Present status of pancreas transplantation in Japan--donation predominantly from marginal donors and modified surgical technique: report of Japan pancreas transplantation registry.

In Japan, organ donation has been still limited because of the strict donor criteria. The aim of this study was to show the effectiveness of pancreas transplantation (PTx) by analyzing the outcomes even under poor donor conditions. Thirty-six cases of PTx (32 simultaneous pancreas and kidney transplantations [SPK], 4 pancreas after kidney transplantations) performed during the last 8 years were examined especially for donor characteristics. Mean donor age of 41.4 +/- 11.9 years was considerably older compared with that in the United States and Europe; donors aged over 40 years comprised 67% of the total. According to the criteria described by Kapur, 29 cases (81%) in our series would be considered marginal. Thus, to increase blood supply into the pancreatic head, the gastroduodenal artery (GDA) was anastomosed using donor artery to common hepatic artery or iliac Y graft. These procedures were performed in 16 of the 24 cases in which there was liver procurement. Eventually, 34 cases (94%) preserved GDA continuity. Mean total cold ischemic time of pancreatic grafts was 12 hours 15 minutes. Of 214 registrants, 17 patients on the waiting list for SPK died of diabetic complications. To date, patient survival remains 100% with a mean follow-up period of 33 months. Pancreas graft survivals at 1, 3, and 5 years posttransplantation were 92%, 80%, and 80%, respectively. In contrast, kidney survivals were 91%, 91%, and 91%, respectively. The integrity of the pancreas head and duodenum by preservation of the GDA continuity might have decreased the risk associated with the marginal donors.

Identification of a tumor-associated target antigen, ATM-1, for a human T-cell clone with activated killer activity and its existence in sera of cancer patients.

Three human T-cell clones with activated killer activity (5B5, 5C1, and 7B5) which could lyse various tumor cell lines were established. The cytotoxic activity of these clones was decreased by incubation with anti-CD3 monoclonal antibody, suggesting that they recognized tumor cells by T-cell antigen receptor. A monoclonal antibody which blocked the cytotoxic activity of clone 5B5 was obtained. This antibody (N1977) blocked the binding and cytotoxic activity of clone 5B5 at the target cell level, suggesting that the antigen defined by N1977 antibody, designated as ATM-1, was a target molecule recognized by 5B5 cells. ATM-1 in the conditioned medium of a cancer cell line (NBT-2) and serum from a patient with lung cancer was characterized by following its immunoreactivity. On gel filtration, both the conditioned medium and the serum gave three peaks of ATM-1 immunoreactivity, corresponding to approximate molecular weights of 1,200,000, 700,000, and 120,000, respectively. They were chromatofocused at pH 4.0, 4.8, and 6.5, respectively. The high molecular weight forms were shown to be molecules with the disulfide-linked elementary glycoprotein with ATM-1 immunoreactivity and approximate molecular weight of 120,000. Most of the molecules with ATM-1 immunoreactivity bound to both concanavalin A and wheat germ agglutinin, and their binding activity to the antibodies was lost by treatment at 60 degrees C for 30 min. An assay of ATM-1 level in sera was performed by a sandwich enzyme immunoassay. The following positive percentages were obtained from preliminary clinical studies: breast cancer, 67% (8 of 12 cases); hepatocellular carcinoma, 83% (10 of 12 cases); gastric cancer, 58% (7 of 12 cases); lung cancer, 41% (5 of 12 cases); hematological malignancies, 0% (0 of 9 cases); systemic lupus erythematosus, 0% (0 of 8 cases); rheumatoid arthritis, 0% (0 of 8 cases).

Hepatic clearances of antipyrine, indocyanine green, and galactose in normal subjects and in patients with chronic liver diseases.

Blood clearance of antipyrine, indocyanine green, and galactose were measured to evaluate the alterations of effective hepatic blood flow and hepatic intrinsic clearances in chronic liver diseases. Galactose blood clearance, which may be taken as effective hepatic blood flow, decreased by approximately 30% in patients with cirrhosis (12.49 +/- 0.76 ml/min/kg; mean +/- SE; n = 17) compared with normal subjects (18.17 +/- 1.03 ml/min/kg; n = 5). In patients with cirrhosis, intrinsic clearances of antipyrine (0.178 +/- 0.014 ml/min/kg; n = 17) and indocyanine green (6.19 +/- 1.38 ml/min/kg; n = 7) showed 61% and 85% reduction, respectively, compared with those of normal subjects (0.462 +/- 0.048 ml/min/kg; n = 5; 41.72 +/- 7.75 ml/min/kg; n = 5). Considering that indocyanine green and antipyrine are eliminated by different hepatic mechanism, these mechanisms may not be equally sensitive to decrements in hepatic function. In addition, fractional reductions of intrinsic clearances for these compounds are thus much greater than that of effective hepatic blood flow.

Twenty-five-year experiences with esophageal transection for esophageal varices.

Results of 287 transthoracoabdominal esophageal transections (Sugiura procedure), 125 transthoracic esophageal transections, 48 transabdominal esophageal transections, and 58 other nonshunting operations performed during the past 25 years were analyzed. Overall operative mortality rate was 5.0% (26/518); however, it was observed only in patients with liver cirrhosis (7.0%) and was higher in emergency cases (23.3%) and patients classified Child C (17.1%). Two hundred two patients died during the follow-up period, which lasted 24 years; 33 patients died of rebleeding, 89 of hepatic failure, 65 of hepatoma, and 35 of other causes. Cumulative survival rates of patients after non-shunting operations differed significantly according to the nature of the original diseases and the severity of liver damage. The cumulative survival rate at 10 years in patients with extrahepatic portal obstruction was 90.7%, 77.6% in idiopathic portal hypertension, and 33.0% in liver cirrhosis and at 20 years, 85.6%, 37.9%, and 8.1% respectively. The cumulative survival rate at 5 years in patients classified Child A was 88.7%, 77.7% in Child B, and 39.5% in Child C, and at 10 years, 73.4%, 45.3%, and 14.1%, respectively. Esophageal transection can be performed safely and is recommended in patients classified Child A or B. Patients in Child C should be treated by endoscopic sclerotherapy and other conservative measures.

Study of new prognostic factors of esophageal variceal rupture by use of image processing with a video endoscope.

BACKGROUND: We studied new prognostic factors of esophageal variceal rupture by analyzing electronic video images of esophageal varices in 30 patients with portal hypertension. METHODS: Fifteen of the patients were emergency or elective cases (bleeders), and the remaining 15 were prophylactic cases (nonbleeders). A comparison was made between the bleeders and nonbleeders in terms of endoscopic findings and the image processing data, especially variceal color tone and red color sign. RESULTS: Endoscopic findings based on the general rules prepared by the Japanese Research Society for Portal Hypertension showed no significant difference between the two groups. However, with regard to the image processing data, both the ratio of red signal and the ratio of value were significantly lower in bleeders than in nonbleeders. In addition, the area ratio of red color sign was significantly higher in the former than in the latter. A follow-up study of nonbleeders also indicated that image processing data were more reliable than traditional endoscopic rules. CONCLUSIONS: By adding these image processing data to the traditional general rules for recording endoscopic findings, it is possible to select patients with varices that have a higher risk of rupture.

Development of a computer-aided surgery system: three-dimensional graphic reconstruction for treatment of liver cancer.

Simulation of the needle puncture and volume estimation for the tumors in the liver were carried out with the three-dimensional image reconstruction system, which consists of a medical image acquisition system, a data processing system, and a graphic display. A set of sliced-image data from a computerized tomography and/or a magnetic resonance imaging was used to reconstruct the liver, the vessels, and the tumors of the patients with liver cancer. A good agreement of anatomic locations of both the intrahepatic vessels and the tumors between the reconstructed liver model and the echography done intraoperatively was observed. Surgical simulations with these graphic models clearly indicated safety areas for needle puncture in the laser coagulation therapy. In addition liver volumes were calculated within 3% of error in comparison to the measured values. These results indicate that the computer-aided surgery system is a highly promising method that avoids cumbersome stereoscopic recognition of the anatomical location of the diseased area and the vessels, before and after surgery.

Safe intraabdominal pressure of carbon dioxide pneumoperitoneum during laparoscopic surgery.

BACKGROUND: The deliberate induction of carbon dioxide pneumoperitoneum during laparoscopic surgery could be a possible source of cardiovascular collapse. The effects of elevated intraabdominal pressure (IAP) on systemic hemodynamics and splanchnic blood flow created by insufflation of carbon dioxide were examined in anesthetized dogs. METHODS: Stepwise increases in IAP of 8 (n = 7), 12 (n = 7), and 16 (n = 7) mm Hg were applied to determine the threshold pressure that had minimum influence on these hemodynamics. Hemodynamic parameters were measured at baseline and 1, 2, and 3 hours after the start of insufflation. RESULTS: At an IAP of 16 mm Hg, cardiac output was decreased significantly by 1 hour after the start of insufflation and became progressively lower during the procedure. Systemic vascular resistance was elevated significantly in parallel with the change in cardiac output. Although hepatic arterial blood flow was not decreased significantly, portal venous and superior mesenteric arterial blood flows were diminished significantly at 16 mm Hg, resulting in a decrease in total hepatic blood flow. No significant changes were observed in these parameters at 8 or 12 mm Hg. CONCLUSIONS: Based on these results, an IAP from 8 to 12 mm Hg is recommended for laparoscopic surgery, to avoid complications caused by hemodynamic derangements.

Leiomyosarcoma of the small intestine associated with von Recklinghausen's disease: report of a case.

A 54-year-old woman with intestinal multiple smooth muscle tumors including leiomyosarcoma, epithelioid leiomyoma, and leiomyomas in association with von Recklinghausen's disease is reported. Thirteen years after the excision of an intestinal leiomyosarcoma, another leiomyosarcoma arose in a different area of the jejunum and was also completely resected. Although leiomyomas are occasionally recognized in patients with von Recklinghausen's disease and a gastrointestinal neoplasm, there have been no other reports of leiomyosarcomas. Careful observation of the tumor is necessary and, if a rapid increase in tumor size is recognized, malignant tumor may have arisen and early surgical treatment is required.

Arteriovenous fistula following central venous catheterization.

We surgically obliterated arteriovenous fistulas in three cases that developed after subclavian catheterization. The first patient presented with heart failure two years after the catheterization, and the other two presented with asymptomatic continuous bruits. The intervals between the removal of the catheter and the appearance of the bruit were 1.5 years, three days, and two months. It took another six months for the appearance of heart failure in the first case. The feeder of the fistula was a branch of the subclavian artery in all cases. In previously reported cases, there was usually some interval between the removal of the catheter and detection of the fistula, and the feeder was much more commonly one of the branches of the subclavian artery than the subclavian artery itself.

False aneurysm as a late complication of division of a patent ductus arteriosus.

A 58-year-old male patient who had a huge false aneurysm as a late sequela of division of patent ductus arteriosus was surgically managed with success. It is noteworthy that 24 years had elapsed from the initial operation until recognition of the aneurysm. The pathogenesis and method of the surgical treatment are discussed.

Aortobronchial fistula after an aortic operation.

A 71-year-old man with a postoperative aortobronchial fistula was successfully treated. The fistula occurred between the left lower lobe and the descending thoracic aorta, to which a distal anastomosis of a temporary bypass graft had been placed during thoracic aortic aneurysmectomy 3 years before. For saving patients with this complication, early surgical treatment during episodes of intermittent hemoptysis is important. The use of an omentum pedicle flap for the isolation of the suture line is a important adjunct.

Activities of thymidylate synthetase and thymidine kinase in gastric cancer.

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.

Therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in gastric cancer.

The therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in 64 inoperable gastric cancer patients are reported. An intermediate-dose treatment was given to 48 patients, and a low-dose treatment to 16 patients. In the intermediate-dose treatment, leukopenia was observed in 11 patients, nausea and vomiting in six patients and diarrhea and stomatitis in two patients each. In the low-dose treatment, no patient developed toxic symptoms of grade 3 or 4. All 9 responders had adenocarcinoma of the poorly differentiated type and the response rate in patients who belonged to this type was 32.1%.

Effects of nonshunting operations on portal venous pressure and hepatic blood flow.

A comparative analysis has been presented of the effect of the nonshunting operation on portal venous pressure and effective hepatic blood flow in patients with liver cirrhosis and idiopathic portal hypertension. A reduction of portal pressure after splenectomy with esophagogastric devascularization in 17 patients with idiopathic portal hypertension was significantly greater than that in 79 patients with liver cirrhosis (-21 +/- 4.1 percent versus -8.9 +/- 1.6 percent, p less than 0.01). Clearance of galactose from the blood, which approximates effective hepatic blood flow, was decreased after the nonshunting operation by 6.7 percent in five patients with liver cirrhosis (p value not significant). On the other hand, there was a 19.4 percent reduction (statistically significant) in galactose clearance in four patients with idiopathic portal hypertension (p less than 0.05). Based on these data, we suggest that in patients with idiopathic portal hypertension, the splenic circuit largely contributes to the portal hypertension, the effective hepatic blood flow, or both. We recommend a nonshunting operation for the treatment of esophageal varices from the hemodynamic viewpoint in cirrhotic patients.

Current strategy for esophageal varices in Japan.

Management of bleeding esophageal varices in Japan includes tamponade, sclerotherapy, devascularization, and shunt procedures. Sclerotherapy is the most widely used treatment in both acute and chronic management. The Japanese Research Society for Sclerotherapy of Esophageal Varices monitors and surveys this treatment method at 152 institutions. Extensive devascularization operations now include a thoracotomy less frequently than previously, and they have a 6.6% rebleeding rate in elective patients. Shunt operations are applied in 20% of cases of bleeding esophageal varices in Japan. Effective medical and surgical treatments have led to changes in management strategy and to diversity in treatment during the last decade. The timing of treatment, the nature of the disease, the patient's liver function, and the distribution of collaterals should all be considered in selecting treatment.

Increased insufflation pressure enhances the development of liver metastasis in a mouse laparoscopy model: possible mechanisms.

BACKGROUND: The effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis was investigated in a mouse model. The possible mechanisms involved in the pressure-related enhancement of liver metastasis were also examined. METHODS: Mice inoculated intraportally with colon 26 cells underwent CO2 pneumoperitoneum at different pressures (5,10, or 15 mmHg) for 30 or 60 min, or received no treatment other than tumor cell inoculation (control). The subsequent growth of liver metastases was examined. Mice injected intraportally with 111In-oxine-labeled colon 26 cells underwent pneumoperitoneum at three different pressures or served as controls. The radioactivity of the liver was determined to evaluate tumor accumulation in the liver. Mice received pneumoperitoneum at three different pressures or received trocar placement alone. Changes in plasma interleukin-6 levels were determined. RESULTS: The growth of liver metastases on day 14 was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged duration of pneumoperitoneum without significant interaction. The 15-mmHg pneumoperitoneum group showed a higher (p < 0.05) accumulation of radioactivity in the liver compared with the 5-mmHg pneumoperitoneum group and controls. Pneumoperitoneum groups with 5 and 10 mmHg showed higher (p < 0.05) peak levels of IL-6 compared with controls. CONCLUSIONS: An elevated insufflation pressure plays an important role in the enhancement of liver metastases, and this pressure-related adverse effect may be partly relevant to facilitating accumulation of tumor cells in the liver.

Pneumoperitoneum with carbon dioxide enhances liver metastases of cancer cells implanted into the portal vein in rabbits.

BACKGROUND: Little is known about the role of the CO2 pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO2 pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model. METHODS: Immediately after intraportal inoculation of 2.5x10(5) cells of VX2 cancer, the rabbits received either CO2 pneumoperitoneum at a pressure of 10 mm Hg for 30 min (pneumoperitoneum group, n = 14) or laparotomy alone for 30 min (laparotomy group, n = 14). RESULTS: The number (p<0.01) and area of cancer nodules (p = 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p<0.001). CONCLUSIONS: Compared with laparotomy, CO2 pneumoperitoneum enhanced the development of liver metastases in this experimental model.

Characteristics of pancreas transplantation currently performed in japan.

The Pancreas Transplantation (tx) Program under the Japanese Organ Transplant Act was started in 2000. PTx is indicated for type 1 diabetic patients on hemodialysis therapy. As of April 2003 93 patients are listed as candidates. Ten cases of PTx with enteric or bladder-drained technique were performed during the last 3 years as well as nine SPK and one PAK. Of 10 cases, nine recipients are insulin-free with HbA1c values ranging from 4.4% to 5.7%, although exogenous insulin was required in six cases temporarily, namely for a median 63 days (12 to 225 days). One case was lost due to pancreatic graft thrombosis. All 10 kidney grafts are functioning. Based on the experiences with 14 cases of pancreas tx using non-heart-beating (NHB) donors, we defined the criteria of NHB donor as: age younger than 40 years and cessation of respiratory support. One case of SPK with graft of NHB donor was done, and the recipient is off insulin. Pancreas and kidney are allocated for SPK if the recipient shares at least one HLA-DR antigen. Marginal donors were defined as higher mean donor age, median 37 (range 18 to 58 years); mean 38 +/- 12 years), and no death cause of by trauma. The revascularization of gastroduodenal artery to the pancreatic graft was performed in eight cases to minimize the risk of ischemic injury to the pancreatic graft and technical failure in cases of marginal donor.

Laparoscopic gastropexy for acute gastric volvulus: a case report.

A 7-year-old girl presented with an acute gastric volvulus that was reduced with a nasogastric catheter. An anterior gastropexy was undertaken laparoscopically. The gastrocolic omentum was deficient along most of the greater curvature, which had allowed organoaxial volvulus. Two years later, gastric volvulus has not recurred. Laparoscopy is an acceptable approach for the evaluation and treatment of children with acute gastric volvulus.

Esmarch's bandage technique in distal bypass surgery.

Esmarch's rubber bandage technique has been applied to 49 distal bypass surgeries in 46 patients during the past ten years. The primary and secondary patency rates at 5 years after femoro-tibial bypass surgery were 82% and 92%, respectively. This technique has the following advantages: (1) it minimizes surgical injury of the arterial wall because there is less dissection around the anastomotic site; (2) it decreases scar formation in the anastomotic area after surgery; (3) it maintains abundant muscular blood flow by preserving small branches to muscles, and (4) it provides a bloodless surgical field and easy handling for fine sutures without using vascular clamps. We consider that the avoidance of long circumferential dissection of the artery may play an important role in improving long-term patency in distal bypass surgery.