Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

SRY is a Key Mediator of Sexual Dimorphism in Hepatic Ischemia/Reperfusion Injury.

OBJECTIVES: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury. BACKGROUND: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined. METHODS: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation. RESULTS: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and promotes phosphorylation and degradation of ß-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of ß-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage. CONCLUSIONS: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/ß-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries.

Cholangiojejunostomy Using a Novel Magnamosis Device: Initial Clinical Results.

BACKGROUND: Cholangiojejunostomy (CJ) is a popular operation; however, no specific anastomotic device is available. A novel magnamosis device for CJ was developed in 2017; here, we evaluated the feasibility and safety of the device. METHODS: Between January 2017 and December 2019, 23 patients who underwent CJ using a novel magnamosis device were enrolled. For the CJ: the parent magnet was placed in the proximal duct, and the purse-string suture was tightened over the rod of the parent magnet. The magnamosis device was introduced into the jejunum, and the mandrel penetrated the jejunum at the anastomotic site, before insertion into the rod of the parent magnet. After rotating the knob, the distance between two magnets was shortened enough to achieve coupling. RESULTS: Sixteen patients (69.6%) underwent open CJ, while 7 (30.4%) underwent laparoscopic CJ; 21 patients (91.3%) underwent choledochojejunostomy, and 2 (8.7%) underwent right or left hepatic duct jejunostomy. The mean time for completion of CJ was 9.2±2.5 min; it was significantly shorter for open CJ than for the laparoscopic way (8±1.2 min vs. 11.8±2.5 min, P<0.05). Only one patient (4.3%) suffered bile leakage after operation and was cured by conservative treatment. The magnets were discharged with a postoperative duration of 66.7±47.2 days, with a 100% expulsion rate. After a median follow-up of 15 months, only one patient (4.3%) developed inflammatory anastomotic stricture. CONCLUSION: The novel magnamosis device is a simple, safe, and effective modality for CJ.

Magnetic Compression Anastomosis in Laparoscopic Pancreatoduodenectomy: A Preliminary Study.

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is a minimally invasive technique widely developed in the last few decades. Although magnetic compression anastomosis (magnamosis) is used during cholangiojejunostomy, its applicability in LPD has not yet been reported. Herein, we evaluated the feasibility and effectiveness of magnamosis in LPD. METHODS: Between January 2018 and December 2019, seven patients who underwent laparoscopic magnetic compression choledochojejunostomy (LMC-CJ) or laparoscopic magnetic compression pancreatojejunostomy (LMC-PJ) in LPD were enrolled. After LPD, a parent magnet with or without a drainage tube was placed in the proximal bile duct and pancreatic duct of each patient. Daughter magnets were introduced to couple with the parent magnets at the desired sites. A close postoperative surveillance of magnet movements was performed. Various relevant data were collected, and all patients were followed up until February 2020. RESULTS: LPD was successfully completed in all seven patients, of which seven underwent LMC-CJ and two received LMC-PJ. The median time needed for completion of LMC-CJ was 11 min (range, 8-16). The cost time for the two cases of LMC-PJ was 12 and 15 min, respectively. After a median time of 50 d (range, 40-170) postoperation, all magnets were expelled. No leakages of LMC-CJ or LMC-PJ were observed after operation. After a median follow-up period of 11 mo (range, 4-18), there was no incidence of anastomotic stricture.

Late pregnancy screening for preeclampsia with a urinary point-of-care test for misfolded proteins.

The aim was to describe and assess a new late pregnancy point-of-care urinary preeclampsia screening test. Urine samples were collected from a consecutive series of 1,532 pregnant women hospitalized at 20-41 weeks gestation in a Chinese single obstetric unit. A simple disposable Congo red based device was newly developed and employed to prospectively test misfolded proteins in pregnant women's urine. A total of 140 preeclampsia cases were clinically diagnosed, 101 severe and 87 pre-term. Detection and false positive rates were similar in the training and validation subsets with combined 74% and 3.0%. The detection rate was 83% in severe, 86% in pre-term, 49% and 50% in mild and term cases (P<0.0001) respectively. In conclusion, a simple point-of-care urinary test for misfolded proteins can be used to screen for preeclampsia in late pregnancy with very high screening performance. To the best of our knowledge, this is the first study to screen for preeclampsia using Congo red based device in Chinese pregnant population.

A novel preoperative scoring system to predict technical difficulty in laparoscopic splenectomy for non-traumatic diseases.

BACKGROUND: Laparoscopic splenectomy (LS) has been proven to be a safe and advantageous procedure. To ensure that resections of appropriate difficulty are selected, an objective preoperative grading of difficulty is required. We aimed to develop a predictive difficulty grading of LS based on intraoperative complications. METHODS: A total of 272 non-traumatic patients who underwent LS were identified from a regional medical center. Patients were randomized into a training cohort (n = 222) and a validation cohort (n = 50). Data on demographics, medical and surgical history, operative and pathological characteristics, and postoperative outcome details were collected. Univariate and multivariate analyses of risk factors for intraoperative complications were performed to develop a difficulty scoring system. The Spearman correlation coefficient was used to evaluate the relationship between the difficulty grading score and intraoperative outcomes. Receiver operating characteristic (ROC) curve was used to evaluate the discriminatory power of this scoring system. RESULTS: Three preoperative factors (spleen weight, esophagogastric varices, and INR) had a significant effect on operative time, bleeding, and conversion to open surgery. We created a difficulty grading score with three levels of difficulty: low (≤ 4 points), medium (5-6 points), and high (≥ 7 points), based on the three preoperative parameters. The correlation was highly significant (P < 0.01) according to Spearman's correlation. The area under the ROC curve was 0.695 (95% CI 0.630-0.755). The external validation showed significant correlations with the present model, with an AUC of 0.725 (95% CI 0.580-0.842). The comparison between our difficulty score and the previous grading system in the 272-patient cohort presented a significant difference in the AUC (0.701, 95% CI 0.643-0.755 vs. 0.644, 95% CI 0.584-0.701, P = 0.0452). CONCLUSION: The present difficulty scoring system, based on preoperative factors, has good performance in predicting the risk of intraoperative complications of LS and could be helpful for enabling appropriate case selection with respect to the current experience of a surgeon.

ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer.

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.

Laparoscopic Magnetic Compression Biliojejunostomy: A Preliminary Clinical Study.

BACKGROUND: Magnetic compression anastomosis is a feasible and effective method for bilioenteric anastomosis (BEA) in animal model. The objective of the present study was to report our initial clinical experience in laparoscopically magnetic compression bilioenteric anastomosis (LMC-BEA). METHODS: Patients with obstructive jaundice who were candidates for LMC-BEA were prospectively enrolled from 2013 to 2015. All the procedures were performed laparoscopically. A mother magnet and drainage tube were placed in the proximal bile duct and tightened by a purse suture after dissection of the common bile duct. The drainage tube was introduced into the jejunal lumen at the anastomotic site and guided a daughter magnet to approximate the mother magnet. The two magnets mated at the anastomotic site. All the patients were routinely followed up for magnets discharge till the end of the study. RESULTS: In total, four patients with malignant obstructive jaundice and one patient with benign biliary stricture were included. The median age was 70 y (range, 49-74 y). The median time for LMC-BEA was 12 min (range, 8-15 min). A complete anastomosis was confirmed after a median time of 21 d (range, 5-25 d) postoperatively by cholangiography via drainage tube. The magnets were expulsed around 41 d after surgery (range, 12-47 d) postoperatively. With a median follow-up of 313 d (range, 223-1042 d), no complications associated with magnetic anastomosis was documented, such as bile leakage or anastomotic stricture. CONCLUSIONS: Magnetic compression is a promising alternate method for laparoscopic BEA. Among the five patients undergoing LMC-BEA, no one developed anastomotic complications.

Magnetic compression anastomosis for biliojejunostomy and pancreaticojejunostomy in Whipple's procedure: An initial clinical study.

BACKGROUND AND AIM: Magnetic anastomosis has been attempted in biliary and intestinal reconstruction. The objective of the current study was to introduce an initial clinical use of magnetic compression anastomosis for pancreaticojejunostomy and biliojejunostomy in Whipple's procedure. METHODS: Patients with peri-ampullary carcinoma and dilated bile and pancreatic ducts were prospectively enrolled from 2016 to 2017. After pancreaticoduodenectomy, an appropriate mother magnet and drainage tube was placed in the proximal bile duct and pancreatic duct. The daughter magnets were introduced to mate with the mother magnets at the anastomotic sites. A close postoperative surveillance and routine cholangiopancreaticography via the drainage tube were performed. RESULTS: One female and three male patients with a median age of 69 years (range, 57-77) were included. The diameter of the common bile ducts and pancreatic ducts ranged from 8 to 15 mm, and 7 to 10 mm, respectively. The median time duration for biliojejunostomy and pancreaticojejunostomy was 7 (range, 5-8 min) min and 9 (range, 8-10 min) min, respectively. The median time of biliojejunostomy and pancreaticojejunostomy formation was 17 (range, 15-21 days) days and 11 (range, 10-18 days), respectively. With a median follow up of 313 days, one patient developed biliary anastomotic stricture at 11 months after surgery, and underwent stent placement via percutaneous transhepatic drainage sinus, and recovered well. CONCLUSIONS: Magnetic anastomosis is safe, effective, and simple for both biliojejunostomy and pancreaticojejunostomy in Whipple's procedure.

Intraoperative Blood Transfusion and Postoperative Morbidity Following Liver Resection.

BACKGROUND Blood transfusion is common during liver resection (LR). The objective of the present study was to investigate the effects of intraoperative transfusion of different blood components on post-LR morbidity. MATERIAL AND METHODS We included 610 patients undergoing LR and grouped them according to intraoperative transfusion of different blood components: packed red blood cells only (PRBC, n=81); frozen fresh plasma, platelets, and cryoprecipitate (FPC, n=38); transfusion only with PRBC + FPC transfusion (n=244); and no blood transfusion (n=247). Propensity score matching (PSM) analysis was used to mitigate selection bias in comparisons. RESULTS The overall blood transfusion rate was 59.5%. In comparison with the no blood transfusion group, PRBC-only and PRBC + FPC transfusion were more common in patients with lower preoperative hemoglobin, worse liver function, larger tumor size, and undergoing a major LR, and thus were associated with increased postoperative morbidity. In contrast, FPC-only transfusion was more frequent in patients with a liver function of Child-Pugh B and lower preoperative albumin vs. the no blood transfusion group. In the propensity model, transfusion of PRBC (PRBC-only and PRBC+FPC) and FPC (FPC-only and FPC+PRBC) were significantly associated with increased postoperative complications vs. the no blood transfusion group (OR and 95% CI, 1.9 [1.2-2.7], p=0.002; OR and 95% CI, 1.6 [1.0-2.4], p=0.029). In contrast, intraoperative PRBC-only or FPC-only transfusion showed no significant adverse effects on postoperative morbidity. CONCLUSIONS Allogenic transfusion of PRBC and FPC blood components was associated with increased postoperative morbidity after liver surgery. Different blood components should be used only when absolutely necessary.

Magnetic Anastomosis for Biliojejunostomy: First Prospective Clinical Trial.

BACKGROUND: Magnetic compression anastomosis (magnamosis, MCA) has been verified safe and effective by us and others in animal bilioenteric anastomosis (BEA). The objective of the present study was to introduce clinical application of magnetic compression bilioenteric anastomosis (MC-BEA) with a unique device in series of patients. METHODS: Patients with obstructive jaundice with an indication of BEA were prospectively enrolled from 2012 to 2015. After dissection of bile ducts, the mother ring and drainage tube were placed in the proximal bile duct and the purse-string suture was tightened over the drainage tube. The drainage tube was introduced into the jejunal lumen at the anastomotic site and used to guide the daughter ring to assemble with the mother ring. All the patients were routinely followed up for magnets discharge or any complications associated. RESULTS: Forty-one patients were included. Thirty-four (82.9%) patients had a malignant primary disease, while seven (17.1%) had benign disease. The median time for MC-BEA was 10.5 min (interquartile range [IQR] 8.3-13.0 min). No perioperative morbidity or mortality associated with MC-BEA was observed. The median time for a patent bilioenteric anastomosis formation was 19.0 days (IQR 14.5-23.0 days), and the magnets were discharged with a median postoperative duration of 35.0 days (IQR 28.0-43.0 days). With a median follow-up of 547.5 days (range 223-1042 days), no patients had biliary fistula, while two (4.9%) developed anastomotic stricture at 4 months and 14 months after surgery, and underwent reoperation for reconstruction of BEA. CONCLUSIONS: MCA is a safe, effective, and time-saving modality for biliojejunostomy.

Perioperative outcome of elderly versus younger patients undergoing major hepatic or pancreatic surgery.

OBJECTIVE: The aim of this study was to determine the safety of elderly cancer patients (≥70 years) undergoing hepatic resection (HR) or pancreaticoduodenectomy (PD) in comparison with younger adults (<70 years). METHODS: A total of 1,012 consecutive patients undergoing HR or PD were included. The incidence and severity of morbidity were documented within 30 days postoperatively and compared between elderly and younger groups. Risk factors associated with postoperative morbidity were investigated by multivariate logistic regression analysis. RESULTS: Elderly patients (n=111, 11.0%) had more comorbidities and worse preoperative general condition and liver function versus younger patients (n=901, 89.0%), and thus were more likely to develop infectious (eg, systemic sepsis and urinary tract infection, both p<0.01) and technical-associated complications (intraperitoneal bleeding and biliary/pancreatic fistula, p=0.029 and p=0.074, respectively). However, the incidence and severity of complications were comparable between elderly and younger patients in the whole cohort, and also in HR and PD surgery groups separately. Preoperative hemoglobin (odds ratio [OR] 1.4, p=0.007) and intraoperative blood transfusion (OR 1.9, p=0.002), rather than age, were independently associated with postoperative morbidity. Hepatitis (OR 2.9, p=0.001), preoperative hemoglobin (OR 1.6, p=0.036), and pancreatic versus hepatic surgery (OR 2.3, p=0.005) were independently associated with postoperative infectious. For elderly patients only, American Society of Anesthesiologists (ASA) score III (OR 2.1, p=0.033) and intraoperative blood transfusion (OR 3.2, p=0.030) were independently associated with postoperative morbidity. CONCLUSION: HR and PD can be safely performed in selected elderly patients versus younger patients. Elderly patients with ASA score III or above should be cautiously selected for major surgeries.

Longikaurin A, a natural ent-kaurane, suppresses stemness in nasopharyngeal carcinoma cells.

Cancer stem cells (CSCs) are a small proportion of tumor cells that may be responsible for tumor metastasis and recurrence. Our recent research indicated that longikaurin A (LK-A) exhibited anti-tumor activity in nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Here, we further investigated whether LK-A could suppress the stemness of NPC cells. Sphere formation assay was used to assess the self-renewal ability of the cells treated with LK-A. Side population (SP) was determined by flow cytometry to measure the influence of LK-A on NPC SPs. The expression of the c-myc and fibronectin was detected by western blotting. The cytotoxicity of LK-A in combination with cisplatin to NPC cells was determined by MTT assay. Colony formation assay was used to verify whether LK-A could sensitize NPC cells to radiation and reverse the radiotherapy resistance. In the present study, we found that LK-A reduced the number and size of spheroid formation and decreased the SP cell percentage of the S18 cell line at a low concentration. Furthermore, LK-A treatment downregulated the expression of c-myc and fibronectin in NPC cell lines. Moreover, LK-A could significantly enhance the chemotherapeutic and radiotherapeutic sensitivity of NPC cell lines and reverse acquired radiotherapy resistance of Sune2-IR. Our data revealed that LK-A could suppress the stemness of NPC cells and may enhance the efficacy of radiotherapy and chemotherapy.

Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis.

AIM: To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis (HLAP). METHODS: A total of 863 patients were admitted to our hospital for acute pancreatitis (AP) from January 2013 to March 2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During follow-up, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test. RESULTS: No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP (50.0% and 77.8%, respectively) than non-smokers (9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23 (26.1%) patients. Multivariate analysis identified current smoking (HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers (23 mo vs 42 mo), but no significant difference was documented between ex-smokers (34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers. CONCLUSION: Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.

Operation Start Times and Postoperative Morbidity from Liver Resection: A Propensity Score Matching Analysis.

BACKGROUND: Surgeons are likely to get progressively fatigued and work less effectively during the course of a normal workday. We sought to examine the effects of surgery start times (morning vs. afternoon) and workload of the surgeons on morbidity of patients after partial liver resection (LR). METHODS: A total of 155 pairs of the patients from 383 patients undergoing LR were generated by propensity score analysis (PSM) according to the start times of surgery: group M (morning surgery, 8 a.m.-1 p.m.) and group A (afternoon surgery, 1 p.m.-6 p.m.). Patients in group A were further divided depending on whether or not the surgeons had performed other surgeries earlier in the day and the exact duration of the other surgeries before the afternoon surgery (≤180 and >180 min). The incidence and severity of postoperative complications were compared between different groups. RESULTS: By using PSM analysis, the patients in group M and group A were well matched in basic characteristics. The incidence and severity of the postoperative complications were similar between the two groups (all p > 0.05). Whether the surgeons had performed other surgeries prior to the afternoon surgery seemed not affecting the postoperative outcome (all p > 0.05). Moreover, the duration of other surgeries the surgeons had performed did not have significant influence on the outcome of patients undergoing afternoon surgery (all p > 0.05). CONCLUSIONS: Surgery start times and workload of surgeons during working time did not measurably affect short-term outcomes of the patients. The negative findings might be a manifestation of professional judgment and self-regulation of the experienced physicians.

Mass Continuous Suture versus Layered Interrupted Suture in Transverse Abdominal Incision Closure after Liver Resection.

BACKGROUND: Abdominal incision closure technique seriously influences patient prognosis. Most studies have focused on the different suture techniques and materials on midline incision, while little data are available in wide transverse or oblique incisions after liver resection (LR). The aim of the present study is to compare the two major incision suture methods after LR in our institute: Mass continuous suture (group P) and layered interrupted suture (group S). STUDY DESIGN: 258 patients undergoing LR with abdominal transverse or oblique incisions were prospectively enrolled. They were divided into two groups according to different abdominal incision suture methods and compared with the preoperative, intraoperative parameters, and postoperative wound complications. RESULTS: There were 118 patients in group P and 140 patients in group S, which was similar in general condition, primary disease, liver, and renal function. Incision length, total operation time, intraoperative blood loss, or perioperative antibiotics use were not different between the two groups. However, abdominal incision closure time and interval time for stitches removing after operation was significantly shorter in group P than group S (both p < 0.001). After a median follow-up of 16 months, the incidence of wound infection and fat liquefaction was more than two times higher in group S than group P, which, however, was not statistically different. Moreover, there was no difference in wound disruption or incisional hernia between the two groups. CONCLUSIONS: Although similar in occurrence of postoperative wound complications, mass continuous suture with polydioxanone seemed to be more timesaving in incision closure and motivated in wound healing.