Fate of small remnant pancreatic tail in splenic hilum after laparoscopic spleen preserving distal pancreatectomy: a retrospective study.

Purpose: When performing laparoscopic spleen-preserving distal pancreatectomy (LSPDP), sometimes, anatomically challenging patients are encountered, where the pancreatic tail is deep in the splenic hilum. The purpose of this study was to discuss the experience with the surgical technique of leaving the deep pancreatic tail of the splenic hilum in these patients. Methods: Eleven patients who underwent LSPDP with remnant pancreatic tails between November 2019 and August 2021 at Samsung Medical Center in Seoul, Korea were included in the study. Their short-term postoperative outcomes were analyzed retrospectively. Results: The mean operative time was 168.6 ± 26.0 minutes, the estimated blood loss was 172.7 ± 95.8 mL, and the postoperative length of stay was 6.1 ± 1.0 days. All 11 lesions were in the body or tail of the pancreas and included 2 intraductal papillary mucinous neoplasms, 6 neuroendocrine tumors, 2 cystic neoplasms, and 1 patient with chronic pancreatitis. In 10 of the 11 patients, only the pancreatic tail was left inside the distal portion of the splenic hilum of the branching splenic vessel, and there was a collection of intraabdominal fluid, which was naturally resolved. One patient with a remnant pancreatic tail above the hilar vessels was readmitted due to a postoperative pancreatic fistula with fever and underwent internal drainage. Conclusion: In spleen preservation, leaving a small pancreatic tail inside the splenic hilum is feasible and more beneficial to the patient than performing splenectomy in anatomically challenging patients.

Pancreatic Metastasectomy for Secondary Malignancy of the Pancreas: A Single-institution Experience.

BACKGROUND/AIM: Metastasis to the pancreas is rare, and the benefit of resection for secondary pancreatic cancer is poorly defined. Furthermore, there are no guidelines for pancreatic metastasectomy in such patients. The purpose of this study was to discuss our experience with the operative management of secondary pancreatic cancer. PATIENTS AND METHODS: This retrospective study included 76 patients who underwent pancreatic metastasectomy for secondary pancreatic cancer between January 2000 and December 2020 at Samsung Medical Center, Seoul, Republic of Korea. RESULTS: Among the study subjects, 44 underwent distal pancreatectomy, 21 pancreaticoduodenectomy, 5 total pancreatectomy, and 6 enucleation or wedge resection for metastasis. The overall survival (OS) and recurrence-free survival (RFS) were higher in the patients with RCC than in patients with other malignancies (p=0.004 and p=0.051, respectively). Statistically significant differences were not observed in OS and RFS between patients with right RCC (rRCC) or left RCC (lRCC; p=0.523 and p=0.586, respectively). CONCLUSION: Pancreatic metastasectomy may offer promising outcomes regarding curative intent in instances of secondary pancreatic metastasis, particularly in the context of RCC. However, regarding the side of primary RCC, no statistically significant differences were found in OS and RFS between rRCC and lRCC.

Comparison between percutaneous transhepatic gallbladder drainage and upfront laparoscopic cholecystectomy in patients with moderate-to-severe acute cholecystitis: a propensity score-matched analysis.

Purpose: In the Tokyo Guidelines 2018 (TG18), emergency laparoscopic cholecystectomy is recognized as a crucial early treatment option for acute cholecystitis. However, early laparoscopic intervention in patients with moderate-to-severe acute cholecystitis or those with severe comorbidities may increase the risk of complications. Therefore, in the present study, we investigated the association between early laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) in moderate-to-severe acute cholecystitis patients. Methods: We retrospectively analyzed 835 TG18 grade II or III acute cholecystitis patients who underwent laparoscopic cholecystectomy at 4 tertiary medical centers in the Republic of Korea. Patients were classified into 2 groups according to whether PTGBD was performed before surgery, and their short-term postoperative outcomes were analyzed retrospectively. Results: The patients were divided into 2 groups, and 1:1 propensity score matching was conducted to establish the PTGBD group (n = 201) and the early laparoscopic cholecystectomy group (n = 201). The PTGBD group experienced significantly higher rates of preoperative systemic inflammatory response syndrome (24.9% vs. 6.5%, P < 0.001), pneumonia (7.5% vs. 3.0%, P = 0.045), and cardiac disease (67.2% vs. 57.7%, P = 0.041) than the early operation group. However, there was no difference in biliary complication (hazard ratio, 1.103; 95% confidence interval, 0.519-2.343; P = 0.799) between the PTGBD group and early laparoscopic cholecystectomy group. Conclusion: In most cases of moderate-to-severe cholecystitis, early laparoscopic cholecystectomy was relatively feasible. However, PTGBD should be considered if patients have the risk factor of underlying disease when experiencing general anesthesia.

Effects of Treating Subclinical Rejection 2 Weeks After Kidney Transplantation, as Determined by Analyzing 1-Year Histologic Outcomes.

Subclinical rejection (SCR) is associated with chronic allograft nephropathy. Therefore, early detection and treatment of SCR through a protocol biopsy (PB) can reduce the incidence of pathologic changes. This study evaluates the impact of early detection and treatment of SCR using a routine PB 2 weeks after kidney transplantation (KT) by examining histologic outcomes 1 year later. We reviewed 624 KT recipients at the Samsung Medical Center between August 2012 and December 2018. Protocol biopsy was planned 2 weeks and 1 year after transplantation. We compared the histologic changes between the 2 biopsies. After a propensity score matching analysis, we divided the patients into 2 groups: the proven normal group (n = 256) and the rejection group (n = 96) at the PB taken 2 weeks post-transplant. The rejection group showed no significant difference from the normal group in the flow of graft function or the Kaplan-Meier curve for graft survival. In the histologic outcomes, the pathologic differences between the groups significantly improved between the 2 time points. Treating SCR through a PB 2 weeks after KT can contribute to the maintenance of graft function and improve histologic changes 1 year after KT.

The Protective Role of Protocol Biopsy for Allograft Kidney Maintenance in Kidney Transplantation.

Many studies have reported that protocol biopsy (PB) may help preserve kidney function in kidney transplant recipients. Early detection and treatment of subclinical rejection may reduce the incidence of chronic antibody-mediated rejection and graft failure. However, no consensus has been reached regarding PB effectiveness, timing, and policy. This study aimed to evaluate the protective role of routine PB performed 2 weeks and 1 year after kidney transplantation. We reviewed 854 kidney transplant recipients at the Samsung Medical Center between July 2007 and August 2017, with PBs planned at 2 weeks and 1 year after transplantation. We compared the trends in graft function, chronic kidney disease (CKD) progression, new-onset CKD, infection, and patient and graft survival between the 504 patients who underwent PB and 350 who did not undergo PB. The PB group was again divided into 2 groups: the single PB group (n = 207) and the double PB group (n = 297). The PB group was significantly different from the no-PB group in terms of the trends in graft function (estimated glomerular filtration rate). The Kaplan-Meier curve showed that PB did not significantly improve graft or overall patient survival. However, in the multivariate Cox analysis, the double PB group had advantages in graft survival, CKD progression, and new-onset CKD. PB can play a protective role in the maintenance of kidney grafts in kidney transplant recipients.

Comparison of Short-Term Surgical Outcomes According to Immediately Postoperative Serum Glucose Level in Non-Diabetic Pancreatic Resection Patients.

The adequate regulation of postoperative serum glucose level (SGL) is widely accepted; however, the effects for non-diabetic patients who underwent major pancreatic surgery have not yet been established. We discerned the relevance of the immediately postoperative SGL to short-term postoperative outcomes from major pancreatic surgery in non-diabetic patients. Between January 2007 and December 2016, 2259 non-diabetic patients underwent major pancreatic surgery at four tertiary medical centers in Republic of Korea. Based on a SGL of 200 mg/dL, patients were classified into two groups by averaging the results of four SGL tests taken on the first day after surgery, and their short-term postoperative outcomes were analyzed. A 1:1 propensity score matching method was conducted to establish the high SGL group (n = 568) and the normal SGL group (n = 568). The high SGL group experienced a significantly higher rate of level C complications in the Clavien-Dindo classification (CDc) than the normal SGL group (24.1% vs. 16.5%, p = 0.002). Additionally, an SGL of more than 200 mg/dL was associated with a significantly high risk of complications above level C CDc after adjusting for other risk factors (hazard ratio = 1.324, 95% confidence interval = 1.048-1.672, p = 0.019). The regulation of SGL of less than 200 mg/dL in non-diabetic patients early after major pancreatic surgery could be helpful for reducing postoperative complications.

Intraoperative Positive Pancreatic Parenchymal Resection Margin: Is It a True Indication of Completion Total Pancreatectomy after Partial Pancreatectomy for Pancreatic Ductal Adenocarcinoma?

BACKGROUND: Total pancreatectomy (TP) can be performed in cases with positive resection margin after partial pancreatectomy for pancreatic cancer. However, despite complete removal of the residual pancreatic parenchyme, it is questionable whether an actual R0 resection and favorable survival can be achieved. This study aimed to identify the R0 resection rate and postoperative outcomes, including survival, following completion TP (cTP) performed due to intraoperative positive margin. METHODS: From 1995 to 2015, 1096 patients with pancreatic ductal adenocarcinoma underwent elective pancreatectomy at the Samsung Medical Center. Among these, 25 patients underwent cTP, which was converted during partial pancreatectomy because of a positive resection margin. To compare survival after R0 resection between the cTP R0 and pancreaticoduodenectomy (PD) R0 cases, propensity score matching was conducted to balance the baseline characteristics. RESULTS: The R0 rate of cTP performed due to intraoperative positive margin was 84% (21/25). The overall 5-year survival rate (5YSR) in the 25 cTP cases was 8%. There was no difference in the 5YSR between the cTP R0 and cTP R1 groups (9.5% versus 0.0%, p = 0.963). However, the 5YSR of the cTP R0 group was significantly lower than that of the PD R0 group (9.5% versus 20.0%, p = 0.022). There was no distinct difference in postoperative complications between the cTP R0 versus cTP R1 and cTP R0 versus PD R0 groups. CONCLUSIONS: In cases with intraoperative positive pancreatic parenchymal resection margin, survival after cTP was not favorable. Careful patient selection is needed to perform cTP in such cases.

Effect of Intraoperatively Detected Bacteriobilia on Surgical Outcomes After Pancreatoduodenectomy: Analysis of a Prospective Database in a Single Institute.

BACKGROUND: Bacteriobilia, the colonization of bacteria in bile, can be caused by obstructive cholangitis or preoperative biliary drainage (PBD), and is not uncommon condition in patients undergoing pancreatoduodenectomy (PD). This study aims to investigate the effect of intraoperatively detected bacteriobilia on surgical outcomes after PD. METHODS: For patients who underwent PD in Samsung Medical Center between 2018 and 2020, an intraoperative bile culture was performed prospectively, and their clinicopathological data were retrospectively reviewed. Surgical outcomes were compared between the patients, classified according to PBD and bacteriobilia. Logistic regression analysis was performed to identify factors increasing postoperative complications. RESULTS: A total of 382 patients were included, and 202 (52.9%) patients had PBD (PBD group). Bacteriobilia was significantly more common in PBD group comparing to non-PBD group (31.1% vs 75.2%, P < 0.001), but there was no difference in postoperative complications. Among PBD group, there were more patients with major complications and CR-POPF in endoscopic drainage group comparing to percutaneous drainage group (37.9% vs 14.6%, P = 0.002; 17.0% vs 4.2%, P = 0.025, respectively). In multivariable analysis, bacteriobilia increased the risk of wound complications (P = 0.041), but not the risks of other short-term adverse outcomes. CONCLUSION: Bacteriobilia itself does not exacerbate short-term postoperative outcomes after PD except for wound complication. Therefore, surgery could be performed as planned regardless of bacteriobilia, without the need to wait for negative cultures.

Prophylactic octreotide for postoperative pancreatic fistula in patients with pancreatoduodenectomy: Risk-stratified analysis.

BACKGROUND: Postoperative pancreatic fistula is one of the most critical complications following pancreatic surgery. This study aimed to evaluate the utility of selective prophylactic octreotide for patients at high risk of developing postoperative pancreatic fistula. METHODS: From June 2019 to July 2020, 263 patients underwent pancreatoduodenectomy with pancreatojejunostomy at Samsung Medical Center. The individual fistula risk scores were calculated using a previously developed nomogram. The clinicopathological data of the patients were retrospectively reviewed. RESULTS: There were 81 patients in the low-risk group and 182 patients in the high-risk group. No statistically significant differences were found in the rates of clinically relevant postoperative pancreatic fistula between octreotide group and the control group in all patients (15.0% vs 14.7%, P = .963) and in the high-risk group (16.1% vs 23.6%, P = .206). In risk factor analysis, postoperative octreotide was not an independent risk factor for clinically relevant pancreatic fistula in all patients and the high-risk group. Drain fluid amylase levels on the first postoperative day were significantly associated with clinically relevant postoperative pancreatic fistula, regardless of the individual risk. CONCLUSIONS: The selective use of octreotide, even in high-risk patients, showed no protective effect against pancreatic fistula. Therefore, the routine use of postoperative octreotide is not recommended.

Adverse Effects of Sarcopenic Obesity on Postoperative Complications after Major Hepatectomy in Patients with Hilar Cholangiocarcinoma.

Sarcopenic obesity (SO), which is defined as a high ratio of visceral adipose tissue to skeletal muscle, is a well-known risk factor for post-hepatectomy outcomes in patients with hepatocellular carcinoma. However, few studies have evaluated the effect of SO on postoperative outcomes in patients with hilar cholangiocarcinoma (CCC). This retrospective study aimed to evaluate the effect of preoperative SO on postoperative outcomes in patients with hilar CCC following major hepatectomy. Preoperative SO was assessed in 328 patients undergoing hepatectomy for hilar CCC at three institutions between 2006 and 2016. SO was calculated from cross-sectional visceral fat and muscle area displayed on preoperative CT imaging. Preoperative SO was present in 98 patients (29.9%). The major complication rate in patients with SO was higher than in those without SO (54.1% vs. 37.0%, p = 0.004). Additionally, postoperative hospital stays were prolonged in patients with SO (18.5 vs. 16.5 days, p = 0.038). After multivariable analysis, SO was identified as an independent risk factor for major complications after hepatectomy in hilar CCC patients (OR = 0.866, 95% CI: 1.148-3.034, p = 0.012). Careful postoperative management is needed after major hepatectomy in hilar CCC patients with SO.

Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation.

BACKGROUND Liver transplantation (LT) has been validated widely all over the world as the curative treatment for hepatocellular carcinoma (HCC). Statins have been reported to prevent the progression of HCC. There are many factors that affect recurrence of HCC, but the precise role of statins is unknown. Therefore, we examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent living-donor LT (LDLT) for HCC. MATERIAL AND METHODS We retrospectively analyzed 844 HCC patients who underwent primary adult-to-adult LDLT in our center between January 2007 and December 2016. Statin therapy was defined as administration of statins for more than 30 cumulative defined daily doses (cDDDs) after LT. We compared HCC recurrence and patient survival between non-statin (n=334) and statin (n=52) groups. RESULTS The recurrence rate was higher in the non-statin group; however, time-dependent multivariate analysis with Kaplan-Meier curves showed that statin users did not significantly benefit in terms of HCC recurrence-related survival or overall survival. Further, risk factor analysis of HCC recurrence and patient survival confirmed multiple regional treatments (≥3 times), high alpha fetoprotein level (≥100 ng/mL), large tumor size (≥3 cm), and microvascular invasion as risk factors for HCC recurrence, but statin treatment was not associated with a significantly lower recurrence rate of HCC or reduced mortality after adjusting for other risk factors. CONCLUSIONS Statin use might be associated with prevention of HCC progression, but no significant decrease in HCC recurrence rates in LDLT patients was recorded in this study.

Healthy Spouses can be Considered as Living Liver Donors.

BACKGROUND: Spousal donors have gradually been accepted as an alternative living liver donors to alleviate the organ shortage and prevent donations from children. No information is available regarding the effects of spousal donation on donor safety and recipient outcomes. Our purpose in this study was to determine how spousal liver grafts in living donor liver transplantation (LDLT) affect donor safety and recipient outcomes compared with those of LDLT from children. METHODS: We retrospectively analyzed 656 patients, including spouses and children, who underwent a right or extended right hepatectomy for living liver donation between January 2009 and December 2018. RESULTS: Spouses represented 18.8% (n = 123) of living liver donors. Female donors comprised 78.9% (n = 97) of spousal donors, and the proportion of male donors in the children group was 72.6% (n = 387). The mean donor operation time of the spousal group was shorter than that of the children group (330 min vs. 358 min; P = 0.011), and the complication rate in the spousal group was lower than that in the children group (12.2% vs. 22.9%; P = 0.006). However, there were no differences in severe complication rates, hospitalization, or liver function tests between the 2 groups at 3 months after donor surgery. The overall survival of recipients in the spousal group was not reduced compared to that of recipients in the children group. CONCLUSION: The present study suggests that, with careful selection, spousal donation is feasible and safe in LDLT.

Development and external validation of a nomogram with inflammatory markers for predicting invasiveness of intraductal papillary mucinous neoplasm of pancreas.

ABSTRACT: Recent studies have reported that inflammatory markers, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and advanced lung cancer inflammation index, are associated with invasiveness of intraductal papillary mucinous neoplasm (IPMN). This study aimed to develop and validate a new nomogram that includes inflammatory markers for predicting the invasiveness of IPMN.The data of 365 patients who underwent surgical resection for IPMN at 4 centers between 1995 and 2016 were retrospectively reviewed to develop a new nomogram. For external validation, a separate patient cohort was used. The predictive ability of the nomogram was evaluated using the area under the receiver operating characteristic curve.The new nomogram was developed using the following variables which were identified as risk factors for invasive IPMN: body mass index, preoperative serum bilirubin level, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, main duct type, presence of solid portion, and tumor size. After external validation, the area under the curve value was 0.649 (95% CI: 0.578-0.720, P < .001).To the best of our knowledge, this study is the first to predict and externally validate the invasiveness in IPMN using inflammatory markers. Further research is necessary to improve predictability of the model for selecting patients for surgical resection.

Does Preoperative Acute Pancreatitis Inevitably Delay Pancreatoduodenectomy in Patients with Periampullary Tumors?

Preoperative acute pancreatitis (PAP) in patients with periampullary tumor can cause technical difficulties when performing pancreatoduodenectomy (PD) but perioperative risks of PAP remain unclear. The purpose of this study was to investigate the impact of PAP on surgical outcomes and determine the optimal timing of PD. Patients undergoing surgery for periampullary tumors between 2009 and 2018 were included. Simple random sampling (1:4) was performed to compare outcomes between the PAP group and the control group. Operative failure was defined as exploration-only or unwanted total pancreatectomy. The rate of operative failure was higher in the PAP group than in the control group (6.6% vs. 0%, p < 0.001). There was no significant difference in postoperative outcomes including complications or in-hospital mortality between the two groups. Surgical outcomes were compared after dividing PAP groups by intervals (2, 3, or 4 weeks) between the onset of PAP and surgery, and there were no differences between the groups. In conclusion, in spite of the increased risk of operation failure, PD could be performed in PAP patients at comparable rates of postoperative complications. Further study is needed to select patients with PAP in proper conditions for performing PD.

Cost-effectiveness and long-term outcomes of liver transplantation using hepatitis B core antibody-positive grafts with hepatitis B immunoglobulin prophylaxis in Korea.

BACKGROUND/AIMS: Hepatitis B core antibody (anti-HBc)-positive donors are used as an extended donor pool, and current guidelines recommend the usage of nucleos(t)ide analogues (NAs) as prophylaxis for preventing de novo hepatitis B virus infection (DNH). We analyzed the long-term outcomes of a large cohort of liver transplantation (LT) patients receiving anti-HBc-positive grafts and evaluated the risk of DNH when hepatitis B immunoglobulin (HBIG) monotherapy was used as prophylaxis. We also compared the cost-effectiveness of HBIG and NAs. METHODS: We retrospectively reviewed 457 patients with anti-HBc-positive grafts and 898 patients with anti-HBc-negative grafts who underwent LT between January 2001 and December 2018. We compared recipient characteristics according to the anti-HBc status of the donor, and compared the costs of using NAs for the rest of the patient's life and using HBIG to maintain hepatitis B surface antibody titers above 200 IU/L. RESULTS: The 1-, 5-, and 10-year patient survival rates were 87.7%, 73.5%, and 67.7%, respectively, in patients with anti-HBc-positive grafts, and 88.5%, 77.4%, and 70.3%, respectively, in patients with anti-HBc-negative grafts (P=0.113). Among 457 recipients with anti-HBc-positive grafts, 117 (25.6%) were non-HBV recipients. The overall incidence of DNH was 0.9%. When using HBIG under insurance coverage, the cumulative cost was lower compared with using NA continuously without insurance coverage in Korea. CONCLUSION: Anti-HBc-positive grafts alone do not affect patient survival or graft survival. HBIG monoprophylaxis has good outcomes for preventing DNH, and the patient's long-term cost burden is low in Korea because of the national insurance system in this cohort.

Safety and effectiveness of kidney transplantation using a donation after brain death donor with acute kidney injury: a retrospective cohort study.

The use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

Recipient efficacy and safety of kidney transplantation from older living donor: consideration for using older kidney as a solution to the shortage of organs.

Background: As a solution to organ shortages, studies on kidney transplantation (KT) from older donors are being conducted. However, many controversies remain about its safety and efficacy. Methods: In Samsung Medical Center, from January 2000 to May 2015, 1,141 patients underwent living KT. Cases of retransplantation, recipient and donor aged younger than 18 years, and multiorgan transplantation were excluded, and a total of 859 cases were selected. Analysis was performed by dividing the patents into two groups a younger donor group (donors <60 years old; n=826) and an older donor group (donors ≥60 years old; n=33). Results: There were no significant differences between the two groups in patient death (log-rank P=0.173) or in postoperative complications. The older donor group had a higher acute rejection (P=0.034; hazard ratio [HR], 1.704) and graft failure rate (P=0.029, HR=2.352). There was no significant difference in the trend of estimated glomerular filtration rate over time (P=0.189). Conclusions: KT using kidneys from old-aged donors is safe, but there is room for improvement due to problems with higher acute rejection and graft failure rate.

Hepatocellular Carcinoma Arising from Hepatocellular Adenoma in an Elderly Male Patient.

Hepatocellular adenoma is a benign tumor of the liver occurring predominantly in young women taking oral contraceptives. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma has rarely been reported. Herein, we report the case of an elderly male patient with hepatocellular carcinoma that developed from hepatocellular adenoma. The patient's high risk for surgery and conflicting biopsy and imaging results made it difficult to determine the treatment direction. Eventually, the mass was completely removed by laparoscopic left hemi-hepatectomy without complications.

AP-1(c-Jun/FosB) mediates xFoxD5b expression in Xenopus early developmental neurogenesis.

AP-1 (activator protein-1) is composed of Jun and Fos proteins and functions in cell proliferation, apoptosis and differentiation. Previous studies have demonstrated that different AP-1 complexes participate in the determination of various cell fates. However, the role of different AP-1 complexes during early vertebrate development is not yet fully understood. In the present study, we demonstrate that AP-1(c-Jun/FosB) regulates neurogenesis via FoxD5b expression. We show that FoxD5 was induced by the inhibition of BMP and that FoxD5b plays roles in neurogenesis. Additionally, we show that the FoxD5b promoter region within -1336 and -1316 contains an AP-1 binding site, which is required for the transcriptional regulation of FoxD5b and is induced by the inhibition of BMP signaling in animal cap explants. Moreover, c-Jun, a component of AP-1, directly binds to the AP-1 binding site of the FoxD5b promoter and induces FoxD5b expression cooperatively with FosB, but not with c-Fos or Fra-1. Altogether, these results suggest that AP-1(c-Jun/FosB) may play a role in neurogenesis via the induction of FoxD5b expression during early vertebrate development.

Preparation and in vivo degradation of controlled biodegradability of electrospun silk fibroin nanofiber mats.

Controlled biodegradability of biomaterials is very important because different functionality and durability are required for various purposes and for specific tissues and organs. From this point of view, silk-based biomaterials have poor usability because of uncontrollable degradability, even though silk fibroin (SF) is highly biocompatible and a number of studies on silk biomaterials have been published to date. In this study, we prepared SF nanofiber mats that were recrystallized in different ways. These mats were fabricated by electrospinning with ethanol/propanol mixtures of various blend ratios, and their biodegradabilities in vitro and in vivo were evaluated using rats. As a result, we can suggest an established method to modulate the degradability of SF nanofibrous materials based on long-term (12 months) observations. In particular, we elucidated how the SF nanofibers are degraded and incorporated with surrounding tissue by observation of fluorescein isothiocyanate-labeled SF nanofiber in vivo. Our findings suggest a method for controlling the degradation rate of SF for medical applications.