Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation / 中华外科杂志

Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.

Laparoscopic versus traditional open splenectomy for hepatocellular carcinoma with hypersplenism / 华中科技大学学报（医学）（英德文版）

This study aimed to examine the efficacy of the laparoscopic vs. traditional open splenectomy for hepatocellular carcinoma (HCC) with hypersplenism. Between 2002 and 2013, 51 Chinese HCC patients with hypersplenism underwent either simultaneous laparoscopic splenectomy plus anticancer therapies (Lap-S&A) (n=25) or traditional open splenectomy plus anti-cancer therapies (TOS&A) (n=26). The outcomes were reviewed during and after the operation. Anti-cancer therapies for HCC included laparoscopic hepatectomy (LH) and laparoscopic microwave ablation (LMA). The results showed that there was no significant difference in the operating time between the two groups, but the blood loss and blood transfusion were less, pain intensity after surgery was weaker, the time to first bowel movement, time to the first flatus and postoperative hospital stay were shorter, and the postoperative complication rate and the readmission rate were lower in the Lap-S&A group than in the TO-S&A group. Two patients in the Lap-S&A group and one patient in the TO-S&A group died 30 days after surgery. However, no significant difference in the mortality rate was noted between the two groups. It was concluded that simultaneous Lap-S&A holds the advantages of more extensive indications, lower complication incidence and less operative expenditure than conventional open approach and it is a feasible and safe approach for HCC with hypersplenism.

Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo / 华中科技大学学报（医学）（英德文版）

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.

Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Smad4 is found mutated in many cancers. It acts as a tumor suppressor in the regulation of TGF-β signaling pathway. The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease.</p><p><b>METHODS</b>Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies. The expression of Smad4 was compared with the clinical pathological characteristics of the patients.</p><p><b>RESULTS</b>The expression of Smad4 was 100% positive in normal liver tissues, which was higher than that in the ICC (44.9%). Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5% (16/26) of poorly to moderately differentiated ICCs, and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P = 0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage I-II and pTNM stage III-IV separately. Furthermore, 72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein. The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P = 0.000).</p><p><b>CONCLUSIONS</b>The expression of Smad4 was associated with the histological grade, clinical stage, and metastasis of ICC (P < 0.05). The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.</p>

Minor liver resection for hilar cholangiocarcinoma of Bismuth-Corlette type III / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate long-term outcomes of minor liver resection for hilar cholangiocarcinoma (HC) of Bismuth-Corlette type III.</p><p><b>METHODS</b>From January 1997 to December 2007, the clinical data of 91 patients with Bismuth-Corlette type III HC underwent hepatectomy were collected and analyzed retrospectively.</p><p><b>RESULTS</b>There were 60 patients underwent minor hepatectomy, and 31 undergoing major hepatectomy. Hepaticojejunostomy was made conventionally in an end-to-side fashion in the patients undergoing major liver resection, and a new technique of hepaticojejunostomy used in the patients undergoing minor liver resection. That was the anterior edges of bile duct stumps which were not sutured after suturing of posterior edges. Instead of, the anterior edge of jejunum loop to the remnant liver on the top of the bile duct stumps were sutured with intermittent "U" sutures. In all patients, in-hospital mortality rate was 0 and rate of bile leakage was only 2.1%. The actual 1-, 3- and 5-year survival rates were 91.6% and 87.0%, 61.6% and 62.0%, 31.6% and 33.0%, respectively (P > 0.05).</p><p><b>CONCLUSIONS</b>Minor liver resection for the selected patients with HC of Bismuth-Corlette type III according to our criteria achieved better long-term outcomes. A new hepaticojejunostomy used in the patients undergoing minor liver resection is a safe and effective method.</p>

TNF-alpha induced reversal of multidrug resistance in human hepatocellular carcinoma cells / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the reversal of multidrug resistance in the cell line HepG2/ADM induced by TNF-alpha.</p><p><b>METHODS</b>HepG2/ADM cells were incubated with different concentrations of TNF-alpha (100, 500 and 2500 U/ml) for 72 h. Real-time PCR was performed to compare the mRNA levels of MDR1 with PPAR-alpha in the different concentrations of TNF-alpha treated cells. The Annexin V assay was used to check cell apoptosis induced by 0.5 mg/L adriamycin. Rhodamine 123 efflux assay and MTT assay were used to study P-gp activity and drug resistance in each group, respectively.</p><p><b>RESULTS</b>TNF-alpha could induce down-regulation of MDR1 and up-regulation of PPAR-alpha. Meanwhile, it could enhance cell cytotoxicity and cell apoptosis induced by 0.5 mg/L adriamycin.</p><p><b>CONCLUSIONS</b>TNF-alpha could partially reverse the multidrug resistance of HepG2/ADM cells by down-regulating the expression of MDR1 and up-regulating the expression of PPAR-alpha.</p>

The role of extracellular signal-regulated kinase/mitogen-activated protein kinase pathway in multidrug resistance of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To elucidate intracellular signal pathway in formation of multidrug resistance (MDR) of hepatocellular carcinoma (HCC) induced by its microenvironment, and to explore the potential role of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in this process.</p><p><b>METHODS</b>Activity of ERK/MAPK was examined by Western blot technique through comparing the ratio of phosphorylation of ERK/MAPK to total ERK/MAPK protein in HepG2 cells exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX. After being treated by the specific ERK/MAPK pathway inhibitor U0126, Western blot technique was used to analyze the alterations of the expression of P-gp, MRP1, LRP and HIF-1alpha at protein level. RT-PCR was used to analyze the alterations of the expression of HIF-1alpha mRNA. Cellular location of HIF-1alpha protein was determined by immunocytochemistry after being treated by U0126.</p><p><b>RESULTS</b>The activations of ERK/MAPK determined by the ratio of phosphorylated ERK/MAPK to the total ERK/MAPK were increased in varying degrees in HepG2 cells respectively exposed to different microenvironment. After being treated by U0126 for 12 h, the expressions of mdr1, MRP1, LRP genes and protein in those cells were decreased to some extent. However, the gene expression of HIF-1alpha was not influenced and only its protein was decreased. HIF-1alpha protein was reversely translocated into cytoplasm from nucleus after being treated by U0126.</p><p><b>CONCLUSIONS</b>ERK/MAPK pathway is involved in the course of the formation of MDR of HCC induced by microenvironment.</p>

Hypoxia-inducible factor-1 alpha dependent expression and significance of the related multidrug resistance genes induced by hypoxia in human hepatocarcinoma cell / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the mechanism of multidrug resistance of hepatocellular carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and multidrug resistance related genes.</p><p><b>METHODS</b>Human hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung resistance protein (LRP) gene at the mRNA and the protein levels in the above two groups were respectively analyzed by real-time fluorescent quantitative PCR and Western-blot technique.</p><p><b>RESULTS</b>In the hypoxia group, the expressions of mdr1, MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1 alpha. Also the increased expression of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid HIF-1 alpha/PCDNA3.</p><p><b>CONCLUSIONS</b>Resistance of hepatocellular carcinoma to chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the upregulation of the expression of the related multidrug resistance genes induced by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of hepatocellular carcinoma.</p>

Massive hemorrhage in hepatectomy: causes and management / 中华外科杂志

<p><b>OBJECTIVE</b>To analyse the causes and the management of massive hemorrhage in hepatectomy.</p><p><b>METHODS</b>With over 1 000 ml of bleeding, 4 368 patients with hepatectomy between 1955 and 2000 were analysed retrospectively.</p><p><b>RESULTS</b>Among 4 368 patients receiving hepatectomy, 286 (6.5%) had massive hemorrhage because of damage to the major hepatic veins, portal hypertension, hepatic insufficiency, and the extensive adhesion around the tumor. Massive hemorrhage was managed by repair and transfixation of the damaged vessels; transfixation or devascularization of variceal bleeding; complete vessels ligation of the hepatic section with mattress suture; resection of the ruptured tumor after temporary occlusion of the porta hepatis; fibrinogen infusion; hot saline compression of the surface of the wound and/or daub biological glue; argon beam coagulation and packs placement.</p><p><b>CONCLUSIONS</b>Light performance and nonforce dragging of liver can reduce massive hemorrhage caused by major vessel injury or tumor rupture. Normothetic occlusion of porta hepatis can reduce blood loss effectively when liver resection. In situ hepatectomy must be adopted if there is extensive adhesion around the tumor. Packs placement is still an effective measure to stop bleeding caused by defective coagulation and extensive blood oozing of wound surface.</p>

Interleukin-12 enhanced tumor necrosis factor related apoptosis-inducing ligand TRAIL-induced apoptosis in human hepatocellular carcinoma by inhibiting expression of survivin / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate therapeutic potential of TRAIL in hepatocellular carcinoma (HCC) and the mechanism of sTRAIL resistance and to reverse the resistance to sTRAIL-inducing apoptosis.</p><p><b>METHODS</b>The expression profiles of TRAILR were determined 60 HCC samples, in 20 normal liver tissues and 2 HCC cell lines HepG2 and SMMC-7721 by in situ hybridization. Cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC-7721 were analyzed after exposure to recombinant protein and after transfection with a cDNA expression construct. In vivo effects of sTRAIL on tumor growth were investigated using a nude mice HCC model of hepG2. Furthermore, the expression of survivin in HCC was detected, and treatment with antisence oligonucleotide was accepted. Finally, therapeutic effect on HCC by combining sTRAIL and interleukin-12 (IL-12) was detected.</p><p><b>RESULTS</b>Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. Recombinant sTRAIL alone was found to have a slight activity as it killed a maximum of 15% of HCC cells within 24 h while killing over 70% of Jurkat cells. In vivo administration of the TRAIL gene couldn't inhibit tumor growth in a nude mice HCC model. Mostly, HCC tissue and both HCC cell lines expressed survivin, whereas normal liver tissue did not express survivin. Treatment with antisence oligonucleotide enhanced sTRAIL-inducing apoptosis. IL-12 significantly augmented sTRAIL-inducing apoptosis and inhibited survivin expression.</p><p><b>CONCLUSIONS</b>HCC cells are insensitive towards TRAIL-mediated apoptosis. Survivin may play a role in resistance to TRAIL-induced apoptosis in HCC, and antisence oligonucleotide could partly reverse the resistance to TRAIL-inducing apoptosis. IL-12 may sensitize HCC cells to TRAIL-induced apoptosis by preventing survivin. Combining gene therapy strategy such as combining gene therapy of TRAIL with IL-12 may be a promising maneuver to HCC.</p>