Completely 3-dimensional laparoscopic pancreaticoduodenectomy with modified Blumgart pancreaticojejunostomy: an analysis of 100 consecutive cases.

PURPOSE: Although laparoscopic pancreaticoduodenectomy (LPD) is increasingly performed in high-volume centers, pancreaticojejunostomy (PJ) is still the most challenging procedure. Pancreatic anastomotic leakage remains a major complication after PD. Thus, various technical modifications regarding PJ, such as the Blumgart technique, have been attempted to simplify the procedure and minimize anastomotic leakage. Three-dimensional (3D) laparoscopic systems have been shown to be particularly helpful in performing difficult and precise tasks. We present a modified Blumgart anastomosis in 3D-LPD and investigate its clinical outcomes. METHODS: A retrospective analysis of 100 patients who underwent 3D-LPD with modified Blumgart PJ from September 2018 to January 2020 was conducted. Data on the preoperative characteristics, operative outcomes, and postoperative characteristics of the patients were collected and analyzed. RESULTS: The mean operative time and duration of PJ were 348.2 and 25.1 min, respectively. The mean estimated blood loss was 112 mL. The overall rate of postoperative complications over Clavien‒Dindo classification III was 18%. The incidence of clinically relevant postoperative pancreatic fistula was 11%. The median postoperative hospital stay was 14.2 days. Only one patient required reoperation (1%), and no patient died in the hospital or 90 days after the operation. High BMI, small main pancreatic duct diameter, and soft pancreatic consistency had a significant influence on the occurrence of CR-POPF. CONCLUSIONS: The surgical outcome of 3D-LPD with modified Blumgart PJ seems to be comparable to other studies in terms of operation time, blood loss, hospital stay, and complication incidence. We consider the modified Blumgart technique in 3D-LPD to be novel, reliable, safe, and favorable for PJ in the PD procedure.

Nicotine downregulates microRNA-200c to promote metastasis and the epithelial-mesenchymal transition in human colorectal cancer cells.

BACKGROUND: Cigarette smoking is the most well-established risk factor for colorectal cancer (CRC). However, the mechanisms of smoking-associated colorectal carcinogenesis are poorly understood. METHODS: The effects of prediagnosis tobacco use on clinical characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed in 396 patients with CRC. Associations between smoking status and OS and RFS were evaluated using Cox's proportional hazards regression. Furthermore, the effects of nicotine on the CRC cell lines SW620 and HT-29 were evaluated using in vitro assays. RESULTS: "Ever smoking" was associated with elevated serum carcinoembryonic antigen, American Joint Committee on Cancer T category, metastasis, and poorer OS and RFS in patients with CRC (OS: hazard ratio [HR] = 1.74, 95% confidence interval [CI], 1.07-2.81, p = 0.025; RFS: HR = 1.66, 95% CI: 1.18-2.34, p = 0.004). MicroRNA (miR)-200c was downregulated in CRC and tumor-adjacent tissues from ever smokers compared with the corresponding tissues from never smokers with CRC. Nicotine inhibited miR-200c expression in a dose- and time-dependent manner in SW620 and HT-29 CRC cell lines. Nicotine induced cell proliferation, migration, and invasion and promoted the epithelial-mesenchymal transition in SW620 and HT-29 cells, and these effects were attenuated by overexpression of miR-200c. CONCLUSION: Our findings support the adverse effects of prediagnosis cigarette smoking on prognosis and clinical behavior in CRC. We demonstrate a novel oncogenic mechanism by which nicotine promotes growth and metastasis in CRC by downregulating miR-200c.

MBD1 promotes the malignant behavior of gallbladder cancer cells and induces chemotherapeutic resistance to gemcitabine.

BACKGROUND: Methyl-CpG binding domain protein 1 (MBD1), which couples DNA methylation to transcriptional repression, has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell cycle progression and development. It has also been proven that MBD1 is involved in tumor development and progression. However, whether MBD1 is involved in tumorigenesis, especially in gallbladder cancer, is totally unknown. METHODS: Human GBC-SD and SGC996 cells were used to perform experiments. Invasion, wound healing and colony formation assays were performed to evaluate cell viability. A CCK-8 assay was performed to assess gallbladder cancer cell viability after gemcitabine treatment. Western blot analysis was used to evaluate changes in protein expression. Human gallbladder cancer tissues and adjacent nontumor tissues were subjected to immunohistochemical staining to detect protein expression. RESULTS: We found that MBD1 expression was significantly upregulated in gallbladder cancer tissues compared with that in surrounding normal tissues according to immunohistochemical analysis of 84 surgically resected gallbladder cancer specimens. These data also indicated that higher MBD1 expression was correlated with lymph node metastasis and poor survival in gallbladder cancer patients. Overexpression and deletion in vitro validated MBD1 as a potent oncogene promoting malignant behaviors in gallbladder cancer cells, including invasion, proliferation and migration, as well as epithelial-mesenchymal transition. Studies have demonstrated that epithelial-mesenchymal transition is common in gallbladder cancer, and it is well known that drug resistance and epithelial-mesenchymal transition are very closely correlated. Herein, our data show that targeting MBD1 restored gallbladder cancer cell sensitivity to gemcitabine chemotherapy. CONCLUSIONS: Taken together, the results of our study revealed a novel function of MBD1 in gallbladder cancer tumor development and progression through participation in the gallbladder cancer epithelial-mesenchymal transition program, which is involved in resistance to gemcitabine chemotherapy. Thus, MBD1 may be a potential therapeutic target for gallbladder cancer.

Acetyl-CoA: An interplay between metabolism and epigenetics in cancer.

Due to its high mortality and severe economic burden, cancer has become one of the most difficult medical problems to solve today. As a key node in metabolism and the main producer of energy, acetyl-coenzyme A (acetyl-CoA) plays an important role in the invasion and migration of cancer. In this review, we discuss metabolic pathways involving acetyl-CoA, the targeted therapy of cancer through acetyl-CoA metabolic pathways and the roles of epigenetic modifications in cancer. In particular, we emphasize that the metabolic pathway of acetyl-CoA exerts a great impact in cancer; this process is very different from normal cells due to the "Warburg effect". The concentration of acetyl-CoA is increased in the mitochondria of cancer cells to provide ATP for survival, hindering the growth of normal cells. Therefore, it may be possible to explore new feasible and more effective treatments through the acetyl-CoA metabolic pathway. In addition, a growing number of studies have shown that abnormal epigenetic modifications have been shown to play contributing roles in cancer formation and development. In most cancers, acetyl-CoA mediated acetylation promotes the growth of cancer cells. Thus, acetylation biomarkers can also be detected and serve as potential cancer prediction and prognostic markers.