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Gut microbiota and its implications in small bowel transplantation

null

《医学前沿（英文）》 2018年第12卷第3期页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要：

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词： gut microbiota small bowel transplantation acute rejection chronic rejection mucosal immunity biomarker microbiota-targeted therapy

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A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

《医学前沿（英文）》 2015年第9卷第1期页码 108-111 doi: 10.1007/s11684-014-0344-0

摘要：

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54-year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour (GIST) of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient’s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

关键词： gastrointestinal stromal tumour hemoperitoneum small bowel GIST small bowel neoplasm imatinib

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Severe adhesive small bowel obstruction

null

《医学前沿（英文）》 2012年第6卷第4期页码 436-439 doi: 10.1007/s11684-012-0221-7

摘要：

Adhesive small bowel obstruction is a frequent cause of hospital admission. Water soluble contrast studies may have diagnostic and therapeutic value and avoid challenging demanding surgical operations, but if bowel ischemia is suspected, prompt surgical intervention is mandatory. A 58-year-old patient was operated for extensive adhesive small bowel obstruction after having had two previous laparotomies for colorectal surgery, and had a complex clinical course with multiple operations and several complications. Different strategies of management have been adopted, including non-operative management with the use of hyperosmolar water soluble contrast medium, multiple surgical procedures, total parenteral nutrition (TPN) support, and finally use of anti-adherences icodextrin solution. After 2 years follow-up the patient was doing well without presenting recurrent episodes of adhesive small bowel obstruction. For patients admitted several times for adhesive small bowel obstruction, the relative risk of recurring obstruction increases in relation to the number of prior episodes. Several strategies for non-operative conservative management of adhesive small bowel obstruction have already addressed diagnostic and therapeutic value of hyperosmolar water soluble contrast. According to the most recent evidence-based guidelines, open surgery is the preferred method for surgical treatment of strangulating adhesive small bowel obstruction as well as after failed conservative management. Research interest and clinical evidence are increasing in adhesions prevention. Hyaluronic acid-carboxycellulose membrane and icodextrin may reduce incidence of adhesions.

关键词： post-operative intraperitoneal adhesions adhesive small bowel obstruction adhesiolysis antiadhesion treatments hyperosmolar water soluble contrast medium

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A better way to do small-for-size liver transplantation in rats

null

《医学前沿（英文）》 2011年第5卷第1期页码 106-110 doi: 10.1007/s11684-011-0113-2

摘要：

Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation. This study aims to explore a simpler and more effective way of establishing a 30% small-for-size liver transplantation in rats. Sprague-Dawley rats were selected as the donors and recipients. Small-for-size orthotopic liver transplantation was performed using Kamada’s two-cuff method. The donor’s liver was flushed via the abdominal aorta and hepatectomy was performed in situ. The animals were divided into three groups depending on the graft selected, with 40 pairs of rats in each group. In group I, the median lobe of the liver was used as graft; in group II, the right half of the median lobe and the right lobe were used as graft; and in group III, the median and right lobes were used as graft. In groups I and II, the bodyweights of donors were the same as those of recipients; however, in group III the bodyweights of donors were 100–120 g less than those of the recipients. The duration needed for transplantation, the 7-day survival rates, and the technical complication rates were compared among these three groups. The time required for hepatectomy was shorter in group III compared with groups I and II (8.8?±?0.7 min vs. 11.5?±?1.1 min and 10.1?±?1.0 min, P = 0.001). The cold ischemia time for the grafts, the anhepatic times, and the transplantation times for the recipients were not significantly different among the three groups. Compared with groups I and II, the incidence of bleeding, bile leakage, and inferior vena caval strictures were significantly decreased in group III (P<0.05). No significant differences between the three groups were found based on other complications after the operation (P>0.05). Group III had better 7-day survival rates and longer median survival times but the differences were not statistically significant. The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30% small-for-size liver transplantation in rats, as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

关键词： liver transplantation small-for-size rats

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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneicperipheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年第15卷第1期页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide allogeneic hematopoietic stem cell transplantation lymphoid malignancies

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Partial liver transplantation

null

《医学前沿（英文）》 2011年第5卷第1期页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要：

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词： partial liver transplantation reduced-size liver transplantation split liver transplantation living donor liver transplantation

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Successful kidney transplantation in highly sensitized patients

null

《医学前沿（英文）》 2011年第5卷第1期页码 80-85 doi: 10.1007/s11684-011-0115-0

摘要：

Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panel-reactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novoproduction of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.

关键词： Kidney transplantation desensitization

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Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients

《医学前沿（英文）》 2023年第17卷第1期页码 58-67 doi: 10.1007/s11684-022-0937-y

摘要： The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≥ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65–70 years (111 recipients, group 65–70) and ≥ 70 years (55 recipients, group ≥ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≥ 70 (30.9% vs. 14.4% in group 65–70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65–70) and 7.3% (group ≥ 70) of patients. Kaplan–Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

关键词： cardiac disease mortality aged population lung transplantation

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Liver surgery and transplantation in China: Progress and Challenges

LAU W Y, LAI E C H

《医学前沿（英文）》 2007年第1卷第1期页码 1-5 doi: 10.1007/s11684-007-0001-y

摘要： From the limited but available information, we traced the history of developments of liver surgery and transplantation in China. Liver surgery first started in the late 1950s in China, and it soon flourished mainly because of the great demand in liver surgery and the emergence of a number of giants in liver surgery. We recognized and honoured the important contributions of these Chinese pioneers in portal hypertension, recurrent pyogenic cholangitis, hepatocellular carcinoma and liver transplantation.

关键词： transplantation pyogenic cholangitis available information important hypertension

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Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

《医学前沿（英文）》 2018年第12卷第2期页码 224-228 doi: 10.1007/s11684-017-0538-3

摘要：

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

关键词： bronchiolitis obliterans syndrome (BOS) hematopoietic stem cell transplantation (HSCT) lung transplantation (LTX)

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Methodologies for the establishment of an orthotopic transplantation model of ovarian cancer in mice

null

《医学前沿（英文）》 2014年第8卷第1期页码 101-105 doi: 10.1007/s11684-014-0315-5

摘要：

This study used different methods to establish an animal model of orthotopic transplantation for ovarian cancer to provide an accurate simulation of the mechanism by which tumor occurs and develops in the human body. We implanted 4T1 breast cancer cells stably-transfected with luciferase into BALB/c mice by using three types of orthotopic transplantation methodologies: (1) cultured cells were directly injected into the mouse ovary; (2) cell suspension was initially implanted under the skin of the mouse neck; after tumor mass formed, the tumor was removed and ground into cell suspension, which was then injected into the mouse ovary; and (3) a subcutaneous tumor mass was first generated, removed, and cut into small pieces, which were directly implanted into the mouse ovary. After these models were established, in vivo luminescence imaging was performed. Results and data were compared among groups. Orthotopic transplantation model established with subcutaneous tumor piece implantation showed a better simulation of tumor development and invasion in mice. This model also displayed negligible response to artificial factors. This study successfully established an orthotopic transplantation model of ovarian cancer with high rates of tumor formation and metastasis by using subcutaneous tumor pieces. This study also provided a methodological basis for future establishment of an animal model of ovarian cancer in humans.

关键词： ovarian cancer orthotopic transplantation animal model

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Gut microbial balance and liver transplantation: alteration, management, and prediction

null

《医学前沿（英文）》 2018年第12卷第2期页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要：

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词： gut microbial balance liver transplantation ischemia–reperfusion acute rejection

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Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death

《医学前沿（英文）》 2022年第16卷第5期页码 760-765 doi: 10.1007/s11684-021-0899-5

摘要： Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311–9.111; P=0.011) and 3.500 (95% CI 1.435–8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

关键词： lung transplantation donation after brain death waitlist

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stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation

《医学前沿（英文）》 2022年第16卷第6期页码 957-968 doi: 10.1007/s11684-021-0910-1

摘要： Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF–AKI–HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760–0.906) and 0.826 (95% CI 0.715–0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections hematopoietic stem cell transplantation risk stratification system mortality

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Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed

《医学前沿（英文）》 2021年第15卷第5期页码 728-739 doi: 10.1007/s11684-021-0833-x

摘要： Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo+m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo+m-DLI in our center. With a median follow-up of 918 (457–1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1%±4.9% and 25.0%±8.4%. The cumulative incidences of relapse were 50.0%±9.8% and 53.5%±9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo+m-DLI.

关键词： second hematopoietic stem cell transplantation acute leukemia relapse chemotherapy modified donor lymphocyte infusion