Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

Acute humoral rejection (AHR) is uncommon after ABO-compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specif ic antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Liver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

Rescue associating liver partition and portal vein ligation for staged hepatectomy after portal embolization: Our experience and literature review

AIM To report a single-center experience in rescue associating liver partition and portal vein ligation for staged hepatectomy(ALPPS), after failure of previous portal embolization. We also performed a literature review.METHODS Between January 2014 and December 2015, every patient who underwent a rescue ALPPS procedure in Toulouse Rangueil University Hospital, France, was included. Every patient included had a project of major hepatectomy and a previous portal vein embolization(PVE) with insufficient future liver remnant to body weight ratio after the procedure. The ALPPS procedure was performed in two steps(ALPPS-1 and ALPPS-2), separated by an interval phase. ALPPS-2 was done within 7 to 9 d after ALPPS-1. To estimate the FLR, a computed tomography scan examination was performed 3 to 6 wk after the PVE procedure and 6 to 8 d after ALPPS-1. A transcystic stent was placed during ALPPS-1 and remained opened duringthe interval phase, in order to avoid biliary complications. Postoperative liver failure was defined using the 50-50 criteria. Postoperative complications were assessed according to the Dindo-Clavien Classification.RESULTS From January 2014 to December 2015, 7 patients underwent a rescue ALPPS procedure. Median FLR before PVE, ALPPS-1 and ALPPS-2 were respectively 263 cc(221-380), 450 cc(372-506), and 660 cc(575-776). Median FLR/BWR before PVE, ALPPS-1 and ALPPS-2 were respectively 0.4%(0.3-0.5), 0.6%(0.5-0.8), and 1%(0.8-1.2). Median volume growth of FLR was 69%(18-92) after PVE, and 45%(36-82) after ALPPS-1. The combination of PVE and ALPPS induced a growth of median initial FLR of +408 cc(254-513), leading to an increase of +149%(68-199). After ALPPS-2, 4 patients had stage Ⅰ-Ⅱ complications. Three patients had more severe complications(one stage Ⅲ, one stage Ⅳ and one death due to bowel perforation). Two patients suffered from postoperative liver failure according to the 50/50 criteria. None of our patients developed any biliary complication during the ALPPS procedure.CONCLUSION Rescue ALPPS may be an alternative after unsuccessful PVE and could allow previously unresectable patients to reach surgery. Biliary drainage seems to reduce biliary complications.

High tacrolimus intra-patient variability is associated with graft rejection,and de novo donor-specific antibodies occurrence after liver transplantation

AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver

Predictive factors of histological response of colorectal liver metastases after neoadjuvant chemotherapy

BACKGROUND Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy(NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases(CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria.More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade(TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.AIM To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.METHODSFrom January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG.Based on their TRG, each patient was either assigned to the responder(R) group(TRG 1, 2, and 3) or to the non-responder(NR) group(TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.RESULTS Seventy-four patients were classified as responders and 76 as non-responders.The postoperative mortality rate was 0.7%, with a complication rate of 38%.Multivariate analysis identified five predictive factors of histological response.Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy(P <0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy(P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr.The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC(P < 0.005).CONCLUSION A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response(TRG 4 or 5).

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Alpha-fetoprotein(AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma(HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/m L could be an exclusion criterion, whereas values of < 15 ng/m L indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.

Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas

AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.

Caval replacement with parietal peritoneum tube graft for septic thrombophlebitis after hepatectomy: A case report

BACKGROUND Caval vein thrombosis after hepatectomy is rare, although it increases mortality and morbidity. The evolution of this thrombosis into a septic thrombophlebitis responsible for persistent septicaemia after a hepatectomy has not been reported to date in the literature. We here report the management of a 54-year-old woman operated for a peripheral cholangiocarcinoma who developed a suppurated thrombophlebitis of the vena cava following a hepatectomy.CASE SUMMARY This patient was operated by left lobectomy extended to segment V with bile duct resection and Roux-en-Y hepaticojejunostomy. After the surgery, she developed Streptococcus anginosus, Escherichia coli, and Enterococcus faecium bacteraemias, as well as Candida albicans fungemia. A computed tomography scan revealed a bilioma which was percutaneously drained. Despite adequate antibiotic therapy,the patient's condition remained septic. A diagnosis of septic thrombophlebitis of the vena cava was made on post-operative day 25. The patient was then operated again for a surgical thrombectomy and complete caval reconstruction with a parietal peritoneum tube graft. Use of the peritoneum as a vascular graft is an inexpensive technique, it is readily and rapidly available, and it allows caval replacement in a septic area. Septic thrombophlebitis of the vena cava after hepatectomy has not been described previously and it warrants being added to the spectrum of potential complications of this procedure.CONCLUSION Septic thrombophlebitis of the vena cava was successfully treated with antibiotic and anticoagulation treatments, prompt surgical thrombectomy and caval reconstruction.

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation

Background:Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma(HCC).Few data exist concerning the prognosis of patients resected for non-cirrhotic HCC.The objectives of this study were to determine the prognostic factors of recurrence-free survival(RFS)and overall survival(OS)and to develop a prognostication algorithm for non-cirrhotic HCC.Methods:French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis:F0,F1 or F2 fibrosis.Results:A total of 467 patients were included in 11 centers from 2010 to 2018.Non-cirrhotic liver had a fibrosis score of F0(n=237,50.7%),F1(n=127,27.2%)or F2(n=103,22.1%).OS and RFS at 5 years were 59.2%and 34.5%,respectively.In multivariate analysis,microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS(P<0.005).Stratification based on RFS provided an algorithm based on size(P=0.013)and number(P<0.001):2 HCC with the largest nodule≤10 cm(n=271,Group 1);2 HCC with a nodule>10 cm(n=176,Group 2);>2 HCC regardless of size Conclusions:We developed a prognostication algorithm based on the number(≤or>2)and size(≤or>10 cm),which could be used as a treatment decision support concerning the need for perioperative therapy.In case of bifocal HCC,surgery should not be a contraindication.

Utility of circulating tumor DNA in patients undergoing hepatectomy for colorectal liver metastases

In this study recently published in Annals of Surgery,Newhook et al.studied the influence of circulating tumor DNA(ctDNA)in the management of patients undergoing hepatic resection for colorectal liver metastases(CRLM)(1).The primary objective was to study the association between the dynamic of ctDNA and somatic mutations with survival after resection of CRLM.The secondary objectives were to evaluate the impact of surgery on perioperative ctDNA dynamics and the impact of its detection on survival.

French editorial from the ACHBPT:blood salvage and autotransfusion during liver transplantation for advanced hepatocellular carcinoma

We read with great interest the recently(Annals of Surgery,March,2021)published article by Kwon and collaborators(1)about the effects of autotransfusion of salvaged blood with single leukoreduction for liver transplant recipients with advanced hepatocellular carcinoma(HCC).This retrospective study assessed the impact of autotransfusion of salvaged blood with post-transplant tumor recurrence.