Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice.

BACKGROUND AND AIMS: Surgical resection remains the gold standard for liver tumor treatment, yet the emergence of postoperative liver failure, known as the small-for-size syndrome (SFSS), poses a significant challenge. The activation of hypoxia sensors in an SFSS liver remnant initiated early angiogenesis, improving the vascular architecture, safeguarding against liver failure, and reducing mortality. The study aimed to elucidate vascular remodeling mechanisms in SFSS and their impact on hepatocyte function and subsequent liver failure. APPROACH AND RESULTS: Mice underwent extended partial hepatectomy to induce SFSS, with a subset exposed to hypoxia immediately after surgery. Hypoxia bolstered posthepatectomy survival rates. The early proliferation of liver sinusoidal cells, coupled with recruitment of putative endothelial progenitor cells, increased vascular density, improved lobular perfusion, and limited hemorrhagic events in the regenerating liver under hypoxia. Administration of granulocyte colony-stimulating factor in hepatectomized mice mimicked the effects of hypoxia on vascular remodeling and endothelial progenitor cell recruitment but failed to rescue survival. Compared to normoxia, hypoxia favored hepatocyte function over proliferation, promoting functional preservation in the regenerating remnant. Injection of Adeno-associated virus serotype 8-thyroxine-binding globulin-hepatocyte nuclear factor 4 alpha virus for hepatocyte-specific overexpression of hepatocyte nuclear factor 4 alpha, the master regulator of hepatocyte function, enforced functionality in proliferating hepatocytes but did not rescue survival. The combination of hepatocyte nuclear factor 4 alpha overexpression and granulocyte colony-stimulating factor treatment rescued survival after SFSS-setting hepatectomy. CONCLUSIONS: In summary, SFSS arises from an imbalance and desynchronized interplay between functional regeneration and vascular restructuring. To improve survival following SFSS hepatectomy, it is essential to adopt a 2-pronged strategy aimed at preserving the function of proliferating parenchymal cells and simultaneously attenuating vascular damage.

Ex Situ Liver Resection and Autotransplantation with Retrohepatic Inferior Vena Cava Reconstruction and Atrial Thrombectomy Under Extracorporeal Circulation for Inferior Vena Cava Leiomyosarcoma.

BACKGROUND: Surgery is the only curative treatment for retrohepatic inferior vena cava (r-IVC) leiomyosarcoma.1 Cavo-hepatic confluence invasion is a poor prognostic situation, requiring extreme liver surgery for selected patients to achieve R0 margins (a crucial prognostic factor). Ex situ liver resection and autotransplantation (ELRA), developed by Pichlmayr et al., permits to achieve such R0 margin.2,3 METHODS: An 84-year-old patient in excellent condition (ECOG 0), without relevant past medical history, was referred for abdominal mass, bilateral lower limbs edema, and dyspnea. Workup revealed a large r-IVC leiomyosarcoma invading cavo-hepatic confluence and protruding in right atrium without any metastasis. After multidisciplinary consultation, surgical treatment was retained. Preoperative transoesophaegal echocardiography confirmed a 4-cm protruding tumoral thrombus in right atrium without abdominalisation possibility. RESULTS: A sterno-laparotomy was performed, consisting of a right nephrectomy for exposure and en bloc total hepatectomy comprising r-IVC after atriotomy for intracardiac thrombectomy under extracorporeal circulation. Tumorectomy (rIVC + segment I and IX) was performed on back table followed by a r-IVC reconstruction through a tubulized homologous venous patch. Native IVC was reconstructed as well, permitting a side-to-side cavo-caval anastomosis for liver reimplantation. Postoperative evolution was eventless except for an early bile leak that required surgical exploration. The patient was discharged on postoperative day 32. Pathological examination confirmed r-IVC-leiomyosarcoma T4N0M0 R0, FNCLCC grade 2. Eight months after surgery, general status was conserved with disappearance of symptoms, and IVC was permeable without leiomyosarcoma recurrence. CONCLUSION: Ex situ liver resection and autotransplantation with atrial thrombectomy is a surgical possibility for R0 r-IVC leiomyosarcoma invading cavo-hepatic confluence in selected patients.

Inferior vena cava reconstruction with non-fascial autologous peritoneum: Retrospective study and literature review.

BACKGROUND: Inferior vena cava (IVC) resection is essential for complete (R0) excision of some malignancies. However, the optimal material for IVC reconstruction remains unclear. Our objective is to demonstrate the efficacy, safety, and advantages of using Non-Fascial Autologous Peritoneum (NFAP) for IVC reconstruction. To conduct a literature review of surgical strategies for tumors involving the IVC. METHODS: We reviewed all IVC reconstructions performed at our institution between 2015 and 2023. Preoperative, operative, postoperative, and follow-up data were collected and analyzed. RESULTS: A total of 33 consecutive IVC reconstructions were identified: seven direct sutures, eight venous homografts (VH), and 18 NFAP. With regard to NFAP, eight tubular (mean length, 12.5 cm) and 10 patch (mean length, 7.9 cm) IVC reconstructions were performed. Resection was R0 in 89% of the cases. Two patients had Clavien-Dindo grade I complications, 2 grade II, 2 grade III and 2 grade V complications. The only graft-related complication was a case of early partial thrombosis, which was conservatively treated. At a mean follow-up of 25.9 months, graft patency was 100%. There were seven recurrences and six deaths. Mean overall survival (OS) was 23.4 months and mean disease-free survival (DFS) was 14.4 months. According to our results, no statistically significant differences were found between NFAP and VH. CONCLUSIONS: NFAP is a safe and effective alternative for partial or complete IVC reconstruction and has many advantages over other techniques, including its lack of cost, wide and ready availability, extreme handiness, and versatility. Further comparative studies are required to determine the optimal technique for IVC reconstruction.

Advancing immunosuppression in liver transplantation: A narrative review.

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation (LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solid-organ transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

Auxilliary Liver Transplantation According to the RAPID Procedure in Noncirrhotic Patients: Technical Aspects and Early Outcomes.

OBJECTIVE: To present technical details and short-term experiences of liver transplantation as a 2-stage procedure using small for size grafts in a multicenter cohort study. BACKGROUND: Two-stage liver transplantation using small for size grafts should be a feasible procedure with lower morbidity and mortality rates. Retrospective cohort study between 2015 and 2022 with multicenter experience. Twenty-three resection and partial liver transplantation with delayed total hepatectomy procedures for noncirrhotic indications were performed in 6 European centers (20 with grafts from living donors and 3 after deceased donation). Procedure's feasibility, graft volumetric changes, morbidity, and mortality of donor and recipient were explored. RESULTS: There was a low donor morbidity (4.3%) in our cohort. Hypertrophy of the graft was rapid (mean graft volume increases 107% between both stages) and offered the opportunity for remnant hepatectomy after a median of 14 days. In all cases, portomesenteric flow was routed to the graft by right remnant portal vein ligation. Portal vein inflow modulation to alleviate transient harmful portal hypertension was not needed in any case. Early postoperative mortality (4.3%) of the recipients were low. Ten patients suffered from complications ≥IIIb according to the Clavien-Dindo classification. CONCLUSIONS: Two-stage liver transplantation is a feasible option for noncirrhotic patients allowing the safe use of small for size grafts and could possibly be extended with caution to liver diseases with portal hypertension and cirrhosis. The resection and partial liver transplantation with delayed total hepatectomy technique might be a viable option for expanding the donor pool given the current organ shortage especially for low-model of end stage liver disease patients.

Meso-Rex bypass for the management of extrahepatic portal vein obstruction in adults (with video).

BACKGROUND: Extrahepatic portal vein obstruction (EHPVO) results in severe portal hypertension (PHT) leading to severely compromised quality of life. Often, pharmacological and endoscopic management is unable to solve this problem. Restoring hepatic portal flow using meso-Rex bypass (MRB) may solve it. This procedure, uncommon in adult patients, is considered the treatment of choice for EHPVO in children. METHODS: From 1997 to 2018, 8 male and 6 female adults, with a median age of 51 years (range 22-66) underwent MRB procedure for EHPVO at the University Hospitals Saint-Luc in Brussels, Belgium. Symptoms of PHT were life altering in all but one patient and consisted of repetitive gastro-intestinal bleedings, sepsis due to portal biliopathy, and/or severe abdominal discomfort. The surgical technique consisted in interposition of a free venous graft or of a prosthetic graft between the superior mesenteric vein and the Rex recess of the left portal vein. RESULTS: Median operative time was 500 min (range 300-730). Median follow-up duration was 22 months (range 2-169). One patient died due to hemorrhagic shock following percutaneous transluminal intervention for early graft thrombosis. Major morbidity, defined as Clavien-Dindo score ≥ III, was 35.7% (5/14). Shunt patency at last follow-up was 64.3% (9/14): 85.7% (6/7) of pure venous grafts and only 42.9% (3/7) of prosthetic graft. Symptom relief was achieved in 85.7% (12/14) who became asymptomatic after MRB. CONCLUSIONS: Adult EHPVO represents a difficult clinical condition that leads to severely compromised quality of life and possible life-threatening complications. In such patients, MRB represents the only and last resort to restore physiological portal vein flow. Although successful in a majority of patients, this procedure is associated with major morbidity and mortality and should be done in tertiary centers experienced with vascular liver surgery to get the best results.

The real incidence of biliary tract complications after adult liver transplantation: the role of the prospective routine use of cholangiography during post-transplant follow-up.

Biliary tract complications (BTCs) still burden liver transplantation (LT). The wide reporting variability highlights the absence of systematic screening. From 2000 to 2009, simultaneous liver biopsy and direct biliary visualization were prospectively performed in 242 recipients at 3 and 6 months (n = 212, 87.6%) or earlier when indicated (n = 30, 12.4%). Median follow-up was 148 (107-182) months. Seven patients (2.9%) experienced postprocedural morbidity. BTCs were initially diagnosed in 76 (31.4%) patients; 32 (42.1%) had neither clinical nor biological abnormalities. Acute cellular rejection (ACR) was present in 27 (11.2%) patients and in 6 (22.2%) BTC patients. Nine (3.7%) patients with normal initial cholangiography developed BTCs after 60 (30-135) months post-LT. BTCs directly lead to 7 (2.9%) re-transplantations and 14 (5.8%) deaths resulting in 18 (7.4%) allograft losses. Bile duct proliferation at 12-month biopsy proved an independent risk factor for graft loss (P = 0.005). Systematic biliary tract and allograft evaluation allows the incidence and extent of biliary lesions to be documented more precisely and to avoid erroneous treatment of ACR. The combination 'abnormal biliary tract-canalicular proliferation' is an indicator of worse graft outcome. BTCs are responsible for important delayed allograft and patient losses. These results underline the importance of life-long follow-up and appropriate timing for re-transplantation.

Total en bloc spondylectomy of T11 and spine shortening performed on a 17-month-old patient: art of the possible.

STUDY DESIGN: Case report. PURPOSE: The authors used spine shortening as an alternative strategy to intercalary graft fixation to restore permanent spine stability for a 17-month-old infant who received total en bloc spondylectomy (TES) of T11 to treat an embryonic rhabdomyosarcoma. TES involves complete removal of vertebra, compensated by spine reconstruction using intercalary allografts and permanent posterior instrumentation, which is not possible for skeletally immature patients with high growth potential and non-ossified vertebrae. METHODS: Surgery was performed over two consecutive days. During the first day, the tumor was released from its dorsal attachments through the posterior approach. During the second day, the tumor was dissected and excised through the anterior approach, leaving a gap between T10 and T12. The two vertebrae were then drawn toward each other until the gap was bridged. The dural sac slipped into the canal under T10 and T12 with no observable kinking. RESULTS: Fifteen weeks after surgery, thoraco-abdominal CT confirmed fusion of the T10 and T12 vertebral bodies. Three years later, the patient lives a normal life with no major neurological deficits or recurrence of sarcoma. CONCLUSIONS: This case report is the first to demonstrate the feasibility of TES with spine shortening of an entire thoracic segment without spine kinking or damage in an infant. This unprecedented surgical technique allowed complete removal of an embryonic rhabdomyosarcoma, while granting rapid stability and growth potential. LEVEL OF EVIDENCE: IV.

Secondary non-resectable liver tumors: A single-center living-donor and deceased-donor liver transplantation case series.

BACKGROUND: During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT. METHODS: Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine (n = 18, 82%) and colorectal metastases (n = 4, 18%); 50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used; the median graft-to-recipient-weight ratios (GRWR) were 1.03% (IQR 0.86%-1.30%) and 0.59% (IQR 0.51%-0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17-107) in the DDLT group and 40 months (IQR 35-116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence. RESULTS: The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively (P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT (P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2-2.2) vs. 3.3 (IQR 2.3-5.2) mg/dL; P = 0.02]. CONCLUSIONS: The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.

Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain.

BACKGROUND: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation (LDLT) is presented. METHODS: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29 (45.3%) females and 35 (54.7%) males was 50.2 years (interquartile range, IQR 32.9-57.5). Twenty-two (34.4%) recipients had no portal hypertension. Three (4.7%) patients had a benign and 33 (51.6%) a malignant tumor [19 (29.7%) hepatocellular cancer, 11 (17.2%) secondary cancer and one (1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months (IQR 41-159) and 39 months (22-91), respectively. RESULTS: Right and left hemi-livers were implanted in 39 (60.9%) and 25 (39.1%) cases, respectively. Median weights of right- and left-liver were 810 g (IQR 730-940) and 454 g (IQR 394-534), respectively. Graft-to-recipient weight ratios (GRWRs) were 1.17% (right, IQR 0.98%-1.4%) and 0.77% (left, 0.59%-0.95%). One- and five-year patient survivals were 85% and 71% (right) vs. 84% and 58% (left), respectively. One- and five-year graft survivals were 74% and 61% (right) vs. 76% and 53% (left), respectively. The patient and graft survival of right and left grafts and of very small (<0.6%), small (0.6%-0.79%) and large (≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3- and 12-month. No donor died while five (7.8%) developed a Clavien-Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three (4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. CONCLUSIONS: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely with low morbidity. The recipient operation carries a major morbidity indicating an important learning curve. Shifting the risk from the donor to the recipient, by moving from the larger right-liver to the smaller left-liver grafts, should be further explored as this policy makes donor hepatectomy safer and may stimulate the development of transplant oncology.

Tacrolimus and Single Intraoperative High-dose of Anti-T-lymphocyte Globulins Versus Tacrolimus Monotherapy in Adult Liver Transplantation: One-year Results of an Investigator-driven Randomized Controlled Trial.

OBJECTIVE: The aim of the study is to evaluate whether intra-operative induction with anti-lymphocytic serum (ALS) is superior to no induction in adult liver transplantation (LT). BACKGROUND: The efficacy of ALS induction remains inconclusive in LT, because of poorly designed trials. METHODS: A randomized controlled trial was conducted, including 206 adults (>15 years) and comparing tacrolimus monotherapy (TAC, n = 109) and tacrolimus plus a single, intraoperative, high-dose (9 mg/kg), rabbit anti-T-lymphocyte globulins (ATLG; n = 97). All patients had similar follow-up, including Banff-scored biopsies. Rejection was considered clinically relevant and treated if pathologic and biochemical changes were concordant. The primary endpoint was immunosuppression minimization to monotherapy; secondary endpoints were biopsy-proven rejection, clinical rejection, patient (PS) and graft (GS) survival. RESULTS: At 1 year, 79/81 (96.3%) ATLG and 101/102 (99.0%) TAC patients were steroid-free (P = 0.585); 28 (34.6%) ATLG, and 31 (30.4%) TAC patients were on double-drug immunosuppression (P = 0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (P = 0.260) and 76% and 90% (P = 0.054).Despite significantly a fewer day-7 moderate-to-severe acute cellular rejections (ACR) in ATLG group (10.0% vs 24.0% in TAC group, P = 0.019), cumulative proportion of patients experiencing steroid-sensitive (11.3% ATLG vs 14.7% TAC, P = 0.539), steroid-resistant (2.1% ATLG vs 3.7% TAC, P = 0.686) and chronic rejection (1.0% ATLG vs 0.9% TAC, P = 1.000) were similar. ATLG administration brought about greater hemodynamic instability and blood products use (P = 0.001). CONCLUSIONS: At 1 year from LT, ATLG induction did not significantly affect immunosuppressive load, treated rejection, patient, and graft survival. The observed adverse events justify a modification of dosing and timing of ATLG infusion. Long-term results are required to judge the ATLG possible benefits on immunosuppressive load and tolerance induction.

Preperitoneal Surgical Approach to Treat Vesicoureteral Anastomotic Leakage, Distal Stenosis or Reflux After Kidney Transplantation.

BACKGROUND: If endourological approaches are not applicable to treat vesicoureteral anastomotic complications after kidney transplantation, the surgical gold standard in many transplant centers is pyeloureterostomy or ureteroureterostomy using the native ureter. We report an original preperitoneal technique that can be used for vesicoureteral reanastomosis in kidney transplant recipients not eligible for endourological treatment. METHODS: Between January 2011 and December 2015, 18 kidney transplant recipients underwent this new surgical procedure. Of this number, 15 subjects with at least 1 year of follow-up were included in the analysis. The indications were vesicoureteral reflux, anastomotic stenosis, and leakage in 8, 5, and 2 patients, respectively. Briefly, a double J stent was preoperatively inserted into the grafted ureter. Surgery was performed through a Pfannenstiel incision. The preperitoneal space surrounding the bladder was dissected and the distal part of the grafted ureter was identified and mobilized. The anastomotic area was resected and another vesicoureteral anastomosis was performed (Lich-Gregoir technique), keeping the JJ stent in place for three weeks. RESULTS: This procedure was performed 213 days (range 17-2608) after kidney transplantation. Median surgical duration was 179 minutes (range 112-314) and median hospital stay 8 days (range 4-14). The success rate was 86.7% (13/15), with a median follow-up of 1148 days (range 517-1808). In two patients, symptomatic recurrence of vesicoureteral reflux required a pyeloureterostomy using the native ureter. CONCLUSIONS: The authors describe a simple technique that avoids transperitoneal dissection, potentially yielding more esthetic results thanks to easy access, as well as excellent outcomes.

The Use of Autologous Peritoneum for Complete Caval Replacement Following Resection of Major Intra-abdominal Malignancies.

OBJECTIVE: Assessment of a simple layer peritoneal tube used as an autogenous inferior vena cava replacement. BACKGROUND: Extensive en-bloc multivisceral resection including major vessels is effective in selected abdominal malignancies, but the need for vascular reconstruction represents a surgical challenge. We describe the use of autologous peritoneum for caval replacement. METHODS: Autogenous parietal peritoneum without fascial backing was harvested and tubularized to replace the inferior vena cava (IVC) in four patients with complex abdominal tumors. Surgical morbidity was evaluated using the Clavien-Dindo classification, and graft patency was systematically evaluated with ultrasound. RESULTS: All four patients had multiorgan resections for malignancies involving the retro-hepatic IVC, and they all required the replacement of infrarenal and suprarenal IVC segments. Additionally, all four required a right nephrectomy, two had a combined major hepatectomy, and one patient needed a veno-venous bypass. All had an R0 resection. A clinical follow-up took place between 5 and 11 months after surgery for each patient. Four-month graft patency was confirmed by ultra-sound and TDM with no sign of disease recurrence. CONCLUSIONS: Autologous peritoneum without fascial backing is a good and safe option for circumferential replacement of IVC after extensive en-bloc tumor resection with IVC involvement.

Surgical Treatment of Colorectal Cancer with Peritoneal and Liver Metastases Using Combined Liver and Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Report from a Single-Centre Experience.

BACKGROUND: Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer. OBJECTIVES: The aims of this study were to evaluate the safety of combining liver surgery (LS) with HIPEC and CRS (which remains controversial) and its impact on overall survival (OS) rates. METHODS: From 2007 to 2015, a total of 77 patients underwent CRS/HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. Twenty-five of these patients underwent concomitant LS for suspicion of liver metastases (LM; group 2), and were compared with patients who underwent CRS/HIPEC only (group 1). Demographic and clinical data were reviewed retrospectively. RESULTS: Among the group 2 patients, two underwent major hepatectomies, six underwent multiple wedge resections, 16 underwent single wedge resections (one with radiofrequency ablation), and one underwent radiofrequency ablation alone. For groups 1 and 2, median peritoneal cancer index was 6 and 10 (range 0-26; p = 0.08), complication rates were 15.4 and 32.0 % (Dindo-Clavien ≥3; p = 0.15), and median follow-up was 34.2 and 25.5 months (range 0-75 and 3-97), respectively. One group 2 patient died of septic shock after 66 days. Pathology confirmed LM in 21 patients in group 2 (four with benign hepatic lesions were excluded from long-term outcome analysis). Two-year OS rates were 89.5 and 70.2 % (p = 0.04), and 2-year recurrence-free survival rates were 38.3 and 13.4 % (p = 0.01) in groups 1 and 2, respectively. CONCLUSIONS: Simultaneous surgery for colorectal LM and PC is both feasible and safe, with low postoperative morbidity. Further longer-term studies would help determine its impact on patient survival.

Association of Serum Levels and Immunohistochemical Labelling of Des-Gamma-Carboxy-Prothrombin in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is one of the main reasons for liver transplantation (LT). Biomarkers, such as alpha-foetoprotein (AFP) and Des-gamma-carboxy-prothrombin (DCP), can be helpful in defining the recurrence risk post LT. This study aims to evaluate the association between the intensity of DCP immunohistochemical labelling and serum DCP levels in patients undergoing LT for HCC. We carried out a prospective monocentric study including patients who all underwent LT for cirrhosis between 2016 and 2018 and all fell under the Milan criteria. The accepted diagnostic criteria for HCC were contrast-enhanced imaging and histology. Thirty-nine patients were followed for a median of 21 months, with HCC lesions categorized into negative, focally positive, and diffusely positive groups based on DCP immunohistochemistry. The serum DCP levels were significantly higher in the positive groups (258 mAU/mL for the focally and 257 mAU/mL for the diffusely positive) than in the negative group (48 mAU/mL) (p = 0.005) at diagnosis and at the time of liver transplantation (220 mAU/mL for the diffuse positive group). Microvascular invasion (58.8% vs. 19.0% for the diffusely positive and negative groups, respectively, p < 0.001) and lesion size (20 mm in the diffusely labelled group versus 12 mm in the other groups, p = 0.002) were significantly correlated with DCP labelling. Late recurrence occurred only in the positive groups; in the negative group, it occurred within the first 3 months after transplantation. DCP labelling in liver lesions correlates with serum levels and a more aggressive tumour profile. Further investigation is needed to determine if highly DCP-labelled tumours allow for the better selection of high-risk patients before LT.

Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

Diagnostic Superiority of Dual-Time Point [18F]FDG PET/CT to Differentiate Malignant from Benign Soft Tissue Tumors.

[18F]FDG PET/CT is used in the workup of indeterminate soft tissue tumors (STTs) but lacks accuracy in the detection of malignant STTs. The aim of this study is to evaluate whether dual-time point [18F]FDG PET/CT imaging (DTPI) can be useful in this indication. In this prospective study, [18F]FDG PET/CT imaging was performed 1 h (t1) and 3 h (t2) after injection. Tumor uptake (SUVmax) was calculated at each time point to define a retention index (RI) corresponding to the variation between t1 and t2 (%). Sixty-eight patients were included, representing 20 benign and 48 malignant tumors (including 40 sarcomas). The RI was significantly higher in malignant STTs than in benign STTs (median: +21.8% vs. -2%, p < 0.001). An RI of >14.3% predicted STT malignancy with a specificity (Sp) of 90% and a sensitivity (Se) of 69%. An SUVmaxt1 of >4.5 was less accurate with an Sp of 80% and an Se of 60%. In a subgroup of tumors with at least mild [18F]FDG uptake (SUVmax ≥ 3; n = 46), the RI significantly outperformed the diagnostic accuracy of SUVmax (AUC: 0.88 vs. 0.68, p = 0.01). DTPI identifies malignant STT tumors with high specificity and outperforms the diagnostic accuracy of standard PET/CT.