Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Outcomes of total pancreatectomy with islet autotransplantation:A systematic review and meta-analysis

BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.

Complex inferior vena cava reconstruction during ex vivo liver resection and autotransplantation:A case report

BACKGROUND Ex vivo liver resection and autotransplantation(ELRA)is an essential approach for treating patients with end-stage hepatic alveolar echinococcosis(AE),and its surgical indications involve severe invasion of important hepatic vessels,which makes in vivo resection impossible.Revascularization is a major step in the process of ELRA,which is extremely challenging when the invaded vessels have huge defects.CASE SUMMARY Herein,we have reported the case of a 26-year-old patient with hepatic AE in an autologous liver graft who underwent complex inferior vena cava(IVC)reconstruction using disease-free IVC,autologous portal vein fragments,and umbilical vein within the ligamentum teres hepatis.The patient showed good surgical recovery without vascular-related complications during the long-term follow-up.CONCLUSION We reviewed three studies that have reported complex revascularization of the IVC.This case report and systematic review showed that the use of autologous perihepatic vessels prevents donor-area trauma,immune rejection,and other adverse reactions.When the blood vessel is severely invaded and a single vascular material cannot repair and reconstruct the defect,ELRA may provide a safe and feasible surgical approach,which has good prospects for clinical application.

Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats

BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.

Compared efficacy of University of Wisconsin and histidine-tryptophan-ketoglutarate solutions in ex-situ liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis patients

Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). Methods: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW ( n = 48) and HTK groups ( n = 33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. Results: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. Conclusions: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.

Clinical Outcomes of Ex Vivo Liver Resection and Liver Autotransplantation for Hepatic Alveolar Echinococcosis

The effectiveness of liver autotransplantation for patients with partial hepatic alveolar echinococcosis was analyzed.We retrospectively studied 6 patients with hepatic alveolar echinococcosis who underwent liver autotransplantation in our hospital from 2008 to 2010.We also summarized the surgical indications of liver autotransplantation for hepatic alveolar echinococcosis and our experience in the management of postoperative complications of liver autotransplantation.Of 6 patients,5 achieved good curative results,and one died of multiple organ failure caused by portal vein thrombosis.Main complications included postoperative bleeding,bile leak and small-for-size liver graft syndrome.Liver autotransplantation offers a new approach to cure hepatic alveolar echinococcosis with non-resectable lesions.It could be the most effective method to cure intractable hepatic alveolar echinococcosis if correct handling in operation and proper prevention of complications are performed.But the long-term outcomes are still needed to be confirmed in longer follow-up.

Ex vivo liver resection followed by autotransplantation in radical resection of gastric cancer liver metastases:A case report

BACKGROUND Radical resection of gastric cancer liver metastases(GCLM)can increase the 5-year survival rate of GCLM patients.However,patients may lose the theoretical feasibility of surgery due to the critical location of liver metastasis in some cases.CASE SUMMARY A 29-year-old woman had a chief complaint of chronic abdominal pain for 1 year.Abdominal computed tomography and magnetic resonance imaging examinations suggested a mass of unknown pathological nature located between the first and second hila and the margin of the lower segment of the right lobe of the liver.The anterior wall of the gastric antrum was unevenly thickened.The diagnosis of(gastric antrum)intramucosal well-differentiated adenocarcinoma was histopathologically confirmed by puncture biopsy with gastroscopy guidance.She underwent radical resection(excision of both gastric tumors and ex vivo liver resection followed by autotransplantation simultaneously)followed by XELOX adjuvant chemotherapy.Without serious postoperative complications,the patient was successfully discharged on the 20th day after the operation.Pathological examination of the excised specimen indicated that gastrectomy with D2 lymph node dissection for primary gastric tumors and R0 resection for liver metastases were achieved.The resected mass was confirmed to be poorly differentiated gastric carcinoma(hepatoid adenocarcinoma with neuroendocrine differentiation)with liver metastases in segments VIII.No recurrence or metastasis within the liver was found during a 7.5-year follow-up review that began 1 mo after surgery.CONCLUSION Application of ex vivo liver resection followed by autotransplantation in radical resection for GCLM can help selected patients with intrahepatic metastases located in complex sites obtain a favorable clinical outcome.

Autotransplantation of Teeth and the Reconstruction of Alveolar Bone Defects Using Artificial Bone: A Case Series

The aim of this study was to evaluate the outcome of autotransplantation or replantation of extracted teeth combining with reconstruction of alveolar bone defects in use of artificial bone grafting clinically and radiographically. This article presents a more useful and convenient method for repairing tooth and reconstruction of bone defecting with some interesting cases. Eleven patients (seven men and four women) in whom teeth with complete root formation were extracted and autotransplanted, the bone of receiving area was Insufficient. All transplanted teeth were stabilized with orthodontic wire and resin or 4-0 silk sutures;at the same time, artificial bone powder was filled. In 11 cases, the missing teeth were restored by autogenous teeth and the alveolar bone defect was restored by artificial bone, the improvement in the radiographic and clinical parameters strongly suggest that it may be a useful therapy to solve the problem of the missing teeth and alveolar bone insufficiency simultaneously. However, the risk of replacement root resorption remains.

The consensus on liver autotransplantation from an international panel of experts

IntroductionMore than 1.0 million patients worldwide are diagnosed with space-occupying lesions in the liver every year, with the number approaching 0.5 million per year in China, and only 20% of the lesions are resectable Due to a lack of available donors, only a limited number of patients underwent allogeneic liver transplantation, the remaining patients simply receive palliative care. Therefore, discovering new options for treating these patients is a high priority. Liver autotransplantation （LAT） is a surgical technique that adopts liver transplantation skills to radically treat spaceoccupying hepatic lesions, benign or malignant,

Autotransplantation of a premolar to the maxillary anterior region in young children- how long should the donor root be? A case report

Autotransplantation of premolars to anterior region after incisor loss due to trauma is accepted as the best restoration procedure with very long follow-ups. There are two main protocols: Premolars with only two thirds of the root or premolars with complete root development. Premolars with two thirds of the root completed remain vital and show complete pulp obliteration while premolars with closed apex require root canal treatment. The problem arises when the child is very young and the root of the donor premolar is developed for only one third. This case report describes the outcome of an autotransplantation of a lower first premolar with only a third of developed root to the anterior region. The donor tooth was extracted with his follicle and placed instead of tooth No. 21. For the first month esthetics was restored with a glass-fibers ribbon attached to tooth No. 11 and composite material. After a month, the crown erupted and was reshaped to mimic an incisor with composite. Orthodontic movement was performed after 5 mo, in order to alleviate the gingival contour. The final restoration was performed after 15 mo. Follow up showed full root development with normal mobility, continuous periodontal ligament and complete pulp obliteration. A multidisciplinary approach and meticulous preparation are necessary for a positive result in autotransplantation of premolars with only a third of root development to the anterior region and this case report show that this method can be performed in very young children.

Intestinal autotransplantation:the next level of complexity in locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a devastating disease,and selecting patients who might benefit from complex arterial resection continues to be a challenge.However,in the era of modern multimodal treatments,surgery for pancreatic cancer has become increasingly safe.Neoadjuvant chemotherapy regimens such as modified-FOLFIRINOX(mFOLFIRINOX)and nab-paclitaxel/gemcitabine are effective in a significant proportion of patients.

A critical review of pancreatectomy with concomitant superior mesenteric artery resection and intestinal autotransplantation

We have read with great interest the study by Liang et al.addressing the role of radical resection combined with intestinal autotransplantation for locally advanced pancreatic cancer after neoadjuvant therapy(1).The study may attract the attention of the pancreato-biliary oncological and surgical community.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis

Background For patients with end-stage hepatic alveolar echinococcosis （AE）, in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure. Methods We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments （II and III） of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases （such as to the lung or brain） could be found. As the first step of treatment, X-ray guided percutaneous transhepatic cholangiodrainage （PTCD） was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 umol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the-left liver were re-implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto-caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems. Results During a 60-day following-up after operation, the patient had a good recovery except for a mildly elevated serum total bilirubin. Conclusions As a radical approach, ex vivo liver resection and liver autotransptantation in a case has shown a optimal potential for treatment of the end-stage hepatic AE. Strict compliance with its indications, evaluation of vessels of patients pre-operatively, and precise surgical techniques are the keys to improve the prognosis of patients.

Thyrotoxicosis Occurring in Secondary Hyperparathyroidism Patients Undergoing Dialysis after Total Parathyroidectomy with Autotransplantation

Secondary hyperparathyroidism （SHPT） is a common complication in chronic kidney disease （CKD） that is characterized by excessive synthesis of parathyroid hormone （PTH） and parathyroid hyperplasia.The prevalence of CKD is estimated to be 5-10%, and the burden of CKD-associated diseases is alarmingly high.Despite advances in medical therapy for SHPT, surgical parathyroidectomy remains the definitive therapy for refractory SHPT, which drastically decreases PTH levels and ameliorates symptoms related to severe SHPT.

Small bowel autotransplantation combined with pancreato-duodenectomy for enormous cavernous hemangioma of the small intestine mesentery

Recent advances in transplantation techniques have allowed pancreatoduodenectomy, distal gastrectomy,hemicolectomy and small bowel autotransplantation to be the therapy of choice for enormous cavernous hemangioma of the small intestine mesentery. There have been a few case reports about small bowel autotransplantation combined with pancreatoduodenectomy for enormous mesenteric cavernous hemangioma of small intestine. The present surgical methods for enormous cavernous bemangioma of the small intestine mesentery mainly included tumor excision and/or small bowel resection. However, these therapies are not effective for those patients in whom the angiocavemoma has infiltrated the mesenteric artery or pancreas, and these patients often give up therapy. It is recognized that enormous cavernous hemangioma of the small intestine mesentery is a benign lesion, and patients may have an excellent prognosis after complete resection of the lesion.

Intestinal autotransplantation

Most abdominal neoplasms involving the root of the superior mesenteric artery and/or celiac artery are difficult to manage with conventional operative techniques because of limited intestinal ischemia times and poor accessibility to the tumor region.Ex vivo surgery followed by intestinal autotransplantation(IATx)is a relatively novel surgical strategy to offer chances for complete resection in such hopeless circumstances.This review aims to assess potential surgical indications,operative techniques and clinical outcomes after IATx.Currently the main indications reported for IATx broadly include pancreatic,mesenteric and retroperitoneal neoplasms closely involving the superior mesenteric vessels.The preliminary results show that radical resection can be effectively achieved in carefully selective patients.Although perioperative morbidity and mortality are relatively high,there are several long-term survivors,particularly after complete resection of benign and low-grade tumor.Early tumor recurrence,however,remains a major problem in patients with high-grade tumor,particularly pancreatic ductal carcinoma.In conclusion,IATx allows patients with selected abdominal neoplasms involving themajormesenteric vessels to be completely resected.However,this aggressive approach is associated with a considerable operative risk,and should only be performed at experienced centers.Additional and adjunctive treatment therapies are required to improve the efficacy of this treatment.

Lung autotransplantation for treating bronchus neoplasms

Lung autotransplantation is a new procedure with pulmonary preservation for patients in the treatment of lung cancer. It was used to treat the stage III central lung cancer of the upper lobe in the patient presented herein when his pulmonary function could not withstand a pneumonectomy and the length of the resected bronchus or pulmonary artery was too long to perform a bronchovascular double sleeve lobectomy.1＇2 In order to preserve pulmonary tissue and improve the quality of life, we performed lung autotransplantation for a case.

Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis

Total pancreatectomy with islet autotransplantation(TPIAT)is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis.The outcome and potential benefits for pre-diabetic and diabetic patients are less well established.Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control:diabetes mellitus(DM)(n=5,15%),pre-DM(n=11,32%)and non-DM(n=18,54%).Pre-operative fasting c-peptide was detectable and similar in all 3 groups.Islet yield in the DM group was comparable to pre-DM and non-DM groups(median islet equivalents[IEQ]was 191,800,111,800,and 232,000 IEQ,respectively).Patients received islet mass of over the target level of 2000 IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group:45%(5/11)and 60%(3/5)for a combined 50%(8/16)rate,respectively,compared to 83%(15/18)for the non-DM group.At 1 year,fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in non-DM.Islet transplantation failed(negative c-peptide)only in 1 patient.Preoperatively,all patients experienced pancreatic pain with daily opioid dependence in 60%to 70%.Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms.Diabetic patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT,with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted islets.Not surprisingly,endocrine outcomes for diabetic and prediabetics patients are substantially worse than in those with normal pre-operative glucose control.

Gastric Submucosa Is Inferior to the Liver as Transplant Site for Autologous Islet Transplantation in Pancreatectomized Diabetic Beagles

Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa（GS） and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS（GS group, n=8） or intrahepatic via portal vein（PV group, n=5）. Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation（mean survival time, 7.16±0.69 days）. However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group（mean survival time, 120±28.58 days; P〈0.01 vs. GS group）. The results of intravenous glucose tolerance test（IVGTT） confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.