[Advances in the study of postpancreatectomy acute pancreatitis].

Postpancreatectomy acute pancreatitis (PPAP) is an acute inflammation of the remnant pancreas in the early postoperative period caused by a variety of factors. With the progress of related research,PPAP has been confirmed as an independent risk factor for many severe complications such as postoperative pancreatic fistula. In some cases, it progresses to necrotizing PPAP, increasing the risk of mortality. Currently, the International Study Group for Pancreatic Surgery has standardized and graded PPAP as an independent complication, taking into account factors including serum amylase, radiological features, and clinical impact. This review summarizes how the concept of PPAP was proposed, as well as the latest progress in the research related to its etiology, prognosis, prevention, and treatment. However, given the large heterogeneity of relevant studies and the fact that they were mostly retrospective, in the future, it is necessary to place more emphasis on PPAP and elucidate the problems through more standardized studies to optimize strategies for the prevention and management of complications after pancreatic surgery.

[The change in nutritional status of pancreatic cancer patients undergoing neoadjuvant therapy and its influence on these patients' postoperative outcomes as well as prognosis].

Neoadjuvant therapy has been one of the standard therapies for borderline resectable pancreatic cancer and locally advanced pancreatic cancer, but it may deteriorate these patients' nutritional status while controlling the progress of cancer, which inevitably influences these patients' postoperative outcomes and prognosis.In this article, we tried to answer this problem by reviewing other studies.And we found that neoadjuvant therapy would influence patients' postoperative outcomes and prognosis by deteriorating their nutritional status.But effective nutritional support can prevent it.It indicates that there is a need for these patients to receive nutritional support as soon as possible.However, in consideration of the limited number of relevant studies and their limitations, there is a need for more studies with strict design to answer this problem.And it can provide evidence for early nutritional support in pancreatic cancer patients who is going to undergo neoadjuvant therapy.

[Impact of the 2016 new definition and classification system of pancreatic fistula on the evaluation of pancreatic fistula after pancreatic surgery].

Objective: To discuss the impact of updated definition and classification system of pancreatic fistula published in 2016 on the postoperative classification of pancreatic fistula. Methods: Retrospective analysis was made on patients who underwent pancreatic surgery at ward 1 in Department of General Surgery, Peking Union Medical College Hospital from January 2015 to December 2016.A total of 408 patients were included in this retrospective study, male/female was 184/224, aged from 9 to 81 years with mean age of 51.6 years.One hundred and fifty-two cases were performed pancreaticoduodenectomy, 125 cases for distal pancreatectomy, 43 cases for spleen preservation distal pancreatectomy, 61 cases for partital pancreatectomy or enucleation, 8 cases for middle pancreatectomy, 6 cases for pancreaticojejunostomy and 13 cases for other procedures.Clinical data including postoperative drainage fluid volume, amylase concentration, duration of hospitalization and drainage were obtained, revaluated and re-analyzed, classified grounded on 2005 edition and 2016 edition, respectively.t-test was adopted for data analysis. Results: According to the previous standards, the incident rate of pancreatic fistula was 57.4%, and the incident rate of B-level plus C-level pancreatic fistula was 35.8%, which decreased to 13.7% based on 2016 edition.Nine patients who received percutaneous puncture or endoscopic drainage was regraded from C-level to B-level. The average duration of postoperative hospitalization of patients without pancreatic fistula was (12.5±6.0)days, demonstrating no significant difference compared to (14.1±7.7)days, duration of postoperative hospitalization of A-level(under 2005 edition of criteria) pancreatic fistula group(t=1.66, P=0.09) and (12.4±6.1)days, duration of postoperative hospitalization of biochemical leakage group(t=0.14, P=0.89). Nevertheless, there was statistical significant difference between the average postoperative duration of hospitalization(30.7±16.9) days of B-level(under 2016 criteria) pancreatic fistula patients and pancreatic fistula-free patients as well as the biochemical leakage group patients (t=7.10, 7.13; both P<0.01). Conclusions: Based on the new diagnostic criteria, the incidence of postoperative pancreatic fistula decreased dramatically.New classification system downgraded part of cases graded C-level pancreatic fistula to B-level and some B-level to biochemical fistula.The new diagnostic classification and criteria facilitated clinical practice, accomplished better conformity to clinical reality and potentially enacted clinical outcome.

[Progress in neoadjuvant and transformation therapy of pancreatic cancer].

Pancreatic adenocarcinoma is a malignant disease with considerable metastatic potential.While surgical resection can be potentially curative, tumor recurrence remains an important cause of treatment failure.Neoadjuvant chemotherapy can increase rate of resectability by decreasing tumor burden and decrease recurrence rate by clearing microscopic disease in lymph nodes and vessels.Currently, neoadjuvant therapy is recommended for patients with resectable who has signs of high risks or borderline resectable pancreatic adenocarcinoma.However, no consensus exists in current literature on the evaluation of treatment response or operative timing.FOLFIRINOX has recently emerged as an effective chemotherapy regimen in several large clinical trials.

Splenic preservation in laparoscopic distal pancreatectomy.

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is designed principally for the removal of benign and low-grade malignant lesions in the left pancreas. The aims of this study were to compare LSPDP with laparoscopic distal pancreatectomy with splenectomy (LDPS), compare two splenic preservation techniques (splenic vessel preservation and Warshaw technique) and investigate factors that influence splenic preservation. METHODS: Information from patients who underwent laparoscopic distal pancreatectomy between December 2004 and January 2016 at a single institution was reviewed. Data were extracted from a prospectively developed database. Intention-to-treat and propensity score matching analyses were employed. Univariable and multivariable analyses were used to investigate factors affecting splenic preservation. RESULTS: There were 206 patients in total (126 planned LSPDP and 80 planned LDPS procedures), of whom 108 underwent LSPDP and 98 LDPS. In intention-to-treat analysis, the duration of surgery was significantly shorter in the LSPDP group than in the LDPS group (mean 191·0 versus 220·5 min respectively; P < 0·001). Tumour size was an independent risk factor for splenic vessel resection in planned splenic vessel preservation operations, and a cut-off value of 3 cm provided optimal diagnostic accuracy. After a median follow-up of 35·9 months, there were no clinically significant splenic infarctions and no patient developed gastrointestinal bleeding after LSPDP. CONCLUSION: Planned LSPDP had a high splenic preservation rate and was associated with significantly shorter operating time than LDPS. Splenic vessel preservation could be predicted using a tumour cut-off size of 3 cm.

Propensity score-matched analysis of robotic versus open surgical enucleation for small pancreatic neuroendocrine tumours.

BACKGROUND: Enucleation of pancreatic neuroendocrine tumours (pNETs) via robotic surgery has rarely been described. This study sought to assess the safety and efficiency of robotic surgery for the enucleation of small pNETs. METHODS: A comparison was conducted of enucleation of pNETs smaller than 2 cm by robotic or open surgery between January 2000 and May 2015. Propensity score matching was used to balance sex, age, BMI, tumour location and tumour diameter. Pathological results, safety-related outcomes (postoperative pancreatic fistula (POPF) rate, estimated blood loss, and short-term mortality and morbidity) and efficiency-related outcomes (duration of surgery and postoperative length of hospital stay) were compared between the groups. RESULTS: A cohort of 120 patients with pNET were enrolled in the study (1 : 1 matched for open or robotic surgery, 60 per group). Ninety-three patients (77·5 per cent) had a grade 1 tumour and 114 (95·0 per cent) had an insulinoma. Robotic surgery had a conversion rate of 5 per cent (3 of 60), and was not associated with an increased POPF rate (10 per cent versus 17 per cent after open surgery; P = 0·283) or grade III-V surgical complications according to the Dindo-Clavien classification (3 versus 10 per cent respectively; P = 0·272). Estimated blood loss was reduced with the robotic approach (32·5 versus 80·0 ml in the open group; P = 0·008), as was duration of surgery (117 versus 150 min; P < 0·001). Length of hospital stay after surgery was similar in the two groups (12·0 versus 13·5 days respectively; P = 0·071). CONCLUSION: Robotic surgery for enucleation of pNETs smaller than 2 cm did not increase POPF or major complication rates, and reduced the duration of surgery and estimated blood loss, compared with open surgery. REGISTRATION NUMBER: NCT02125929 ( https://www.clinicaltrials.gov/).

Emerging role of tumor markers and biochemistry in the preoperative invasive assessment of intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: We explored the significance of laboratory examinations in predicting invasive carcinoma derived from intraductal papillary mucinous neoplasm (IPMN). METHODS: We retrospectively reviewed preoperative laboratory examination data and postoperative pathological data for 87 patients with IPMN who underwent surgical resection at Peking Union Medical College Hospital from February 2008 to March 2015. RESULTS: Histological review of 87 patients with surgical resection revealed 4 cases of mild-grade dysplasia (4.6%), 34 cases of intermediate dysplasia (39.1%), 16 cases of high-grade dysplasia (18.4%) and 33 cases of invasive carcinoma (37.9%). The first 3 grades were considered noninvasive. In univariate analyses, increased serum concentrations of CA19-9 (p<0.001), CA24-2 (p<0.001), CEA (p<0.001) and hsCRP (p=0.027) were significantly associated with invasive carcinoma. Multivariate analysis showed that increased serum concentrations of CA19-9 (p=0.009) and CEA (p=0.042) were significant independent predictors of invasiveness. The combination of CA19-9, CA 24-2 and CEA improved the accuracy of prediction, and the sensitivity and specificity were 71.0% and 87.7% respectively. CONCLUSIONS: The development of diagnostic laboratory tests has important implications for pre-operative IPMN evaluation. Increased serum CA19-9 and CEA concentrations are independent predictors of invasive carcinoma derived from IPMN, and increased serum CA24-2 and hsCRP concentrations are significantly associated with the risk of invasiveness. Combined detection of CA19-9+CA24-2+CEA proved to be the most accurate in predicting the invasiveness of IPMN.

Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants.

BACKGROUND: In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. OBJECTIVE: The objective of this study is to compare BDNF concentrations of subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants with those of controls with common sequence MC4R. METHODS: Circulating BDNF was measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian heritage ((mean±s.d.): age, 15.7±6.5 years; body mass index z-scores (BMI-Z), 1.63±1.03) and 69 subjects of Hispanic heritage (10.8±3.6 years; BMI-Z, 1.57±1.07). MC4R variants were characterized in vitro by cell surface expression, receptor binding and cyclic AMP response after agonist administration. BDNF single-nucleotide polymorphisms (SNPs) rs12291186, rs6265 and rs7124442 were also genotyped. RESULTS: In the Pima cohort, no significant differences in serum BDNF was observed for 43 LOF subjects versus 65 LOF-matched controls (age, sex and BMI matched; P=0.29) or 20 GOF subjects versus 20 GOF-matched controls (P=0.40). Serum BDNF was significantly associated with genotype for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99); BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the Hispanic cohort, plasma BDNF was not significantly different among 21 LOF subjects, 20 GOF subjects and 28 controls (P=0.79); plasma BDNF was not predicted by BDNF genotype or BDNF-x-MC4R genotype interaction. CONCLUSIONS: Circulating BDNF concentrations were not significantly associated with MC4R functional status, suggesting that peripheral BDNF does not directly reflect hypothalamic BDNF secretion and/or that MC4R signaling is not a significant regulator of the bulk of BDNF expression in humans.

Oncolytic vaccinia virus in combination with radiation shows synergistic antitumor efficacy in pancreatic cancer.

Combining oncolytic viruses with conventional therapy such as radiation is an innovative option for pancreatic cancer. We demonstrated that combination of GLV-1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest effect achieved in the AsPC-1cell line. Combination treatment significantly increased apoptosis compared with either single treatment or the control group. In mice bearing human pancreatic tumor xenografts, combination treatment resulted in significantly enhanced inhibition of tumor growth. No evidence of toxicity was observed in mice. These results indicate that the combination of GLV-1h151 and radiation has great potential for translation into clinic practice.

Inhibition of cytochrome P450 2A participating in coumarin 7-hydroxylation in pig liver microsomes.

Five commonly used human cytochrome P450 (CYP) inhibitors were examined for their effects on coumarin 7-hydroxylase (CYP2A) activity in pig liver microsomes. The K(m) and V(max) values for coumarin 7-hydroxylation in pig liver microsomes were estimated to be 1 µm and 0.26 nmol·mg/min, respectively. The following human CYP inhibitors caused little or no inhibition of CYP2A as defined by a K(i) > 200 µm: quinidine (CYP2D6), troleandomycin (CYP3A4), and sulfaphenazole (CYP2C9). The other two human CYP inhibitors were classified as strong inhibitors of CYP2A: 8-methoxypsoralen (CYP2A6) and α-naphthoflavone (CYP1A1/2). In the absence of a preincubation period, 8-MOP inhibited the 7-hydroxylation of coumarin with a K(i) value of 1.1 µm, which decreased to 0.1 µm when 8-MOP was preincubated with pig liver microsomes for 3 min. α-Naphthoflavone inhibited the 7-hydroxylation of coumarin with a K(i) value of 32 µm, which did not increase ability to inhibitor CYP2A when α-naphthoflavone was preincubated with pig liver microsomes for 3 min. These results of this study suggest that 8-MOP is a potent, mechanism-based inhibitor of pig CYP2A activity in pig liver microsomes.

Synergistic action of oncolytic herpes simplex virus and radiotherapy in pancreatic cancer cell lines.

BACKGROUND: Despite much research in chemotherapy and radiotherapy, pancreatic adenocarcinoma remains a fatal disease, highly resistant to all treatment modalities. Recent developments in the field of herpes simplex virus (HSV) engineering have allowed the generation of a number of promising virus vectors for treatment of many cancers, including pancreatic tumours. This study examined the use of one such virus, NV1023, in combination with radiation therapy in pancreatic cancer cell lines. METHODS: HSV therapy in combination with radiotherapy was investigated in pancreatic cancer cell lines Hs766T, Panc-1 and MIA PaCa-2. Multiple therapy effect analysis was performed by computerized simulation. Mechanisms underlying synergy, such as virus replication and apoptosis, were investigated. RESULTS: The combination of NV1023 and radiation yielded a synergistic oncolytic effect in all tested pancreatic cancer cell lines, with the greatest effect achieved in MIA PaCa-2. This effect was not mediated by an increase in rapid viral replication, but by a substantial increase in apoptosis. CONCLUSION: The synergistic oncolytic actions of HSV and radiotherapy observed in pancreatic cancer cell lines encourage further testing of this multimodality treatment.

Cloning, chromosome mapping and expression characteristics of porcine ANGPTL3 and -4.

Angiopoietin-like protein 3 and -4 (ANGPTL3 and -4) are two members of angiopoietin-like proteins (ANGPTLs), which have the signature structure of the angiopoietin family but cannot bind to the TIE2 receptor. It has been reported that they both affect lipid metabolism by inhibiting the activity of lipoprotein lipase (LPL). Here we report the cDNA cloning, chromosome mapping and expression analysis of ANGPTL3 and -4 in pigs. Sequence analysis shows that ANGPTL3 contains an open reading frame of 1,389 bp, which encodes 462 amino acids, and ANGPTL4 contains a coding region of 1,239 bp, which encodes 412 amino acids. Porcine ANGPTL3 deduced amino acid sequence shares 83% and 73.7% identity with human and mouse, respectively, and ANGPTL4 shares 79.4% and 77.7% amino acid identity with human and mouse, respectively. Porcine ANGPTL3 and -4 were mapped to the 6q31-->q35 and 2q21-->q24 region, respectively, by radiation hybrid mapping. Tissue distribution analysis indicated that porcine ANGPTL3 mRNA was exclusively expressed in liver, and porcine ANGPTL4 was ubiquitously expressed with the highest abundance in white adipose tissue. Furthermore, the mRNA level of ANGPTL3 and -4 in liver and the mRNA level of ANGPTL4 in white adipose tissue were significantly higher in genetically obese pigs than in their lean counterparts. This is the first report of molecular cloning and characterization of ANGPTL3 and -4 in pigs, which will be helpful for a better understanding of the role of ANGPTLs in lipid metabolism.

Cloning and characterization of porcine resistin gene.

Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance.

Cloning, expression and chromosome localization of porcine adiponectin and adiponectin receptors genes.

Adiponectin is a cytokine secreted specifically by adipocytes that has been proposed to enhance insulin sensitivity and prevent atherosclerosis. Adiponectin receptors (adipoR1 and adipoR2) are recently found in mice which act as receptors for globular and full-length adiponectin to mediate the fatty-acid oxidation and glucose uptake in muscle and liver. The primary goal of this study was to examine chromosome localization of porcine adiponectin and adiponectin receptors and the gene expression pattern in various tissues of pigs of the three genes. Radiation hybrid mapping demonstrated that porcine adiponectin, adipoR1 and adipoR2 were located to chromosome13q36-41, 10p11 and 5q25, in the regions that were syntenic to the homologs of human genes, respectively. Semi-quantitative RT-PCR showed that porcine adiponectin mRNA was specifically expressed in adipose tissue and porcine adipoR1 and adipoR2 mRNA were ubiquitously expressed in many tissues except brain. Comparison to adipoR2 mRNA which was highly expressed in liver, heart, kidney, adipose tissues and lung, adipoR1 mRNA was expressed at relatively high levels in porcine muscle, leukocytes and epididymis. Our data provide basic molecular information useful for the further investigation on the function of the three genes.

Size-fractionated plutonium isotopes in a coastal environment.

We have examined the distribution of individual Pu isotopes (239Pu, 240Pu, and 241Pu) in seawater from the Gulf of Maine (GOM). Samples were size-fractionated with a 1 kD cross-flow ultrafiltration (CFF) membrane. Subfractioned samples were radiochemically purified and Pu isotopes were analyzed using a three-stage thermal ionization mass spectrometer (TIMS). To our knowledge, this is the first time that both size class and Pu isotopic data have been obtained for seawater samples. Within measurement uncertainties a single 240Pu/239Pu atom ratio of 0.18 was found for all sample collection depths and sample size fractions. This signifies a current, single Pu source in GOM waters, namely global fallout, and suggests that no measurable isotopic fractionation occurred during CFF processing. The majority of Pu was found in the low molecular weight fraction (< 1 kD). Colloidal Pu varied from 8% of the total in surface waters to < 1% in the deepest (250 m) seawater sample. Evidence suggests that the vertical distribution of Pu in GOM is primarily controlled by conservative mixing processes. The high Pu fraction found in the low molecular size fraction implies that most of the Pu is in the non-particle-reactive oxidized fraction, and is consistent with the conservative Pu behavior. The activity levels are in agreement with other studies which show a slow decrease in Pu with time due to continued mixing and relatively slow particle removal.

2-D time-of-flight (TOF) MRA of thrombophlebitis of upper extremity and subclavian veins. A case report.

In this report, the authors present a case of segmental thrombosis of left subclavian vein that was inaccessible to conventional venography and inconclusive in magnetic resonance techniques (spin echo, gradient echo) but was clearly demonstrated by two-dimensional time-of-flight magnetic resonance angiography (2D TOF MRA). This technique is very sensitive to detect slow flow or partial occlusion of the vessels and is of great help in solving the problem of axillary-subclavian venous obstruction or thrombophlebitis.