[A Case Report of Cancer Chemotherapy for Disseminated Carcinomatosis of the Bone Marrow Associated with Gastric Cancer Accompanied by Disseminated Intravascular Coagulation].

A 72-year-old woman was admitted to our hospital because of symptoms of bleeding diathesis such as hematuria and purpura. A blood test revealed disseminated intravascular coagulation(DIC). Upper gastrointestinal endoscopy showed advanced gastric cancer. Bone marrow aspiration cytology demonstrated diffuse hyperplasia of large atypical cells, and metastasis of the epithelial tumor was suspected on immunohistochemical examination. She was diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC. She was treated with weekly infusion of methotrexate 100 mg/m2 plus 5-fluorouracil 600 mg/m2 for 4 courses; and she completely recovered from DIC. She received oral tegafur/gimeracil/oteracil as an outpatient. However, DIC recurred 126 days after the initial chemotherapy, and 5-fluorouracil plus cisplatin was administered subsequently. After 1 course, she died 166 days after the initial chemotherapy. Although the prognosis of patients with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC is extremely poor, this case shows that secession of DIC and prognostic improvement by chemotherapy could occur. Chemotherapy could be considered a potentially effective treatment in this case.

Cessation of In-line Filters in Central Venous Catheters Does Not Significantly Influence the Incidence of Bloodstream Infections and Mortality in a Hospital Hematological Ward.

Objective The use of intravenous in-line filters is effective for the mechanical removal of large particles, precipitates, bacteria, fungi, large lipid globules, and air. However, the routine use of in-line filters remains controversial. Many patients with hematological diseases frequently suffer from bloodstream infections (BSIs) with fatal outcomes. Methods The year before cessation of an in-line filter was defined as the "filter period" and the year after its cessation was defined as the "non-filter period." The number of central line-associated bloodstream infections (CLABSIs), which are defined through surveillance, the catheter utilization rate, the number of patient deaths within 7 days after removal of the central venous catheters (CVCs), and the overall survival rate following CVC insertion were measured. Results During both periods, 84 patients had a total of 140 CVCs with a total number of catheter days of 3,407. There were 10 CVCs with CLABSIs, and the overall CLABSI rate was 2.9/1,000 catheter days, including 4 CVCs with CLABSIs (2.5/1,000 catheter days) during the filter period and 6 CVCs with CLABSIs (3.3/1,000 catheter days) during the non-filter period. The CLABSI rate, catheter utilization rate, and mortality did not differ significantly between the two periods. The only independent variable that was found to be significantly associated with the development of CLABSIs was a neutrophil count of <500×10(6)/L (p<0.05). Conclusion Our study revealed that the cessation of in-line filters from CVCs does not significantly influence the incidence of BSIs and mortality in patients with hematological disease. To confirm our results, however, a large-scale randomized controlled study is warranted.

Successful diagnosis of type II enteropathy-associated T-cell lymphoma using flow cytometry and the cell block technique of celomic fluid manifesting as massive pyoid ascites that could not be diagnosed via emergency laparotomy.

Enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor of intraepithelial T lymphocytes, is a rare and highly aggressive disease. We herein describe a case of type II EATL with massive pyoid ascites in which a histological examination could not be performed despite emergency laparotomy that was successfully diagnosed using flow cytometry and the cell block technique to analyze the celomic fluid. This case suggests that EATL should be included in the differential diagnosis of pyoid ascites of unknown origin and that flow cytometry and the cell block technique of assessing celomic fluid are useful procedures for diagnosing EATL, especially in cases in which conducting a histological examination is impossible.

Ectopic ileal varices associated with recurrent bleeding: report of a case.

Bleeding from ectopic varices of the ileum associated with portal hypertension is occasionally life-threatening. However, it is not easy to make an accurate preoperative diagnosis. A 62-year-old woman presented with hematochezia and anemia. Conventional examinations could not locate the bleeding point, but subsequent capsule endoscopy indicated gastrointestinal bleeding from hemorrhaging ileal varices. Contrast-enhanced abdominal computed tomography, three-dimensioned abdominal computed tomography, and mesenteric angiography demonstrated the presence of ileal and right ovarian varices. The patient then underwent an exploratory laparotomy which confirmed these findings, and resection of the affected ileum and right ovary was performed safely. Capsule endoscopy should be a diagnostic option for patients with obscure gastrointestinal bleeding, and ileal varices should be considered as one of the differential diagnoses.

Intralobar pulmonary sequestration associated with marked elevation of serum carbohydrate antigen 19-9.

This report describes a 62-year-old man who experienced elevated serum carbohydrate antigen 19-9 (CA19-9) levels (>500 U/mL) for 4 years, and was finally diagnosed with right intralobar pulmonary sequestration. Surgery confirmed the presence an aberrant artery arising from the descending thoracic aorta and entering the right lower lobe basal segment. Immunohistochemistry demonstrated markedly positive staining of CA19-9 in the ciliated cylindrical epithelia, alveoli, and mucus in the cysts. After pulmonary resection, CA19-9 levels decreased to within a normal range. Therefore, the cause of the elevated serum CA19-9 levels in this case was almost certainly due to intralobar pulmonary sequestration.

Risk factors of liver dysfunction after extended hepatic resection in biliary tract malignancies.

BACKGROUND: Postoperative hepatic insufficiency is a critical complication after extended hepatic resection in patients with biliary tract malignancies, the majority of whom suffer from obstructive jaundice. The aim of this study was to assess clinical parameters linked to this type of liver dysfunction. METHODS: A total of 111 patients were retrospectively reviewed. Patient background, pre- and intraoperative parameters, and a ratio of remnant liver volume/entire liver volume (RLV/ELV) as a volumetric parameter were compared between patients with and without postoperative hyperbilirubinemia and subsequent fatal outcome. RESULTS: Logistic regression indicated that only RLV/ELV ratio was an independent factor influencing postoperative hyperbilirubinemia, and RLV/ELV ratio and indocyanine green retention rate at 15 minutes (ICG-R15) were factors affecting survival. Patients with RLV/ELV less than 40% had 7.6 times the risk of postoperative hyperbilirubinemia, while no patients with RLV/ELV greater than 40% and ICG-R15 less than 25% died of liver failure. CONCLUSIONS: The RLV/ELV ratio was the factor with the greatest impact on liver dysfunction after extended hepatectomy in patients with biliary tract malignancies.

Inflammatory myofibroblastic tumor causing ileoileal intussusception: an unusual cause of an unusual neoplasm in an adult, with a clinicopathological review of the literature.

An inflammatory myofibroblastic tumor (IMT) of the ileum is a very rare lesion of the gastrointestinal tract. A 36-year-old female presented with abdominal fullness and colicky pain of 5 days' duration. Plain abdominal radiography showed an intestinal obstruction with dilated jejunal loops. Abdominal computed tomography and ultrasonography demonstrated a well-defined intraluminal solid mass surrounded by the typical mural layers of an invaginated ileum. The patient then underwent an exploratory laparotomy under a clinical diagnosis of intussusception caused by a small bowel tumor. The surgical findings revealed a large mass leading to an ileoileal intussusception, with regional lymph node enlargement and a small bowel resection accompanied by lymph node dissection was performed. The definitive diagnosis of IMT was confirmed by both conventional histopathology and minute immunohistochemistry.

Analysis of risk factors associated with complications of hyperbaric oxygen therapy.

PURPOSE: The aim of this study was to verify independent risk factors of pressure equalization problems associated with hyperbaric oxygen (HBO(2)) therapy. METHODS: We reviewed a single-institutional study of 1609 patients with 17604 treatments who had HBO(2) therapy in a multiplace chamber, in which the factors examined and their relationship to complications were assessed, using multivariate analyses, to determine the significantly independent risk factors of complications related to HBO(2) therapy. RESULTS: The compression rate was 0.067 atmospheres absolute/min (6.8 kPa/min). Pressure equalization problems of the middle ear, expressed as pain or discomfort, such as cranial sinus pain, and teeth pain were observed in 156 patients (9.7%). Sixty-six of them could not continue HBO(2) therapy because of these problems. Peripheral circulatory disorders with refractory ulcers or nonhealing wounds and the interval between clinical symptoms and the first day of HBO(2) therapy were independent risk factors of pressure equalization problems. Independent risk factors of cessation due to pressure equalization problems were identified as age more than 61 years, female sex, and interval between symptoms and the first day of HBO(2) therapy. CONCLUSION: It is suggested that chamber compression must be performed with particular care when patients have peripheral circulatory disorders and have short interval between clinical symptoms and the first day of HBO(2) therapy.

Effect of hyperbaric oxygen therapy on patients with adhesive intestinal obstruction associated with abdominal surgery who have failed to respond to more than 7 days of conservative treatment.

BACKGROUND/AIMS: To investigate the effects of hyperbaric oxygen (HBO) therapy on patients with adhesive intestinal obstruction who have failed to respond to more than 7 days of conservative treatment. METHODOLOGY: Six hundred eighty-five patients, who were admitted a total of 879 times for adhesive intestinal obstruction, were divided into groups according to the treatment and interval between the first day of the therapy and clinical symptoms of obstruction; tube decompression therapy within 7 days after appearance of clinical symptoms (Group I: n = 321), clinical symptoms that have persisted for less than 7 days before the start of HBO therapy (Group II: n = 498), and for more than 7 days (Group III: n = 60). RESULTS: The overall resolution and mortality rates in the cases of adhesive intestinal obstruction were 79.8% and 2.2% in Group I, 85.9% and 1.4% in Group II, and 81.7% and 1.6% in Group III, respectively. Group II had significantly better resolution rates than Group I (odds ratio 1.6, p < 0.02). CONCLUSIONS: HBO therapy may be useful in management of adhesive intestinal obstruction associated with abdominal surgery, even in patients who fail to respond to other conservative treatments. HBO therapy may be a preferred option for treatment of patients for whom surgery should be avoided.

Hyperbaric oxygen therapy as a prophylactic and treatment against ileus and recurrent intestinal obstruction soon after surgery to relieve adhesive intestinal obstruction.

BACKGROUND AND AIM: Nonoperative management of cases of adhesive intestinal obstruction would be ideal, especially for patients who have recently undergone surgery to relieve the same condition. We aimed to examine whether hyperbaric oxygen (HBO) therapy might have therapeutic potential for the treatment of postoperative paralytic ileus and recurrent adhesive intestinal obstruction soon after surgery, to relieve adhesive intestinal obstruction, because of its unique mechanisms in these contexts. METHODS: A total of 133 patients were enrolled in the present study. We examined non-per os periods, hospital stay, and clinical course according to the postoperative course of the 133 patients. RESULTS: After surgical intervention, 75 patients left the hospital without morbidity. Nineteen patients were successfully administered prophylactic HBO therapy to facilitate intestinal motility and to prevent paralytic ileus. The remaining 39 patients suffered from postoperative paralytic ileus or early recurrence of obstruction during the same hospitalization period. The patients who underwent prophylactic HBO therapy had significantly shorter non-per os periods and hospital stays after surgery than those who were not initially given HBO therapy (P < 0.05). Similarly, there were significant differences in duration of hospital stay after surgery between patients with HBO therapy as treatment and those who received other conservative therapies (P < 0.05). CONCLUSIONS: HBO therapy may have a prophylactic effect on postoperative paralytic ileus and may be of therapeutic benefit in the management of early recurrent adhesive intestinal obstruction following surgery to relieve adhesive intestinal obstruction.

Hyperbaric oxygen therapy for the treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery: experience with 626 patients.

BACKGROUND/AIMS: The results of hyperbaric oxygen (HBO) therapy for treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery are unknown. METHODOLOGY: A retrospective review of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery in 626 patients required 758 admissions who underwent HBO therapy was undertaken to examine the efficacy of HBO therapy. RESULTS: The overall resolution rates for patients receiving HBO therapy in cases of postoperative paralytic ileus and adhesive intestinal obstruction were 92% and 85%, respectively. Among patients who were more than 75 years old, the therapies resolved 35 (97%) of 36 cases of postoperative paralytic ileus and 42 (81%) of 52 cases of adhesive intestinal obstruction, which was comparable to the results for patients less than 75 years old. The mortality rate was 1.2% overall. Complications related to HBO therapy occurred in 3.8% of the admissions, and most of them were not serious. CONCLUSIONS: These results suggest that HBO therapy might deserve further assessment for use in management of postoperative paralytic ileus and adhesive intestinal obstruction as a new modality. HBO therapy is safe and non-invasive, and may be useful in the elderly patients, since mortality was relatively low in this series.

Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy.

AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and alpha-smooth muscle actin (alpha-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-beta1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-beta1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (alpha-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-beta1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-beta1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.

Increased plasma levels of IL-6 and IL-8 are associated with surgical site infection after pancreaticoduodenectomy.

OBJECTIVES: Cytokines and chemokines potentially modulate postoperative immune response. Association of circulating cytokines and chemokines with postoperative infectious complications after pancreaticoduodenectomy was evaluated. METHODS: Plasma concentrations of interleukin (IL) 6, IL-10, IL-8, macrophage chemoattractant protein 1, heat shock protein 70, and amylase, as well as amylase levels in peritoneal exudative fluid, were measured perioperatively in 60 consecutive patients who underwent pancreaticoduodenectomy. RESULTS: Of the 60 patients, 27 patients had surgical site infection (SSI), including peritoneal infection in all, intra-abdominal abscess in 14, and radiologically visualized pancreatic leakage in 6. Postoperative plasma levels of IL-6, IL-8, and macrophage chemoattractant protein 1, as well as peritoneal amylase levels, were significantly higher in patients with SSI than in those without SSI (P < 0.05). Nonpancreatic cancer as a histopathologic diagnosis, high pancreatic juice flow, and increased levels of IL-6 and IL-8 were independently associated with SSI (P < 0.05) in multiple logistic regression analysis. Plasma levels of IL-6 and IL-10 among patients with SSI were significantly higher in those with pancreatic leakage than in those without leakage. CONCLUSIONS: These results suggest that, in addition to pancreatic exocrine function, IL-6 and IL-8 are associated with postoperative SSI, including pancreatic leakage after pancreaticoduodenectomy.

Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection.

BACKGROUND: Humoral mediators are potentially involved in the pathogenesis of postoperative complications following surgery. The aim of the present study is to evaluate the postoperative responses of circulating cytokines, chemokines, and stress hormones following liver resection, and their effects on postoperative infectious complications and organ dysfunction. PATIENTS AND METHODS: Perioperative plasma concentrations of interleukin (IL)-6, IL-10, IL-4, IL-8, macrophage chemoattractant protein (MCP)-1, cortisol, macrophage migration inhibitory factor (MIF), and leptin were measured by immunoassays in 128 consecutive patients undergoing liver resection. RESULTS: Forty-three patients had postoperative infection and 11 had infection-related organ dysfunction. Plasma levels of all mediators except for IL-4 increased postoperatively. Postoperative levels of IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin were significantly higher in patients with organ dysfunction than in those without organ dysfunction (P < 0.05). However, postoperative MIF levels were not affected by postoperative infection or organ dysfunction. Plasma levels of IL-6, IL-10, IL-8, and MCP-1 were positively correlated with operation time (P < 0.0001) or blood loss (P < 0.0001), and higher in patients with jaundiced liver (P < 0.05). In univariate logistic regression analyses, elevated IL-6, IL-10, IL-8, and MCP-1, advanced age, large volume of blood loss, long operation time, long hepatic ischemia time, and major liver resection were significantly correlated with postoperative infection (P < 0.05). In multivariate analyses, IL-6 and IL-10 were significant predisposing factors for postoperative infection (P < 0.05), and blood loss and IL-6 for organ dysfunction (P < 0.01). CONCLUSIONS: These results suggest that IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin are released after liver resection in response to surgical stress and correlated with postoperative infection and organ dysfunction, and that of these circulating mediators, IL-6 and IL-10, have a close relationship to the complications.

[Portal vein stenting for portal hypertension caused by local recurrence following hepato-pancreatoduodenectomy for bile duct cancer].

The patient was a 73-year-old man diagnosed with bile duct cancer. He underwent hepato-pancreatoduodenectomy and a combined resection of portal vein in July 2002. The post operative course was uneventful. In December 2003 he had a loss of consciousness, and was admitted to our hospital as an emergency patient. Abdominal CT scan and angiography revealed the presence of portal vein stenosis due to local recurrence of bile duct cancer resulting in portal hypertension. Thus, a metallic stent was placed in the portal vein to maintain portal blood flow. A non-covered metallic stent, 10 mm in diameter and 80 mm in length (SMART stent, Cordis Endovascular), was deployed through the stenotic portal vein. Portography after the stent placement showed a relief of the portal vein stenosis. Intravenous heparin administration was performed at a dose of 5,000 IU per day for 5 days after the stent placement, and this was followed by oral warfarin potassium administration. The clinical course was uneventful and the patient was discharged 21 days after portal stent placement. Portal stenting successfully improved portal hypertension due to stenosis of the portal vein without any complication. Our experience suggests that the portal vein stenting using the SMART stent is useful palliative therapy for portal vein stenosis.

Long-term survival after extended surgical resection of intrahepatic cholangiocarcinoma with extensive lymph node metastasis.

We present a case of long-term survival in a patient that involved intrahepatic cholangiocarcinoma that metastasized to the paraaortic lymph nodes. A 62-year-old man underwent extended left hepatic lobectomy with caudate lobe resection, extrahepatic bile duct resection, portal vein resection and reconstruction, and middle hepatic vein resection and reconstruction with lymph node dissection for a liver tumor that was located in the caudate lobe. Histological examination of the resected specimen revealed moderately differentiated adenocarcinoma compatible with cholangiocarcinoma, and lymph node metastases were found in the area of the hepatoduodenal ligament and the paraaortic region. After surgical resection, recurrence was detected twice in the lymph nodes at the site of the left supraclavicular region. These recurrent tumors were completely eliminated by systemic chemotherapy with cisplatin or mitomycin C. The patient is now doing well 6 years and 5 months after surgical treatment. In this case, there was only one tumor, and the preoperative serum carbohydrate antigen 19-9 level was normal. In addition, heterozygosity was retained at the loci on chromosome 8p. These findings suggested that tumor in the present case was less aggressive, despite the nodal spread. The extensive surgical approach may have contributed to the long-term survival of this patient, while the recurrent tumor was sensitive to antitumoral agents.

Should the inferior vena cava be reconstructed after resection for malignant tumors?

BACKGROUND: Caval replacement after circumferential resection of the inferior vena cava remains controversial. The aim of the current study is to determine whether or not inferior vena cava replacement should be performed. METHODS: We reviewed 36 cases undergoing resection of the inferior vena cava concomitant with resection of malignant neoplasms. Our criteria for circumferential resection of the inferior vena cava were half or more of the circumference of the vessel wall invaded by tumor, a primary tumor of the caval wall, or massive intraluminal tumor thrombus suspected of adhering to the caval wall. We detailed 10 patients undergoing circumferential resection of the inferior vena cava. RESULTS: Most of patients who did not undergo replacement of the inferior vena cava showed no sign of swelling of the lower limbs, but one showed persistent leg edema with oliguria. This patient had poor development of collateral circulation and mild obstruction of the inferior vena cava before surgery. Two patients who underwent replacement of inferior vena cava had no venous sequelae, although they had poor development of collateral circulation before surgery. CONCLUSION: Caval replacement after circumferential resection of the inferior vena cava may be necessary in patients who have preoperative poor development of collateral circulation or who have oliguria or unstable hemodynamics intraoperatively.

[Hilar cholangiocarcinoma].

Surgical resection has been reported to be only hope for cure for the patients with hilar cholangiocarcinoma. Therefore, first of all, radical surgical resection should be considered to be a therapeutic option for hilar cholangiocarcinoma as much as possible. In preoperative staging for hilar cholangiocarcinoma, various extensive patterns of cancer such as the involvements of bile duct, portal vein, hepatic artery and lymph node etc, should be evaluated in each patient. As most patients are associated with obstructive jaundice at presentation, liver function has to be evaluated by appropriate tests for deciding the suitable surgical procedure. When the future remnant liver volume is less than 40% or severe liver functional damage exists or greater surgical stress is expected, preoperative portal vein embolization might have to be selected. On the other hand, if hilar cholangiocarcinoma involves limited region of the hilar bile duct confluence, parenchyma preserving hepatectomy such as S1 resection and S1 + S4 resection should be selected for avoiding the occurrence of liver failure. Combined portal vein resection should be done for the case of the cancer involvement of the portal vein without hesitation to improve the prognosis. However, hepatic artery resection and reconstruction in the involved case should be carefully performed only in severely selected cases. By using several useful pre-operative and intra-operative therapeutic modalities, hilar cholangiocarcinoma should be surgically resected with curative intent and without increasing surgical morbidity and mortality rates.

Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats.

AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy. METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes, sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively. RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION: Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.

Early biological and immune response to semi-identical liver or kidney allograft in miniature swine.

In inbred miniature swine, semi-identical liver allograft recipients survive up to 3 months without immunosuppression, whereas similarly mismatched kidney allografts are uniformly rejected within 2 weeks. The early biological and immunological events were assessed in this unique model. SLA(d/d) pigs (MGH, Harvard Medical School, Boston, MA, USA) received liver or kidney allograft from heterozygous SLA(c/d) miniature swine. Survival, graft function, histology, intragraft cytokines, peripheral lymphocyte and platelet count, plasma cortisol level and cellular/humoral anti-donor immune response were assessed. Kidney allografts were uniformly rejected within 2 weeks, whereas liver allografts survived for up to 87 days. After both liver and kidney transplantation, the peripheral lymphocyte count decreased during the first week concomitantly to a significant elevation of plasma cortisol level. Early decrease of peripheral platelet count was observed after liver but not renal transplantation. Up-regulation of transforming growth factor beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) was observed during the first postoperative week in semi-identical liver allografts and IFN-gamma as well as IL-10 in kidney allografts. In liver recipients, labelled autologous lymphocytes accumulated in the liver graft and native spleen, whereas after renal allograft, lymphocytes accumulated in the native spleen and liver but never in the kidney allograft. Specific cellular anti-donor unresponsiveness was observed from the first post-transplant day in both liver and kidney recipients, while the humoral anti-donor response remained intact. In semi-identical liver allograft, recipient rejection is milder and slower than in similarly matched kidney allograft. The intragraft up-regulation of TGF-beta1 in semi-identical liver allograft might be one mediator to explain the modulation of rejection after liver transplant. The rapid, nonspecific accumulation of recipient lymphocytes in the liver allograft but not in kidney allograft might also play a role in the different survival time in this model.