A stable rat model of obstructive jaundice reversed by internal bile drainage using microsurgical techniques / 中国现代普通外科进展

Objective:To better understand the pathogenesis of obstructive jaundice (O J),a variety of rat OJ and biliary drainage models have been tried;however,complications are still common.We aimed to establish a stable rat model of OJ using microsurgical techniques,and to assess its reversal by internal bile drainage(IBD).Methods:After the pilot study,we developed a standardized surgical procedure.All operations were carried out under an operating microscope.In the first laparotomy,the proximal common bile duct (CBD) of the rat was ligated and transected.A tube was introduced into the distal end of the duct,and the other end of the tube was sealed and fixed.In the second laparotomy,the drainage tube was inserted into the (by now markedly dilated) proximal CBD,and ligated into position.We evaluated the general condition of the rats,the status of the liver and pancreas before and after IBD.Results:Complications such as intestinal reflux and bile duct blockage,were not found.Pancreatic injury was not evident by day 4 after the first laparotomy.After biliary drainage,the serum glucose and albumin concentration rapidly returned to normal levels.Liver weight/body weight ratio increased.The biochemical indicators and ultrasonographic elastography results for the liver gradually returned to normal.Conclusion:Using microsurgical techniques,we have developed a stable rat model of OJ reversed by IBD.

A simple rat model of in situ reversible obstructive jaundice in situ reversible obstructive jaundice model

PURPOSE: To develop a simple and reliable rat model of in situ reversible obstructive jaundice with low morbidity and mortality rates. METHODS: Rats were divided into 4 groups with 8 rats each: the sham-operated (SH) group only underwent laparotomy, the control internal drainage (ID-C) group underwent choledochoduodenostomy, the new internal drainage (ID-N) group and the long-term internal drainage (ID-L) group underwent choledochocholedochostomy. Common bile duct ligation was performed in all the drainage groups 7 days before reversal procedures. All rats were sacrificed for samples 7 days after the last operation except rats of the ID-L group that survived 28 days before sacrifice. Body weight, liver function, histopathological changes, morbidity and mortality were assessed. RESULTS: One rat died and 2 rats had complications with tube blockage in the ID-C group. No death or complications occurred in the ID-N and ID-L groups. The drainage tube remained patent in the long-term observation ID-L group. Body weight showed no significant difference between the ID-C and ID-N groups after 7 days drainage. Liver function was not fully recovered in the ID-C and ID-N groups after 7 days drainage, but statistical differences were only observed in the ID-C group compared with the SH and ID-L groups. Periportal inflammation and bile duct proliferation showed severer in the ID-C group than in the ID-N group. CONCLUSION: The present study provided an efficient, simple, and reliable rat model that is especially suitable for long-term or consecutive studies of reversible obstructive jaundice.

A simple rat model of in situ reversible obstructive jaundice in situ reversible obstructive jaundice model

PURPOSE: To develop a simple and reliable rat model of in situ reversible obstructive jaundice with low morbidity and mortality rates. METHODS: Rats were divided into 4 groups with 8 rats each: the sham-operated (SH) group only underwent laparotomy, the control internal drainage (ID-C) group underwent choledochoduodenostomy, the new internal drainage (ID-N) group and the long-term internal drainage (ID-L) group underwent choledochocholedochostomy. Common bile duct ligation was performed in all the drainage groups 7 days before reversal procedures. All rats were sacrificed for samples 7 days after the last operation except rats of the ID-L group that survived 28 days before sacrifice. Body weight, liver function, histopathological changes, morbidity and mortality were assessed. RESULTS: One rat died and 2 rats had complications with tube blockage in the ID-C group. No death or complications occurred in the ID-N and ID-L groups. The drainage tube remained patent in the long-term observation ID-L group. Body weight showed no significant difference between the ID-C and ID-N groups after 7 days drainage. Liver function was not fully recovered in the ID-C and ID-N groups after 7 days drainage, but statistical differences were only observed in the ID-C group compared with the SH and ID-L groups. Periportal inflammation and bile duct proliferation showed severer in the ID-C group than in the ID-N group. CONCLUSION: The present study provided an efficient, simple, and reliable rat model that is especially suitable for long-term or consecutive studies of reversible obstructive jaundice.

Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery.</p><p><b>METHODS</b>The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery.</p><p><b>RESULTS</b>The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively.</p><p><b>CONCLUSION</b>The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.</p>

Effect of leukoreduction on tumor-associated cytokine accumutation in supernatant of stored packed red cells and its effect on tumor cell proliferation in vitro / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate whether prestorage leukoreduction could decrease the accumulative concentration of tumor-associated cytokines in supernatant of stored packed red blood cells (pRBC) and to study the effect of prestorage leukoreduction on proliferation of HepG2 tumor cells by in vitro. The leukoreduced (LR) and non-leukoreduced (NLR) pRBC were equally obtained from one donation and were stored under 2 °C-6°C. The supernatants of pRBC in these two group were performed by centrifugation with 1 006×g for 10 min at day 0 and 35 d. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of normal T cells and secretory factor (RANTES/CCL5), as well as the accumulative concentrations of tumor-necrosis factor (TNF-α), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) in pRBC supernantant of above-mentioned two groups. After HepG2 cells was cultured with the supernatant of NLR-pRBC and LR-pRBC at the end of day 35 together for 48 hours, the methyl thiazolil tetracolium (MTT) method was used to measure the proliferation of tumor cells in vitro.</p><p><b>RESULTS</b>The accumulative concentration of 5 cytokines in supernatants of above menthioned two groups increased in different degrees along with the prolongation of storage time,that is, the accumulative concentrations of 5 cytokines at 35 d were higher than that at day 0, in which the change of VEGF accumu-lative concentration showed statistical significance, its accumulative concentration in NLR group at day 35 elevated to 549.61 ± 299.43 pg/ml, and was higher than that in LR group (95.46 ± 110.87 pg/ml) (P < 0.05). The experiment of HepG2 cell proliferation indicated that the supernatant of LR pRBC group produced less proliferation of tumor cells with OD value 0.40 (95% CI, 0.38-0.42) than that of NLR pRBC group with OD value 0.49 (95% CI, 0.43-0.55) (P < 0.05).</p><p><b>CONCLUSION</b>The prestorage leukoreduction has been confirmed to decrease the accumulative level of cytokines, particalarly decrease the accumulative level of VEGF, moreover, it may be a factor for inhibiting the proliferation of tumor cells in vitro.</p>

Effect of Storage Time on Cumulation of Platelet-related Growth Factors in the Supernatant of Leukoreduced Packed Red Cells and Tumor Cell Proliferation In Vitro / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of storage time on accumulation of platelet-related growth factors in the supernatant of leukoreduced packed red blood cells (LR-pRBC) and on tumor cell proliferation in vitro.</p><p><b>METHODS</b>LR-pRBC were quartered and stored at 2 °C-6 °C. The supernatant of pRBC was obtained by centrifugation with 1 006 × g for 10 min at day 0, 14, 21 and 35 d. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of platelet-derived growth factor(PDGF) and vascular endothelial growth factor (VEGF). After HepG2 cells was cultured with the supernatant of LR pRBC at day 0 and day 35 together for 48 hours, methylthiazoliltetracolium (MTT) method was used to measure the proliferation of tumor cells in vitro.</p><p><b>RESULTS</b>The concentrations of 2 cytokines were still increased with the storage time prolonging. As compared to LR-pRBC at day 0 [611.84 (95%CI, 356.45-867.23) pg/ml], the level of VEGF reached 900.16 (95% CI, 552.26-1248.07) pg/ml (P<0.05). There was a similar tendency in PDGF level with less increment in the supernatant of LR pRBC at day 35 [2.23 (95% CI, 0-5.37) ng/L vs 5.66 (95% CI, 0-12.48), P=0.073], but there was no significant statistical difference. Likewise, in vitro study of HepG2 cell proliferation showed that the LR-pRBC at day 35 promoted more proliferation of tumor cells with OD value 0.40 (95% CI, 0.38-0.42) (P<0.05).</p><p><b>CONCLUSION</b>The residual platelets in LR-pRBC were activated, disintegrated and released the dense granules and α-granules which induce the accumulation of VEGF and PDGF. It seemed that the supernatant of LR-pRBC promoted the proliferation of tumor cells in vitro.</p>

Transient hepatic venous occlusion induced liver hemodynamic change and reperfusion injury in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the hemodynamic change and reperfusion injury cause by transient hepatic venous occlusion and transient hepatic inflow occlusion in rats.</p><p><b>METHODS</b>The rat liver was divided into 3 different areas: the ischemia reperfusion (IR) area: the inflow of the right superior lobe was clamped for half an hour; the non-isolated lobe congestive reperfusion (NIL-CR) area: the outflow of the right median lobe was clamped for half an hour; and the isolated lobe congestive reperfusion (IL-CR) area: the outflow of the left lobe was clamped for half an hour. The flux value and the oxygen saturation of microcirculation were monitored before at clamping for 30 minutes, and on 1 day, 3 days ,and 7 days after reperfusion. The hepatic damage and Suzuki's score were evaluated.</p><p><b>RESULTS</b>After clamping for 30 minutes, the flux value in the IR area was significantly higher than in NIL-CR area (P<0.01) and IL-CR area (P<0.01), the oxygen saturation in the IR area was significantly higher than in NIL-CR area (P<0.01) and IL-CR area (P<0.05). Compared with IR area, both NIL-CR area and IL-CR area were found having more severe liver damage in terms of Suzuki's score in early postoperative period (at clamping for 30 minutes and on 1 day, P<0.01). However, there was no significant difference between NIL-CR area and IL-CR area in flux value, oxygen saturation, and Suzuki's score (P>0.05).</p><p><b>CONCLUSIONS</b>Hepatic venous occlusion can more effectively decrease the blood perfrusion and oxygen saturation; thus, compared to the IR, CR can result in more severe liver damage. The presence of normal liver tissue around the congestion area can not influence liver damage in transient hepatic venous occlusion.</p>

Effects of different hepatic inflow occlusion methods on liver regeneration following partial hepatectomy in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of different hepatic inflow occlusion methods on liver regeneration in rats after partial hepatectomy (PH).</p><p><b>METHODS</b>Male Wistar-Furth rats were randomly assigned to three groups: control group, underwent 68% hepatectomy alone; occlusion of portal triad (OPT) group, subjected to occlusion of portal triad under portal blood bypass; and occlusion of portal vein (OPV) group, subjected to occlusion of portal vein under portal blood bypass. Blood flow was occluded for 20, 30, and 40 minutes before 68% hepatectomy. According to the 7-day survival of each group, a same occlusion time T was set. Each group was divided into two subgroups (n = 8), in which animals were killed 3 and 7 days later. Liver regeneration was calculated as a percent of initial liver weight. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki-67 was performed to quantify proliferating cells. In addition, functional liver volume represented by 99Tc(m)-GSA radioactivity was assessed.</p><p><b>RESULTS</b>The safe tolerance limit time was 30 minutes for OPT group and 40 minutes for OPV group. At 3 days after PH, no significant difference was observed in the regeneration rate of each group (P > 0.05). However, liver radioactive activity, PCNA labeling index, and Ki-67 index of OPV group was significantly higher than those of OPT group (P < 0.05); the latter were similar to those of control group (P > 0.05). At 7 days after PH, no significant difference was observed in all indexes among three groups (P > 0.05).</p><p><b>CONCLUSION</b>Compared with Pringle maneuver, preserving the hepatic artery flow during portal triad blood inflow occlusion can promote remnant liver regeneration early after PH.</p>

Metabolic disturbance and insulin resistance in patients with colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate whether insulin resistance exists in patients with colorectal cancer and its clinical significance.</p><p><b>METHODS</b>A total of 135 patients with colorectal cancer were included as the study group, and 120 healthy subjects were included as the control group. Height, weight, and blood pressure were recorded. Fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C), and insulin were measured. Insulin resistance index(lnHOMA-IR) was calculated.</p><p><b>RESULTS</b>The lnHOMA-IR was 0.84±0.38 in the study group and 0.42±0.08 in the control group(P<0.05). The incidence of metabolic syndrome was 34.1%(46/135) in the study group and 22.5%(27/120) in the control group(P<0.05). Insulin resistance index did not differ between the groups according to metabolic syndrome(0.98±0.41 vs. 0.74±0.22, P>0.05). There were no significant associations between insulin resistance index and tumor differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM staging(P>0.05).</p><p><b>CONCLUSION</b>Insulin resistance exists in colorectal cancer patients, and it is possibly associated with metabolic syndrome and the tumor.</p>

Hepatic resection: an analysis of the impact of operative and perioperative factors on morbidity and mortality rates in 2008 consecutive hepatectomy cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatectomy is a standard hepatic surgical technique. The safety of hepatectomy has been improved in line with improvements in surgical techniques. This study analyzed the operative and perioperative factors associated with hepatectomy.</p><p><b>METHODS</b>A total of 2008 patients who underwent consecutive hepatectomies between January 1986 and December 2005 were investigated retrospectively. Diagnoses were made based on pathological findings.</p><p><b>RESULTS</b>Malignant and benign liver diseases accounted for 58.5% and 41.2%, respectively, of the conditions requiring resections. Primary liver cancers accounted for 76.1% of the malignant tumors, while hilar cholangiocarcinomas accounted for 6.7%. Hemangiomas (41.7%) and hepatolithiasis (29.6%) were the most common of the benign conditions. Microwave in-line coagulation was used in 236 of our liver resection cases. The overall postoperative complication rate was 14.44%, of which 12.54% of resections were performed for primary liver cancer, 16.40% for secondary liver cancer, and 16.32% for hepatolithiasis. The overall hospital mortality was 0.55%, and that for malignant liver disease was 0.51%. A high mortality (2.53%) was associated with extensive liver resections for hilar cholangiocarcinomas (two deaths in 79 cases). Microwave in-line pre-coagulation resection, Child-Pugh grading, operating time, postoperative length of stay, and preoperative serum albumin level were independent predictors of morbidity. Blood loss, Child-Pugh grading, operating time and preoperative serum albumin level were independent predictors of mortality.</p><p><b>CONCLUSIONS</b>Hepatectomy can be performed safely with low morbidity and mortality, provided that it is carried out with optimal perioperative management and innovative surgical techniques.</p>

Liver resection: single center experiences of 2008 consecutive resections in 20 years / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze operative and perioperative factors associated with hepatectomy.</p><p><b>METHODS</b>2008 consecutive patients undergoing hepatectomy from January 1986 to December 2005 at Chinese People's Liberation Army General Hospital were investigated retrospectively according to their medical documentation. Diagnoses were made on basis of pathological results.</p><p><b>RESULTS</b>Malignant and benign liver diseases accounted for 58.5% and 41.2%, respectively. In the former, primary liver cancer accounted for 76.1% and hilar cholangiocarcinoma for 6.7%. Hemangioma (41.7%) and hepatolithiasis (29.6%) were listed in the first two in the latter group with relatively more patient ratios. Isolated caudate lobe resection was performed in 25 patients and micro-wave inline coagulation was induced in 236 cases of liver resection. In all cases, those with blood loss less than 200 ml accounted for 50.5% (1015/2008), whereas those with more than 400 ml accounted for 28.4% (570/2008). In patients performed micro-wave inline coagulation liver resection, those with blood loss less than 200 ml and more than 400 ml accounted for 60.6% (143/236) and 19.9% (47/236), respectively, which differed significantly from the average level (P < 0.05). The postoperative complication incidence was 14.44% for all cases, 12.54% for primary liver cancer, 16.40% for secondary liver cancer, and 16.32% for hepatolithiasis. Complication incidence of primary liver cancer with tumor size smaller than 5 cm was 11.65% and that with tumor larger than 10 cm was 14.69%. There was no significant difference between the two groups. All-case hospital mortality was 0.55% and that for liver malignant disease was 0.60%, hilar cholangiocarcinoma 2.53%.</p><p><b>CONCLUSION</b>Hepatectomy can be performed safely with low mortality and low complication incidence, provided that it is carried out with optimized perioperative management and innovative surgical technique.</p>

Liver resection in hepatolithiasis: 20-year's evolution / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze operative and perioperative factors associated with hepatectomy in hepatolithiasis.</p><p><b>METHODS</b>245 consecutive hepatolithiasis patients undergoing hepatectomy from January 1986 to December 2005 at Chinese People's Liberation Army General Hospital were investigated retrospectively according to medical documentation.</p><p><b>RESULTS</b>Hepatolithiasis accounted for 29.6% (245/827) in all benign liver diseases treated with hepatectomy during this time period. There were 88 cases in male and 157 cases in female, the average age was (46.9 +/- 11.3) years. Cases of right liver resection and hepatic segments resection were much more than that in 1963 - 1985. Blood transfusion during operation was given in 45.3% of cases. Complication incidence was 16.3%, with infection 3.3% and bile leakage 2.4%. Length of stay after operation was (15.7 +/- 9.2) days. Perioperative mortality rate was 0.4% (1/245).</p><p><b>CONCLUSIONS</b>Individualized hepatectomy is the important surgical treatment of hepatolithiasis. Hepatectomy can be performed safely with low mortality and low complication incidence, provided that it is carried out with optimized perioperative management and innovative surgical technique.</p>