Search

With a view toward furthering the development of artificial liver systems, we have been culturing hepatocytes in vitro. The object of this research was to investigate the ideal conditions of oxygen tension for the efficient functioning of hepatocytes. Viable hepatocytes isolated from rat livers were cultured under five different oxygen tensions: 5, 10, 20, 50 and 90% O2. DNA contents, gluconeogenesis, urea synthesis, adenosine triphosphate (ATP) levels, and lipid peroxidation of hepatocytes were evaluated. Under the 5% oxygen conditions, the function of hepatocytes was very inferior and was accompanied by a low ATP level. However, hepatocytes cultured under 90% oxygen tension functioned less effectively than the control (20% O2) with elevated lipid peroxidation. The data in this study suggest that the optimum oxygen condition for cultured hepatocytes is 10 approximately 50%, and that especially under conditions of 20% oxygen tension, i.e., that of the ordinary atmosphere, hepatocytes can function most effectively.

Since 1987, we have been developing a bioartificial liver (BAL) using multiplated cultured hepatocyte monolayers. With the goal of promoting hepatic functions of cultured hepatocyte monolayers, we combined the use of a collagen gel layer over the monolayers of hepatocytes and/or cocultured hepatocytes with nonparenchymal cells (NPCs). The study was divided into four groups according to culture configurations: Group 1: hepatocyte monolayer culture (control); Group 2: coculture of hepatocytes and NPCs; Group 3: hepatocyte monolayer with a overlaid collagen gel layer; and Group 4: coculture with a overlaid collagen gel layer. The culture continued for 14 days. Morphological changes and hepatic functions were evaluated by urea and albumin syntheses. The morphological status of the hepatocytes remained for 2 weeks in Groups 3 and 4. Deterioration and detachment of hepatocytes and/or NPCs started in Group 1 and 2 on the third day in culture. Significantly high urea synthesis was noted in Group 4 (p < 0.001 compared with Group 1 and 2: p = 0.0014 compared with Group 3). Although there was no significant difference in albumin synthesis among the four groups, those hepatocytes covered by the collagen gel (Groups 3 and 4) tended to secrete albumin throughout the observation period. These results indicted that the environment, although artificial (but close to the in vivo state), supplied with collagen gel and the coculture, enhanced the activities of the cultured hepatocyte monolayers. We suggest that use of cocultured hepatocytes under a collagen gel is a promising candidate for a bioreactor of multiplated BAL.

The effect of adjuvant immunochemotherapy including OK-432 (Picibanil) on survival was assessed in patients who underwent curative resection of gastric cancer. Patients enrolled in this randomized controlled study were randomly assigned to group A or group B. Group A patients received 800 mg/d 5'-DFUR (Furtulon) for 2 years from 2 weeks after the operation. Group B patients received OK-432 plus 5'-DFUR by the same regimen as in group A. This study enrolled 288 patients, and 1 patient with malignant lymphoma was excluded. Among the remaining 287 patients, 143 and 144 were allocated to group A and group B, respectively, and their data were included in statistical analysis. The 5-year survival rates for groups A and B were 62.9% and 63.8%, respectively, showing no significant difference (P = 0.7996).

A prospective randomized multi-center study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of futraful (FT) and tamoxifen (TAM) for postoperative adjuvant therapy for stage II breast cancer after curative surgery.Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX) 20 mg/body on the day of surgery and 10 mg/body the next day, followed by oral FT 600 mg/day for 2 years from the 14th day after surgery; treatment B, the same pattern of DOX administration followed by combined therapy with FT and TAM 20 mg/day for 2 years. The number of patients was 428 (treatment A 210 and treatment B 218), of whom 418 (97.7%) were followed for 10 years for analysis.Significantly higher 5- and 10-year overall survival (OS) rates were observed with treatment B compared with treatment A (p=0.0101 and 0.0219). Node-positive patients appeared to derive more benefit from TAM than node-negative patients. The difference in 10-year OS between treatment A and treatment B was more evident than that of the 5-year OS in patients with more than 4 positive nodes (p=0.0313 vs. 0.0479). No increase in adverse reactions was seen as a result of combining TAM with FT.The study results demonstrate that for stage II breast cancer concomitant administration of FT and TAM is superior to FT alone for postoperative adjuvant therapy, and administration of TAM for 2 years may contribute not only to 5-year survival rates but also to 10-year survival rates of node-positive patients.

Purpose: Hepatoblastoma is the most common malignant liver tumor in childhood. Multicenter studies elucidate the optimal pre- or postoperative chemotherapeutic regimens. This report reviews the results of the Japanese Study Group for Pediatric Liver Tumor Protocol-1 (JPLT-1) and compares its outcomes with published reports of other studies. Methods: From March 1991 to December 1999, 154 patients with malignant liver tumor including 145 cases of hepatoblastomas were enrolled in the JPLT study. Data from 134 cases were analyzed in this study. JPLT-1 protocol 91A was used for patients with stage I or II hepatoblastoma. The chemotherapy regimen consisted of repeated courses of cisplatin (CDDP), 40 mg/m 2 , and tetrahydropyranyl (THP)-Adriamycin, 30 mg/m 2 . JPLT-1 protocol 91B was administered to patients with stage IIIA, IIIB, or IV hepatoblastoma. The chemotherapy regimen consisted of repeated courses of CDDP, 80 mg/m 2 , and THP-Adriamycin, 30 mg/m 2 /day for 2 days. Courses were repeated every 4 weeks as tolerated. Results: Seven patients died of chemotherapy-related side effects. Six of them died of sepsis caused by leukopenia and 1 case of liver failure. Overall survival rate (3-year/6-year) was 100%/100% for stage I (n = 9), 100%/95.7% for stage II (n = 32), 76.6%/73.8% for stage IIIA (n = 48), 50.3%/50.3% for stage IIIB (n = 25), 64.8%/38.9% for stage IV (n = 20), and 77.8%/73.4% overall. For stage IIIA and B disease, intravenous chemotherapy was better than intraarterial chemotherapy (66.4% v 38.1% for event-free survival and 69.3% v. 57.1% for overall survival). Patients less than 1 year of age had a better prognosis than older patients, but age was not a significant prognostic factor by multivariate analysis. Conclusions: The overall and event-free survival rates of the JPLT-1 study of hepatoblastoma were comparable with the results of other multicenter studies in Europe and the United States. The event-free survival rate at 3 years for stage IIIB and IV disease was under 50%. New treatment strategies are needed for patients with advanced hepatoblastoma. J Pediatr Surg 37:851-856. Copyright 2002, Elsevier Science (USA). All rights reserved.

Purpose: To elucidate the efficacy of intensive induction and consolidation chemotherapy regimens (Study Group of Japan for Advanced Neuroblastoma [JANB] 85) for patients with advanced neuroblastoma aged I year or older. Patient and Methods: One hundred fifty-seven patients with newly diagnosed advanced neuroblastoma were entered into this study between January 1985 and December 1990. Eligible patients were 12 months old or older with stage III or IV disease. The patients first received six cyclic courses of intensive induction chemotherapy (designated regimen All consisting of cyclophosphamide (1.200 mg/m 2 ). vincristine (1.5 mg/ m 2 ), tetrahydro-pyranyl Adriamycin (pirarubicin; 40 mg/m 2 ), and cisplatin (90 mg/m 2 ). The patients were further treated with three different consolidation protocols: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea, dacarbazine, and bone marrow transplantation. Results: Overall survival rates for patients with stage III disease without reference to the consolidation protocols were 80.8%, 76.9%, and 66.3% at 2, 5, and 10 years, respectively. The overall survival rates for patients with stage IV disease were 58.8%, 34.4%, and 28.9% at 2, 5, and 10 years, respectively. There were no statistically significant differences between the three consolidation treatment groups. Patients who did not achieve complete remission (CR) with induction chemotherapy and surgery all died, suggesting that CR is essential for the cure of advanced neuroblastoma. The overall 5-year survival rate of the 24 patients with N-myc amplified stage III and IV disease was 33.3%, and the longest survival time of a relapse-free patient was 103 months. Conclusion: The intensive induction chemotherapy regimen used in this study may be of significant value in increasing the CR rate and survival for patients with N-myc amplified and nonamplified advanced neuroblastoma.

We analyzed the outcome of 1408 patients who underwent laparoscopic cholecystectomy (LC) between February 1991 and October 1993 in affiliated community hospitals around Hokkaido, Japan. LC was performed for symptomatic gallstones (68%) and asymptomatic gallstones (29%) using the pneumoperitoneum (96%) or abdominal wall lift (4%) techniques. Intraoperative and postoperative complications occurred in 105 patients (10%), including bile duct injuries in 9 patients (0.9%). Conversion to open surgery or reoperation was required in 89 patients (8%) mainly because of unclear anatomy, difficulties with hemostasis, or bile duct injury. One patient died of congestive heart failure, resulting in a mortality rate of 0.07%. The patients were discharged after an average of 8 days, and returned to work after an average of 14 days. The complication and conversion rates were high; however, the incidences of reoperation, bile duct injuries, postoperative bile leaks, and deaths were low. In conclusion, LC was performed with acceptable safety in our community hospitals. The reason for this is most likely that conventional cholecystectomy was preferred to LC in difficult cases during this early period.

Background: Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility hasbeendiscussed that chemoendocrine therapy combined with endocrine agents is more effective. Methods: In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breastcancer, we ran a pilot study during the period from July 1994to July 1996. Results: Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m 2) i.v. and 5-fluorouracil (500 mg/body) i.v, on day 1 (repeated every3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10 %), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response ratewas 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity andhematological toxicity, butthesewereclinically well tolerated. No serious cardiac, liver or renal symptom was seen. Conclusions: Based on these results, we consider the addition of high-dose toremifene to the CAFtherapy to be useful in the treatment of advanced and recurrent breast cancer.

We report an extremely rare case of internal herniation through an abnormal defect in the left broad ligament. A 57-year-old woman complaining of epigastralgia and vomiting was admitted to the hospital because of ileus. Plain abdominal radiograph showed some air-fluid levels of small bowel loops. Because lower abdominal pain appeared and was intensified, abdominal ultra-sonographic (US) and computed-tomographic (CT) stydies were performed. US and CT studies showed the mesenterium and dilated small bowel loops from left side of the fundus and body of uterus to the Douglas's fossa. Therfore, the patient was diagnosed as having a mechanical ileus strangulated in the left side of lesser pelvic cavity, and an emergency laparotomy was performed. At surgery, there was an abnormal defect in the left broad ligament, 4.0cm in diameter, with 150cm of ileum herniated through this defect. The herniated ileum was reduced and put back as usual, and defect of broad ligament was sutured and closed. It is suggested that US and CT studies are useful in preoperative diagnosis of this condition.

The second 5-year study of postoperative adjuvant therapy in patients with breast cancer between 1985 and 1988 was performed by the Study Group for Adjuvant Chemoendocrine Therapy for Breast Canecr (ACETBC). This report describes the results of a meta-analysis of the outcome. A total of 3012 patients with stage II, estrogen-receptor-positive primary breast cancer who underwent radical surgery (total mastectomy with at least axillary dissection) were eligible for the analyses. On the day of surgery, all patients received 13 mg/m(2) of mitomycin C (MMC) intravenously. Patients were then given one of two adjuvant chemoendocrine therapies for 2 years:regimen A, consisting of tamoxifen citrate (TAM) 30 mg/day, or regimen B, consisting of TAM 30 mg/day plus tegafur (Futraful, FT)600 mg/day. The results from all eligible patients were included in a meta-analysis according to the method of Peto et al. The odds reduction rate was 12 +/-13% (log-rank test, P= 0.35)for the 5-year survival rate and 16 +/- 10% (log-rank test, P=0.093)for the 5-year non-recurrence rate. In terms of the 5-year non-recurrence rate. regimen B(with FT)yielded slightly, but not significantly, better results than regimen A. In addition, stratified analyses were carried out with respect to the 5-year non-recurrence rate. Regimen B(with FT)yielded significantly better results than regimen A in patients with four or more positive axillary nodes (log-rank test, P= 0.039) and yielded slightly, but not significantly, better results than regimen A in premenopausal patients (log-rank test, P= 0.079).

The influence of warm ischemia on calcium mobilization in liver transplantation was investigated. Twenty-four porcine orthotopic liver transplantations were performed by a temporary portal arterialization technique. Swine were divided into three groups according to warm ischemia time; I (0 min,n=9), II (30 min,n=8), and III (60min,n=7). Ionized calcium was measured in arterial and hepatic venous blood, in initial perfusate, and in initial perfused blood. In group I, all the pigs survived, while in group III all succumbed. In group II, four survived and four died. Ionized calcium level in influx showed no differences, but the level in the initial perfusate in group I was significantly higher than that in group III. The level in the initial perfused blood in group I was significantly higher than levels in groups II and III. Retrospective analysis in group II showed that ionized calcium value in the initial perfused blood in the survivors was significantly higher than that in the non-survivors. A substantial amount of ionized calcium accumulated after revascularization in the graft loaded with warm ischemia, and, in group II, significantly more ionized calcium accumulated in the non-survivors.

Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.

Carcinoma of the ampulla of Vater is closely associated with tubular and villous adenomas of the ampulla. Its prognosis is strongly related to the degree of invasion and nodal involvement. However, th

Alveolar echinococcosis of the liver (AEL) takes a progressive and malignant course. Intra-abdominal dissemination of the parasite has a miserable outcome. Complete resection of the lesion is indispensable for the curative treatment of AEL. We experienced an extremely rare case of intra-abdominal rupture of AEL. The patient had repeated recurrences of AEL following the traumatic rupture of the lesion. After repeated resections of the lesions and appropriate medication, the patient is still alive more than 25 years since the initial onset of the disease. AEL differs from unilocular echinococcosis in terms of biological behavior. We compare the pathophysiology of the two conditions.

A reliable method for recognizing lymph node metastasis is indispensable for the attending physician to recommend less extensive treatment for early gastric carcinoma. Here we review 1137 consecutive patients with a single primary lesion, and the incidence and distribution of nodal involvement were investigated for correlations with pathologic findings. The overall incidence of metastasis was 9.5%: 2.6% for mucosal and 16.5% for submucosal carcinomas, a significant difference. The occurrence of metastasis was highest for lesions of the macroscopically mixed type, microscopically diffuse type, and large size. The involved nodes were most frequently found in the perigastric nodes along the lesser and greater curvatures, and it was well correlated with the tumor location, macroscopically depressed/mixed type, cancer depth, and histology. The diffuse-type carcinomas were most likely to metastasize to distant nodes. The distribution of involved nodes for early gastric carcinoma was similar to that for advanced carcinoma, as previously been reported. The submucosal carcinomas in this series had no indications for less extensive treatment, such as endoscopic or laparoscopic limited surgery. These carcinomas should be subject to standard surgery with gastrectomy and combined dissection of lymph nodes, especially node stations 1 and 3 to 8. The mucosal carcinomas sometimes involved the perigastric nodes, and such cases underwent gastrectomy and lymphadenectomy of node stations 1 and 3 to 7. Mucosal carcinomas 10 mm or less in size were negative for lymph node metastasis and were considered appropriate for less extensive treatment.

Background Tumor invasiveness is a factor that influences the prognosis of patients with hepatocellular carcinoma. Urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR) play an important role in malignant invasion. This study estimated the invasion potential of u-PA and u-PAR by hepatocellular carcinoma cells in vitro.

Cure of alveolar echinococcosis of the liver can be achieved by complete removal of the lesion, this being possible only by hepatic resection. Nevertheless, 25% of patients have unresectable lesions. The purpose of this work was to analyze the clinical sequelae and prognosis of patients after curative and palliative surgery for alveolar echinococcosis of the liver. The 10-year survival rate of patients who underwent hepatectomy with complete resection of the lesion was 100% compared with 63% in the patients who had hepatectomy with incomplete resection of the lesion. Thirty-seven patients with unresectable hepatic echinococcosis were divided into two groups; the 10 patients in group A underwent only exploratory laparotomy, and the 27 patients in group B had palliative surgery. In group B, marsupialization or cyst drainage was performed in 17 patients, biliary drainage in 6 patients, and biliary reconstruction in 4 patients. The outcome after surgery was compared in the two groups. The 5-year survival of the patients in group A was 30%, and all patients died of liver failure within 7 years. The survival rates of patients in group B were 60% at 5 years, 55% at 10 years, and 35% at 15 years. Complete removal of the lesion by hepatectomy results in satisfactory prognosis. Palliative surgery may offer improvement in terms of survival and quality of life when complete removal is not possible.

Decreased skin reactions using five kinds of recall antigens correlate d with the stage of colorectal cancer. Immunosuppressive factors in the serum (IS index) increased with the progression of the stage in cancer patients, but interleukin (IL)-I and IL-2 production in peripheral mononuclear cells (PBMC) did not correlate with the advance of the disease. In patients with low immunosuppressive factors, the score of skin reactions was significantly higher than that in patients with high immunosuppressive factors. Increased serum immunosuppressive factors seem to reduce skin reactions in the patients. Furthermore, significant difference in skin reaction score was observed between patients with high IL-1 production of PBMC and patients with low IL-1 production of PBMC. These results suggest that skin reaction might be controlled by serum immunosuppressive factors and IL-1 production of PBMC, and that the score of skin reaction using multirecall antigens is a useful parameter to learn the host immunity in colorectal cancer.

Hemobilia and persistent fever-up following a blunt liver trauma is often a strong suspicion of infection of biloma, and may be certain signs of poor prognosis. We have experienced a successfully saved patient suffering from this status. A 23-year-old male injured in a motorcycle accident was admitted to the hospital because of an abdominal pain. We diagnosed him with liver trauma classified IIIa by The Japanese Association for The Surgery of Trauma. Suturing of the liver was performed, and hemorrhaging stopped. On the 5th postoperative day (POD), abdominal CT showed a biloma. It became larger and larger, and the drainage was esterblished on the 25th POD. On the 31st POD, he suddenly had an abdominal pain, hematemesis and anal bleeding, and massive blood was found in the drainage tube. With a diagnosis of hemobilia he was treated conservatively, but hemobilia occerred often. Finally, on the 68th POD he underwent a right lobectomy. Thereafter, he was stable and discharged from the hospital on the 107th POD. Biloma accompanied by liver trauma is frequently infected, and when it gets larger hemobilia should be suspected with high a probability. Radical resection of the diseased liver may be applied to such a patient.

Werner's syndrome is an autosomal recessive disease with premature senility, scleroderma-like changes, characteristic habitus & stature, and often complicated with a malignant tumor. This paper reports on a very rare case of breast cancer as a complication in Werner's syndrome. A 48-year-old female was seen at our department because of 1cm tumor in A region of her left breast. The tumor was diagnosed as left breast cancer (T2a, No, Mo, stage II). Modified radical mastectomy was performed. Pathological diagnosis was solid-tubular carcinoma, f, s, no. DNA ploidy pattern was aneuploidy. Amplification of c-erbB-2 gene was not found. Postoperative course was uneventrul. We should entertain a possible association of breast cancer in the treatment of Werner's syndrome, though it occurs in a low frequency.

An adult case of giant retroperitoneal matured teratoma with high serum levels of CEA and CA19-9 is described together with a review of the literature. A 20-year-old woman was seen at the hospital because of a mass in the right lateral abdomen which was detected at an artificial abortion in another hospital. On admission serum CEA and CA19-9 were as high as 59.8ng/dl and 166.2U/ml, respectively. In computed tomography and magnetic resonance imaging, the tumor was visualized as a giant multiloculated and cystic mass showing various components comprizing of fat, bone and fluid. An abdominal angiography revealed that the tumor was hypovascular in nature and encasement and tumor stain were not observed. Under a diagnosis of retroperitoneal teratoma, extirpaion of the tumor was performed. Macroscopically, the specimen was cystic multiloculated tumor, consisting of white transparent fluid and yellowish pappy materials containing hairs. The tumor was 26.5×17.5×9.3cm in size and 2.325g in weight. Examination of the tumor markers in the content showed remarkably high levels of CEA of >10, 000ng/dl and CA19-9 of >10, 000U/ml. The histological examination revealed that the tumor was matured benign teratoma with components from three germ layers. After extirpation of the tumor, serum levels of CEA and CA19-9 decreased to the normal levels. The patient has been in good health without any sign of recurrence for 18 postoperative months. The patient is followed on ambulant basis.

門脈右枝内の腫瘍塞栓および肝S7領域の腫瘍性病変を合併したalpha-fetoprotein (AFP) 産生胃癌を経験した. 症例は52歳の男性. 胃噴門部にBorrmann 3型胃癌を認め, 血清AFP値は818.5ng/mlと高値を示した. 手術は胃全摘・肝右葉切除・門脈内腫瘍塞栓摘除術を施行した. 病理組織学的に胃腫瘍, 肝腫瘍および門脈内腫瘍塞栓はすべて同じ低分化型腺癌であり, 免疫組織学的にAFPの存在が証明された. 以上より, 肝腫瘍は門脈を介した胃腫瘍の転移性病変と推測された. 血清AFP値は術後33.3ng/mlまで低下した. 臨床的に血清AFP値が高値で, 門脈内腫瘍塞栓を合併した肝腫瘍を認める場合, その原発巣として, まれながらAFP産生胃癌も考慮に入れる必要があると考えられた.

肝細胞癌 (HCC) 患者において凝固線溶系とthrombin-antithrombin III complex (以下, TATと略記), plasmin-α2-plasmin inhibitor complex (以下, PICと略記), D-dimerとの関連を, 臨床所見および病理組織学的因子から検討した.最近3年間に教室で肝切除術を施行した75症例を対象とした.TAT, PIC, D-dimerの平均値 (mean±S.E.) はそれぞれ4.49±0.58μg/l, 1.36±0.07μg/ml, 1.325±0.270μg/mlであり, いずれも高値であった.非癌部肝組織像, 腫瘍細胞の分化度, 被膜形成の有無, 門脈侵撃の有無と相関はなかった.StageとTATは正の相関がみられ (p=0.064), 肝内転移とDdimerは有意な正の相関をみとめた (p=0.005), HCCの肝内転移の進展と凝固線溶亢進との関連が示唆された.

Adrenocortical tumors, usually adrenocortical carcinoma, producing hormonal symptoms are very rare in children. A 4-year-old girl with acne, general obesity, moon face and hypertrichosis was admitted to our hospital. Hormonal studies demonstrate high urinary excretion of 17-OHCS and 17-KS, and a high serum testosterone concentration. The serum ACTH concentration low was and the cortisol level was within the normal range. A right adrenal tumor was detected by CT scan, MRI and ultrasound. Complete extripation of the tumor, weighing 126g, was carried out successfully. Pathologically a diagnosis of adrenocortical car-cinoma was made because of the presence of venous and capsular invasion by the tumor cells. It is very difficult to make a pathological diagnosis in this tumor. Although prognosis of adrenocor-tical carcinoma is poor, the patients is doing well with no signs of postoperative recurrence.

1980年より札幌厚生病院で経験した初発進行胃癌732例中, 5型胃癌は258例であり, 肉眼的に早期と診断された早期癌型群 (53例), 肉眼的に進行癌と考えられ, IIcに類似する進行癌としたIIc-ad. 群 (143例), 上記以外の形態を呈する分類不能群 (62例) の3群に亜分類し比較検討した. 平均腫瘍径は, 分類不能群が62.9mm, 早期癌型群39.1mm, IIc-ad. 群47.7mmであった. 深達度ではpmの頻度が早期癌型群は64.2%, n0例の頻度は71.7%といずれも他の2群より有意に高率であった (p

A 67-year-old man with a chief complaint of a right abdominal mass was admitted in August, 1989. There was a previous history of several fisutulectomies after appendectomy in 1944. Histopathological examination of the fistula showed benign pseudomyxoma peritonei. On admission, a CT scan showed a low density tumor in the right abdominal region with a high serum CEA level. With diagnosis of possibile recurrence of pseudomyxoma peritonei, surgery for reduction was performed. Microscopic examination showed mucinous adenocarcinoma/pseudomyxoma peritonei. Serum CEA levels remained low for 5 months, but abdominal CT revealed recurrent pseudomyxoma peritonei in January, 1990. A third operation was performed for recurrence during the next three years, the tumor gradually increased, and the patient died in September 13th 1993. He survived for 49 years after initial treatment.

症例は69歳の男性.脳梗塞の既往があり, 定期検査でアミラーゼ高値の指摘を受け精査目的に入院.超音波検査にて脾門部に直径39mmの低エコー腫瘍が認められた.CT検査では, 単純CTにて脾臓の辺縁にやや不鮮明な低吸収域が存在し, 造影CTでは腫瘍部はほとんどenhanceされなかった.dynamic CTでは腫瘍部はhypovascular, delayed enhancementを認めた.MRI検査で, 腫瘍はT1強調画像でhigh signal intensity area, T2強調画像でlow signal intensity areaとして認められた.Gadrinium-DTPAのdynamic studyはlatephaseでenhancementを認めた.血管造影では, 明らかな腫瘍濃染は認めなかった.以上より, 脾血管腫, 過誤腫などを強く疑うも, 悪性リンパ腫なども否定できず, 手術を施行した.摘出脾内には, 3.8×3.5cmの白色隆起性病変を認めた.病理診断は, 脾原発innammatory pseudotumorであった.

The authors have developed a system to measure the volume of the liver parenchyma and tumors using computed tomographic images printed on film. The present study was carried out to clarify the usefulness of this method to assess both liver volume and the relationship between the volume increase and the functional recovery. We investigated 55 patients who underwent a hepatic resection of more than one segment. We calculated the effective resection of ratio and the liver volume increase at the 4th postoperative week to evaluate postoperative hepatic insufficiency. The liver volume increase 4 weeks after surgery correlated significantly with the effective resection ratio and also showed an inverse correlation with the severity of chronic changes in the liver. The liver volume increase also inversely correlated with the preoperative retention of indocyanine green at 15 min. Patients with postoperative hepatic insufficiency tended to show a smaller liver volume increase than expected for their resection ratio. In contrast, noncirrhotic patients had no such particular tendency. In conclusion, measurement of the liver volume using this technique appears to be a simple and useful method to evaluate liver volume after resection; as such, it may also be used to evaluate hepatic regeneration after resection.

1990年4月より93年9月までの間に, 5症例に対して無水エタノールを用いた経皮経肝門脈塞栓術 (PTPE) を行った. いずれも肝右葉に腫瘍が存在し, 門脈右枝に対してPTPEを行い, その後, 右葉切除を行った. 非塞栓葉である左葉の体積は前値348.4±120.3cm3より, 2週後563.0±149.6cm3, 4週後675.0±173.1cm3に増加した. 右葉は912.0±329.6cm3から2週後841.0±261.9cm3, 4週後668.0±350.1cm3に減少した. 無水エタノールを20ml用いた症例では, 肝壊死範囲が広く, ALTの上昇が著明であり, 塞栓葉は57±23%に縮小し, 非塞栓葉は249±80%に増大した. 病理組織学的にはH-E染色で塞栓部の細胞が強い好酸性を示すのに対して, 非塞栓部の細胞は分泌顆粒が増加し明るくみえ, 細胞は腫大し, 再生肝の特徴を呈していた. PTPEは術前に残存予定肝体積を増加させ肝癌切除例にとって有効な方法と考えられた

We report a rare case of cystadenocarcinoma of the liver treated with resection. A 58-year-old man was admitted to another hospital because of a loss of appetite. A unilocular lesion of 7 cm in diameter was revealed in the medial and anterior segments of the liver by ultrasonography and computed tomography. A deroofing under laparoscopy was performed with a diagnosis of simple cyst. However, pathological examination of the surgical specimen indicated cystadenocarcinoma. The patient was transferred to the hospital and a right trisegmentectomy of the liver with lymph node dissection was carried out. It was pathologically proved that the cystic wall was consisted partially of benign epithelium and mostly of moderately differentiated papillary adenocarcinoma, with invasion into the surrounding parenchyma as tubular adenocarcinoma. This lesion was diagnosed as cystadenocarcinoma originated from a simple cyst or cystadenoma. Neither definition nor classification of the cystadenocarcinomas of the liver has been established yet, but a segmental hepatectomy with lymph node dissection and/or resection of extrahepatic bile duct would provide the most favorable prognosis. A serious problem in our patient is the dissemination of cancer cells into the abdominal cavity at the laparoscopic deroofing. It is thought that a cautious observation for the recurrence is required.

To assess the possibility of using hepatocytes from ischemic liver, as a bioreactor of a hybrid artificial liver, we investigated the influence of warm ischemia on the isolation and culture of hepatocytes in rats. Warm ischemia was induced by clamping the liver hilus and the animals were divided into 3 groups according to the duration of ischemia: group A (no ischemia), group B (10 minutes) and group C (20 minutes). Hepatocytes were isolated by the collagenase perfusion method and cultured for 5 days. The yield and viability of the isolated hepatocytes were lower in group C. Rate of attachment was decreased as the duration of ischemia increased. There was no significant difference observed in functions in culture. Sufficient hepatocytes, as a bioreactor, can be isolated and cultured from warm ischemic liver within 10 minutes. Though the number of available hepatocytes were diminished, hepatocytes procured from longer warm ischemic liver could be utilized as a bioreactor.

We rarely encounter a case of postoperative intraabdominal foreign body granuloma due to retained gauze and the like, and often have difficulty in diagnosis preoperatively. This paper describes a preoperatively diagnosed case of intraabdominal foreign body granuloma, which presented with pleuritis and mimicked a hepatoma. A 54-year-old man was seen at another hospital because of worsening dyspnea lasting for about two months, and was suspected to have a hepatoma with pleuritis. The patient was referred to the hospital. There was a previous history of undergoing cholecystectomy for an 1.5-year prolonging positive discharge 12 years before entry. By chest-abdominal CT and ultrosonography US, followed by US guided biopsy, the tumor was diagnosed as intraabdominal foreign body granuloma locating between the right diaphragm and right lobe of the liver. Whirl like appearance was not detected. Coarse calcification around the outer layer of the tumor and irregular pattern at the inner layer were noticed. US findings, a low echoic outer layer of the tumor and irregular high echoic inner layer, were observed. The tumor was extirpated safely through the right subcostal margin incision. The tumor was encapsulated with fibrous tissue and was relatively easily removed. It was 1, 530g in weight. Histologically, the foreign body granuloma was originated from a retained gauze. The postoperative course was uneventful. The patient was discharged from the hospital ont he 46th day after the operation.

Background. Great progress in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) has led to an increased number of resectable cases. Much attention has been paid to the factors affecting long term survival of patients with HCC after partial hepatectomy. Methods. Survival rates for approximately 5800 patients with HCC registered by the Liver Cancer Study Group of Japan who received partial hepatic resection from January 1, 1982 to December 31, 1989 were calculated relative to 14 clinicopathologic variables. Cox's multivariate analysis and the stepwise method then were performed to determine significant prognostic variables and to investigate the appropriate combination of these variables for predicting prognosis. Results. The use of Cox's multivariate proportional hazard model indicated that significant prognostic indicators were alpha-fetoprotein level, tumor size, number of tumors, accompanying cirrhosis, age, surgical curability, and portal involvement. The stepwise method showed that the most valuable prognostic factor was portal involvement, followed by number of tumors, alphafetoprotein level, tumor size, accompanying cirrhosis, age, and surgical curability. Furthermore, it was found that the best predictive combination of two factors was number of tumors and alpha-fetoprotein level and that the best predictive combination of three factors was the alpha-fetoprotein level, tumor size, and number of tumors. Conclusion. This extensive analysis provides information that can be used to predict the prognosis of patients with HCC after undergoing partial hepatectomy.

A 2 1/2-year-old boy with biliary atresia underwent orthotopic living-related liver transplantation. On the 7th postoperative day, he had an episode of hepatic arterial thrombosis following disseminated intravascular coagulation (DIC) due to severe intraabdominal sepsis. Tissue plasminogen activator was administered regionally and the hepatic arterial flow recovered promptly. On postoperative day 33, portal vein thrombosis occurred and direct tissue plasminogen activator injections into the portal vein improved portal blood flow. However, the patient eventually died of poorly controlled DIC. Throughout the course, color Doppler ultrasonogram and arterial ketone body ratio were good indicators of hepatic arterial and portal blood flow. When hepatic arterial thrombosis and portal vein thrombosis occur, retransplantation is often inevitable. Thus, while the patient is awaiting a suitable donor, it could be possible to maintain blood flow to the graft with this new thrombolytic therapy.

In 1985, a nationwide single protocol (cyclophosphamide, vincristine, tetrahydropyranyl Adriamycin, and cisplatin) for the treatment of advanced neuroblastoma was begun in Japan and was found to significantly increase the 3-year survival rate—to 70% for stage III, and to 45% for stage IV. In this study, the authors investigated the efficacy of this protocol for advanced neuroblastoma with or without N- myc amplification. In 159 of the 233 patients with advanced neuroblastoma treated with this protocol (between January 1985 and March 1993), genomyc amplification of N- myc was determined. These 159 patients were divided into two groups according to the number of N- myc copies, ie, those with fewer than 10 copies (105 patients) and those with 10 or more copies (54 patients). The survival curves for the two groups were significantly different. The 5-year survival rate for patients with 10 or more copies was 43.9%; this is surprisingly high in comparison to results of previous studies in which no survivors were expected in cases of advanced neuroblastoma with highly amplified N- myc . Persistent bone marrow suppression was common, but there were no deaths attributable to drug side effects. Five patients with fewer than copies of N- myc amplification died more than 3 years after initial treatment. Three of the five had tumors with an unfavorable Shimada classification, and two had diploid nuclear DNA content. The authors conclude that the protocol resulted in dramatic improvement in the patients with advanced neuroblastoma, even with high N- myc amplification. However, a more aggressive approach is needed to increase the survival rate for the patients without N- myc amplification who have other poor prognostic factors.

A prospective randomised multicentre clinical study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa disease, were age 75 or below and had undergone radical mastectomy. Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX), 20 mg on the day of surgery and 10 mg the next day, followed by oral FT 50 mg day-1 for 2 years from the 14th day; treatment B, the same pattern of DOX administration for the first 2 days, followed by a combined therapy of FT and TAM 20 mg day-1 for 2 years. The number of patients was 546 (treatment A 274 and treatment B 272), of whom 34 (6%) were ineligible. The remaining 512 patients (treatment A 254 and treatment B 258) were followed up for 5 years for analysis. Significantly higher 5 year disease-free rate and 5 year survival rates were observed with treatment B compared with treatment A. When seen in terms of background factors, node-positive patients appeared to derive more benefit from tamoxifen than node-negative patients, but the oestrogen receptor-negative and premenopausal subgroups appeared to derive about the same benefit as those who were oestrogen receptor positive and post-menopausal. Indeed, survival in the premenopausal group was significantly better with tamoxifen (P = 0.04). No increase in side-effects was seen by combining TAM with FT. The study results demonstrate that concomitant administration of FT and TAM is better than FT alone for post-operative adjuvant therapy for breast cancer.

Between January 1985 and June 1992, 208 cases of hepatocellular carcinoma (HCC) were resected in the institute. In this study 22 cases of giant HCC (larger than 10cm in diameter) were clinicopathologically compared to the other 186 cases of HCC (smaller than 10cm). The mean age of 22 patients with giant HCC was 51.0 years old. There were 14 males and 8 females. The frequency of positive HBsAg was higher, while the frequency of concomitant liver cirrhosis was lower than the smaller HCC group. More than 50% of cases showed higher α-fetoprotein above 1000ng/ml. Eighteen cases out of 22 cases underwent more than 2 segment hepatectomy. Portal invasion and intrahepatic metastasis showed significantly higher frequency. The cumulative 3-year survival rate of giant HCCs was 28.4%, versus 61.7% in the smaller HCC group. Three out of 22 cases alived more than 5 years after the operation. These cases were treated by adjuvant chemotherapy, 2 of them received 5-FU via the portal vein and the other was infused adriamycin via the hepatic artery after hepatectomy.

To analyze prognostic factors for colon cancers, clinicopathological factors affecting the postoperative cumulative 5-year survival rate were investigated in patients with a single advanced conon cancer from 1977 to 1990. Sex, age and laboratory data, values of Hb and CEA were chosen as clinical factors, and various items written in General Rules for Clinical and Pathological Studies on Cancer of Colon, Rectum and Anus, were also employed as pathological factors. The 5-year survival rate was significantly and strongly correlated with value of serum CEA (p

手術時切除肝を用いてヒト肝細胞の分離培養を行い,単離肝細胞の収量,viability,培養肝細胞機能が入手肝組織の温阻血時間といかなる関係にあるかを検討した.肝細胞の分散はコラゲナーゼとディスパーゼの混合液を灌流することにより行い,分散された肝細胞を10日間培養し,糖新生能,尿素合成能,DNA量を測定した.入手肝組織の温阻血時間は,0-300分であった.その結果,単離肝細胞のviabilityは肝温阻血時間と関係がなく87.9%であったが,収量との間には有意の相関関係を認めた(p

This paper describes a case of anomalous arrangement of pancreatobiliary duct which was detected in a patient with stoneless cholecystitis. The patient was a 40-year-old woman complaining of upper abdominal pain. Ultrasonography visualized hypertrophy of the gallbladder wall. Endoscopic retrograde cholangio-pancreatography revealed anomalois arrangement of pancreatobility duct. Cholecystectomy and excision of the extrahepatic bile duct were carried out. Pathologically the hypertrophy of the cystic wall and mild chronic inflammatory picture were confirmed, but no heteroplasia was observed. This patient appears to belong to a high risk group for gollbladder carcinoma, because she is relatively young, there was mild dilatation of extrahepatic bile duct, and she had anomalous arrangement of pancreatobiliary duct without stones.

比較的まれと思われる肺癌からの転移性空腸腫瘍による腸重積症の1例を経験したので報告する.症例は69歳の男性で, イレウス症状を呈して入院.小腸造影, 腹部CT検査より空腸腸重積症を疑い緊急開腹術を施行した.Treitz靱帯より約40cm肛門側に腫瘍を先進部とした空腸腸重積症をみとめ, 空腸部分切除術を施行した.空腸腸間膜リンパ節, および肝臓に多発性の転移性腫瘍をみとめたが, 他の腹腔内臓器には異常をみとめなかった.腫瘍は粘膜下層を中心として発育しており, 病理組織学的には, 転移性腫瘍の特徴を有した未分化癌であった.胸部単純写真, 胸部CTにて右S6の直径2cmの腫瘍と, 右肺門部異常陰影をみとめ, 喀痰細胞診より肺癌と診断し, 臨床的に肺が原発巣と考えられた.

The effects of hyperthermia (HT) on multidrug-resistant human hepatocellular carcinoma (HCC) were evaluated experimentally. This tumor, an AFP-producing human HCC, in which MDR1 mRNA and P-glycoprotein were overexpressed, was transplanted subsequently on nude mice. Ten days after the inoculation of the tumor into the rear section of the nude mice, either or both an intra-peritoneal injection of 8 mg/kg of adriamycin (ADR) was administered or hyperthermia (HT) was induced. HT was performed immediately by immersing the mice into a water bath at a temperature of 42-degrees-C for a period of 30 minutes. Hyperthermic therapy combined with ADR significantly inhibited the tumor growth compared with ADR or HT alone. Using ADR in combination with HT, the ADR concentration in the tumor remained at a significantly higher level for a prolonged period compared with ADR alone. The results indicate that HT enhanced the anti-tumor effect of chemotherapy even for multidrug-resistant HCC.

We investigated whether Pyrimidine nucleoside phosphorylase (PyNPase) activity in breast cancer tissue correlated with biological characteristics of breast cancer. PyNPase activity, ER, PgR, EGFR, DNA ploidy pattern, PCNA positive cells and amplification of the c-erbB-2 gene were determined in specimens from 138 patients. PyNPase activity was significantly higher in ER negative than ER positive carcinomas (p

To investigate the relationships of the gross appearance to cancer depth and microinvasion in gallbladder cancer, thirty-three cancers were macroscopically subgrouped: papillary (n=8), nodular (n=6), papillo-invasive (n=1), nodulo-invasive (n=11), and invasive (n=7) type, respectively. Papillary type cancers were limited to the mucosa or the muscularis propria, without microinvasion. Most nodular type cancers infiltrated to the subserosa with moderate microinvasion. The other types of cancer frequently invaded the subserosa or more, with high incidence of microinvasion. Only the papillary type cancers indicated simple cholecystectomy, the other types should be operated in accordance with infiltration depth and degree of involvement.