A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

A Prospective Study Using Propensity Score Matching to Compare Long-term Survival Outcomes After Robotic-assisted, Laparoscopic, or Open Liver Resection for Patients With BCLC Stage 0-A Hepatocellular Carcinoma.

OBJECTIVE: To compare the short- and long-term outcomes of robot-assisted (RALR), laparoscopic (LLR), or open liver resection (OLR) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Following the Balliol IDEAL classification, long-term oncological outcomes can be used to evaluate the value of minimally invasive techniques in the treatment of HCC, and to assess whether they should become a standard practice. METHODS: Data from prospective cohorts of patients with BCLC stage 0-A HCC who underwent curative liver resection using OLR, LLR, or RALR at Tongji Hospital were reviewed. The short-term and long-term oncological outcomes of these 3 different surgical approaches after adequate follow-up were compared using propensity score matching to reduce selection bias. RESULTS: Of 369 patients included in this study (71, RALR; 141, LLR; and 157, OLR), 56 patients in each of the 3 groups were chosen for further comparison, after propensity score matching. In the minimally invasive group (RALR+LLR), both the operative time and duration of Pringle's maneuver were significantly longer than those in the OLR group; however, the length of hospital stay was significantly shorter. There were no significant differences in the other intraoperative parameters and the incidence of postoperative complications among the 3 groups. HCC recurrence in the minimally invasive group when compared with the OLR group was characterized by a significantly higher proportion of single lesion or early-stage HCC. However, there were no significant differences in the 5-year disease-free survival (63.8%, 54.4%, and 50.6%) or overall survival rates (80.8%, 78.6%, and 75.7%, respectively) among the 3 groups. Clinically significant portal hypertension was the only risk factor that negatively affected the 5-year disease-free survival rate. Multivariate Cox regression analysis showed that clinically significant portal hypertension, serum alpha-fetoprotein level (≥400 ng/mL), and Edmondson-Steiner grading (III+IV) were independent risk factors for poor long-term survival. CONCLUSION: Both robotic and laparoscopic hepatectomies were safe and effective for patients with BCLC stage 0-A HCC when compared with open hepatectomy.

Anatomical Resection Improved the Outcome of Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis of a Retrospective Cohort.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy after hepatocellular carcinoma (HCC), with a dismal prognosis and high heterogeneity. The oncological advantages of anatomical resection (AR) and nonanatomical resection (NAR) in HCC have been studied, but surgical strategies for ICC remain controversial with insufficient investigations. Materials and Methods: From Jan 2013 to Dec 2016, 3880 consecutive patients were retrospectively reviewed from a single center. Patients with ICC undergoing AR or NAR have been enrolled according to inclusion and exclusion criteria. Propensity score matching (PSM) analysis was performed between two groups with a 1 : 1 ratio. The primary endpoint was overall survival (OS), and the secondary endpoints included disease-free survival (DFS), intraoperative patterns, postoperative morbidity, mortality, complications and recurrence. A prognostic nomogram was developed by a multivariate Cox proportion hazard model. Results: After PSM, 99 paired cases were selected from 276 patients enrolled in this study. Patients in the AR group achieved better 1-, 3-, and 5-year OS (70%, 46%, and 34%, respectively) and DFS (61%, 21%, and 10%, respectively) than patients in the NAR group with statistical significance after PSM analysis. The postoperative complications and recurrence patterns were comparable between the two groups. Multivariate analysis identified NAR, tumor size >5 cm, multiple tumors, and poor differentiation as independent risk factors for OS (p < 0.05). Selected patients can benefit most from AR, according to subgroup analysis. A prognostic nomogram based on six independent risk factors for OS and factors with clinical significance was constructed to predict OS in ICC patients. Conclusion: AR improved the long-term survival of ICC with comparable postoperative complications and similar recurrence patterns. AR is suggested in ICC patients with sufficient remnant liver volume. In addition to surgery strategy, malignant characteristics of tumors are risk factors for ICC prognosis.

Clinical Value of Trans-parenchymal Compressing Suture to Decrease the Cutting Surface Related Complications after Non-anatomical Liver Resection.

Non-anatomical liver resection with appropriate resection margin is regarded as a potential curative treatment for selected major hepatic carcinoma due to preserving maximal normal liver, especially in cirrhotic patients. But occurrence of cutting surface related complications becomes a main challenge. From June 2010 to June 2016, 448 patients with major hepatic carcinoma received non-anatomical liver resection in our liver surgery center. After excluding 66 cases that were incongruent with the purpose of study, 235 patients undergoing transparenchymal compressing suture (TCS) to "not good" cutting surface were allocated as study group; 147 patients with exposed surface (ES) were matched as control group. The characteristics of postoperative drainage, postoperative hepatic and renal functions, hospital days, and outcomes were collected retrospectively. We further compared cutting surface related complications under different levels of liver cirrhosis between the two groups. Compared with ES group, patients in TCS group had a decreased incidence of cutting surface related complications (14.3% vs. 6.8%, P=0.011) and a decreased probability of interventions for cutting surface related complications (8.2% vs. 3.4%, P=0.042). TCS application was much more effective to prevent cutting surface related complications in patients with moderate and severe cirrhosis (5.4% vs. 15.8%, P=0.003). Postoperative hepatic and renal function, hospital days and mortality did not differ between the two groups. In conclusion, TCS decreases the probability of cutting surface related complications and postoperative interventions for related complications, especially in patients with moderate and severe cirrhosis.

Effect of surgical liver resection on circulating tumor cells in patients with hepatocellular carcinoma.

BACKGROUND: This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in patients with hepatocellular carcinoma (HCC). METHODS: One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch™ System. RESULTS: Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC < 2 to postoperative CTC ≥ 2) had significantly shorter disease-free survival (DFS) and overall survival (OS) than did patients with persistent CTC < 2. Patients with persistent CTC levels of ≥2 had the worst prognoses. CONCLUSIONS: Surgical liver resection is associated with an increase in CTC counts, and increased postoperative CTC numbers are associated with a worse prognosis in patients with HCC.

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease.

The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy.

Extracellular ATP signaling and clinical relevance.

Since purinergic signaling was discovered in the early 1970s, it has been shown that extracellular nucleotides, and their derivative nucleosides, are released in a regulated or unregulated manner by cells in various challenging settings and then bind defined purinergic receptors to activate intricate signaling networks. Extracellular ATP plays a role based on different P2 receptor subtypes expressed on specific cell types. Sequential hydrolysis of extracellular ATP catalyzed by ectonucleotidases (e.g. CD39, CD73) is the main pathway for the generation of adenosine, which in turn activates P1 receptors. Many studies have demonstrated that extracellular ATP signaling functions as an important dynamic regulatory pathway to coordinate appropriate immune responses in various pathological processes, including intracellular infection, host-tumor interaction, pro-inflammation vascular injury, and transplant immunity. ATP receptors and CD39 also participate in related clinical settings. Here, we review the latest research in to the development of promising clinical treatment strategies.

Personalized stepwise vascular control during complex hepatectomy involving hepatocaval confluence.

BACKGROUND: This study introduces an innovative stepwise vascular control technique to address the high risk of massive bleeding from main hepatic veins and the retro-hepatic inferior vena cava during hepatectomy involving hepatocaval confluence. METHODS: From January 2010 to July 2016, 80 patients underwent stepwise vascular occlusion during complex liver resection involving hepatocaval confluence. Relevant clinical data were collected and compared with those obtained in parallel studies. The protocol has been registered in the Protocol Registration and Results System as protocol NCT02996006. RESULTS: All 80 patients underwent portal triad (PT), infra-hepatic inferior vena cava (IIVC) and supra-hepatic inferior vena cava (SIVC) preparation for occlusion in that order; PT, PT + SIVC and PT + IIVC + SIVC occlusions were performed during liver resection for six, 42 and 32 patients, respectively. The PT, IIVC and SIVC clamping times were 12.9 ± 2.5, 9.1 ± 2.1 and 5.1 ± 1.4 min, respectively. The mean blood loss was 504.1 ± 234.5 mL. Sixteen patients received blood transfusions. Haemodynamic parameters remained stable. No patients had life-threatening complications or died (Clavien-Dindo grade IV or V). Compared with other techniques used in parallel studies, this technique has the advantage of decreased blood loss in less warm ischaemia time. CONCLUSION: For complex hepatectomy involving hepatocaval confluence, this newly described stepwise vascular control technique was efficacious and feasible for controlling intraoperative bleeding.

Surgical Treatment of Giant Liver Hemangioma Larger Than 10 cm: A Single Center's Experience With 86 Patients.

The ideal surgical treatment of giant liver hemangioma is still controversial. This study aims to compare the outcomes of enucleation with those of resection for liver hemangioma larger than 10 cm in different locations of the liver and establish the preoperative predictors of increased intraoperative blood loss.Eighty-six patients underwent enucleation or liver resection for liver hemangioma larger than 10 cm was retrospectively reviewed. Patient demographic, tumor characteristics, surgical indications, the outcomes of both surgical treatment, and the clinicopathological parameters influencing intraoperative blood loss were analyzed.Forty-six patients received enucleation and 40 patients received liver resection. Mean tumor size was 14.1 cm with a range of 10-35 cm. Blood loss, blood product usage, operative time, hepatic vascular occlusion time and frequency, complications and postsurgical hospital stay were similar between liver resections and enucleation for right-liver and left-liver hemangiomas. There was no surgery-related mortality in either group. Bleeding was more related to adjacency of major vascular structures than the size of hemangioma. Adjacency to major vascular structures and right or bilateral liver hemangiomas were independently associated with blood loss >550 mL (P = 0.000 and 0.042, respectively).Both enucleation and liver resection are safe and effective surgical treatments for liver hemangiomas larger than 10 cm. The risk of intraoperative blood loss is related to adjacency to major vascular structures and the location of hemangioma.

Primary combined hepatocellular-cholangiocellular sarcoma: An unusual case.

Primary liver carcinosarcoma is rare. Here we report an unusual case of liver carcinosarcoma containing combined hepatocellular cholangiocarcinoma. A mass in the right liver lobe of a 45-year-old man was accidentally discovered by ultrasonic inspection and computed tomography (CT) scan. Surgical resection was performed following a diagnosis of primary liver cancer. Micropathologically, both carcinomatous and sarcomatous elements were present, and diagnosis of liver carcinosarcoma was confirmed. The carcinomatous element consisted of hepatocellular carcinoma and foci of cholangiocellular carcinoma. The sarcomatous element was composed of spindle cells and bizarre cells, as well as foci of osteosarcoma and chondrosarcoma. Hepatocellular carcinoma cells diffusely expressed both hepatocyte specific markers cytokeratin (CK) 8/18 and cholangiocyte specific markers CK19, and sarcoma cells were positive for vimentin. Interestingly, both carcinomatous and sarcomatous cells expressed epithelial membrane antigen. CD117-positive ductular reactions and small undifferentiated cells were observed. A liver progenitor cell origin of the liver carcinosarcoma was proposed.

The regulation role of interferon regulatory factor-1 gene and clinical relevance.

IRF-1, a kind of transcription factors, is expressed constitutively in all cells types except early embryonal cells. By virtue of its interaction with specific DNA sequence, IRF-1 regulates the transcription of a set of target genes which play essential roles in various physiological and pathological processes, including viral infection, tumor immune surveillance, pro-inflammatory injury, development of immunity system. What's more, IRF-1 also interacts with other transcription factors to regulate the specific genes transcription in the nucleus. In immunity system, IRF-1 is suggested to provide a link between innate and adoptive immune system. Although IRF-1 has been demonstrated with essential role in human immunity, the comprehensive understanding of the role of IRF-1 has been restrained because of extensive target genes, Here, we review the clinical relevance of IRF-1 and underlying mechanism based on the latest researches.

Chen's U-suture technique for end-to-end invaginated pancreaticojejunostomy following pancreaticoduodenectomy.

BACKGROUND AND PURPOSE: Internationally, postoperative pancreatic fistula (POPF) remains a leading cause of morbidity and mortality after pancreaticoduodenectomy (PD). In order to reduce the incidence of POPF, a number of technical modifications for pancreato-enteric anastomosis after PD have been proposed. In 1995, we established a new technique with transpancreatic transverse U-sutures for end-to-end invaginated pancreaticojejunostomy after a PD, and the preliminary results were quite encouraging. This study aims to review a new surgical approach, the Chen's U-stitch technique, for end-to-end invaginated pancreaticojejunostomy, which involves two to four transpancreatic transverse U-sutures, and to evaluate the effectiveness of this approach with reducing the incidence of POPF formation. METHODS: To evaluate this new approach, during 2002-2012, a total of 264 patients who received the new Chen's U-stitch technique after a PD were included in this study. Postoperative morbidity and mortality, including the incidence of POPF, were analyzed. RESULTS: Postoperative morbidity was 22.3 % (59/264) and mortality was 0 % (0/264). The POPF rate was 3.4 % (9/264) for Grade A, 0.8 % (2/264) for Grade B, and 0 % (0/264) for Grade C. CONCLUSIONS: This new surgical technique (Chen's U-stitch), which involves an end-to-end invaginated pancreaticojejunostomy with two to four transpancreatic transverse U-sutures, provides excellent outcomes at reducing the incidence of POPF after PD.

Step-by-step vascular control for extracapsular resection of complex giant liver hemangioma involving the inferior vena cava.

Massive hemorrhage remains an important clinical problem in extracapsular resection of giant liver hemangiomas (GLHs), especially for those involving the proximal hepatic veins and/or inferior vena cava. Between July 2004 and March 2012, 87 patients with a complex GLH scheduled for surgical treatment were included in this study. All patients were underwent vascular preparation (Step 1), advanced hepatic artery clamping (Step 2), and stepwise vascular occlusion (Step 3). Intraoperative blood loss, blood transfusion volume, degree of ischemia-reperfusion injury, and postoperative complications were recorded. No patients required urgent vascular preparation to manage intraoperative bleeding. In total, 87, 64, and 21 patients had portal triad (PT), infrahepatic inferior vena cava (IVC), and suprahepatic IVC preparation; and 17, 43, and 11 patients had PT, PT and suprahepatic IVC, and all three (PT, infra-, and suprahepatic IVC) occlusions. The PT, infrahepatic IVC, and SIVC occlusion times were 12.1 ± 3.7 minutes, 7.9 ± 2.4 minutes, and 3.2 ± 1.4 minutes, respectively. Mean blood loss was 291.9 ± 124.5 mL, and only four patients received blood transfusions. No patients had life-threatening complications or died (Clavien-Dindo Grade 4, 5). Compared with paralleled studies, this technique has an advantage to decrease the blood loss in less liver ischemia time. For complex GLH resections, the described step-by-step vascular control technique was efficacious and feasible for controlling intraoperative bleeding.

Long-term outcomes of repeat hepatic resection in patients with recurrent hepatocellular carcinoma and analysis of recurrent types and their prognosis: a single-center experience in China.

BACKGROUND: Recurrent hepatocellular carcinoma (HCC) after curative resection usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO). The long-term outcomes of repeat hepatic resection in patients with different types of recurrence have not been evaluated in a large number of patients. The surgical indications for recurrent HCC remain controversial. The purpose of this study was to investigate long-term outcomes of repeat hepatic resection and clinicopathologic factors associated with different types of recurrent HCC, and to single out principle differentiating factors between IM and MO. METHODS: 82 patients who underwent repeat hepatic resection for recurrent HCC were retrospectively studied. The recurrent type was evaluated by histopathologic analysis of primary and recurrent HCC. The recurrence and survival rates as well as clinicopathologic factors associated with different types of recurrence were analyzed. RESULTS: 45 patients (54.9%) had confirmed with IM, and 37 patients (45.1%) had with MO. The recurrence rates in the MO patients after initial or repeat resection were significantly lower than those in the IM patients (p < 0.001). The overall survival rates in the MO patients after initial or repeat resection were significantly higher than those in the IM patients (p < 0.001). Recurrence-free time was identified as the most significant differentiating factor between IM and MO. A recurrence-free time of 18 months after initial resection was a significant cutoff time point for differentiating between IM and MO. A recurrence-free time of less than or equal to 18 months and microvascular invasion at repeat resection were independent adverse prognostic factors for overall survival after repeat hepatic resection. CONCLUSIONS: Repeat hepatic resection resulted in much higher survival rates in the MO patients than in the IM patients. Repeat hepatic resection could be recommended for those patients in whom the recurrent HCC occurs more than 18 months after initial resection.

Alternative management of anatomical right hemihepatectomy using ligation of inflow and outflow vessels without hilus dissection.

BACKGROUND AND AIM: The conventional method of anatomical right hemihepatectomy (ARHH) requires hilus dissection. We report a method without hilus dissection to minimize intraoperative bleeding. METHODS: We retrospectively evaluated data of 107 patients who received ARHH involving ligation of corresponding inflow and outflow vessels (LCIOV) without hilus dissection between January 2000 and October 2008. Results were compared to those of patients who underwent non-anatomical right hemihepatectomies (NARHH). RESULTS: The two groups had similar gender and age (both, P>0.05). The LCIOV group had a higher percentage of patients without intrahepatic metastases (94.6% vs 80.3%, P=0.003). Hepatocellular carcinoma (HCC) lesion size (9.3 vs 10.2, P=0.023), durations of inferior vena cava occlusion (4 vs 4.7, P<0.001) and portal triad occlusion (7 vs 11, P<0.001), blood loss (430 vs 580 mL, P=0.001), transfusion volume (300 vs 520 mL, P<0.001), and measures of postoperative liver function (e.g. maximum aspartate aminotransferase [AST]) of the LCIOV group were also significantly less than the NARHH group. Larger hepatic cavernous hemangiomas (HCH) lesion size (16.2 vs 13.0, P<0.001), longer operative time (168 vs 154 min, P=0.017), and a lower percentage of patients with inferior vena cava occlusion (17.8% vs 35.2%, P=0.001), pleural effusions (19.3% vs 30.9%, P=0.042), and blood transfusions (10.3% vs 75.0%, P<0.001) were found in the LCIOV group. CONCLUSION: The reported method is a safe and bloodless technique for right hemihepatectomy in select patients.

[Minor liver resection for hilar cholangiocarcinoma of Bismuth-Corlette type III].

OBJECTIVE: To evaluate long-term outcomes of minor liver resection for hilar cholangiocarcinoma (HC) of Bismuth-Corlette type III. METHODS: From January 1997 to December 2007, the clinical data of 91 patients with Bismuth-Corlette type III HC underwent hepatectomy were collected and analyzed retrospectively. RESULTS: There were 60 patients underwent minor hepatectomy, and 31 undergoing major hepatectomy. Hepaticojejunostomy was made conventionally in an end-to-side fashion in the patients undergoing major liver resection, and a new technique of hepaticojejunostomy used in the patients undergoing minor liver resection. That was the anterior edges of bile duct stumps which were not sutured after suturing of posterior edges. Instead of, the anterior edge of jejunum loop to the remnant liver on the top of the bile duct stumps were sutured with intermittent "U" sutures. In all patients, in-hospital mortality rate was 0 and rate of bile leakage was only 2.1%. The actual 1-, 3- and 5-year survival rates were 91.6% and 87.0%, 61.6% and 62.0%, 31.6% and 33.0%, respectively (P > 0.05). CONCLUSIONS: Minor liver resection for the selected patients with HC of Bismuth-Corlette type III according to our criteria achieved better long-term outcomes. A new hepaticojejunostomy used in the patients undergoing minor liver resection is a safe and effective method.

[Preliminary study on cardiac allograft rejection in mice by Extractum trametes robiniophila murr].

OBJECTIVE: To study the effect of Extractum trametes robiniophila murr on cardiac allograft rejection in mice. METHODS: All abdominal heterotopic heart transplantation models were divided into three groups as follows: (A) Extractum trametes robiniophila murr group. (B) Rejection group. (C) Isograft group. In each group, mean survival times (MST) of transplanted hearts and their pathologic histological changes at postoperative fifth day were observed. With fluoroimmunoassay, granzyme B and CD8(+) expressions were examined. RESULTS: The MST of heart allografts in group A were (6.38 +/- 0.69) d, significantly shorter than that of group B [(8.31 +/- 0.59) d] (P < 0.01). In group A, acute rejection was present in advance; transplanted hearts were seriously damaged into acute rejection pathological grade 3, and CD8(+) T lymphocytes infiltrated diffusely and the expression of granzyme B increased significantly as compared with other groups. CONCLUSIONS: Exclusive application of Extractum trametes robiniophila murr can promote the acute rejection of graft in early phase of postoperation, and the mechanism may be the promoted proliferation and infiltration of CD8(+) T lymphocytes and the increased expression of granzyme B.

B7-H4 transfection prolongs beta-cell graft survival.

B7-H4, a recently discovered member of B7 family, can negatively regulate T cell responses. However, it is not clear whether B7-H4 negatively function in cell transplantation. In this study we investigated the immunosuppressive effect of B7-H4 on beta-cell transplantation. An insulinoma cell line, NIT-1, transfected with B7-H4 (B7-H4-NIT) was established, and transplanted to diabetic C57BL/6 mice by intraperitoneal injection. Proliferation assay of splenocytes in vitro showed that B7-H4-NIT suppressed alloreactive T cell activation. The proportion of IFN-gamma-producing cells in recipient spleen was significantly reduced and the number of Treg cells was upregulated in B7-H4-NIT group compared to the control, EGFP-NIT. The expression of mRNA coding IFN-gamma was lower but that of IL-4 was higher in B7-H4-NIT transplanted recipients than in the control animals. The results of ELISA also revealed the same trends. Diabetic mice reached normalglycemic quickly and gained weight after transplantation of B7-H4-NIT. More importantly, the survival time for recipients transplanted with B7-H4-NIT cells was significantly longer than that with EGFP-NIT cells. These results indicate that B7-H4 transfection prolongs beta-cell graft survival.