[Intraoperative Endoscopic Evaluation of the Aortic Valve in Aortic Valve Repair].

This report discusses intraoperative endoscopic evaluation of the aortic valve performed in 2 cases of aortic valve repair. The "direct" or real image by the endoscopy helped to confirm the preoperatively-known lesion and even to detect a new legion which was not detected preoperatively. The endoscopy also enabled the evaluation of the aortic valve under the pressure-loaded condition without releasing the aortic clamp. Postoperative aortic regurgitation was grade I or less in both cases, although it progressed to grade II at 1 year in case 2. Echocardiographic parameters demonstrated no change in the size of the aortic root configuration for 8 and 5 years in case 1 and case 2, respectively. Intraoperative aortic endoscopy was useful to define the pathogenesis of aortic regurgitation and to evaluate the cusp repair procedures, which may contribute to a good mid-term result of aortic valve repair.

Mesohepatectomy with total caudate lobectomy of the liver for hepatocellular carcinoma.

BACKGROUND: Mesohepatectomy with total resection of the caudate lobe and extrahepatic bile duct is sometimes performed for hilar cholangiocarcinoma or gallbladder carcinoma; however, only a few reports on mesohepatectomy with total caudate lobectomy of the liver for hepatocellular carcinoma are available. METHODS: A 71-year-old woman was preoperatively diagnosed with hepatocellular carcinoma in the central bisections (Couinaud's segments 4, 5, and 8) and the paracaval portion of the caudate lobe. Mesohepatectomy with total caudate lobectomy of the liver permitted the removal of tumors to provide a cancer-free raw surface of the liver. Mobilization of the caudate lobe is an important procedure in this surgery. Before the liver parenchyma was dissected, all short hepatic veins were ligated and divided from the left to the right side as the left lateral section was retracted to the right, and the caudate lobe branches of the portal vein and hepatic artery were ligated and divided. After the liver parenchymal dissection, both between the left lateral and medial sections and between the right anterior and posterior sections, the Glissonean branches of the caudate lobe were ligated and divided as the central bisections were anteriorly retracted. Finally, liver parenchymal dissection was performed between the caudate lobe and the right posterior section, which was along the right side of the inferior vena cava. RESULTS: The surgery time was 538 minutes and blood loss was 1,207 mL. No blood transfusions were required during or after surgery. The postoperative course was uncomplicated. The patient is still alive 25 months after hepatectomy. CONCLUSION: Although mesohepatectomy with total caudate lobectomy of the liver is technically more difficult than mesohepatectomy of the liver because the caudate lobe must be completely detached from the inferior vena cava and the hilar plate, it is a safe and effective treatment method in selected patients with hepatocellular carcinoma located at both the central bisections and the paracaval portion of the caudate lobe.

Anatomical liver segmentectomy 2 for combined hepatocellular carcinoma and cholangiocarcinoma with tumor thrombus in segment 2 portal branch.

BACKGROUND: Hepatic resection is the only effective treatment for combined hepatocellular carcinoma and cholangiocarcinoma. CASE PRESENTATION: A 52-year-old man was preoperatively diagnosed with hepatocellular carcinoma in segment 2 with tumor thrombus in the segment 2 portal branch. Anatomical liver segmentectomy 2, including separation of the hepatic arteries, portal veins, and bile duct, enabled us to remove the tumor and portal thrombus completely. Modified selective hepatic vascular exclusion, which combines extrahepatic control of the left and middle hepatic veins with occlusion of left hemihepatic inflow, was used to reduce blood loss. A pathological examination revealed combined hepatocellular carcinoma and cholangiocarcinoma with tumor thrombus in the segment 2 portal branch. No postoperative liver failure occurred, and remnant liver function was adequate. CONCLUSION: The separation method of the hepatic arteries, portal veins, and bile duct is safe and feasible for a liver cancer patient with portal vein tumor thrombus. Modified selective hepatic vascular exclusion was useful to control bleeding during liver transection. Anatomical liver segmentectomy 2 using these procedures should be considered for a patient with a liver tumor located at segment 2 arising from a damaged liver.

[Total arch replacement through a mediansternotomy for an aortic arch aneurysm with an aberrant right subclavian artery].

The patient was a 77-year-old man. In 2004, he developed thrombosed aortic dissection extending from the distal aortic arch to the renal artery bifurcation. He was discharged after his condition improved with conservative treatment. He was followed up as an outpatient because there was an aneurysm, which measured 50 mm in diameter, at the aortic arch. Thereafter the aneurysm gradually enlarged. In May 2009, computed tomography (CT) showed that the aneurysm had increased to 10 cm in diameter and the patient began to have back pain. Thus, surgery was planned. CT revealed that the right subclavian artery originated distal to the left subclavian artery and coursed posterior to the esophagus and trachea. Surgery was performed using median sternotomy. Arch replacement and right subclavian artery reconstruction were performed under hypothermic circulatory arrest with selective cerebral perfusion. The right subclavian artery was controlled at the right border of the trachea, and cerebral perfusion was performed at this site. An end-to-side anastomosis to the reconstructed right common carotid artery was performed by an anterior tracheal approach. The patient had no cerebral complications and his postoperative course was uneventful.

Ultrafast charge transfer process of 9,9'-bianthryl in imidazolium ionic liquids.

Excited state dynamics of 9,9'-bianthryl (BA) in 1-butyl-3-methylimidazolium ionic liquids with three different types of anions was investigated by means of femtosecond to nanosecond transient absorption (TA) spectroscopy and time-resolved fluorescence (TRF) measurements. TA spectroscopy revealed that charge transfer (CT) occurred multiexponentially in the time scale of hundreds of picoseconds while TRF measurement revealed that red-shift of the BA fluorescence peak extended into the nanosecond regime. It is concluded that an energy relaxation process slower than the CT reaction, which could be the solvation dynamics in the product state, is observed.

Partial aortic root remodelling for fistula between the non-coronary sinus and the right atrium.

This report describes a rare case of the fistula between the non-coronary sinus and the right atrium (RA) after ascending aortic replacement for chronic aortic dissection. A 67-year-old lady had been suddenly suffering from severe dyspnoea with general fatigue for a couple of days. Trans-thoracic echocardiogram in the emergency room demonstrated massive shunt flow from the non-coronary sinus to the RA with remarkable dilatation of the RA, right ventricle (RV) and inferior vena cava, similar to the rupture of sinus of Valsalva (Konno-type IV). The fistula was successfully treated by partial remodelling of the aortic root in an emergency basis because of her life-threatening illness. Some remaining diseased aortic root, which may be related to initial dissection or inappropriate use of gelatin-resorcin-formalin glue at the previous ascending aortic replacement, may cause this kind of serious events. Modified aortic root remodelling method with only diseased sinus resected was successfully applied to the localised aortic root disorder.

Successful Balloon-Assisted Hepatic Tract Embolization Using the Pull-Through Technique to Remove a Malpositioned Chest Tube Penetrating the Liver and into the Right Ventricle.

Intra-abdominal injury is an uncommon complication of chest tube insertion. A 66-year-old man had empyema and underwent chest tube insertion for drainage. Massive hemorrhage occurred; the postprocedural radiograph showed the malpositioned chest tube in the mediastinum. Computed tomography scan showed that the tube's tip penetrated through the liver capsule and passed through the hepatic vein to the right ventricle. Hepatic tract embolization with coiling was performed during chest tube removal under a controlled condition with the hepatic tract occluded by a balloon catheter. The balloon catheter was placed from the right jugular vein using the pull-through technique, establishing a through-and-through guidewire. This is the first report of successful removal of a chest tube malpositioned in the hepatic vein by balloon-assisted hepatic tract embolization without complication.

Flt3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: possible application for cancer immunotherapy.

Current in vitro culture systems allow the generation of human dendritic progenitor cells (CFU-DCs). The aim of this study was to assess the effect of Flt3 ligand (FL) on the proliferation of human peripheral blood-derived myeloid CFU-DCs and their differentiation into more committed precursor cells (pDCs) using in vitro culture systems. Immunomagnetically separated CD34+ cells were cultured in serum-free, as well as in serum-containing, liquid suspension cultures to investigate the expansion and/or proliferation/differentiation of CFU-DCs, pDCs, and more mature dendritic cells (DCs). FACS-sorted CD34+Flt3+/- cells were cultured in methylcellulose to assay hematopoietic progenitors, including CFU-DCs. In the clonal cell culture supplemented with granulocyte/macrophage (GM) colony-stimulating factor (CSF), interleukin-4, and tumor necrosis factor alpha, the frequency of CFU-DCs was significantly higher in the CD34+Flt3+ fraction than in the CD34+Flt3- population, thus suggesting functional Flt3 expression on CFU-DCs. Serum-free suspension culture of CD34+ cells revealed the potent effect of FL on the expansion of CFU-DCs in synergy with GM-CSF and thrombopoietin (TPO). In addition, FL strongly induced the maturation of CFU-DCs into functional CD1a+ pDCs in serum-containing liquid suspension culture. Moreover, these FL-generated pDCs showed remarkable potential to differentiate into mature DCs with surface CD83/CD86 expression, which induced a distinct allogeneic T-cell response. These results clearly demonstrate that FL supports not only the proliferation of early hematopoietic progenitor cells, but also the maturation process of committed precursor cells along with the DC-lineage differentiation. Therefore, it is possible to develop a more efficient DC-based cancer immunotherapy using this specific cytokine combination, GM-CSF+TPO+FL in vitro in the near future.

Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.

Primary malignant melanoma of the esophagus (PMME) is a very rare disease with an extremely poor prognosis. Surgery is currently considered its best treatment, while any other measures are ineffective. We studied the effect of active specific immunotherapy using monocyte-derived dendritic cells (DCs) pulsed with the epitope peptides of melanoma-associated antigens (MAGE-1, MAGE-3) in patients with PMME after surgery, for the first time. The patient received passive immunotherapy with lymphokine-activated killer cells concomitantly. Two HLA-A24-positive patients with PMME were treated. Both patients initially received radical esophagectomy with regional lymphadenectomy, followed by adjuvant chemotherapy with dacarbazine, nimustine, vincristine and interferon-alpha. In the case 1 patient, active specific immunotherapy was used to treat a large abdominal lymph node metastasis that became obvious 21 months after surgery. The disease remained stable for 5 months, and the patient survived for 12 months after the initiation of immunotherapy. In the case 2 patient, immunotherapy was tried as post-operative adjuvant treatment after adjuvant chemotherapy. There was no tumor recurrence for 16 months after the immunotherapy. As of 49 months after esophagectomy, the patient is still alive. In both patients, the ability of peripheral lymphocytes to produce IFN-gamma in vitro in response to peptide stimulation was significantly enhanced and delayed-type hypersensitivity skin test response to MAGE-3 peptide was turned positive after immunotherapy. In conclusion, active specific immunotherapy for PMME with the use of DCs and MAGE peptides was safe and capable of inducing peptide-specific immune responses. This case report warrants further clinical evaluation of this immunotherapy for PMME.

Configurations of the mitral valve during off-pump coronary artery bypass grafting: endoscopic and three-dimensional analysis.

BACKGROUND AND AIM OF THE STUDY: During off-pump coronary artery bypass grafting (CABG), mitral regurgitation (MR) has been experienced in relation to the procedures. The study aim was to evaluate the mitral valve configuration, with particular focus on annular behavior, during off-pump CABG, using cardiac endoscopy and digital 3-D ultrasound sonomicrometry. METHODS: Following implantation of six crystals of the digital 3-D ultrasound sonomicrometer around the mitral annulus, and two crystals on the epicardial base of the papillary muscles, off-pump CABG was simulated in seven beagle dogs. The heart was perfused with pellucid Krebs-Henseleit solution in situ, with controlled left ventricular end-diastolic pressure (LVEDP). The behaviors of the mitral annulus and leaflets were then observed endoscopically with only cardiac displacement, 15 min occlusion of the left anterior descending artery (LAD), or 15 min occlusion of the left circumflex artery (LCx) with cardiac displacement. Dimensions between the crystals were also recorded using digital 3-D ultrasound sonomicrometry. RESULTS: With only cardiac displacement, no MR was observed endoscopically, and no major changes occurred in annular configuration when coronary perfusion was maintained. In one dog, MR was observed only from the anterolateral site after LAD occlusion. MR from the posteromedial site was observed by occlusion of the LCx in all cases, with significant (p < 0.01) enlargement of the mitral annular dimensions. CONCLUSION: Cardiac displacement alone did not cause MR if coronary perfusion was maintained. Occlusion of the LAD rarely caused MR from the anterolateral site, whereas occlusion of the LCx normally caused MR from the posteromedial site; the posteromedial annulus was enlarged, even when the LVEDP was controlled.

The Adamkiewicz artery: demonstration by intra-arterial computed tomographic angiography.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of using multidetector-row CT angiography (CTA) with intra-arterial contrast injection (IA-CTA) to depict the artery of Adamkiewicz (arteria radicularis magna, ARM). METHODS: We performed IA-CTA in 27 preoperative patients with aneurysm or dissection of the descending thoracic or thoracoabdominal aorta. ARM was examined on multiplanar and curved planar reformation images and on the paging method, and we investigated detectability and visualization of the ARM, the level of branching, and right/left frequency as well as continuity from the origin to the ARM. Furthermore, the bolus characteristic of contrast medium in IA-CTA was investigated and compared with CTA with intravenous contrast injection (IV-CTA). The bolus characteristic of the contrast medium was assessed by the determination of the CT value in the aorta in each of the 16 cases in which both IA-CTA before surgery and intravenous IV-CTA at the time of admission were performed. RESULTS: The ARMs were clearly visualized and at least one ARM to be reserved was determined in all patients (100%). The average number of ARM observed was 1.4+/-0.58 per patient (39/27). Innate origin was determined in 90% (35/39) of ARMs and it ranged between the 8th thoracic vertebra and the 3rd lumbar vertebra levels, and branching from the left accounted for 63.2% (24/38). It was possible to observe the exact continuity from the innate origin to the ARM as well as from the secondary origin to the ARM mediated by collateral vesseles in 61.5% of the total ARMs (24/39). The CT value in the aorta calculated on IA-CTA was significantly higher than that on IV-CTA (p<0.05). As a result, the high bolus characteristic of contrast medium in IA-CTA was confirmed. CONCLUSION: It was possible to detect the ARM in all patients and to obtain information about the origin by IA-CTA. This method is considered useful for preoperative assessment of a descending thoracic or a thoracoabdominal aorta for aortic aneurysm or dissection.

Should the annulus be fixed in aortic valve-sparing root replacement with remodeling?

OBJECTIVES: If the aortic root dilates after native aortic valve-sparing root reconstruction with remodeling, aortic regurgitation may recur. However, it has not been demonstrated clearly that the aortic root dilates after remodeling. METHODS: This study enrolled 15 patients who underwent an aortic valve-sparing operation with remodeling (2002-2014) but without any ventriculo-aortic junction (VAJ) fixation. Technically, special care was taken to pass the sutures through the fibrous annulus. The diameter of the aortic root (VAJ, neosinus of Valsalva, and sinotubular junction), degree of aortic regurgitation, and effective height of the aortic valve were measured in the patients. All patients had postoperative follow-up, and the median follow-up period was 7.3 (IQR: 3.1-8.3) years. RESULTS: The mean preoperative diameters of the VAJ, sinus of Valsalva, and sinotubular junction were 23.5 ± 2.3 (20-27) mm, 51.1 ± 7.2 (43-60) mm, and 42.4 ± 9.4 (29-58) mm, respectively. The postoperative diameters of the VAJ changed from 21.6 ± 2.6 (early) to 21.8 ± 2.9 mm (late) (p = 0.75). The diameters of the sinus of Valsalva and sinotubular junction changed from 26.5 ± 3.0 (early) to 28.5 ± 4.2 mm (late) (p = 0.0013), and 22.4 ± 3.0 (early) to 24.3 ± 3.3 mm (late) (p = 0.0003), respectively. The effective height of the aortic valve changed from 9.7 ± 1.3 (early) to 8.9 ± 2.0 mm (late) (p = 0.08). The degree of aortic regurgitation (grade: 0-4) changed from 0.3 ± 0.5 (early) to 1.2 ± 0.8 (late) (p = 01558). CONCLUSIONS: Significant VAJ dilation and changes in aortic valve configuration after our remodeling procedure were not observed. Therefore, fixation of the annulus with remodeling may not be needed for cases without preoperative dilation of the annulus.

Successful non-operative management of traumatic extrahepatic portal venous injury without intraperitoneal hemorrhage: a case report.

Case: A 52-year-old woman was admitted to our hospital with hypotension after falling from the fifth floor of an apartment building. Contrast-enhanced computed tomography showed liver injury with extravasation of contrast material from the hepatic artery, and extrahepatic portal venous injury with extravasation and pseudoaneurysm. Intra-abdominal hemorrhage was not observed, and bleeding was confined to the retroperitoneal space. Hepatic arteriography showed extravasation, while portal venography showed pseudoaneurysm but no extravasation. After transarterial embolization, the patient's vital signs improved. Non-operative management was selected for the portal venous injury. Outcome: Computed tomography on the 58th hospital day revealed disappearance of the portal venous pseudoaneurysm. The patient was discharged on the 90th hospital day without any complications. Conclusion: This case shows that non-operative management can be selected for portal venous injury when there is no retroperitoneal injury and bleeding is confined to the retroperitoneal space.

Involvement of GSK-3ß Phosphorylation Through PI3-K/Akt in Cerebral Ischemia-Induced Neurogenesis in Rats.

Glycogen synthase kinase (GSK)-3ß, which is abundantly expressed in the central nervous system, regulates various cellular processes including gene expression, cell proliferation, and differentiation. However, involvement of GSK-3ß in cerebral ischemia-induced endogenous neurogenesis is not yet fully understood. Appropriate strategies to prevent ischemic cell damage and subsequent severe sequelae are needed. The purpose of the present study was to determine the relationship between pathophysiological alteration of the GSK-3ß signaling pathway and cerebral ischemia-induced endogenous neurogenesis in rats. Severe cerebral ischemia was produced by the injection of 700 microspheres into the right internal carotid artery of rats. We demonstrated that phosphorylation of GSK-3ß at its Ser9 and that of Akt was significantly enhanced on day 7 after the cerebral ischemia, as was the number of NeuroD-positive cells. Treatment with a phosphatidylinositol 3-kinase (PI3-K) inhibitor decreased the cerebral ischemia-induced phosphorylation of Akt and that of GSK-3ß at its Ser9. In addition, as the protein levels of insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) were decreased, they might not have been essential for activation of the PI3-K/Akt/GSK-3ß pathway after severe cerebral ischemia. Although it remains to be determined what factors activate this pathway, our results suggest that PI3K/Akt-dependent GSK-3ß signaling and subsequent expression of NeuroD were involved in the neurogenesis elicited by cerebral ischemia.

Induction of cytotoxic T lymphocytes against human cancer cell lines using dendritic cell-tumor cell hybrids generated by a newly developed electrofusion technique.

Recently, dendritic cells (DCs) and DC-tumor cell hybrids (DC-tumor hybrids) have been used for cancer vaccine therapy in a clinical trial. DC-tumor hybrids combine the potent antigen-presenting capacity of DCs with the ability to present all tumor antigens expressed on tumor cells to T cells. We used DC-tumor hybrids as stimulator cells to induce tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. DC-tumor hybrids were generated from human monocyte-derived DCs and human cancer-cell lines (GT3TKB, lung cancer; GCIY, gastric cancer) by our newly developed electrofusion technique, established and refined with the use of mouse cells. To evaluate the capacity of DC-tumor hybrids generated by our method to induce tumor antigen-specific CTLs, we performed a cytotoxic assay and an interferon-gamma release assay using CD8-dominant effector lymphocytes induced by them. DC-tumor hybrids more effectively induced tumor-specific primary T-cell response than did stimulation with DCs co-cultured with irradiated tumor cells overnight, irradiated tumor cells alone, or a mixture of DCs and irradiated tumor cells. DC-tumor hybrids were generated at a high fusion rate by our electrofusion technique. When CTLs were induced by DC-tumor hybrids in vitro, the high fusion rate did not contribute to the induction of CTLs with increased tumor-specific cytotoxicity. The addition of interleukin-12 to the culture medium did not augment the cytotoxicity of CTLs. Overall, our results suggest that DC-tumor hybrids effectively induce human tumor-specific CTLs and may thus be applicable for clinical trials of adoptive immunotherapy.

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Potassium oxonate, an enzyme inhibitor compounded in S-1, reduces the suppression of antitumor immunity induced by 5-fluorouracil.

S-1 is an oral formulation combining tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. We examined whether Oxo reduces the immunosuppression induced by 5-fluorouracil (5-FU) in the rat. The body weight of rats treated with S-1 (FT + CDHP + Oxo) for seven consecutive days was significantly higher than that of rats treated with a combination of FT plus CDHP (FT + CDHP) for a similar period. The number of peripheral leukocytes was significantly higher in the S-1-treated rats (S-1 group) than that in the FT + CDHP-treated rats (FT + CDHP group). There was no apparent difference between the two treated groups in phenotypic changes of CD3-, CD45-, CD4-, or CD8-positive cells from the spleen or mesenteric lymph nodes. However, the natural killer activities of both spleen cells and mesenteric lymph node cells were significantly higher in the S-1 group than in the FT + CDHP group. Interleukin (IL)-2 production by spleen cells stimulated with concanavalin A was significantly lower in the FT + CDHP group than in the S-1 group. Although IL-2 production by mesenteric lymph node cells in the S-1 group was lower than that in untreated rats, it was higher than that in the FT + CDHP group. These findings suggest that Oxo in S-1 may reduce the suppression of antitumor immunity induced by 5-FU.

A novel immunotherapeutic modality with direct hemoperfusion targeting transforming growth factor-beta prolongs the survival of tumor-bearing rats.

Immune responses are frequently depressed in patients with cancer. One of the reasons for a poor immune response is the presence of increased levels of immunosuppressive substances associated with tumor growth. Transforming growth factor-beta (TGF-beta), a representative immunosuppressive cytokine, plays various roles in the progression of cancer. To remove immunosuppressive substances from tumor-bearing hosts, we developed an immunosuppressive substance adsorption (ISA) column for direct hemoperfusion (DHP) treatment. It is filled with extra-fine fibers that can adsorb TGF-beta. In this study, we investigated the effects of this DHP treatment on serum levels and activities of TGF-beta, cellular immune responses, and anti-tumor effects in KDH-8 (TGF-beta-producing hepatocellular carcinoma cell line)-bearing rats. We further studied the ability of ISA fibers to adsorb tumor-associated immunosuppressive cytokines [TGF-beta, interleukin (IL)-6 and vascular endothelial growth factor (VEGF)] in samples of body fluids obtained from patients with metastatic cancer. DHP treatment decreased serum levels and activities of TGF-beta in tumor-bearing rats and restored T lymphocyte response to mitogen. Tumor growth in rats treated by DHP was significantly slower than that in untreated rats. The survival time of treated rats was significantly longer than that of untreated rats. The concentrations of TGF-beta, IL-6, and VEGF in the samples of human body fluids were decreased markedly by in vitro treatment with ISA fibers. These results suggest that DHP treatment with an ISA column, which removes TGF-beta and other immunosuppressive substances from the sera of tumor-bearing hosts, is potentially a new immunotherapeutic strategy for cancer.