Jiabin Jin

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6

Recent studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates breast cancer cell growth. However, the role of gas5 in pancreatic cancer progression remains largely unknown. In the current study, we assay the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. We verify that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. Overexpression of gas5 in pancreatic cancer cells inhibits cell proliferation, whereas gas5 inhibition induces a significant decrease in G0/G1 phase and an increase in S phase. We further demonstrate that gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA-induced cell proliferation. These data suggest an important role of gas5 in the molecular etiology of pancreatic cancer and implicate the potential application of gas5 in pancreatic cancer therapy.

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.

Pancreatic enucleation using the da Vinci robotic surgical system: a report of 26 cases

As a tissue‐sparing procedure, pancreatic enucleation has become an alternative for benign or borderline pancreatic tumours; it has been proved to be safe and feasible. To date, a large sample size of robotic pancreatic enucleation has not been reported. This study aimed to discuss the clinical evaluation and postoperative complications after robotic pancreatic enucleation and compare it with open surgery.

Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery

Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133+CXCR4+ cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects.

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

BackgroundEnucleation 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.MethodsFifty-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.ResultsThe 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).ConclusionRobotic 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.

Minimally invasive distal pancreatectomy for PNETs: laparoscopic or robotic approach?

Background The most effective and radical treatment for pancreatic neuroendocrine tumors (PNETs) is surgical resection. Minimally invasive surgery has been increasingly used in pancreatectomy. Initial results in robotic distal pancreatectomy (RDP) have been encouraging. Nonetheless, data comparing outcomes of RDP with those of laparoscopic distal pancreatectomy (LDP) in treating PNETs are rare. The aim of this study was to compare the safety and efficacy of RDP and LDP for PNETs. Methods From September 2010 to January 2017, operative parameters and perioperative outcomes in an initial experience with 43 consecutive patients undergoing RDP were collected and compared with those in 31 patients undergoing LDP. Results Patients undergoing RDP and LDP demonstrated equivalent age, sex, ASA score, tumor location and tumor size. Operating time, length of resected pancreas, postoperative length of hospital stay and rates of conversion to open, pancreatic fistula, transfusion and reoperation were not statistically different. Patients in the RDP group were associated with significantly higher overall (79.1 vs. 48.4 %, P = 0.006) and Kimura spleen preservation rates (72.1 vs. 16.1%, P < 0.001) and had reduced risk of excessive blood loss (50 vs. 200mL, P < 0.001). Oncological outcomes in this series were superior for the RDP group with more lymph node harvest for G2 and G3 PNETs (3.5 vs. 2, P = 0.034). Conclusions Both RDP and LDP are efficacious and safe methods in treating PNETs located in the body or tail of pancreas. Robotic approach offers advantages with less intraoperative blood loss, higher spleen preservation rate and more lymph node harvest. It may be sensible to choose RDP for patients who fit indications for scheduled spleen preservation.

Outcomes of robotic surgery for pancreatic ductal adenocarcinoma.

BACKGROUND To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC). METHODS The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. RESULTS Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. CONCLUSIONS Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.

Robot-Assisted Middle Pancreatectomy for Elderly Patients: Our Initial Experience

Background The aim of this study was to evaluate the indications, safety, feasibility, and short- and long-term outcomes for elderly patients who underwent robot-assisted middle pancreatectomies (MPs). Material/Methods Ten patients (≥60 years) underwent robot-assisted middle pancreatectomies from 2012 to 2015. The perioperative data, including tumor size, operating time, rate of postoperative pancreatic fistula (POPF), postoperative morbidity, and other parameters, were analyzed. We collected and analyzed the follow-up information. Results The mean age of patients was 64.30 years (range, 60–73 years). The average tumor size was 2.61 cm. The 10 cases were all benign or low-grade malignant lesions. The mean operating time was 175.00 min. The mean blood loss was 113.00 ml with no blood transfusion needed. Postoperative fistulas developed in 5 patients; there were 2 Grade A fistulas and 3 grade B fistulas. There were 3 patients who underwent postoperative complications, including 2 Grade 1 or 2 complications and 1 Grade 3 complication. No reoperation and postoperative mortality occurred. The mean hospital stay was 19.91 days. After a median follow-up of 23 months, new onset of diabetes mellitus developed in 1 patient and none suffered from deterioration of previously diagnosed diabetes or exocrine insufficiency, and no tumor recurrence happened. Conclusions Robot-assisted middle pancreatectomy was safe and feasible for elderly people. It had low risk of exocrine or endocrine dysfunction and benefited patients’ long-term outcomes. Incidence of POPF was relatively high but we could prevent it from resulting in bad outcomes by scientific perioperative care and systemic treatment.

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.