Severe veno-occlusive disease/sinusoidal obstruction syndrome after deceased-donor and living-donor liver transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.

Serum regulates cortisol bioactivity by corticosteroid-binding globulin-dependent and independent mechanisms, as revealed by combined bioassay and physicochemical assay approaches.

CONTEXT: Corticosteroid-binding globulin (CBG) is the principal carrier of natural glucocorticoids in the circulation, and we hypothesized that it modulates glucocorticoid bioactivity (GBA). Alterations in CBG, the presence of noncortisol, naturally occurring glucocorticoids and the use of potent, synthetic glucocorticoids, all make it difficult to assess adrenal activity in-vivo; these problems can be addressed by a glucocorticoid bioassay. DESIGN AND SUBJECTS: A bioassay was developed for serum GBA and a physicochemical ultrafiltration-liquid chromatography-tandem mass spectrometry assay for free serum cortisol (FreeF). We studied individuals homozygous and heterozygous for a nonfunctioning CBG variant (CBG G237V) and healthy controls. RESULTS: FreeF concentrations were similar in healthy controls, and those with absent functional CBG, but surprisingly we found low GBA in CBG null individuals. This may suggest that CBG delivers cortisol to target cells. However, further experiments revealed that dilution of serum in the bioassay caused release of cortisol from CBG, resulting in elevated GBA measurements in all but the CBG G237V homozygotes. Furthermore, we identified a specific and potent inhibitory effect of high concentration serum on glucocorticoid sensitivity of the recipient cells used in the bioassay. Analysis of inflammatory synovial fluid, a filtrate of serum with lower CBG concentration, revealed elevated free cortisol compared to noninflammatory synovial fluid, a change not attributable to interconversion between cortisol and cortisone. CONCLUSIONS: Our findings reveal that dilution of CBG enhances cortisol release, and so bioactivity, and also that serum potently induces glucocorticoid resistance in target cells.

Role of transcription factors in small intestinal ischemia-reperfusion injury and tolerance induced by ischemic preconditioning.

BACKGROUND: Small intestinal ischemia-reperfusion (I/R) injury, a clinically important condition, induces severe organ damage. Ischemic preconditioning (IPC) produces tolerance to long-term I/R by inducing a short-term I/R. Herein, we have examined the reduction in the extent of injury by IPC. METHODS: Small intestinal I/R injury was induced in rats by clamping the superior mesenteric artery (SMA) for 30 minutes followed by reperfusion for various 30 minutes. The IPC + I/R group underwent a short-term I/R (IPC) prior to long-term I/R. Nuclear factor-κB (NF-κB) activity was analyzed by an electrophoretic mobility shift assay and cytokine mRNA levels, by reverse transcription-polymerase chain reaction. Apoptosis-related genes were analyzed by Western blotting and immunohistochemistry, and apoptotic cells, by TUNEL staining. RESULTS: The animals were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. NF-κB activity increased in the I/R group and decreased in the IPC + I/R group. The IPC + I/R group showed decreased cytokine in mRNA levels. Expression of the proapoptotic gene caspase-3 was increased in the I/R and decreased in the IPC + I/R group. Expression of the antiapoptotic gene Bcl-xL was increased in the IPC + I/R group. The number of apoptotic cells was increased in the I/R and decreased in the IPC + I/R group. CONCLUSION: Small intestinal I/R injury was reduced by IPC produced by clamping the SMA; thus, IPC may have potential clinical applications in the future.

Learning of thoracoscopic radical esophagectomy: how can the learning curve be made short and flat?

Attainment of proficiency in video-assisted thoracoscopic radical esophagectomy (VATS) for thoracic esophageal cancer requires much experience. We have mastered this procedure safely under the direction of an experienced surgeon. After adoption of the procedure, the educated surgeon directed induction of this surgical procedure at another institution. We evaluated the efficacy of instruction during the induction period by comparing the results at the two institutions in which VATS had been newly induced. We defined the induction period as the time from the beginning of VATS to the time when the last instruction was carried out. From January 2003 to December 2007, 53 patients were candidates for VATS at Kanazawa University (institution 1). Of these, 46 patients underwent curative VATS by a single operator. We divided this period into three parts: the induction period of VATS, post-induction period, and proficient period when the educated surgeon of institution 1 directed the procedure at Maebashi Red Cross Hospital (institution 2). At institution 1, 12 VATS were scheduled, and nine procedures (75%) (group A) including eight instructions were completed during the induction period (from January 2003 to August 2004). Thereafter, VATS was performed without instruction. In the post-induction period, nine VATS were scheduled, and eight procedures (88.8%) (group B) were completed from September 2004 to August 2005. Subsequently, 32 VATS were scheduled, and 29 procedures (90.6%) (group C) were completed during the proficient period (from September 2005 to December 2007). The surgeon at Maebashi Red Cross Hospital (institution 2) started to perform VATS under the direction of the surgeon who had been educated at institution 1 from September 2005. VATS was completed in 13 (76.4%) (group D) of 17 cases by a single surgeon including seven instructions during the induction period at institution 2 from September 2005 to December 2007. No lethal complication occurred during the induction period at both institutions. We compared the results of VATS among four groups from the two institutions. There were no differences in the background and clinicopathological features among the four groups. The number of dissected lymph nodes and amount of thoracic blood loss were similar in the four groups (35 [22-52] vs 41 [26-53] vs 32 [17-69] vs 29 [17-42] nodes, P = 0.139, and 170 [90-380] vs 275 [130-550] vs 220 [10-660] vs 210 [75-543] g, P = 0.373, respectively). There was no difference in the duration of the thoracic procedure during the induction period at the two institutions. However, the duration of the procedure was significantly shorter in the proficient period of institution 1 (group C: 266 [195-555] minutes) than in the induction period of both institutions (group A: 350 [280-448] minutes [P = 0.005] and group D: 345 [270-420] mL [P = 0.002]). There were no surgery-related deaths in any of the groups. The incidence of postoperative complications did not differ among the four groups. Thoracoscopic radical esophagectomy can be mastered quickly and safely with a flat learning curve under the direction of an experienced surgeon. The educated surgeon can instruct surgeons at another institution on how to perform thoracoscopic esophagectomy. The operation time of thoracoscopic surgery is shortened by experience.

Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer.

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells.

Small cell lung cancer (SCLC) is an aggressive tumour with an abysmal prognosis. These cancers are characteristically resistant to glucocorticoid (Gc) action, owing to impaired expression of the glucocorticoid receptor (GR). We identified reduced GR expression in human SCLC cell lines, compared to a non-SCLC cell line. The SCLC cells also showed no Gc inhibition of proliferation, in contrast to non-SCLC cells. Retroviral overexpression of GR resulted in significantly increased cell death, which was partially blocked by the GR antagonist, RU486. Indeed, in cells sorted for GR expression, there was rapid, near complete loss of live cells by 72 h, in contrast to control cells that proliferated as expected. Flow cytometry using Annexin V revealed that cell death was by apoptosis. In addition, confocal analysis of fixed cells showed that cells overexpressing GR displayed a significant increase in fragmenting apoptotic nuclei. Microarray studies showed that transgenic GR expression upregulated the proapoptotic genes, BAD and BAX. We have, therefore, identified a profound apoptotic effect of GR in SCLC cells, which may explain the low levels of endogenous GR in SCLC cells. Understanding how GR overexpression leads to apoptotic cell death in SCLC cells may uncover new therapeutic strategies.

Multiple organ failure caused by end-stage liver disease successfully treated with living donor liver transplantation using perioperative percutaneous cardiopulmonary support: a case report.

A 54-year-old female diagnosed with primary biliary cirrhosis (PBC) 10 years earlier was referred for a living donor liver transplant (LDLT). During her workup, she developed pulmonary edema and respiratory failure due to aspiration pneumonia, which required artificial ventilation. The PaO2/FiO2 (P/F) ratio at that time was 60. Although continuous hemodiafiltration (CHDF) and plasma exchange (PE) were initiated, improvement in the P/F ratio was limited to 133. As transplantation was the only approach to save this patient, we performed LDLT using a right lobe graft aided by percutaneous cardiopulmonary support (PCPS). The graft weight was 650 g and the graft weight/recipient weight ratio was 1.6%. During LDLT, the patient's cardiopulmonary function was stable with PCPS, and the surgical procedure was completed without complications. Following the surgery, she continued to have high-end inspiratory pressure and progressed to the chronic phase of adult respiratory distress syndrome (ARDS). We treated her with low-dose steroid therapy and she improved gradually. The patient was weaned off mechanical ventilation and was discharged approximately 25 weeks after LDLT. In the condition of cardiac or respiratory failure, cadaveric liver transplantation using plasmapheresis is contraindicated because of the associated high mortality rate. Our case suggests that if infections are controlled, a patient with multiple organ failure (MOF) due to end-stage liver disease might be successfully treated with LDLT aided by plasmapheresis and PCPS.

Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer.

BACKGROUND AND STUDY AIMS: Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. We report on the utility of laparoscopy and its indications in the detection of peritoneal metastasis in gastric cancer. PATIENTS AND METHODS: A total of 39 patients with gastric cancer underwent laparoscopy and peritoneal cytology investigation in our department, between April 1992 and April 2000. Laparoscopic diagnosis for peritoneal metastasis (LP-P) was determined through macroscopic, pathological and cytological diagnoses. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound before laparoscopy. Carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA125 levels in serum and peritoneal fluid were measured using enzyme immunoassay. RESULTS: Laparoscopic diagnosis for peritoneal metastasis gave negative results in 21 patients and positive results in 18. All the patients with negative LP-P findings underwent surgery; 18 of the 21 patients showed no peritoneal metastasis, but three were diagnosed as having peritoneal metastasis, one at the pouch of Douglas and two at the mesentery. The diagnosis of all the patients with positive LP-P findings was finally confirmed as correct. The specificity, sensitivity, and accuracy of laparoscopy for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 86 % (18/21, 95 % CI 0.64 - 0.97), and 92 % (36/39, 95 % CI 0.79 - 0.98), respectively. The specificity, sensitivity, and accuracy of diagnostic imaging for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 38 % (8/21, 95 % CI 0.18 - 0.62), and 67 % (26/39, 95 % CI 0.50 - 0.81), respectively. All of the 11 patients showing high levels of serum CA125 (equal to or more than 35 U/ml) had peritoneal metastasis whereas 17 of the 26 patients with low levels of serum CA125 (less than 35 U/ml) did not ( P < 0.001). CONCLUSIONS: The sensitivity of laparoscopy for peritoneal metastasis was much higher than that of diagnostic imaging. Laparoscopy and serum CA125 level both predicted peritoneal metastasis, but the degree, volume, or distribution of peritoneal metastasis was disclosed only by laparoscopy. Laparoscopy is a useful way of detecting peritoneal metastasis in gastric cancer, and patients with an elevated level of serum CA125 are the best candidates for laparoscopy.

Enhanced invasiveness of pancreatic adenocarcinoma cells stably transfected with cationic trypsinogen cDNA.

Various studies have described increased expression of cationic trypsinogen in malignant tumor cells. To explore the role of secreted cationic trypsinogen in invasion by cancer cells, we introduced cationic trypsinogen cDNA into Panc-1, a pancreatic adenocarcinoma-derived cell line that lacks expression of endogeneous trypsinogen. Four independent clones (designated Panc-1-Try-7, -9, -11 and -24) stably expressing cationic trypsinogen mRNA were isolated and processed for further study. In a zymographic analysis, gelatinolytic activity for cationic trypsinogen was detectable in serum-free conditioned media obtained from all 4 transfectants but not in media from mock-transfected or parental Panc-1 cells. A Matrigel invasion assay revealed that all trypsinogen-expressing transfectants acquired significantly greater invasive ability than that shown by mock-transfected and parental Panc-1 cells. In addition, enhanced invasiveness of the transfectants was suppressed by FUT-175, a serine protease inhibitor, to the level seen in parental cells. These results provide direct evidence that cationic trypsinogen can increase the invasive ability of carcinoma cells.

[Chemotherapy (low-dose CDDP + UFT) to advanced pancreatic cancer in an ambulatory setting improved survival and quality of life].

The prognosis of pancreatic cancer is very poor. Past attempts to treat advanced pancreatic cancer with single agent or combination chemotherapy have yielded low response rates and little reproducible impact on patient survival or quality of life. We performed systemic chemotherapy in case of unresectable or recurrent pancreatic cancer with CDDP 25 mg/body intravenous weekly or biweekly and oral administration of UFT (300-400 mg/day) as an outpatient treatment. Tumor markers were well controlled for about over one year or more. This ambulatory combination is a well-tolerated regimen that results in improved survival and quality of life.

[A case report of rectal cancer with liver and pulmonary metastases responding to TS-1].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Adenomyomatosis of the papilla of Vater: a case illustrating diagnostic difficulties.

AIMS: To describe the extremely rare case of an adenomyoma of the papilla of Vater. CASE REPORT: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. CONCLUSION: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.

Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer.

BACKGROUND/AIMS: Anomalous pancreaticobiliary junction is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between anomalous pancreaticobiliary junction, especially if it is not associated with common bile duct dilatation, and gallbladder carcinoma, we retrospectively reviewed data of 126 patients with gallbladder carcinoma. METHODOLOGY: All these patients had undergone direct cholangiography either by endoscopic retrograde cholangiopancreaticography or percutaneous transhepatic cholangiography. RESULTS: Among 126 patients with gallbladder cancer, 23 patients (18.3%) exhibited anomalous pancreaticobiliary junction. Patients with anomalous pancreaticobiliary junction were younger (mean age: 54 +/- 9.1 years) than patients without anomalous pancreaticobiliary junction (mean age: 65 +/- 9.7 years). The incidence of gallstones in patients with anomalous pancreaticobiliary junction (17%) was significantly lower than in those without this anomaly (64%) (P < 0.01). Among the 23 patients with anomalous pancreaticobiliary junction, 12 patients (52%) had no bile duct dilatation and, 11 patients (48%) had bile duct dilatation in the form of fusiform or cylindrical dilatation. However, no cases with severe cystic dilatation were found. Patients of anomalous pancreaticobiliary junction without common bile duct dilatation had more advanced disease and poor prognosis than those with common bile duct dilatation. CONCLUSIONS: The present study revealed that gallbladder cancer in the patients of anomalous pancreaticobiliary junction without common bile duct dilatation was diagnosed at advanced stage and the prognosis was very poor. Therefore, if a minor abnormality is detected in the wall of acalculous gallbladder on ultrasonography, direct cholangiography should be done to exclude this anomaly.

[Indication for and problems of hepatopancreatoduodenectomy for carcinoma of the biliary tract based on the statistical registry in Japan].

Hepatopancreatoduodenectomy (HPD) as radical surgery for advanced carcinoma of the biliary tract was previously eschewed due to the high rate of postoperative complications. However, recently many institutes have performed it due to the improvement of operative procedures, such as hepatectomy and pancreatoenterostomy, and of pre-intra-postoperative management. Four hundred and sixty-five patients undergoing HPD were registered in Japan during the past 10 years, of whom 355 had carcinoma of the gallbladder and 110 carcinoma of the bile duct. The 30-day operative mortality rate was 9.2% (43 patients). The 5-year survival rates according to the Kaplan-Meier method was 18.1% (32 patients). Survival rates of those with ss and se or si gallbladder cancer were 36% and more than 10%, respectively, but that of those with se or si bile duct cancer was less than 6%. Only 3 patients with 16 lymph node metastases survived for more than 5 years. Fewer patients with biliary infiltration survived for more than 5 years compared with those with hepatic infiltration in carcinoma of the gallbladder. For such patients, extended surgery combining so-called total resection of the hepatoduodenal ligament is thought necessary.

Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway.

The aims of this study were to evaluate the functional expression of Fas receptors (Fas) in human pancreatic cancer cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2 and to search for the mechanisms of receptor-mediated inhibition of Fas signaling in these cells. Despite the expression of Fas receptors at considerable levels, exposure of these cells to agonistic Fas antibodies (500 ng/ml) induced only minimal apoptosis in 4 cell lines. The mechanisms allowing resistance to Fas-mediated apoptosis are complex. Using RT-PCR, we identified molecules which might counteract the apoptogenic signal at several levels of Fas signal transduction pathway. The most striking findings were the overexpression of Fas decoy receptors (DcR3), Fas associated phosphatase-1 (FAP-1), and FLICE-inhibitory protein (c-FLIP) in the resistant cell lines as well as in pancreatic cancer surgical specimens. In conclusion, pancreatic cancer cells express three molecules that can abrogate Fas function at different levels of Fas signaling cascade, resulting in resistance to Fas-mediated apoptosis, and this may promote the progression of this malignancy.

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells.

The aim of this study was to examine whether a specific PPARgamma ligand can inhibit the growth of human pancreatic cancer cells through induction of terminal differentiation. PPARgamma was expressed in five human pancreatic cancer cell lines: Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. Treatment of these cells with a specific PPARgamma ligand, thiazolidinedione (TZD), resulted in inhibition of both cellular and clonogenic growth, and G1 cell cycle arrest. Finally, thiazolidinedione treatment resulted in induction of p21WAF-1 and increased expression of differentiation markers. These results suggest that thiazolidinedione treatment inhibits growth and induces cellular differentiation in pancreatic cancer cells and thereby reduces their development in favor of differentiated and stable cell phenotype.

[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.

[A case of a combined aortectomy with dissection of recurrent paraaortic lymph nodes of sigmoid colon cancer].

A combined aortectomy was performed on a patient with recurrence of sigmoid colon cancer in the paraaortic lymph nodes. The 48-year-old woman was found to have tumor recurrence in the lymph nodes in the area between the aortic bifurcation and the paraaortic area, accompanied by left hydronephrosis, four years after surgery for sigmoid colon cancer (H0, P0, ss, n3, stage IIIb). No metastasis to distant areas was detected at that time. The woman thus underwent a reoperation. Intraoperatively, the aortic bifurcation and the lymph nodes were seen as a mass. The mass involved the left common iliac vein and the left ureter, as well. Therefore, we resected the area from the aortic bifurcation to the bilateral common iliac arteries, the left common iliac vein, the left ureter and the left kidney en bloc, and replaced them with a Y-shaped graft. One year after the reoperation, a tumor metastasis to the liver was detected, and a partial hepatectomy was performed. At present, the patient is being managed at our outpatient clinic. The results suggest that extended resection, involving the aorta as well, is sometimes useful when dealing with tumor recurrence in the paraaortic lymph nodes, unaccompanied by blood-borne metastasis.

Trypsinogen expression in colorectal cancers.

The purpose of this study was to evaluate the trypsinogen expression in human colorectal cancers. We observed the trypsinogen-1 mRNA expression in five of ten human colorectal cancer cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), and gelatinolytic activity in conditioned medium of cancer cells at acidic pH by gelatin zymography. Furthermore, trypsinogen protein expression was observed in 68 out of 154 (44.2%) surgical specimens of colorectal cancer immunohistochemically. However, there was no statistically significant relationship between the trypsinogen expression and the clinicopathological findings. These findings suggest that trypsinogen might be involved in cancer invasion and metastasis throughout the cancer progression.