Clinical imaging features and prognosis of von Hippel-Lindau syndrome associated with pancreatic lesions / 中华消化外科杂志

Objective:To investigate the clinical imaging features and prognosis of von Hippel-Lindau (VHL) syndrome associated with pancreatic lesions.Method:The retrospective case-control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Results:(1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them ( Z=-3.384, χ2=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them ( Z=-4.030, χ2=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow-up. The follow-up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive. Conclusions:The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.

Diagnosis and surgical treatment of autoimmune pancreatitis / 中华普通外科杂志

Objective:To explore the indications and effect of surgical treatment of autoimmune pancreatitis.Methods:Clinical data of these 15 patients with autoimmune pancreatitis diagnosed and treated at the Department of General Surgery, the First Hospital of Peking University from 2010 to 2021 were retrospectively analyzed.Results:The main clinical symptoms were obstructive jaundice, abdominal pain, distension and weight loss. The diagnosis of AIP was confirmed by EUS-FNA in 6 patients,among them, 4 did not relapse after oral hormone treatment, 2 did not receive relevant treatment, and 1 developed gastric cancer one year later. Under a suspicion of malignancy, 9 patients underwent surgical laparotomy ,and the diagnosis was established by pathology. There was no recurrence after oral hormone therapy in 1 patient who underwent laparotomy and pancreatic biopsy. One out of the 3 patients with choledochojejunostomy relapsed after 3 years. Of the 5 patients who underwent pancreatectomy, 4 had no obvious recurrence, and 1 had recurrence after 3 years.Conclusions:Untypical autoimmune pancreatitis is likely to be misdiagnosed as pancreatic cancer. For patients with suspicious malignancy, operational management and biopsy may benefit.

Risk factors analysis and treatment of postpancreaticoduodenectomy hemorrhage / 中华消化外科杂志

Objective:To investigate the risk factors and treatment of postpancreatico-duodenectomy hemorrhage(PPH).Methods:The retrospective case-control study was conducted. The clinical data of 712 patients who underwent pancreaticoduodenectomy in Peking University First Hospital from January 2012 to November 2021 were collected. There were 392 males and 320 females, aged from 16 to 89 years, with a median age of 62 years. Observation indicators: (1) diagnosis of PPH; (2) analysis of influencing factors for PPH; (3) treatment of PPH. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Univariate analysis was performed using the chi-square test or Fisher exact probability, and multivariate analysis was performed using the Logistic regression model. Results:(1) Diagnosis of PPH. Of the 712 patients, 72 cases had PPH and 7 cases died. The incidence of PPH was 10.11%(72/712), and PPH related mortality was 9.72%(7/72). There were 7 cases of early PPH and 65 cases of delayed PPH. There were 23 cases of mild PPH and 49 cases of severe PPH. (2) Analysis of influencing factors for PPH. Results of univariate analysis showed that preoperative serum total bilirubin (TBil), extended surgery, postoperative pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection were related factors for delayed PPH ( χ2=13.17, 3.93, 87.89, 22.77, 36.13, P<0.05). Results of multivariate analysis showed that preoperative serum TBil ≥171 μmol/L, postoperative grade B or C pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection were independent risk factors for delayed PPH ( odds ratio=1.91, 8.10, 2.11, 2.42, 95% confidence interval as 1.09-3.33, 4.62-14.20, 1.06-4.23,1.35-4.31, P<0.05). (3) Treatment of PPH. ① Treatment of early PPH. Of the 7 cases with early PPH, 4 cases had mild PPH and 3 cases had severe PPH. The 4 cases with mild PPH were stanched by conservative treatment. The bleeding location of the 3 cases with severe PPH were the posterior wall of pancreatoenteric anastomosis, the pancreatic uncinate stump and the unintentional puncture of the jejunostomy tube of the left upper abdominal wall vessels and the 3 cases were stanched by reoperation. All the 7 cases were discharged without other complications. ② Treatment of delayed PPH. Of the 65 cases with delayed PPH, 19 cases had mild PPH and 46 cases had severe PPH. Of the 19 cases with mild PPH, 18 cases were stanched by conservative treatment including 2 cases died of pancreatic fistula and abdominal infection, 1 case were stanched by endoscope therapy. Of the 46 cases with severe PPH, 18 cases with stable vital signs and slow bleeding were stanched by conservative treatment including 1 case died of infectious toxic shock and the other 28 cases underwent invasive treatment, including 2 cases undergoing gastroscopy, 20 cases undergoing interventional treatment and 6 cases under-going reoperation as the initial treatment. Of the 22 cases taking endoscope or interventional treatment as the initial treatment, 5 cases underwent rebleeding and 2 cases died, with the reblee-ding rate and mortality as 22.7%(5/22) and 9.1%(2/22), respectively. Of the 6 cases taking reopera-tion as the initial treatment, 3 cases underwent rebleeding and 2 cases died, with the rebleeding rate and mortality as 3/6 and 2/6, respectively. There was no significant difference in the rebleeding rate and mortality in patients taking endoscope or interventional treatment as the initial treatment and patients taking reoperation as the initial treatment ( P>0.05). Of the 28 cases undergoing invasive treatment, 10 cases underwent secondary surgical treatment, including 6 cases taking reoperation and 4 cases taking interventional treatment as the initial treatment for hemorrhage, and 4 cases died with the mortality as 4/10, and the other 18 cases who did not receive secondary surgical treatment survived. There was a significant difference in the mortality between patients with or without secondary surgical treatment ( P<0.05). Conclusions:Preoperative serum TBil ≥171 μmol/L, post-operative grade B or C pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection are independent risk factors for delayed PPH. Surgical treatment should be performed decisively for early severe PPH. For delayed severe PPH patients who undergoing conservative treat-ment without effect, endoscope therapy and interventional treatment should be the first choice, and surgical treatment should be performed if those above procedures not working.

The expression of miR-324-5p in pancreatic cancer and its effects and mechanisms on proliferation and migration of pancreatic cancer cells / 中华肝胆外科杂志

Objective:To investigate the expression and clinical relevance of micro RNA (miR)-324-5p in pancreatic cancer tissues, and to explore the effects and potential mechanisms of miR-324-5p on the proliferation and migration of pancreatic cancer cells.Methods:Real-time quantitative PCR was used to detect the expression of miR-324-5p in 34 pairs of pancreatic cancer and adjacent normal tissues resected at Peking University First Hospital from October 2018 to September 2019. The correlations between miR-324-5p expression and clinicopathological characteristics and prognosis of pancreatic cancer were analyzed using data from the Cancer Genome Atlas (TCGA) database. Real-time PCR was used to detect the expression of miR-324-5p in pancreatic cancer cell lines, and PANC-1 cell was used for functional study by overexpressing miR-324-5p via mimic transfection. CCK8 assay was used to evaluate cell proliferation. Both transwell and scratch wound healing assay were used to assess the cancer cell migration ability. Related proteins were detected by Western blot. The potential downstream target genes of miR-324-5p were selected using data from miRNA target genes predicted webs, in combination with functional analysis and their expressional correlation with miR-324-5p.Results:Data from TCGA database showed that the expression of miR-324-5p in tumor tissues was significantly lower than that in normal pancreatic tissues. And low level of miR-324-5p in pancreatic cancer was correlated with poor prognosis. Analysis of 34 pairs pancreatic cancer and adjacent normal tissues showed that miR-324-5p expression in tumor tissues (11.7±2.0) was significantly lower than that in adjacent normal tissues (70.9±14.4), and the pancreatic cancer patients who had the nerve invasion cancer showed low level of miR-324-5p (82.1%, 23/28) was significantly higher than that patients with high level of miR-324-5p (33.3%, 2/6). The expression of miR-324-5p in human pancreatic cancer cell line was also significantly lower than that in normal pancreatic ductal cells. CCK-8 assay showed that the proliferation ability of PANC-1 cell was significantly decreased when miR-324-5p was overexpressed. Transwell and wound healing assays showed that the capabilities of vertical migration and the horizontal movement were significantly inhibited in PANC-1 cell with miR-324-5p overexpressed [(30.11±5.2) and (174.6±27.0) μm, respectively] than those in control groups [(63.6±4.2) and (458.3±22.3) μm, respectively]. Moreover, Western blots showed a significant overexpression of miR-324-5p inhibited epithelial-mesenchymal transition (EMT). According to the data from miRNA target genes prediction and the functional analysis we found KLF3, MGAT3, PBX1 and ZNRF2 were considered as the potential downstream target genes of miR-324-5p.Conclusions:Our results indicated that miR-324-5p is lowly expressed and acts as the tumor suppressor gene in pancreatic cancer, and low level of miR-324-5p is correlated to a higher rate of nerve invasion and poor prognosis. In human pancreatic cancer cell, miR-324-5p may regulate EMT by directly inhibiting target genes such as KLF3, MGAT3, PBX1, ZNRF2, which in turn suppresses cancer cell proliferation and migration.

MicroRNAs as potential therapeutic targets for pancreatic cancer / 中华医学杂志(英文版)

Pancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

Clinicopathological characteristics and treatment strategies of undifferentiated carcinoma with osteoclast-like giant cells of pancreas / 中华消化外科杂志

Objective:To investigate the clinicopathological characteristics and treatment strategies of undifferentiated carcinoma with osteoclast-like giant cells of pancreas (UCOGCP).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with UCOGCP who were admitted to Peking University First Hospital from January 2004 to January 2019 were collected. There were 1 male and 4 females, aged from 33 to 71 years, with a median age of 56 years. Patients underwent preoperative laboratory test, imaging and histopatho-logical examinations. Patients with pancreatic head tumors underwent pancreaticoduodenectomy, and those with tumors in the body or tail of pancreas underwent distal pancreatectomy combined with splenectomy. All patients underwent standard lymph node dissection. Postoperative adjuvant therapy was individually decided by a multidisciplinary team. Observation indicators: (1) preopera-tive examination and treatment; (2) postoperative histopathological situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence of patients up to January 2020. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers. Results:(1) Preoperative examination and treatment: of the 5 UCOGCP patients, CA19-9 was elevated as 65.43 U/mL in only 1 patient preoperatively, while the CA19-9 was normal in other 4 patients. Four patients showed a solid cystic mass on preoperative contrast-enhanced computed tomography (CT) scan, and 1 patient showed a delayed peripheral enhancement of the solid tumor with central necrosis. The magnetic resonance imaging (MRI) scan showed hypointense signals on T1, T2 and weighted diffusion sequences in all 5 patients. Three of the 5 patients were resectable according to imaging data, 1 patient had locally advanced tumor, infiltrating the transverse colon, stomach, and partial small intestine, with the portal vein thrombus, and 1 patient had pancreatic head tumor with a liver metastatic lesion of 0.4 cm diameter which was detected on position emission tomography CT and was diagnosed as UCOGCP by endoscopic ultrasound-guided fine-needle aspiration biopsy. All patients underwent radical resection. Of the 3 patients with resectable tumors, 2 patients underwent pancreaticoduo-denectomy and 1 patient underwent distal pancreatectomy combined with splenectomy. One patient with locally advanced tumor in the body and tail of pancreas underwent distal pancreatectomy + transverse colostomy + partial gastrectomy + portal vein thrombectomy, and 1 patient with pancreatic head tumor and liver metastasis underwent pancreatoduodenectomy combined with left lateral hepatectomy. Of the 5 patients, 2 received postoperative adjuvant chemotherapy with single-agent gemcitabine, 1 received albumin-paclitaxel+gemcitabine combination chemotherapy, 1 received S1 as single agent chemotherapy, and 1 did not receive adjuvant chemotherapy. (2) Postoperative histopathological situations: of the 5 patients, 4 cases showed a cystic solid appearance of gross specimens, and 1 case had a solid appearance with central hemorrhagic necrosis. The tumor diameter was 5.2 cm(range, 2.0?14.0 cm). All the 5 patients achieved negative margins. Of the 5 patients, there was 1 case with portal vein invasion, 2 cases with vascular invasion, 3 cases with perineural invasion, and 2 cases with regional lymph node metastasis. One patient may had multiple tumor invasion and metastasis. Four of 5 patients had paraffin specimens available for immuno-histochemical staining. Four patients were positive for both CD68 and vimentin stains, while 3 patients were positive for programmed death ligand-1 (PD-L1), including 2 samples with 5% positive cells and 1 sample with 25% positive cells. Postoperative pathological examination showed a large number of spindle histiocytoid sarcoma cells scattered with osteoclast like giant cells and pleomorphic carcinoma giant cells. The tumor mutation burden in the 4 patients was 3.23 Muts/Mb(range, 2.61?21.77 Muts/Mb). Microsatellite status was stable in 4 patients. The next generation sequencing of 4 patients showed that all patients had KRAS mutation which was the most frequently mutation in pancreatic ductal adenocarcinoma. Of the 4 patients, 1 case had germline pathogenic mutation in TP53, 1case had somatic mutation in TP53, 1 case had somatic mutation in TP53, BLM, CDKN2A, and 1 case had somatic mutation in ARID1A. (3) Follow-up: 5 patients were followed up for 14?173 months, with a median follow-up time of 46 months. During the follow-up, 4 patients achieved disease-free survival and 1 patient had local recurrence at postoperative 11 months.Conclusions:UCOGCP is a rare variant of pancreatic tumor that exhibits a cystic solid mass in imaging examinations. High expression of PD-L1 is common in UCOGCP. The prognosis for UCOGCP is favorable following radical surgery. Patients may benefit from extended radical surgery even if the tumor has locally progression or distant metastasis.

Application and thinking of the concept of enhance recovery after surgery in pancreatic surgery / 临床肝胆病杂志

In recent years, the concept and clinical path of enhanced recovery after surgery (ERAS) have been widely accepted and applied in clinical practice in China, and it is gradually used in the field of pancreatic surgery. Objective factors such as complexity of disease, difficulties in pancreatic surgeries, and a high incidence rate of postoperative complications have led to the great difference in the clinical application of ERAS concept across pancreas centers, and the application and implementation of related clinical paths in this field is still late than that in other disciplines. At present, there is still a lack of high-level evidence for the application effect of the ERAS concept in pancreatic surgery, and high-quality clinical trials are needed to confirm its safety and efficacy. This article reviews the feasibility of the implementation of ERAS in pancreatic surgery and other hot topics, so as to provide a reference for the research in this field.

Circulating tumor cells in pancreatic cancer patients: progression in the detection methods and clinical application / 中华外科杂志

Circulating tumor cells (CTC) disseminate from primary tumors by undergoing epithelial mesenchymal transition that allow their entry into the circulation to drive metastatic formation in pancreatic cancer patients.Technological advances in detection and characterization of CTC are conducive to the early diagnosis, differential diagnosis, monitoring disease progression and predicating the probability of canceration or the chemotherapeutic efficacy. Nowadays, detection methods of CTC can be based on immunomagnetic beads technique, cell filtration or microfluidic chips technology, but there are great differences in the sample throughput, CTC recovery rate, purity, and CTC viability among them.Owing to the dilemma in detection methods, the intrinsic relevance between the biological characteristics of CTC and clinical manifestations is still not exactly elucidated. By the improved methodology, next generation sequencing technology and exploring the technique for culturing CTC in vitro and establishing xenotransplanted tumor model in nude mice, more and more biological information will be revealed, and finally, individualized treatment is achieved.

Current research status and progress in molecular subtyping of pancreatic cancer / 中华消化外科杂志

Rational molecular subtyping of pancreatic cancer based on genome,transcriptome,proteomics and metabolomics data,in combination with systematic biological analysis,have greatly enriched the traditional histopathological typing methods based on morphology.The introduction of molecular subtyping reflects the progress in deep understanding of the essence of tumorigenesis of pancreatic cancer,providing a necessary foundation for the development of molecular targeted therapy and implementation of precision medicine.Therefore,molecular subtyping of pancreatic cancer has broad application prospects.The current article reviews the current research status and recent progress of molecular subtyping of pancreatic cancer,and discusses the clinical significance of different subtyping methods.

The effects of targeted inhibition of hedgehog signaling pathway on proliferation, apoptosis and metastasis of hepatocellular carcinoma / 中华肝胆外科杂志

Objective To observe Hedgehog signaling pathways of liver cancer cell growth and the influence of the metastatic potential targeted inhibit Hedgehog.Methods Construction of Smo shRNA plasmid,The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened after lipofection.The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened,The cell cycle,apoptosis,invasion and metastasis of QGY-7701 cells were detected by Western blot,flow cytometry,CCK8 and transwell assay.Subcutaneous implantation of hepatocarcinoma cells in nude mice.Study on the growth and metastasis of hepatocarcinoma cells with low expression of Smo in.The ultrastructural changes of hepatoma cells with low expression of Smo were observed under electron microscope.Results RT-PCR and Western blot showed stable shR-Smo cell line was successfully constructed.Cell cycle test showed that compared with the control group,G0/G1 cells increased in shR-Smo,cells in S phase decreased;apoptosis,CCK8 and Transwell tests showed that Smo-gene silencing could significantly increase the apoptosis percentage of the hepatic cancer cells to (5.46％ ± 1.46％),proliferation activity decreasedand and the migration rates reduced to (7.82％ ±2.14)％;nude mice model showed that Smo-gene silencing could inhibit the growth of hepatocellular carcinoma cells in vivo,electron microscopy revealed that lysosomes increased significantly in Smo-gene silence cells.Conclusions Blocking Hh signaling pathways,liver cancer cells in vitro malignant degree of decline.Hedgehog in treating liver cancer have hidden meaning.

Diagnosis and treatment of pancreatic neuroendocrine neoplasmas in Von Hippel-Lindau syndrome / 中华外科杂志

Von Hippel-Lindau(VHL) syndrome is a rare autosomal dominant hereditary disease, and pancreas is one of the frequently involved intra-abdominal organs, including simple pancreatic cysts, pancreatic serous cystadenomas and neuroendocrine neoplasmas. Most of the VHL-related pancreatic neuroendocrine neoplasmas (VHL-pNEN)were non-functional, but they still have a tendency to be malignant. Treatment options for VHL-pNEN include regular follow-up, surgical resection, and medication therapy. When compared with sporadic pNEN, the malignant degree of VHL-pNEN is lower, with a better prognosis, so the surgical treatment should be carefully considered. The indications of surgery for VHL-pNEN include big primary lesions (≥3 cm), fast tumor doubling time (<500 days), VHL gene mutation on exon 3, malignant manifestations on imaging findings, and functional pNEN lesions. The function-preserving approach should be performed to keep the functional pancreatic parenchyma as much as possible. Even for patients with a late stage malignancy that cannot be radically resected, active medication therapy may still lead to a long-term survival.

The feasibility of enhance recovery after surgery in pancreatic surgery / 中华消化外科杂志

In recent years,enhanced recovery after surgery (ERAS) has been proved to be beneficial in terms of improving the postoperative outcomes,and shortening postoperative hospital stay in the context of gastrointestinal,gynecologic and urologic surgery.However,the role of ERAS for pancreatic surgery is still unclear and controversial,as the complex surgical procedure and high risk of postoperative complications,and moreover,high-quality randomized controlled trials are still lacking.In this article,authors try to discuss the current issues of the feasibility of the application of ERAS in pancreatic surgery.

Clinical features and surgical indications and malignant risk factors analysis of intraductal papillary mucinous neoplasms of the pancreas / 中华消化外科杂志

Objective To investigate the clinical features and surgical indications of subtypes of intraductal papillary mucinous neoplasm (IPMN) of the pancreas,and analyze its malignant risk factors.Methods The retrospective case-control study was conducted.The clinicopathological data of 77 patients with IPMN of the pancreas who were admitted to the First Hospital of Peking University from January 2008 to December 2016 were collected.The subtypes of IPMN of the pancreas detected by preoperative imaging examination included main-duct type (MD-IPMN) in 46 patients,branch-duct type (BD-IPMN) in 12 patients,mixed type (MT-IPMN) in 19 patients.The surgical indications were consulted from the Guideline for the diagnosis and treatment of pancreatic cystic lesions composed by the Pancreatic Surgery Group of Surgery Branch of China Medical Association.Surgical procedure was selected according to the location and size of the IPMN.Four to 6 cycles of chemotherapy with S-1 and/or Gemcitabine were conducted for patients with malignant IPMN according to the tolerance and baseline characteristics.Observation indicators included:(1) comparison of the clinical features MD-IPMN,MT-IPMN and BD-IPMN;(2) surgical and postoperative conditions;(3) results of postoperative pathological examination and malignant risk factors analysis;(4) accuracy evaluation of Sendai and Fukuoka guidelines for the diagnosis of malignant IPMN of the pancreas;(5) follow-up results and survival.Patients were followed up by outpatient examination and telephone interview till December 2016.The postoperative adjuvant therapy,tumor recurrence and metastasis of malignant IPMN patients and postoperative survival condition of all the patients were collected.Measurement data with normal distribution were expressed as (x)±s or average (range),and pairwise comparison was analyzed by t test.Measurement data with skewed distribution were expressed by median (range).Comparison between count data and univariate analysis were done by chi-square test.Multiple factors analysis was done by Logistic regTession model.The survival curve was drawn and the survival rate were calculated by Kaplan-Meier method.The comparison of survival was done by Log-rank test.Results (1) Comparison of clinical features between MD-IPMN,MT-IPMN and BD-IPMN:The numbers of patients with symptoms,jaundice,those complicated with diabetes and elevated CA19-9 were 55,20,43 and 28 in MD-IPMN and MT-IPMN,and 6,0,3 and 1 in BD-IPMN,with statistically significant difference (x2=5.421,3.516,5.525,3.834,P＜0.05).(2) Surgical and postoperative conditions:the operations for all the 77 patients were successfully done,including pancreaticoduodenectomy with or without preservation of pylorus on 45 patients,resection of head of pancreas with duodenum preservation on 3 patients,distal pancreatectomy on 23 patients,distal pancreatectomy combined with partial resection of spleen and stomach on 2 patients (with greater curvature of stomach involvement),segmental pancreatectomy on 2 patients,total pancreatectomy on 2 patients.A total of 26 surgery-related complications were detected,including pancreatic fistulas (13),delayed gastric emptying (9),wound infection (2),abdominal hemorrhage (2),and all the complications were improved by conservative treatment.There was no perioperative mortality.The mean duration of hospital stay of the 77 patients was 16 days (range,6-68 days).(3) Results of postoperative pathological examination and malignant risk factor analysis:① results of postoperative pathological examination:no residual tumor was detected at the resection margin in all the 77 patients,including 47 with benign IPMN (29 with adenoma and 18 with mid-severe atypical hyperplasia and without lymph node involvement) and 30 with malignant IPMN (all of them were invasive malignancy,including 17 patients with negative lymph node metastasis and 13 with positive lymph node metastasis).② Malignant risk factor analysis of IPMN:multivariate analysis showed that age,jaundice,elevated carcinoembryonic antigen (CEA),elevated CA19-9,tumor diameter,tumor subtypes were associated with malignancy (x2 =6.531,14.755,10.243,12.062,6.416,6.143,P ＜ 0.05).Multivariate analysis showed that jaundice,elevated CEA,elevated CA19-9,tumor diameter ≥3.0 cm,MD-IPMN were independent risk factors influencing the malignancy of IPMN (OR =9.656,42.853,23.243,34.387,69.883,95％ confidence interval:1.392-66.968,2.088-879.674,2.991-180.628,3.313-356.878,1.247-3 915.467,P＜0.05).(4) Accuracy evaluation of the Sendai and Fukuoka guidelines in diagnosis of malignant IPMN.The sensitivity,specificity,positive and negative predictive values were 100.0％(30/30),14.9％ (7/47),42.9％ (30/70) and 100.0％ (7/7) for the Sendai guideline and 86.7％ (26/30),48.9％ (23/47),52.0％ (26/50),85.2％ (23/27) for the Fukuoka guideline in diagnosis of malignant IPMN,with no significant difference in the sensitivity between the 2 guidelines (x2=2.250,P＞0.05),while significant difference in the specificity between the 2 guidelines were detected (x2 =12.500,P＜0.05).(5) Follow-up and survival:Seventy of 77 patients were followed up,including 42 with benign IPMN and 28 with malignant IPMN.The median survival time was 35.0 months (range,6.0-94.0 months).All the malignant IPMN patients received adjuvant therapy.The 1-,3-,5-year overall survival rates of 47 patient with benign IPMN were 100.0％,96.2％and 96.2％,respectively,and 1 patient died of cardiac infarction.The 1-,3-,5-year overall survival rates of 30 patients with malignant IPMN were 96.6％,81.8％,38.6％,respectively,and 11 patients died of tumor recurrence or metastasis with median time of tumor recurrence or metastasis of 20.5 months (6.0-61.6 months).The 1-,3-,5-year overall survival rates of 17 patients with negative lymph node metastasis were 100.0％,100.0％ and 60.0％,respectively,and the 1-,3-,5-year overall survival rates of 13 patients with positive lymph node metastasis were 91.7％,57.1％ and 0,respectively.There was statistically significant difference between patients with benign and malignant IPMN (x2 =12.530,P＜0.05).There was statistically significant difference between patients with negative lymph node metastasis and those with positive lymph node metastasis (x2 =16.977,P＜ 0.05).Conclusions Patients with MD-IPMN or MT-IPMN are more vulnerable to be complicated with diabetes,jaundice,elevated CA19-9 and high malignancy,and thus surgery is recommended.Jaundice,elevated CEA and CA19-9,tumor diameter≥3.0 cm,MD-IPMN are the independent risk factors influencing the malignancy of IPMN.

Clinical features and surgical indications and malignant risk factors analysis of intraductal papillary mucinous neoplasms of the pancreas / 中华消化外科杂志

Objective To investigate the clinical features and surgical indications of subtypes of intraductal papillary mucinous neoplasm (IPMN) of the pancreas,and analyze its malignant risk factors.Methods The retrospective case-control study was conducted.The clinicopathological data of 77 patients with IPMN of the pancreas who were admitted to the First Hospital of Peking University from January 2008 to December 2016 were collected.The subtypes of IPMN of the pancreas detected by preoperative imaging examination included main-duct type (MD-IPMN) in 46 patients,branch-duct type (BD-IPMN) in 12 patients,mixed type (MT-IPMN) in 19 patients.The surgical indications were consulted from the Guideline for the diagnosis and treatment of pancreatic cystic lesions composed by the Pancreatic Surgery Group of Surgery Branch of China Medical Association.Surgical procedure was selected according to the location and size of the IPMN.Four to 6 cycles of chemotherapy with S-1 and/or Gemcitabine were conducted for patients with malignant IPMN according to the tolerance and baseline characteristics.Observation indicators included:(1) comparison of the clinical features MD-IPMN,MT-IPMN and BD-IPMN;(2) surgical and postoperative conditions;(3) results of postoperative pathological examination and malignant risk factors analysis;(4) accuracy evaluation of Sendai and Fukuoka guidelines for the diagnosis of malignant IPMN of the pancreas;(5) follow-up results and survival.Patients were followed up by outpatient examination and telephone interview till December 2016.The postoperative adjuvant therapy,tumor recurrence and metastasis of malignant IPMN patients and postoperative survival condition of all the patients were collected.Measurement data with normal distribution were expressed as (x)±s or average (range),and pairwise comparison was analyzed by t test.Measurement data with skewed distribution were expressed by median (range).Comparison between count data and univariate analysis were done by chi-square test.Multiple factors analysis was done by Logistic regTession model.The survival curve was drawn and the survival rate were calculated by Kaplan-Meier method.The comparison of survival was done by Log-rank test.Results (1) Comparison of clinical features between MD-IPMN,MT-IPMN and BD-IPMN:The numbers of patients with symptoms,jaundice,those complicated with diabetes and elevated CA19-9 were 55,20,43 and 28 in MD-IPMN and MT-IPMN,and 6,0,3 and 1 in BD-IPMN,with statistically significant difference (x2=5.421,3.516,5.525,3.834,P＜0.05).(2) Surgical and postoperative conditions:the operations for all the 77 patients were successfully done,including pancreaticoduodenectomy with or without preservation of pylorus on 45 patients,resection of head of pancreas with duodenum preservation on 3 patients,distal pancreatectomy on 23 patients,distal pancreatectomy combined with partial resection of spleen and stomach on 2 patients (with greater curvature of stomach involvement),segmental pancreatectomy on 2 patients,total pancreatectomy on 2 patients.A total of 26 surgery-related complications were detected,including pancreatic fistulas (13),delayed gastric emptying (9),wound infection (2),abdominal hemorrhage (2),and all the complications were improved by conservative treatment.There was no perioperative mortality.The mean duration of hospital stay of the 77 patients was 16 days (range,6-68 days).(3) Results of postoperative pathological examination and malignant risk factor analysis:① results of postoperative pathological examination:no residual tumor was detected at the resection margin in all the 77 patients,including 47 with benign IPMN (29 with adenoma and 18 with mid-severe atypical hyperplasia and without lymph node involvement) and 30 with malignant IPMN (all of them were invasive malignancy,including 17 patients with negative lymph node metastasis and 13 with positive lymph node metastasis).② Malignant risk factor analysis of IPMN:multivariate analysis showed that age,jaundice,elevated carcinoembryonic antigen (CEA),elevated CA19-9,tumor diameter,tumor subtypes were associated with malignancy (x2 =6.531,14.755,10.243,12.062,6.416,6.143,P ＜ 0.05).Multivariate analysis showed that jaundice,elevated CEA,elevated CA19-9,tumor diameter ≥3.0 cm,MD-IPMN were independent risk factors influencing the malignancy of IPMN (OR =9.656,42.853,23.243,34.387,69.883,95％ confidence interval:1.392-66.968,2.088-879.674,2.991-180.628,3.313-356.878,1.247-3 915.467,P＜0.05).(4) Accuracy evaluation of the Sendai and Fukuoka guidelines in diagnosis of malignant IPMN.The sensitivity,specificity,positive and negative predictive values were 100.0％(30/30),14.9％ (7/47),42.9％ (30/70) and 100.0％ (7/7) for the Sendai guideline and 86.7％ (26/30),48.9％ (23/47),52.0％ (26/50),85.2％ (23/27) for the Fukuoka guideline in diagnosis of malignant IPMN,with no significant difference in the sensitivity between the 2 guidelines (x2=2.250,P＞0.05),while significant difference in the specificity between the 2 guidelines were detected (x2 =12.500,P＜0.05).(5) Follow-up and survival:Seventy of 77 patients were followed up,including 42 with benign IPMN and 28 with malignant IPMN.The median survival time was 35.0 months (range,6.0-94.0 months).All the malignant IPMN patients received adjuvant therapy.The 1-,3-,5-year overall survival rates of 47 patient with benign IPMN were 100.0％,96.2％and 96.2％,respectively,and 1 patient died of cardiac infarction.The 1-,3-,5-year overall survival rates of 30 patients with malignant IPMN were 96.6％,81.8％,38.6％,respectively,and 11 patients died of tumor recurrence or metastasis with median time of tumor recurrence or metastasis of 20.5 months (6.0-61.6 months).The 1-,3-,5-year overall survival rates of 17 patients with negative lymph node metastasis were 100.0％,100.0％ and 60.0％,respectively,and the 1-,3-,5-year overall survival rates of 13 patients with positive lymph node metastasis were 91.7％,57.1％ and 0,respectively.There was statistically significant difference between patients with benign and malignant IPMN (x2 =12.530,P＜0.05).There was statistically significant difference between patients with negative lymph node metastasis and those with positive lymph node metastasis (x2 =16.977,P＜ 0.05).Conclusions Patients with MD-IPMN or MT-IPMN are more vulnerable to be complicated with diabetes,jaundice,elevated CA19-9 and high malignancy,and thus surgery is recommended.Jaundice,elevated CEA and CA19-9,tumor diameter≥3.0 cm,MD-IPMN are the independent risk factors influencing the malignancy of IPMN.

Diagnosis and surgical treatment of pancreatic neuroendocrine neoplasms / 中华肝胆外科杂志

Objective To study the diagnosis,treatment and prognostic factors of pancreatic neuroendocrine neoplasms (pNENs).Methods The clinical,pathological and follow-up data of 44 patients with pNENs treated at the Peking University First Hospital from Jan.2007 to Dec.2016 were retrospectively studied.Survival analysis was performed with the Kaplan-Meier method.Results There were 21 male and 23 female patients.The mean age was (54.8 ± 14.0) years.25 patients had non-functional,while 19 had functional pNENs.Curative resection was performed in 40 patients.Neural invasion and intravascular cancer emboli were found in 7 and 5 patients,respectively.The pathologic data showed that the number of patients with G1,G2,G3 were 23 (52.3 ％),15 (34.1％),6 (13.6％),respectively.The number of patients with stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ were 23 (52.3 ％),16 (36.4％),2 (4.5 ％) and 3 (6.8 ％),respectively.The predictive factors on prognosis included curative resection or not,WHO grade,TNM staging,lymph node metastasis and distant metastasis (P ＜ 0.05).Conclusions Curative surgical resection is the first choice of treatment for pNENs.WHO grade,TNM staging,lymph node metastasis and distant metastasis were significantly related to the prognosis of pNENs.

Advance of Aquatic Therapy for Autistic Children (review) / 中国康复理论与实践

The aquatic therapy is a part of comprehensive rehabilitation. Aquatic therapy may benefit the social interaction, stereotyp-ing and motor learning of children with autism, which may associate with the physical and mental mechanism. The programs applied for the autism include game in water, swimming, physical fitness training in water, etc. The assessment tools include scales and video, and so on.

Risk factors of postoperative pancreatic fistula after pancreaticoduodenectomy and its predictive score / 中华外科杂志

<p><b>OBJECTIVE</b>To develop and test a scoring system to predict the risks of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy(PD).</p><p><b>METHODS</b>Clinic data and postoperative complications of the 445 consecutive patients who underwent a PD procedure between January 2008 and April 2015 in Peking University First Hospital were retrospectively collected and analyzed.The patients were randomly selected to modelling and validation sets at a ratio of 3∶1, respectively.The patient data were subjected to univariate and multivariate analysis in the modelling set of patients.A score predictive of POPF was designed and tested in the validation set.</p><p><b>RESULTS</b>POPF occurred in 88 of 334 patients(26.4%) in the modelling set.The multivariate analysis showed that body mass index (BMI, P<0.01) and pancreatic duct width(P=0.001) are associated with POPF independently.A risk score to predict POPF was constructed based on these factors and successfully tested.The area under the receiver operating characteristic curve were 0.829(95% CI: 0.777-0.881) on the modelling set and 0.885(95% CI: 0.825-0.945) on the validation set, respectively.</p><p><b>CONCLUSIONS</b>BMI and pancreatic duct width were associated with POPF after PD. The preoperative assessment of a patient's risk for POPF is feasible.The present risk score is a valid tool to predict POPF in patients undergoing PD, to make the selection on anastomosis types, and to take precautions against POPF.</p>

Surgical procedure selection for chronic pancreatitis / 中华消化外科杂志

Objective To investigate the surgical procedure selection for chronic pancreatitis.Methods The clinical data of 80 patients with chronic pancreatitis who were admitted to the Peking University First Hospital from January 2000 to August 2013 were retrospectively analyzed.Thirty-eight patients were with or without pancreatic duct stone,and the dilation of the pancreatic duct was above 7 mm,44 patients were with common bile duct dilation,32 patients were with inflammatory mass in the head of the pancreas,and 3 patients were with splenomegaly and esophagogastric varices.Surgical procedures were selected according to the symptoms and results of imaging examination.The remission or recurrence of pain was judged according to the visual analog scales.Patients were followed up via out-patient examination,mail or phone call till December 2013.Results Choledochojejunostomy was done on 27 patients,Partington-Rochelle pancreaticojejunostomy on 24 patients,PartingtonRochelle pancreaticojejunostomy + choledochojejunostomy on 6 patients,pancreaticoduodenectomy on 7 patients,resection of the body and tail of the pancreas on 4 patients,Beger's procedure on 3 patients,splenectomy on 3 patients,Frey's procedure + fenestration of bile duct in the head of the pancreas on 3 patients,Frey's procedure on 2 patients,common bile duct exploration + T tube drainage on 1 patient.The remission rate of abdominal pain was 95.2％ (60/63).One patient died of abdominal infection and multiple organ dysfunction syndrome perioperatively.Three patients were complicated with abdominal infection,2 with pancreatic fistula,1 with biliary fistula and 1 with abdominal bleeding.All the complications were cured by conservative treatment.Seventy-nine patients were followed up,and the mean time of follow-up was 58.6 months (range,4-156 months).Thirty patients had recurrence or new onset of abdominal pain,and the recurrence rate was 38.0％ (30/79).Of the 32 patients with inflammatory mass in the head of the pancreas,17 received choledochojejunostomy,and the recurrence rate of abdominal pain was 9/17 ; the other 15 patients received pancreatoduodenectomy,Beger' procedure or Frey's procedure,and the recurrence rate of abdominal pain was 1/15.Of the 41 patients without inflammatory mass,10 received choledochojejunostomy,and the recurrence rate of abdominal pain was 7/10; 30 received PartingtonRochelle pancreaticojejunostomy,and the recurrence rate of abdominal pain was 33.3％ (10/30).Conclusions Complete drainage could relieve the symptoms for patients with pancreatic duct dilation.Surgical resection or combined surgical procedure is effective for the treatment of patients with inflammatory mass in the head of the pancreas.

Diagnosis and treatment of pancreatic cystic neoplasms / 中华普通外科杂志

Objective To investigate the risks and benefits of different surgical treatments for cystic neoplasms of the pancreas (CNP).Methods The clinical data of 243 CNP patients were reviewed retrospectively.Different surgical treatments were adopted according to the site,size and invasiveness of the tumors.A long term follow-up was carried out for patients with small benign CNP,and a surgical excision is proposed if tumors progressed during the observation.Results 58 outpatients with no evidence of malignancy was followed up and had long-term survival,in which 4 patients received a surgical resection in case of tumor progression,and all of them were confirmed benign tumors.185 cases received surgical treatments,with a resection rate of 97.3％ (180/185),including 127 non-invasive tumors,and 58 cases of invasive tumors.Perioperative mortality was 2/185,and morbidity rate was 41/185.Pancreatic fistula was the most frequent complication,which was significantly associated with tumor site and excision extension.All patients with non-invasive CNP acquired a long term survival after surgical treatments.The postoperative 1,3,5 year survival rates for patients with invasive lesions were 89.6％,52.1％ and 29.2％,respectively.Conclusions Long term follow-up and observation is feasible for asymptomatic patients with benign CNP.A radical resection should be performed for malignancy,and a combined multi-organ resection may improve the prognosis for local advanced tumors.

Diagnosis and treatment of hepatic focal nodular hyperplasia / 中华普通外科杂志

ObjectiveTo investigate the clinical features,diagnosis and treatment of focal nodular hyperplasia (FNH) of the liver.MethodsClinical data of 42 FNH patients confirmed by pathology at our hospital between 2004 and 2011 were analyzed retrospectively.Thirty-eight cases underwent resection,and the other 4 patients were diagnosed by liver biopsy. ResultsThe 42 cases consisted of 25 males and 17 females,and age ranged from 14 to 51 years.Most of the patients (95.2％) had no significant clinical symptoms,and the liver function test was normal in 97.6％ (41/42) patients.The typical imaging features of FNH was the central scar and the radiating pattern.Thirty-eight cases underwent liver resection without any postoperative complication,and no recurrence was observed within 6 -90 months of follow up.For the other 4 cases,observation with periodic imaging follow up was performed after liver biopsy for 27 - 88 months without changes in all the lesions. ConclusionsFNH is a benign tumor of the liver.Observative follow up is recommended for asymptomatic patients with a definite diagnosis preoperatively.Surgical resection should be performed for symptomatic patients (epigastric pain or discomfort),or for patients with a suspicion of malignancy.