Mitsuhiro Mukaiya

Lack of Survival Benefit of Extended Lymph Node Dissection for Ductal Adenocarcinoma of the Head of the Pancreas: Retrospective Multi-institutional Analysis in Japan

Abstract. It has not been established that extended lymph node resection is necessary for ductal adenocarcinoma of the head of the pancreas. According to the general rules for the study of pancreatic cancer, a multiinstitutional, retrospective clinical study was undertaken to investigate the efficiency of extended lymph node dissection for this malignancy. Altogether 501 patients underwent resection of the pancreas between 1991 and 1994 at 77 medical facilities; the surgical procedures, staging, lymph node dissection, curability, and survival rate were analyzed retrospectively. Eighteen of the patients died within 30 postoperative days, leaving 483 patients to be studied. The resection was curative microscopically in 94 patients, resulting in a 3-year survival of 29%. Macroscopically curative resection resulted in a 3-year survival of 14%; noncurative resection produced a 3-year survival of 6%. Although extended lymph node dissection was performed on 38 patients in stage I, 42 patients in stage II, 206 patients in stage III, and 1 patient in stage IV, there was no improvement in survival when the results were compared to those seen after standard or palliative lymph node dissection. The extent of lymph node dissection has not affected the prognosis for ductal adenocarcinoma of the head of the pancreas at any stage of the course of the disease. Excessive lymph node dissection in advanced cases does not necessarily lead to a favorable prognosis. The patients who undergo a radical operation with an adequate lymph node dissection have longer survivals.

Inhibition of Liver Metastasis of Human Pancreatic Carcinoma by Angiogenesis Inhibitor TNP‐470 in Combination with Cisplatin

The anti‐tumor and anti‐metastatic effects of O‐(chloroacetyl‐carbamoyl) fumagillol (TNP‐470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti‐neoplastic agent, were investigated using our established liver‐metastasizing pancreatic carcinoma line, HPC‐3H4. HPC‐3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP‐470, a group receiving 90 mg/kg TNP‐470, a group receiving 90 mg/kg TNP‐470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP‐470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP‐470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP‐470 in combination with 0.25 mg/kg CDDP. TNP‐470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP‐470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP‐470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC‐3H4 cells was only mildly inhibited by TNP‐470, but the production of vascular endothelial growth factor (VEGF) by HPC‐3H4 was clearly inhibited by TNP‐470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP‐470 in combination with low‐dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.

Identification of segments VI and VII of the liver based on the ramification patterns of the intrahepatic portal and hepatic veins.

We describe the pattern of intrahepatic vessel ramification in the right posterior hepatic sector in a population of 197 adults. Each specimen was dissected from its visceral (inferior) surface in order to demonstrate variations in the distribution of the portal vein branches to the hepatic segments of the right lobe, especially to segments VI (S6) and VII (S7) as described by Couinaud. We also examine whether three hepatic veins, i.e., the right hepatic vein (RHV), middle hepatic vein (MHV), and the short hepatic vein (SHV), aid the identification of segmental portal branches in the lower posterior sector. Four major patterns of branching of the posterior sectorial trunk of the portal vein system are described. In group A (32.0%) a single posterior trunk formed an arch‐like pattern sending multiple branches to S6 and S7 (P6 and P7). We named the multiple branches to the apparent S6 the inferoposterior portal branches. It was difficult to identify which of these branches were equivalent to P6. In group B (27.9%), the posterior sectorial trunk bifurcated to form P6 and P7. In most of the specimens in this group, therefore, we were able clearly to identify both S6 and S7 based on the portal vein system. In group C (6.6%), the trunk trifurcated to form P6, P7, and an intermediate branch, which supplied both segments or a gray zone between them. Group D (33.5%) included variations of the anterior segmental branches, and in specimens of this group, the anteromedial border of the sector was difficult to identify. Notably, the three‐dimensional interdigitating topographical relationship of the hepatic veins and the portal branches was not evident in the lower posterior sector, since tributaries of the RHV and the portal branches followed similar courses and paralleled each other in the region and since the territory of the SHV was usually restricted to the superficial parenchyma near the inferior surface. In group A, tributaries of the RHV/SHV (>3 mm in diameter) passed between the inferoposterior portal branches in only 22.2%/14.3% of the specimens. Thus the hepatic veins often did not reveal which of the multiple inferoposterior branches was P6. Moreover, in the subset of Group B in which the segments were identified based on the portal vein ramification, tributaries of the RHV/SHV (>3 mm in diameter) showed the intersegmental interdigitating arrangement in only 32.0%/6.0% of the specimens. In addition, a thick tributary of the MHV, sometimes arising from S6, did not run along, but penetrated the S5/S6 border plane from the lateral to the medial side. Therefore, the three hepatic veins (RHV, SHV, MHV) often did not aid the identification of the liver segments in the region. Consequently, the less than ideal combinations of irregular configurations of the portal and hepatic venous systems suggest that the right posterior segments cannot be conclusively identified anatomically in 30–40% of cases. Other means of identification, such as the conventional proportional manner (the upper and lower halves of the posterior sector roughly correspond to S6 and S7) may be required. Clin. Anat. 12:229–244, 1999.

Congenital Arteriovenous Malformation of the Pancreas : Its Diagnostic Features on Images

To analyze diagnostic features on images of congenital arteriovenous malformation (AVM) of the pancreas, we analyzed the diagnostic findings in six patients with the disease, using gray-scale ultrasonography (US), color Doppler US, computed tomography, and angiography and analyzed previously reported cases. AVM characteristic findings on images were multiple, small hypoechoic nodules on US, mosaic appearance of the lesion and pulsatile wave form in the portal vein on color Doppler US, conglomerated small nodular enhancement of the lesion and early appearance of the portal vein on CT, and a racemose network and early appearance of the portal vein on angiography. Five of the six patients underwent surgery, and all resected specimens were histologically found to be AVMs of the pancreas; however, one with developed portal hypertension at surgery died of repeated bleeding from esophageal varices. From analysis of total of 35 cases including our six cases, a mosaic appearance of the lesion was found in 100% and a pulsatile wave form in the portal vein in 77.8% on color Doppler US. Color Doppler US is noninvasive and useful for detecting congenital AVM of the pancreas at an early stage, preventing the portal hypertension causing esophageal varices and their rupture.

Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal carcinomas.

Aim: To determine whether superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) could replace intravenous contrast-enhanced spiral CT (iv-CT) and spiral CT during arterial portography (CTAP) combined with spiral CT hepatic angiography (CTHA) in the diagnosis of liver metastases from colorectal carcinomas. Methods: Twenty-six adult patients with liver metastases were studied preoperatively by means of iv-CT, CTAP/CTHA, and SPIO-MRI. Preoperative diagnoses using iv-CT, CTAP/CTHA, and SPIO-MRI were compared with intraoperative and pathological findings in resected specimens. The gold standard for the lesions that were resected was histological examination. Intraoperative findings represented the gold standard for lesions that were not resected. Results: Twenty-six patients were found to have a total number of 43 liver metastases. The sensitivities of iv-CT, CTAP/CTHA, and SPIO-MRI were 74.4, 100, and 90.7%, respectively. SPIO-MRI was significantly superior to iv-CT (p < 0.05). The positive predictive values of iv-CT, CTAP/CTHA, and SPIO-MRI were 97.0, 91.5, and 100%, respectively. CTAP/CTHA yielded four false-positive lesions. In contrast, we detected no false-positive findings using SPIO-MRI. Conclusions: These results suggest that SPIO-MRI might not completely replace CTAP/CTHA, but could replace iv-CT in the diagnosis of liver metastases from colorectal carcinomas. It is thought that SPIO-MRI is a promising imaging modality for diagnosing liver metastases in patients with colorectal carcinoma because of its relatively high sensitivity and extremely high specificity.

Changes in portal hemodynamics and hepatic function after partial splenic embolization (PSE) and percutaneous transhepatic obliteration (PTO)

Since April 1985, we have performed a multidisciplinary therapy consisting of partial splenic embolization (PSE), percutaneous transhepatic obliteration (PTO) or transileocolic vein obliteration (TIO), and endoscopic injection sclerotherapy (EIS) for patients with severe gastroesophageal varices and those with a portacaval shunt associated with portal hypertension. In this study, PSE and percutaneous transhepatic portography (PTP) were performed at the same time in seven liver cirrhosis patients with hypersplenism, gastroesophageal varices, or hepatocellular carcinoma. The changes in portal blood flow/pressure and hemodynamics were examined by a thermodilution method. The effects of PSE on blood biochemical parameters such as the platelet count, ICG R15, redox tolerance index (RTI), and oral glucose tolerance test (75 g OGTT) were also evaluated. PSE induced a decrease in the blood flow of the splenic artery and in the splenic vein pressure without decreasing the portal blood flow. The platelet count in the peripheral blood and the RTI increased significantly. These results suggest the possibility that PSE may reduce the potential perioperative risk in hepatocellular carcinoma complicated with liver cirrhosis.

Macrocystic serous cystadenoma of the pancreas : importance of co-existent tiny cysts depicted by EUS

Abstract: The case of a 38-year-old man with an unusual type of serous cystadenoma of the pancreas is reported. A multilocular cystic tumor in the head of the pancreas was detected on abdominal ultrasonography and computed tomography. On endoscopic ultrasonography, the major cysts ranged from 2.0 to 4.5 cm in size. In addition to these large cysts, a few small cysts were detected. Based on these findings, this tumor was diagnosed as a macrocystic type serous cystadenoma. Because endoscopic retrograde pancreatogram showed a compression of the main pancreatic duct around the tumor, and because the size of the tumor had been increasing over a 3-year period, surgical intervention was performed. The resected tumor consisted of macrocysts, with a few small cysts, and was histologically diagnosed as serous cystadenoma. Endoscopic ultrasonography appears to provide an excellent inside image of this unusual tumor, and because of its ability to detect small cystic lesions clearly, it could be useful in the diagnosis of macrocystic serous cystadenoma.

A Chylous Cyst of the Mesentery : Report of a Case

A case is presented of an adult chylous cyst of the mesentery that was preoperatively diagnosed to be a pancreatic cystadenoma. A 66-year-old asymptomatic male was followed up for 15 months under the diagnosis of a benign pancreatic cyst. On October 1997, computed tomography showed a 45 x 40 mm cystic mass in the upper abdomen which came in contact with the pancreas. Endoscopic ultrasonography revealed a multilocular mass with a 7 x 4 mm elevated lesion. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed the cystic mass to be unrelated to the pancreatic duct. The preoperative diagnosis was a pancreatic cystadenoma or cystadenocarcinoma. A laparotomy showed a 50 x 40 mm cystic mass containing chylous fluid, that arose from the mesentery of the upper part of the jejunum. The pathological diagnosis was a chylous cyst of the mesentery. The preoperative diagnosis in this case was very difficult because the chylous cyst appeared to be attached to the pancreas and this phenomenon is considered to be extremely rare.

Changes in serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy

The clinical significance of serum apolipoprotein A‐1 levels as an indicator of hepatic protein synthesis after hepatectomy was investigated. A total of 50 patients who had undergone hepatectomy at our department from 1997 to 1999 were selected for this study. The serum levels of apolipoprotein A‐1, indocyanine green dye retention at 15 minutes, lectin‐cholesterol acyltransferase, prealbumin, and high‐density lipoprotein cholesterol were measured in these patients preoperatively and on postoperative days 7 and 14. The type of hepatic resection conducted was partial resection in 13 cases, subsegmentectomy in 13 cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the patients tolerated the operation, and none of the cases had any severe complications, such as liver failure. In most cases, the serum apolipoprotein A‐1 levels decreased on postoperative day 7 and recovered by day 14. There were no significant differences in the changes in apolipoprotein A‐1 levels between patients with the individual types of operative procedures. The serum apolipoprotein A‐1 levels showed significant correlations with the serum high‐density lipoprotein cholesterol, lectin‐cholesterol acyltransferase and prealbumin levels on postoperative days 7 and 14; however, there was no significant correlation with the indocyanine green retention test. When the cases were divided into three groups according to the serum level of apolipoprotein A‐1 on postoperative day 7 (group A: over 81 mg/dl, group B: 61–80 mg/dl, group C: under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin‐cholesterol acyltransferase and high‐density lipoprotein cholesterol levels in group C were significantly lower than those in group A on postoperative day 7. On the basis of these results, it is suggested that the pattern of changes in the serum apolipoprotein A‐1 levels may be a good indicator of the hepatic protein synthetic ability during the perioperative period after hepatectomy.

Establishment and characterization of human pancreatic carcinoma lines with a high metastatic potential in the liver of nude mice.

To investigate of human pancreatic cancer metastasis to the liver, a pancreatic carcinoma line, HPC-3, was injected into the spleens of nude mice. The cells from a few liver metastatic foci of the mice injected with HPC-3 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these procedures, we were able to obtain a cell line, designated HPC-3H4. The mice were observed to have liver metastasis in 6 of 6 (100%) cases injected with HPC-3H4, whereas the rate was 0% at 3 weeks after the intrasplenic injection of HPC-3. The tumorigenicity of HPC-3H4 was more rapid than that of HPC-3. The motile activity of HPC-3H4 was also stronger than that of HPC-3, and the adhesion to the extracellular matrix of HPC-3H4 was stronger than that of HPC-3. We also analyzed the cell surface expression of the metastasis-related adhesion molecules. As a result, no substantial changes were observed in the expression level of adhesion molecules. These results suggest that HPC-3H4 is useful for studies aimed at the prevention of liver metastasis.