Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits".

Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.

Impact of Robotic Assistance on Complications in Bariatric Surgery at Expert Laparoscopic Surgery Centers: A Retrospective Comparative Study With Propensity Score.

OBJECTIVE: To investigate the way robotic assistance affected rate of complications in bariatric surgery at expert robotic and laparoscopic surgery facilities. BACKGROUND: While the benefits of robotic assistance were established at the beginning of surgical training, there is limited data on the robot's influence on experienced bariatric laparoscopic surgeons. METHODS: We conducted a retrospective study using the BRO clinical database (2008-2022) collecting data of patients operated on in expert centers. We compared the serious complication rate (defined as a Clavien score≥3) in patients undergoing metabolic bariatric surgery with or without robotic assistance. We used a directed acyclic graph to identify the variables adjustment set used in a multivariable linear regression, and a propensity score matching to calculate the average treatment effect (ATE) of robotic assistance. RESULTS: The study included 35,043 patients [24,428 sleeve gastrectomy (SG); 10,452 Roux-en-Y gastric bypass (RYGB); 163 single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S)], with 938 operated on with robotic assistance (801 SG; 134 RYGB; 3 SADI-S), among 142 centers. Overall, we found no benefit of robotic assistance regarding the risk of complications (average treatment effect=-0.05, P =0.794), with no difference in the RYGB+SADI group ( P =0.322) but a negative trend in the SG group (more complications, P =0.060). Length of hospital stay was decreased in the robot group (3.7±11.1 vs 4.0±9.0 days, P <0.001). CONCLUSIONS: Robotic assistance reduced the length of stay but did not statistically significantly reduce postoperative complications (Clavien score≥3) following either GBP or SG. A tendency toward an elevated risk of complications following SG requires more supporting studies.

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH. METHODS: A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Occurrences of biliary and vascular complications, rejection, sepsis, retransplantation and death were collected during the first year after LT. RESULTS: A total of 344 patients (78.8% of women, 17.0% of (sub)fulminant hepatitis and 19.2% of chronic liver diseases transplanted in the context of acute-on-chronic liver failure [ACLF]) were included, with a median age at LT of 43.6 years. Acute rejection, sepsis, biliary and vascular complications occurred in respectively 23.5%, 44.2%, 25.3% and 17.4% of patients during the first year after LT. One-year graft and patient survivals were 84.3% and 88.0% respectively. The main cause of early death was sepsis. Pre-LT immunosuppression was not associated with an increased risk for early infections or surgical complications. Significant risk factors for septic events were LT in the context of (sub)fulminant hepatitis or ACLF, acute kidney injury at the time of LT (AKI) and occurrence of biliary complications after LT. AKI was the only independent factor associated with graft (HR = 2.5; 95% CI: 1.1-5.4; p = .02) and patient survivals (HR = 2.6; 95% CI: 1.0-6.5; p = .04). CONCLUSION: Early prognosis is good after LT for AIH and is not impacted by pre-LT immunosuppression but by the presence of AKI at the time of LT.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). METHODS: A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded. RESULTS: The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0 months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4-6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2-5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5-5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4-6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2-3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0-3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2-3.5; p = 0.006) complications. CONCLUSION: Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.

Unplanned surgery after colorectal resection: laparoscopy at the index surgery is a protective factor against mortality.

BACKGROUND: The aim of this study was to assess risk factors of mortality after unplanned surgery following colorectal resection. METHODS: All the consecutive patients who underwent colorectal resection between 2011 and 2020 in a French national cohort were retrospectively included. Perioperative data of the index colorectal resection (indication, surgical approach, pathological analysis, postoperative morbidity), and characteristics of unplanned surgery (indication, time to complication, time to surgical redo) were assessed in order to identify predictive factors of mortality. RESULTS: Among 547 included patients, 54 patients died (10%; 32 men; mean age = 68 ± 18 years, range 34-94 years). Patients who died were significantly older (75 ± 11 vs 66 ± 12 years, p = 0.002), frailer (ASA score 3-4 = 65 vs 25%, p = 0.0001), initially operated through open approach (78 vs 41%, p = 0.0001), and without any anastomosis (17 vs 5%, p = 0.003) than those alive. The presence of colorectal cancer, the time to postoperative complication and the time to unplanned surgery were not significantly associated to the postoperative mortality. After multivariate analysis, 5 independent predictive factors of mortality were identified: old age (OR 1.038; IC 95% 1.006-1.072; p = 0.02), ASA score = 3 (OR 5.9, CI95% 1.2-28.5, p = 0.03), ASA score = 4 (OR 9.6; IC95% 1.5-63; p = 0.02), open approach for the index surgery (OR 2.7; IC95% 1.3-5.7; p = 0.01), and delayed management (OR 2.6; IC95% 1.3-5.3; p = 0.009). CONCLUSION: After unplanned surgery following colorectal surgery, one out of 10 patients dies. The laparoscopic approach during the index surgery is associated with a good prognosis in the case of unplanned surgery.

SAGES SAFE CHOLE program changes surgeons practice in France-results of the FCVD implementation of SAFE CHOLE in France.

BACKGROUND: With the Society of Gastrointestinal and Endoscopic Surgeons supervision, the Safe Cholecystectomy Task Force (SAFE CHOLE) was translated into French by the the Federation of Visceral and Digestive Surgery (FCVD) and adopted to run on its national e-learning platform for surgical continuing medical education (CME). The objective of this study was to assess the impact of the SAFE CHOLE (SF) program on the knowledge and practice of French surgeons performing cholecystectomy and participating in the FCVD lead CME activity. METHODS: To obtain CME certification, each participant must fill out three FCVD validated questionnaires regarding (1) the participants' routine practice for cholecystectomy, (2) the participants' knowledge and practice after successful completion of the program, and (3) the educational value of the SC program. RESULTS: From 2021 to 2022, 481 surgeons completed the program. The overall satisfaction rate for the program was 81%, and 53% of the surgeons were practicing routine cholangiography before the SC program. Eighty percent declared having acquired new knowledge. Fifty-six percent reported a change in their practice of cholecystectomy. Of those, 46% started routinely using the critical view of safety, 12% used a time-out prior transection of vital structures, and 11% adopted routine intraoperative cholangiography. Sixty-seven percent reported performing a sub-total cholecystectomy in case the CVS was unobtainable. If faced with BDI, 45% would transfer to a higher level of care, 33% would seek help from a colleague, and 10% would proceed with a repair. Ninety percent recommended adoption of SC by all general surgeons and 98% reported improvement of patient safety. CONCLUSIONS: Large-scale implementation of the SC program in France is feasible within a broad group of diverse specialty surgeons and appears to have a significant impact on their practice. These data should encourage other surgeons and health systems to engage in this program.

Systemic causes are important risk factors for failure after unscheduled colorectal revision surgery.

BACKGROUND: The rates of unscheduled revision surgery (URS) after colorectal surgery and failure to rescue-surgical (FTR-s) are 2.4% and 11-17% respectively. The aim of this study was to evaluate the causes of URS lethality to reduce this rate after colorectal surgery. METHODS: From 2011 to 2021, 337 surgeons collected 547 URS. Type of procedure, time course, diagnostic and detection means, time to decision, time to complication(s), causes of URS, delay of URS, and death were recorded and allowed for multivariate systemic analysis of risk factors for death (FTR-s) after URS. Systemic causes of delay were analyzed as assessment of urgency, communication, skills, organization of the operative program, and transport. RESULTS: The two main causes of URS were infectious (66% of which 50% by fistula or anastomotic release) and vascular (18%). The rate of FTRs was 10%. The systemic causes rate of FTR-s were 35%. The FTRs were related to the patient (ASA score 3-4: RR: 6 [1-40]; age: RR: 1.05 [1-1.1]), to the surgical procedure (laparotomy: RR: 4.5 [1.6-12]) and to the systemic causes responsible for the delay in the realization of URS (RR: 4.1 [1.4-12]). CONCLUSION: By avoiding systemic causes, more than one third of the deaths from FTR-s after colorectal surgery could be avoided.

Five-year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study.

BACKGROUND AND AIMS: To report 5-year outcomes of the CERTITUDE study. METHODS: An observational study in patients with liver transplantation (LTx) compared the long-term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6-month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow-up. RESULTS: Of the 143 enrolled patients, 119 completed the 5-year follow-up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, -15.53 ml/min/1.73 m2 and EVR, -14.56 ml/min/1.73 m2 ). In the treatment subgroups based on actual treatment received, renal function was preserved better in the EVR subgroup compared with other subgroups (p = .051). Treated biopsy-proven acute rejection was higher in the EVR group (15.4% vs. 6.4%); however, the majority of events were mild in severity. MACE occurred in 9.2% vs. 14.1% of patients in the EVR and TAC groups respectively (p = .370). De novo cancer was reported in 14 and 5 patients in EVR and TAC groups respectively. Hepatocellular carcinoma (HCC) recurrence was observed in the TAC group alone (n = 4). Adverse events and treatment discontinuation owing to an adverse event were higher in the EVR group. CONCLUSIONS: The CERTITUDE study demonstrated that EVR- and TAC-based regimens have comparable efficacy, safety and tolerability up to 5 years post-LTx.

Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival.

BACKGROUND AND AIMS: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors. METHOD: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres. RESULTS: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035). CONCLUSION: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.

Mesenchymal Stem Cells and Platelet Rich Plasma Therapy to Treat Leak After Sleeve Gastrectomy.

BACKGROUND: One of the most feared and life-threatening complications after sleeve gastrectomy (SG) is staple line leak, with an incidence between 1 and 4%. Stable patients may be managed conservatively, with antibiotics, percutaneous drainage and endoscopy-based treatment. We propose mesenchymal stem cells (MSC) and platelet rich plasma (PRP) therapy as an innovative technique to treat leak after SG. MATERIAL AND METHODS: Bone marrow MSCs is obtained by centrifugation of tibial puncture specimen. A peripheral whole blood sample is retrieved from the patient and centrifuged to obtain PRP. During endoscopy, the first 10 mL are injected in 4quadrants (equal volume) in the submucosae around the internal orifice. The second 10 mL are injected in the wall of the fistula tract. RESULTS: The immediate course following the endoscopy was uneventful in both reported cases. The leaks healed in 30 and 42 D, respectively. Oral nutrition was progressively started during the third WK and fourth WK following the injection for both patients. No adverse event was noted during the follow-up period. CONCLUSION: The management of fistulas post SG is controversial and actual available treatments present a relatively prolonged healing time. MSC administration retains a high potential value in the treatment of these fistulas. Further studies and wider clinical trials are mandatory to determine the impact of MSC administration.

Malignancy in bariatric surgery patients: a French multisite cohort.

BACKGROUND: Bariatric surgery is associated with decreased cancer-related mortality. An indefinite proportion of patients that undergo bariatric surgery have a history of malignancy or will develop cancer. In these patients, weight loss and oncologic evolution needed to be assessed. The aim of this study was to report the results of patients diagnosed with malignancy before and after bariatric surgery in a French multisite cohort. METHODS: We conducted a retrospective cohort study of all patients who underwent bariatric surgery in six university centers. Patients were divided in two groups: patients with a preoperative history of malignancy and patients diagnosed with malignancy during the follow-up. Both groups were compared with control groups of patients that underwent surgery during the same period. RESULTS: From 2008 to 2018, 8927 patients underwent bariatric surgery. In patients with a history of malignancy (n = 90), breast and gynecologic cancers were predominant (37.8%). Median interval between malignancy and surgery was 60 (38-118) months. After a follow-up of 24 (4-52) months, 4 patients presented with cancer recurrence. Comparative analysis demonstrated equivalent weight loss one year after surgery. In patients with postoperative malignancy (n = 32), breast and gynecologic cancers were also predominant (40.6%). Median interval between surgery and malignancy was 22 (6-109) months. In the comparative analysis, weight loss was similar at 2 years. CONCLUSIONS: History of malignancy should not be considered as an absolute contraindication for bariatric surgery. Gynecological cancer screening should be reinforced before and after surgery. The development of malignancy postoperatively does not seem to affect mid-term bariatric outcomes.

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.

Results of the FUSE Evaluation Project in France.

BACKGROUND: The Federation of Visceral and Digestive Surgery (FCVD) is in charge in France of the continuing medical education of digestive surgeons. Since 2016 and in collaboration with SAGES, it has offered the Fundamental Use of Surgical Energy (FUSE) program as part of the continuing education for surgeons including eLearning and hands-on workshops. METHODS: The aim of this study was to evaluate the impact of the FUSE program on the participants by participating in a knowledge test and completing a survey. RESULTS: 485 participants fully completed the knowledge test of 18 questions. Post-test assessment showed an increase in the mean score with respect to pre-test assessment, and the surgeons who have participated to the hands-on workshops had a better score. 304 participants filled the survey of 6 questions. The majority were satisfied by the FUSE program and felt that the objectives were achieved. CONCLUSIONS: The FUSE program developed by SAGES and adopted by the FCVD in France was very much appreciated by the participants and achieved its educational objectives. Our goal is to spread it as widely as possible to all members of the operating room team.

Feasibility and Efficiency of Sutureless End Enterostomy by Means of a 3D-Printed Device in a Porcine Model.

Objective. The aim of this study is to present a 3-dimensional (3D)-printed device to simply perform abdominal enterostomy and colostomy. Summary Background Data. Enterostomy and colostomy are frequently performed during abdominal surgery. 3D-printed devices may permit the creation of enterostomy easily. Methods. The device was designed by means of a CAD (computer-aided design) software, Rhinoceros 6 by MC Neel, and manufactured using 3D printers, Factory 2.0 by Omni 3D and Raise 3D N2 Dual Plus by Raise 3D. Colostomy was scheduled on a human cadaver and on 6 Pietrain pigs to test the device and the surgical technique. Results. The test on the cadaver showed that the application of the device was easy. Test on porcine models confirmed that the application of the device was also easy on the living model. The average duration of the surgical procedure was 32 minutes (25-40 minutes). For the female pigs, return to full oral diet and recovery of a normal bowel function was observed at postoperative day 2. The device fell by itself on average on the third day. Until day 10, when euthanasia was practiced, the stoma mucosa had a good coloration indicating a perfect viability of tissues. No complications were observed. Conclusions. This is the first study that describes the use of a 3D-printed device in abdominal surgery. End-type colostomy using a 3D-printed device can be safely and easily performed in an experimental porcine model, without postoperative complications. Further studies are needed to evaluate its utility in the clinical setting.

Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial.

Background A prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study. Purpose To evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC. Materials and Methods This prospective single-arm phase II study was conducted between January 2015 and January 2017. Participants with unresectable HCC were included in the trial and underwent TACE with idarubicin-eluting beads. The primary end point was 6-month ORR assessed with independent central review by using modified Response Evaluation Criteria in Solid Tumors. Secondary end points were best ORR during the first 6 months, overall survival, progression-free survival, time to progression, and safety. A two-stage Fleming statistical design was used. Results Forty-six study participants (mean age, 71.2 years ± 10.2; six women and 40 men) were included; 44 participants underwent at least one TACE session. The 6-month ORR was 52% (23 of 44). The best ORR achieved was 68% (30 of 44). Fourteen of 44 (32%) participants underwent a curative treatment after TACE. Median progression-free survival, time to progression, and overall survival were 6.6 months, 9.5 months, and 18.6 months, respectively. TACE was discontinued for toxicity in four of 44 (9%) participants. The most frequent grade 3-4 adverse events were elevated aspartate aminotransferase (14 of 44, 32%), elevated γ-glutamyl transpeptidase (eight of 44, 18%), hyperbilirubinemia (seven of 44, 16%), elevated alanine aminotransferase (seven of 44, 16%), and pain (seven of 44, 16%). Conclusion Idarubicin-eluting beads showed a good safety profile and promising objective response rate and time to progression when used as part of a transarterial chemoembolization regimen for unresectable hepatocellular carcinoma. © RSNA, 2019 See also the editorial by Padia in this issue.

Early Switch From Tacrolimus to Everolimus After Liver Transplantation: Outcomes at 2 Years.

The observational CERTITUDE study follows liver transplant patients who completed the SIMCER trial. SIMCER randomized patients at month 1 after transplant to everolimus (EVR) with stepwise tacrolimus (TAC) withdrawal or to standard TAC, both with basiliximab induction and mycophenolic acid ± steroids. After completing SIMCER at 6 months after transplant, 65 EVR-treated patients and 78 TAC-treated patients entered CERTITUDE. At month 24 after transplant, 34/65 (52.3%) EVR-treated patients remained calcineurin inhibitor (CNI) free. Mean estimated glomerular filtration rate (eGFR) was significantly higher with EVR versus TAC during months 3-12. At month 24, eGFR values were 83.6 versus 75.3 mL/minute/1.73 m2 , respectively (P = 0.90) and adjusted mean change in eGFR from randomization was -8.0 versus -13.5 mL/minute/1.73 m2 (P = 0.15). At month 24, 45.9%, 31.1%, and 23.0% of EVR-treated patients had chronic kidney disease stages 1, 2, and 3, respectively, versus 25.7%, 45.7%, and 28.6% of TAC-treated patients (P = 0.05). Treated biopsy-proven acute rejection affected 4 EVR-treated patients and 2 TAC patients during months 6-24. Adverse events led to study discontinuation in 15.4% and 7.7% of EVR-treated and TAC-treated patients, respectively. Grade 3 or 4 hematological events were rare in both groups. A CNI-free EVR-based maintenance regimen appears feasible in approximately half of liver transplant patients. It preserves renal function effectively with good efficacy without compromising safety or hematological tolerance.

Treatment of complex recurrent fistula-in-ano by surgery combined to autologous bone marrow-derived mesenchymal stroma cells and platelet-rich plasma injection.

PURPOSE: We report a case of successful management of complex recurrent cryptoglandular fistula-in-ano by surgery combined with autologous bone marrow-derived mesenchymal stroma cells (MSCs) and platelet-rich plasma (PRP) injection. METHODS: Clinical, radiological, and surgical data of the patient were reviewed, as well as the current literature on complex fistula-in-ano. RESULTS: A 37-year-old man with a recurrent cryptoglandular perianal fistula was addressed to our department. Inflammatory bowel disease was excluded by clinical history, endoscopy, and blood tests. Physical examination and MRI showed an anterior external orifice on the midline, 5 cm from the anal verge, with an internal orifice on the same line. Surgery combined to injection of MSC-PRP solution was successfully performed. MSC-PRP solution was prepared while the patient was under general anesthesia: bone marrow MSCs were obtained by centrifugation of a tibial puncture specimen and PRP from a peripheral whole blood sample of the patient. There were no adverse events post-operatively. Clinical and MRI examination 4 months after treatment confirmed the absence of perianal fistula. More than 2 years after surgery, there has been no recurrence. CONCLUSIONS: Treatment of complex recurrent cryptoglandular fistula-in-ano by surgery combined to autologous bone marrow-derived MSCs and PRP injection seems safe in selected patients, allowing long-term healing. This procedure seems promising but further evaluation by clinical trials is warranted.

Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients.

De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08-2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09-2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68-3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97-9.48), esophageal (SIR = 4.76; 95% CI, 3.56-6.24), lung (SIR = 2.56; 95% CI, 2.21-2.95), and lip-mouth-pharynx (SIR = 2.20; 95% CI, 1.72-2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.

Pancreatectomy combined with multivisceral resection for pancreatic malignancies: is it justified? Results of a systematic review.

BACKGROUND: Multivisceral resections combined with pancreatectomy have been proposed in selected patients with tumor invasion into adjacent organs, in order to allow complete tumor resection. Some authors have also reported multivisceral resection combined with metastasectomy in very selected cases. The utility of this practice is debated. The aim of the review is to compare the postoperative results and survival of pancreatectomies combined with multivisceral resections with those of standard pancreatectomies. METHODS: A systematic literature search was performed to identify all studies published up to February 2017 that analyzed data of patients undergoing multivisceral and standard pancreatectomies. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. RESULTS: Three studies were retrieved, including 713 (80%) patients undergoing standard pancreatectomies and 176 (20%) undergoing multivisceral resections (MVR). Postoperative morbidity ranged from 37% to 50% after standard resections and from 56% to 69% after MVR. In-hospital mortality ranged from 4% after standard pancreatectomies to 10% after MVR. Median survival ranged from 20 to 23 months in standard resections and from 12 to 20 months after MVR, without significant differences. DISCUSSION: The current literature suggests that multivisceral pancreatectomies are feasible and may increase the number of completely resected patients. Morbidity and mortality are higher than after standard pancreatectomies, and these procedures should be reserved to selected patients in referral centers. Further studies on the role of neoadjuvant therapy in this setting are advisable.