[Diagnosis and surgical treatment of 98 cases with adult primary retroperitoneal malignant tumor].

OBJECTIVE: To investigate the diagnosis and surgical treatment of adult primary retroperitoneal malignant tumor (APRMT). METHODS: The clinical data of 98 cases with APRMT underwent resection from January 1990 to April 2003 were analyzed retrospectively. RESULTS: Among the 98 cases, complete excision were performed in 79 cases (80.6%), palliative excision in 16 cases (16.3%), tumor biopsy only in 3 cases (3.1%). Resection of involved adjacent organs were carried out in 25 cases (25.5%) and the re-operation rate for recurrence was 28.6% (28 cases). The 1, 3, 5 year survival rates for 79 cases with complete resection were 93.7%, 73.4% and 34.2%, respectively. The 1, 3, 5 year survival rate for 16 cases with palliative resection were 75.0%, 6.3% and 6.3%, respectively. CONCLUSIONS: Certain imaging examinations are crucial to the diagnosis and preoperative evaluation of APRMT. Resection of the involved organs could improve resection rate and prognosis. For the recurrent cases, earlier reoperation is strongly recommended.

Effects of 5-fluouracil combined with sulfasalazine on human pancreatic carcinoma cell line BxPC-3 proliferation and apoptosis in vitro.

BACKGROUND: Most pancreatic carcinomas are clinically insensitive to chemotherapeutics. The exact mechanisms of their apoptosis and multiple drug resistance are obscure at present. This study was undertaken to explore the influence of chemotherapy on anti-proliferation, apoptosis and the cell cycle, and lay a fundamental basis for further research into the apoptotic mechanisms and prevention of multiple drug resistance in pancreatic carcinoma. METHODS: The human pancreatic carcinoma cell line BxPC-3 was cultured in vitro. The growth inhibition rate, cell cycle and apoptotic rate of cells treated with 5-fluorouracil (5-FU), sulfasalazine alone or a combination at different concentrations were evaluated with the MTT method and flow cytometry. Phase-contrast microscopy was used to observe morphological changes in the cells treated with 5-FU, sulfasalazine or both for 24 hours. RESULTS: The growth inhibition rate of the BxPC-3 cells treated with 5-FU and sulfasalazine significantly increased in a time- and dose-dependent manner. The growth inhibition rate of the cells treated with 5-FU gradually increased, but decreased at different concentrations of sulfasalazine for a prolonged period. The apoptotic rate of the BxPC-3 cells induced by sulfasalazine (200 mg/L), 5-FU (100 mg/L) or both for 12 hours were (2.68+/-0.36)%, (6.59+/-0.90)%, and (10.52+/-0.55)%, respectively, compared with the corresponding control values were (3.17+/-0.08)%, (1.50+/-0.06)%, and (4.08+/-0.31)% [(t=2.33 (P>0.05), 9.78 and 17.56 (P<0.01)]. It increased to (7.63+/-0.68)%, (40.43+/-1.79)%, and (64.69+/-0.82)% for 48 hours, in comparison with the control that was (29.20+/-2.18)%, (5.61+/-0.13)%, and (12.02+/-0.52)% [t=17.06, 33.66 and 94.51 (P<0.01)]. The apoptotic rate, proportion of cells in S-phase and proliferative index rose after use of 5-FU (12.5, 25, 50, 75, and 100 mg/L) alone for 24 hours. However, the apoptotic rate at augmented concentrations of sulfasalazine for 24 hours slowly increased from (1.47+/-0.08)% to (3.45+/-0.28)%, the proportion of cells in G0/G1-phase increased from (35.13+/-0.32)% to (54.32+/-1.45)%, the proportion of cells in S-phase decreased from (45.37+/-1.48)% to (16.67+/-2.73)%, and the proliferative index gradually lowered. The proportion of G0/G1-phase cells treated by 5-FU (100 mg/L) and sulfasalazine (200 mg/L) increased from (43.31+/-1.52)% (12 hours) to (85.05+/-0.24)% (48 hours) compared with the corresponding controls [t=7.93 (12 hours), 21.30 (48 hours), P<0.01], and the proportion of cells in S-phase decreased from (11.63+/-1.11)% (12 hours) to (4.47+/-0.68)% (48 hours) in contrast to the controls [t=37.68 (12 hours), 8.60 (48 hours), P<0.01]. Most cells after the combined use of the two agents for 24 hours displayed pyknosis and oval shape by phase-contrast microscopy. The cells treated with 5-FU (100 mg/L) for 24 hours were pyknotic and oval shaped. A few of cells in the group treated with sulfasalazine (200 mg/L) were pyknotic at 24 hours. CONCLUSIONS: Sulfasalazine may enhance the inhibitory proliferation and apoptosis effect on BxPC-3 cells induced by 5-FU, which is closely related to synergistically the cell cycle arrested in G0/G1-phase.

Surgical management of 143 patients with adult primary retroperitoneal tumor.

AIM: To analyze the surgical management of adult primary retroperitoneal tumors (APRT) and the factors influencing the outcome after operation. METHODS: Data of 143 cases of APRT from 1990 to 2003 in the First Affiliated Hospital of China Medical University were evaluated retrospectively. RESULTS: A total of 143 cases of APRT were treated surgically. Among them, 122 (85.3%) underwent complete resection, 16 (11.2%) incomplete resection, and 3 (3%) surgical biopsies. Twenty-nine (20.2%) underwent tumor resection plus multiple organ resections. Ninety-five malignant cases were followed up for 1 mo to 5 years. The 1-year, 3-year, and 5-year survival rates of the patients subject to complete resection was 94.9%, 76.6% and 34.3% and that of patients with incomplete resection was 80.4%, 6.7%, and 0%, respectively (P < 0.001). The Cox multi-various regression analysis showed the completeness of tumor, sex and histological type were associated closely with local recurrence. CONCLUSION: Sufficient preoperative preparation and complete tumor resection play important roles in reducing recurrence and improving survival.

Effects of nitric oxide on reperfusion injury following pancreaticoduodenal transplantation in rats.

OBJECTIVE: To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplantation in rats. METHODS: The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-arginine (L-Arg) group received intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-Arginine methyl ester (L-NAME) group received intravenous injection of L-NAME at a dose of 10 mg/kg, and control group received saline. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) determined by enzyme-linked immunosorbant assay, expression of CINC mRNA detected by Northern blot assay, and myeloperoxidase (MPO) activity in the pancreas graft were measured. Histological observation was performed. RESULTS: The amount of NO in the L-Arg group was higher than in the control group, while in the L-NAME group was lower than in the control group (P < 0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with significant difference among groups. Expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group was lower than in the control group, the L-NAME group was higher than control group (P < 0.05). MPO activity in the L-Arg group obviously decreasd compared with other groups. The pancreas inflammation was ameliorated in L-Arg group, and pancreas damage was aggravated in L-NAME group. CONCLUSIONS: L-Arg can increase the amount of NO and inhibit the elevation of CINC, CINC mRNA expression, and early neutrophil accumulation in the transplanted pancreas. NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation.

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis.

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n=21) received no treatment after the SAP model was established; group B (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r= -0.748, -0.827, -0.723; P<0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P<0.01, P<0.05), but the expression of MCP was not influenced (P>0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P<0.05), but the expression of CD59 and MCP did not change (P>0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.

[The protective role of gadolinium chloride in lung injury associated with acute necrotizing pancreatitis].

OBJECTIVE: To discuss the role of gadolinium chloride (GdCl(3)) in lung injury associated with acute necrotizing pancreatitis (ANP). METHODS: Experimental animals were randomized into five groups (n = 18 for each group): normal control group, ANP group, GdCl(3) pretreatment group, ANP GdCl(3) pretreatment group, ANP GdCl(3) treatment group. Rat ANP model was induced by intraductal administration of 3% sodium taurocholate. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage. The blood gas assay, the ratio of wet/dry tissue, protein content of bronchoalveolar lavage fluids (BALF), the myeloperoxidase (MPO) of lung tissue and generation of TNFalpha and NO by AM were evaluated. The apoptosis of AM was checked by agarose gel electrophoresis analysis, transmission electric microscopy observation and cytometry propidium iodide single stained method. The lung tissue was examined by histology. RESULTS: The parameter of GdCl(3) pretreatment group compared with normal control group had no statistical significance (P > 0.05). The indicators of ANP GdCl(3) pretreatment group and ANP GdCl(3) treatment group were elevated compared with the normal control group and had statistical significance (P < 0.05). But compared to the ANP group, they were all decreased and also had the statistical significance (P < 0.05). The 180 - 200 bp ladder pattern unique to apoptosis in agarose gel electrophoresis and the apoptotic typical morphologic feature in AM by transmission electric microscopy and typical subdiploid peak in DNA content figure could be observed in ANP GdCl(3) pretreatment group and ANP GdCl(3) treatment group, while the other three groups could not. CONCLUSIONS: Lung injury associated with ANP could be ameliorated by application of GdCl(3) through inducing apoptosis of AM of ANP.

Protective effects of L-arginine on reperfusion injury after pancreaticoduodenal transplantation in rats.

BACKGROUND: Post-transplantation pancreatitis and graft thrombosis are two major complications of pancreas transplantation that contribute to morbidity, mortality, and graft loss. Nitric oxide(NO) is a potent vasodilator agent formed when L-arginine (L-Arg) is converted to L-citrulline by the action of NO synthase (NOS), and plays a major role in microcirculatory changes. We therefore investigated the effect of L-Arg on reperfusion injury following pancreaticoduodenal transplantation in rats. METHODS: The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-Arg-treated rats received the intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-arginine methyl ester (L-NAME)-treated rats at a dose of 10 mg/kg. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbant assay, the expression of CINC mRNA was detected by Northern blot assay in the pancreas graft, and the activity of myeloperoxidase (MPO) was measured. Histological examination was performed. RESULTS: The amount of NO was higher in the L-Arg group than in the control group, while it was lower in the L-NAME group than in the control group (P<0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with the difference among the groups being significant. The expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group (7.66+/-1.53 microg/L) was lower than in the control group (26.31+/-2.01 microg/L), while in the L-NAME group (34.18+/-3.12 microg/L) it was higher than that in the control group (P<0.05). The activity of MPO in the L-Arg group was obviously decreased as compared with in the other groups. The pancreas inflammation was ameliorated when L-Arg was administered, whereas the pancreas damage was aggravated when L-NAME was administered. CONCLUSIONS: L-Arg can increase the amount of NO and inhibit the elevation of CINC, the CINC mRNA expression and early neutrophil accumulation in the pancreas. NO has protective effects on ischemia/reperfusion injury in pancreaticoduodenal transplantation.

Surgical treatment of nonfunctioning islet cell tumor: report of 41 cases.

BACKGROUND: Nonfunctioning islet cell tumor (NIT) as a rare pancreatic endocrine neoplasm is characterized by unspecific clinical symptoms and is hard to diagnose. In China, NIT accounts for 15%-41% in pancreatic endocrine neoplasms just next to insulinoma. In this study, we evaluated the surgical modalities of NIT. METHODS: From January 1978 through February 2002, 41 patients with NIT were treated at the Department of Surgery of the First Affiliated Hospital, China Medical University, Shenyang, China. Tumors in the head of the pancreas were noted in 28 patients, and in the body or in the tail in 13 patients. The mean diameter of the tumors was 10.7 cm. Fifteen patients underwent enucleation and 21 received pancreatectomy. Tumors were unresectable in 5 patients because of extensive infiltration. The mean diameter was 9.6 cm in patients treated by enucleation, 13.1 cm in those by pancreaticoduodenectomy, 9.9 cm in those by distal pancreatectomy, and 11.6 cm in those with unresectable tumors. RESULTS: The curative resection rate was 88% (n=36), and the complication rate after enucleation and pancreatectomy was 33% (n=5) and 14% (n=3), respectively. No local recurrence was found after both enucleation and pancreatectomy. Liver metastases occurred in 3 patients treated by enucleation. CONCLUSIONS: Both enucleation and pancreatectomy are effective for NIT of the pancreas. No local recurrence has been found in patients treated by the two surgical procedures. The complication rates of the two modalities are comparable.

[The role of nitric oxide in lung injury associated with acute necrotizing pancreatitis].

OBJECTIVE: To discuss the role of nitric oxide (NO) in lung injury associated with acute necrotizing pancreatitis (ANP). METHODS: One hundred and twenty SD rats were randomized into five groups: control group, ANP group, L-arginine (L-arg) pretreatment group, L-NAME pretreatment group, and mixed pretreatment group (n = 24 for each group). Rat ANP model was induced by intraductal administration of 3% sodium taurocholate. Alveolar macrophages (AMs) were obtained by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids (BALF), the myeloperoxidase (MPO) of lung tissue and generation of tumor necrosis factor alpha (TNFalpha)and NO by alveolar macrophages were evaluated. The expression of TNFalpha mRNA and iNOS mRNA was also measured. RESULTS: Lung injury was aggravated gradually with progression of the disease. The level of MPO of lung tissue and the protein content of BALF showed a steady increase with time and peaked at the 12(th) hour (10.8 +/- 0.6 U/g for MPO and 2,011.0 +/- 105.5 micro g/ml for protein, respectively). TNFalpha and NO secreted by AMs were elevated gradually and peaked at the 6(th) hour (1,624.2 +/- 149.2 pg/ml and 88.8 +/- 6.5 micro mol/L respectively) but decreased at the 12(th) hour. The expression of TNFalpha mRNA and iNOS mRNA was similar with the change of TNFalpha and NO. The parameters of the groups of L-arg, L-NAME and the mixed pretreatment were similar to those of ANP group. The parameters compared with those of the control group showed a significant difference (P < 0.05). The parameters of groups of L-Arg and L-NAME pretreatment in comparison with those of the ANP group showed significant difference (P < 0.05). CONCLUSIONS: Over production of NO mediated by iNOS aggravates lung injury caused by acute necrotizing pancreatitis. Administration of exogenous NOS substrate would worsen lung injury, whereas administration NOS inhibitor would alleviate lung injury.