Pharmacokinetics and tissue distribution of intraperitoneal 5-fluorouracil with a novel carrier solution in rats.

AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9% sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high-performance liquid chromatography. RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAES-steri than those with physiologic saline at 1, 6, 12, 18, and 24 h (P = 0.047, 0.009, 0.005, 0.005 and 0.005 respectively, the percentages of remaining peritoneal fluid volume were 89.9 +/- 5.6 vs 83.4 +/- 4.9, 79.9 +/- 2.8 vs 56.2 +/- 15.7, 46.8 +/- 5.5 vs 24.7 +/- 9.7, 23.0 +/- 2.8 vs 0.0 +/- 0.0 and 4.2 +/- 1.7 vs 0.0 +/- 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3, 12 and 18 h (P = 0.009, 0.009 and 0.005 respectively, the concentrations were 139.2768 +/- 28.2317 mg/L vs mg/L, 11.5427 +/- 3.0976 mg/L vs 0.0000 +/- 0.0000 mg/L and 4.7724 +/- 1.0936 mg/L vs 0.0000 +/- 0.0000 mg/L respectively). Mean plasma 5-fluorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 +/- 0.8128 mg/L vs 0.8794 +/- 0.2394 mg/L, 0.6203 +/- 0.9935 mg/L vs 0.0112 +/- 0.0250 mg/L, 0.3725 +/- 0.3871 mg/L vs 0.0000 +/- 0.0000 mg/L, and 0.2469 +/- 0.1457 mg/L vs 0.0000 +/- 0.0000 mg/L respectively), but significantly lower at 1 h (P = 0.009, the concentrations were 4.1957 +/- 0.6952 mg/L vs 7.7406 +/- 1.2377 mg/L). There were no significant differences in the plasma 5-fluorouracil in inferior caval vein at each time-point. 5-fluorouracil concentrations were significantly greater with HAES-steri at 18 h in gastric tissue (P = 0.016, the concentrations were 0.9486 +/- 0.8173 mg/L vs 030392 +/- 0.0316 mg/L), at 18 h in colon (P = 0.009, the concentrations were 0.1730 +/- 0.0446 mg/L vs 0.0626 +/- 0.0425 mg/L), at 3, 6, 12 and 24 h in liver (P = 0.009, 0.013, 0.034 and 0.013 respectively, the concentrations were 0.6472685 +/- 0.5256 mg/L vs 0.1554 +/- 0.1043mg/L, 0.8606826 +/- 0.7155 mg/L vs 0.0014 +/- 0.0029 mg/L, 0.0445 +/- 0.0330 mg/L vs 0.0797 +/- 0.1005 mg/L and 0.0863 +/- 0.0399 mg/L vs 0.0034 +/- 0.0075 mg/L respectively) and at 18 h in lung (P = 0.009, the concentrations were 0.0886 +/- 0.0668 mg/L vs 0.0094 +/- 0.0210 mg/L). There were no differences in 5-fluorouracil concentrations in renal tissue at each time-point. CONCLUSION: The use of intraperitoneal 5-fluoro-uracil with HAES-Steri carrier solution provides a pharmacokinetic advantage for a local-regional killing of residual tumor cells and improve the accumulated penetrability of 5-fluorouracil with decreased systemic toxicity. Further clinical feasibility studies on the use of HAES-steri as carrier solution for intraperitoneal chemotherapy with 5-fluorouracil are warranted.

Application of laparoscopy in diagnosis and treatment of massive small intestinal bleeding: report of 22 cases.

AIM: To investigate the diagnostic and therapeutic value of laparoscopy in patients with massive small intestinal bleeding. METHODS: Twenty-two patients with massive small intestinal bleeding and hemodynamic alteration underwent laparoscopic laparotomy in our unit from December 2002 to April 2005. Post pathologic sites were found, laparoscopy- or laparoscopy-assisted part small intestinal resection including pathologic intestinal site and enteroanastomosis was performed in all these patients. RESULTS: The bleeding sites were successfully detected by laparoscopy in all these 22 patients. Massive small intestinal bleeding was caused by jejunum benign stromal tumor in 8 cases, by jejunum potential malignant stromal tumor in 5 cases, by jejunum malignant stromal tumor in 1 case, by Mechel's diverticulum in 5 cases, by small intestinal vascular deformity in 2 cases, and by ectopic pancreas in 1 case. A total of 16 patients underwent laparoscopy-assisted enterectomy and enteroanastomosis of small intestine covering the diseased segment and 6 patients received enterectomy of the diseased segment under laparoscope. No surgical complications occurred and the outcome was satisfactory. CONCLUSION: Laparoscopy in diagnosis and treatment of massive small intestinal bleeding is noninvasive with less pain, short recovery time and definite therapeutic efficacy.

[Construction and application of Access database of colorectal carcinoma cases].

OBJECTIVE: To construct a database using Access software in which clinical information of colorectal cancer cases can be loaded, to facilitate relevant large-sample clinical studies. METHODS: A retrospective study was conducted in 1 374 cases of colorectal carcinoma with surgical treatment between 1975 to 1999 in Nanfang Hospital. According to the National Standards for Pathological Study of Colorectal Carcinoma, an Access2000 database consisting of 1 145 pathologically confirmed colorectal carcinoma cases was established, designated as The Specialized Access Database of Colorectal Carcinoma. RESULTS AND CONCLUSION: The database system has been successfully constructed and operates smoothly, which possesses powerful capacity for information processing of colorectal cancer cases.

[Prognosis of rectal cancer in relation to the selection of the surgical approaches].

OBJECTIVE: To investigate the prognostic significance of surgical approach selection in patients with rectal cancer. METHODS: A retrospective analysis of the relation of surgical approach selection to the prognosis was conducted in 112 cases of rectal cancer between July 2000 to June 2002. RESULTS: In this group of cases, local resection of the tumor was performed in 10 cases, Dixon operation in 75 cases and Miles operation in 27 cases. A total of 106 patients survived the operations with 10 had tumor recurrence (a recurrence rate of 8.93 %). All the 10 patients receiving local resection of the tumor survived without episodes of tumor recurrence or metastasis. After the operations, 101 patients (90.18 %) retained normal sexual function and 109 (97.32 %) were with normal urinary function. CONCLUSION: The postoperative quality of life of the patients with rectal cancer very much relies on the selection of adequate surgical procedures.

[p53 expression and cancer cell invasion in the distal bowel wall of patients with rectal carcinoma].

OBJECTIVE: To determine an adequate distal bowel length to be excised for safe surgical removal of rectal carcinoma. METHODS: p53 expression and patterns of cancer cell invasion into the bowel wall distal to the tumors were studied in 68 surgically removed rectal carcinoma specimens with immunohistochemical and routine pathological methods respectively. RESULTS: In 52.9% (36/68) of the cases, cancer cell infiltration in the bowel was found microscopically, among which 32 (88.9%) had the infiltration confined within 2 cm from the primary tumors, with the rest cases within 3 cm. The scope of the distal infiltration of the cancer cells was correlated to the gross morphology, histological type and Dukes' stages of the primary tumors. Of the 16 cases (23.5%) positive for p53 expression in the distal bowel mucosa, 13 had p53 expression profile detected within 2 cm, all within 3 cm. The expression of p53 in the distal bowel mucosa was not correlated with the clinical and pathological features of the primary rectal carcinoma. CONCLUSION: Excision till the compromised bowel 3 cm distal to the tumor may ensure safe removal of rectal cancer.

Effect of parenteral nutrition with L-arginine supplementation on postoperative immune function in patients with colorectal cancer.

OBJECTIVE: To study the effects of parenteral nutrition (PN) supplemented with L-arginine on the immune function of patients with colorectal cancer after operation. METHODS: Forty randomly chosen patients with colorectal cancer were enrolled in this study, who received either standard PN or PN supplemented with 20 g/d L-arginine for 7 d after surgical removal of the tumors. Tests of the immune function (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), interleukin-2R, natural killer cells, C3, C4, CH50, IgA, IgM, IgG) were performed preoperatively and at different time periods postoperatively. RESULTS: Data analysis with ANOVA demonstrated immune suppression in the patients before operation, and the condition was improved (as evidenced by increased CD4(+),CD4(+)/CD8(+), natural killer cells and interleukin-2R levels) in L-arginine group as compared with the results in the control group at days 4 and 7 (P<0.05). CONCLUSION: Arginine can improve the immune function in patients with colorectal cancer after operation and enhance PN effect.

[Comparison of the tri-cuff and classical methods for vascular anastomosis in heterotopic small bowel transplantation in rats].

OBJECTIVE: To explore the effect of the tri-cuff vascular anastomosis for simplifying the surgical procedure and improving the success rate. METHOD: Sixty recipient Wistar rats were randomized into experimental group and the control group, the former was subjected to the tri-cuff vascular anastomosis for heterotopic small bowel transplantation while the latter had vascular anastomosis using classical methods. The effects of the two methods for anastomosis were compared. RESULTS: The tri-cuff vascular anastomosis was superior to the classical methods in view of the total operation time, arterial anastomosis time, and hot-ischemia time of the small bowel graft. CONCLUSION: Compared with the classical methods, the tri-cuff vascular anastomosis is safer and time-saving.

[Surgical approach for carcinoma in the gastric cardia].

OBJECTIVE: To explore the optimal surgical approach for carcinoma in the gastric cardia. METHODS: A total of 157 patients with carcinoma in the gastric cardia were assigned into 2 groups according to the surgical approaches adopted, namely transabdominal (57 patients) and transthoracic approaches (100 patients), and the therapeutic effects of the two approaches were compared. RESULTS: In the transabdominal group, the average volume of intraoperative blood transfusion was 164.91+/-36.83 ml, average operative time 219.04+/-10.72 min and average hospital stay 14.39+/-1.39 d, with an average number of 6.04+/-2.84 lymph nodes removed. In the transthoracic group, the 4 parameters were 575.50+/-40.12 ml, 286.40+/-7.94 min, 20.32+/-0.81 d, and 3.62+/-2.56 respectively. None of the cases developed pleural effusion in the former group, which had a tumor recurrence rate of 22.80% within the follow-up period for 3 to 60 months. In contrast, 15 cases had pleural effusion in the latter group with a tumor recurrence rate of 41.00%. There was a significant difference between the two groups in terms of the therapeutic effects. CONCLUSION: Transabdominal approach is the better alternative to transthoracic one for operation of carcinoma in the gastric cardia.

[Effects of FOLFOX4 neoadjuvant chemotherapy on the non-tumoral liver in patients with metastatic colorectal carcinoma].

OBJECTIVE: To investigate the effect of FOLFOX4 neoadjuvant chemotherapy on the non-tumoral liver in patients with metastatic colorectal carcinoma. METHODS: A large series of surgically resected liver metastases(n=42) was selected and the morphological changes were examined by light and electron microscope. The mRNA and protein levels of connective tissue growth factor (CTGF) expression were detected by semi-quantitative RT-PCR and Western blotting analysis. RESULTS: Twelve (63.2%) of the 19 post-chemotherapy liver resection specimens had sinusoidal dilatation and hemorrhage. In contrast, 23 livers treated by surgery alone remained normal. Neoadjuvant chemotherapy could significantly enhance the mRNA and protein levels of CTGF expression in hepatic stellate cells. CONCLUSION: Systemic FOLFOX4 neoadjuvant chemotherapy in metastatic colorectal carcinoma frequently causes morphological injuries involving hepatic microvasculature and induces CTGF expression in hepatic stellate cells to participate in hepatic fibrosis.

[Relationship between micro-lymphatic vessel density and lymphatic metastasis in follicular thyroid carcinoma].

AIM: To investigate the relationship between micro-lymphatic vessel density (MLVD) and lymphatic metastasis in follicular thyroid carcinoma (FTC). METHODS: MLVD and micro-vascular density (MVD) were determined and counted by Envision immunohistochemistry using D2-40 and CD34 monoclonal antibodies in 35 specimens of follicular thyroid carcinoma(FTC)and 20 of nodular goiter. The relationship between MLVD and lymphatic metastasis was analyzed. RESULTS: MLVD and MVD in follicular thyroid carcinoma were closely related with lymphatic metastasis. At the same time, the cancer embolus in the micro-lymphatic vessel was significantly related with the lymphatic metastasis (P<0.01). CONCLUSION: The metastasis process of follicular thyroid carcinoma (FTC) is associated with the formation of the micro-lymphatic vessel and micro-vascular. Inhibition of the lymphatics formation may be a potential therapeutic maneuver for thyroid neoplasms in the future.

Diagnosis and treatment of small intestinal bleeding: retrospective analysis of 76 cases.

AIM: To investigate the causes of small intestinal bleeding as well as its diagnosis and therapeutic approaches. METHODS: A retrospective analysis was conducted according to the clinical records of 76 patients with small intestinal bleeding admitted to our hospital in the past 5 years. RESULTS: In these patients, tumor was the most frequent cause of small intestinal bleeding (37/76), followed by Mecke's diverticulum (21/76), angiopathy (15/76) and ectopic pancreas (3/76). Of the 76 patients, 21 were diagnosed by digital subtraction angiography, 13 by barium and air double contrast X-ray examination of the small intestine, 11 by 99mTc-sestamibi scintigraphy of the abdominal cavity, 6 by enteroscopy of the small intestine, 21 by laparoscopic laparotomy, and 4 by exploratory laparotomy. Although all the patients received surgical treatment, most of them (68/76) received part enterectomy covering the diseased segment and enteroanastomosis. The follow-up time ranged from 1 year to 5 years. No case had recurrent alimentary tract bleeding or other complications. CONCLUSION: Tumor is the major cause of small intestinal bleeding followed by Meckel's diverticulum and angiopathy. The main approaches to definite diagnosis of small intestinal bleeding include digital subtraction angiography, 99mTc-sestamibi scintigraphy of the abdominal cavity, barium and air double contrast X-ray examination of the small intestine, laparoscopic laparotomy or exploratory laparotomy. Part enterectomy covering the diseased segment and enteroanastomosis are the most effective treatment modalities for small intestinal bleeding.