International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

International Expert Consensus on Precision Anatomy for minimally invasive distal pancreatectomy: PAM-HBP Surgery Project.

BACKGROUND: Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021). METHODS: Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts. CONCLUSIONS: The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide.

Comparison of robotic and open pancreaticoduodenectomy for primary nonampullary duodenal adenocarcinoma: a retrospective cohort study.

PURPOSE: Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA. METHODS: Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS: Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200 ml, p < 0.001), time to oral intake (4.0 vs. 4.0 days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0 days, p = 0.01) compared with the OPD group. However, no differences were observed between the two groups in terms of operative time and the rates of major complications, grade B and C POPF, PPH, grade B and C DGE, biliary fistular, reoperation, and 90-day readmission. No patient died within 90 days. There were no significant differences in tumor size, differentiation, TNM stage, number of harvested lymph nodes, and the rates of nerve invasion, lymph node invasion, R0 resection, and the median overall survival between the two groups (p > 0.05) CONCLUSIONS: RPD is a safe, feasible, and effective treatment for PNDA compared with OPD and can be used as an alternative for surgeons in the treatment of PNDA. Further multicenter randomized controlled trials are needed to evaluate the effectiveness of RPD in patients with PNDA.

International expert consensus on precision anatomy for minimally invasive pancreatoduodenectomy: PAM-HBP surgery project.

BACKGROUND: The anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD. METHODS: Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection. CONCLUSIONS: MIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD.

A comparative study of end-to-end pancreatic anastomosis versus pancreaticojejunostomy after robotic central pancreatectomy.

Robotic central pancreatectomy has been applied for 20 years with the advantage of minimally invasive surgery. The general pancreatic reconstruction approaches include pancreaticojejunostomy and pancreaticogastrostomy. Recently, our group reported a few preliminary cases of application of end-to-end pancreatic anastomosis in robotic central pancreatectomy. This novel approach has not been compared with the conventional approach on a large scale. The objective of this study is to compare end-to-end pancreatic anastomosis with pancreaticojejunostomy after robotic central pancreatectomy based on the perioperative and long-term outcomes. Clinical data consist of demographics, clinicopathologic characteristics, perioperative and long-term outcomes of patients who underwent robotic central pancreatectomy from March 2015 to December 2019 were collected and analyzed. Seventy-four patients received a robotic central pancreatectomy with either end-to-end pancreatic anastomosis (n = 52) or pancreaticojejunostomy (n = 22). End-to-end pancreatic anastomosis was associated with shorter operative time and reduced blood loss. Despite a higher incidence of clinically relevant postoperative pancreatic fistula (69.2% vs. 36.4%, p = 0.009), the newer anastomotic technique was also associated with earlier removal of nasogastric tube and resumption of oral intake. Long-term results, in terms of either endocrine or exocrine function, were not affected by the anastomotic technique. We have shown the feasibility of robotic central pancreatectomy with end-to-end pancreatic anastomosis. Despite streamlined technique, the newer anastomosis appears to improve early post-operative results while preserving endocrine and exocrine functions in the long-term period. Evaluation of the true potential of robotic central pancreatectomy with end-to-end pancreatic anastomosis requires a prospective and randomized study enrolling a large number of patients.

Robotic pancreatectomy for intraductal papillary mucinous neoplasm of the pancreas: A large-scale study.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a mucin-producing tumor that develops from the epithelial lining of the main pancreatic duct or branch pancreatic ducts. Here, we assessed the feasibility and safety of various robotic pancreatectomy approaches to treating IPMN, and short- and long-term outcomes of robotic IPMN resection. METHODS: Data from patients who underwent robotic pancreatectomy for IPMN between 2012 and 2019 at our hospital were retrospectively analyzed. The survival outcomes for patients were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 174 patients who underwent robotic pancreatectomy, 120 and 54 patients had benign or malignant tumors, respectively. Patients with malignant IPMN had lost more weight in the 6 months prior to surgery (P = .008), and a higher serum level of CA19-9 (P < .001) and CEA (P < .001). Postoperative pancreatic or biliary fistula occurred in 17 or 6 patients overall, respectively. The pathology of the IPMN (P = .030), tumor diameter (P = .016), mural nodule (P = .023), tumor capsule (P = .003) and CA19-9 (P = .024) values were all independent risk factors for survival. The median OS time after surgical resection for the malignant IPMN group was 29.0 months (range, 21.6-36.4). The OS was significantly different in patients with IPMN according to their different pathology, tumor capsule, mural nodule group, CA19-9 level, or tumor diameter. CONCLUSIONS: This large-scale survey of 174 patients indicated that various robotic pancreatectomy approaches were feasible and safe for IPMN. Patients had an acceptable prognosis, indicating that robotic pancreatectomy represents a feasible potential therapeutic strategy for IPMN.

Robotic resection of liver focal nodal hyperplasia guided by indocyanine green fluorescence imaging: A preliminary analysis of 23 cases.

BACKGROUND: Focal nodal hyperplasia (FNH) is a common benign tumor of the liver. It occurs mostly in people aged 40-50 years and 90% of the patients are female. FNH can be cured by local resection. How to locate and judge the tumor boundary in real time is often a challenge for surgeons. AIM: To summarize the technique and feasibility of robotic resection of FNH guided by indocyanine green (ICG) fluorescence imaging. METHODS: The demographics and perioperative outcomes of a consecutive series of patients who underwent robotic resection of liver FNH guided by ICG fluorescence imaging between May 1, 2018 and September 30, 2019 were retrospectively analyzed. ICG was injected through the median elbow vein in all the patients at a dose of 0.25 mg/kg 48 h before the operation. During the operation, the position of FNH in the liver was located in the fluorescence mode of the Da Vinci Si robot operating system and the tumor boundary was determined during the resection. RESULTS: Among the 23 patients, there were 11 males and 12 females, with a mean age of 30.5 ± 9.3 years. Twenty-two cases completed robotic resection, while one (4.3%) case converted to open surgery. In the robotic surgery group, the operation time was 35-340 min with a median of 120 min, the intraoperative bleeding was 10-800 mL with a median of 50 mL, and the postoperative hospital stay was 1-7 d with a median of 4 d. Biliary fistula occurred in two (8.7%) patients after robotic operation and they both recovered after conservative treatment. One (4.3%) patient received blood transfusion and there was no death in this study. The postoperative hospital stay in the small tumor group was significantly shorter than that in the large tumor group (P < 0.05). CONCLUSION: ICG fluorescence imaging can guide the surgeon to perform robotic resection of liver FNH by locating the tumor and displaying the tumor boundary in real time. It is a safe and feasible method to ensure the complete resection of the tumor.

Retrocolic versus antecolic gastrointestinal reconstruction in robotic pancreaticoduodenectomy.

BACKGROUND: With the advancement of robotic pancreaticoduodenectomy (RPD), several reconstruction methods have been advocated to make RPD more effective and safer. In this study, we investigated the safety and effectiveness of RPD using a left retrocolic (L-port) technique and compared it with those of RPD using an antecolic technique. METHODS: Between October 2015 and August 2016, we retrospectively reviewed consecutive cases of RPD before and after introducing the L-port technique for gastrointestinal reconstruction. The L-port technique was mainly performed for retrocolic gastrojejunal reconstruction and some cases of duodenojejunal reconstruction. The perioperative and postoperative outcomes were compared in the two groups. RESULTS: Eighty-three cases of RPD were retrieved for statistical analysis. Compared with the antecolic group, the L-port group was significantly associated with a shorter operative time (median time [IQR] 345 [307-384] min vs. 390 [370-455] min, P < 0.001), reconstruction time (54 [48-59] min vs. 84 [75-98] min, P < 0.001) and lower incidence of delayed gastric emptying. There were no cases of re-operation due to internal herniation, colonic ischemia, or bowel volvulus in the L-port group during the 1-year follow-up period. CONCLUSIONS: Our results demonstrated that the L-port technique of RPD is a safe and feasible technique for gastrointestinal reconstruction.

Robotic vs laparoscopic hemihepatectomy: A comparative study from a single center.

BACKGROUND: Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH. METHODS: Data on the demographics, clinicopathologic characteristics, and perioperative outcomes of consecutive patients who underwent robotic or LH in a single center between November 2011 and July 2017 were analyzed. RESULTS: A total of 92 patients underwent robotic and 48 LH. Multiple linear regression analysis showed no significant difference in perioperative outcomes including operative time, postoperative hospital stay, postoperative complications, and mortality between the groups. Compared to the laparoscopic cohort, the robotic cohort had a significantly less estimated blood loss (120.24 mL; 95% confidence interval, 53.72-186.76) and a significantly lower conversation rate (1.09% vs 10.42%; P = .034). Stratified and interaction analyses demonstrated that disease type had an interaction effect on the association between the operative approach and the estimated blood loss. CONCLUSIONS: Robotic hemihepatectomy was safe and feasible in selected patients. It had similar perioperative outcomes as LH and was better than LH regarding estimated blood loss and open conversion.

An end-to-end pancreatic anastomosis in robotic central pancreatectomy.

BACKGROUND: Suturing the proximal pancreatic stump and performing pancreaticoenterostomy for the distal pancreatic stump following central pancreatectomy is a conventional procedure. This reconstruction after resection of the pathological pancreatic lesion brings changes in anatomy and physiology. In this study, an innovative one-stage robotic end-to-end pancreatic anastomosis was reported to replace the conventional pancreaticoenterostomy following central pancreatectomy. MATERIALS AND METHODS: The clinical data of 11 consecutive patients who underwent robotic central pancreatectomy with end-to-end pancreatic anastomosis between August 2017 and December 2017 were analyzed retrospectively. RESULTS: All operations were completed successfully without any conversion to open surgery. Nine patients had benign tumors, one had a mass-forming chronic pancreatitis, and one had an isolated pancreatic metastasis from a renal cancer. The mean gap left after central pancreatectomy was 4.3 ± 1.0 cm. The median operative time was 121 (range, 105 to 199) min. The median blood loss was 50 (range, 20 to 100) ml. Seven (63.6%) patients developed complications which included Clavien-Dindo Grade I complications in five patients, a Grade II complication in one patient, and a Grade IIIa complication in one patient. Seven patients developed a Grade B postoperative pancreatic fistula, and two patients a biochemical leak. There was no Grade C or worse pancreatic fistula. Magnetic resonance cholangiopancreatography at postoperative 6 months showed no stricture in any of the main pancreatic ducts. Three patients had an asymptomatic and small pancreatic pseudocyst. CONCLUSION: Robotic central pancreatectomy with end-to-end pancreatic anastomosis was safe and feasible. It restores the normal anatomy of the pancreas. With its good short-and long-term outcomes, it could be an alternative reconstructive method to pancreaticoenterostomy following central pancreatectomy.

Impact of resection margins on long-term survival after pancreaticoduodenectomy for pancreatic head carcinoma.

BACKGROUND: The impact of resection margin status on long-term survival after pancreaticoduodenectomy (PD) for patients with pancreatic head carcinoma remains controversial and depends on the method used in the histopathological study of the resected specimens. This study aimed to examine the impact of resection margin status on the long-term overall survival of patients with pancreatic head carcinoma after PD using the tumor node metastasis standard. METHODS: Consecutive patients with pancreatic head carcinoma who underwent PD at the Chinese People's Liberation Army General Hospital between May 2010 and May 2016 were included. The impact of resection margin status on long-term survival was retrospectively analyzed. RESULTS: Among the 124 patients, R0 resection was achieved in 85 patients (68.5%), R1 resection in 38 patients (30.7%) and R2 resection in 1 patient (0.8%). The 1- and 3-year overall survival (OS) rates were significantly higher for the patients who underwent R0 resection than the rates for those who underwent R1 resection (1-year OS rates: 69.4% vs 53.0%; 3-year OS rates: 26.9% vs 11.7%). Multivariate analysis showed that resection margin status and venous invasion were significant risk factors for OS. CONCLUSION: Resection margin was an independent risk factor for OS for patients with pancreatic head carcinoma after PD. R0 resection was associated with significantly better OS after surgery.

Application of End-to-end Anastomosis in Robotic Central Pancreatectomy.

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of pancreatic body. With technological development, the robotic surgical system has shown its advantage in minimally invasive surgery and been increasingly applied in central pancreatectomy. However, reconstruction of the continuity of pancreas with end-to-end anastomosis after robotic central pancreatectomy has not been applied. In this study, we report surgical techniques for robotic central pancreatectomy with end-to-end anastomosis. The pancreas is reconstructed by duct-to-duct anastomosis of the pancreatic duct with a pancreatic stent inserted in the two stumps of pancreatic duct, and by end-to-end anastomosis of the pancreatic parenchyma. Compared with traditional central pancreatectomy with pancreaticoenteric anastomosis, this approach decreases the operative injury to the patient, and also conserves the integrity and continuity of the digestive duct and pancreatic duct. The robotic surgical system integrated with multiple instruments with flexible and precise movement is particularly suitable for the dissection and reconstruction of the pancreatic duct. We found that robotic central pancreatectomy with end-to-end anastomosis is safe and feasible, and we need more experience to evaluate its best indications and long-term outcomes.

Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. METHODS: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted. RESULTS: PANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-γ. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (χ2 = 4.550, P = 0.030), poor histological differentiation (χ2 = 5.690, P = 0.017), and lymph node metastasis (χ2 = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma. CONCLUSIONS: The study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target.

Skeletal myoblast transplantation on gene expression profiles of insulin signaling pathway and mitochondrial biogenesis and function in skeletal muscle.

AIM: The study aims to investigate the gene expression profiling of insulin signaling pathway and mitochondrial biogenesis and function in the skeletal muscle of KK mice. METHODS: KK mice were divided into the following groups: KK control group, basal medium (M199) only; KK fibroblast group, with human fibroblast transplantation; KK myoblast group, with human skeletal myoblast transplantation. C57BL mice received hSkM transplantation as a normal control. Cells were transplanted into mice hind limb skeletal muscle. All animals were treated with cyclosporine for 6 weeks only. The mice were sacrificed in a fasting state at 12 weeks after treatment. Hind limb skeletal muscle was harvested and used for study of gene expression profiling. RESULTS: hSkMs survived extensively in mice skeletal muscle at 12 weeks after cell transplantation. Glucose tolerance test showed a significant decrease of blood glucose in the mice of KK myoblast group compared to the KK control and fibroblast groups. Transcriptional patterns of insulin signaling pathway showed alterations in KK myoblast as compared with KK control group (23 genes), KK fibroblast group (7 genes), and C57BL group (8 genes). Transcriptional patterns of mitochondrial biogenesis and function also had alterations in KK myoblast as compared with KK control group (27 genes), KK fibroblast group (9 genes), and C57BL group (6 genes). CONCLUSIONS: These data demonstrated for the first time that hSKM transplantation resulted in a change of gene transcript in multiple genes involved in insulin signaling pathway and mitochondrial biogenesis and function.

A preliminary study of imaging paclitaxel-induced tumor apoptosis with (99)Tc(m)-His10-Annexin V.

BACKGROUND: In tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model. METHODS: (99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity. RESULTS: (99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01). CONCLUSION: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats.

The small (SK3) and intermediate (IK1) conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats (250-300 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group (P < 0.05). The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.

Effect of endothelin-1 on cyclooxygenase-2 expression in human hormone refractory prostate cancer cells.

The present study aimed to explore the effects and possible mechanisms of recombinant human endothelin (ET)-1 on cyclooxygenase (COX)-2 expression in human hormone refractory prostate cancer PC3 cells. PC3 cells were treated with 100 nmol/l ET-1 for the indicated times (3, 6, 9, 12 and 24 h) and concentrations (0.1, 1, 10 and 100 nmol/l) for 24 h. Moreover, 100 nmol/l ET-1 was used to treat PC3 cells alone or in combination with endothelin A receptor (ET(A)R) antagonist BQ123 (1 µmol/l), endothelin B receptor (ET(B)R) antagonist BQ788 (1 µmol/l), MAPK/extracellular signal-regulated kinase kinase (MEK)-selective inhibitor, PD98059 (10 µmol/l), p38 mitogen-activated protein kinase (MAPK) antagonist SB203580 (5 µmol/l) or epidermal growth factor receptor (EGFR) antagonist AG1478 (0.1 µmol/l) for 24 h. COX-2 mRNA and protein expression was detected in the PC3 cells by reverse transcription-polymerase chain reaction and Western blot analysis. ET-1 induced a time- and dose-dependent increase in the mRNA and protein expression of COX-2 in the PC3 cells. BQ123, LY294002, SC203580 and AG1478 prevented the expression of COX-2 in the PC3 cells (P<0.05), while BQ788 did not. ET-1 induced the up-regulation of COX-2 in the PC3 cells. ET(A)R may be involved in the process. Several signaling pathways, including p42/44 MAPK, p38 MAPK and EGFR, are therefore implicated in the regulation of COX-2 expression.

Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression.

Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus-transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR beta-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A(1c)-lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.

[Implantation brachytherapy with 32P-chromic phosphate-poly (L-lactide) delayed-release particles for prostate cancer in nude mice].

OBJECTIVE: To study the effects of implantation brachytherapy with delayed-release particles of 32P-chromic phosphate-poly (L-lactide) (32P-CP-PLLA) on prostate cancer (PCa) in nude mice. METHODS: We established a subcutaneous transplantable PCa model in nude mice, and randomly divided them into six groups, Groups A, B and C implanted intratumorally with 32P-CP-PLLA delayed-release particles at 3.7, 7.4 and 14.8 MBq, Groups D, E and F with 125I particles at the same doses as the former three, and another six nude mice were included in Group G as the blank control. Then we killed the mice at 21 days after the treatment, observed the effects of the particles on the morphology of the tumor and their inhibition of tumor growth, counted WBCs and platelets (PLTs) in the peripheral blood, and detected the toxic reaction of the blood. RESULTS: At 21 days after the treatment, the solid tumor tissues exhibited bleeding and necrotic changes, and the rates of tumor inhibition were positively correlated with the doses of administration. Groups A, B and C showed statistically significant differences from Groups D, E, F and G in the rate of tumor inhibition ([ 65.72 +/- 6.95]%, [77.58 +/- 4.32]% and [82.64 +/- 4.03]% versus [35.61 +/- 5.61]%, [43.30 +/- 6.94]% and [69.01 +/- 4.98]%), WBC count ([1.72 +/- 0.37] x 10(9)/L, [1.23 +/- 0.27] x 10(9)/L and [0.86 +/- 0.25] x 10(9)/L versus [1.45 +/- 0.40] x 10(9)/L, [0.51 +/- 0.24] x 10(9)/L, [0.37 +/- 0.26] x 10(9)/L and [3.96 +/- 0.26] x 10(9)/L), PLT count ([1.18 +/- 0.11] x 10(11)/L, [0.97 +/- 0.10] x 10(11)/L and [0.72 +/- 0.11] x 10(11)/L versus [0.97 +/- 0.15] x 10(11)/L, [0.76 +/- 0.16] x 10(11)/L, [0.64 +/- 0.12] x 10(11)/L and [2.89 +/- 0.21] x 10(11)/L) and body weight ([18.60 +/- 0.66] g, [17.60 +/- 0.39] g and [16.90 +/- 0.68] g versus [17.86 +/- 0.60] g, [15.56 +/- 0.39] g, [14.61 +/- 0.65] g and [19.95 +/- 0.73] g) (P < 0.01). CONCLUSION: Intratumoral implantation of 32P-CP-PL-LA is a safe, simple and effective radionuclide interventional therapy for prostate cancer.

[Epidermal growth factor up-regulates the mRNA expression of endothelin-1 and its receptors in prostate cancer PC-3 cell lines].

OBJECTIVE: To investigate the effects of the epidermal growth factor on the mRNA expression of endothelin-1 and its receptors (ET(A)R, ET(B)R) in hormone refractory prostate cancer (HRPC) PC-3 cell lines. METHODS: PC-3 cells were cultured in vitro. After the treatment with EGF, the mRNA expressions of endothelin-1, ET(A)R and ET(B)R were detected by RT-PCR in PC-3 cell lines. The levels of the mRNA expression of endothelin-1 and its receptors were examined at different time points by RT-PCR. RESULTS: The expressions of endothelin-1 and ET(A)R mRNA but not the mRNA expression of ET(B)R was observed in PC-3 cell lines. After 24 hours of treatment with EGF, the expressions of endothelin-1 and ET(A)R in PC-3 cell lines were both up-regulated and there was significant difference (P < 0.05) between the experimental and control groups. Different expression levels of endothelin-1 and ET(A)R mRNA were noted at different time points of EGF intervention, up-regulated with the increase of treatment time, and with significant difference (P < 0.05). CONCLUSION: EGF can up-regulate the mRNA expressions of endothelin-1 and ET(A)R in PC-3 cell lines and play a great role in prostate cancer progression, which may offer a substructure of molecular biology for the treatment of HRPC.