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Purpose: To assess the utility of secretin‐stimulated dynamic MR cholangiopancreatography (MRCP) for the visualization of pancreaticobiliary reflux in patients with anomalous pancreaticobiliary junction (PBJ). Material and Methods: Ten controls and seven patients diagnosed as having anomalous PBJ were prospectively examined by dynamic MRCP after secretin injection using a breath‐hold, single‐shot turbo spin‐echo T2‐weighted sequence. The optimal MRCP section was repeated 35 times at approx. 10‐second interval after secretin injection; the acquisition time was 4 s per image. The signal intensity (SI) changes of the extrahepatic and intrahepatic bile ducts, presence or absence of intraluminal signal void, caliber change of the bile duct, duodenal filling, and peak time of the SI ratio of the extrahepatic bile duct after secretin injection were compared between the controls and patients. Results: In the controls, the extrahepatic and intrahepatic bile ducts showed neither enhancement nor caliber change over the observation period, providing no apparent peak time. Of the seven patients, the extrahepatic bile duct showed retrograde enhancement and sequential delay in occurrence of the peak time from its distal third to its proximal third ( n=6) with a signal void in its distal part ( n=4); its caliber increased subsequently to pancreatic secretion ( n=5); the intrahepatic bile ducts showed a slight enhancement following SI increase of the proximal extrahepatic bile duct ( n=6); duodenal filling grade tended to be lower in the patients than volunteers ( P Conclusion: In patients with anomalous PBJ pancreaticobiliary reflux were demonstrated by dynamic secretin‐stimulated MRCP.

We studied the efficacy of continuous hepatic arterial infusion of high-dose 5-FU (high-dose CHAI) in two patients with multiple (five or more) bilobar liver metastases of gastric cancer. 5-FU was given continuously via the hepatic artery at 1 g/day for 3 days, followed by one day off therapy and repetition of the initial treatment as one course. Case 1 was a 67-year-old man with Borrmann type 2 gastric cancer who had undergone total gastrectomy. Metachronous multiple liver metastases (maximum diameter: 3.5 cm) were detected at 11 months after surgery. One month later, we started high-dose CHAI and gave two courses with a 4-day interval between them. After that, 5-FU was given twice by hepatic arterial infusion (HAI) at dose of 1.5 g/week. The tumor diameter had decreased by 50% at 3 months after high-dose CHAI. Case 2 was a 64-year-old man with Borrmann type 3 gastric cancer who had synchronous multiple liver metastases (maximum diameter: 9 cm) and liver dysfunction. One month after distal gastrectomy, we started high-dose CHAI and finished one course. After that, liver function returned to normal and 5-FU was given by HAI at dose of 1 g/week on an outpatient basis. The tumor diameter decreased to 1/3 of the initial size at four months after high-dose CHAI. High-dose CHAI using 5-FU may be safe and effective for liver metastases from gastric cancer.

A 74-year-old man had multiple liver recurrence of hepatocellular carcinoma (HCC) after extended left hepatectomy. He was treated by continuous hepatic arterial infusion (HAI) chemotherapy with low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) via an implanted reservoir. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. The patient was administered 10 mg of CDDP on day 1 and 500 mg/day of 5-FU for 4 days as one course. Four courses were administered and the PIVKA-II level decreased from 427 to 216 mAU/ml. However, infusion port problems led to interruption of chemotherapy and PIVKA-II increased to 798 mAU/ml. His chemotherapy was changed to 10 mg of CDDP on day 1 and 750 mg/day of 5-FU for 2 days. After five courses were administered, PIVKA-II decreased to 540 mAU/ml. This patient is still alive 15 months after the start of therapy. This case suggests that HAI with low-dose CDDP and 5-FU might be useful for prolonging the survival of HCC patients with a good quality of life.

We here report a 53-year-old woman who had undergone resection of a choledochal cyst and hepaticojejunostomy three years before. She was readmitted because of intermittent fever, and abdominal computed tomography revealed a 4-cm tumor in the head of the pancreas. We performed pancreatoduodenectomy, and examination of the resected specimen showed well-differentiated papillary adenocarcinoma. Only 5 cases of carcinoma occurring after the resection of a choledochal cyst have been reported, and to our knowledge, this is the second case of carcinoma of the head of the pancreas.

Malignant tumor resection of the hepatic caudate lobe has recently received attention. However, there are few reports about metastatic liver tumor in the caudate lobe from colorectal carcinoma, and its clinical features still remain unknown. In this paper, three patients operated on in our institute and 15 reported cases from the published literature were analyzed in order to reveal clinical features of this disease. Many cases had advanced liver tumors, such as invasion in to major vessels at the time of operation. Isolated complete caudate lobectomy was performed in 8 patients and major hepatectomy was carried out in 6 instances. Seven cases also underwent partial resection of the inferior vena cava. Recurrence of disease was observed in 11 patients: seven cases had relapse only in the residual liver, five of whom underwent another hepatectomy. The median survival time of those patients who died was 25 months, and that of seven cases with IVC resection, 18 months. Two patients out of five who received a second hepatectomy survived for longer than 90 months. It is suggested that aggressive surgical treatment including repeated hepatectomy results in the prolongation of survival. Earlier diagnosis and surgical treatment at a more appropriate stage of the disease may further improve the survival rate.

In our hospital, combination therapy, mainly intra-arterial infusion, is performed for multiple liver metastases of colorectal cancer. The median survival time of the combination group (n = 18), the hepatectomy only group (n = 3) and the best supportive care group (n = 7) were 21.7, 12.5 and 6.1 months, respectively. The prognosis of the combination group was significantly better than that in the other groups (p0.0001). Univariate analysis against the combination group revealed that serum CEA was a significant prognostic factor (p = 0.0196). Moreover, we divided the combination group into two groups on the basis of serum CEA either below or above 50 ng/ml. The prognosis of the low CEA group (n = 11), whose median survival time was 25.9 months, was significantly better than the high CEA group (n = 7), whose median survival time was 17.8 months (p = 0.0031). It therefore appears that combination therapy may be of no benefit when serum CEA is above 50 ng/ml.

Hepatic arterial infusion chemotherapy with 5-FU and CDDP is one of the more attractive regimens for liver metastases from gastric cancer. We report here two chemotherapy related deaths from unexpected complications associated with acute depression of consciousness level due to hepatic arterial infusion chemotherapy.

One hundred and fifty-three patients with liver metastases from colorectal cancer underwent hepatectomy from 1979 to 1998. Recurrence in the residual liver occurred in 71 of the 129 patients with curative B resection, and re-hepatectomy has been done in 21 of these 71 patients since 1984. The 5-year survival rate is 37.0%. MCT has been performed in ten of these 71 patients who could not undergo re-hepatectomy and one patient received both therapies. The 3-year survival rate is 66.7%, which is statistically better than that of 35 patients who could not undergo re-hepatectomy before we started MCT (3-year survival rate of 20.0%). Re-hepatectomy is quite effective for recurrent liver remetastasis after hepatectomy, and MCT is probably of similar value.

Hepatectomy has the highest cure rate among the various methods for treating liver metastasis from colorectal cancer. We previously reported that continuous hepatic arterial infusion (HAI) of 5-FU is effective for improving the prognosis of patients with liver metastasis. In this study, we examined the efficacy of short-term continuous HAI of 5-FU for treating liver metastasis from colorectal cancer. A 57-year-old woman with a solitary liver metastasis from rectal cancer was treated by continuous HAI of 5-FU (1,000 mg/day) for 6 days. Her elevated serum CEA level (20.7 ng/ml) then returned to normal. Computed tomography revealed a decrease of 55.6% in the size of the liver tumor. Partial segmentectomy (S7) was subsequently performed. Histological examination of the resected tumor showed marked degeneration, necrosis, fibrosis, and calcification with viable moderately differentiated adenocarcinoma cells. These results suggest that preoperative HAI of 5-FU is safe and worth trying in patients with liver metastasis from colorectal cancer.

Whether L-Arginine (L-ARG) ameliorates or aggravates renal function and histopathological changes in several models of renal disease remains controversial as L-ARG is the substrate for nitric oxide (NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to differences in the dose and period of L-ARG administration and the animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24-hour urinary excretion of protein (UP), NO metabolites (NO2(-) + NO3-) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. These 5/6 nephrectomized SD rats were divided into 4 groups: 1. L-ARG 0.2 g/kg/day (0.2 g ARG), 2. L-ARG 1 g/kg/day (1 g ARG), 3. L-ARG 2 g/kg/day (2 g ARG), 4. No administration of L-ARG(ARG(-)). Compared with ARG(-)MBP, UP and ADMA were significantly decreased and NO2(-) + NO3-, cGMP were significantly increased in the 0.2 g ARG. SI group and %INT were significantly increased in the 2 g ARG group and decreased in the 0.2 g ARG group. A small dose of L-ARG ameliorated glomerulosclerosis and interstitial fibrosis while a larger dose did not. SI, %INT and ADMA were inversely correlated with NO2(-) + NO3-. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

A patient with advanced intrahepatic cholangiocarcinoma had a tumor embolus in the right main branch of the portal vein and lymph node metastases. Hepatic arterial infusion (HAI) therapy with 5-FU (1 g/day) was given as a continuous infusion for 6 days. The treatment was repeated after a one-week interval. As a result the tumor diameter decreased by half, and the tumor embolus contracted. Cytoreductive surgery was then performed. The patient has been disease-free for over 9 months postoperatively with adjuvant HAI with 5-FU. We consider preoperative HAI with 5-FU (two courses of 1 g/day x 6 days) is both safe and effective.

Fifteen patients with liver metastases of colorectal cancer were entered in our study, and 5-FU was given continuously by hepatic intra-arterial route at 1 g/day over 6 days. No leukopenia (3,000/mm3), anemia (10 g/dl), or thrombocytopenia (75,000/mm3) occurred, and no elevation of serum AST (150 IU/l) or serum T-Bil (2 mg/ml) appeared. One patient (4.2%) had nausea with vomiting 1-5 per day, and another (4.2%) had mucositis requiring treatment. In patients with multiple liver metastases, survival of the continuous infusion group [total dose of 5-FUor = 12 g] (n = 5) seems to be longer than those of the hepatectomy only group (n = 3) or the control group (n = 7). We suggest that this continuous intra-arterial infusion of high-dose 5-FU is a useful chemotherapy with few side effects or complications.

We evaluated the role of magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), in estimating regional liver function in a rat ischemia-reperfusion model. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 min (I-90 group). The ischemic lobes in the I-60 and I-90 groups was clearly visualized as a high intensity area in the T1 images at late phase of Gd-EOB-DTPA enhancement, Moreover, the T1/2 of signal intensity in ischemic lobes significantly correlated with the duration of vascular clamping. We also observed significant correlation between T1/2 and ATP concentration in the liver tissue (r = -0.719, P = 0.04). Our results indicate that MR imaging with Gd-EOB-DTPA is useful for evaluation of regional liver function in rats.

There is now evidence from three randomized controlled trials (from Minnesota, Nottingham and Funen) that screening average-risk individuals for colorectal cancer (CRC) with fecal-occult-blood tests (FOBT) can reduce mortality from CRC. In Japan, mortality rates from CRC have increased and mass screening with FOBT has been performed since 1992. Although there is growing proportion of CRC with FOBT, there is no conclusive evidence that they reduce mortality from this cause. We evaluated the feature of CRC with FOBT, as one of the methods for evaluation of the efficacy of screening with this test.Between January, 1982 and December, 1996, 2071 cases with CRC resected in our hospital were considered. We evaluated the clinicopathological findings about age, sex, location of tumor, size depth, incidence of lymph node metastasis, stage and prognosis of CRC with FOBT (376) compared with CRC with no screening (controls; 1695).CRC with FOBT were earlier stage and smaller-sized cancers than controls. No significant difference was found in the incidence of lymph node metastasis at each depth and prognosis in each stage.By screening with FOBT, we can detect at an earlier stage and with a smaller cancer, with the same biological behavior as controls. Now, we must encourage colon screening, continuing to research ways to improve identification of high-risk subgroups and increase complicance.

From 1979 to 1997, 146 patients had hepatectomy for metastases of colorectal cancer (curative B: 122; curative C: 24). We categorized the severity of liver metastases as follows, H1: one lobe; H2: bilateral but less than five, and H3: bilateral with five or more lesions. In H1 and H2 patients, we compared the survival rate after resection alone (including repeat hepatectomy) with that after combination therapy (resection and prophylactic arterial chemoinfusion of 12-24 g of 5-FU). In H1 patients, the 3-year survival rate of the resected group (n = 74) and combination group (n = 6) was 47.2 and 53.3, respectively. In H2 patients, the resected group (n = 16) and combination group (n = 7) had survival rates of 34.5 and 100%, respectively. In H1 cases, the 3-year recurrence rate in the remnant liver was 63.4 versus 16.7% and in H2 cases it was 58.0 versus 0%. H3 patients received one week of continuous prophylactic arterial chemoinfusion [total dose of 5-FU = 6 g]. All four patients in the H3 combination group are alive at 20, 13, 13, and 12 months after resection, while the median survival of the resection only group (n = 4) was 12.5 months. We suggest that our combination therapy may be applicable to all patients with liver metastases of colorectal cancer.

Colorectal cancer (CRC) infiltrating the submucosa (sm cancer) and the proper muscle (mp cancer) represent an early and an intermediate stage in the development of CRC, and sm and mp cancer are therefore appropriate to discuss the natural history of CRC. A total of 337 sm cancers and 291 mp cancers resected in our series were evaluated. We divided sm and mp cancers into three categories, respectively, sm 1, sm 2, sm 3, mp 1, mp 2, and mp 3, according to the depth of infiltration of the submucosa or the proper muscle. The deeper the invasion, the larger of the tumor size, and the proportion of depressed type in their configuration increases. On the contrary, the proportion of tumors with adenomatous component decreases. A larger proportion of tumors in all categories of infiltration showed PG more of ten than that of NPG in their marginal structure. In this study, 17% of sm cancer and 23% of mp cancer might develop not via the adenoma-carcinoma sequence.

We studied a new two-part therapy for patients of multiple (more than five) bilobar liver metastases from colorectal cancer, in which one lobe is treated with partial hepatectomy and the other with arterial chemotherapy. The patient was a 72-year-old woman who had undergone sigmoidectomy and partial hepatectomy on March 9, 1995, for advanced sigmoid cancer with liver metastasis. In December 1995, new foci were detected in the remaining liver. Intraoperative echography during reoperation revealed 6 foci in the right lobe, 2 in the left lobe and 1 in the caudate lobe. During reoperation, we performed partial hepatectomy at the left lobe metastases and microwave coagulation in the caudate lobe. A catheter was inserted into the right hepatic artery, and the right hepatic artery was ligated with the catheter. From 2 weeks after operation, CDDP (20 mg) and 5-FU (1,500 mg) were given weekly by infusion from the arterial root. As a result, the serum CEA level fell to 3.6 ng/ml on June 26, 1996, and 1.9 mg/ml on August 14, 1996. A right lobectomy would have been performed if no metastasis appeared in the remainder of the left lobe over a one-year period. However, no foci were detected on a CT scan on March 26, 1997. This new two-part therapy warrants detailed investigation for bilobar bilateral liver metastases of colorectal cancer.

We developed a maneuver for holding and lifting the intraperitoneal organs from the extracorporeal side using a new instrument, the leading bar, by which we could guide the tape or the thread to the outside of the abdomen. In the case of cholecystolithiasis with a thickened wall or a stone stuck in the neck, we lifted the round ligament and gallbladder for better exposure of Calot's triangle, using the tape or thread through the abdominal wall to the extracorporeal side, and then clamped them with Kocher's forceps. With this technique, a good view of Calot's triangle was maintained so that the surgeon could expose the cystic duct easily and safely using both hands.

We devised a new therapeutic modality for multiple hepatocellular carcinoma (HCC) consisting of transarterial immuno-embolization (TIE) using OK-432 and fibrinogen, and applied the treatment to 22 patients with advanced HCC who had been insensitive to TAE, and 21 patients who had no treatment. Nineteen patients had a high AFP level of more than 200 ng/ml. The serum AFP level decreased in 15 patients after TIE, and in 7 patients the AFP level decreased to less than 30%. Furthermore, a marked reduction in tumor size was observed in 69% after TIE. We report 61% 1-year, and 3-year survival rate for cases who had been insensitive to TAE, and 86% 2-year survival rate for those who selected TIE as the first choice. A high fever of more than 38 degrees C occurred in all cases, and hypotension less than 80 mmHg was observed in 42% patients. No deterioration of liver function and no disturbance of the coagulation-fibrinolysis system due to TIE except in one patient with liver failure after TIE.

Tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) were isolated from 5 patients with multiple hepatocellular carcinoma (HCC) and with metastatic liver tumor. Proliferation of lymphocytes was observed following addition of interleukin-2 (700 JRU/ml) into the culture media. After analysis of LAK cells by FACS, the antitumor activities were examined. Higher levels of cytotoxic activity against tumor cells (K 562 and Daudi) have continued during the culture period ranging from 2 to 5 weeks. Adoptive immunotherapy was performed using TIL-LAK and PBL-LAK via hepatic artery for three patients with HCC and one patient with metastatic tumor. The average number of administered lymphocytes was 1 x 10(9). Reduction of tumor size was observed after this therapy, which caused no severe side effects exclusive of high fever and pleural effusion. Our results indicate that the treatment using lymphokine activated killer cells and interleukin-2 may be a promising modality for patients with multiple HCC.

We studied and analysed the effects of combination therapy with TAE and PEIT for unresectable HCC. The subjects were 28 patients (21 males, 7 females) with 31 tumors treated in the Department of Surgery, Osaka Teishin Hospital. The patients were divided into four groups on the basis of the tumor size (3 cm, 3-5 cm, 5-8 cm,8 cm). The therapeutic effect on the tumors was evaluated on the basis of the maximum reduction rate within 3 months after TAE and PEIT. The response rates after treatment were 87.5%, 60.0%, 25.0% and 0% for3 cm, 3-5 cm, 5-8 cm, and8 cm tumor size, respectively. The 50% survival period was 50.9 months. The 1-, 2-, 3- and 5-year survival rates were 92%, 76%, 52% and 32%, respectively. In the cases of over 8 cm, this combination therapy had no effects on the survival period. The findings of the present study suggest that the combination therapy was useful for the unresectable HCC of under 5 cm in diameter.

The efficacy of transarterial immuno-embolization therapy (TIE) was examined in six operable patients with hepatocellular carcinoma (HCC). We administered OK-432, fibrinogen (30 mg/ml) and thrombin (1 U/ml) through a catheter which was inserted into the tumor-feeding artery. In all patients with a high level of tumor markers (AFP and PIVKA-II), the level decreased promptly to less than the pretreatment level after TIE therapy. The therapy has not caused any serious side effects. No disturbance of the coagulation-fibrinolysis system due to TIE was observed in any patient. Histological examination of resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests, and lytic necrosis as well as coagulation necrosis of the main tumor and the intrahepatic metastases. Our results indicate that TIE may be an effective and promising modality for HCC patients.

A 36-year-old man with anemia due to gastrointestinal bleeding, diagnosed to have a leiomyoma of the duodenum, is described. The conventional barium meal study and gastroendoscopy were useful for diagnosing the lesion. More invasive radiological methods, such as abdominal angiography and technetium-99m scintigraphy failed to detect the tumor. Early diagnosis and resection of the tumor would result in a good prognosis.

Nine patients with multiple metastases including liver from breast cancer were treated with transarterial chemoembolization through hepatic artery using 40-50 mg of 4'-epi-adriamycin and Lipiodol, followed by 800-1,200 mg/day of medroxyprogesterone acetate. Of 9 patients thus treated, there were 4 partial response (44%), 2 no change and 3 progressive disease. Duration of disease control ranged from 4 to 46 months (mean 24.5 months). Seven out of 9 patients died within 6 to 37 months (mean 15.3 months) after diagnosis of liver metastases. The 3- and 5-year survival rates were 45% and 11%, respectively. We conclude that this therapy is a useful treatment modality for controlling liver metastases of breast cancer.

4152 Background: Gemcitabine (GEM) remains the standard of care for advanced pancreatic cancer. The rationale to develop the pretreatment of 5-fluorouracil (5-FU) and GEM combination in pancreatic ...