The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

Objective:To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation.Methods:A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics.Results:The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population ( P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden’s index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence ( P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup ( P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml ( P = 0.017) and cumulative tumor diameter > 9 cm ( P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ2 test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria ( P < 0.05). Conclusion:Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

PURPOSE: Our aim was to detect the potential role of interleukin 11 (IL-11) in the development of chemo-resistance in gastric cancer and to reveal the mechanism involved in the process. MATERIALS AND METHODS: Here, we used flow cytometry to examine the percentage of cancer-associated-fibroblasts in tumor samples from chemo-resistant and -sensitive gastric cancer patients. Using MTT assay, we detected the cell viability under different conditions. Using quantitative real-time polymerase chain reaction and Western blotting, we determined the target expressions in mRNA and protein levels. We also performed immunohistochemistry and immunofluorescence to detect the target proteins under different conditions. Animal models were constructed to verify the potential role of IL-11 in chemo-resistant develop in vivo. RESULTS: Herein, we observed enriched cancer associated fibroblasts in drug resistant tumor tissues from gastric patients. Those fibroblasts facilitate the chemotherapeutic drugs resistance development through the secretion of IL-11, which activates the IL-11/IL-11R/gp130/JAK/STAT3 anti-apoptosis signaling pathway in gastric cancer cells. We found that the combination of chemotherapeutic drugs and JAK inhibitor overcomes the resistance and increases the survival of mice with gastric cancer xenografts. CONCLUSION: Ourresults demonstrated that IL-11 contributed to the obtain ofresistance to chemotherapy drugs through gp130/JAK/STAT3/Bcl2 pathway, and targeting the IL-11 signaling pathway induced by fibroblasts might be a promising strategy to overcome the multi-drugs resistant cancer in clinic.
Animals ; Blotting, Western ; Cell Survival ; Drug Resistance ; Drug Therapy ; Fibroblasts* ; Flow Cytometry ; Fluorescent Antibody Technique ; Heterografts ; Humans ; Immunohistochemistry ; Interleukin-11* ; Mice ; Models, Animal ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Stomach Neoplasms*

Objective: To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma. Methods: Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old). Abdominal enhanced CT, pancreatic MRI, PET-CT were performed on all patients to evaluate the lesion and exclude metastasis.Follow-up were done with out-patient clinic or telephone consultancy until October 2017. Results: All patients underwent pure Lap-RAMPS.The medium operative time was 250 minutes(180-445 minutes), and the blood loss was 150 ml(50-500 ml). The medium first flatus time and diet resumption time were 3.0 days(1-5 days) and 3.5 days(1-7 days) respectively.The medium postoperative hospital stay was 9 days(4-18 days). Morbidity occurred in 8 patients with gastric empty delay(n=1), bleeding(n=1), fluid collection(n=3). There was no mortality.The medium overall number of retrived lymph nodes was 15.6 and the positive rate was 41.7%. The R0 rate was 100%.The medium follow-up was 10 months.One patient was diagnosed as liver metastasis after 8 months and accepted chemotherapy.One patient died after 14 months for tumor recurrence and metastasis.Others survived without tumor recurrence or metasitasis. Conclusion Lap-RAMPS is safe and feasible with accepted oncological outcomes for selected left side pancreatic adenocarcinoma under skilled hands.

Objective To investigate the treatment efficacy,feasibility and safety of laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm.Methods The clinical data of 31 patients who underwent laparoscopic resection of large gastric GISTs between Jan 2010 and Jun 2017 at Sir Run Run Shaw Hospital and People's Hospital of Zhejiang Province were retrospectively analyzed.Results All operations were successful.Two patients were converted to open surgery.The mean tumor size was (7.2 ±0.5) cm.The mean operation time was (127 ± 12) min,intraoperative blood loss was (83 ±25) ml.The first flatus time was (2.2 ±0.8) days,the first diet resumption time was (2.4 ± 1.2) days,and the median postoperative hospital stay was (5.5 ± 1.5) days.The median follow-up time was 25 months.One patient developing liver metastasis 41 months after primary resection received oral mesylate imatinib therapy for 24 months and was still alive at the last follow-up.One patient died of lung cancer 33 months after primary operation without recurrence of gastric GIST.Conclusions Laparoscopic surgery for gastric GIST larger than 5 cm on laparoscopicaly accessible location is feasible and safe.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.