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Background: Carbohydrate antigen 19-9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment. Methods: Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative N-glycosylation proteomics was used to examine N-glycosylation alterations. Results: Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-N-acetylglucosamine (UDP-GlcNAc) was an intermediate product between glutamine and CA19-9. Conclusions: Pancreatic cancer cells crave glutamine for CA19-9 biosynthesis. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.

Mast cells (MCs) are crucial cells participating in both innate and adaptive immune processes that play important roles in protecting human health and in the pathophysiology of various diseases, such as allergies, cardiovascular diseases, and autoimmune diseases. In the context of tumors, MCs are a non-negligible population of immune cells in the tumor microenvironment (TME). In most tumor types, MCs accumulate in both the tumor tissue and the surrounding tissue. MCs interact with multiple components of the TME, affecting TME remodeling and the tumor cell fate. However, controversy persists regarding whether MCs contribute to tumor progression or trigger an anti-tumor immune response. This review focuses on the context of the TME to explore the specific properties and functions of MCs and discusses the crosstalk that occurs between MCs and other components of the TME, which affect tumor angiogenesis and lymphangiogenesis, invasion and metastasis, and tumor immunity through different mechanisms. We also anticipate the potential role of MCs in cancer immunotherapy, which might expand upon the success achieved with existing cancer therapies.

With the development of modern society, human living standards have improved substantiallythus altering their lifestyles, particularly eating habits. These changes haveresulted in an increased incidence of colorectal cancer (CRC) in recent years. More than one million new cases of CRC are diagnosed worldwide and more than half a million deaths occur due to CRC, each year, making CRC the main cause of cancer-related mortality. In this study, we explored the role of myosin-related phosphatase 3 (MTMR3) in the invasion and metastasis of CRC by transfecting the human CRC cell line, HCT116 cells, with lentivirus-mediated short interfering RNA. A wound healing assay was performed to evaluate the effect of MTMR3 knockdown on cell migration ability. The effect of MTMR3 knockdown on the endothelial-mesenchymal transition and cell apoptosis was evaluated by western blot analysis. Our results indicate that knockdown MTMR3 significantly reduced the invasion and metastatic ability of HCT116 cells and promoted cell autophagy (p

Although rapid progress has been achieved in laparoscopic pancreaticoduodenectomy (PD) over the last decade, laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) remains a challenging surgery that has been rarely reported due to not only requiring complicated pancreaticojejunostomy (PJ) but also ensuring sufficient blood supplies to duodenum and common bile duct (CBD). We completed LDPPHR for 22 patients safely and efficiently with innovative techniques. Clinical outcomes, including rate of conversion to laparotomy, time of residual pancreatic duct reconstruction, incidence of postoperative complications, and time of hospital stay, were collected for 22 consecutive patients who underwent LDPPHR with innovative techniques as follows: application of indocyanine green (ICG) to visualize and preserve CBD and the vessels supplying the duodenum and CBD, Hong’s PJ, and pancreatic duct end-to-end anastomosis (ETEA) for the residual pancreas. All surgeries were performed successfully under laparoscopy except for one case. The duration of ETEA was significantly shorter than PJ (18.2 ± 5.1 min versus 27.5 ± 8.3 min, p

Radical resection is the only curative option for patients with hilar cholangiocarcinoma (HCCA) to achieve long-term survival. However, due to the fact that radical resection of HCCA has high technical requirements, the safety and efficacy of laparoscopic resection for HCCA remains controversial. From January 2015 to December 2018, 23 cases of HCCA underwent radical resection in our center. Clinical data of those patients were collected and analyzed retrospectively. 14 patients underwent laparoscopic resection and 9 cases received open resection. 2 patients in laparoscopic group were converted to laparotomy. Operation time in laparoscopic group was significantly longer than that in open group (519.4 ± 155.4 min vs 366.7 ± 93.1 min). Estimated blood loss (620.0 ± 681.2 ml vs 821.4 ± 713.8 ml) and incidence of intraoperative blood transfusion (5/9 vs 8/14) did not differ significantly between two groups. Pathological outcomes were comparable between two groups. Length of postoperative hospital stay (23.4 ± 13.4 days vs 17.8 ± 7.1 days), severe postoperative morbidity (3/9 vs 5/14), bile leakage of Grade A or B (5/9 vs 5/14), intra-abdominal bleeding (0/9 vs 1/14), intra-abdominal abscess (1/9 vs 0/14), wound infection (0/9 vs 1/14), pulmonary infection (2/9 vs 0/14), and liver failure (0/9 vs 0/14) did not differ significantly between two groups. One patient in laparoscopic group died (1/14) at 21 postoperative days due to intra-abdominal bleeding, while no 30-day mortality was observed in open group. Our results demonstrate that laparoscopic radical resection of HCCA is safe and feasible in experienced hands. Although laparoscopic resection for HCCA, which is still in initial and exploratory stage, fails to show any advantage over open resection in this study, we are optimistic with its wide application in future with the improvement of surgical techniques and experience.

Long non-coding RNAs are associated with cancer progression. Long intergenic non-protein coding RNA (linc)-regulator of reprogramming (ROR) enhances tumor development in hepatocellular carcinoma (HCC). However, the effect of chemoresistance and its underlying mechanisms in HCC are not completely understood. The present study aimed to identify the effect of ROR on sensitivity to doxorubicin (DOX) in HCC cells. In the present study, Cell Counting Kit-8 and EdU assays were performed to assess cell viability and proliferation, respectively. In addition, E-cadherin and vimentin protein expression levels were assessed via western blotting and immunofluorescence. The results of the present study demonstrated that HCC cells with high linc-ROR expression levels were more resistant to DOX, and linc-ROR knockdown increased HCC cell DOX sensitivity compared with the control group. The results indicated that compared with the NC siRNA group, linc-ROR knockdown notably suppressed epithelial-mesenchymal transition by downregulating twist family bHLH transcription factor 1 (TWIST1) expression. TWIST1 knockdown displayed a similar effect on HCC cell DOX sensitivity to linc-ROR knockdown. Moreover, linc-ROR knockdown-induced HCC cell DOX sensitivity was inhibited by TWIST1 overexpression. The present study provided evidence that linc-ROR promoted HCC resistance to DOX by inducing EMT via interacting with TWIST1. Therefore, linc-ROR might serve as a therapeutic target for reducing DOX resistance in HCC.

Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. Methods We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. Results GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). Conclusions GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

Gallbladder neuroendocrine carcinoma (GB-NEC) is a group of rare and heterogeneous neoplasms and there are few reports at present. We analyzed the clinical and pathological features of 7 patients with GB-NEC who were admitted to Zhejiang Provincial People's Hospital from January 2011 to October 2019. The median age of 7 patients was 58 years with male to female ratio of 1:2.5. Right upper quadrant discomfort was the main complaint and no patients presented carcinoid syndrome-related symptoms. In contrast-enhanced computed tomography (CT) examination, 5 of 6 patients showed well-defined margin and continuous thin line-like contrast enhancement on the mucosa. Among the patients with liver metastases before surgery, 66.7% of patients were cancer antigen 125 (CA-125) positive, and among the patients presented with liver metastases during follow-up period, all patients were CA-125 positive. All patients with elevated CA-125 did not have ascites, ovarian carcinoma, peritoneal carcinoma, and endometrial carcinoma. According to postoperative pathological report, 1 patient was stage IIIA, and the other 6 patients were stage IVB. Six patients underwent surgery, and 1 patient just underwent liver biopsy. Two patients underwent laparoscopic radical cholecystectomy, and neither of them encountered serious complications after surgery with the overall survival time of 4.6 and 16.8 months, respectively. Compared with the patients without chemotherapy, 3 patients postoperatively treated with chemotherapy lived longer. The median survival of all 7 patients was 4.6 months and the 1-, 2-year survival rates were 14.29%, 0%. Surgical resection, including laparoscopic radical cholecystectomy, is feasible for the treatment of advanced GB-NEC in selected patients and has the advantages of prolonging survival in combination with chemotherapy. The elevation of CA-125 can be utilized as an important predictor of poor prognosis, while more investigations are necessary to confirm it.

Resistance to chemotherapy drugs remains a significant problem for the treatment of many types of cancer. Fascin‑1 (FSCN‑1) is an actin-bundling protein involved in the invasion and metastasis of a variety of tumors. However, its involvement in drug resistance in hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the function of FSCN‑1 in HCC resistance to doxorubicin (DOX). FSCN‑1 expression was increased in DOX-resistant HCC cell lines (SNU449 and SNU387) compared with DOX-sensitive cell lines (Huh7 and Hep3B). The resistance of HCC cells to DOX was decreased following FSCN‑1 knockdown with small interfering RNA. FSCN‑1 knockdown also significantly altered the expression of key markers of epithelial-mesenchymal transition (EMT). Notably, vimentin expression was reduced and epithelial‑cadherin expression was increased. Furthermore, when EMT was suppressed through knockdown of Twist, an essential pathway of DOX-induced EMT, the viability of HCC cells following treatment with DOX was not affected by FSCN‑1 expression. Furthermore, FSCN‑1 knockdown eliminated hypoxia-induced doxorubicin resistance and EMT. The results of the present study indicated that FSCN‑1 expression increased DOX resistance in HCC cells via the promotion of EMT, and this phenomenon was maintained in a hypoxic environment. FSCN‑1 potentially represents a novel target to overcome resistance to DOX in HCC.

Background Postoperative pancreatic fistula (POPF) is the leading determinant of morbidity and mortality and reaches up to 49.9% of patients underwent pancreaticoenteric anastomosis during pancreaticoduodenectomy (PD). This study was to evaluate the feasibility of pancreaticoenteric anastomosis during pancreaticoduodenectomy (PD), and to evaluate the strategies of reducing the incidence of postoperative pancreatic fistula. Methods This prospective study included 119 patients who underwent PD for resectable tumors. The patients were divided into two groups according to the diameter of the pancreatic duct: those with a dilated (≥3 mm) and those with small ( Results The pancreatic duct diameter was significantly smaller in the HBPG than in DM anastomosis group (2.26 ± 0.53 mm vs. 5.03 ± 1.76 mm, P n = 4; Grade B, n = 2) and 8 of 63 (12.7%) patients in the DM anastomosis group (Grade A, n = 6; Grade B, n = 2). The overall complication rate was 37.0%; complications affected 24 of 56 (42.9%) patients in the HBPG group and 20 of 63 (31.7%) patients in the DM anastomosis group. Grade >IIIa complications occurred in 8 (14.3%) and 6 (9.5%) patients in the HBPG and DM anastomosis groups, respectively. The average postoperative hospital stay was 15.39 ± 6.88 days in the HBPG group and 13.24 ± 4.72 days in the DM anastomosis group. There were no significant differences in the frequency of complications such as postoperative bleeding, biliary fistula, delayed gastric emptying, gastrointestinal anastomotic fistula, reoperation rate, or readmission rate between the two groups. Conclusions The individual strategy based on the pancreatic duct diameter might effectively reduce the incidence of postoperative pancreatic fistula and other severe complications of PD. HBPG anastomosis is suitable for patients with pancreatic duct smaller than 3 mm. The size of the pancreatic duct is also one of the considerations for the selection of pancreatic and enteric duct anastomosis.

Rationale: Gallbladder perforation is a serious clinical condition and associated with high morbidity and mortality. A definitive diagnosis is contentious before surgery. Patient concerns: We herein report a case of perforation of the gallbladder neck secondary to chemotherapy and radiation for nasopharyngeal carcinoma patient. Diagnoses: Gallbladder perforation secondary to chemotherapy and radiation. Interventions: To decrease the mortality associated with gallbladder perforation, Laparoscopic cholecystectomy and peritoneal lavage were performed followed for gallbladder perforation patient because of chemotherapy and radiation. Outcomes: The patient recovered fully without serious complication and discharged on the 10th postoperative day. A pathological examination of the resected gallbladder revealed cholecystitis in the thinning of the neck. Lessons: Early diagnosis and surgical intervention of gallbladder perforation in relation to asopharyngeal carcinoma chemotherapy and radiation are of prime importance. The laparoscopic procedure is safe and feasible in the selected patients.

Our research was conducted to analyze the outcomes of two laparoscopic splenectomy plus pericardial devascularization (LSPD) techniques in the management of portal hypertension (PTH) and hypersplenism. Between May 2012 and May 2013, 41 patients with PTH and hypersplenism undergoing LSPD were retrospectively analyzed. Of them, 29 patients received LSPD by LigaSure™ Vessel Sealing System (LVSS) and Endo-GIA™ universal endoscopic vascular linear staplers (Endo-GIA) (EG Group) and 12 patients received LSPD by LVSS and Hem-o-Lock (HL Group). Operating time, intraoperative blood loss, postoperative course, and hospitalization costs were compared between the two LSPD combination techniques. There were no significant differences in preoperative patient characteristics of the two groups. Significantly less operating time, intraoperative blood loss, and postoperative complications were observed in EG Group. The incidence of portal vein thrombosis was lower in the EG Group (3.4 vs. 8.3 %), as well as the incidence of pancreatic fistula (0 vs. 8.3 %). Upper gastrointestinal hemorrhage was not observed in either group. Uncontrolled bleeding warranted conversion to open surgery in one case in EG Group (conversion rate 3.4 %) and in two cases in HL Group (conversion rate 16.7 %). Two patients (16.7 %) in HL Group underwent successful emergency exploratory laparotomy due to uncontrolled intraabdominal bleeding postoperatively. No re-operation was needed in EG Group. Two patients experienced liver failure after surgery in each group. Of those, three patients were managed successfully and one patient refused further therapy. While the overall complication rate was significantly lower in EG Group (17.2 vs. 58.3 %, P

Background Splenectomy and pericardial devascularization (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and specificity than the Child-Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD. Methods From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classification, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively. Results Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7–20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7–17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function compensation was 31.2%, which offered a sensitivity of 68.4% and a specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were significantly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of postoperative liver function recovery ( P =0.020). Conclusions ICGR15 has outperformed the Child-Pugh classification for assessing liver function in cirrhotic patients with portal hypertension. ICGR15 may be a suitable prognostic indicator for cirrhotic patients after SPD.

To assess the effect of cholesterol in bile on cholecystokinin receptor (CCK-R) in the gallbladder.One hundred Guinea pigs were randomly divided into four groups, 25 animals for each. The control group was fed a standard diet, and the cholesterol group fed a diet containing 2% cholesterol. After taking the 2% cholesterol diet for two weeks, the natural group persisted on the standard diet, and the treated group was perfused by traditional Chinese medicine. Serum cholecystokinin (CCK) level in the portal vein and maximal binding capacity (B(max)) and Kd of CCK-R in the gallbladder were measured in the four groups by RIA and RBA, and the concentrations of cholesterol in bile were also observed.Compared with the control group, after high-cholesterol feeding for two weeks, the gallbladder emptying rate [(65.83 +/- 7.32)% approximately (47.22 +/- 5.24)%] and B(max) of CCK-R [(60 +/- 27) approximately (32 +/- 13) fmol/mg protein] and in decreased fasting gallbladder volume (FV) [(0.89 +/- 0.26) approximately (1.34 +/- 0.61) cm(3)] and concentration of cholesterol [(0.44 +/- 0.11) approximately (0.60 +/- 0.13) mmol/L] in bile increased, but no change was in the serum CCK level and Kd of CCK-R in the cholesterol group. Compared with the natural group, after two-week in take of herb decoction of qingre lidan and liqi huoxue, FV [(1.27 +/- 0.60) approximately (0.90 +/- 0.27) cm(3)], RV [(0.85 +/- 0.45) approximately (0.32 +/- 0.12) cm(3)], FB [(0.92 +/- 0.35) approximately (0.73 +/- 0.21) cm(3)], RB [(0.76 +/- 0.34) approximately (0.29 +/- 0.08) cm(3)] in the treated group decreased significantly; but gallbladder emptying rate [(43.06 +/- 4.27)% approximately (67.01 +/- 6.82)%] increased significantly. The concentration of cholesterol in bile was lower in the treated group than in the natural group [(0.59 +/- 0.14) approximately (0.43 +/- 0.10) mmol/L], but no change was found in the serum CCK level. Bmax of CCK-R in the treated group increased significantly [(39 +/- 19) approximately (59 +/- 11) fmol/mg protein], Kd of CCK-R showed no significant changes between the treated group and natural group.High cholesterol in gallbladder bile causes defective muscle contraction by down-regulating CCK-R in the gallbladder, so the reduction of cholesterol concentration of bile may contribute to gallbladder contraction.

Malignant melanoma is an extremely aggressive cancer arising from melanocytes, associated with the development of metastases in up to 20% of patients. Although the liver is a frequent metastatic site of malignant melanoma, primary hepatic melanoma (PHM) is rare. The treatment of PHM is controversial, and the prognosis for affected patients remains poor. We present two PHM patients who underwent partial hepatectomy at our institution and review the clinical and pathological data from these cases. Our results suggest that it is difficult to make a preoperative diagnosis of PHM without pathological results. For patients with resectable PHM, surgical resection is a potentially curative treatment.