[Current status and hotspot of minimally invasive surgery for pancreatic head carcinoma].

With the improvement of laparoscopic equipment and surgical technology,pancreatic surgery has entered the "minimally invasive era".However,the use of minimally invasive pancreaticoduodenectomy in patients with pancreatic head cancer remains controversial.In recent years,China's pancreatic surgeons have been at the forefront of the world in terms of surgical technology,however,surgical philosophy, selection of indication,and perioperative management should be further stregthened. Additionally, the development of medical standards in various regions of China is seriously uneven,and minimally invasive pancreaticoduodenectomy still needs to be further standardized and popularized.Through this article,the author discusses the development status of minimally invasive surgery for pancreatic head cancer and related hot topics with fellow surgeons,in order to further improve the standard diagnosis and treatment of pancreatic cancer in China.

[Rethinking of surgical indications for pancreatic cystic tumors].

With the progress of imaging technology and the popularization of healthy examination, the detection rate of pancreatic cystic neoplasm(PCN) has increased significantly. PCN has complex disease spectrum, strong heterogeneity, and diverse surgical treatment strategies. Surgical timing and methods directly affect patients' prognosis. Therefore, how to identify malignant tumors and formulate reasonable treatment strategies are the keys to treat PCN. Many guidelines for clinical diagnosis and treatment of PCN have been released, but there are still many disputes about its surgical indications. Hence, fully assessing the surgical indications is of great significance to improve the PCN patients' prognosis. This paper deeply discusses on the surgical indications of PCN by reviewing the current clinical diagnosis, treatment and research progress of PCN, in order to standardize the diagnosis and treatment of PCN.

[Interpretation of the guidelines for neoadjuvant therapy of pancreatic cancer in China(2020 edition)].

Pancreatic cancer is a highly malignant tumor in the digestive system.The role of neoadjuvant therapy in pancreatic cancer has been highlighted with the understanding of pancreatic cancer biological behavior and popularization of comprehensive treatment.Therefore,Study group of Pancreatic Surgery in China Society of Surgery of Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association has formulated the guidelines for neoadjuvant therapy of pancreatic cancer in China(2020 edition).This guidelines elaborated key issues of the neoadjuvant therapy of pancreatic cancer,and provided reference for clinical practice.This article aims to interpret the guidelines about the preparation before neoadjuvant therapy, indication, regimen selection, therapeutic effect evaluation and surgery strategy, with further discussion about controversial issues of neoadjuvant therapy in pancreatic cancer.

[Challenges and stratigies of neoadjuvant therapy for pancreatic cancer].

In recent years, more and more attention has been paid on the role of neoadjuvant therapy in the comprehensive treatment of pancreatic cancer. There is increasing evidence indicates that neoadjuvant therapy improves the R0 resection rate and patient's prognosis. However, the indication, therapy selection and efficacy evaluation of neoadjuvant therapy in patients with pancreatic cancer are still controversial, thus its clinical application is not very mature. This article aims to analyze the clinical implementation dilemma of neoadjuvant therapy for pancreatic cancer, and discuss the scientific and reasonable neoadjuvant treatment mode for pancreatic cancer patients.

[The value of extended surgery for pancreatic cancer in the context of neoadjuvant therapy].

Pancreatic cancer has a high degree of malignancy and a poor prognosis, and the treatment effect is still not ideal. For patients with advanced pancreatic cancer, extended surgery for pancreatic cancer alone cannot benefit the patients. However, with the development of neoadjuvant therapy in the field of pancreatic cancer, some cases have obtained radical operation. Studies have shown that neoadjuvant therapy, combined with extended surgery for pancreatic cancer, can improve the overall prognosis of patients, indicating that surgical techniques themselves are still useful. In this article, combined with the relevant guidelines and clinical research progress of pancreatic cancer, the controversy and progress of the extended surgery for pancreatic cancer in the context of neoadjuvant therapy is summarized, and the resectability and prognosis evaluation index after neoadjuvant therapy is discussed, in order to standardize the treatment of pancreatic cancer, enhance the understanding of extended surgery for pancreatic cancer, and further improve the prognosis of pancreatic cancer.

[The long coding RNA GSTM3TV2 acts an oncogene to promote chemoresistance in pancreatic cancer].

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm(3)) was significantly larger than that in the control group((566.414±81.087) mm(3)) by treated with nab-paclitaxel(t=4.230,P<0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions: The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.

[Experience and reflection of diagnosis and treatment in insulinomas].

The insulinoma, which is the most common pancreatic neuroendocrine tumor, can be misdiagnosed and mistreated easily.Recently, the misdiagnosis rate has decreased significantly owing to the establishment of diagnosis and treatment system.However, the misconception about its diagnosis and treatment still exists because the diagnosis and treatment level varies greatly among different centers.This article aims to summarize the experience in the diagnosis and treatment of insulinoma in Peking Union Medical College Hospital, and introduce the qualitative and localization diagnosis, surgical and interventional treatment and perioperative management about insulinoma, so as to standardize the diagnosis and treatment procedure in China.

[(68)Ga-exendin-4 PET-CT for the localization of occult insulinomas: a prospective cohort study].

Objective: To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with (68)Ga-exendin-4. Methods: In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. (68)Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated. Results: A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive (68)Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of (68)Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7. Conclusion: (68)Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.

[The expression of KLK7 in pancreatic cancer and the effects on the biological behavior of pancreatic cancer cells].

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ(2) test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues (P<0.05). KLK7 expression was correlated with vascular invasion(χ(2)=7.535, P<0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ(2)=7.535, P<0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group (t=4.479, P<0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group(t=2.831, P<0.05). Conclusions: The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.

[Opportunities and challenges in the development of pancreatic surgery].

Pancreatic surgery is characteristic of various and complicated diseases and difficult surgeries. Pancreatic surgeons are required to grasp the new concept, apply new techniques and comprehend the study trends of pancreatic diseases. Otherwise, pancreatic surgeons should fully realize the opportunities and challenges resulted from application of new concept and techniques as well as learning new concept and techniques. Meanwhile, they should grasp the updating guidelines and research progress, intensively promote the development of prospective multicenter research involved in multidisciplinary team, and then promote the rapid development of pancreas surgery in China.

[Bit1 mediates the malignant behaviors in pancreatic cancer and its potential clinical significance].

Objective: To investigate the potential role of Bit1 in the pathogenesis of pancreatic ductal cancer cells(PDAC) and its potential clinical application value. Methods: Real-time PCR and Western blot were employed to detect the expression of Bit1 in six pancreatic cancer cells, then the tool cells were selected to further study the function of Bit1.PolyHEMA was used to monitor the suspended cell culture condition in vitro.The invasion and migration abilities of pancreatic cancer cells were detected through Transwell assay. Western blot and confocal assay were used to explore the potential mechanism of Bit1 in the process of metastasis.The expression of Bit1 was detected through tissue microarray, the potential relationship between Bit1 and other clinical factors were analyzed. Results: The results of real-time PCR and Western blot indicated that the expression of Bit1 was highest in the PANC1 cells and lowest in the Mia paca2 cells (gene: 3.13±0.40 vs. 1.00±0.35, protein: 1.77±1.00 vs. 0.23±0.45). The shBit1 PANC1 and Bit1-OE(over expression) Mia paca2 cells were successfully constructed.Bit1 over expression could promote the anoikis rate of Mia paca2 cells, and Bit knockdown could inhibit the anoikis incidence.Bit1 over expression suppressed the motility and invasion of Mia paca2 cells, but Bit1 knockdown could accelerate the migration and invasion ability of PANC1 cells.Bit1 could potentially affect pancreatic cancer cells' malignant behaviors through epithelial-mesenchymal transition process.Bit1 expression was significantly associated with pancreatic cancer's neural invasion (P<0.05). Conclusions: Bit1 could affect the anoikis incidence of pancreatic cancer, Bit1 negatively affect the migration and invasion abilities of PDAC, the EMT process was potentially involved in the whole modulation process.Bit1 expression is associated with neural invasion in pancreatic cancer patients.

[Correlation between miR-1178 expression and clinicopathological significance in human pancreatic cancer].

Objective: To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism. Methods: The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion. Establish a nude mice subcutaneously transplanted tumor model, 4 weeks after vaccination for tumor volume and weight measurement.Student t-test, rank sum test, and χ(2) test was used respectively to compare the data between two groups. Cox regression was adopted to improve the single factor and multiple factors analysis. Results: The results of hybridization in situ showed the expression of miR-1178 was increased in 72 cases with pancreatic cancer compared to that in paired normal pancreatic tissues (50/72 vs. 11/72, χ(2)=43.26, P<0.05). miR-1178 expression was positively associated with tumor lymph node stage (χ(2)=4.189, P=0.041). Univariate and multivariate analysis revealed that miR-1178 was an independent adverse prognostic indicator for patients with pancreatic cancer (HR=2.364, 95%CI: 1.114-5.019, P=0.025). Transwell assay indicated the over-expression of miR-1178 increased the number of AsPC-1 cells that penetrated the ECM-coated membrane (177.0±19.8 vs. 119.7±15.9)(χ(2)=8.21, P<0.05). For the in vivo experiment, overexpression of miR-1178 significantly promoted tumor growth, compared with control group (tumor volume: (5 122.4±760.2)mm(3) vs. (1 976.8±601.8)mm(3), t=2.413, P<0.05; tumor weight: (1.55±0.21)g vs. (0.67±0.17)g, t=2.960, P<0.05). Over-expression of miR-1178 down-regulated the expression of Stub1 and elevated the expression of FAK/MMP-9 signal pathway(P<0.05). Conclusions: MiR-1178 is overexpressed in pancreatic cancer, and is effective for predicting patients' prognosis. MiR-1178 regulate Stub1/FAK/MMP-9 signal pathway and promote the invasion of AsPC-1 cells.

[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.

[Developing laparoscopic pancreaticoduodenectomy step by step].

Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complicated operations in laparoscopic field.After been widely reported nowadays, LPD has been cautiously regarded as feasible and safe for radically resection.At present, several large pancreatic surgery centers in China have successively carried out this kind of surgery, with over one thousand cases in all.However, partly due to its complexity and steep learning curve, this procedure only remains limited to a few selected large pancreatic centers.Large sample prospective random control test studies are still required.We suggest that in China, LPD should only be developed steadily and step by step by highly skilled open and laparoscopic surgeons who have minimally invasive concept, contrary to fears and could grasp technical expertise.

[The 454th case: a 29-week pregnant woman with abdominal pain, hyperlipemia and multiorgan dysfunction].

A 32 year-old woman in the third trimester of pregnancy was admitted for severe acute pancreatitis due to hypertriglyceridemia. During hospitalization she developed multiorgan dysfunction, infected pancreatic necrosis, abdominal compartment syndrome and intrauterine fetal death. She was successfully treated by multidisciplinary team including department of emergency medicine, ICU, gastroenterology, obstetrics, endocrinology, ultrasonography, radiology, infectious disease, nutrition and surgery.

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/).

[Diagnosis and treatment of solid pseudopapillary neoplasms of the pancreas].

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare neoplasm which primarily affects young women without specific clinical manifestation. Computed tomography and magnetic resonance imaging contribute to the preoperative diagnosis of SPN. Surgery is the main treatment approach for SPN and more research of radiation and chemotherapy is needed. Tumor diameter larger than 5 cm, tumor infiltrating nerve, vessel or adipose tissue can increase the risk of recurrence. However, these patients can still get good prognosis after surgical resection.

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.

In situ generation of surface plasmon polaritons using a near-infrared laser diode.

We demonstrate a semiconductor laser-based approach which enables plasmonic active devices in the telecom wavelength range. We show that optimized laser structures based on tensile-strained InGaAlAs quantum wells-coupled to integrated metallic patternings-enable surface plasmon generation in an electrically driven compact device. Experimental evidence of surface plasmon generation is obtained with the slit-doublet experiment in the near-field, using near-field scanning optical microscopy measurements.