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Though the outcome of resection for locally invasive pancreatic cancer is still poor, it has gradually improved in Japan, and the 5-year survival is now about 10%. However, the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial. We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design.Patients with pancreatic cancer who met our preoperative criteria for inclusion (pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery, or without distant metastasis) underwent laparotomy. Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group (200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy) without resection. The 2 groups were compared for mean survival, hazard ratio, 1-year survival, quality of life scores, and hematologic and blood chemical data.Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group. There was 1 operative death. The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival (62% vs 32 %, P=.05), mean survival time (17 vs 11 months, P.03), and hazard ratio (0.46, P=.04). There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection.Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.

Background. Fluid mechanical factors are suspected to be involved in the pathogenesis and localization of intimal hyperplasia in anastomosed vessels. However, no direct correlation has been established between the flow and the exact sites of intimal hyperplasia. Hence we have studied the relationship between the flow and preferred sites of wall thickening in 90-degree- and 45-degree-cut and end-to-end anastomosed vessels. Methods. Twenty-five 90-degree and twenty-five 45-degree end-to-end anastomoses were performed on the femoral arteries of 17 adult mongrel dogs. The vessels were harvested at 3 months after operation, fixed at 100 mm Hg, dehydrated with ethanol, and rendered transparent by immersing them in methyl salicylate. Exact locations and sizes of intimal thickening and characteristics of the flow prevailing at sites of anastomoses were studied in detail by means of flow visualization and cinemicrographic techniques. Results. It was found that a perfect correlation exists between the preferred sites of intimal thickening and the regions of slow recirculation flows with low wall shear stresses. In both 90-degree and 45-degree anastomosed vessels, intimal thickening developed only in those vessels in which formation of slow recirculation flows was observed. It was also found that although a pronounced and localized intimal thickening developed in 45-degree anastomosed vessels, the degree of circumferential constriction caused by both surgical procedures and development of intimal thickening was much milder in 45-degree than 90-degree anastomosed vessels. Conclusions. The results suggest that key hemodynamic factors involved in the localization of intimal thickening in end-to-end anastomosed vessels are low velocity of flowing blood and the resultant low shear stresses acting on the vessel wall.

Background It is suspected that blood flow and flow-induced shear stress play an important role in the pathogenesis and localization of intimal hyperplasia in anastomosed vessels. However, experimental data that demonstrate the correlation between the flow and the sites of intimal thickening obtained in the same vessel are scarce. For this reason, we have studied the relationship between the flow and precise locations of wall thickening specific to the particular vessel by performing diameter-mismatched vein graft interpositions. This method created more flow disturbances than those found in our previous study, which was carried out by dividing an artery and simply suturing its ends back to their original positions. Methods In the current study, grafting procedures consisting of 26 saphenous vein interpositions and 10 jugular vein interpositions were carried out on the femoral arteries of 22 adult mongrel dogs. The vessels were harvested at 3 months after operation, perfusion-fixed, and rendered transparent. The precise location and the size of intimal thickening and characteristics of the flow, such as flow patterns, distributions of fluid velocity, and wall shear stress, were studied in detail by means of flow visualization and cinemicrographic techniques. Results It was found that the diameters of interposed saphenous vein grafts, which were about one-half the diameter of host arteries, increased drastically and became almost the same as those of the host arteries. Intimal thickening was found distal to the distal anastomotic junction in smaller diameter saphenous vein–interposed vessels and distal to the proximal anastomotic junction in larger diameter jugular vein–interposed vessels. In both cases, flow was disturbed with the formation of a slow recirculation flow due to a sudden enlargement of vessel diameter caused by a mismatch of vessel diameters at the anastomotic junction and at the location where the wall shear stress was low. Conclusions The results suggest that the key hemodynamic factors involved in the localization of intimal thickening are the low velocity of flowing blood and the resultant low shear stress acting on the vessel wall.

Background. The purpose of this study was to clarify the still poorly understood dynamics of peritoneal inflammatory cells (PICs) in acute pancreatitis. Methods. Acute pancreatitis of 3 different degrees of severity was induced in male Wistar rats. Peritoneal lavage was performed at 1, 6, 12, and 24 hours after the induction, and the fluids collected were analyzed for the number and subpopulation of PICs. The levels of apoptosis and necrosis, cytokines, and bacterial infection were also investigated. Results. The number of PICs was increased in mild and moderate pancreatitis, and the infiltration of inflammatory cells had occurred. In severe pancreatitis, the number of PICs increased until 6 hours after the induction, but thereafter the number decreased. Infiltration of neutrophils occurred 6 hours after the induction, but it was not sustained thereafter and infiltration of peritoneal macrophages did not occur. Cytokines in the lavage fluid increased in all 3 models during the first 6 hours after the induction. Subsequently, cytokines were reduced in mild and moderate pancreatitis but significantly increased in severe pancreatitis. The level of bacterial infection increased according to the severity. Conclusions. The relationship between the PIC dynamics and cytokine levels in severe pancreatitis is very different from that observed in mild or moderate pancreatitis. (Surgery 2002;132:86-92.)

Background: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. Methods: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. Results: IL-12/3T3 cells producing 7.2 ng/10 6 cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. Conclusions: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers. (Surgery 1999;125:257-64.)