Predictive value of C-reactive protein for postoperative liver-specific surgical site infections.

BACKGROUND: C-reactive protein is a useful biological tool to predict infectious complications, but its predictive value in detecting organ-specific surgical site infection after liver resection has never been studied. We aimed to evaluate the predictive value of c-reactive protein and determine the cut-off values to detect postoperative liver resection-surgical site infection. METHODS: A multicentric analysis of consecutive patients with liver resection between 2018 and 2021 was performed. The predictive value of postoperative day 1, postoperative day 3, and postoperative day 5 C-reactive protein levels was evaluated using the area under the receiver operating characteristic curve. Cut-off values were determined using the Youden index in a 500-fold bootstrap resampling of 500 patients treated at 3 centers, who comprised the development cohort and were tested in an external independent validation cohort of 166 patients at a fourth center. RESULTS: Among the 500 patients who underwent liver resection of the development cohort, liver resection-surgical site infection occurred in 66 patients (13.2%), and the median time to diagnosis was 6.0 days (interquartile range, 4.0-9.0) days. Median C-reactive protein levels were significantly higher on postoperative day 1, postoperative day 3, and postoperative day 5 in the liver resection-surgical site infection group compared with the non-surgical site infection group (50.5 vs 34.5 ng/mL, 148.0 vs 72.5 ng/mL, and 128.4 vs 35.2 ng/mL, respectively; P < .001). Postoperative day 3 and postoperative day 5 C-reactive protein-level area under the curve values were 0.76 (95% confidence interval, 0.64-0.88, P < .001) and 0.82 (95% confidence interval, 0.72-0.92, P < .001), respectively. Postoperative day 3 and postoperative day 5 optimal cut-off values of 100 mg/L and 87.0 mg/L could be used to rule out liver resection-surgical site infection, with a negative predictive value of 87.0% (interquartile range, 70.2-93.8) and 76.0% (interquartile range, 65.0-88.0), respectively, in the validation cohort. CONCLUSION: Postoperative day 3 and postoperative day 5 C-reactive protein levels may be valuable predictive tools for liver resection-surgical site infection and aid in hospital discharge decision-making in the absence of other liver-related complications.

The falciform/round ligament "flooring," an effective method to reduce life-threatening post-pancreatectomy hemorrhage occurrence.

PURPOSE: Late post-pancreatectomy hemorrhage (PPH) represents the most severe complication after pancreatic surgery. We have measured the efficacy of major vessels "flooring" with falciform/round ligament to prevent life-threatening grade C late PPH after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: All consecutive patients who underwent PD and DP between 2013 and 2021 were retrospectively reviewed on a prospectively maintained database. The cohort was divided in two groups: "flooring" vs. "no flooring" method group. The "no flooring" group had omental flap interposition. Patient characteristics and operative and postoperative data including clinically relevant postoperative pancreatic fistula (CR-POPF), late PPH (grade B and C), and 90-day mortality were compared between the two groups. RESULTS: Two hundred and forty patients underwent pancreatic resections, including 143 PD and 97 DP. The "flooring" method was performed in 61 patients (39 PD and 22 DP). No difference was found between the two groups concerning severe morbidity, CR-POPF, delayed PPH, and mortality rate. The rate of patients requiring postoperative intensive care unit was lower in the "flooring" than in the "no flooring" method group (11.5% vs. 25.1%, p = 0.030). Among patients with grade B/C late PPH (n = 30), the rate of life-threatening grade C late PPH was lower in the "flooring" than in the "no flooring" method group (28.6% (n = 2/7) vs. 82.6% (n = 19/24), p = 0.014). Risk factor analysis showed that the "flooring" method was the only protective factor against grade C late PPH occurrence (p = 0.013). CONCLUSION: The "flooring" method using the falciform/round ligament should be considered during pancreatectomies to reduce the occurrence of life-threatening grade C late PPH.

PVRIG Expression Is an Independent Prognostic Factor and a New Potential Target for Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequent and deadly cancer in need of new treatments. Immunotherapy has shown promising results in several solid tumors. The TIGIT/DNAM-1 axis gathers targets for new immune checkpoint inhibitors (ICIs). Here, we aimed at highlighting the potential of this axis as a new therapeutic option for HCC. For this, we built a large transcriptomic database of 683 HCC samples, clinically annotated, and 319 normal liver tissues. We interrogated this database for the transcriptomic expression of each member of the TIGIT/DNAM-1 axis and tested their prognostic value for survival. We then focused on the most discriminant one for these criteria, i.e., PVRIG, and analyzed the clinical characteristics, the disease-free and overall survivals, and biological pathways associated with PVRIG High tumors. Among all members of the TIGIT/DNAM-1 axis, PVRIG expression was higher in tumors than in normal liver, was heterogeneous across tumors, and was the only member with independent prognostic value for better survival. PVRIG High tumors were characterized by a higher lymphocytic infiltrate and enriched for signatures associated with tertiary lymphoid structures and better anti-tumor immune response. These results suggest that patients with PVRIG High tumors might be good candidates for immune therapy involving ICIs, notably ICIs targeting the TIGIT/DNAM-1 axis. Further functional and clinical validation is urgently required.

An Ex Situ Cadaver Liver Training Model Continuously Pressurized to Simulate Specific Skills Involved in Laparoscopic Liver Resection: the Lap-Liver Trainer.

BACKGROUND: Laparoscopic liver resection (LLR) requires delicate skills. The aim of the study was to develop a training model mimicking as much as possible intraoperative bleeding and bile leakage during LLR. We also assessed the educational value of the training model. METHODS: The Lap-liver trainer (LLT) combined a continuously pressurized ex situ cadaver liver and a customized mannequin. The customized mannequin was designed by computer-aided design and manufactured by 3D printing. The left lateral sectionectomy (LLS) was chosen to assess the feasibility of a LLR with the LLT. Eighteen volunteers were recruited to perform LLS and to assess the educational value of the LLT using a Likert scale. RESULTS: The customized mannequin consisted of a close laparoscopic training device based on a simplified reconstruction of the abdominal cavity in laparoscopic conditions. Ex situ cadaver livers were pressurized to simulate blood and bile supplies. Each expert surgeon (n = 3) performed two LLS. They were highly satisfied of simulation conditions (4.80 ± 0.45) and strongly recommended that the LLT should be incorporated into a teaching program (5.00 ± 0.0). Eight novice and 4 intermediate surgeons completed a teaching program and performed a LLS. Overall, the level of satisfaction was high (4.92 ± 0.29), and performing such a procedure under simulation conditions benefited their learning and clinical practice (4.92 ± 0.29). CONCLUSIONS: The LLT could provide better opportunities for trainees to acquire and practice LLR skills in a more realistic environment and to improve their ability to deal with specific events related to LLR.

Predictive factors of non-operative management failure in 494 blunt liver injuries: a multicenter retrospective study.

Non-operative management (NOM) has become the major treatment of blunt liver trauma (BLT) with a NOM failure rate of 3-15% due to liver-related complications. The aim of the study was to determine the predictive factors and a risk-stratified score of NOM failure. From 2013 to 2021, all patients with BLT in three trauma centers were included; clinical, biological, radiological and outcome data were retrospectively analyzed. Predictive factors and a risk-stratified score associated with NOM failure were identified. Four hundred and ninety-four patients with BLT were included. Among them, 80 (16.2%) had isolated BLT. Fifty-nine patients (11.9%) underwent emergent operative management (OM) on the day of admission and 435 (88.1%) had a NOM. NOM failure rate was 11.5%. Patients with a NOM failure more frequently had a hemoperitoneum (p < 0.001), liver bleeding (p < 0.001), blood transfusion (p < 0.001) and angioembolization (p < 0.001) compared to patient with a successful NOM. In multivariate analysis, the presence of hemoperitoneum (OR = 5.71; 95 CI [1.29-25.45]), angioembolization (OR = 8.73; 95 CI [2.04-38.44] and severe liver injury (AAST IV or V) (OR = 8.97; 95 CI [3.36-23.99]) were independent predictive factors of NOM failure. When these three factors were associated, NOM failure rate was 83.3%. The AAST grade, the presence of hemoperitoneum and the realization of liver angioembolization on the day of admission are three independent predictive factors of NOM failure. Our risk-score based on these three factors stratify the risk of NOM failure in BLT and could be used for a more appropriate level of medical survey adapted to each patient. Level of evidence: prospective observational cohort study, Level III.

New 5-mm laparoscopic pneumodissector device to improve laparoscopic dissection: an experimental study of its safety in a swine model.

BACKGROUND: To improve the laparoscopic surgical dissection, the aim of the study was to assess the safety of burst of high-pressure CO2 using a 5-mm laparoscopic pneumodissector (PD) operating at different flow rates and for different operating times regarding the risk of gas embolism (GE) in a swine model. METHODS: The first step was to define the settings use of the PD device ensuring no GE. Successive procedures were conducted by laparotomy: cholecystectomy, the PD was placed 10 mm deep in the liver and the PD was directly introduced into the lumen of the inferior vena cava. Different PD flow rates of 5, 10, and 15 mL/s were used. The second step was to assess the safety of the device (PD group) during a laparoscopic dissection task (cystic and hepatic pedicles dissection, cholecystectomy and right nephrectomy) in comparison with the use of a standard laparoscopic hook device (control group). PD flow rate was 10 mL/s and consecutive burst of high-pressure CO2 was delivered for 3-5 s. RESULTS: In the first step (n = 17 swine), no GE occurred during cholecystectomy regardless of the PD flow rate used. When the PD was placed in the liver or into the inferior vena cava, no severe or fatal GE occurred when a burst of high-pressure CO2 was applied for 3 or 5 s with PD flow rates of 5 and 10 mL/s. In the second step (PD group, n = 10; control group, n = 10), no GE occurred in the PD group. The use of the PD did not increase operative time or blood loss. The quality of the dissection was significantly improved compared to the control group. CONCLUSIONS: The 5-mm laparoscopic PD appears to be free from CO2 GE risk when consecutive bursts of high-pressure CO2 are delivered for 3-5 s with a flow rate of 10 mL/s.

Development of a novel educational tool to assess skills in laparoscopic liver surgery using the Delphi methodology: the laparoscopic liver skills scale (LLSS).

BACKGROUND: No specific performance assessment scales have been reported in laparoscopic liver resection. This study aimed at developing an objective scale specific for the assessment of technical skills for wedge resection in anterior segments (WRAS) and left lateral sectionectomy (LLS). METHODS: A laparoscopic liver skills scale (LLSS) was developed using a hierarchical task analysis. A Delphi method obtained consensus among five international experts on relevant steps that should be included into the LLSS for assessment of operative performances. The consensus was predefined using Cronbach's alpha > 0.80. RESULTS: A semi-structured review extracted 15 essential subtasks for full laparoscopic WRAS and LLS for evaluation in the Delphi survey. Two rounds of the survey were conducted. Three over 15 subtasks did not reach the predefined level of consensus. Based on the expert's comments, 13 subtasks were reformulated, 4 subtasks were added, and a revised skills scale was developed. After the 2nd round survey (Cronbach's alpha 0.84), 19 subtasks were adopted. The LLSS was composed of three main parts: patient positioning and intraoperative preparation (task 1 to 8), the core part of the WRAS and LLS procedure (tasks 9 to 14), and completion of procedure (task 15 to 19). CONCLUSIONS: The LLSS was developed for measuring the skill set for the education of safe and secure laparoscopic WRAS and LLS procedures in a dedicated training program. After validation, this scale could be also used as an assessment tool in the operating room and extrapolated as an operative roadmap to other complex procedures.

Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study.

PURPOSE: Splenic vessel involvement occurs frequently in pancreatic ductal adenocarcinoma (PDAC) of the body and the tail (B/T) but the impact on survival is unknown. We assessed the influence of radiological and pathologic involvement of splenic artery (p-SA +) and vein (p-SV +) on patient outcomes after distal pancreatectomy (DP) for PDAC. METHODS: From 2013 to 2019, all DP for PDAC in five centers were included. Factors associated with overall (OS) and disease-free (DFS) survival were identified. RESULTS: Among the 76 patients included, 5 (6.6%) had p-SA + only, 11 (14.5%) had p-SV + only, and 24 (31.6%) had both p-SA + and p-SV + . The preoperative CT-scan accuracy to predict p-SV + and p-SA + was high (sensitivity: 91.4% and 82.8%, respectively; negative predictive value: 89.7% and 88.3%, respectively). The 5-year OS and DFS rates were 3.9% and 8.3%, respectively. Multivariate analysis identified splenic vessel involvement (i.e., p-SA + or p-SV + , or both p-SA + and p-SV +) as the only independent factor influencing DFS (HR 4.04; 95% CI [1.22-13.44], p = 0.023). Tumor size ≥ 30 mm was the only independent factor influencing OS (HR 4.04; 95% CI [1.26-12.95], p = 0.019) and was associated with a high risk of p-SA + (p = 0.001) and p-SV + (p < 0.001). CONCLUSION: Tumor size ≥ 30 mm and splenic vessel involvement occurred in more than half of the patients who underwent DP for PDAC and had negative impact on long-term survival. Preoperative CT-scan was reliable to identify splenic vessel involvement in B/T PDAC. Large tumor size and radiological splenic vessel involvement could be taken into account to propose a neoadjuvant treatment.

Postoperative day 1 combination of serum C-reactive protein and drain amylase values predicts risks of clinically relevant pancreatic fistula. The "90-1000" score.

BACKGROUND: Several scoring systems predict risks of clinically relevant postoperative pancreatic fistula after pancreatectomy, but none have emerged as the gold standard. This study aimed to evaluate the accuracy of postoperative day 1 drain amylase and serum C-reactive protein levels in predicting clinically relevant postoperative pancreatic fistula compared with intraoperative pancreatic characteristics. METHODS: Patients who underwent pancreatectomy between 2017 and 2019 were included prospectively. Cutoff values were determined using receiver operating characteristic curves, and a score combining postoperative day 1 drain amylase and serum C-reactive protein was tested in a multivariate logistic regression model to evaluate clinically relevant postoperative pancreatic fistula risk. RESULTS: A total of 274 pancreatic resections (182 pancreaticoduodenectomies and 92 distal pancreatectomies) were included. The pancreatic gland texture was "soft" in 47.8% (n = 131), and 55.8% (n = 153) had a small size main pancreatic duct (≤3 mm). Clinically relevant postoperative pancreatic fistula occurred in 58 patients (21.2%). Drain amylase ≥1,000 UI/L and serum C-reactive protein ≥90 mg/L were identified as the optimal cutoffs to predict clinically relevant postoperative pancreatic fistula. On multivariate analysis these cutoffs were independent predictors of clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies (drain amylase: P < .001, serum C-reactive protein: P = .006) and distal pancreatectomies (drain amylase: P = .009, serum C-reactive protein: P = .001). The postoperative day 1 "90-1000" model, a 2-value score relying on these cutoffs, significantly (P < .001) outperformed intraoperative pancreatic parenchymal characteristics in predicting clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies and distal pancreatectomies. A postoperative day 1 "90-1000" score = 0 had a negative predictive value of 97% and 94%, respectively, after pancreaticoduodenectomy and distal pancreatectomies. CONCLUSION: A combined score relying on postoperative day 1 values of drain amylase and serum C-reactive protein levels was accurate in predicting risks of clinically relevant postoperative pancreatic fistula after pancreatectomy.

Surgery of small bowel melanoma metastases in the era of efficient medical therapies: a retrospective cohort study.

Surgery of small bowel melanoma metastases has to be reconsidered in the era of targeted treatments and immunotherapy. To retrospectively assess context and outcomes of small bowel melanoma metastases resections. All consecutive melanoma patients who underwent resection of small bowel metastases between 2011 and 2017, in a single referral center, were retrospectively analyzed through melanoma-specific survival (MSS). A total of 20 patients were included with a 47.8 months median follow-up. Before small bowel surgery, eight patients (40%) were asymptomatic while seven had anemia and five patients had abdominal pain. All resections were decided on tumor boards except for three surgeries performed in the emergency setting. In the whole cohort, MSS was 89.5 months with 50% of patients alive at the study endpoint. We classified surgical indications in three groups: (1) surgery as a pivotal treatment for mono- or oligo-metastases limited to the small bowel (n = 6); (2) salvage surgery for symptomatic patients in order to preserve their chances to switch to an active line of medical treatment (n = 8); and (3) surgery of small bowel dissociated metastatic progression for patients otherwise controlled (n = 6), aiming at keeping patients with the same treatment or active follow-up. In these three situations, the objective of surgery was usually met, and most patients had a long median MSS after surgery: 70.3 months, 89.5 months and 72.4 months, respectively. Although medical treatments have dramatically improved survival in metastatic melanoma, surgical control of life-threatening localization like small bowel metastases is often a condition for long survival.

Delayed post-pancreatectomy hemorrhage and bleeding recurrence after percutaneous endovascular treatment: risk factors from a bi-centric study of 307 consecutive patients.

PURPOSE: Delayed post-pancreatectomy hemorrhage (PPH) is still one of the most dreaded complications after pancreatic surgery. Its management is now focused on percutaneous endovascular treatments (PETs). METHODS: Between 2013 and 2019, 307 patients underwent pancreatic resection. The first endpoint of this study was to determine predictive factors of delayed PPH. The second endpoint was to describe the management of intra-abdominal abscesses (IAA). The third endpoint was to identify risk factors of bleeding recurrence after PET. Patients were divided into two cohorts: A retrospective analysis was performed ("cohort 1," "learning set") to highlight predictive factors of delayed PPH. Then, we validated it on a prospective maintained cohort, analyzed retrospectively ("cohort 2," "validation set"). Second and third endpoints studies were made on the entire cohort. RESULTS: In cohort 1, including 180 patients, 24 experienced delayed PPH. Multivariate analysis revealed that POPF diagnosis on postoperative day (POD) 3 (p=0.004) and IAA (p=0.001) were independent predictive factors of delayed PPH. In cohort 2, association of POPF diagnosis on POD 3 and IAA was strongly associated with delayed PPH (area under the curve [AUC] 0.80; 95% confidence interval [CI] [0.59-0.94]; p=0.003). Concerning our second endpoint, delayed PPH occurred less frequently in patients who underwent postoperative drainage procedure than in patients without IAA drainage (p=0.002). Concerning our third endpoint, a higher body mass index (BMI) (p=0.027), occurrence of postoperative IAA (p=0.030), and undrained IAA (p=0.011) were associated with bleeding recurrence after the first PET procedure. CONCLUSION: POPF diagnosis on POD 3 and intra-abdominal abscesses are independent predictive factors of delayed PPH. Therefore, patients presenting an insufficiently drained POPF leading to intra-abdominal abscess after pancreatic surgery should be considered as a high-risk situation of delayed PPH. High BMI, occurrence of postoperative IAA, and undrained IAA were associated with recurrence of bleeding after PET.

Intra-pancreatic distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: a common short and long-term prognosis?

The aim of the study was to compare histological features, postoperative outcomes, and long-term prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. From 2005 to 2017, 188 pancreaticoduodenectomies (pancreatic ductal adenocarcinoma n = 151, distal cholangiocarcinoma n = 37) were included. Postoperative outcomes were compared after matching on pancreatic gland texture and main pancreatic duct size. Matching according to tumor size, lymph node invasion and resection margin was used to compare overall and disease-free survival. Distal cholangiocarcinoma patients had more often "soft" pancreatic gland (P = 0.002) and small size main pancreatic duct (P = 0.001). Pancreatic ductal adenocarcinoma patients had larger tumors (P = 0.009), and higher lymph node ratio (P = 0.017). Severe morbidity (P = 0.023) and clinically relevant pancreatic fistula (P = 0.018) were higher in distal cholangiocarcinoma patients. After matching on gland texture and main pancreatic duct diameter, clinically relevant postoperative pancreatic fistula was still more frequent in distal cholangiocarcinoma patients (P = 0.007). Tumor size > 20 mm was predictive of impaired overall survival (P = 0.024) and disease-free survival (P = 0.003), tumor differentiation (P = 0.027) was predictive of impaired overall survival. Survival outcomes for distal cholangiocarcinoma and pancreatic ductal cholangiocarcinoma were similar after matching patients according to tumor size, lymph node invasion and resection margin. Long-term outcomes after pancreaticoduodenectomy for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma patients are similar. Postoperative course is more complicated after pancreaticoduodenectomy for distal cholangiocarcinoma than pancreatic ductal adenocarcinoma. After pancreaticoduodenectomy, patients with distal cholangiocarcinoma and pancreatic ductal adenocarcinoma have similar long-term oncological outcomes.

Prospective study on predictability of complications by pancreatic surgeons.

PURPOSE: We evaluated the intuition of expert pancreatic surgeons, in predicting the associated risk of pancreatic resection and compared this "intuition" to actual operative follow-up. The objective was to avoid major complications following pancreatic resection, which remains a challenge. METHODS: From January 2015 to February 2018, all patients who were 18 years old or more undergoing a pancreatic resection (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or central pancreatectomy [CP]) for pancreatic lesions were included. Preoperatively and postoperatively, all surgeons completed a form assessing the expected potential occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF: grade B or C), postoperative hemorrhage, and length of stay. RESULTS: Preoperative intuition was assessed for 101 patients for 52 PD, 44 DP, and 5 CP cases. Overall mortality and morbidity rates were 6.9% (n = 7) and 67.3% (n = 68), respectively, and 38 patients (37.6%) developed a POPF, including 27 (26.7%) CR-POPF. Concordance between preoperative intuition of CR-POPF occurrence and reality was minimal, with a Cohen's kappa coefficient (κ) of 0.175 (P value = 0.009), and the same result was obtained between postoperative intuition and reality (κ = 0.351; P < 0.001). When the pancreatic parenchyma was hard, surgeons predicted the absence of CR-POPF with a negative predictive value of 91.3%. However, they were not able to predict the occurrence of CR-POPF when the pancreas was soft (positive predictive value 48%). CONCLUSIONS: This study assessed for the first time the surgeon's intuition in pancreatic surgery, and demonstrated that pancreatic surgeons cannot accurately assess outcomes except when the pancreatic parenchyma is hard.

Learning Curve in Laparoscopic Liver Resection, Educational Value of Simulation and Training Programmes: A Systematic Review.

BACKGROUND: The laparoscopic approach is widely accepted as the procedure of choice for abdominal surgery. However, laparoscopic liver resection (LLR) has advanced slowly due to the significant learning curve (LC), and only few publications have dealt with advanced training in LLR. METHODS: Two reviewers conducted systematic research through MEDLINE and EMBASE with combinations of the following keywords: (learning curve OR teaching OR training OR simulation OR education) AND (liver OR hepatic) AND (laparoscopic OR laparoscopy). Robotic-assisted, hand-assisted and hybrid LLRs were excluded. RESULTS: Nineteen studies were retrieved. Overall, the level of evidence was low. Thirteen articles assessed the LC during real-life LLR, and six articles focussed on simulation and training programmes in LLR. The LC in minor LLR comprised 60 cases overall, and 15 cases for standardised left lateral sectionectomy. For major LLR (MLLR), the LC was 50 cases for most studies, but was reported to be 15-20 cases in more recent studies, provided MLLR is performed progressively in selected patients. However, there was heterogeneity in the literature regarding the number of minor LLRs required before MLLR, with 60 minor LLRs reported as the minimum. Six studies showed a potential benefit of simulation and training programmes in this field. The gradual implementation of LLR combined with simulation-based training programmes could reduce the clinical impact of LC. CONCLUSIONS: The LC in LLR is a long process, and MLLR should be gradually implemented under the supervision of experienced surgeons. Training outside the operating room may reduce the LC in real-life situations.