Surgical treatment of acute calculous cholecystitis complicated with hepatic dysfunction.

To evaluate the timing, feasibility, and necessity of early laparoscopic cholecystectomy (LC) in the management of patients with acute calculous cholecystitis complicated with hepatic dysfunction.The clinical data of 60 patients with acute calculous cholecystitis complicated with hepatic dysfunction treated from January 2016 to January 2018 were analyzed retrospectively. A total of 32 patients underwent LC within 72 hours of the cholecystitis attack, 28 patients after 72 hours. The results were compared with those from 28 patients with delayed LC.All the patients were operated by experienced surgeons, and no LC transfer to open operation. No significant differences were detected in the operation time, postoperative complications, intraoperative blood loss, white TBIL, ALT, GGT before and after the operation between the 2 groups (P > .05). Patients who underwent early LC had a short hospital stay and fewer hospital costs (P < .05). All the patients were cured.It is safe, feasible, and necessary to perform LC within 72 hours in patients with acute calculous cholecystitis complicated with hepatic dysfunction. Such patients show a high positive correlation between the inflammation of acute calculous cholecystitis and the damage of hepatic function.

Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Sorafenib may provide survival benefits for patients with advanced hepatocellular carcinoma. However, tumor cells can display primary or secondary resistance to Sorafenib. To identify genes capable of conveying Sorafenib resistance, we performed a genome-wide CRISPR transcriptional activation library (SAM) in human Huh7 cells. We identified that a group of sgRNAs were significantly enriched in Sorafenib resistant Huh7 cells, which indicated that these sgRNAs up-regulated their target genes and induced resistance. We finally identified LRP8 as a key gene that can drive HCC cell to acquire sorafenib resistance. All three sgRNAs targeting LRP8 were identified in Sorafenib resistant Huh7 cells with high copy. We also showed that sorafenib-acquired resistant Huh7 cells have much higher LRP8 expression level than parental Huh7 cells. We proved that overexpression of LRP8 in HCC cell lines activated ß-catenin and significantly promoted its resistance to Sorafenib. We further showed that overexpression of LRP8 reduced the apoptosis level of HCC cell lines. To summary, genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

MTF2 Induces Epithelial-Mesenchymal Transition and Progression of Hepatocellular Carcinoma by Transcriptionally Activating Snail.

BACKGROUND: Metal regulatory transcription factor 2 (MTF2) has been previously reported as a protein binding to the metal response element of the mouse metallothionein promoter, which is involved in chromosome inactivation and pluripotency. However, the function of MTF2 in tumor formation and progression has not yet been completely elucidated. METHODS: The expression of MTF2 and clinicopathological characteristics were evaluated by hepatocellular carcinoma (HCC) tissue microarray of 240 specimens. The role of MTF2 on HCC progression was determined using MTT, crystal violet, and transwell assays. Tumor growth was monitored in a xenograft model, and intrahepatic metastasis models were established. RESULTS: The expression of MTF2 was increased in HCC and strongly associated with the clinical characteristics and prognosis. Forced expression of MTF2 in HCC cells significantly promoted cell growth, migration, and invasion in vitro. In contrast, downregulation of MTF2 inhibited cell growth, migration, and invasion in vitro. Moreover, knock down of MTF2 suppressed tumorigenesis and intrahepatic metastasis of HCC cells in vivo. Mechanistically, MTF2 overexpression may promote growth and epithelial-mesenchymal transition processes of HCC cells by facilitating Snail transcription. CONCLUSION: MTF2 promotes the proliferation, migration, and invasion of HCC cells by regulating Snail transcription, providing a potential therapeutic candidate for patients with HCC.

[Surgical management of incidental gallbladder cancer discovered during or after laparoscopic cholecystectomy].

OBJECTIVE: To analyze the surgical management of incidental gallbladder cancer (IGBC) discovered during or after laparoscopic cholecystectomy (LC) and to evaluate the associated factors of survival. METHODS: A retrospective analysis of patients with IGBC between January 2002 and December 2013 was performed. A total of 10 080 consecutive patients underwent LC operation for presumed gallbladder benign disease in Chinese People's Liberation Army General hospital. And among them, 83 patients were histologically diagnosed as IGBC. Data covering clinical characteristics, surgery records, local pathological stage, histological features and factors for long term survival were reviewed. The survival analysis was performed using Kaplan-Meier method, and the results were examined using the log-rank test.For multivariate statistical analyses of prognostic factors, a Cox proportional hazards model was carried out. RESULTS: A total of 83 patients with IGBC:68.7% females (57/83), median age of 61 years (range 34-83 years). There were 47 cases accepted the initial simple LC, 18 cases converted to open extended radical cholecystectomy, 16 cases with radical second resection, and 2 cases with re-laparotomy; the 5-year survival rates for each group were 89.4%, 38.9%, 87.5%, and 0, respectively. The 5-year survival rates in T1a, T1b, T2, and T3 stage patients were 95.7% (22/23), 90.0% (18/20), 75.0% (15/20), and 40.0% (8/20), respectively. Univariate analysis for prognostic factors associated with cancer-specific death showed that depth of invasion, lymph-node status, vascular or neural invasion, tumor differentiation, extent of resection, bile spillage during prior LC and type of surgery were statistically significant.In multivariate analysis, depth of invasion, extent of resection and bile spillage were the most important prognostic factors related to both cancer-specific mortality and disease relapse (P < 0.05). CONCLUSIONS: Simple LC is appropriate for T1a patients with clear margin and unbroken gallbladder. An extended radical resection in patients with T1b or more is highly recommended, and provided as a potentially curative R0 resection only if it is necessary.

Surgical treatment of incidental gallbladder cancer discovered during or following laparoscopic cholecystectomy.

BACKGROUND: The optimal surgical management of patients with incidental gallbladder cancer (IGBC) and their long-term survival remains unclear. OBJECTIVE: The purpose of this study was to examine the long-term prognosis of patients with IGBC diagnosed during or after LC. METHODS: Between January 2002 and January 2012, a total of 7,582 consecutive patients underwent LC for presumed gallbladder benign disease in the Chinese PLA General Hospital, China. Among them, 69 patients (0.91%) were diagnosed to have IGBC. Their medical records, imaging data, surgery records, pathological findings, and survival data were retrospectively reviewed. RESULTS: Median age was 61 years (range: 34-83). After a median follow-up period of 61 months, the 1-, 3-, and 5-year survival rates of patients were 89.9, 78.3, and 76.8%, respectively. The 5-year survival rates of patients with T1a, T1b, T2, and T3 stages were 95.5, 93.8, 69.2, and 44.4%, respectively. The 5-year survival rates in simple LC (n = 45), converted to open extended cholecystectomy (n = 16), and radical second resection (n = 8) groups were 91.1, 37.5, and 75.0%, respectively. Local port-site tumor recurrence was identified in one patient. Prognostic factors including depth of invasion, lymph node status, vascular or neural invasion, tumor differentiation, extent of resection, bile spillage, and type of surgery were statistically significant (p < 0.05). CONCLUSIONS: Simple LC is appropriate for T1a patients with clear margin and unbroken gallbladder, whereas extended radical resection is recommended for patients with T1b or more advanced IGBC. An intact surgical specimen and the use of plastic retrieval bags are important to reduce the risk of port-site recurrences and disease relapse. Early diagnosis, meticulous perioperative assessment, and precise surgery are essential factors to obtain good results in IGBC treatment.

Diagnostic and therapeutic strategies to manage post-pancreaticoduodenectomy hemorrhage.

OBJECTIVE: To explore the causes, diagnosis and treatment of post-pancreaticoduodenectomy hemorrhages (PPHs). METHODS: A database of 703 pancreaticoduodenectomy patients in our institution (January 2008-July 2013) was analyzed retrospectively. RESULTS: PPHs occurred in 62 patients of which, 38 had clear causes and 15 died because of uncontrolled bleeding and multiple organ failure. Pancreatic fistula and abdominal infection rates were significantly higher in the PPH group compared to the group who did not experience hemorrhages (P < 0.05) but did not significantly increase the mortality of PPH patients. Hemostasis was attempted by endotherapy in 7 patients and was successful in 4 (57.1 %). Angioembolization was performed in 12 patients and was successful in 10 (83.3 %) and relaparotomy in 24 patients successful in 13 (54.2 %). All deceased patients belonged to International Study Group of Pancreatic Surgery clinical grade C and sentinel bleeding occurred in 60 % of PPH mortalities (9/15) (P = 0.005). CONCLUSION: Pancreatic fistulae and abdominal infections are associated with PPH. Control of early mild upper gastrointestinal hemorrhages could be attempted by endotherapy, but angiography with intervention or surgical treatments were always required for delayed bleeding. The mortality in cases with sentinel bleedings was obviously increased.

Effects of substance P on growth of fibroblast-like cells derived from bile duct: an in vitro cell culture study.

BACKGROUND: The possible role of substance P (SP) during wound healing has been the primary research focus in recent years, but its effect on the healing process after bile duct injury is little understood. This study aimed to investigate the effects of SP on growth of fibroblast-like cells derived from rabbit bile duct. METHODS: Fibroblast-like cells derived from rabbit bile duct were identified and divided randomly into control and experimental groups. SP-treated cells at different concentrations of 10(-9)-10(-5) mol/L and control group were incubated, respectively, for 48 hours. After incubating, the effects of SP on cell proliferation were assessed by cell counts and MTT test. Apoptosis rate (AR) of cells was measured by flow cytometry. RESULTS: Cultured rabbit bile duct cells were fibroblast-like in morphology, and these cells were stained positively for vimentin and negatively for desmin. After SP was added to nonconfluent cells for 48 hours, cell numbers were significantly increased in experimental groups than in controls (P < 0.05). The maximum stimulation of cell proliferation was achieved at SP of 10(-5) mol/L. Bile duct fibroblast-like cells in the SP group showed a higher proliferating activity and lower AR than those in the control group or in the SP + Spantide group (P < 0.05). Spantide partly inhibited the effects of SP on fibroblast-like cells. Examination under transmission electron microscopy revealed rough endoplasmic reticulum and prominent Golgi complexes after SP treatment. CONCLUSIONS: SP has a growth regulatory property on cultivated bile duct fibroblast-like cells in vitro, suggesting that SP may involve in wound healing after bile duct injury by promoting wound fibroblast proliferation and inhibiting apoptosis and participate in pathological scar formation.

An end-to-end anastomosis model of guinea pig bile duct: A 6-mo observation.

AIM: To establish the end-to-end anastomosis (EEA) model of guinea pig bile duct and evaluate the healing process of bile duct. METHODS: Thirty-two male guinea pigs were randomly divided into control group, 2-, 3-, and 6-mo groups after establishment of EEA model. Histological, immunohistochemical and serologic tests as well as measurement of bile contents were performed. The bile duct diameter and the diameter ratio (DR) were measured to assess the formation of relative stricture. RESULTS: Acute and chronic inflammatory reactions occurred throughout the healing process of bile duct. Serology test and bile content measurement showed no formation of persistent stricture in 6-mo group. The DR revealed a transient formation of relative stricture in 2-mo group in comparation to control group (2.94 ± 0.17 vs 1.89 ± 0.27, P = 0.004). However, this relative stricture was released in 6-mo group (2.14 ± 0.18, P = 0.440). CONCLUSION: A simple and reliable EEA model of guinea pig bile duct can be established with a good reproducibility and a satisfactory survival rate.