study, HSI was used to evaluate bowel perfusion intraoperatively. METHODS: Fifty-two patients undergoing elective colorectal surgeries for neoplasia (n = 40) or diverticular disease (n = 12), were enrolled. Intestinal perfusion was assessed with HSI (TIVITA®, Diaspective Vision, Am Salzhaff, Germany). This device generates a perfusion heat map reflecting the tissue oxygen saturation (StO2) amount. Prior to anastomose creation, the clinical transection line (CTL) was highlighted on the proximal bowel and imaged with HSI. Upon StO2 heat map evaluation, the hyperspectral transection line (HTL) was identified. In case of CTL/HTL discrepancy > 5 mm, the bowel was always resected at the HTL. HSI outcomes were compared to the clinical ones. RESULTS: AL occurred in one patient who underwent neoadjuvant radiochemotherapy and ultralow anterior resection for rectal cancer. HSI assessment was feasible in all patients, and StO2-values were significantly higher at proximal segments than distal ones. Twenty-six patients showed CTL/HTL discrepancy, and these patients had a lower mean StO2 (54.55 ± 21.30%) than patients without discrepancy (65.10 ± 21.30%, p = 0.000). Patients undergoing neoadjuvant radiochemotherapy showed a lower StO2 (51.41 ± 23.41%) than non-neoadjuvated patients (60.51 ± 24.98%, p = 0.010). CONCLUSION: HSI is useful in detecting intraoperatively marginally perfused segments, for which the clinical appreciation is unreliable. Intestinal vascular supply is lower in patients undergoing neoadjuvant radiochemotherapy, and this novel finding together with the clinical impact of HSI perfusion quantification deserves further investigation in larger trials.

Adjuvant chemotherapy after neoadjuvant chemo-radiotherapy and surgery in locally advanced rectal cancer. A systematic review of literature with a meta-analysis of randomized clinical trials.

HIGHLIGHTS: Although no definitive data exist in literature, adjuvant chemotherapy is usually recommended in patients with radically resected stage III rectal cancer treated with neo-adjuvant chemo-radiotherapy. We performed a systematic review of literature with direct and indirect comparisons to assess the role of adjuvant mono- or poli-chemotherapy in radically resected rectal cancer treated with neoadjuvant chemo-radiotherapy. Neither chemotherapy (mono-or poli-chemotherapy) nor polichemotherapy with oxaliplatin-containing regimens seems to improve Overall Survival and Disease-Free Survival in patients with radically resected rectal cancer treated with neoadjuvant chemo-adiotherapy. Neither the entire population of patients radically resected after neoadjuvant chemotherapy, nor high risk patients seem to benefit from adjuvant chemotherapy. Our data seem to suggest the need of review the actual international guidelines that suggest the need of adjuvant chemotherapy at least in high risk rectal cancer treated with surgery and neoadjuvant chemo-radiotherapy.

ERAS program adherence-institutionalization, major morbidity and anastomotic leakage after elective colorectal surgery: the iCral2 multicenter prospective study.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs influence morbidity rates and length of stay after colorectal surgery (CRS), and may also impact major complications and anastomotic leakage rates. A prospective multicenter observational study to investigate the interactions between ERAS program adherence and early outcomes after elective CRS was carried out. METHODS: Prospective enrolment of patients submitted to elective CRS with anastomosis in 18 months. Adherence to 21 items of ERAS program was measured upon explicit criteria in every case. After univariate analysis, independent predictors of primary endpoints [major morbidity (MM) and anastomotic leakage (AL) rates] were identified through logistic regression analyses including all significant variables, presenting odds ratios (OR). RESULTS: Institutional ERAS protocol was declared by 27 out of 38 (71.0%) participating centers. Median overall adherence to ERAS program items was 71.4%. Among 3830 patients included in the study, MM and AL rates were 4.7% and 4.2%, respectively. MM rates were independently influenced by intra- and/or postoperative blood transfusions (OR 7.79, 95% CI 5.46-11.10; p < 0.0001) and standard anesthesia protocol (OR 0.68, 95% CI 0.48-0.96; p = 0.028). AL rates were independently influenced by male gender (OR 1.48, 95% CI 1.06-2.07; p = 0.021), intra- and/or postoperative blood transfusions (OR 4.29, 95% CI 2.93-6.50; p < 0.0001) and non-standard resections (OR 1.49, 95% CI 1.01-2.22; p = 0.049). CONCLUSIONS: This study disclosed wide room for improvement in compliance to several ERAS program items. It failed to detect any significant association between institutionalization and/or adherence rates to ERAS program with primary endpoints. These outcomes were independently influenced by gender, intra- and postoperative blood transfusions, non-standard resections, and standard anesthesia protocol.

Intraoperative Guidance Using Hyperspectral Imaging: A Review for Surgeons.

Hyperspectral imaging (HSI) is a novel optical imaging modality, which has recently found diverse applications in the medical field. HSI is a hybrid imaging modality, combining a digital photographic camera with a spectrographic unit, and it allows for a contactless and non-destructive biochemical analysis of living tissue. HSI provides quantitative and qualitative information of the tissue composition at molecular level in a contrast-free manner, hence making it possible to objectively discriminate between different tissue types and between healthy and pathological tissue. Over the last two decades, HSI has been increasingly used in the medical field, and only recently it has found an application in the operating room. In the last few years, several research groups have used this imaging modality as an intraoperative guidance tool within different surgical disciplines. Despite its great potential, HSI still remains far from being routinely used in the daily surgical practice, since it is still largely unknown to most of the surgical community. The aim of this study is to provide clinical surgeons with an overview of the capabilities, current limitations, and future directions of HSI for intraoperative guidance.

Deep Learning Analysis of In Vivo Hyperspectral Images for Automated Intraoperative Nerve Detection.

Nerves are critical structures that may be difficult to recognize during surgery. Inadvertent nerve injuries can have catastrophic consequences for the patient and lead to life-long pain and a reduced quality of life. Hyperspectral imaging (HSI) is a non-invasive technique combining photography with spectroscopy, allowing non-invasive intraoperative biological tissue property quantification. We show, for the first time, that HSI combined with deep learning allows nerves and other tissue types to be automatically recognized in in vivo hyperspectral images. An animal model was used, and eight anesthetized pigs underwent neck midline incisions, exposing several structures (nerve, artery, vein, muscle, fat, skin). State-of-the-art machine learning models were trained to recognize these tissue types in HSI data. The best model was a convolutional neural network (CNN), achieving an overall average sensitivity of 0.91 and a specificity of 1.0, validated with leave-one-patient-out cross-validation. For the nerve, the CNN achieved an average sensitivity of 0.76 and a specificity of 0.99. In conclusion, HSI combined with a CNN model is suitable for in vivo nerve recognition.

Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy.

BACKGROUND: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib. AIMS AND METHODS: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival. RESULTS: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34-0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue. CONCLUSION: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.

The Role of Anti-Angiogenics in Pre-Treated Metastatic BRAF-Mutant Colorectal Cancer: A Pooled Analysis.

Background. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC. Methods. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of BRAF-mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to BRAF mutational status, was the primary focus. Results. Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29-0.85) (p = 0.01). Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.