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浸潤癌に進展したため手術適応となった分枝型膵管内乳頭粘液性腫瘍(IPMT)の3例を経験したので報告する.症例1, 2, 3は分枝型IPMTの診断で6カ月ごとの経過観察を行っていた.初診から各々約4年, 1.5年, 15年後に画像上,症例1, 2では総胆管に浸潤する腫瘤像を,症例3では膵体部に腫瘤像を認め,各々膵頭十二指腸切除術,膵全摘術,膵全摘残胃全摘術を施行した. 3例とも病理組織学的には, IPMT由来の浸潤癌であった. IPMTにおいても本症例のように浸潤型に進展する症例が存在する.経過観察時は,膵全体および隣接臓器をよりいっそう注意深く観察する必要があると思われた.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Somatostatin and its analogs have been included in experimental treatment protocols for advanced pancreatic adenocarcinoma based on their known antisecretory and antiproliferative properties. Somatostatin receptor type 2 (sstr2A) mediates antiproliferative actions of somatostatin and has the strongest affinity to the therapeutically used somatostatin analog--octreotide. We investigated localization of sstr2A in 27 pancreatic adenocarcinomas in relation to tumor histological features and neuroendocrine differentiation confirmed by immunoreactivity for chromogranin A (CgA), chromogranin B (CgB), or somatostatin. Immunoreactivity for sstr2A generally coincided with tumor neuroendocrine differentiation demonstrated by staining for CgA and was present on the cell membranes of pancreatic islet cells and endocrine cells occasionally present in the wall of normal pancreatic ducts. Thirteen pancreatic adenocarcinomas contained cells immunoreactive for sstr2A in numbers ranging from occasional single cells, cell clusters, or carcinoma duct segments. In two cases, cells immunoreactive for sstr2A and CgA represented more than 30 and 10% of the total tumor cell population (case 1 and 15, respectively). Case 1 fulfills the diagnostic criteria of mixed ductal endocrine carcinoma. We conclude that immunohistochemical staining for a generic neuroendocrine marker such as CgA would facilitate identification of a subgroup of pancreatic adenocarcinomas expressing sstr2A receptors. Future studies need to evaluate the responsiveness of these tumors to somatostatin analogue treatment.

Interleukin 12 (IL-12) is a heterodimeric cytokine that exerts a potent antitumor effect through its pleiotropic actions. It was recently reported that IL-12 has also a potent antiangiogenic effect through the induction of IFN-gamma, which triggers the production of chemokines such as IP-10 that has been shown to have antiangiogenesis properties. In this study we transfected the IL-12 gene into a human pancreatic adenocarcinoma cell line (PK-1). PK-1 cells transfected with the green fluorescence protein (gfp) gene were used as positive controls. The in vitro growth curve and in vivo tumor growth of transfectants (IL-12/PK-1 and gfp/PK-1) were compared with those of parental cells. The SCID mice used in this study were administered antiasialo GM-1 Ab (100 microg, i.p., twice weekly) to deplete the remaining immunoeffector cells, NK cells. Using a skinfold chamber model, we observed and recorded tumor angiogenesis by intravital microscopy. In vitro growth of IL-12/PK-1 and gfp/PK-1 cells was not different from that of wild-type PK-1 cells (wt/PK-1). However, IL-12 transfected PK-1 cells did not develop into tumors as did the wt/PK-1 cells after subcutaneous inoculation in antiasialo GM-1 Ab administered SCID mice. The growth of IL-12/PK-1 tumors was restored in mice treated with anti-IL-12 antibody. We found that IL-12/PK-1, in contrast to gfp/PK-1 and wt/PK-1, failed to initiate an angiogenic response, as observed in the skinfold chamber model. These results indicate that the antiangiogenesis effect of IL-12 alone, without immune system involvement, is sufficient to block the growth of human pancreatic cancer.

症例は52歳の女性. 腹痛を主訴として前医受診, 手術にてIVC原発腫瘍と判明したため当院紹介された. IVC造影ではIVCの閉塞, 側副血行路の形成は見られなかった. 開腹すると腫瘍は中部IVCより壁外性に発育しており, 右腎静脈への浸潤を認めた. 右腎静脈を大伏在静脈にて再建した後, IVCの単純遮断下に腫瘍をIVCとともに切除し, IVCは人工血管にて再建した. 病理組織診断は平滑筋肉腫であった. 術後6か月のMRI検査ではIVCのpatencyは保たれていた. 術後17か月経過した現在, 再発の兆候なく外来通院中である. 下大静脈原発平滑筋肉腫は本邦での報告は自験例を含めて53例で, IVC切除後人工血管にて再建された症例は12例である. IVC切除にあたっては血流遮断時の体外循環の必要性, 腎静脈の処理方法などをIVC造影, 術中所見から判断することが重要である.

Pancreatic cancer has one of the poorest prognoses among malignant diseases. To understand its molecular mechanisms, we studied allelic losses on the long arm of chromosome 6. Using 55 paired DNAs of tumors and their corresponding normal tissues and 30 microsatellite markers that spanned the entire 6q chromosome arm, we found three distinct regions of common allelic loss: region A, a less than 500-kb region bordered by D6S449 and D6S283 on 6q21 with a loss of heterozygosity (LOH) frequency of 69% (38/55); region B, a 7-cM region bordered by D6S292 and D6S308 on 6q23-q24 with a LOH frequency of 60% (33/55); and region C, a 13-cM region bordered by D6S305 and D6S264 with a LOH frequency of 51% (28/55). We further focused on region A and constructed a physical map using yeast artificial chromosome (YAC) clones, their derived cosmid clones, and bacterial artificial chromosome (BAC) clones. Region A was completely covered by three overlapping BAC clones. Our results in the present study should shed light on the cloning and characterization of tumor suppressor genes in pancreatic carcinogenesis.

Leukocyte infiltration in the pancreas is involved in the aggravation of acute pancreatitis from edematous phase into necrotic change, and mild disease into severe disease; however, the mechanism responsible for leukocyte accumulation is not fully understood. This study was designed to clarify the mechanism underlying leukocyte accumulation into the pancreas and to elucidate the therapeutic efficacy of a novel diamino-pyridine derivative, IS-741 on leukocyte-endothelial cell interaction using rat necrotizing pancreatitis model. The number of adherent leukocytes to pancreatic collecting venules assessed by in vivo fluorescence microscopy increased significantly in necrotizing pancreatitis animals in a time-dependent manner. The expression of CD11b on circulating neutrophils determined by flow cytometric analysis was enhanced to approximately 500% after 2 h. IS-741 attenuated the leukocyte adherence significantly, accompanied by a lower up-regulation of CD11b. These findings were further supported by the histological examination that the accumulation of leukocytes in the pancreas was remarkably inhibited by IS-741. These results suggest that the leukocyte accumulation in the early phase of acute necrotizing pancreatitis may be mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. IS-741 attenuated the leukocyte endothelial cell interaction as a consequence of its inhibitory effect on CD11b upregulation.

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

This paper reviewed our experience with the nonsurgical management of acute necrotizing pancreatitis (ANP) by continuous regional arterial infusion (CRAI) of protease inhibitor (nafamostat mesilate, 240 mg/day) and antibiotic (imipenem, 0.5 g every 12 h). 47 patients with ANP admitted within 7 days were treated with intensive care and CRAI for 5 days prospectively. 40 patients responded to CRAI therapy and the mortality rate in these patients was 2.5%. 7 patients (14.9%) did not respond to CRAI. 5 of 7 nonresponders died of multiple organ failure although pancreatic necrosis was persistently sterile. The remaining 2 patients who underwent necrosectomy for infected pancreatic necrosis recovered after surgery. In 34 patients treated with CRAI in the early stage within 72 h after the onset, 31 (91.2%) responded. The mortality rate was 5.9% and the incidence of infected pancreatic necrosis was 2.9% in these 34 patients. These results demonstrated that most patients with ANP responded to conservative management combined with CRAI with nafamostat and imipenem when employed within 72 h after the onset. Early intervention of CRAI with protease inhibitor and antibiotic has a significant role in the nonsurgical management of ANP.

Abnormality of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 appears to play a limited role in pancreatic ductal carcinogenesis.Recently, a human G/T-specific TDG gene was identified. This protein acts in a system correcting G/T mispairs to G/C pairs. TDG was mapped to chromosome bands 12q22-q24.1, one of the regions frequently lost in pancreatic cancer. Therefore, there is the possibility that the TDG gene on 12q is one of the genes responsible for pancreatic ductal carcinogenesis.Nucleotide sequences of the entire coding region of the TDG gene were analyzed in 21 human pancreatic cancer cell lines. mRNA expression of the TDG gene was also analyzed by Northern hybridization in several human tissues and 21 human pancreatic cancer cell lines.Decreased levels of mRNA expression were detected in the pancreatic cancer cell lines, but no somatic mutations were observed.

Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36.The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines.MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56.MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

Differences between the clinical staging system of the Japan Pancreas Society (JPS) and the Union Internationale Contre le Cancer (UICC) stage classification may account for reported differences in the prognosis of pancreatic carcinoma between Japan and the West. In the review, we compared the characteristics of the JPS and UICC staging in 1689 patients, registered with the JPS from 1981 to 1990, who underwent resection for carcinoma of the pancreatic head. The survival rates correlated well with the JPS stage classification. The UICC staging did not reflect differences in prognoses among the stages. The current JPS staging system, introduced in 1993, still differs from that of the UICC. To compare the results of treatment for patients with pancreatic cancer it is important to establish a more practical and universal staging system for carcinoma of the pancreas.

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18.

The Japanese grading system for severity of acute pancreatitis has evolved from results of a national survey on 2,553 patients managed in 523 major medical centers in Japan between 1982 and 1986. It was devised to embrace the predictive factors that would offer high sensitivity and specificity in rendering an accurate diagnosis. In this system, computed tomographic (CT) examination is used for estimating the severity of acute pancreatitis. Combining criteria from laboratory data, clinical signs, and CT findings, the system appears cumbersome. However, it is actually more flexible in that only few criteria, from the wide range of findings actually covered, are needed to predict severity. Its rationale stems from a national effort to improve the outcome of this life-threatening disease. Further prospective studies are needed to determine its accuracy and superiority.

We have used comparative genomic hybridization (CGH) to survey genomic regions with aberrant copy numbers of DNA sequences in pancreatic adenocarcinoma. In 12 cell lines and 6 primary tumors from 18 patients with pancreatic adenocarcinomas, highly frequent losses (>60%) were observed on chromosome arms 6q, 9p, and 18q and the Y chromosome. Moderately frequent losses (40–60%) were observed on chromosome arms 3p, 4q, 8p, and 21q. Interestingly, these samples showed extremely high frequencies of increases in copy numbers of DNA sequences on the long arm of chromosome 20 (15/18, 83%). We further analyzed five cell lines by fluorescence in situ hybridization (FISH) with probes on chromosome 20 to define the increase in copy number more accurately, and we found that 20q was increased to between 5 and 8 copies per cell. These results suggest the existence of an oncogene or oncogenes on 20q that play a role in the development and/or the progression of pancreatic carcinogenesis. Genes Chromosom. Cancer 19:161–169, 1997. © 1997 Wiley-Liss Inc.

To evaluate appropriate surgical treatment and to predict prognosis for mucin-producing tumors (MPTs) of the pancreas, we conducted a retrospective clinicopathological study in 25 patients with MPT. Eight patients who had mild dysplasia of the pancreas were diagnosed with benign disease and 17 patients with ductal lesions of the pancreas with severe dysplasia/carcinoma in situ or with invasive foci were diagnosed as malignant. Clinical symptoms and histories, tumor markers, cytological examination, and radiological and gross pathological features were compared in the benign and malignant groups. Clinical symptoms, history, and tumor markers were of no value for predicting prognosis. Cytological examination results were ambiguous because of too many falsenegatives. Radiological features, including the diameters of the cystic space and of the main pancreatic duct (MPD) were shown to be valuable. The significant maximal diameters, above which malignancy was seen, were 30mm for the diameter of the cystic space and 10mm for the MPD. In regard to gross features, the uniformly dilated main duct-type and focally dilated main duct-type were significant indicators of malignancy. Long term follow-up was available in 22 patients. Seven patients died of recurrence of the tumor or other malignancies. We could have predicted prognosis by the radiological features and gross appearance. Surgical treatment should be considered the primary choice for MPT. Total pancreatectomy would be ideal for patients with the uniformly dilated main duct-type. Because of the probability of multicentricity and the transforming potential of mild dysplasia, very careful follow-up is necessary for patients with MPT.

It is suggested that this liver metastasis model formed by a highly metastatic variant (KLM-1) is valuable for the study of the liver metastatic processes of human pancreatic cancer.Liver metastasis in the early postoperative period is one of the causes for the poor prognosis of patients with resected pancreatic cancer. Therefore, it is necessary to establish an experimental model to study the mechanisms of liver metastasis in pancreatic cancer.Human pancreatic cancer cell lines (PK-1, PK-9, and KLM-1) were injected into the portal vein of nude mice with or without pretreatment with antiasialo GM1, and colonies of liver metastases were counted for comparison of metastatic ability of these cell lines. Biological and histopathological characteristics of the highly liver metastatic cell line (KLM-1) were compared with its parent cell line (PK-1).PK-1 cells and PK-9 cells rarely formed liver metastasis foci, but pretreatment with antiasialo GM1 promoted liver metastasis. KLM-1 cells formed liver metastases at the rate of 70% even without antiasialo GM1 pretreatment. KLM-1 cells had such biological characteristics as short doubling time, short lag phase, and resistance to NK cytotoxicity. After intraportal injection of 125I-labeled KLM-1 cells, radioactivity as well as micrometastases were detected in the liver at 72 h.

A new strategy for the treatment of acute necrotizing pancreatitis (ANP) is reported. In this prospective study, all patients received intensive medical support. Surgery was performed in patients with infected pancreatic necrosis and/or sepsis. Continuous regional arterial infusion (CRAI) of the protease inhibitor, nafamostat mesilate, and the antibiotic imipenem was initiated in patients with ANP referred to our hospital within 7 days of the onset of the disease. Sixty patients with ANP were allocated to three groups: group I, no CRAI (n =16); group II, CRAI of nafamostat only (n=22); and group III, CRAI of nafamostat mesilate and imipenem (n=22). The mortality rate was 43.3% in group I, 13.6% in group II (P

Forty male rats weighing 150 g were operated on with gastrectomy with esophagoduodenostomy, antrectomy, fundectomy, or bilateral truncal vagotomy with pyloroplasty. Unoperated rats served as controls.

The influence of tumor size on early and long-term outcome of resection of ductal pancreatic cancer was studied in 127 patients. Tumor size tended to decrease with time, and small tumors (≦2cm) were less advanced, according to the Hermreck classification [Hermreck AS, Thomas CY, Friesen SR (1974)Importance of Pathologic Staging in the Surgical Management of Adenocarcinoma of the Exocrine Pancreas. Am J Surg 127:635–657] There was, however, no difference in lymph node status or histological differentiation between patients with small and bigger tumors. Tumor size did neither affect postoperative mortality and morbidity, nor long-term survival. It is concluded that tumor size itself is without influence on both the early and the late course in patients with resectable exocrine pancreatic cancer.

Background/Aims New therapeutic approach is required for pancreatic cancer, one of the most intractable malignancies. The role of angiogenesis in the tumor growth of a Syrian hamster pancreatic cancer cell line HPD-NR, which closely resembles its human counterpart, was investigated. Methods Angiogenic activity was measured as stimulation of growth of human umbilical vein endothelial cells (HUVEC), and angiogenic factors produced by HPD-NR cells were identified by reverse-transcription polymerase chain reaction and Northern blot analysis. Then in vitro and in vivo antitumor effects of a potent angiogenesis inhibitor, O -(chloroacetylcarbamoyl)fumagillol (AGM-1470), were examined. Results The conditioned medium of HPD-NR cells stimulated the growth of HUVEC, and four hamster angiogenic factors were detected with an overexpression of transforming growth factor α and vascular endothelial growth factor messenger RNAs. AGM-1470 specifically inhibited the growth of HUVEC and that of HPD-NR tumors in vivo with decreased vascularity of the tumors but not the growth of HPD-NR cells in vitro. Conclusions The results suggest that angiogenesis plays an important role in tumor growth of HPD-NR cells and can be a new target of medical therapy for pancreatic cancer.

高圧CO2によりたばこ葉から高品質フレーバーを抽出するための最適操作条件の決定法の確立を目的として, 液体および超臨界CO2を溶剤とし, 半回分と回分抽出実験を行い, 操作条件とフレーバー品質との関係の体系化を行った.まず, フレーバー成分を化学的特性から水溶性フレーバー, 精油, 不揮発性フレーバーの3つの成分に分類する汎用的な方法を提案した.この方法に基づきたばこフレーバー成分を分類し, 各成分の主要成分としてニコチン, ネオフィタジエン, ソラネソールをそれぞれ選定した.次に, 操作条件と抽出物の主要成分組成ならびに品質との関係について検討した.その結果, 操作条件により抽出物の主要成分組成を広範囲に制御できることがわかり, 操作条件と主要成分組成との関係を表す操作マップを作成した.また, 官能検査から高品質なフレーバーの主要成分組成は特定の領域にあることが明らかとなり, 品質と主要成分組成との関係を組成マップとして表した.操作マップと組成マップの両者を用いることで, 目標品質のたばこフレーバーが得られる最適操作条件を決定することが可能となった.

The findings in 35 surgically treated patients with insulinoma and 43 tumors of these patients were analyzed to confirm the efficacy of diagnostic modalities and surgical interventions. The rate of accurate preoperative tumor localization was 72% by angiography, 53% by computed tomographic scan, 55% by ultrasonography, and 83% by percutaneous transhepatic portal vein sampling. Extensive operative exposure and palpation detected 81% of the tumors and intraoperative ultrasonography demonstrated 96% of the tumors. Intraoperative ultrasonography was significantly better than any other diagnostic procedure and was able to demonstrate the anatomical relationship of the insulinoma to the essential structures of the pancreas. Intraoperative ultrasonography also helped determine the safest route for enucleating the insulinomas. Five patients (14%) in our series had metastatic diseases; 2 of these patients with metastases beyond the lymph nodes died due to the growth of tumors. The other 33 patients were free of insulinoma syndrome after the removal of the insulinomas. Streptozotocin was used in 1 patient with recurrent malignant insulinoma, with encouraging results.

Infected pancreatic necrosis which spreads extensively in the retroperitoneal space requires open drainage to prevent the formation of residual abscess. With open drainage and repeated debridement, we often encountered patients who suffered from abdominal complications such as prolapse of the small intestine through the wound and injury to the intestine. In order to improve the open drainage method, we combined diverting ileostomy with open drainage. Diverting ileostomy was effective in decompressing the small intestine; this prevented prolapse and reduced the incidence of paralytic ileus. Prophylactic diverting ileostomy appears to result in the reduction of complications during open drainage and has advantages in the subsequent management of critically ill patients with infected pancreatic necrosis.

Background. Mucus-hypersecreting tumor of the pancreas appears as dilated ducts and cystic spaces filled with mucus. To determine where such tumors arise and how they extend, computer-aided three-dimensional reconstruction was done of the ductal system. This also was used to visualize the spatial relationships among epithelial hyperplasia, dysplasia, and carcinoma in situ (CIS). Methods. Surgically removed pancreases were studied from 12 patients with mucus-hypersecreting tumors. The specimens were fixed in buffered formaldehyde solution lo%, embedded in paraffin and semiserially sectioned at 3 pm at an interval of 60 pm. The ductal contours were diffentiated among ducts lined by ordinary epithelia, hyperplastic epithelia, dysplastic cells, or CIS and were inputted into a computer system that integrated a three-dimensional image of ducts in the display. Results and Conclusions. (1) The tumors arose in the main pancreatic duct or its subbranches, and the cysts corresponded to segments expanded by the superficial growth of tumor cells; (2) areas of CIS arose in zones of preceding dysplasia, suggesting a dysplasia-carcinoma sequence; and (3) dysplastic or cancerous cells often extended intraductally over the dilated segments of ducts.

YAMADA, S., TAKAI, Y., NEMOTO, K., OGAWA, Y., KAKUTO, Y., Rosin, A., SAKAMOTO, K., KIMURA, Y. and KOBARI, M. Intraoperative Radiation Therapy Combined with Hyperthermia against Pancreatic Carcinoma. Tohoku J. Exp. Med., 1992, 166 (3), 395-401 - Fourteen patients with pancreatic carcinoma were treated by intraoperative radiation therapy (TORT) combined with hyperthermia (hyperthermia group). Their treatment results were compared with those of fifty five patients treated by TORT without hyperthermia (control group). Most of patients underwent some kind of chemotherapy for the carcinoma and some of them received post-operative irradiation. Although there was no significant difference in pain relief between hyperthermia group and control group, the local tumor control rate of the former group was a little better. The survival rate of all patients was 14.5% at one year, 2.9% at two years, 2.9% at three years and 0% at four years after surgery. The survival rate of the hyperthermia group was 21.4% at one year and 7.1% at two years and that of the control group was 12.7% at one year and 1.8% at two years. The survival of the hyperthermia group was a little better than that of control group, but the difference was not significant. Only 36% of patients of hyperthermia group were successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would be possibly improved.

十二指腸膜様狭窄症はまれな先天性疾患であるが, 多くは幼児期に診断され成人例は少ない.今回, 幼児期に発症しながら成人になって初めて診断された十二指腸膜様狭窄症を経験したので報告する.症例は24歳女性, 幼児期より頻回に嘔吐を繰り返していたが, 成長障害がなかったため放置していた.1989年7月, 腹痛で来院, 上部消化管造影および内視鏡検査で十二指腸内のリング状透亮像と膜様物を認め十二指腸膜様狭窄症と診断した.開腹術下に膜様物切除術を施行し, 術後経過良好である.本症例では膜様物に副膵管が開口しており, Vater乳頭は膜様物近傍の肛門側に存在した.膜様物切除に際しては膜様物近傍に開口する胆管, 膵管の損傷を防止するために術中secretin静注や胆嚢圧迫試験により開口部を確認することが重要と考えられた.

教室で経験した非機能性膵島細胞腫瘍7例について臨床病理学的検討を行った.症例は全例女性で, 病理組織学的に4例が悪性, 3例が良性であった.腫瘍径が10cm以上では悪性例が多い傾向を認めた.臨床症状や血清生化学検査に特徴的な所見はなかったが, 画像診断では腹部血管造影の有用性が評価された.腫瘍占居部位は尾側が多く, 全例で肉眼的治癒切除が施行された.内訳は膵頭切除術2例, 膵尾側切除術3例, 腫瘍摘出術2例である.術後13年以上生存中の悪性例があり, 予後は比較的良好と考えられるが, 腫瘍摘出術後に肝転移と癌性腹膜炎で再発死亡した例もあるため, 早期診断, 適切な術式選択, 切除標本の十分な検索を行ったうえで, 長期間経過観察する姿勢が必要と考えられた.

膵癌では治癒切除術後にも肝転移再発が多いため, 予後の改善には肝転移形成機構を解明し, 肝転移防止対策を確立することが必要である.膵癌細胞の肝細胞に対する接着および浸潤遊走における基底膜蛋白laminin (以下LN), fibronectin (FN) の関与について, 教室で樹立した膵癌培養細胞株6株を用いて検討した.LN, FN両者に対し高い接着率を示す細胞株 (PK-1, PK-45P, PK-47) が, 肝細胞に対しても高い接着率を示した.また, 肝転移巣由来 (PK-1, PK-45H, PK-59) あるいは高度脈管侵襲陽性例由来 (PK-47) の細胞株はLNあるいはFNにより浸潤遊走能が誘導され, また肝細胞を培養したfilterを介しての遊走性をも示した.蛍光抗体法により肝細胞表面にLN, FNの存在が観察された.肝転移巣形成初期においては, 肝細胞表面のLN, FNを介した接着あるいは遊走性の強弱が重要な役割を果たし, これらの強い細胞が中心となり肝転移巣が形成されている可能性が示唆された.

慢性膵炎に対する外科治療の効果を, 疼痛への効果および遠隔成績について検討しさらに成因, 病態, 術式別に累積生存率を求めた.対象は教室で経験した慢性膵炎手術例174例で計185回の手術が行われ, 85%で疼痛が手術適応に関与した.術式は膵管像, 炎症の局在, 合併症などから厳密に決定したが, 膵管空腸側側吻合術64回を含む膵管減圧手術が76回と多く, 次いで膵切除術が58回, その他が51回であった.疼痛に対する効果は術式による差が無く, 全体では消失70%, 軽快26%, 不変4%であった.遠隔成績も術式による差は無く全体で良好67%, やや良好18%であったが不良例も15%に認められそのほとんどがアルコール性であった.累積生存率は各術式, 成因間では有意差ないが術前OGTTで糖尿病型の症例では5年で77%, 10年で68%, 15年で48%と低下し, 境界型と正常型での20年にわたる80%以上の生存率とは著しい差が認められ, 生命予後に糖尿病が最も影響することが明らかであった.

TSAI, J., KOBARI, M., TAKEDA, K., MIYASHITA, E., RAHMAN, M.M, and MATSUNO, S. Changes of Duodenal pH and Pancreatic Exocrine Function after Upper G-I Intraluminal Ethanol Administration. Tohoku J. Exp. Med., 1991, 164 (1), 81-91-Using 3 outbred dogs with pancreatic, gastric and jejunal fistulas, we examined changes in pancreatic exocrine secretion, duodenal pH and plasma CCK concentration after intragastric or intrajejunal administration of ethanol. Intragastric administration of 20% or 40% ethanol significantly lowered the pH in the duodenal cavity, and pancreatic fluid secretion and bicarbonate excretion were stimulated. Intrajejunal administration of ethanol elicited stronger responses. Plasma CCK concentration was not changed or was only slightly lowered by ethanol administration in the digestive tract. It is assumed that stimulation of pancreatic exocrine secretion was mediated by the secretion of gastric acid.

To retrospectively assess 64-detector row computed tomography (CT) in the preoperative depiction of the cystic duct and cystic arteries in and around the Calot triangle.Institutional review board approval was obtained, with waiver of informed consent. A total of 245 consecutive patients (133 men, 112 women), including 48 patients who subsequently underwent cholecystectomy, were examined. Two independent observers evaluated the CT data set on the basis of axial sections, coronal and sagittal multiplanar reformations, and three-dimensional volume rendering. The relationship between the cystic arteries and the Calot triangle--which is bordered by the undersurface of the liver, common hepatic duct, and cystic duct--was also evaluated, and each patient was classified on the basis of the origin of the cystic arteries and the course to the Calot triangle. Statistical analysis was performed, and percentages and confidence intervals were calculated.The cystic arteries were delineated in 234 of the 245 patients. Both the Calot triangle and the cystic arteries were delineated in 223 patients. One cystic artery was seen in the Calot triangle in 173 patients, and two cystic arteries were seen in the Calot triangle in 12. One artery in the Calot triangle with accessory arteries from different origins outside the Calot triangle was seen in 18 patients, and no cystic artery was identified in 20. Cystic arteries were seen in 42 (92%; 95% confidence interval: 87%, 98%) of the 48 patients who subsequently underwent cholecystectomy. The relationship between the cystic arteries and the Calot triangle was in agreement with the surgical records for all patients.The configuration of the cystic duct and cystic arteries can be depicted preoperatively with 64-detector row CT in patients scheduled to undergo cholecystectomy.

Sensitivities to anti-tumor drugs, mitomycin C (MMC), aclarubicin hydrochloride (ACR), doxorubicin hydrochloride (ADR), cisplatin, and 5-fluorouracil (5FU), were examined using PK-1, -8, -9, -12, -14, and -16 cell lines derived from human pancreatic cancer. These cell lines showed different sensitivities to each of the above anti-tumor drugs. The concentrations required for 50% growth-inhibition (IC50) after 2 hours of exposure were 0.096 to 0.35 micrograms/ml for MMC, 0.0074 to 0.0076 micrograms/ml for ACR, 0.033 to 0.23 micrograms/ml for ADR, 0.35 to 1.9 micrograms/ml for cisplatin, and 21 to 42 micrograms/ml for 5FU, IC50 of each anti-tumor drug decreased significantly after 48 hours of exposure. The combination of any two out of MMC, ACR, and 5FU showed synergistic inhibition of the growth of PK-1 and PK-8 cell lines. These results show that MMC, ACR, ADR, cisplatin, and 5FU have sufficient anti-tumor effect against six human pancreatic cancer cell lines even at clinically achievable concentrations and exposure times, and chemotherapy for pancreatic cancers requires naturally effective drug delivery into cancer tissues.

薄層植物材料であるたばこへの香料の吸着速度について検討した.たばこ材料へのエタノールの吸着速度は材料内拡散律速モデルによってよく表わすことができた.理論吸収曲線と実測値との比較から有効拡散係数を求めた結果, 一定の吸着水量におけるエタノールの有効拡散係数はcorrected diffusivityと吸着平衡関係から推算できることがわかった.さらに, 吸着のみによるたばこの加香操作について検討し, この操作によって, 従来の香料滴の散布による加香操作よりも均一な香料の添加が期待できることを明らかにした.

We report a case of superficial bile duct carcinoma showing extensive intraductal spread without dilatation of the bile duct in which diagnosis was established preoperatively by transpapillary forceps biopsy and intraductal ultrasonography. A 78-year-old man was given a diagnosis of acute cholecystitis, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed. Cholangiography via the PTGBD tube revealed a tiny irregularity in the hilar bile duct. Transpapillary intraductal ultrasonography showed that this irregularity extended from the intrahepatic bile duct to the middle of the bile duct. Bile duct biopsy revealed malignancy, and thus bile duct resection and hepaticojejunostomy were performed. Histological examination verified a well-differentiated adenocarcinoma confined to the epithelium and the fibromuscular layer.

We investigated the mode of progression of intraductal papillary-mucinous neoplasm of the pancreas (IPMN) in patients who underwent follow-up in order to elucidate the characteristics of malignancy and to establish an effective treatment strategy.Fifty-one patients with IPMN (branch-duct type, 47; main-duct type, 4) who had undergone follow-up study by endoscopic ultrasonography (EUS) were included (mean follow-up duration, 41.0+/-32.3 months; average number of EUS examinations performed during follow-up, 4.4). Chronological changes in EUS findings and histological findings of resected specimens were evaluated.Of the patients with the branch-duct type, only 2% showed enlargement of the dilated branches. In the main-duct-type group, an increase in size of the main pancreatic duct (MPD) was observed in 75% of the patients. In 14 patients with papillary protrusions, an increase in size and lateral spread was observed in 71% and 43%, respectively. No patients developed invasive cancer. In 15 patients who had thick septum-like structures (TSS), the development of papillary protrusions and that of invasive cancer were observed in 53% and 13%, respectively. Twenty-nine patients who had thin septum-like structures showed no change. Two patients with dense multilocular large cysts and TSS developed invasive cancer without change in the cystic lesions. One patient developed carcinoma with multifocal stromal invasion.Patients with branch-duct type IPMNs without papillary protrusions or TSS are not immediate candidates for surgery. Those who have small papillary protrusions have a benign course. It is recommended that patients with the large branch-duct type with TSS should undergo surgery. Attention should be paid to the entire pancreas when performing follow-up examinations in patients with branch-duct type IPMN, as invasive ductal adenocarcinoma can develop at a site in the pancreas different from that of the IPMN.

We herein report a case of pancreatic serous cystadenoma in a patient who presented with jaundice, and we provide a review of the literature. A 53-year-old man was admitted with complaints of jaundice and weight loss. With a preoperative diagnosis of pancreatic serous cystadenoma with obstructive jaundice, he underwent pylorus-preserving pancreatoduodenectomy. A cystic tumor partially protruding into the bile duct was observed in the pancreatic head. Histology verified serous cystadenoma of the pancreas. Histologically, no atypia was proven in the epithelium. There have been only eight case reports dealing with serous cystadenoma of the pancreas with obstructive jaundice. Although serous cystadenoma of the pancreas has essentially a benign nature, pylorus-preserving pancreatoduodenectomy is the treatment of choice when available to avoid the recurrence of obstructive jaundice.

Decompression of the gastrointestinal tract and drainage of the pancreatic juice and bile are important procedures for the prevention of postoperative complications following pancreaticoduodenectomy. We have developed a new Y-silicone tube which enables the drainage of both the pancreatic juice and the bile through the same transhepatic route. This Y-tube, which we have called a retrograde transhepatic pancreaticobiliary drainage (RTPBD) tube, was employed for duodenopancreatectomized patients. While the Y-tubes were in situ, we did not experience any complications such as hemobilia or ascending cholangitis. The Y-tube is safe and efficient for drainage and can be employed for any patients undergoing pancreaticoduodenectomy.

Precise localization and surgical excision is the therapeutic strategy for insulinomas. However, it is often difficult to localize the insulinomas, because of their small size. Surgeons may not localize and remove all of them together, particularly in patients with multiple insulinomas. We reviewed our experience to confirm the efficacy of blood glucose and intraoperative immunoreactive insulin (IRI) monitoring for surgical management of insulinomas.Thirty-nine patients with insulinoma were surgically treated in our department. Perioperative blood glucose monitoring was performed in 14 patients, intraoperative quick IRI assay of the peripheral blood in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer.Rebound response of blood glucose to insulinoma removal was not always noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum IRI levels within 15 minutes after removal of the insulinoma. The other two patients showed a rebound response of peripheral blood glucose or portal IRI. All the patients who had intraoperative monitoring of peripheral blood and peripheral and portal IRI had no recurrent insulinoma syndrome after surgical removal of their insulinomas.Combined monitoring of peripheral blood glucose and peripheral and portal IRI are helpful in the surgical management of insulinomas, as they can indicate that no insulinoma remains.

BackgroundThe prognosis of patients with resected pancreatic cancer remains poor. This study evaluated the effect of adoptive immunotherapy (AIT) using intraportal infusion of lymphokine-activated killer (LAK) cells after curative resection and intraoperative radiation therapy (IORT) on advanced pancreatic cancer.MethodsTwenty-nine consecutive patients with advanced pancreatic cancer (Japan Pancreas Society stage III or IV) were divided into two groups. The control group (n = 17) underwent tumour resection and IORT. The treatment group (n = 12) underwent resection, IORT and intraportal infusion of LAK cells combined with recombinant interleukin 2 (rIL-2). The incidence of liver metastasis and the survival rate of these two groups were compared.ResultsAlthough the overall survival between groups was not statistically different (P = 0·082), there were more patients (four) alive 3 years after operation in the test group (36 per cent versus zero), and the incidence of liver metastases in the treatment group was significantly lower (three of 12 versus ten of 15; P < 0·05). LAK therapy influenced survival positively in multivariate analysis.ConclusionThese preliminary observations suggest that AIT warrants further study as a possible adjuvant for patients undergoing curative resection and IORT for pancreatic cancer.

Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT).Retrospective study.University hospital from January 1988 through December 1994.We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT.The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease.Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.