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.

Long live the health care system in Japan.

In Japan, a cost-containment policy has been implemented with health care system reform. Increasing medical expenses are inevitable due to aging of the population, health transitions, and expanded and advanced medical services. Policies such as the introduction of regressive reimbursement for inpatient services as part of social insurance, the reduction in the number of hospital beds, fewer medical examinations, and curtailed usage of medical tests have jeopardized the accessibility and quality of medical services, especially for the elderly. Compared to other developed countries, both the proportion of the government's payment of health expenses and the proportion of health expenses in proportion to GDP are lower in Japan. To confront the challenges of an aging society in terms of finances and the health care system, policymakers from the Ministry of Health should take a comprehensive approach instead of a mere cost-containment policy.

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.

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.

[Tumoral levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in elderly colorectal cancer patients].

Fluoropyrimidine therapy for elderly colorectal cancer patients remains controversial. Tumoral levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and the ratio of TP to DPD determined by an enzyme-linked immunosorbent assay were compared between colorectal cancer patients aged 75 or over (elderly group, n = 25) and those 74 years or less (control group, n = 87), in order to examine the characteristics of colorectal cancers in the elderly from the viewpoint of metabolic and anabolic pathways of fluoropyrimidines. The level of TP was 78.4 +/- 47.0 unit/mg protein in the elderly group and 82.4 +/- 70.9 unit/mg protein in the control group (p = 0.86). The level of DPD was 53.7 +/- 43.1 unit/mg protein in the elderly group and 52.6 +/- 37.7 unit/mg protein in the control group (p = 0.73). The ratio of TP to DPD was 2.0 +/- 1.2 in the elderly group and 1.8 +/- 0.9 in the control group (p = 0.44). These three parameters did not differ between the groups when divided according to Dukes' stage (Dukes' A.B versus Dukes' C.D). These results suggest that there are no age-specific characteristics in relation to conversion of fluoropyrimidines such as capecitabine and doxifluridine to 5-fluorouracil (FU) and degradation of 5-FU in colorectal cancers.

[Training in specialties and subspecialties of surgery: current system in Japan and a proposal for the future].

The maintenance of quality care of surgical patients is the primary concern of surgeons. The Japan Surgical Society has taken the responsibility for establishing standards for the quality care of patients in surgery and surgical subspecialties. The society introduced training systems for surgeons and developed qualifying examinations after 4 years of training in general surgery in 1984, but after 24 years, in response to the demands from surgeons and patients, new training, certification, and recertification programs are under investigation by the Japan Surgical Society and its related societies of subspecialties. Currently, a 3-year training system and subsequent qualifying examination for gastroenterological surgery, pediatric surgery, cardiovascular surgery and pulmonary surgery are being proposed after completing 4-year training and qualifying examination in general surgery. The pros and cons of this system are discussed and a more desirable system for the future is proposed.

Liver metastasis following pneumoperitoneum with different gases in a mouse model.

BACKGROUND: The validity of using CO2 in laparoscopic tumor surgery has not yet been established. To address this question, we investigated the growth of liver metastases following insufflation with different gases in a mouse laparoscopy model. METHODS: Male BALB/C mice inoculated intraportally with colon 26 cells were randomized to undergo pneumoperitoneum with CO2 (n = 16), helium (n = 16), argon (n = 16), or air (n = 17), or to act as controls without insufflation (n = 17). RESULTS: The growth of cancer nodules on the liver 14 days after surgery was greater in mice following insufflation with CO2 (p < 0.01), helium (p < 0.01), argon (p = 0.01), and air (p = 0.07) than in control mice. No significant differences were found between the four insufflation groups in the growth of liver metastases. CONCLUSION: These results suggest that insufflation plays an important role in the development of liver metastases but that the choice of gas may not affect their growth.

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

Despite the widespread use of laparoscopic techniques for colorectal cancer surgery, little is known about the potential risk of liver metastasis following CO2 pneumoperitoneum. We investigated the effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis in a mouse model. Six- to 7-week old male BALB/C mice were intraportally inoculated with 2 x 10(4) Colon 26 cells and randomly allocated to receive either CO2 pneumoperitoneum at different pressures (5 mmHg, 10 mmHg, or 15 mmHg), xiphoid-pubic laparotomy, or no treatment other than tumor cell inoculation. Mice undergoing pneumoperitoneum or laparotomy were then subdivided by the duration of treatment (30 minutes or 60 minutes). Cancer nodules on the liver surface from a total of 122 mice were evaluated on the 14th postoperative day. Similar to full laparotomy, CO2 pneumoperitoneum at 10 mmHg and 15 mmHg for 60 minutes, and pneumoperitoneum at 15 mmHg for 30 minutes significantly promoted the growth of cancer nodules on the liver surface. Enhancement of tumor growth was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged length of pneumoperitoneum (p = 0.53) without significant interaction (p = 0.49). These results suggest that an increased insufflation pressure promotes the growth of liver metastases as well as laparotomy in this animal model. growth of liver metastases in a mouse laparoscopy model, following different pressures and durations of CO2 pneumoperitoneum, which is used most often in laparoscopic procedures.

[Clinical significance of determinations of dihydropyrimidine dehydrogenase levels in primary and hepatic lesions of colorectal cancer patients].

Dihydropyrimidine dehydrogenase (DPD) levels were determined by enzyme-linked immunosorbent assay in primary tumors and adjacent normal mucosa from 114 colorectal cancer patients, including 9 with synchronous liver metastases. The level of intratumoral DPD was 55.0 +/- 38.7 unit/mg protein (n = 114) and that of mucosal DPD was 55.0 +/- 38.7 unit/mg protein (n = 114). The ratio of intratumoral DPD to mucosal DPD was 1.8 +/- 0.8 in patients developing metachronous liver metastases (n = 7), 1.0 +/- 0.5 in patients without recurrence (n = 61), and 1.0 +/- 1.1 in patients with synchronous liver metastases (n = 31) (p = 0.01, metachronous liver metastasis group versus recurrence-free and synchronous liver metastasis groups). The levels of DPD were higher in primary lesions than in synchronous liver metastasis (n = 9, p < 0.05). These results indicate that: (1) degradation of 5-fluorouracil (5-FU) is enhanced in hepatic lesions more than in primary lesions, which is consistent with previous findings showing the therapeutic advantage of hepatic arterial infusion over intravenous infusion in relation to the treatment of 5-FU for liver metastases of colorectal cancer patients; and (2) predicting the effectiveness of hepatic arterial infusion of 5-FU for patients with metachronous liver metastases is difficult based on DPD determination of primary lesions alone.

[Problems concerning the prices of surgical operations in Japan. Union of Social Medical Insurance Committee Members of Surgical Societies in Japan].

The Union of Social Medical Insurance Committee Members of Surgical Societies in Japan was established in 1967. The union has tried to develop scientific methods to assess the price of surgical operations in Japan and proposed a tentative plan for the assessment of the price of operations. The price of an operation includes personnel expenses and other costs such as the prime costs to repay loans for land and buildings, and taxes. Personnel expenses are calculated by the grade of technical difficulties, the number of doctors and nurses and the duration of the operation. A more precise method to judge the difficulties of the operation seems to be necessary. To examine the recent increase in expenses for surgical materials, the cooperation of main hospitals authorized by surgical societies will be necessary. The prices of surgical operations presented by the Ministry of Health and Welfare of Japan correlated well with the prices proposed by the Union.

[Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study].

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.

The influence of different insufflation pressures during carbon dioxide pneumoperitoneum on the development of pulmonary metastasis in a mouse model.

BACKGROUND: The effects of different insufflation pressures on the development of pulmonary metastasis was investigated in a mouse laparoscopy model. METHODS: BALB/C mice intravenously inoculated with colon 26 cells were randomized to one of five treatment groups (10 mice per group): pneumoperitoneum at different pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control. Cancer nodules on the lung surface 19 days postoperatively were compared between groups. RESULTS: (a) As compared with the control group, pneumoperitoneum at 10 and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p < 0.01). (b) The growth of metastases also was greater in laparotomy group mice than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05). CONCLUSIONS: These results suggest that the effects of different insufflation pressures on the growth of pulmonary metastases are not identical, and that pneumoperitoneum with high pressure may promote pulmonary metastases similar to those with laparotomy.

Effect of CO(2) pneumoperitoneum on growth of liver micrometastases in a rabbit model.

Little is known about the risk of metachronous liver metastases following laparoscopic resection for gastrointestinal malignancies. The effect of CO(2) pneumoperitoneum on the growth of established liver micrometastases was investigated in a rabbit model. Male Japanese white rabbits weighing 2.8 to 3.3 kg were randomized to three groups (n = 15 per group) 3 days following intraportal inoculation of a tumor suspension containing 5 x 10(4) cells of VX(2) cancer. In the pneumoperitoneum group, insufflation with CO(2) was maintained at a pressure of 10 mmHg for 30 minutes. In the laparotomy group the abdominal cavity remained open through a 45 mm midline incision for 30 minutes; in the control group no treatment other than anesthesia was performed. Cancer nodules on the liver surface were compared among the three groups on day 17. There was no difference in the number of cancer nodules among the groups (p = 0. 72). A significant difference in the total area of cancer nodules (mean +/- SEM) was found only between the pneumoperitoneum group (696.0 +/- 177.0 mm(2)) and the control group (247.2 +/- 60.7 mm(2)) (p < 0.05). The frequency of cancer nodules larger than 3.0 mm in maximal diameter tended to be highest in the pneumoperitoneum group (p = 0.053). These results suggests that CO(2) pneumoperitoneum may promote the growth of established liver micrometastases in this animal model.

[Future of surgery].

Most current surgical techniques were developed in the 20th century, especially during the past 50 years. Open heart surgery, vascular surgery, neonatal surgery, organ transplantation and artificial organs, microsurgery, intravenous hyperalimentation, and, more recently, endoscopic surgery emerged during the past five decades. Many of the dreams of surgeons in the past have now been realized. These advances in surgery were made possible by the development of new technologies and instrumentation, but most importantly were initiated by the pioneering spirit of surgeons. This will continue on in the next century, since history shows that classical or conventional treatment modalities are constantly changing and being replaced by new ones based on new ideas and technologies. In this age of molecular biology, gene therapy, computer science, and the Internet, the pace of change in medicine and surgery will accelerate. Systems for training and communications, and even medical ethics, will inevitably change. We may not be able to predict precisely the future changes in surgery and surgeons, but we must be prepared for them and steer the future of surgery for the benefit of patients.

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.

[A case of diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa effectively treated with sequential MTX.5-FU and 5'-DFUR].

A 37-year-old man was diagnosed as having a diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa. Sequential methotrexate (MTX).5-fluorouracil (5-FU) therapy with oral administration of doxifluoridine (5'-DFUR) was started. After 9 cycles of the MTX.5-FU therapy (total dose: MTX = 900 mg/body, 5-FU = 7,500 mg/body), radiographic examinations showed a partial response in the primary and pulmonary lesion, and paraaortic lymph nodes. Histological evaluation of the resected specimen by Hartmann's operation showed a grade 2 effect in the primary lesion and metastatic lymph nodes. This chemotherapy was repeated postoperatively. The patient died of pulmonary disease, deteriorating rapidly 60 days postoperatively. Diffusely infiltrating carcinoma of the large-bowel is generally far advanced at the time of diagnosis. The results suggest that sequential MTX.5-FU therapy and oral administration of 5'-DFUR are worth performing in clinical trials for patients with diffusely infiltrating carcinoma of the large-bowel.

Influence of trocar placement and CO(2) pneumoperitoneum on port site metastasis following laparoscopic tumor surgery.

BACKGROUND: The mechanisms involved in the development of port site metastasis following laparoscopic tumor surgery remain controversial. Therefore, we decided to investigate the influence of trocar placement and CO(2) pneumoperitoneum on abdominal wound implantation in relation to intraperitoneal tumor growth in a rabbit model. METHODS: Rabbits received either CO(2) pneumoperitoneum with insertion of nine trocars (pneumoperitoneum group, n = 15), insertion of nine trocars alone (nonpneumoperitoneum group, n = 15), or nine abdominal incisions (control group, n = 13) 3 days after intraperitoneal inoculation of VX(2) cancer cells. RESULTS: The frequency of overall wound implantation on day 17 in the pneumoperitoneum group (24.4%) and nonpneumoperitoneum group (27.4%) tended to be higher than that in the control group (15.3%) (p = 0. 06). There was no significant difference among the three groups in the growth of cancer nodules on the omentum. CONCLUSIONS: The presence of a trocar may be a factor contributing to port site metastasis but CO(2) pneumoperitoneum appears not to be a factor.

The facilitation of peritoneal dissemination of a tumor by laparotomy in a rabbit model.

The effects of conventional laparotomy and laparoscopic surgery on the peritoneal dissemination of VX2 tumors were evaluated in a rabbit model. Either 5 x 10(3) or 5 x 10(4) of VX2 tumor cells were inoculated into the peritoneal cavities of rabbits which were divided into three groups according to the procedure performed, namely, a conventional laparotomy group (group 1), a laparoscopy group (group 2), and a control group (group 3). All the animals were killed 2 weeks after the treatment to examine the spread of the VX2 tumor in the omentum. In the experiment in which 5 x 10(3) tumor cells were inoculated, no significant difference was found in the number of metastases among the three groups. Conversely, after inoculating 5 x 10(4) tumor cells, the mean numbers of metastatic colonies greater than 1 mm in diameter in the greater omentum were 14.4+/-4.7 in group 1, 9.9+/-2.4 in group 2, and 3.3+/-1.1 in group 3, with a significant difference between groups 1 and 3, and between groups 2 and 3, but not between groups 1 and 2. In conclusion, conventional laparotomy facilitated the greatest peritoneal dissemination of a VX2 tumor in this animal model when 5 x 10(4) tumor cells were inoculated. Furthermore, laparoscopic surgery influences tumor growth to almost the same degree as conventional laparotomy.

Creation, evaluation, and continuing assurance of excellence of the certified surgical specialist.

A position paper on the subject of certified surgical specialists was published in 1966 under the direction of Professor Charles Wells of Liverpool, England. President John Terblanche of the International Federation of Surgical Colleges brought together leaders in surgical education from four nations (Australia, Japan, South Africa, United States) to update current "state-of-the art" views. Presentations were made at the 38th Congress of the International Society of Surgery, August 18, 1999 in Vienna, Austria. After careful review of the four presentations, it was clear that surgeons all over the world have made great improvements in the many facets of surgical education. Yet the advances remain spotty, with gaps noted when viewed from an international perspective.

[Clinical trial of prophylactic hepatic arterial chemotherapy for liver metastases in patients with Dukes' C colorectal cancer].

Preliminary results of a prospective non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from colorectal cancer are presented. Twenty-two colorectal cancer patients (infusion group) in Dukes' C stage were given hepatic arterial infusion of 5-FU (500 mg/body for 1 hr per week, repeated 50 times) and peroral UFT-E (2.0 g/body, daily). Informed consent was obtained from all patients. Adverse effects and postoperative recurrence in the infusion group were compared with those of patients with UFT-E alone (control group). Complications related to hepatic arterial infusion in the infusion group were also demonstrated. There was no adverse effect in the control group, while diarrhea (grade 1) developed in one patient (5%) and pigmentation in five (24%) in the infusion group. Complications related to infusion were found in five patients (5%). Three patients in the infusion group presented with metachronous hepatic lesions, two of which were resected successfully. In the control group, one patient died of marked hepatic metastases, and one developed ovarian metastasis with lymph node involvement. Our regimen appears hematologically safe, however, the high frequency of pigmentation should be kept in mind. The oncological benefit of this chemotherapy would be clarified by a larger series of cases and longer follow-up.