Obesity and pancreatic cancer: An update of epidemiological evidence and molecular mechanisms.

Despite advances in therapy and achievements in translational research, pancreatic cancer (PC) remains an invariably fatal malignancy. Risk factors that affect the incidence of PC include diabetes, smoking, obesity, chronic pancreatitis, and diet. The growing worldwide obesity epidemic is associated with an increased risk of the most common cancers, including PC. Chronic inflammation, hormonal effects, circulating adipokines, and adipocyte-mediated inflammatory and immunosuppressive microenvironment are involved in the association of obesity with PC. Herein, we systematically review the epidemiology of PC and the biological mechanisms that may account for this association. Included in this review is a discussion of adipokine-mediated inflammation, lipid metabolism, and the interactions of adipocytes with cancer cells. We consider the influence of bariatric surgery on the risk of PC risk as well as potential molecular targets of therapy. Our review leads us to conclude that targeting adipose tissue to achieve weight loss may represent a new therapeutic strategy for preventing and treating PC.

Cystic pancreatic neuroendocrine tumors: A distinctive subgroup with indolent biological behavior? A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity. METHODS: We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed. RESULT: The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively). CONCLUSIONS: Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.

Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries.

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

Early detection of pancreatic cancer: Where are we now and where are we going?

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.

A propensity score-matched case-control comparative study of laparoscopic and open gastrectomy for locally advanced gastric carcinoma.

PURPOSE: The aim of this study was to compare the surgical and long-term outcomes of laparoscopic and open gastrectomy with radical intent for locally advanced gastric carcinoma in case-controlled patient groups using the propensity score. METHODS: Between January 2009 and December 2014, 389 patients who underwent gastrectomy with radical intent for locally advanced gastric carcinoma were enrolled. These patients were divided into two groups according to the method of operation: the laparoscopy group (patients who underwent laparoscopic gastrectomy) and the open group (patients who underwent open gastrectomy). To correct different demographic and clinical factors in the two groups, a propensity score matching was used at a 1:1 ratio, and, finally, 184 patients were enrolled in this study, 92 patients in each group. Preoperative characteristics, surgical results, and long-term results were analyzed. RESULTS: Preoperative baseline variables were well balanced in both groups. There were no differences of the extent of surgery between the two groups. With the exception of shorter postoperative hospital stay and less blood loss in the laparoscopy group as compared with the open group, there were no significant differences in surgical, pathological, and long-term outcomes. The 5-year overall survival rates were 57% in the laparoscopy group and 50% in the open group (p=0.606). The 5-year disease-free survival rates were 48% in the laparoscopy group and 42% in the open group (p=0.515). CONCLUSION: Laparoscopic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes were comparable to those who underwent open resection.

Mannose-mediated inhibitory effects of PA-MSHA on invasion and metastasis of hepatocellular carcinoma via EGFR/Akt/IκBß/NF-κB pathway.

BACKGROUND & AIMS: Elevation of high-mannose glycans is a common feature of malignant cells and has been suggested to be the basis for alternative cancer therapy for several years. Here we want to investigate the antitumour effect of pseudomonas aeruginosa-mannosesensitive haemagglutinin (PA-MSHA), a genetically engineered heat-inactivated PA strain with mannose-sensitive binding activity, on hepatocellular carcinoma (HCC). METHODS: Tumourigenicity and metastatic potentials of HCC were studied after PA-MSHA treatment by utilizing the in vitro/in vivo model of HCC. Expression of apoptosis-associated proteins and epithelial-mesenchymal transition (EMT) related genes were evaluated, and possible signalling pathways involved were investigated. RESULTS: PA-MSHA induced significant cell proliferation inhibition and cell cycle arrest of HCC through decreasing the levels of cyclins D1, cyclins E, CDK2, CDK4, proliferating cell nuclear antigen (PCNA), and increasing the level of p21 and p27. Moreover, PA-MSHA suppressed the invasion, migration and adhesion of HCC through inhibiting epithelial-mesenchymal transition (EMT). PA-MSHA also inhibited EGFR/Akt/IκBß/NF-κB pathway and overexpression of NF-κB significantly abrogated PA-MSHA induced EMT inhibition. In addition, competitive inhibition of the mannose binding activity of PA-MSHA by D-mannose significantly blocked its effect on cell cycle arrest and EMT. PA-MSHA also abrogated lung metastasis of HCC and significantly inhibited tumour growth in the in vivo study. CONCLUSIONS: Our study demonstrated the essential role of EGFR/Akt/IκBß/NF-κB pathway in the inhibitory effect of PA-MSHA on invasion and metastasis of HCC through suppressing EMT, and revealed an attractive prospect of PA-MSHA as a novel candidate agent in the treatment of HCC.

Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer.

BACKGROUND: The prognostic value of lymph node ratio (LNR) in pancreatic cancer remains controversial. In the current retrospective study, we assessed the value of LNR on predicting the survival of postoperative patients with pancreatic cancer. METHODS: Medical records of patients who underwent pancreatic resection for pancreatic cancer in the department of general surgery, Qilu Hospital, Shandong University were reviewed retrospectively. Demographic, clinicopathological, tumor-specific data, and histopathological reports were collected. Univariate and multivariate survival analyses were performed. RESULTS: A total of 83 patients with pancreatic cancer were collected. The mean number of examined LN was 8.2 ± 6.1 (0 to 26). Differential degree (low) (P = 0.019, hazard ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to 4.424) and LNR >0.2 (P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756) were independent adverse prognostic factors according to the multivariate survival analysis. CONCLUSIONS: Our study indicated that LNR >0.2 was an independent adverse prognostic factor for pancreatic cancer, which may provide important information for prognostic assessment.

Antiapoptotic gene BAG-1 vector structure of RNA interference and endogenous targeted screening in colon cancer cell lines.

The purposes of the present work were to construct the shRNA plasmids for BAG-1 gene of human and test the expression of mRNA and protein of BAG-1. Recombinant plasmids containing green fluorescent protein reporter genes are constructed using gene cloning methods. The shRNA plasmids for the BAG-1 gene are constructed by RNA interference technology. We applied fluorescent plasmid-transfected target cells in the cell transfection experiments and monitored the transfection rate of plasmids by observing the fluorescence amount. We transfected three synthesized shRNA in target screening cell and adopted RT-PCR and Western test to identify the difference of target gene transfection and translation level in cells. The specific shRNA plasmid for the BAG-1 gene was successfully recombined, and stably transfected colon cancer Lo Vo cell lines were obtained. The results present that the constructed shRNA plasmids significantly inhibited the expression of mRNA and protein of Lo Vo cell BAG-1, and can maintain the effect for a long term. pGPH1/GFP/Neo-BAG-1-homo-825 was screened as the optimum sequence of interference so as to lay a solid foundation to explore into the research on the BAG-1 gene and the biological behavior of colon cancer cells. It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Coexpression of recombinant adenovirus carrying GDNF and EDNRB genes in neural stem cells in vitro.

Gene therapy and nerve stem cells isolated from the developing human enteric nervous system (ENS) are significant. They may open the route for the cell therapy of Hirschsprung's disease (HD). We have constructed the recombinant adenovirus-carrying glial cell line-derived neurotrophic factor (GDNF) and endothelin receptor B (EDNRB) gene, and investigated the exosomatic coexpression in neural stem cells. The recombinant adenovirus Ad-GE coexpressing GDNF and EDNRB gene was constructed by the AdEasy system and confirmed by the reverse transcription polymerase chain reaction (RT-PCR) method. Expression of exogenous genes in neural stem cells after transfection was confirmed by the flow cytometry and real-time fluorescence quantitative PCR. Fragments of pAd Track-CMV-GE were consistent with GDNF and EDNRB. The green fluorescence of the positive cells was followed by fluorescence microscopy at 24 h after NSCs had been transfected, reaching a peak at 72 h after transfection. Flow cytometry showed that the efficiency of transfection was 15.0, 23.6, and 25.4% at 24, 48 and 72 h respectively. Real-time fluorescence quantitative PCR showed the expression levels of mRNA of GDNF and EDNRB in 48 and 72 h groups were obviously higher than that in 24 and 96 h groups. Recombinant adenovirus carrying GDNF and EDNRB genes are coexpressed in neural stem cells, which may offer the possibility of a novel approach to local combination gene therapy for Hirschsprung's disease.

Gamma-aminobutyric acid binds to GABAb receptor to inhibit cholangiocarcinoma cells growth via the JAK/STAT3 pathway.

BACKGROUND: Gamma-aminobutyric acid (GABA) has been reported to inhibit the growth of cholangiocarcinoma QBC939 cells, but the mechanisms are still not fully understood. AIMS: To explore the mechanisms of the anti-cancer effect of GABA on QBC939 cells. METHODS: An initial immunohistochemistry study of the expressions of GABA receptors in cholangiocarcinoma tissues was followed by the culture and treatment of QBC939 cells for 48 h with GABA, GABA + bicuculine (GABAA receptor antagonist), GABA + phaclofen (GABAB receptor antagonist), and GABA + AG490 (Janus Kinase inhibitor). MTT and Annexin V-FITC/PI binding assays were used to determine the proliferation and apoptosis of the QBC939 cells. The expression of the signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (Tyr705) [p-STAT3 (Tyr705)] was evaluated by the western blot assay. The effect of GABA on the growth of QBC939 xenograft tumors in athymic nu/nu mice was examined, and p-STAT3 (Tyr705) expression in xenograft tumors was detected by immunohistochemistry. RESULTS: A significant difference was only observed in GABAB receptor expression between cholangiocarcinoma and normal bile tissues. The MTT and Annexin V-FITC/PI assays showed that the antiproliferative and proapoptotic effects of GABA on QBC939 cells could be antagonized by phaclofen and AG490, but not bicuculine. GABA significantly down-regulated p-STAT3 (Tyr705) expression; this action was also antagonized by phaclofen and AG490. GABA also effectively inhibited xenograft tumor growth, and p-STAT3 (Tyr705) expression was significantly decreased in GABA-treated xenograft tumors. CONCLUSIONS: GABA may inhibit the growth of cholangiocarcinoma QBC939 cells through the GABAB receptor, and the anti-cancer effects may be partly mediated via the JAK/STAT3 pathway.

The choice of surgical timing for biliary duct reconstruction after obstructive bile duct injury: an experimental study.

BACKGROUND/AIMS: The surgical time of obstructive bile duct injury when biliary-enteric reconstruction is needed remains controversial till now. METHODOLOGY: Sixty dogs models of bile duct injury were established and divided into six groups according to the days (0, 5, 10, 15, 20, 30 days) of injury. At the time of surgery, biopsy was taken and Roux-en-Y hepaticojejunostomy was performed. The morphology and local histopathology of bile duct, the liver function in different periods were observed. Surgical complications and survival were also evaluated. RESULTS: In the early time (5-10 days), the proximal bile ducts dilated continuously and showed acute inflammation change, but slow in the later period (10-30 days). Moreover, the bile duct wall gradually transformed into fibroplasias from the inflammatory edema after 10 days. During the development of jaundice, the liver function was damaged, especially after 20 days. After reconstructing, the bile leakages in the groups that repaired within 10 days were more than the ones in other groups (7 vs. 3, p < 0.05), and the malnutrition or organ failure occurring in 3 months was most at the 30-day group (n = 7, p < 0.05). CONCLUSIONS: The period between 10 and 20 days after bile duct obstruction may be optimal for surgical repair.

The interventional therapy for diabetic peripheral artery disease.

BACKGROUND: Diabetic peripheral arterial disease is the main cause of lower limb amputation in patients with diabetes. To summarize the technique and experiences and evaluate the clinical effects of blood vessel intervention operation on diabetic peripheral artery disease. METHODS: 81 patients with diabetic peripheral artery disease from October 2007 to September 2011, 81 cases of the observation group were treated by balloon PTA. By adopting the Seldinger puncture technology, intubation was placed into a cobra catheter or a pig tail artery catheter and directed to the ipsilateral lower extremity artery. A guidewire was used to reach the lesion part of patients and a long balloon with a diameter of 4-6 mm was used to expand the artery with a pressure of 6-10 atm. RESULTS: 81 patients in the observation group received the PTA surgery. The technical succesful rate was 100%, no complication happened. The skin temperature increased after treatment. The blood supply improved significantly. The pulsation of the foot dorsal artery was strengthened. The numbness and pain symptoms were moderated significantly. We observed better results in the observation group in lower limb vessel diameter and foot ulceration healing. None of the patients received amputation surgery. Its short-term effects were satisfactory. CONCLUSION: PTA is a feasible technique for diabetic peripheral artery disease. It has great clinical significance in treating diabetic peripheral arterial disease. Although its short-term effects is satisfactory, the long-term effects is necessary for follow up.

F-box only protein 2 exacerbates non-alcoholic fatty liver disease by targeting the hydroxyl CoA dehydrogenase alpha subunit.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major health burden with an increasing global incidence. Unfortunately, the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures. AIM: To explore the molecular mechanism of NAFLD. METHODS: Whole genome sequencing (WGS) analysis was performed on liver tissues from patients with NAFLD (n = 6) and patients with normal metabolic conditions (n = 6) to identify the target genes. A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2 (FBXO2) overexpression mouse model were used for in vivo studies. Plasmid transfection, co-immunoprecipitation-based mass spectrometry assays, and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies. RESULTS: A total of 30982 genes were detected in WGS analysis, with 649 up-regulated and 178 down-regulated. Expression of FBXO2, an E3 ligase, was upregulated in the liver tissues of patients with NAFLD. Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice. Overexpression of FBXO2 aggravated odium oleate (OA)-induced lipid accumulation in HepG2 cells, resulting in an abnormal expression of genes related to lipid metabolism, such as fatty acid synthase, peroxisome proliferator-activated receptor alpha, and so on. In contrast, knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes. The hydroxyl CoA dehydrogenase alpha subunit (HADHA), a protein involved in oxidative stress, was a target of FBXO2-mediated ubiquitination. FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells. Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells. CONCLUSION: FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD.

Effect of oligofructose on resistance to postoperative high-fat diet-induced damage of metabolism in diabetic rats after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) can induce prominent remission of type 2 diabetes mellitus. However, the long-term remission rate of diabetes usually decreases over time. Oligofructose has been verified to modulate host metabolism. The aim of this study was to explore the protective effect of oligofructose on high-fat diet (HFD)-induced metabolic dysfunction after SG. AIM: To study the effect and mechanism of oligofructose on diabetic remission in diabetic rats after SG. METHODS: SG and SHAM operation were performed on diabetes rats induced with an HFD, nicotinamide, and low-dose streptozotocin. Then the rats in the SHAM and SG groups were continuously provided with the HFD, and the rats in sleeve gastrectomy-oligofructose group were provided with a specific HFD containing 10% oligofructose. Body weight, calorie intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance, lipid profile, serum insulin, glucagon-like peptide 1 (GLP-1), total bile acids, lipopolysaccharide (LPS), and colonic microbiota levels were determined and compared at the designated time points. All statistical analyses were performed using Statistic Package for Social Science version 19.0 (IBM, United States), and the statistically significant difference was considered at P < 0.05. RESULTS: At 2 wk after surgery, rats that underwent SG exhibited improved indexes of glucose and lipid metabolism. Compared with the SG group, the rats from SG-oligofructose group exhibited better parameters of glucose and lipid metabolism, lower body weight (526.86 ± 21.51 vs 469.25 ± 21.84, P < 0.001), calorie intake (152.14 ± 9.48 vs 129.63 ± 8.99, P < 0.001), homeostasis model assessment of insulin resistance (4.32 ± 0.57 vs 3.46 ± 0.52, P < 0.05), and LPS levels (0.19 ± 0.01 vs 0.16 ± 0.01, P < 0.05), and higher levels of insulin (1.17 ± 0.17 vs 1.58 ± 0.16, P < 0.001) and GLP-1 (12.39 ± 1.67 vs 14.94 ± 1.86, P < 0.001), and relative abundances of Bifidobacterium (0.0034 ± 0.0014 vs 0.0343 ± 0.0064, P < 0.001), Lactobacillus (0.0161 ± 0.0037 vs 0.0357 ± 0.0047, P < 0.001), and Akkermansia muciniphila (0.0050 ± 0.0024 vs 0.0507 ± 0.0100, P < 0.001) at the end of the study. However, no difference in total bile acids levels was observed between the two groups. CONCLUSION: Oligofructose partially prevents HFD-induced glucose and lipid metabolism damage after SG, which may be due to the changes of calorie intake, insulin, GLP-1, LPS, and the gut microbiota in rats.

Hepatocyte infusions improve the results of liver transplantation in rats.

BACKGROUND/AIMS: The results of liver transplantation were influenced by miscellaneous factors. The aim was the notion that hepatocyte infusions might improve results of liver transplantation in rats. METHODOLOGY: Survival, serum analytes, FasL production, and histologic degree of rejection of transplanted rats pretreated with hepatocyte infusions (Hepatocyte) was compared to that of rats pretreated with either bone marrow cell infusions (Marrow) or saline infusions (Control). RESULTS: Hepatocyte rats had longer median survivals, less biochemical evidence of liver damage, more albumin production, a lower degree of histologic rejection, and increased FasL production than did either Marrow or Control rats (p < 0.05 for each analysis), which did not differ from one another (p > 0.05 for each analysis). CONCLUSIONS: Hepatocyte infusions improve the results of liver transplantation in rats.

Transumbilical single port laparoscopic cholecystectomy with a simple technique: initial experience of 33 cases.

Transumbilical single port laparoscopic cholecystectomy is a novel laparoscopic surgical technique for cholecystectomy utilizing only a transumbilical incision, which eliminates any visible abdominal scars and improves cosmesis. As the true single port laparoscopic technique, we presented an easy and feasible method for transumbilical laparoscopic cholecystectomy. A total of 33 patients were presented for transumbilical single port laparoscopic cholecystectomy. A 1.5 cm incision was made at the umbilicus. We used one sterile glove and designed a simple method for this procedure. All the operations were completed successfully. The operative time of the first case was 189 min, the average time of the following two cases was 90 min, and the mean of the latest ten cases was 50 min. Operative blood loss was <30 ml for all patients. No drainage tube was placed and no postoperative complications such as bleeding or biliary leakage occurred after three to six months of follow-up. All the patients were discharged 24h after the operation. There were no visible scars on the abdominal wall at the second weekend. Transumbilical single port laparoscopic cholecystectomy by our designed methods was technically simple, feasible and safe. Furthermore, development of newer instruments, accumulation of experience and enhancement of operative technique may facilitate this new operative approach.

[A clinicopathologic study of biliary intraductal papillary neoplasm].

OBJECTIVE: To investigate the clinicopathologic features, diagnosis and treatment of biliary intraductal papillary neoplasm (IPN-B). METHODS: The clinical, histopathological, treatment and prognosis data of 23 patients with IPN-B treated from January 1998 to December 2007 were retrospectively analyzed. RESULTS: There were 13 male and 10 female, aged from 30 to 80 years [mean age was (61 +/- 12) years]. The clinical manifestation included 10 cases with asymptomatic, 7 cases with abdominal pain, 4 cases with jaundice, 1 case with emaciation, and 1 case with acute cholangitis, respectively. Nine patients were also associated with hepatolithiasis. The average diameter of the tumors was (6 +/- 4) cm, 4 lesions were located in the right lobe, 15 in the left lobe, and 4 in the extrahepatic bile duct. Histopathologically, there were 4 adenomas, 1 borderline neoplasm, 6 carcinomas in situ, and 12 carcinomas. All patients received operation;the mean duration of follow-up was (33 +/- 28) months. Overall 3-year and 5-year survival rates of IPN-B were 85.3% and 68.2% respectively. CONCLUSIONS: IPN-B represents a distinct clinicopathologic entity. Favorable prognosis for IPN-B is offered by curative resection.

Sleeve gastrectomy ameliorates endothelial function and prevents lung cancer by normalizing endothelin-1 axis in obese and diabetic rats.

BACKGROUND: Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated. AIM: To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats. METHODS: SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4th, 8th, and 12th weeks. The risk was also evaluated using nuclear phosphorylation of H2A histone family member X as a marker of DNA damage (double-strand break). RESULTS: Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery. CONCLUSION: Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.

Endoscopic thyroidectomy by a modified anterior chest approach: a single institution's 5-year experience.

Endoscopic thyroidectomy embodies the features of both minimally invasive surgery and aesthetic surgery. However, none of the established approaches is minimally invasive and meanwhile maximally cosmetic. Here we applied a modified anterior chest approach to achieve excellent cosmesis with reduced physical invasion. Fifty-six patients with benign thyroid diseases accepted this procedure. A 10mm longitudinal incision was made about one-fourth of the distance from the xiphoid to the sternal notch. Bilateral transversal incisions (5mm and 10mm) were performed about one-third of the distance from the nipple to the sternoclavicular joint. The subfascial space was maintained with CO(2) insufflation. Endoscopic lobectomy or subtotal thyroidectomy was performed according to the diseases. Fifty-four of the 56 procedures were successfully performed endoscopically, including 41 unilateral lobectomies and 13 subtotal thyroidectomies. The mean operative time for uni- and bilateral procedures was 117.2 min and 184.5 min, respectively. Conversion occurred in two cases due to bleeding and malignant frozen section analysis, respectively. Postoperative complications included one temporary recurrent nerve palsy, one transient hypocalcemia, and one subcutaneous emphysema. 96.2%(50/52) of the patients were extremely satisfied or satisfied with the cosmetic effect. This procedure is more likely to be accepted by patients older than 30 years. Endoscopic thyroidectomy by the modified anterior chest approach is an effective procedure with both excellent aesthetic benefits and reduced physical injury.