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Fibroadenoma of the gallbladder is extremely rare tumor, with only two cases reported in the world. It is characterized by abundant loose edematous connective tissue, glandular structure, polypoid structure covered by epithelia, and a filamentous pedicle. We report a case of 78-year-old woman histopathologically diagnosed after surgery. Macroscopically, the tumor was a dark-greenish solid mass with a short stalk, filling the gallbladder cavity, and it measured 11.5 x 4.0 x 3.5 cm in diameter. Microscopically, the tumor was composed of abundant loose stroma and a glandular component. Some of the glandular cells had hyperchromatic nuclei with disturbed polarity and were positively stained by p53 (30%) and Ki-67 (30-40%). Part of the stromal component revealed hypercellularity with an irregular nucleus, mitosis (2-3 cells/10 high-power fields), and positivity for Ki-67 (20%) and p53 (50%). We diagnosed this peculiar tumor as "fibroadenoma of the gallbladder with borderline malignancy". We present the details of this extremely rare case and discuss the pathological findings, comparing them to those in the two previously reported cases and to carcinosarcoma of gallbladder.

Three different types of treatment were conducted to clarify the properties of a novel immunomodulator, FTY720, in canine kidney allograft models. Survival, biochemical and hematological tests, pharmacokinetics, and histopathology of grafts and extra-renal organs were analyzed. Accompanying a remarkable reduction in circulating lymphocytes, single-drug treatment of FTY720, ranging from 0.05 to 10 mg/kg, exhibited significant prolongation of graft survival without a dose-dependent effect. Short-course induction with FTY720 at 5 mg/kg per day exhibited similar anti-rejection effects as did single-drug treatment but no advantage in rescuing ongoing rejection. In combination with cyclosporine (CsA; 5 mg/kg) or tacrolimus (FK; 0.5 mg/kg), FTY720 had an additive effect. Trough blood concentrations of FTY720 were linearly correlated with dose. No animal showed critical adverse effects at any point. FTY720 holds promise as a candidate in a new category of drugs that can be combined with conventional agents for induction and maintenance immunosuppression in clinical organ transplantation.

Background. Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A 2 (PLA2) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type II PLA 2 inhibitor, LY329722, could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. Methods. Eighteen beagle dogs, subjected to a 2-hr THVE, were divided into three groups. Group 1 (n56) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n56) intravenously (0.2 mg·kg 21 ·hr 21 ) for 60 min before ischemia, and to animals in group 3 (n56) for 60 min starting 15 min before reperfusion (0.2 mg·kg 21 ·hr 21 ). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B 2 and endothelin-1 levels, phospholipid levels and tumor necrosis factor-a mRNA expression in liver tissue, and histopathologic findings were evaluated. Results. Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnic hemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B 2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-a mRNA expression, and lessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. Conclusion. The present study demonstrated that a type II PLA 2 inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs. Phospholipase A 2 (PLA2) accelerates breakdown of membrane phospholipids of the heart, liver, and kidney under warm ischemia (1‐3), and leads to the release of free fatty acids including arachidonic acid, and lysophospholipids. The arachidonic acids are metabolized via the cyclooxygenase pathway to thromboxane (TX) A 2 and prostaglandins (PGs), or via 5-lipoxygenase pathway to leukotrienes. Lysophospholipids are metabolized to platelet-activating factor (PAF) by acetyltransferase. Most of these lipid derivatives have proinflammatory and vasoconstrictive actions and contribute to postischemic organ dysfunction, which is attenuated by nonspecific PLA 2 inhibitors ( 4‐6 ). PLA 2 is classified generally into two subtypes: cPLA2 and sPLA 2 (7). cPLA2 is involved in the breakdown of membrane phospholipids of intracellular organelles. Of the secretory PLA 2 (sPLA2), type I PLA2 is contained in the exocrine pancreas and type II PLA 2 is involved in inflammatory events, particularly the ischemia and reperfusion (I/R) injury of the heart, liver, kidney, and intestine (8 ‐11). LY329722 is a novel selective type II PLA 2 inhibitor (12), which is derived from synthetic LY315920/S-5920 (13). In this study, we tested whether LY329722 could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs.

クローン病に合併する肝膿瘍は,非常に稀であり,欧米では約0.5%の頻度として報告されているが,死亡例が存在するなど,予後に与える影響は大きい,われわれはクローン病に合併した肝膿瘍に対し開腹ドレナージを行い軽快した症例を経験したので報告する.症例は26歳,女性♂昭和61年にクローン病の診断を受け,再燃寛解を繰り返し,平成4年11月18日に腸瘻,小腸皮膚瘻のため開腹手術を施行.その後外来にて経過観察していたが,平成5年11月より右上腹部痛,発熱,嘔吐を主訴として来院し,US,CTにて多発性肝膿瘍,胆嚢周囲膿瘍と診断され入院.入院後膿瘍が多発しており,全身状態の悪化が見られたため,開腹ドレナージ術を施行した.本症例は肝道系感染症からの直接波及によって肝膿瘍に至ったものと考えられた.開腹手術によって救命し得た貴重な1症例と思われたので報告する.

患者は16歳,男性.下腹部痛を主訴として来院.来院の4週間前に自転車同士の衝突事故により全身打撲の既往があった.注腸造影検査にて直腸に壁外からの圧迫によると思われる狭窄を認めた.大腸内視鏡検査では,肛門縁より10cmの部位に粘膜下腫瘍様病変を認めた.腹部超音波検査,CT,MRIで病変は,内部が均一な嚢胞状腫瘤として抽出された.仙骨前面の血腫が最も疑われたが,すでに受傷より1ヵ月経過しており術前,確定診断は困難であった.粘膜下腫瘍も否定できなかったため,外科的療法の適応と考えられ低位前方切除術を施行した.組織標本では,固有筋層から漿膜下層にかけて凝血塊を認め,直腸壁内血腫であった.非常に稀と考えられる直腸壁内血腫の1例を経験したので,本邦報告の9例とともに文献的考察を加え報告する.

Background Adenosine is known to exert protective roles in hepatic ischemia and reperfusion injury, while all adenosine receptors do not play the cytoprotective roles. We have tested our hypothesis that blockage of adenosine binding to A 1 receptor by its antagonist, KW3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] attenuates hepatic ischemia-reperfusion injury. Methods Adult female beagle dogs underwent a 2 h total hepatic vascular exclusion (THVE) with a venovenous bypass. Nontreated animals that underwent THVE with a venovenous bypass alone were used as the control (Group CT, n = 6). KW3902 was given to the animals by continuous intraportal infusion for 60 min before ischemia at a dose of 1μg/kg/min (Group KW, n = 6). Two wk survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, energy metabolism, cAMP concentration, and histopathological findings were studied. Results Two wk animal survival was significantly improved in group KW compared with that in group CT (group CT: 16.7% versus group KW: 83.3%). HTBF, liver function, and hepatic adenine nucleotide concentration were remarkably better in group KW than group CT. In addition, cAMP concentration in group KW was maintained significantly higher than group CT. Histopathological examination revealed preservation of hepatic architecture and suppression of neutrophil infiltration into hepatic tissue in group KW. Conclusion Administration of adenosine A 1 receptor antagonist before ischemia attenuates hepatic ischemia-reperfusion injury. To elicit the beneficial effect of adenosine against ischemia and reperfusion injury of the liver, it is important to oppose adenosine A1 receptor activation.

A 72-year-old man with common bile duct cancer was treated by pylorus preserving pancreatoduodenectomy with D3 lymph node dissection and preventive radiotherapy at hepaticojejunostomy. At 4 months after surgery, CT demonstrated multiple liver metastatic tumors. Single drug chemotherapy, UFT 600 mg, was started. After 6 months, the liver metastatic tumor could not be seen by CT. UFT may be a first candidate for chemotherapy for recurrence of bile duct cancer.

A 67-year-old man with gallbladder cancer was treated by cholecystectomy and extrahepatic bile duct resection with regional lymph node dissection. At 10 months after surgery, CT demonstrated para-aortic lymph node recurrence. Single drug chemotherapy of UFT at 400 mg was started. After one month, the lymph node recurrence could not be detected by CT. UFT may be the primary candidate for chemotherapy for lymph node recurrence of gallbladder cancer.

A 67-year-old man was referred to our department because of a mass in the pancreas tail. Pancreatic tail cancer with lymph node metastasis was diagnosed, based on various radiological findings. Computed tomography (CT) revealed a slightly enhanced tumor mass around the celiac plexus, and endoscopic retrograde pancreatography (ERP) showed complete obstruction of the main pancreatic duct at the tail, although magnetic resonance imaging (MRI) demonstrated no elevation of the mean pixel value of the tumor after gadolinium (Gd) injection, and tumor markers of pancreas cancer were within normal limits. At surgery, the mass around the celiac plexus was found to be blood coagulation, and the pancreas tail tumor was found to be a focal hematoma in the pancreas. Pathologically, the hematoma was not encapsulated, and it was diagnosed as hemorrhage in the pancreas parenchyma. Both hemorrhagic lesions were suspected to have developed respectively. It is difficult to distinguish pancreas hemorrhage from carcinoma in the pancreas with chronic pancreatitis, especially when the hemorrhage is small in size and there are other extrapancreatic hemorrhagic lesions. For such diagnosis, the superiority of MRI with Gd injection is indicated.

Background The immunosuppressive effect and other properties of a novel immunosuppressant, FTY720, have been studied mostly in the experimental transplantation of various extrahepatic organs. In this experiment, we evaluated the antirejection potency and adverse effects of this agent on liver grafts using a canine liver transplantation model. Methods. Forty-eight orthotopic liver transplantations were performed by the standard technique under a veno-venous bypass. Liver recipients were divided into two studies: a single-dose study with FTY720 at various doses and a combined dose study with conventional immunosuppressants (cyclosporine or tacrolimus) alone and combined with FTY720. Survival, biochemical and hematological tests, blood levels of immunosuppressants, and postmortem histology were determined. Results. The median survival of untreated control animals was 9 days, whereas treatment with FTY720 at a dose of 0.1 mg/kg/day prolonged graft survival to 49.5 days. FTY720 at 1 mg/kg/day showed a slight but insignificant prolongation to 16 days, but when the dose was increased to 5 mg/kg/day, the graft was rejected at 10 days. The combination of FTY720, 0.1 mg/kg/day, with a subtherapeutic dose of cyclosporine, 5 mg/kg/ day, prolonged median animal survival from 40 days with cyclosporine alone to 74 days. A combination of FTY720 (0.1 mg/kg/day) with tacrolimus (0.5 mg/kg/ day) compromised animal survival, reducing survival from 83.5 days with tacrolimus alone to 30.5 days due to infectious complication and emaciation by overimmunosuppression. No evident drug-induced side effects were observed. Conclusions. FTY720 has a potent immunosuppressive effect when used alone at 0.1 mg/kg/day in canine liver transplantation. FTY720 is a promising candidate for future clinical application in orthotopic liver transplantation.