The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study.

BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.

Somatostatin vs. Octreotide for Prevention of Postoperative Pancreatic Fistula The PREFIPS Randomized Clinical Trial A FRENCH 007 - ACHBT Study.

OBJECTIVE: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. PATIENTS AND METHODS: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 µg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs. DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. RESULTS: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a non-dilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 d). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (Chi-2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. CONCLUSIONS: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.

An unusual case of primary splenic soft part alveolar sarcoma: case report and review of the literature with emphasis on the spectrum of TFE3-associated neoplasms.

BACKGROUND: Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis. CASE PRESENTATION: In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis. CONCLUSION: We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.

Comparison of Two Dexmedetomidine Administration Strategies on the Incidence of Postoperative Respiratory Complications: A Retrospective, Inverse Probability of Treatment Weighted Study.

Randomized controlled trials have shown a higher risk of postoperative hypoxemia and delayed extubation with opioid-free anesthesia (OFA), compared with opioid anesthesia. The practice of OFA is not standardized. The objective of this study is to investigate the association between the dexmedetomidine administration protocol used and the occurrence of postoperative respiratory complications. This work is a retrospective, propensity score-adjusted study (inverse probability of treatment weighting) conducted between January 2019 and September 2021 in a French tertiary care university hospital, including 180 adult patients undergoing major digestive surgery. Comparison of 2 anesthesia protocols: with a continuous intravenous maintenance dose of dexmedetomidine following a bolus (group B+M, n = 105) or with a bolus dose alone (group B, n = 75). The main outcome measure was a composite respiratory end point within 24 hours of surgery. There was no significant difference in the incidence of overall respiratory complications, as assessed by the primary end point. Nevertheless, there were more patients with postoperative hypercapnia in group B+M than in group B (16% vs 2.5%, P = .004). Patients in group B+M were extubated later than patients in group B (group B+M, median 40 minutes, IQR 20-74 minutes; group B, median 20 minutes, IQR 10-50 minutes; P = .004). Our study showed negative results for the primary end point. However, data on the increased risk of postoperative hypercapnia in patients receiving a maintenance dose of dexmedetomidine are new. Other prospective randomized studies with greater power are necessary to confirm these data and to make OFA safer, by reducing the prescribed doses of dexmedetomidine.

Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching.

BACKGROUND: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.

When Gastroplasty Is Not Feasible in Ivor Lewis Esophagectomy: A Single-Center Study of Intrathoracic Esophagojejunostomy.

Objective: The surgical management of tumors of the esophagogastric junction is increasingly performed by minimally invasive Ivor Lewis esophagectomy. However, gastroplasty is not always feasible. The creation of a long loop is an alternative for esophageal reconstruction. The aim of this study was to evaluate the technical feasibility of using a minimally invasive thoracoscopic approach in esophagojejunostomy and to describe the contraindications for gastroplasty. Methods: All patients who had intrathoracic esophagojejunostomy in our center were identified in our database. Since 2016, the preferred approach for intrathoracic esophagojejunostomy is minimally invasive laparoscopy and thoracoscopy, using a long Roux-en-Y jejunal loop with a semimechanical triangular anastomosis technique. Results: Between January 1, 2012 and January 1, 2022, 12 patients who had esophagojejunostomy in our center were included in the study. Among them, 6 had thoracotomy and 6 had total minimally invasive thoracoscopy, representing 3.5% of surgical procedures for esophagogastric junction tumors since 2016. The mean operative time was 416.9 ± 107.47 minutes. No anastomotic leakage was observed in the minimally invasive group versus 2 leakages in the thoracotomy group. The main complication was pneumonia in 3 patients (27.3%). Finally, the main indication for intrathoracic esophagojejunostomy was tumor size with a mean of 4.72 ± 2.35 cm and the patient's surgical history. Conclusion: A total minimally invasive approach using a long jejunal loop with triangular anastomosis could be a feasible and reproducible alternative to gastroplasty to restore continuity in Ivor Lewis esophagectomy when the stomach cannot be used.

ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. OBJECTIVES: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC. METHODS: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS. RESULTS: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival. CONCLUSIONS: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup.

BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Can the Realization of an External Wirsungostomy be an Option for High-Risk Pancreatic Anastomosis After Pancreaticoduodenectomy?

BACKGROUND: Clinically relevant postoperative pancreatic fistula (POPF) occurs in 15-20% of patients after pancreaticoduodenectomy (PD) and reintervention in the setting of Grade C POPF remains associated with a mortality rate of up to 25%. In patients at high risk of POPF, PD with external wirsungostomy (EW) could be a safe alternative that avoids pancreatico-enteric anastomosis while preserving the remnant pancreas. METHODS: Of the 155 consecutive patients who underwent PD from November 2015 to December 2020, 10 patients were managed using an EW, all with a fistula risk score (FRS) ≥ 7 and BMI ≥30 kg/m2, and/or major associated abdominal surgery. The pancreatic duct was cannulated with a polyethylene tube to allow good external drainage of the pancreatic fluid. We retrospectively analyzed postoperative complications and endocrine and exocrine insufficiencies. RESULTS: The median alternative FRS was 36.9% [22.1-45.2]. There was no postoperative death. The 90-day overall severe complication (grade ≥3) rate was 30% (n = 3 patients), no patient required reoperation, and 2 hospital readmissions occurred. 3 patients experienced Grade B POPF (30%), managed using image-guided drainage for 2 patients. The external pancreatic drain was removed after a median drainage time of 75 days [63-80]. Two patients presented with late symptoms (> 6 months) warranting interventional management (pancreaticojejunostomy and transgastric drainage). Six patients experienced significant weight loss (> 2 kg) 3 months after surgery. One year after surgery, 4 patients still complained of diarrhea and were treated with transit-delaying drugs. One patient presented new-onset diabetes one year after surgery, and 1 of the 4 patients with preexisting diabetes experienced worsening disease. CONCLUSION: EW after PD might be a solution to reduce post-operative mortality following PD in high-risk patients.

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

Paradigm shift: should preoperative 3D reconstruction models become mandatory before hepatectomy for hepatocellular carcinoma (HCC)? Results of a multicenter prospective trial.

BACKGROUND: A preoperative surgical strategy before hepatectomy for hepatocellular carcinoma is fundamental to minimize postoperative morbidity and mortality and to reach the best oncologic outcomes. Preoperative 3D reconstruction models may help to better choose the type of procedure to perform and possibly change the initially established plan based on conventional 2D imaging. METHODS: A non-randomized multicenter prospective trial with 136 patients presenting with a resectable hepatocellular carcinoma who underwent open or minimally invasive liver resection. Measurement was based on the modification rate analysis between conventional 2D imaging (named "Plan A") and 3D model analysis ("Plan B"), and from Plan B to the final procedure performed (named "Plan C"). RESULTS: The modification rate from Plan B to Plan C (18%) was less frequent than the modification from Plan A to Plan B (35%) (OR = 0.32 [0.15; 0.64]). Concerning secondary objectives, resection margins were underestimated in Plan B as compared to Plan C (-3.10 mm [-5.04; -1.15]). CONCLUSION: Preoperative 3D imaging is associated with a better prediction of the performed surgical procedure for liver resections in HCC, as compared to classical 2D imaging.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

Evaluation of sarcopenia biomarkers in older patients undergoing major surgery for digestive cancer. SAXO prospective cohort study.

BACKGROUND: The aim of the study was to prospectively evaluate different biomarkers to identify the most reliable for anticipating complications after major abdominal surgery for digestive cancer in older patients and compare their performance to the existing definition and screening algorithm of sarcopenia from EWGSOP. METHODS: Ninety-five consecutive patients aged over 65 years who underwent elective surgery for digestive cancer were prospectively included in the SAXO study. Sarcopenia was defined according to EWGSOP criteria (four level from no sarcopenia to severe sarcopenia). Strength and physical performance were evaluated with the handgrip test (HGT) and gait speed test (GST), respectively. CT scan analysis was used to calculate the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Measures were adjusted to body mass index (BMI). Complication grading was performed using the Clavien‒Dindo classification. A doubly robust estimator with multivariable regression was used to limit bias. RESULTS: Sixteen patients presented with sarcopenia. Adjusted to BMI, sarcopenic patients had an increased IMATBMI (0.35 vs. 0.22; p = 0.003) and increased VATBMI (7.85 vs. 6.13; p = 0.048). In multivariable analysis, IMAT was an independent risk factor for minor and severe complications (OR = 1.298; 95% CI [1.031: 1.635] p = 0.027), while an increased SAT area was a protective factor (OR = 0.982; 95% CI [0.969: 0.995] p = 0.007). Twenty-two patients were obese (BMI ≥30 kg/m2). While no association was observed between obesity and sarcopenia (according to EWGSOP definition), obese patients had increased IMATBMI (0.31 vs. 0.23; p = 0.010) and VATBMI (8.40 vs. 6.49; p = 0.019). The combination of SAT, VAT and IMAT performed well to anticipate severe complication (AUC = 0.759) while AUC of EWGSOP 2010 and 2019 algorithm were 0.660 and 0.519, respectively. DISCUSSION: Non-invasive and imaging related measures of IMAT, SAT and VAT seems to be valuable tools to refine risk-assessment of older patients in surgery and specially to detect myosteatosis in obese ones.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

Circulating DNA changes are predictive of disease progression after transarterial chemoembolization.

Transarterial chemoembolization (TACE) is used to treat patients with unresectable hepatocellular carcinoma (HCC). We evaluated the clinical impact of a-fetoprotein (AFP) and circulating cell-free and tumor DNA (cfDNA and ctDNA) changes around the TACE procedure. Our prospective monocentric study enrolled consecutive patients treated with TACE, with samples collected at baseline (D - 1), Day 2 (D + 2) and 1 month (M + 1) after TACE. cfDNA was quantified by the fluorometric method, and ctDNA was quantified by digital polymerase chain reaction designed for two hotspot TERT mutations. Computerized tomography scans or magnetic resonance imaging were performed at M + 1 every 3 months following TACE and independently reviewed. The objective was to identify thresholds of cfDNA, ctDNA and AFP changes associated with progressive disease (PD) using receiver operating characteristic curves. Thirty-eight patients were included from March 2018 to March 2019. All markers significantly increased from D - 1 to D + 2 (P < .005), and cfDNA and ctDNA significantly decreased from D + 2 to M + 1 (P < .0001). The analysis of changes from D - 1 to M + 1 identified thresholds at +31.4% for cfDNA and 0% for ctDNA that were significantly associated with PD at M + 1 (44.4% [>+31.4%] vs 3.8% [≤+31.4%] and 50.0% [>0%] vs 5.0% [≤0%], respectively). No significant threshold was identified for AFP. Using a score combining cfDNA and ctDNA, the patients were classified into high- or low-risk PD groups at M + 1, with PD rates of 80.0% vs 4.3% (P = .001) and median progression-free survival times of 1.3 vs 10.3 months (P = .002). Our study suggests that cfDNA and ctDNA increases around the TACE procedure and are associated with therapeutic failure.