Shigeaki Takeda

Coagulopathy in Disseminated Intravascular Coagulation due to Abdominal Sepsis: Determination of Prothrombin Fragment 1+2 and Other Markers

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence of disseminated intravascular coagulation (DIC) in obstructive jaundice and its relation to biliary tract infection.

Coagulation studies were done on 78 consecutive cases of obstructive jaundice with or without biliary tract infection. Among 26 cases with biliary tract infection 20 cases showed no bleeding tendency but remarkable hypercoagulability with decreased fibrinolytic activity. Other six cases developed diffuse bleeding tendency in addition to the signs of hypotension and multiorgan dysfunction such as oliguria, respiratory distress and mental confusion. Most showed marked coagulation defects characterized by thrombocytopenia, decreased fibrinogen, antithrombin III and plasminogen levels and narrowing of maximal amplitude in thrombelastogram as well as the increase of fibrin degradation products and positive soluble fibrin monomer complexes. All except one died and three cases were autopsied. In two cases postmortem examination revealed multiple fibrin thrombi in lungs and other organs. A cause of the development of bleeding tendency in obstructive jaundice presently observed may likely to be due to the occurrence of disseminated intravascular coagulation (DIC), i.e. hypercoagulability caused by the biliary tract infection is responsible.

Increased fibrin/fibrinogen degradation products without increase of plasmin-α2-plasmin inhibitor complex after hepatectomy for hepatocellular carcinoma

To clarify the meaning of increased serum fibrin/fibrinogen degradation products (FDP) in the postoperative period of hepatectomy, blood coagulation and fibrinolysis were studied using recently devised laboratory assays of a group of 30 patients with hepatocellular carcinoma. Twenty of these cases were associated with liver cirrhosis. As a control group, 15 patients with colorectal carcinoma without liver diseases were also selected. In the early postoperative period following hepatectomy, a hypercoagulable state designated as intravascular thrombin generation was confirmed from the finding of increased plasma levels of fibrinopeptide A (FPA). Fibrinopeptide B beta 15-42 (B beta 15-42) in the plasma also increased immediately after the peak of FPA, followed by a gradual decline in B beta 15-42 levels. On the other hand, FDP in the serum increased significantly rather late in the postoperative period following hepatectomy without increased levels of plasmin-alpha 2-plasmin inhibitor complex. However, postoperative increase of fibrin/fibrinogen degradation products-D (FDP-D) was modest and not different from the colectomy group. Therefore, the relevance of intravascular coagulation in the hepatectomy for the patients with liver cirrhosis seems not to be significant, and then such an increase of FDP in the serum seems to be related to other mechanisms.

Hepatocellular Carcinoma Arising from Autoimmune Hepatitis: Report of a Case

We describe an operative case of a 64-year-old woman with hepatocellular carcinoma (HCC) associated with autoimmune hepatitis (AIH) during a 4.8-year follow-up. Sixty-seven cases of HCC with AIH have been previously reported as a sporadic complication of AIH. The survival rate after diagnosis with HCC showed the 5-year survival rate to be 10.4%, thus indicating the majority of patients to have either extensive HCC or severe liver dysfunction. Immunosuppressant therapy helped to postpone the hepatocarcinogenesis but it did not improve the prognosis of the patients demonstrating HCC with AIH. A univariate analysis of factors associated with prognosis disclosed that the histology of nontumorous lesion at diagnosis with HCC, tumor size, tumor number, and treatment for HCC were independent prognostic predictors. Patients with AIH were not recognized to be a high-risk group for developing HCC because HCC occasionally occurred even in patients with long-standing cirrhosis in the absence of hepatitis B virus and hepatitis C virus infection.

Tubular carcinoma of the breast: a histologic subtype indicative of breast-conserving therapy.

Abstract We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5–3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended.

A collision tumor composed of adenocarcinoma and malignant lymphoma in the remnant stomach after pancreatoduodenectomy: report of a case.

Abstract The occurrence of a collision tumor in the stomach, consisting of adenocarcinoma and malignant lymphoma, is extremely rare. We report herein the case of a patient who had undergone a pancreatoduodenectomy for bile duct cancer 5 year earlier, in whom an ulcerating tumor of the remnant stomach developed and grew rapidly within 5 months. Surgical exploration revealed a tumor in the remnant stomach, multiple liver metastases, and multiple lymph node metastases. Total resection of the remnant stomach was performed, and pathological examination revealed a collision tumor consisting of adenocarcinoma and malignant lymphoma. The patient died of liver metastases and lymph node metastases 7 months after his second operation. The coexistence of both adenocarcinoma and malignant lymphoma of the remnant stomach and the etiology of this unusual combination, never previously reported, is discussed.

Metachronous Mature Cystic Teratomas in the Left Ovary and Bilateral Diaphragm: Report of a Case

Mature cystic teratomas are found often in gonadal sites, but rarely in extragonadal sites, such as the retroperitoneum, mediastinum, central nerve system, lung, and liver. To our knowledge, only seven cases of pathologically benign mature cystic teratoma originating in the diaphragm have been reported. We report the case of a 45-year-old woman found to have a mature cystic teratoma below the left side of her diaphragm. She had undergone oophorectomy for a huge mature cystic teratoma in the left ovary 34 years earlier, followed 1 year later by excision of a tumor in the right side of the diaphragm. All sections of the pathological specimen showed evidence of a mature cystic teratoma and pathologically resembled the specimens obtained in the previous two operations. Although this tumor might have been a recurrence of the mature cystic teratoma in the left ovary, it is more likely that multicentric teratomatous foci metachronously developed in the gonadal and extragonadal sites.

A 10-year survivor with unresectable hepatic metastases from sigmoid colon carcinoma treated with regional chemotherapy.

We treated a man with unresectable hepatic metastases from sigmoid colon carcinoma who has since survived for more than 10 years. A sigmoidectomy with lymph node dissection was performed and a continuous hepatic arterial infusion of 5-fluorouracil (5-FU) with intermittent infusion of mitomycin C (MMC) was administered for about 3 months after this operation. The total doses of 5-FU and MMC were 16 g and 84 mg, respectively. Tegafur also was administered orally at a dose of 600 mg/day for about 8 months. The carcinoembryonic antigen (CEA) level (which had reached 4,409 ng/ml preoperatively) normalized 4 months after surgery, and still remains normal. Very few patients with unresectable hepatic metastases survive for 5 or more years. However, regional chemotherapy can be effective in some patients.

The Role of Disseminated Intravascular Coagulation in Shock Induced by Transfusion of Human Blood in Dogs

Hemolytic blood transfusion reactions were produced in 20 dogs. Animals transfused with human blood twice in a two‐week interval demonstrated a significant increase in anti‐human red blood cell agglutination titer at the time of the second transfusion. Eighteen dogs that survived from the first transfusion reaction were divided into two groups with or without heparin treatment. The hemolytic transfusion reaction in the sensitized animals was characterized by shock and multiple coagulation abnormalities. Heparin failed to prevent shock, hemoglobinemia and thrombocytopenia, and decreased the mortality rate in heparinized animals. Pathologic examination revealed that the thrombi in the splanchnic organs were less common in the heparinized dogs.

Appropriate use of fresh frozen plasma after hepatic resection, based on prothrombin time.

肝切除術後のfresh frozen plasma (FFP) の適正な使用基準について肝細胞癌切除66例を2期にわけ検討した. 前期29例にはFFPを制限を設けずに使用し, 後期37例にはprothrombin time (PT) を指標にできる限り使用節減の方向で術後管理を行った. その結果, 後期ではFFPの1人あたり使用総量で前期より約40%節減でき, FFP非使用例は前期2例より後期14例に増加した. 後期にPT延長例が増加したが出血傾向の発生に差はなく, 肝不全などの致命的合併症は前期3例 (10%), 後期2例 (5%) にみられ, いずれも術後1週間以内にPTが15秒を越えた症例であった. 以上の成績から, 凝固因子補充を目的としてFFPを輸注する場合, 術後1週間以内にPTが15秒以上に延長した時使用を考慮すればよいと考える.