Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study.

BACKGROUND: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings. METHODS: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort. RESULTS: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88). CONCLUSION: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.

Laparoscopic Extended Segmentectomy VIII Guided by Three-Dimensional Reconstruction and Hepatic Veins with a Cranio-Caudal Approach.

INTRODUCTION: Minimally invasive resection of segment VIII is a technically challenging procedure, made even more challenging when the resection is extended to segment IV and/or segment VII. Parenchymal-sparing resections are frequently used in the management of liver metastases but expose to the risk of R1 resection, especially with a minimally invasive approach. Preoperative surgical planning with 3D reconstruction and intraoperative guidance with hepatic vein is helpful for laparoscopic oncological liver resection.1-3 PATIENT AND METHODS: We present the case of a 58-year-old female with three metachronous liver metastases from epidermoid anal cancer. The disease was stable 6 months after cessation of chemotherapy. Metastases were mainly located in segment VIII (with a large segment VIII dorsal) but also in the territory of glissonian pedicles from segments IV and VII. Prior to surgery, three-dimensional (3D) reconstruction showed that a segmentectomy VIII would not be sufficient to have a safety margin and showed the relation between metastases and hepatic veins. Transection of the liver was performed with an ultrasonic dissector. Exposure of the hepatic veins was performed by gently pulling of the hepatic tissue from the vein, using the nonactive blade of the ultrasonic device. Activation of ultrasonic energy was performed only for sealing and dividing small collateral veins. Three transection lines were necessary. The posterior transection line, in segment VII, was determined with intraoperative ultrasound (IOUS), at 1 cm below the metastasis. The liver was transected superficially only. The medial transection line, in segment IV, was determined with IOUS, at 1 cm on the left of the metastasis, parallel to the middle hepatic vein. Finally, the inferior transection line, between segment V and segment VIII, was approximately determined with IOUS, vertically aligned with the hepatic vein of segment V. The transection line was further corrected after clamping the glissonian pedicle of segment VIII, according to fluorescence. The surgical procedure began with the mobilization of the right liver, including division of the hepato-caval ligament, followed by the superficial transection of the posterior margin in segment VII. Then, transection of segment IV was performed near the termination of the middle hepatic vein, which was further exposed with a cranio-caudal approach to minimize the risk of vein injury. The hepatic vein of segment V was then used as a landmark for the identification of the Glissonian pedicle of segment VIII, which was transected.4 Termination of the right hepatic vein (RHV) was then identified, and the ventral branch of the RHV was transected. The dorsal branch of the RHV was exposed with a cranio-caudal approach. Finally, transection of segment VII was performed toward the transection line made initially. RESULTS: Operative time was 360 min with 450 mL blood loss. The Pringle maneuver was used during 148 min. The patient was discharged on the seventh postoperative day. Pathological examination confirmed R0 resection, with 20-60% necrosis of the three liver metastases. The resected liver weight was 225 g. Six months after liver resection, the patient had a recurrence in a celiac lymph node, which was treated by radiotherapy. Fifteen months after liver resection, the patient is free of disease without active treatment. CONCLUSION: Preoperative virtual hepatectomy facilitates surgical planning by increasing the understanding of the tumors-vessels relationship. Intraoperative hepatic vein guidance with a cranio-caudal approach enables to follow preoperative surgical planning and to perform safe complex laparoscopic liver resection.

Ampullary tumors: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, ACHBT, AFC, SFRO, RENAPE, SNFCP, AFEF, SFP, SFR).

BACKGROUND: Management of ampullary tumors (AT) is challenging because of a low level of scientific evidence. This document is a summary of the French intergroup guidelines regarding the management of AT, either adenoma (AA) or carcinoma (AC), published in July 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: A collaborative work was conducted under the auspices of French medical, endoscopic, oncological and surgical societies involved in the management of AT. Recommendations are based on recent literature review and expert opinions and graded in three categories (A, B, C), according to quality of evidence. RESULTS: Accurate diagnosis of AT requires at least duodenoscopy and EUS. All patients should be discussed in multidisciplinary tumor board before treatment. Surveillance may only be proposed for small AA in familial adenomatous polyposis. For AA, endoscopic papillectomy is the preferred option only if R0 resection can be achieved. When not possible, surgical papillectomy should be considered. For AC beyond pT1a N0, pancreaticoduodenectomy is the procedure of choice. Adjuvant monochemotherapy (gemcitabine, 5FU) may be proposed. For aggressive tumors (pT3/T4, pN+, R1, poorly differentiated AC, pancreatobiliary differentiation) with high risk of recurrence, 6 months polychemotherapy (CAPOX/FOLFOX for the intestinal subtype and mFOLFIRINOX for the pancreatobiliary or the mixed subtype) may be a valid alternative. Clinical and radiological follow up is recommended for 5 years. CONCLUSIONS: These guidelines help to homogenize and highlight unmet needs in the management of AA and AC. Each individual case should be discussed by a multidisciplinary team.

[Prophylactic gastrectomy]. / Gastrectomies prophylactiques.

One to 3% of gastric cancers are secondary to genetic predisposition, notably hereditary diffuse gastric cancers (HDGC) caused by CDH1 gene mutations. According to French recommendations, in case of CDH1 gene mutation, a prophylactic total gastrectomy should be performed between 20 and 30 years old. This gastrectomy should remove all the gastric mucosa at both extremities (duodenal and esophageal sides). Histopathological examinations of prophylactic total gastrectomies in asymptomatic CDH1-mutated patients reveal microscopic foci of diffuse-type cancer in 90 to 100% of cases. Lymph node involvement and lympho-vascular invasion are extremely rare, justifying the use of a D1-only lymphadenectomy. In the context of prophylaxis, limited lymphadenectomy and the development of minimally invasive oesogastric surgery, the minimally invasive approach might be the preferred approach, in expert centers. Surgical outcomes seem to be similar to those after gastrectomy for cancer. Prophylactic total gastrectomy is the cornerstone of CGDH management, associated with multidisciplinary follow-up and mammary surveillance in women.

False-Negative Neuroendocrine Tumor Identified With 68 Ga-DOTATOC PET/CT : A Case of Well-Differentiated Somatostatinoma.

ABSTRACT: We report the case of a 25-year-old man who was undergoing follow-up for neurofibromatosis type 1. The man underwent 68 Ga-DOTATOC PET/CT for a suspected well-differentiated duodenal neuroendocrine tumor. This examination did not reveal any significant uptake, whereas complementary 18 F-FDG PET/CT showed moderate 18 F-FDG uptake in the primary tumor as well as the adenopathy. Histology, a well-differentiated duodenal neuroendocrine tumor was confirmed, consistent with the diagnosis of somatostatinoma. Although rare, this well-differentiated neuroendocrine tumor should be kept in mind as a possible source of false-negative somatostatin receptor PET/CT findings.

Clinical outcomes after inferior vena cava resection for malignant disease. A single center experience of 51 vena cava resections.

BACKGROUND AND OBJECTIVE: For tumors involving inferior vena cava (IVC), surgery with complete resection remains the first line treatment. Management of IVC after resection, either ligation without reconstruction or primary reconstruction, is debated. Our study aimed to evaluate type of venous reconstruction, anticoagulation management and morbidity. METHODS: A French single center database of patients who underwent partial or total circumferencial resection of the IVC for malignant disease was analyzed. Inclusion criteria were any oncologic procedure for a retroperitoneal neoplasm requiring concomitant resection of the IVC with or without venous reconstruction with prosthesis. Exclusion criteria were surgery before year 2000. Data were descriptive and reverse Kaplan Meier was used for follow-up calculation. The endpoints were the rate of prosthetic reconstruction, the use of anticoagulation and the post-operative outcomes. RESULTS: Fifty - one patients were included with a median duration of follow-up of 54.8 months. The majority of patients were men (56.9%). Median age of the population was 44.1 years. Most of the patients underwent surgery for primary testicular cancer and for sarcoma. Complete IVC resections were performed in 46 (90,2%) patients, 32 having a concomitant prosthetic replacement. Eight patients underwent aortic resection in the same operative time. Postoperative morbidity was 33.3%. Post-operative anticoagulation was done in 24 patients. At 1 month, four patients developed thrombosis in the prosthesis. CONCLUSIONS: IVC resections are feasible and safe. Venous reconstruction and postoperative management were planned according to the preoperative imaging and intraoperative findings. We propose a decision-tree for peri-operative management and anticoagulation.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BACKGROUND: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. METHODS: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. RESULTS: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91). CONCLUSIONS: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

Anastomotic leakage and functional outcomes following total mesorectal excision with delayed and immediate colo-anal anastomosis for rectal cancer: Two single-arm phase II trials.

BACKGROUND: Anastomotic leakage (AL) remains a major cause of morbidity following total mesorectal excision (TME). A diverting ileostomy reduces the risk of AL but impairs quality of life (QoL). Delayed colo-anal anastomosis (DCAA) may be an alternative to immediate colo-anal anastomosis (ICAA) without creation of a diverting ileostomy. STUDY DESIGN: Patients with T3 or N+ rectal tumours were treated with neoadjuvant chemoradiation and TME. To evaluate DCAA or ICAA with diverting ileostomy, a two multicenter single-arm phase II trials was designed. The primary endpoint was the rate of AL requiring a diverting ileostomy up to 30 days postoperatively. Secondary endpoints were 30-day postoperative complications, 1- and 2-year disease-free survival; QoL at baseline, 6 months and anorectal function measured by the low anterior resection syndrome questionnaire and Wexner score at baseline, 6 months and a late assessment at median 8 years following surgery. RESULTS: AL requiring diverting ileostomy occurred in one patient (2.1%; 95% confidence interval (CI) [0; 11.1]) in the DCAA group and in five patients (8.6%; 95%CI [3.2; 21.0]) in the ICAA group. Thirty-day postoperative complications occurred in 13 patients (27.1%) in the DCAA group and in 10 patients (19.2%) in the ICAA group. Short and long-term functional outcomes showed similar patterns. CONCLUSION: These two single-arm phase II trials showed that DCAA has low rates of AL requiring a diverting ileostomy and acceptable long-term functional results. DCAA seems a good choice to restore bowel continuity.

Dorsal Lipomodeling to Treat Donor Site After Latissimus Dorsi Flap: Safety and Effectiveness.

BACKGROUND: The latissimus dorsi flap (LDF) is a classic and efficient technique for breast reconstruction. However, its use has recently diminished in surgical practice due to dorsal disadvantages and to the increased use of microsurgical techniques for breast reconstruction, such as the deep inferior epigastric artery perforator flap. OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of managing dorsal problems such as asymmetry, irregularities, and dysesthesia by lipomodeling the back region during the associated surgery for breast reconstruction. METHODS: A series of 300 patients operated by the last author for dorsal lipomodeling to correct sequelae after harvesting the total LDF, between November 2012 and March 2019, was analyzed. RESULTS: The results show a very good improvement in the dorsal region in 6.7% of cases, good improvement in 86.7% cases, and fair improvement in 6.7% of cases. There was a good improvement in dorsal comfort in 90% of cases, a very good improvement in 6.66% of cases, and a fair improvement in 6.66% of cases. In 5% of cases 2 sessions were required to obtain a satisfactory result. No major complications were registered, and the only complication encountered were oil cysts in 2.6% of cases that were treated during consultation with percutaneous puncture. CONCLUSIONS: This study showed that lipomodeling in the back area after LDF harvesting is an efficient and safe technique that corrects secondary dorsal sequelae such as irregularities, asymmetry, sensitivity, and dysesthesia. This technique should increase the indications for LDF because it decreases donor site sequelae, which are some of the main drawbacks of the LDF approach.

Quantitative ultrasound techniques for assessing thermal ablation: Measurement of the backscatter coefficient from ex vivo human liver.

BACKGROUND: Understanding the changes occurring in biological tissue during thermal ablation is at the heart of many current challenges in both therapy and medical imaging research. PURPOSE: The objective of this work is to quantitatively interpret the scattering response of human liver samples, before and after thermal ablation. We report acoustic measurements performed involving n = 21 human liver samples. Thermal ablation is achieved at temperatures between 45 and 80°C and quantification of the irreversible changes in acoustic attenuation and Backscattering Coefficient (BSC) is reported, with a particular attention to the latter. METHODS: Both attenuation coefficient and BSCs were measured in the frequency range from 10 to 52 MHz. Scans were performed before heating and after cooling down. Attenuation coefficients were calculated using spectral difference method and BSC estimated using the reference phantom method. RESULTS: Strong increases of attenuation coefficients and BSCs with heating temperature were observed. Quantitative ultrasonic parameters obtained with the polydisperse structure factor model (poly-SFM)are compared to histological observations and seen to be close to hepatocyte mean diameter (HMD). CONCLUSIONS: The results presented in this study provide a description of the impact of thermal ablation in human liver tissue on acoustic attenuation and the BSC. For the first time, quantitative agreement between the Effective Scatterer Diameter (ESD) estimated from BSC and HMD was shown, highlighting the important role of cellular network in the scattering response of the medium. This core result is an important step toward the determination of the nature of scattering sources in biological tissues.

Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study.

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.

Intra-operative High-Intensity Focused Ultrasound in Patients With Colorectal Liver Metastases: A Prospective Ablate-and-Resect Study.

OBJECTIVE: High-intensity focused ultrasound (HIFU) is a recent, non-ionizing and non-invasive technology of focal destruction. Independence from the heat-sink effect of blood flow makes HIFU an interesting technique for focal ablation of liver tumors. Current available technology is based on extracorporeal treatment that limits use of HIFU for the treatment of liver tumors, as elementary ablations are small and must be juxtaposed to treat tumors, resulting in long-duration treatment. We developed an HIFU probe with toroidal technology, which increases the volume of ablation, for intra-operative use, and we assessed the feasibility and efficacy of this device in patients with colorectal liver metastasis (CLM) measuring less than 30 mm. METHODS: This study was an ablate-and-resect, prospective, single-center, phase II study. All ablations were performed in the area of liver scheduled for liver resection to avoid loss of chance of recovery. The primary objective was to ablate CLM with safety margins (>5 mm). RESULTS: Between May 2014 and July 2020, 15 patients were enrolled and 24 CLM were targeted. The HIFU ablation time was 370 s. In total, 23 of 24 CLM were successfully treated (95.8%). No damage occurred to extrahepatic tissues. HIFU ablations were oblate shaped with an average long axis of 44.3 ± 6.1 mm and an average shortest axis of 35.9 ± 6.7 mm. On pathological examination, the average diameter of the treated metastasis was 12.2 ± 4.8 mm. CONCLUSION: Intra-operative HIFU can safely and accurately produce large ablations in 6 min with real-time guidance (ClinicalTrials.gov identifier: NCT01489787).

Surgical outcomes in pelvic exenteration for advanced and recurrent malignancy: a high volume single institution experience.

PURPOSE: Pelvic exenteration remains the only curative treatment for advanced pelvic malignancies. However, identification of predictive factors for successful surgical outcomes is still a controversial issue at present time. METHODS: This retrospective study included data from all adult patients with colorectal or anal advanced pelvic malignancy registered for pelvic exenteration at the Leon Berard Cancer Center (Lyon, France). The primary endpoint was the surgical outcomes and aimed to define the predictive factors for postoperative complications. Secondary endpoints included overall survival and progression free survival in patients having experienced pelvic exenteration (PE). RESULTS: Data from 141 patients with locally advanced tumor (N = 81) or recurrent malignancies (N = 60) diagnosed between May 1994 and November 2018 were collected. The median age was 63.3 years (95%CI 20.0-92.0). Malignancies included different locations (rectal: 69.5%, left colon: 17.0% and anal: 13.5%). Posterior pelvectomy was the most frequent surgery (81.6%). The median length of hospital stay was 23.3 days (95%CI 3.0-82.0). The major complication rate at 30 days was 24.8% and 38.1% at 90 days. The median overall survival was 54.5 months (95%CI 41.5-104.1) and the median PFS was 34.5 months (95%CI 19.6-NA). CONCLUSION: In selected patients, pelvic exenteration is associated with good surgical and survival outcomes.

Curative-intent treatment of pulmonary metastases from colorectal cancer: A comparison between imaging-guided thermal ablation and surgery.

BACKGROUND: Pulmonary metastases (PM) are the most frequent extra-abdominal metastases from colorectal cancer. Lung resection and imaging-guided thermal ablation (IGTA) are used as curative-intent treatment. We compared the outcomes of patients with PM, treated with resection or ablation. METHODS: We retrospectively analyzed data from patients who underwent surgery or IGTA for colorectal PM between April 2011 and November 2020. Surgery was performed for peripheral PM and IGTA for deep-located PM not in contact with major vessels. Patients who had both procedures were excluded. Patients were compared using propensity score matching (PSM) analysis, stratified according to number, size, and unilaterality of PM. RESULTS: One hundred and fourty-six patients were included, 65 (44.5%) underwent surgery and 81 (55.5%) underwent IGTA. After PSM analysis, each group contained 46 patients. IGTA patients had a lower morbidity rate (13.1% vs. 15.2%, p = 0.028) and a shorter length of stay (5.13 vs. 2.63 days, p < 0.001). Oncological outcomes were similar in both groups with 5-year OS of 80% and 5-year progression-free survival (PFS) of 30% (p = 0.657 and p = 0.504, respectively) with similar recurrence patterns. CONCLUSION: Lung resection and IGTA seem to have similar oncologic outcomes for both OS and PFS. IGTA could be an alternative effective treatment for small PM, whenever technically feasible.

Non-invasive High-Intensity Focused Ultrasound Treatment of Liver Tissues in an In Vivo Porcine Model: Fast, Large and Safe Ablations Using a Toroidal Transducer.

A toroidal high-intensity focused ultrasound (HIFU) transducer was used to non-invasively treat liver tissues in vivo in a pig model. The transducer was divided into 32 concentric rings with equal surface areas operating at 2.5 MHz. First, attenuation of skin, fat, muscle and liver tissues was measured in fresh animal samples to adjust the energy delivered to the focal zone. Then, 8 animals were included in the present protocol and placed in a dorsal decubitus proclive position at an angle of 15°. The device was held by hand, and sonications were performed during apnea. Two thermal HIFU lesions were created in 40 s in each animal. The average abdominal wall thickness was 14.8 ± 1.3 mm (12.5-17.6 mm). The longest and shortest axes of the HIFU ablations were 20.9 ± 6.3 mm (14.0-33.7 mm) and 14.2 ± 5.5 mm (7.0-22.0 mm), respectively. All HIFU lesions were visible on sonograms. The correlation between the dimensions of the HIFU lesions observed on sonograms and those obtained during gross examination was r = 0.84. Creating large and fast ablations with reliable ultrasound imaging guidance in the liver using this handheld device may represent a new therapeutic option for patients with liver tumors.

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial.

OBJECTIVE: To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. DESIGN: Multicentre, randomised, double blind, placebo controlled trial. SETTING: 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. PARTICIPANTS: 926 adults scheduled for elective colorectal surgery. INTERVENTION: Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. RESULTS: Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%). CONCLUSION: Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618720.

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.