Beneficial effect of splenic artery ligation on bacterial translocation after major liver resection in rats.

OBJECTIVE: In major liver resection, bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infection. This study was designed to investigate the effects of splenic artery ligation on bacterial translocation after major liver resection. MATERIALS AND METHODS: Rats were divided into three groups: the sham operation group (SO group), the two-thirds partial hepatectomy group (PHx group) and the two-thirds partial hepatectomy plus splenic artery ligation group (PHx+Sp group). Bacterial translocation, endotoxemia, d-lactic acid and intestinal histology were analyzed among three groups. RESULTS: The rate of bacterial translocation was higher in the PHx rats than in the SO rats (65.0% vs. 6.67%; P=0.001), so that in the PHx+Sp rats (25.0%; P=0.011). Endotoxemia was not evident in the SO rats (0pg/ml) and blood endotoxin levels decreased in the PHx+Sp rats (1.47pg/ml) compared with the PHx rats (4.05pg/ml, P<0.001). d-lactic acid was also higher in both the PHx and PHx+Sp rats compared with the SO rats (39.09mg/ml, 23.36mg/ml, and 1.68mg/ml; P<0.01). CONCLUSION: Splenic artery ligation enhanced intestinal barrier function and diminished blood endotoxin levels and bacterial translocation in rats with major liver resection.

Diagnosis and management of acute variceal bleeding: Asian Pacific Association for Study of the Liver recommendations.

BACKGROUND: Acute variceal bleeding (AVB) is a medical emergency and associated with a mortality of 20% at 6 weeks. Significant advances have occurred in the recent past and hence there is a need to update the existing consensus guidelines. There is also a need to include the literature from the Eastern and Asian countries where majority of patients with portal hypertension (PHT) live. METHODS: The expert working party, predominantly from the Asia-Pacific region, reviewed the existing literature and deliberated to develop consensus guidelines. The working party adopted the Oxford system for developing an evidence-based approach. Only those statements that were unanimously approved by the experts were accepted. RESULTS: AVB is defined as a bleed in a known or suspected case of PHT, with the presence of hematemesis within 24 h of presentation, and/or ongoing melena, with last melanic stool within last 24 h. The time frame for the AVB episode is 48 h. AVB is further classified as active or inactive at the time of endoscopy. Combination therapy with vasoactive drugs (<30 min of hospitalization) and endoscopic variceal ligation (door to scope time <6 h) is accepted as first-line therapy. Rebleeding (48 h of T (0)) is further sub-classified as very early rebleeding (48 to 120 h from T (0)), early rebleeding (6 to 42 days from T (0)) and late rebleeding (after 42 days from T (0)) to maintain uniformity in clinical trials. Emphasis should be to evaluate the role of adjusted blood requirement index (ABRI), assessment of associated comorbid conditions and poor predictors of non-response to combination therapy, and proposed APASL (Asian Pacific Association for Study of the Liver) Severity Score in assessing these patients. Role of hepatic venous pressure gradient in AVB is considered useful. Antibiotic (cephalosporins) prophylaxis is recommended and search for acute ischemic hepatic injury should be done. New guidelines have been developed for management of variceal bleed in patients with non-cirrhotic PHT and variceal bleed in pediatric patients. CONCLUSION: Management of acute variceal bleeding in Asia-Pacific region needs special attention for uniformity of treatment and future clinical trials.

Experimental study of pancreaticojejunostomy completed using anastomotic chains.

The most difficult, time-consuming, and complication-prone step in pancreaticoduodenectomy is the pancreaticojejunostomy step. The largest disadvantage of this kind of anastomosis is the high incidence of postoperative anastomotic leakage. Once pancreatic leakage occurs, the patient death rate can be very high. The aim of this study was to design a pancreaticojejunostomy procedure using anastomotic chains, which results in the cut end of the jejunum being attached to the pancreatic stump without suturing, and to evaluate the safety and efficacy of this procedure in domestic pigs. The pancreaticojejunal anastomotic chains had the following structures: the chains consisted of two braceletlike chains made of titanium, named chain A and chain B. The function of chain A was to attach the free jejunal end onto the pancreatic stump, whereas the function of chain B was to tighten the contact between the jejunal wall and the surface of the pancreatic stump to eliminate gaps between the two structures and ensure tightness that is sufficient to guarantee that there is no leakage of jejunal fluid or pancreatic juice. The following procedure was used to assess the safety and efficacy of the procedure: pancreaticojejunostomies were performed on ten domestic pigs using anastomotic chains. The time required to complete the pancreaticojejunal anastomoses, the pressure tolerance of the pancreaticojejunal anastomoses, the pig death rate, and the histopathological examinations of the pancreaticojejunostomy tissues were recorded. The average time required to complete the pancreaticojejunal anastomosis procedure was 13+/-2 min. The observed tolerance pressure of the pancreaticojejunal anastomoses was more than 90 mm H(2)O. All ten domestic pigs that underwent operations were still alive four weeks after the operations. Pathological examinations showed that the anastomotic surfaces were completely healed, and the pancreatic cutting surfaces were primarily epithelialized. In conclusion, the use of anastomotic chains in pancreaticojejunostomy procedures results in a decrease in or elimination of pancreatic leakage. In addition, the procedure is simple to perform, is not time-intensive, and appears to be safe in a pig model.

Ultrasound-guided percutaneous microwave coagulation therapy with a "cooled-tip needle" for the treatment of hepatocellular carcinoma adjacent to the gallbladder.

BACKGROUND: Curative percutaneous microwave coagulation therapy is difficult or contraindicated in patients with tumors adjacent to the gallbladder because of the associated risk of injury. To date, no clinical data have been published regarding the effects and safety of percutaneous microwave coagulation therapy on tumors that are adjacent to the gallbladder. AIMS: We investigated the efficacy and safety of a combined treatment involving laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy in patients with hepatocellular carcinoma adjacent to the gallbladder. METHODS: Twenty-three patients with hepatocellular carcinoma nodules (of less than 5 cm diameter) and adjacent to the gallbladder were treated by percutaneous microwave coagulation therapy with a "cooled-tip needle" after laparoscopic cholecystectomy. The therapeutic efficacy was evaluated with enhanced helical computed tomography and sonography, and the rates of complete necrosis as well as postoperative complications were also analyzed. RESULTS: All of the patients exhibited complete necrosis of their tumor lesions after treatment with percutaneous microwave coagulation therapy. During the follow-up period (which lasted more than 21 months), 22 of 23 patients were alive. Recurrent nodules appeared in other subsegments, but not at the original site treated with percutaneous microwave coagulation therapy. Of note, no fatal complications were observed in any of the patients treated with percutaneous microwave coagulation therapy. CONCLUSION: Our results suggest that combined treatment comprising both laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy is an effective and safe approach for patients with small (<5 cm) hepatocellular carcinomas that are adjacent to the gallbladder.

Deficient proliferation of bone marrow-derived mesenchymal stem cells in patients with chronic hepatitis B viral infections and cirrhosis of the liver.

In this study, we determined whether the proliferation of bone marrow-derived mesenchymal stem cells (MSCs) is impaired in patients with chronic hepatitis B viral infection and cirrhosis of the liver. MSCs from 15 patients with chronic hepatitis B and cirrhosis of the liver (CIR-MSCs) and 11 normal donors (ND-MSCs) were collected and characterized in vitro. CIR-MSCs displayed an intact immunophenotype. The percentage of S-phase nuclei in CIR-MSCs (4.34%), however, was significantly lower than that in ND-MSCs (P < 0.001), indicating impaired proliferation of CIR-MSCs. Growth factor receptor expression (e.g., IGF1, PDGFalpha, and PDGFbeta) on the surface of CIR-MSCs decreased compared to that on ND-MSCs (P < 0.03). We found no evidence that CIR-MSCs were infected with the hepatitis B virus (HBV). Deficient proliferation of CIR-MSCs may result from the decreased expression of growth factor receptors and unbalanced production of cytokines in patients with HBV infection. Our results indicate that autologous MSCs of patients with chronic hepatitis B and cirrhosis of the liver may not be suitable for therapeutic purposes.

A novel canine model of esophageal varices with a balloon dilatation constrictor.

BACKGROUND AND OBJECTIVE: The canine model of esophageal varices with an agar constrictor has been used for studies of the endoscopic treatment of esophageal variceal bleeding, but it has limitations in both stability and successful rate. This study was designed to enhance the model's efficiency and success rate by using a novel approach with a balloon dilatation constrictor. METHODS: We used 22 adult mongrel dogs to establish the model by progressively compressing and constricting the portal vein through a rechargeable balloon dilatation constrictor in combination with side-to-side portocaval shunt and inferior vena cava (IVC) ligation to increase portal vein pressure (PVP). The rechargeable balloon dilatation constrictor was composed of a hyaline polypropylene (PP) ring, a silica gel tube with a balloon, and an injection pedestal (silica gel) in an implantable vascular access port. The effects were evaluated with pre- and post-shunt PVP measurement, weekly gastroscopy, and portocaval venography. RESULTS: The mean PVP increased significantly from a preoperative (before side-to-side portocaval shunt and IVC ligation) 12.86 +/- 0.18 cmH(2)O to 26.75 +/- 0.39 cmH(2)O after the model had been established (P < 0.05). After the model was established, gastroscopy performed to assess esophageal varix size demonstrated four varicose veins of grade I, six of grade II, eight of grade III and four of grade IV. The portocaval angiography showed that the IVC and portal vein were completely blocked, that the anastomosis stoma was unobstructed and that the blood flow through esophageal varices via splenetic and gastric veins was blocked. CONCLUSION: The novel canine model developed with a rechargeable balloon dilatation constrictor is feasible and reliable for modeling esophageal varices.

Predictive value of D-dimer for portal vein thrombosis after portal hypertension surgery in hepatitis B virus-related cirrhosis.

AIM: To evaluate the predictive value of D-dimer as a predictive indicator of portal vein thrombosis (PVT) after portal hypertension surgery in hepatitis B virus-related cirrhosis. METHODS: A prospective study was carried out in 52 patients who had undergone surgery for portal hypertension in hepatitis B virus-related cirrhosis. Changes in perioperative dynamic D-dimer were observed. The sensitivity, specificity, positive predictive values and negative predictive values of D-dimer were calculated, and ROC curves were analyzed. RESULTS: The D-dimer levels in the group developing postoperative PVT was significantly higher than those in the group not developing PVT (P = 0.001), and the ROC semiquantitative and qualitative analysis of D-dimer showed a moderate predictive value in PVT (semi-quantitative value Az = 0.794, P = 0.000; qualitative analysis: Az = 0.739, P = 0.001). CONCLUSION: Dynamic monitoring of D-dimer levels in patients with portal hypertension after surgery can help early diagnosis of PVT, as in cases where the D-dimer levels steadily increase and exceed 16 microg/mL, the possibility of PVT is very high.

Contribution of mononuclear bone marrow cells to carbon tetrachloride-induced liver fibrosis in rats.

AIM: To study the inhibitory effect of mononuclear bone marrow cell (BMC) transplantation on carbon tetrachloride (CCl(4)) -induced liver fibrosis in rats. METHODS: Rat liver fibrosis models were induced by CCl(4) and alcohol administration. After 8 wk, twenty rats were randomly allocated into treatment group (n = 10) and control group (n = 10). BMC were infused into the rats in treatment group via the portal vein, while heparinized saline was infused in control group. CCl(4) was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12, all rats were humanely sacrificed. Liver samples were taken and stained with HE or Masson trichrome. The general conditions, liver fibrosis (hydroxyproline and collagen fibre) and liver pathological grades in rats were evaluated. RESULTS: The general conditions of the rats in treatment group improved markedly, but not in control group. Hydroxyproline was 504.6 +/- 128.8 microg/g in treatment group, and 596.0 +/- 341.8 microg/g in control group. The percentage of collagen fibre was 3.75% +/- 0.98% in treatment group and 5.02% +/- 0.44% in control group. There was a significant difference between the two groups (P < 0.05). Liver pathological grade decreased from grade IV to grade III partially in treatment group (P < 0.05) with no obvious improvement in control group (P > 0.05). There was a significant difference between treatment group and control group (P < 0.05). CONCLUSION: Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.

Glutamine and recombinant human growth hormone protect intestinal barrier function following portal hypertension surgery.

AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery. METHODS: This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gln and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-alpha and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7 +/- 5.5 vs 31.0 +/- 5.4, P < 0.05, (1.17 +/- 0.32 vs 1.05 +/- 0.15, P < 0.05, 13.94 +/- 1.09 vs 12.33 +/- 1.33, P < 0.05, and 368.12 +/- 59.25 vs 318.12 +/- 45.65, P < 0.05, respectively), whereas the increase in serum TNF-alpha concentration was significantly reduced (41.02 +/- 27.56 vs 160.09 +/- 35.17, P < 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 +/- 0.0017 vs 0.0339 +/- 0.0028, P < 0.05). Moreover, mucosal integrity in the supplemental group was better than in the control group. CONCLUSION: Postoperative administration of TPN supplemented with Gln and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.

Splenectomy with endoscopic variceal ligation is superior to splenectomy with pericardial devascularization in treatment of portal hypertension.

AIM: To investigate the therapeutic efficacy and complications of splenectomy with endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization (i.e. Hassab's operation) in patients with portal hypertension. METHODS: A total of 103 patients with liver cirrhosis and portal hypertension were randomly selected to receive either splenectomy with EVL (n = 53, group A) or Hassab's operation (n = 50, group B). RESULTS: The portal blood flow volume, the presence of portal vein thrombosis, gastric emptying time and free portal venous pressure (FPP) before and after the operation were determined. Patients were followed up for up to 64 mo with an average of 45 mo, and the Dagradi classification of variceal veins and the grading of portal hypertension gastropathy (PHG) were evaluated. It was found that all esophageal varices were occluded or decreased to grade II or less in both groups. There was little difference in the recurrence rate of esophageal varices (11.9% vs 13.2%) and the re-bleeding rate (7.1% vs 5.3%) between groups A and B. The incidence of complications and the percentage of patients with severe PHG after the operation were significantly higher in group B (60.0% and 52.0%) than in group A (32.1% and 20.8%, P < 0.05). No patients died of operation-related complications. There was no significant difference in gastric emptying time, FPP and portal blood flow volume between the two groups. CONCLUSION: The results suggest that splenectomy with EVL achieves similar therapeutic efficacy to that of Hassab's operation in terms of the recurrence rate of esophageal varices and the re-bleeding rate, but the former results in fewer and milder complications.

Evaluation of the effects of combined endoscopic variceal ligation and splenectomy with pericardial devascularization on esophageal varices.

AIM: To detect the hemodynamic alterations in collateral circulation before and after combined endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization by ultrasonography, and to evaluate their effect using hemodynamic parameters. METHODS: Forty-three patients with esophageal varices received combined EVL and splenectomy with pericardial devascularization for variceal eradication. The esophageal vein structures and azygos blood flow (AZBF) were detected by endoscopic ultrasonography and color Doppler ultrasound. The recurrence and rebleeding of esophageal varices were followed up. RESULTS: Patients with moderate or severe varices in the esophageal wall and those with severe peri-esophageal collateral vein varices had improvements after treatment, while the percentage of patients with severe para-esophageal collateral vein varices decreased from 54.49% to 2.33%, and the percentage of patients with detectable perforating veins decreased from 79.07% to 4.65% (P < 0.01). Color Doppler flowmetry showed a significant decrease both in AZBF (43.00%, P < 0.05) and in diameter of the azygos vein (28.85%, P < 0.05), while the blood flow rate was unchanged. The recurrence rate of esophageal varices was 2.5% (1/40, mild), while no re-bleeding cases were recorded. CONCLUSION: EVL in combination with splenectomy with pericardial devascularization can block the collateral veins both inside and outside of the esophageal wall, and is more advantagious over splenectomy in combination with pericardial devascularization or EVL in preventing recurrence and re-bleeding of varices.

[Effects of different treatment complex on esophageal vascular structures in patients with portal hypertension].

OBJECTIVE: To assess the effects of different treatment complex on esophageal vascular structures in patients with portal hypertension. METHODS: Patients (142 cases) with esophageal varices received either endoscopic variceal ligation (EVL) alone (54 cases), pericardial devascularization procedure (PDP) alone (23 cases), a combination of EVL and partial splenic embolization (PSE) (34 cases), or a combination of EVL and PDP (31 cases) for variceal eradication. Esophageal vascular structures were examined with miniature ultrasonic probe. The recurrence and rebleeding of esophageal varices were investigated. RESULTS: Esophageal submucous varices were obliterated and collateral veins remained unchanged in patients treated by EVL or EVL combined with PSE; esophageal submucous varices were diminished in size and collateral veins were obliterated by PDP, and both esophageal submucous varices and collateral veins were obliterated by the combination of EVL and PDP. CONCLUSIONS: The combination of EVL and Hassab's procedure can effectively shut off the portoazygous shunt, prevent esophageal varices from bleeding and recurrence. It's a simply and less cost procedure.

Therapeutic effects of endoscopic variceal ligation combined with partial splenic embolization for portal hypertension.

AIM: To evaluate the feasibility of a new strategy of endoscopic variceal ligation combined with partial splenic embolization (EVL-PSE) for patients with cirrhosis and portal hypertension. METHODS: From May 1999 to May 2002, 41 cases with cirrhosis and portal hypertension underwent EVL-PSE. Hemodynamics of the main portal vein (MPV), the left gastric vein (LGV) and azygos vein, including maximum velocity, flow rate and vein diameter, were assessed by Doppler ultrasonography. RESULTS: One case died from pulmonary artery embolism. One case complicated with splenic abscess was successfully managed by laparotomy. The esophageal varices and hypersplenism were well controlled after EVL-PSE in other patients. After EVL-PSE, the flow rate and velocity of MPV was significantly reduced (P<0.05), as well as the flow rate of the LGV and azygos vein. During the follow-up, no recurrent bleeding was found. CONCLUSION: Being more convenient and less invasive, EVL-PSE is hopeful to be a proper intervention strategy for portal hypertensive patients with impaired hepatic function or those intolerant to shunting or devascularization surgery.

[Splenectomy combined with endoscopic variceal ligation in treating portal hypertension].

OBJECTIVE: To investigate the therapeutic effect of endoscopic variceal ligation (EVL) combined with splenectomy on patients with portal hypertension. METHODS: The eliminating rate of varicose veins and recurrent bleeding rate were evaluated. Fifty-one paitents with cirrhosis of liver and portal hypertension were randomly divided into 2 groups. We treated 25 portal hypertensive patients using splenectomoy plus EVL. The therapeutic effect of pericardial devascularization in 26 patients with upper gastrointestinal bleeding due to portal hypertension served as the control. RESULTS: All patients were followed up for 12 months. There was no death due to the operation. All patients in the study group had no upper gastrointestinal rebleeding during the 12-month follow-up. The rebleeding rate in the control group was 11.5% (3/26). The varicose venis eliminating rate was 96% (24/25) in the study group and 50% (13/26) in the control group (P < 0.01). It showed no effect on portal hypertensive gastropathy in the study group, and pericardial devascularization procedure exacerbated the portal hypertensive gastropathy. The thrombosis rate in the portal vein after the operation was 8% (2/25) in the study group and 34.6% (9/26) in the control group (P < 0.05). CONCLUSION: EVL combined with splenectomy has less trauma, fewer postoperative complications and high eradication of esophageal varices. It can be used safely in treating portal hypertension.

[Treatment of portal hypertension by endoscopic esophageal ligation of varicose veins combined with partial splenic embolization].

OBJECTIVE: To evaluate the feasibility and efficacy of a new method of endoscopic esophageal variceal ligation combined with partial splenic embolization (EVL-PSE) for the patients with portal hypertension. METHODS: From May 1999 to February 2003, sixty-eight patients with portal hypertension underwent EVL-PSE, and hemodynamics of the portal trunk (PT), the left gastric vein and azygos vein, including maximum velocity, flow volume, vein diameter, were assessed using color ultrasound Doppler. RESULTS: The esophageal varices and hypersplenism were greatly ameliorated after operation in patients who had undergone EVL-PSE. Postoperative portal trunk flow volume and velocity were significantly reduced (P < 0.05), and flow volume of the left gastric vein as well as the azygos vein were also reduced after operation. During 2 - 24-month follow-up, no recurrent bleeding was found. CONCLUSIONS: EVL-PSE is less traumatic with less complications, and results in marked eradication of esophageal varices, it can be carried out safely in the clinical treatment for patients with portal hypertension.