The inverted U-shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte.

BACKGROUND: The relationship between epinephrine and cancer can be dose-dependent in in vivo study. Whether it is the same in human body still needs verification. METHOD: We used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K-M method and Cox regression. Disturbance of blood cell count and C-reactive protein and identification of related potent intermediary factors were also analyzed. RESULTS: K-M plot and Cox regression all showed the inverted U-shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%. CONCLUSION: Epinephrine played an anti-tumor or pro-tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro-tumor effect of epinephrine to PDAC.

[The Efficacy of 17 Cases of Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction by Using Robotic Operation System (with Video)].

OBJECTIVE: To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. METHODS: The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. RESULTS: There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. CONCLUSION: It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.

Robotic pancreatectomy for solid pseudopapillary tumors in the pancreatic head: A propensity score-matched comparison and analysis from a single center.

BACKGROUND: Robotic surgery is the most advanced minimally invasive technique for the treatment of complicated solid pseudopapillary tumors (SPT). The aim of this study is to evaluate feasibility of robotic surgery for the treatment of SPTs in the pancreatic head. METHODS: A retrospective analysis of the clinical data of 83 SPTs in pancreatic head was conducted. Clinical characteristics were extracted and propensity score matching (PSM) was used to compare and evaluate mid-term outcomes of the two techniques. RESULTS: Pancreaticoduodenectomy (PD), duodenum-preserving partial pancreatic head resection (DPPHR-P) and tumor enucleation (En) were performed in 51, 24, and 8 patients, respectively. The robotic approach was associated with a significantly lower volume of blood loss, lower need for transfusion, and faster time to post-surgery recovery. Major complications and costs were comparable for both techniques. CONCLUSION: A robotic approach provides an alternative to open surgery for SPTs in the pancreatic head without increasing the incidence of clinically relevant pancreatic fistula (CRPF) or other major complications and with good patient outcomes.

Higher body mass index deteriorates postoperative outcomes of pancreaticoduodenectomy.

BACKGROUND: Previous studies presented controversies in impact of body mass index (BMI) on perioperative complications in pancreatectomy, and mainly focused on Western population. This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduodenectomy. METHODS: Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese (BMI ≥25 kg/m2), overweight (BMI ≥23 kg/m2 and <25 kg/m2), or normal weight (BMI ≥18.5 kg/m2 and <23 kg/m2). Associations of these BMI groups with perioperative outcomes were evaluated. RESULTS: The overweight and obese groups experienced higher risk of clinically related postoperative pancreatic fistula (CR-POPF) (7.6% vs. 9.9% vs. 17.6%, P = 0.002) and re-operation (1.1% vs. 2.5%  vs. 5.1%, P = 0.017), and longer systemic inflammation response syndrome (SIRS) duration [2 (1-9) d vs. 2 (1-7) d vs. 3 (1-10) d, P = 0.003] and postoperative hospital stay [19 (2-84) d vs. 19 (7-158) d vs. 23 (8-121) d, P = 0.023] than the normal weight group did. The multiple logistic regression models showed obese as an independent risk factor for CR-POPF (P = 0.013). The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay (P = 0.005). CONCLUSIONS: Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduodenectomy. Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients, with intensive perioperative management.

Robot-assisted duodenum-preserving pancreatic head resection with pancreaticogastrostomy for benign or premalignant pancreatic head lesions: a single-centre experience.

BACKGROUND: The purpose of this study was to compare short- and long-term outcomes of modified robot-assisted duodenum-preserving pancreatic head resection (RA-DPPHR) versus robot-assisted pancreaticoduodenectomy (RA-PD). METHODS: Matched for age, sex, ASA classification, tumour size, history of abdominal surgery and pathological type, 34 patients undergoing RA-DPPHR and 34 patients undergoing RA-PD between January 2010 and December 2016 were retrospectively analyzed. RESULTS: The RA-DPPHR group had shorter surgical time (188.2 vs. 386.3 min, p < 0.001) and less blood loss (168.2 vs. 386.3 ml, p = 0.026) but higher complication rate (47.1% vs. 32.4%, p = 0.105) and pancreatic fistula rate (32.4% vs. 17.6%, p = 0.161). Hospital mortality was 2.9%. Exocrine insufficiency was lower in the RA-DPPHR group (3.0% vs. 24.2%, p = 0.027). Endocrine insufficiency was observed in one RA-DPPHR patient and 5 RA-PD patients (p = 0.197). CONCLUSIONS: Modified RA-DPPHR benefits in terms of better conservation of exocrine and endocrine pancreatic functions at the expense of a significant morbidity and non-zero mortality.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

Robot-assisted laparoscopic versus open middle pancreatectomy: short-term results of a randomized controlled trial.

OBJECTIVE: This first prospective randomized controlled trial was performed to compare short-term outcomes of robot-assisted laparoscopic middle pancreatectomy (RA-MP) with open middle pancreatectomy (OMP). BACKGROUND: RA-MP is a novel minimally invasive surgical technique for benign or borderline tumors in the pancreatic neck or body. Its short-term effectiveness and safety remain unknown, compared to OMP. METHODS: Patients eligible for MP from August 2011 to November 2015 were randomized into the RA-MP or OMP group. The primary endpoint was length of hospital stay (LOS). Secondary endpoints were intraoperative parameters, and postoperative and recovery variables. RESULTS: A total of 100 patients were included into the study to analyze primary and secondary endpoints. Demographic characteristics and pathological parameters were similar in both groups. Furthermore, LOS was significantly shorter (15.6 vs. 21.7 days, P = 0.002), median operative time was reduced (160 vs. 193 min, P = 0.002), median blood loss was lower (50 vs. 200 mL, P < 0.001), rate of clinical postoperative pancreatic fistula (POPF) was lower (18 vs. 36.0 %, P = 0.043), nutritional status recovery was better, off-bed return to activity was expedited (3.1 vs. 4.6 days, P < 0.001), and resumption of bowel movement was faster (3.5 vs. 5.0 days, P < 0.001) in the RA-MP group, compared to the OMP group. CONCLUSION: RA-MP was associated with significantly shorter LOS, reduced operative time, blood loss and clinical POPF rate, and expedited postoperative recovery, compared to OMP.

Prognostic Value of the Combination of Preoperative Hemoglobin, Lymphocyte, Albumin, and Neutrophil in Patients with Locally Advanced Colorectal Cancer.

BACKGROUND Systemic inflammatory response and nutritional status are important to the prognosis of patients with colorectal cancer (CRC). This study aimed to investigate the prognostic value of the combination of preoperative hemoglobin, lymphocyte, albumin, and neutrophil (HLAN) in patients with locally advanced CRC (LACRC). MATERIAL AND METHODS We performed a retrospective analysis in 536 LACRC patients undergoing radical surgery. The value of HLAN was defined as follow: HLAN=Hemoglobin (g/L)×Lymphocyte (/L)×Albumin (g/L)/Neutrophil (/L)/100. The X-tile program was used to determine the optimal cut-point of HLAN, and the prognostic value of HLAN for overall survival (OS) was evaluated with the Cox proportional hazard model. RESULTS The cut-point of HLAN was set at 19.5. Compared with the high-HLAN group, the low-HLAN group had a 1.50-fold (95% confidence interval 1.09-2.05) increased risk of death and a significantly lower OS rate (P<0.001). Furthermore, the risk stratification model based on HLAN (AUC=0.72) displayed better accuracy in OS prediction than the TNM system (AUC=0.61). CONCLUSIONS HLAN is a valuable prognostic marker for patients with LACRC.

Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A Retrospective Analysis and Comparison from a High-Volume Centre in Asia.

BACKGROUND: Enucleation is increasingly performed for benign or borderline tumours of the pancreas because it is a parenchyma-sparing and less invasive procedure compared to conventional pancreatectomy, which reduces the risk of exocrine and endocrine insufficiency. This study retrospectively evaluated and compared the pre-, intra-, and post-operative clinical characteristics after open and robotic approaches for pancreatic enucleation. METHODS: Fifty-six cases of enucleation for benign or borderline tumours of the pancreas treated from March 2010 to July 2015 were identified by a retrospective search. These included 25 patients who underwent an open approach and 31 patients who underwent a robotic approach. The clinical characteristics were extracted and compared. RESULTS: The two groups had a similar location and pathology of the tumour. The robotic group had a significantly shorter operation time and significantly less blood loss than the open group. The rates of clinical pancreatic fistula (PF) formation and major complications were similar. The robotic approach could be applied for a tumour on the right side of the pancreas without increasing the incidence of clinical PF or other major complications. The patients with clinical PF had a significantly shorter distance between the lesion and the main pancreatic duct (MPD). CONCLUSION: Robotic enucleation appears to be a feasible and safe approach for benign or borderline tumours of the pancreas and was associated with similarly favourable surgical outcomes as the open approach. Identifying and avoiding the MPD is an important step during enucleation.

TMEM45B promotes proliferation, invasion and migration and inhibits apoptosis in pancreatic cancer cells.

In the present study, we focused on the expression and biological functions of TMEM45B in pancreatic cancer tissues and cell lines. Real-time PCR and Western blotting were used to examine the expression levels of TMEM45B in pancreatic cancer tissues and cell lines. The functions of TMEM45B were evaluated using CCK-8, flow cytometry and transwell analysis. Our results showed that TMEM45B exhibited high expression in pancreatic cancer tissues and cell lines compared with the normal pancreatic tissues and cells. Using gene set enrichment analysis (GSEA), we found that TMEM45B may regulate multiple genes involved in the cell cycle and metastasis pathways. Downregulation of TMEM45B by RNA interference significantly reduced proliferation, invasion and migration of SW1990 and PANC-1 cells, accompanied by the induction of cell cycle arrest and apoptosis, whereas overexpression of TMEM45B promoted proliferation, invasion and migration of CFPAC-1 cells as well as apoptosis inhibition. Taken together, our study provides evidence that TMEM45B is an oncogene involved in the tumorigenesis of pancreatic cancer and may represent a new molecular target for pancreatic cancer treatment.

Impact and Clinical Predictors of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors.

BACKGROUND: The optimal surgical management of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is still controversial. Here, we evaluated the impact of lymph node status on postoperative recurrence in patients with NF-PNET and the potential of preoperative variables for predicting lymph node metastasis (LNM). METHODS: In this mono-institutional retrospective cohort study conducted in 100 consecutive patients who underwent NF-PNET resection between January 2004 and December 2014, we evaluated risk factors for survival using the Kaplan-Meier method and the Cox regression model. Predictors of LNM were evaluated using the logistic regression model, and the power of predictive models was evaluated using receiver operating characteristic curve analysis. RESULTS: Five-year disease-free survival of resected NF-PNET was 64.1%. LNM was independently associated with postoperative recurrence (hazard ratio = 3.995, P = 0.003). Multivariate analysis revealed tumor grade as an independent factor associated with LNM (G2 vs. G1: odds ratio [OR] =6.287, P = 0.008; G3 vs. G1: OR = 12.407, P = 0.001). When tumor grade was excluded, radiological tumor diameter >2.5 cm (OR = 5.430, P = 0.013) and presence of symptoms (OR = 3.366, P = 0.039) were significantly associated with LNM. Compared to neoplasms with radiological diameter >2.5 cm (32.1%), tumors ≤2.5 cm had an obviously lower risk of LNM (7.7%), indicating the reliability of this parameter in predicting LNM (area under the curve, 0.693). Incidentally discovered NF-PNETs ≤2.5 cm were associated with a low-risk of LNM and excellent survival. CONCLUSIONS: LNM is significantly associated with postoperative recurrence. Radiological tumor diameter is a reliable predictor of LNM in NF-PNETs. Our results indicate that lymphadenectomy in small (≤2.5 cm) NF-PNETs is not routinely necessary.

Robotic approach improves spleen-preserving rate and shortens postoperative hospital stay of laparoscopic distal pancreatectomy: a matched cohort study.

BACKGROUND: Spleen preservation (SP) is beneficial for patients undergoing distal pancreatectomy of benign and borderline tumors; however, the conventional laparoscopy approach (C-LDP) is less effective in controlling splenic vessel bleeding. The benefits of the robotic-assisted approach (RA-LDP) in SP have not been clearly described. This study aimed to evaluate whether a robotic approach could improve SP rate and effectiveness/safety profile of laparoscopic distal pancreatectomy (LDP). METHODS: Matched for scheduled SP, age, sex, ASA classification, tumor size, tumor location, and pathological type, 69 patients undergoing RA-LDP and 50 undergoing C-LDP between January 2005 and May 2014 were included. Main outcome measures included SP rate, operative time (OT), blood loss, transfusion frequency, morbidity, postoperative hospital stay (PHS), and oncologic safety. RESULTS: Among matched patients scheduled for SP, RA-LDP was associated with significantly higher overall (95.7 vs. 39.4%) and Kimura SP rates (72.3 vs. 21.2%), shorter OT (median 120 vs. 200 min), less blood loss (median 100 vs. 300 mL), lower transfusion frequency (2.1 vs. 18.2%), and shorter mean PHS (10.2 vs. 14.5 days). Among matched patients scheduled for splenectomy, RA-LDP was associated with similar OT, blood loss, transfusion frequency, and PHS. The two approaches were similar in overall morbidity, frequency of pancreatic fistula, and oncologic outcome among patients undergoing splenectomy for malignant tumors. CONCLUSIONS: RA-LDP was associated with a significantly better SP rate and reduced OT, blood loss, transfusion requirement, and PHS for patients undergoing SP compared to C-LDP, but offered less benefits for patients undergoing splenectomy.

Robot-assisted laparoscopic versus open pancreaticoduodenectomy: a prospective, matched, mid-term follow-up study.

BACKGROUND: Robot-assisted laparoscopic pancreaticoduodenectomy is a novel minimally invasive surgery technique, and its effectiveness and safety remain unknown in patients with borderline malignant or malignant diseases. This study aimed to prospectively evaluate the effectiveness and safety of RLPD versus open PD (OPD). METHODS: Between January 2010 and December 2013, 180 eligible patients were prospectively hospitalized for elective RLPD (n = 60) or OPD (n = 120). They were matched for tumor location, tumor type, tumor size, ASA classification, age, and sex. The main outcome measures included demographics, intraoperative variables, morbidity, postoperative recovery, and mid-term evaluation. RESULTS: Over the study period, the RLPD group had a significantly longer but decreasing operative time (median 410 vs. 323 min; P < 0.001), less blood loss (median 400 vs. 500 mL; P = 0.005), better nutritional status recovery, expedited off-bed return to activity (3.2 vs. 4.8 d; P < 0.001), faster resumption of bowel movement (3.6 vs. 5.2 d; P < 0.001), and shorter hospital stay (20 vs. 25 d; P = 0.002) compared to the OPD group. The two groups had similar surgical morbidities and mortality as well as R0 resection rate and number of lymph nodes resected. Among patients with pancreatic adenocarcinoma, the two groups had similar overall and disease-free survival (ACTRN12614000299606). CONCLUSIONS: This first largest, prospective matched study demonstrated that for treating selected borderline and malignant pathologies, RLPD was associated with a significant learning curve effect and expedited postoperative recovery, but had a surgical and oncological safety profile similar to OPD.

Clinical significance of RECK promoter methylation in pancreatic ductal adenocarcinoma.

The aim of this study was to analyze the clinical significance of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) promoter methylation in pancreatic ductal adenocarcinoma (PDA). Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of RECK in 60 pairs of PDA tissue samples and adjacent non-cancerous tissue samples. Statistical analyses were applied to test the associations between RECK promoter methylation status, clinicopathologic factors, and prognosis. The rate of RECK promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (P < 0.001). RECK methylation status was significantly associated with clinical stage (P = 0.017), histological differentiation (P = 0.046), and lymph node metastasis (P = 0.003), but was not associated with gender, age, and tumor location (all P > 0.05). Additionally, RECK promoter methylation is associated with malignant behavior and poor prognosis. In conclusion, determination of RECK promoter methylation status in tumor tissues may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.

Robotic-assisted pancreatic resection: a report of 47 cases.

BACKGROUND: There are few reports of robot-assisted pancreatic surgery. Our purpose was to report our surgical and clinical experiences and outcomes of 47 cases of robot-assisted pancreatic resection to show that minimally invasive pancreatic surgery is both feasible and effective. METHODS: The medical records of 47 patients who underwent robot-assisted pancreatic resections for adenocarcinoma, cystic tumours or other pancreatic diseases at our institution by a single surgical team from March 2010 to December 2011 were retrospectively analysed. RESULTS: There were 32 females and 15 males with a mean age of 48.7 ± 15.4 years, of whom 13 patients had pathologically diagnosed malignancies, 25 had cystic tumours or chronic pancreatitis, three had solid pseudopapillary tumours of pancreas, and six had other lesions. Sixteen patients underwent pancreatoduodenectomy, 16 distal pancreatectomies (nine of which had spleen resections), 10 middle pancreatectomies, four Beger's procedure, and one had enucleation of a pancreatic lesion. The mean surgical time was 299.2 ± 133.5 (range 70-540) min and mean blood loss was 431.8 ± 309.0 (range 50-1100) ml. Nine patients required a blood transfusion (mean transfusion volume 597.2 ± 543.3 ml). There were no conversions to laparotomy. The mean hospital stay was 29.4 ± 9.1 (range 8-41) days. Pancreatic fistula occurred in 20 cases, anastomotic bleeding in three patients and anastomotic leakage in one patient. Two patients, one who received a PD and one who received a distal pancreatectomy, required a second surgery. All other complications were resolved with conservative management. Surgical margins were negative in all cases, with a postoperative histopathological diagnosis of malignancy. Eleven of the 13 patients with malignancies were alive and well without recurrence at the time of publication, while two patients died. CONCLUSIONS: Our series of 47 robot-assisted pancreatic resections adds further evidence that this technique is feasible and effective.

Radical resection of gallbladder cancer: could it be robotic?

BACKGROUND: The only potentially curative option for patients with gallbladder cancer is radical resection. This is the first report that describes the successful application of a minimally invasive, robot-assisted radical resection, including lymphadenectomy, in five gallbladder cancer patients. METHODS: Medical records of patients who underwent radical resection of gallbladder cancer via the da Vinci robotic surgical system in the Hepato-Bilio-Pancreatic Surgical Department of the Shanghai Ruijin Hospital, China, between March 2010 and July 2011 were reviewed and analyzed. RESULTS: Robot-assisted radical resection was successful in all five patients. The mean number of excised lymph nodes was 9 (range = 3-11), mean operative time was 200 min (range = 120-300 min), mean intraoperative blood loss was 210 ml (range = 50-400 ml), and mean length of hospital stay was 7.4 days (range = 7-8 days). All patients were discharged with no reported complications. Mean postoperative follow-up was 11 months (range = 1-17 months). One patient died due to tumor recurrence 10 months postsurgically, but there was no recurrence in the remaining four patients during the follow-up period. CONCLUSIONS: Robot-assisted radical resection for gallbladder cancer is both feasible and safe. Compared to laparoscopic surgery, the robotic surgery system is better suited for subtle dissection in a narrow, deep space. This is advantageous for both the removal of lymph nodes near the pancreas and hepatoduodenal ligament and the skeletonization of the hepatoduodenal ligament, the hepatic artery, and the celiac axis. The long-term outcome and direct comparisons to laparotomy in a larger patient cohort are needed to provide more clinical data supporting the superiority of this approach.

SKP1-CULLIN1-F-box (SCF)-mediated DRG2 degradation facilitated chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells.

Developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved member of the DRG subfamily in the GTP-binding protein, is thought to play an essential role in the control of cell growth and differentiation. However, the role of DRG2 in hepatocellular carcinoma cells is largely unknown. Here, we show that DRG2 is down-regulated during chemotherapeutic drug induced apoptosis in four hepatocellular carcinoma cell lines. We further provided evidence that DRG2 was a substrate of a SKP1-CULLIN1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis. Moreover, over-expression of DRG2 inhibited doxorubicin induced apoptosis in hepatocellular carcinoma cells. Taken together, these results demonstrate that regulated degradation of DRG2 has a role in chemotherapeutic drug induced hepatocellular carcinoma cells apoptosis.

Early experience for the robotic duodenum-preserving pancreatic head resection.

BACKGROUND: The duodenum-preserving pancreatic head resection (DPPHR) has been accepted as a valid surgical alternative to more extensive standard resections for the treatment of benign and low malignant tumors at the head of the pancreas. In this article, a new minimally invasive operation, the robot-assisted laparoscopic technique, is introduced for this procedure. METHODS: From March 2010 to Dec 2010, four patients (three women and one man), with a mean age of 42.3 years (range: 21-62 years), underwent robot-assisted laparoscopic DPPHR at the Hepato-Bilio-Pancreatic Surgical Department of Rui Jin Hospital in Shanghai, China. The preoperative symptoms include two cases of repeated upper abdominal pain, one case with no obvious preoperative symptoms, and one case of repeated hypoglycemia. The da Vinci Surgical System was used to perform the main steps of the operation. All patients underwent a pancreaticogastrostomy for pancreaticoenteric reconstruction to the distal stump. RESULTS: All four surgeries were successfully performed. There were no deaths. The mean operative time was 298.8 (270-335) min, average blood loss was 425 ml (range: 100-600 ml). The mean postoperative hospital stay was 26.8 days (range: 20-30 days). The one patient with an islet cell tumor has had normal blood glucose levels since the operation, and the other three patients have had no hyperglycemia. Three of the patients developed a pancreatic fistula that was cured by conservative treatment. CONCLUSIONS: The robotic surgical system is technically fully capable of performing the complex DPPHR procedure with an acceptable range of surgical complications. It breaks through the bottleneck of the traditional laparoscopic technology and expands the range of its applications. However, this new technology is still at an exploratory stage, and the long-term effect remains to be validated by additional clinical data.

Clinical and pathological analysis of 27 patients with combined hepatocellular-cholangiocarcinoma in an Asian center.

BACKGROUND: Our purpose was to assess the clinicopathological features and surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an Asian center. METHODS: Between 1998 and 2009, 27 patients were diagnosed with combined HCC-CC at our hospital. Their medical records were reviewed and clinicopathological data retrospectively analyzed. RESULTS: The 27 patients included 24 (88.9%) males and 3 (11.1%) females with a mean age of 58.26 ± 11.18 years. Cirrhosis was present in 10 patients (37.0%), and 12 patients had hepatitis C or hepatitis B virus infection. Serum alpha fetoprotein was >20 ng/ml in 7 of the 19 patients in whom it was measured (36.8%). Twenty-five patients underwent hepatic resections and 2 received liver transplantations. Five (18.5%) patients had separate HCC and CC within the same liver (type I), 21 (77.8%) had tumors with mixed components (type II), and 1 patient had a type III tumor (3.7%). Of 22 patients with immunohistochemical data, 19 (86.4%) were cytokeratin (CK) 7-positive, 20 (90.9%) were CK19-positive, and 4 (18.2%) were CK20-positive. Mean follow-up was 25.8 months. The 1- and 2-year survival rates were 72.5 and 49.4%, respectively. The 1- and 2-year disease-free survival rates were 54.2 and 41.3%, respectively. Symptoms at the time of diagnosis, and regional lymph node metastases, were associated with higher mortality and recurrence. CONCLUSIONS: Lymph node metastasis and positive resection margins are important factors affecting HCC-CC surgical outcomes.

[The analysis of pancreatic fistula in middle segmental pancreatic resection].

OBJECTIVE: To analyze the influence of pancreatic fistula in middle segmental pancreatic resection and summarize the experience in dealing with the stump. METHODS: The data of 40 cases undergoing middle pancreatectomy were reviewed retrospectively to analyze the curative effect and pancreatic fistula between April 2003 and December 2009. Of these, 36 patients with benign cases outcomes were compared with 2 separate control groups, 44 pancreaticoduodenectomy (PD) and 26 extended distal pancreatectomy (EDP). RESULTS: The mean operating time of group MSP was 222 min, which was significantly shorter than that of group PD. The mean blood loss of group MSP was 316 ml, which was less than that of others. Otherwise, the postoperative nutritional status and blood sugar control in group MSP was superior to the other 2 groups. Through long-term follow-up, the patients in group MSP retained endocrine and exocrine function better. Only 1 patient developed new-onset diabetes mellitus after operation, and no patient required enzyme substitution. No lesion recurred. The rate of pancreatic fistula was highest (42%), but didn't result in the significant deference of overall discharge time with group PD and EDP. The pancreatic fistula level and the mean postoperative time in hospital didn't differ significantly from the other 2 groups. CONCLUSIONS: Middle segmental pancreatectomy is a safe and feasible technique that is indicated for selected patients with benign or low malignant lesion in the neck and body of the pancreas. Though the rate of pancreatic fistula is higher, the risk of which is reduced by the marked curative effect. It is very important to deal with the stump reasonably.