How to deal with right hepatic artery coming from the superior mesenteric artery during minimally invasive pancreaticoduodenectomy: A systematic review

Background: Anatomical variations in the liver arterial supply are quite common and can affect the surgical strategy when performing a minimally invasive pancreaticoduodenectomy(MIPD). Their presence must be preemptively detected to avoid postoperative liver and biliary complications. Data sources: Following the PRISMA guidelines and the Cochrane protocol we conducted a systematic review on the management of an accessory or replaced right hepatic artery(RHA) arising from the superior mesenteric artery when performing an MIPD. Results: Five studies involving 118 patients were included. The most common reported management of the aberrant RHA was conservative(97.0%);however, patients undergoing aberrant RHA division without reconstruction did not develop liver or biliary complications. No differences in postoperative morbidity or long-term oncological related overall survival were reported in all the included studies when comparing MIPD in patients with standard anatomy to those with aberrant RHA. Conclusions: MIPD in patients with aberrant RHA is feasible without increase in morbidity and mortality. As preoperative strategy is crucial, we suggested planning an MIPD with an anomalous RHA focusing on preoperative vascular aberrancy assessment and different strategies to reduce the risk of liver ischemia.

Impact of body mass index in elderly patients treated with laparoscopic liver resection for hepatocellular carcinoma

BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.

Epidemioclinical Aspects of Childhood Domestic Accidents in the Emergency Department of Boffa Hospital

Introduction: Domestic accidents are defined as accidents that occur in the home or its immediate surroundings. Objective: To describe the epidemioclinical and therapeutic aspects. Patients and Methods: Prospective, descriptive study from July 1, 2019 to June 30, 2020 in the emergency department of Boffa prefectural hospital included all children aged 0 to 15 years admitted for domestic accidents. Results: Of 120 cases of accidental trauma, 56 were domestic accidents. The mean age was 7.08 years. The 0 - 5 and 11 - 15 age groups were the most represented (35.71%). The sex ratio was 1.55 in favor of boys. Domestic accidents were represented by falls (26.78%), thermal burns (21.43%), snakebite wounds (17.86%) and dog bites (10.71%), drowning (5.36%), and electrification by lightning (3.60%), one case or 1.78% of each of the following: esophageal foreign body by palm nut, firearm, wall collapse, stretching of upper limb. Paracetamol was the molecule most frequently used (89.28%). The outcome was favorable in 92.86% of cases. However, four (4) deaths were recorded. Conclusion: Domestic accidents remain a significant pathology at Boffa prefectural hospital.

Surgical Management of Recent Traumatic Epiphyseal Fractures-Detachments of the Distal Femur at Gabriel TouréUniversity Hospital

Traumatic epiphyseal detachment fractures of the distal end of the femur are a rare lesion whose severity is linked to disabling sequelae such as limb length inequality or most often axial deviation. In this report, surgical treatment aims to reconstruct the anatomy of the distal femur, to avoid secondary displacements and to allow early mobilization of the knee. Surgery carried out mainly by the technique of plugging in or screwing, opened or better still closed, can be a source of complications including migration of pins, infections, knee stiffness, and growth disorders. The aim of this work was to describe their epidemiological, anatomo-clinical, therapeutic and evolutionary aspects in the Department of Orthopedics-Traumatology at the CHU Gabriel TOURE. It was a retrospective study over 30 months from July 2019 to December 2021. In fact, it concerned 42 patients with traumatic epiphyseal detachment of the distal femur occurring within 21 days or less, on a healthy knee with cartilage fertile treated surgically and followed in the department. However, the diagnosis of traumatic epiphyseal detachment of the distal femur was retained thanks to the clinical examination and supplemented by radiographic images of the knee from the front and from the side. The treatment was surgical. The functional results were evaluated according to the functional criteria of the Eastern Orthopedic Traumatology Society (SOTEST). Forty-two patients included 32 boys and 10 girls of average age of 12 years with extremes of 8 years and 16 years. The lesions were classified according to the Salter Harris classification. We noted 24% type I (n = 10), type II 71% (n = 30), type III 2% (n = 1), type IV 2% (n = 1). Union was achieved in all patients within an average of 6 weeks with extremes of 4 and 12 weeks. The functional result was considered good in 20% of cases and very good in 80%. Traumatic epiphyseal detachment fractures of the distal end of the femur are a rare lesion whose severity is linked to disabling sequelae such as limb length inequality or most often axial deviation. Surgical treatment aims to reconstruct the anatomy of the distal femur, to avoid secondary displacements and to allow early mobilization of the knee.

Peri-operative score for elderly patients with resectable hepatocellular carcinoma

BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.

Evaluating pediatric ureteropelvic junction obstruction:Dynamic magnetic resonance urography vs renal scintigraphy 99mtechnetium mercaptoacetyltriglycine

BACKGROUND Ureteropelvic junction obstruction(UPJO)is a common congenital urinary tract disorder in children.It can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic occurrence.AIM To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography(dMRU)and scintigraphy 99m-technetium mercaptoacetyltriglycine(MAG-3)for the functional evaluation of UPJO.METHODS Between 2016 and 2020,126 patients with UPJO underwent surgery at Robert DebréHospital.Of these,83 received a prenatal diagnosis,and 43 were diagnosed during childhood.Four of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging evaluation.Split renal function was evaluated preoperatively using scintigraphy MAG-3(n=28),dMRU(n=53),or both(n=40).In this study,we included patients who underwent surgery for UPJO and scintigraphy MAG-3+dMRU but excluded those who underwent only scintigraphy MAG-3 or dMRU.The patients were divided into groups A(<10%discrepancy)and B(>10%discrepancy).We examined the discrepancy in split renal function between the two modalities and investigated the possible risk factors.RESULTS The split renal function between the two kidneys was compared in 40 patients(28 boys and 12 girls)using scintigraphy MAG-3 and dMRU.Differential renal function,as determined using both modalities,showed a difference of<10%in 31 children and>10%in 9 children.Calculation of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both kidneys.CONCLUSION Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UPJO.

Rib Osteosynthesis for Sub-Acute Management of a Flail Chest in a Tertiary Centre in a Low-Middle Income Country of Sub-Saharan Africa: Case Report at Douala Laquintinie Hospital

Background: Costal fracture surgical is still a debate, therefore we shall select between early and delay surgical management. Case Report: We are reporting two cases of post road traffic clash delay ribs fractures osteosynthesis involving a 63-year-old man with multistage fractures on the left and pulmonary pinning of one of the costal arches, complicated by a homolateral haemothorax and a 41-year-old man with a bilateral flail chest. Conclusion: The simple postoperative course and the immediate postoperative improvement in the patient’s clinical respiratory condition enabled us to discuss the time frame for management, in this case the indication for early or later surgery.

Laparoscopic liver resection:Experience based guidelines

Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

Lateral lymph node dissection for low rectal cancer: Is it necessary?

Rectal cancer constitutes a major public health issue.Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s.Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes.However,when cancer spreads to the lateral lymph nodes(located along the iliac and obturator arteries)Western and Japanese practices differ.Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally,the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment.Herein,we review the current literature regarding both therapeutic strategies,with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.

Tropomyosin-related kinase B/brain derived-neurotrophicfactor signaling pathway as a potential therapeutic targetfor colorectal cancer

Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors.

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

Predictive factors for compliance with transanal irrigation for the treatment of defecation disorders

AIM To investigate compliance with transanal irrigation(TAI) one year after a training session and to identify predictive factors for compliance.METHODS The compliance of one hundred eight patients [87 women and 21 men; median age 55 years(range 18-83)] suffering from constipation or fecal incontinence(FI) was retrospectively assessed. The patients were trained in TAI over a four-year period at a single institution. They were classified as adopters if they continued using TAI for at least one year after beginning the treatment or as non-adopters if they stopped. Predictive factors of compliance with TAI were based on pretreatment assessments and trainingprogress. The outcomes of the entire cohort of patients who had been recruited for the TAI treatment were expressed in terms of intention-to-treat.RESULTS Forty-six of the 108(43%) trained patients continued to use TAI one year after their training session. The patients with FI had the best results, with 54.5% remaining compliant with TAI. Only one-third of the patients who complained of slow transit constipation or obstructed defecation syndrome continued TAI. There was an overall discontinuation rate of 57%. The most common reason for discontinuing TAI was the lack of efficacy(41%). However, 36% of the patients who discontinued TAI gave reasons independent of the efficacy of the treatment such as technical problems(catheter expulsion, rectal balloon bursting, instilled water leakage or retention, pain during irrigation, anal bleeding, anal fissure) while 23% said that there were too many constraints. Of the patients who reported discontinuing TAI, the only predictive factor was the progress of the training(OR = 4.9, 1.3-18.9, P = 0.02).CONCLUSION The progress of the training session was the only factor that predicted patient compliance with TAI.

Liver resection and metabolic disorders: An undescribed mechanism leading to postoperative mortality

AIM: To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders.METHODS: The link between Metabolic Syndrome and non-alcoholic fatty liver disease is currently demonstrated. Various metabolic disorders and the Metabolic Syndrome(the association of ≥ 3 metabolic disorders) have been recently described as a risk factor of perioperative mortality in major liver resection. Patients who passed away during perioperative course of major liver resection and presenting with the association of ≥ 2 metabolic disorders without any other known cause of liver disorders were reviewed.RESULTS: From January 2001 to May 2010 in a tertiary centre, ten patients presenting with ≥ 2 metabolic disorders without any other known cause of liver disorders died during perioperative course of major liver resection. The same four-consecutive-steps sequence of events occurred, including jaundice. The analysis of this series suggested a rapidly deteriorating congestive liver resulting in an increased portal hypertension leading to hepatorenal syndrome and lately to multiorgan failure(mimicking septic collapse) as the mechanism leading to exitus. The acute portal hypertension is mainly related to the surgical procedure. The chronic portal hypertension is indeterminate. Patients with ≥ 2 metabolic disorders should be considered as potentially presenting with portal hypertension possibly evolving towards hepatorenal syndrome; thus, they should be considered as having a high perioperative risk and should be carefully evaluated before undergoing major liver resection.CONCLUSION: As fibrosis was not present or marginal in liver specimens, the real cause of portal hypertension in patients with multiple metabolic disorders should be investigated with further studies.

Combined radiologic and endoscopic treatment(using the “rendezvous technique”) of a biliary fistula following left hepatectomy

Despite the ongoing decrease in the frequency of complications after hepatectomy, biliary fistulas still occur and are associated with high morbidity and mortality rates. Here, we report on an unusual technique for managing biliary fistula following left hepatectomy in a patient in whom the right posterior segmental duct joined the left hepatic duct. The biliary fistula was treated with a combined radiologic and endoscopic procedure based on the "rendezvous technique". The clinical outcome was good, and reoperation was not required.

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.Symp-toms 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 interven-tion 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 expe-rienced with vascular liver surgery to get the best results.

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers

AIM:To investigate the polymorphic simple sequencerepeat in intron 1 of the epidermal growth factor receptorgene(EGFR)(CA-SSRⅠ),which is known to affect theefficiency of gene transcription as a putative target of themismatch repair(MMR)machinery in colorectal tumors.METHODS:The CA-SSRⅠgenotype was analyzed ina total of 86 primary colorectal tumors,selected upontheir microsatellite instability(MSI)status[42 with highfrequency MSI(MSI-H)and 44 microsatellite stable(MSS)]and their respective normal tissue.The effect of the CA-SSRⅠgenotype on the expression of the EGFR gene wasevaluated in 18 specimens using quantitative real-timereverse transcription PCR and immunohistochemistry.RESULTS:Mutations in CA-SSRⅠwere detected in 86%(36 of 42)of MSI-H colorectal tumors and 0%(0 of 44)ofMSS tumors,indicating the EGFR gene as a novel putativespecific target of the defective MMR system(P<0.001).Impaired expression of EGFR was detected in most ofthe colorectal tumors analyzed[6/12(50%)at the mRNAlevel and 15/18(83%)at the peptide level].However,noassociation was apparent between EGFR expression andCA-SSRⅠstatus in tumors or normal tissues.CONCLUSION:Our results suggest that CA-SSRⅠsequence does not contribute to the regulation of EGFRtranscription in colon,and should thus not be consideredas a promising predictive marker for response to EGFRinhibitors in patients with colorectal cancer.

Genome-wide differences in hepatitis C-vs alcoholism-associated hepatocellular carcinoma

AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS:With a liver-oriented microarray,transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism,12;hepatitis C,10)and 5 controls.Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set(12+10) and a test set(6+7). RESULTS:A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism)or-2(hepatitis C)and ontology indicated a predominant inflammatory response(alcoholism)or changes in cell cycle regulation,transcription factors and interferon responsiveness(hepatitis C).A stringent selection of 23 transcripts whose differences betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis.These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION:Etiology-specific abnormalities(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C.This may open novel avenues for differential therapies in this disease.

Epidemiology of Urological Emergencies at the Regional University Hospital Center of Ouahigouya, Burkina Faso

Introduction: Urological emergencies are less frequent compared to other emergencies, particularly traumatological and digestive emergencies. The objective of this study was to determine the epidemiological profile of urological emergencies in a regional hospital in Burkina Faso. Patients and methods: This was a cross-sectional study of urological emergencies admitted to the Surgical Department of the Ouahigouya Regional University Hospital in Burkina Faso over a period of 41 months. The study covered a 41-month period from March 2015 to July 2018. Ethical clearance was taken from the institutional ethics committee. Results: Urological emergencies accounted for 3.7% of all emergencies. The mean age of the patients was 56.59 ± 25.93 years (range 1 year - 95 years). The sex ratio was 12.05. Bladder urinary retention was the main urological emergency in 48.28% of cases. Suprapubic cystostomy was the most performed surgical procedure (56.25%) followed by debridement of external genitalia gangrene (27.68%). Conclusion: Urological emergencies occupy a significant place in our work context. An increase in the number of urologists would improve their management.

French pre-hospital trauma triage criteria:Does the “prehospital resuscitation” criterion provide additional benefit in triage?

AIM:To evaluate the performance of the specific French Vittel "Pre-Hospital(PH) resuscitation" criteria in selecting polytrauma patients during the pre-hospital stage and its potential to increase the positive predictive value(PPV) of pre-hospital trauma triage.METHODS: This was a monocentric prospective cohort study of injured adults transported by emergency medi-cal service to a trauma center. Patients who met any of the field trauma triage criteria were considered "triage positive". Hospital data was statistically linked to prehospital records. The primary outcome of defining a "major trauma patient" was Injury Severity Score(ISS) > 16. RESULTS: There were a total of 200 injured patients evaluated over a 2 years period who met at least 1 triage criterion. The number of false positives was 64 patients(ISS < 16). The PPV was 68%. The sensitivity and the negative predictive value could not be evaluated in this study since it only included patients with positive Vittel criteria. The criterion of "PH resuscitation" was present for 64 patients(32%),but 10 of them had an ISS < 16. This was statistically significant in correlation with the severity of the trauma in univariate analysis(OR = 7.2; P = 0.005; 95%CI: 1.6-31.6). However,despite this correlation the overall PPV was not significantly increased by the use of the criterion "PH resuscitation"(68% vs 67.8%).CONCLUSION: The criterion of "pre-hospital resuscitation" was statistically significant with the severity of the trauma,but did not increase the PPV. The use of "prehospital resuscitation" criterion could be re-considered if these results are confirmed by larger studies.

Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats

AIM To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation(OLT) in rats.METHODS Allogeneic OLTs were performed using Dark Agoutilivers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin(1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats. Skin grafts from Dark agouti or from F344 RT were performed at day 30 on liver grafted rats treated with rapamycin.RESULTS An 8-d course of rapamycin treatment initiated 4 d following transplantation resulted in the survival of grafted rats for more than 100 d. In contrast, untreated rats died of liver failure within 13 to 21 d. The analysis of the cellular compartment revealed an increase in two cellular subpopulations, specifically myeloid-derived suppressor cells(MDSCs) and CD8+CD45RClow T cells, without major modifications in the regulatory T cell(Treg) compartment in treated rats in the early stages after grafting. We evaluated the ability of treated rats to reject third-party allogeneic skin grafts to confirm their immune competence. In contrast, when skin was collected from rats syngeneic to the grafted liver, it was not rejected.CONCLUSION Our results demonstrate that short and delayed rapamycin treatment allows for tolerance in allogeneic OLT. The results also allowed for the identification of the mechanisms of tolerance induced by rapamycin by identifying MDSCs and CD8+CD45RClow T cells as associated with the state of tolerance.