mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote KrasG12D-Induced Acinar-to-Ductal Metaplasia and Early Pancreatic Carcinogenesis.

BACKGROUND & AIMS: Oncogenic KrasG12D induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM), an actin-based morphogenetic process, and drives pancreatic ductal adenocarcinoma (PDAC). mTOR (mechanistic target of rapamycin kinase) complex 1 (mTORC1) and 2 (mTORC2) contain Rptor and Rictor, respectively, and are activated downstream of KrasG12D, thereby contributing to PDAC. Yet, whether and how mTORC1 and mTORC2 impact on ADM and the identity of the actin nucleator(s) mediating such actin rearrangements remain unknown. METHODS: A mouse model of inflammation-accelerated KrasG12D-driven early pancreatic carcinogenesis was used. Rptor, Rictor, and Arpc4 (actin-related protein 2/3 complex subunit 4) were conditionally ablated in acinar cells to deactivate the function of mTORC1, mTORC2 and the actin-related protein (Arp) 2/3 complex, respectively. RESULTS: We found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote KrasG12D-driven ADM in mice and in vitro. They use the Arp2/3 complex as a common downstream effector to induce the remodeling the actin cytoskeleton leading to ADM. In particular, mTORC1 regulates the translation of Rac1 (Rac family small GTPase 1) and the Arp2/3-complex subunit Arp3, whereas mTORC2 activates the Arp2/3 complex by promoting Akt/Rac1 signaling. Consistently, genetic ablation of the Arp2/3 complex prevents KrasG12D-driven ADM in vivo. In acinar cells, the Arp2/3 complex and its actin-nucleation activity mediated the formation of a basolateral actin cortex, which is indispensable for ADM and pre-neoplastic transformation. CONCLUSIONS: Here, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.

Lipopolysaccharide stimulates endogenous ß-glucuronidase via PKC/NF-κB/c-myc signaling cascade: a possible factor in hepatolithiasis formation.

Hepatolithiasis is commonly encountered in Southeastern and Eastern Asian countries, but the pathogenesis mechanism of stone formation is still not well understood. Now, the role of endogenous ß-glucuronidase in pigment stones formation is being gradually recognized. In this study, the mechanism of increased expression and secretion of endogenous ß-glucuronidase during hepatolithiasis formation was investigated. We assessed the endogenous ß-glucuronidase, c-myc, p-p65, and p-PKC expression in liver specimens with hepatolithiasis by immunohistochemical staining, and found that compared with that in normal liver samples, the expression of endogenous ß-glucuronidase, c-myc, p-p65, and p-PKC in liver specimens with hepatolithiasis significantly increased, and their expressions were positively correlated with each other. Lipopolysaccharide (LPS) induced increased expression of endogenous ß-glucuronidase and c-myc in hepatocytes and intrahepatic biliary epithelial cells in a dose- and time-dependent manner, and endogenous ß-glucuronidase secretion increased, correspondingly. C-myc siRNA transfection effectively inhibited the LPS-induced expression of endogenous ß-glucuronidase. Furthermore, NF-κB inhibitor pyrrolidine dithiocarbamate or PKC inhibitor chelerythrine could effectively inhibit the LPS-induced expression of c-myc and endogenous ß-glucuronidase, and the expression of p-p65 was also partly inhibited by chelerythrine. Our clinical observations and experimental data indicate that LPS could induce the increased expression and secretion of endogenous ß-glucuronidase via a signaling cascade of PKC/NF-κB/c-myc in hepatocytes and intrahepatic biliary epithelial cells, and endogenous ß-glucuronidase might play a possible role in the formation of hepatolithiasis.

Transumbilical single-incision laparoscopic cholecystectomy: long-term review from a single center.

BACKGROUND: Currently, researches about single-incision laparoscopic cholecystectomy (SILC) are various, but long-term reviews assessing relevant complications after SILC with considerable amount of case series are rare. STUDY DESIGN: We retrospectively reviewed a large series of 529 patients undergoing SILC to assess the long-term postoperative recovery, including postoperative complications, retained symptoms, and quality of life. Finally, we assessed its associated risk factors related to SILC patients' recovery in the long term. RESULTS: During a mean follow-up period of 36.8 ± 8.8 months after SILC, 402 (76.0 %) patients underwent complete resolution. Frequent diarrhea (12.1 %) and recurrent omphalitis (5.9 %) were most commonly seen among other complications and retained symptoms within overall the patients. We identified 1 (0.3 %) incision hernia and 1 (0.3 %) intra-abdominal abscess among overall the patients, while 3 (0.8 %) common bile duct stones and 1 (0.3 %) biliary pancreatitis among the patients with symptomatic cholelithiasis during long-term review period. No significant differences were identified between patients with symptomatic cholelithiasis and gallbladder polyps when considering other incidences (all p > 0.05). Patients undergoing SILC with older age (p = 0.023) or female gender (p = 0.020) contributed to complete resolution. CONCLUSIONS: SILC via traditional devices is feasible and safe with acceptable postoperative incidence rate in the long run. Patients with older age or female gender, who have no severe systemic diseases, tend to benefit more from the surgical intervention.

Transumbilical single-incision laparoscopic distal pancreatectomy: primary experience and review of the English literature.

BACKGROUND: Single-incision laparoscopic surgery (SILS) may represent an improvement over conventional laparoscopic surgery, and has been applied in many surgical procedures. However, for pancreatic surgery, experience is rather limited. METHODS: The clinical records of 11 cases in which transumbilical single-incision laparoscopic distal pancreatectomy (TUSI-LDP) was performed at our institution since June 2009 were retrospectively analyzed, and all the literatures concerning TUSI-LDP were retrospectively reviewed. RESULTS: All the 11 patients were female. The ages ranged from 20 to 73 years, with an average age of 38.0 years. The average body mass index (BMI) was 22.67 (18.6-26.2). Most TUSI-LDPs were successfully performed, with only one conversion to multi-incision surgery. Splenic preservation was performed in six cases. The mean operation time was 163.18 ± 63.18 minutes (range 95-300), and the mean intraoperative blood loss was 159.09 ± 181.02 ml (range 10-500 ml). The surgical wounds healed well, with good cosmetic wound healing, and the patients were discharged from hospital in a mean of 7.45 ± 1.44 days (range 5-10). Only one patient developed pancreatic leakage, which ceased spontaneously with only a drain for 61 days. The parameters were comparable with those found in the English literature. CONCLUSIONS: These recent experiences suggest that SILS in pancreatic surgery is feasible for a select group of patients with relatively small lesions and low BMI, and that, with the gradual accumulation of surgeons' experience with SILS and improvement of laparoscopic instruments, it might become a safe option for some patients.

Transumbilical single-incision laparoscopic distal pancreatectomy: preliminary experience and comparison to conventional multi-port laparoscopic surgery.

BACKGROUND: Single-incision laparoscopic surgery (SILS), which has been demonstrated to be safely applied on kinds of surgeries, may represent an improvement over conventional multi-port laparoscopic surgery. However, there are still few clinical experiences of SILS in pancreatic surgery until now. In this study, we will summarize our experience of transumbilical single-incision laparoscopic distal pancreatectomy (TUSI-LDP), and compare its related parameters with conventional multi-port laparoscopic distal pancreatectomy (C-LDP). METHODS: A retrospective analysis was conducted for the patients who underwent C-LDP or TUSI-LDP in our department. The demographic data, operative parameters, and postoperative complications in the two groups were summarized and compared. RESULTS: Laparoscopic distal pancreatectomy was performed in a total of 21 cases, among which TUSI-LDP was performed in 14 cases. As far as the demographical results concerned, there were no significant differences between the two groups. The conversion to open surgery was conducted in one case in the TUSI-LDP group because of severe adhesion between pancreatic cyst and surrounding tissues, while in the C-LDP group the only one conversion was for the difficult detection of small lesion. The mean operating time and intraoperative blood loss in TUSI-LDP group was a little shorter (166.4 ± 57.4 versus 202.1 ± 122.5 minutes, p > 0.05, and 157.1 ± 162.4 versus 168.6 ± 157.4 ml, p > 0.05). The postoperative pain and post-operation lengths of hospital stay in the TUSI-LDP group were also less, though there was no significant statistical difference between the two groups. For the post-operation complications, in TUSI-LDP group the pancreatic leakage occurred in only one case, and ceased spontaneously with only a drain for 61 days. There were no other complications including postoperative hemorrhage, venous thrombosis, infections and so on in both groups. CONCLUSION: For the experienced laparoscopic surgeons, in selected patients, TUSI-LDP is a feasible technique, with excellent cosmetic effect, less postoperative pain and post-operation lengths of hospital stay. With the experience accumulated, the operating time and intraoperative blood loss of TUSI-LDP could also gradually reduce.

Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis.

Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.

The role of hepatocyte nuclear factor 4alpha in metastatic tumor formation of hepatocellular carcinoma and its close relationship with the mesenchymal-epithelial transition markers.

BACKGROUND: Mesenchymal-epithelial transition (MET) is now suggested to participate in the process of metastatic tumor formation. However, in hepatocellular carcinoma (HCC) the process is still not well revealed. METHODS: Paraffin-embedded tissue samples were obtained from 13 patients with HCC in Shengjing Hospital of China Medical University. The expression of E-cadherin, Fibronectin, N-cadherin, Vimentin, Hepatocyte nuclear factor 4alpha (HNF4alpha), Snail and Slug was assessed in primary tumors and their corresponding metastases by immunohistochemical staining. Next, the expression of HNF4alpha and E-cadherin in four HCC cell lines was examined. Furthermore, SK-Hep-1 cells were transfected with human HNF4alpha expression vector, and the change of E-cadherin expression was assessed. RESULTS: 45.2% (14/31) of the lesions in the metastases showed increased E-cadherin expression compared with the primaries, suggesting the possible occurrence of MET in metastatic tumor formation of HCC, as re-expression of E-cadherin is proposed to be the important hallmark of MET. The occurrence of MET was also confirmed by the reduced expression of Fibronectin (54.8%, 17/31), N-cadherin (38.7%, 12/31) and Vimentin (61.3%, 19/31) in the metastases. 45.2% (14/31) of the lesions in the metastases also showed increased HNF4alpha expression, and 67.7% (21/31) and 48.4% (15/31) of metastases showed decreased Snail and Slug expression respectively. Statistical results showed that the expression of HNF4alpha was positively related with that of E-cadherin, and negatively correlated with that of Snail, Slug and Fibronectin, suggesting that the expression change of the MET markers in the metastatic lesions might be associated with HNF4alpha. Among the four HCC cell lines, both HNF4alpha and E-cadherin expressed high in Hep3B and Huh-7 cells, but low in SK-Hep-1 and Bel-7402 cells. Furthermore, the expression of E-cadherin increased accordingly when SK-Hep-1 cells were transfected with human HNF4alpha expression vector, further confirming the role of HNF4alpha in the regulation of E-cadherin expression. CONCLUSIONS: Our clinical observations and experimental data indicate that HNF4alpha might play a crucial role in the metastatic tumor formation of HCC, and the mechanism may be related with the process of phenotype transition.

Macrophages and derived-TNF-α promote lipopolysaccharide-induced upregulation of endogenous ß-glucuronidase in the epithelial cells of the bile duct: A possible facilitator of hepatolithiasis formation.

BACKGROUND: Hepatolithiasis is prevalent in Southeast Asian regions, and the role of endogenous ß-glucuronidase (ß-GD) in the formation of hepatolithiasis is being gradually recognised. Revealing the regulation mechanism of the expression of endogenous ß-GD will provide new therapeutic strategies for intervening in the formation of hepatolithiasis. METHODS: Liver specimens from patients with hepatolithiasis were examined by immunohistochemistry to assess the expression of macrophage markers including CD68, CD80, and CD206, as well as that of TNF-α and endogenous ß-GD, compared with that in normal liver samples. HiBEpiC cells were co-cultured directly or indirectly with induced M2 macrophages or directly stimulated with TNF-α, and the expression of the endogenous ß-GD was examined. A PKC inhibitor, chelerythrine, and an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), were used to elucidate the possible regulation mechanism. RESULTS: The expression of macrophage markers including CD68 and CD206, as well as that of TNF-α and endogenous ß-GD significantly increased in liver specimens from patients with hepatolithiasis compared with that in normal liver samples. The expression of CD68, CD206 and TNF-α was positively correlated with that of endogenous ß-GD. When HiBEpiC cells were co-cultured directly or indirectly with M2 macrophages, following stimulation with lipopolysaccharide (LPS), the expression of endogenous ß-GD was significantly higher in the indirect co-culture group than that in the direct co-culture group, or in HiBEpiC cells or M2 macrophages cultured alone. Further experiments revealed that following stimulation with LPS, TNF-α secretion increased in both the indirect and direct co-culture groups compared with that in HiBEpiC cells cultured alone. TNF-α increased the expression of endogenous ß-GD in HiBEpiC cells, in a dose- and time-dependent manner. In addition, TNF-α significantly increased the expression levels of p-P65 and proliferating cell nuclear antigen (PCNA), and PDTC effectively inhibited the TNF-α-induced expression of PCNA and ß-GD. CONCLUSIONS: Infiltration of macrophages, especially M2 macrophages, may be involved in the hepatolithiasis formation. LPS activates the macrophages, inducing the secretion of TNF-α, which can further increase the expression of endogenous ß-GD in the epithelial cells of the bile duct, possibly via the NF-κB/PCNA signalling cascade.

Clinical characteristics of the primary hepatic malignant fibrous histiocytoma in China: case report and review of the literature.

BACKGROUND: A malignant fibrous histiocytoma is a soft tissue tumor that most commonly occurs in the extremities, but rarely involves the liver. The clinical characteristics and therapeutic experiences of primary hepatic malignant fibrous histiocytoma are still limited. METHODS: Two cases of primary hepatic malignant fibrous histiocytoma were analyzed retrospectively, and all the literature concerning primary hepatic malignant fibrous histiocytoma was analyzed. RESULTS: In China, a total of 76 cases had been reported, among which 50 were men, with a male to female ratio of 1.9:1. Mean age of the patients was 51.0 years old, and more than 85 percent were older than 40 years. 82.9 percent (63/76) of hepatic MFH were solitary lesions, with tumor size ranging from 2.5 to 23.5 cm (average 10.3 cm). Major clinical presentation (78.4%) was abdominal pain or discomfort, accompanied with some other non-specific symptoms such as malaise, anorexia, weight loss, jaundice and fever, and small cases (14.9%) were asymptomatic. Computed tomography and ultrasound usually revealed the location of lesions. The rate of pre-operative misdiagnosis was extremely high, and 14.9 percent of patients were even misdiagnosed as a benign liver cyst, liver abscess or hematoma. Integrated resection was performed among the most cases (49/68), among which only a few ones (12 cases) were introduced to have no recurrence or metastasis or be still alive with no detail information provided, while among the cases with palliative operation or only a biopsy, the cases that were followed-up all died. CONCLUSIONS: Hepatic malignant fibrous histiocytoma is a rare malignant mesenchymal tumor. The variable features of clinical presentations and images make the diagnosis difficult. Though the prognosis of primary hepatic malignant fibrous histiocytoma was rather poor, integrated resection might provide a few cases a good opportunity for surviving, suggesting that surgery might be an effective treatment.

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis.

The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.

Application of Laparoscopic Technique in the Treatment of Hepatolithiasis.

Hepatolithiasis is commonly encountered in Southeastern and East Asian countries, and its incidence is increasing in Western countries. For symptomatic hepatolithiasis or asymptomatic hepatolithiasis with signs of liver atrophy or malignancy, surgical intervention is needed, especially when peroral cholangioscopy and percutaneous transhepatic cholangioscopic lithotomy are not suitable or fail to be performed. Currently, laparoscopic surgery is gradually replacing traditional open surgery and becoming a better option. Various types of laparoscopic surgeries, including laparoscopic hepatectomy, laparoscopic biliary exploration through the common bile duct or the hepatic duct stump, and robotic-assisted laparoscopic surgery, have been developed for the treatment of simple hepatolithiasis, hepatolithiasis concomitant with choledocholithiasis, recurrent hepatolithiasis, and complicated hepatolithiasis. The related clinical experience is gradually accumulating. In this review, the laparoscopic applications and their advantages will be summarized. In most cases, the laparoscopic technique could provide the advantages of less trauma, reduced blood loss, and faster postoperative recovery.

Inflammation and Inflammatory Cytokine Contribute to the Initiation and Development of Ulcerative Colitis and Its Associated Cancer.

Dysregulated inflammatory responses play a pivotal role in the initiation, development, and progression of tumors, as demonstrated by the association between ulcerative colitis and the increased risk of colon carcinoma. In this review, the underlying mechanisms for the initiation and development of ulcerative colitis and colitis-associated cancer are described, mainly focusing on the inflammation and inflammatory cytokine. Disruption of the intestinal mucosal barrier and bacterial invasion resulted in intestinal inflammation; and further TLR4/NF-κB stimulation in intestinal epithelial cells, inflammatory cell infiltration, and inflammatory cytokine release all confer survival advantages to or promote abnormal proliferation in susceptible cells. Importantly, the respective roles of TLR4/NF-κB, TNF-α, and IL-6 in intestinal epithelial cells and inflammatory cells are summarized in detail. A thorough understanding of these molecular mechanisms may help researchers and clinicians to explore novel approaches for the prevention and treatment of colitis-associated cancer.

T-tube-free single-incision laparoscopic common bile duct exploration plus cholecystectomy: a single centre experience.

BACKGROUND: The present study aimed to explore the indications and feasibility of T-tube-free trans-umbilical single-incision laparoscopic common bile duct exploration (SILCBDE) plus laparoscopic cholecystectomy (LC) for treating choledocholithiasis. METHODS: Patients hospitalized in the Second Affiliated Hospital (Shengjing Hospital) of China Medical University from January 2010 to January 2017 with the diagnosis of common bile duct stones and treated with T-tube-free trans-umbilical single-incision LC plus common bile duct exploration were retrospectively analysed. RESULTS: A total of 37 male/female choledocholithiasis patients (mean age 65 years, range 29-86) were treated with T-tube-free trans-umbilical SILCBDE plus LC. No intraoperative complication or conversion to open surgery occurred in any of the cases. The mean operative time was 99.8 min (range 84-125) for endoscopic nasobiliary drainage group (n = 6), 113.8 min (range 70-150) for endoscopic retrogradebiliary drainage group (n = 2), 131.1 min (range 75-161) for pigtail J-tube group (n = 24), 113.7 min (range 100-150) for primary closure group (n = 5). The mean post-operative hospital stay length was 5.5 days (range 4-7) for endoscopic nasobiliary drainage group, 12.5 days (range 10-15) for endoscopic retrogradebiliary drainage group, 6.5 days (range 4-10) for J-tube group, 5.8 days (range 4-9) for primary closure group. Pancreatitis, bile leakage and peritonitis were not presented in any of the group. After 17-101 months follow-up, three patients presented recurrent common bile duct stones. CONCLUSION: In selected cases, T-tube-free trans-umbilical SILCBDE plus LC is feasible and safe for experienced surgeons, and can achieve similar therapeutic effects as common LC plus common bile duct exploration procedures.

Application of stapling devices in liver surgery: Current status and future prospects.

The liver is a vascular-rich solid organ. Safe and effective dissection of the vessels and liver parenchyma, and control of intraoperative bleeding are the main concerns when performing liver resection. Several studies have confirmed that intraoperative blood loss and postoperative transfusion are predictors of postoperative morbidity and mortality in liver surgery. Various methods and instruments have been developed during hepatectomy. Stapling devices are crucial for safe and rapid anastomosis. They are used to divide hepatic veins and portal branches, and to transect liver parenchyma in open liver resection. In recent years, laparoscopic liver surgery has developed rapidly, and is now preferred by many surgeons. Stapling devices have also been gradually introduced in laparoscopic liver surgery, from dividing vascular and biliary structures to parenchymal transection. This may be because staplers make manipulation more simple, rapid and safe. Even in single incision laparoscopic surgery, which is recognized as a new minimally invasive technique, staplers are also utilized, especially in left lateral hepatectomy. For safe application of stapling devices in liver surgery, more related designs and modifications, such as application of a suitable laparoscopic articulating liver tissue crushing device, a staple line reinforcement technique with the absorbable polymer membrane or radiofrequency ablation assistance, are still needed. More randomized studies are needed to demonstrate the benefits and find broader indications for the use of stapling devices, to help expand their application in liver surgery.

Single-incision laparoscopic biliary bypass for malignant obstructive jaundice.

Biliary bypass is a major management of resolution to malignant obstructive jaundice. Laparoscopic approach is an ideal alternative to open surgery with the less recurrence compared with endoscopic stenting. Single incision surgery approach has not been applied to biliary bypass due to technical challenge. The aim of this study is to evaluate the safety and feasibility of single-incision laparoscopic biliary bypass. Eighteen patients with periampulla tumor underwent single-incision laparoscopic cholecystojejunostomy. The preoperation and postoperation data were retrospectively analyzed. All the cases underwent surgery successfully without conversion to open or traditional laparoscopic surgery. The operation time and blood loss were 172.8 min and 101.1 ml, respectively. The postoperative hospital stay was 9.9 days. The jaundice was released, and the liver function was improved after the surgery. The mean survival of the patients was 9.5 months. The single-incision laparoscopic cholecystojejunostomy is safe and feasible with acceptable short-term outcomes in selected patients. The benefits still need to be evaluated in comparative study.

Transumbilical single-incision laparoscopic resection of focal hepatic lesions.

BACKGROUND AND OBJECTIVES: Transumbilical single-incision laparoscopic surgery (SILS) is gaining in popularity as a minimally invasive technique. The reduced pain and superior cosmetic appearance it affords make it attractive to many patients. For this study, we focused on SILS, analyzing the outcomes of transumbilical single-incision laparoscopic liver resection (SILLR) achieved at our institution between January 2010 and February 2013. PATIENTS AND METHODS: Pre- and postoperative data from 17 patients subjected to transumbilical SILLR for various hepatic lesions (8 hemangiomas, 2 hepatocellular carcinomas, 2 metastases, 2 calculi of left intrahepatic duct, and 3 adenomas) were assessed. Altogether, eight wedge resections, seven left lateral lobectomies, a combination wedge resection/left lateral lobectomy, and a proximal left hemihepatectomy segmentectomy were performed, as well as four simultaneous laparoscopic cholecystectomies. In each instance, three ports were installed through an umbilical incision. Once vessels and bleeding were controlled, the lesion(s) were resected with 5-mm margins of normal liver. Resected tissues were then bagged and withdrawn through the umbilical incision. The follow-up period lasted for a minimum of 6 months. RESULTS: All 17 patients were successfully treated through a single umbilical incision. The procedures required 55 to 185 minutes to complete, with blood loss of 30 to 830 mL. Subjects regained bowel activity 0.8 to 2.3 days postoperatively and were discharged after 3 to 10 days. There were few complications (23.5%), limited to pleural effusion, wound infection, and incisional hernia. CONCLUSIONS: Transumbilical SILLR is challenging to perform through conventional laparoscopic instrumentation. The risk of bleeding and technical difficulties is high for lesions of the posterosuperior hepatic segment. Surgical candidates should be carefully selected to optimize the benefits of this technique.

The efficacy of additional bevacizumab to cytotoxic chemotherapy regimens for the treatment of colorectal cancer: an updated meta-analysis for randomized trials.

BACKGROUND: The addition of bevacizumab (BEV) to cytotoxic chemotherapy regimens (CTX) was believed to be effective; however, its magnitude of benefits is still controversial. So a meta-analysis and systematic review seems to be necessary. METHODS: PubMed and the Cochrane library were systematically searched. All relevant citations comparing CTX with/without BEV were considered for inclusion. Sensitivity and meta-regression analysis were performed to identify potential confounders. All pooled estimates were performed using a random-effects model. All statistical analyses were performed by StataSE 12.0. RESULTS: The search strategy identified 10 eligible random control trials (RCTs) (n=1366). In our pooled estimates, the additional benefits of BEV to CTX were identified in overall survival (OS) hazard ratio (HR, 0.76; 95% CI, 0.69 to 0.82) and progression-free survival (PFS) (HR, 0.56; 95% CI, 0.51 to 0.60), and prolonged survival duration were also identified for OS (18.2 vs. 16.3, p=0.0003) and PFS (8.9 vs. 6.5, p<0.001). Subgroup analyses stratified by CTX was also performed, evident benefits of additional BEV in OS and PFS can be identified in all subgroups, except for the CTX containing capecitabine in OS. Moreover, the increased rate of incidence was also identified in hypertension, thrombosis, proteinuria, gastrointestinal perforation, and fatigue. CONCLUSION: BEV, acting as a targeted agent to CTX, its additional benefit to CTX is at the cost of increased toxicity.

Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation.

Cancer metastasis consists of a sequential series of events, and the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are recognized as critical events for metastasis of carcinomas. A current area of focus is the histopathological similarity between primary and metastatic tumors, and MET at sites of metastases has been postulated to be part of the process of metastatic tumor formation. Here, we summarize accumulating evidence from experimental studies that directly supports the role of MET in cancer metastasis, and we analyze the main mechanisms that regulate MET or reverse EMT in carcinomas. Given the critical role of MET in metastatic tumor formation, the potential to effectively target the MET process at sites of metastasis offers new hope for inhibiting metastatic tumor formation.