Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

Effect of Inflammation on Costimulation Blockade-Resistant Allograft Rejection

Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8⁺ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8⁺ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8⁺ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8⁺ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8⁺ T cells to induce costimulation blockade-resistant allograft rejection.     

Late-onset chylothorax after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer

Late-onset chylothorax occurred 49 days after right lower lobectomy for lung cancer in a 76-year-old man. Chylothorax was successfully managed by conservative treatment with chest tube drainage and an enteral low-fat diet. Chylothorax may occur in the late period after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer, for which conservative management is the treatment of choice.     

Human Tumor–infiltrating Lymphocytes Transfected with Tumor Necrosis Factor Gene Could Augment Cytotoxicity to Autologous Tumor Cells

Human tumor–infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) a gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene–transfected TILs exhibited an augmented killing of autologous tumor cells.     

Neuroradiological analysis of small infarcts in deep subcortical structure detected by CT

We studied angiographic findings of 56 patients who were diagnosed as lacunar infarcts in the basal ganglia or deep subcortical white matter based on clinical symptomatology and brain computed tomography. In 26 patients with CT lesions less than 15 mm in diameter, only eight (31%) showed minor angiographic findings. In 30 patients with lesion of 15 mm or more, however, 22 (73%) had abnormal angiographic findings. Fourteen of the 22 patients had minor irregularities, three had 25-75% stenosis, five had 75% less than stenosis at the bifurcation of the common carotid artery or the horizontal portion of the middle cerebral artery. Our findings support the notion that a small lesion on CT can result from an occlusion of the perforating artery itself and a larger lesion is much related to the major vessel or heart diseases, i.e., emboli from the parent artery or heart, obstruction of perforators at their origin by an atheromatous plaque of the horizontal portion of the middle cerebral artery, or terminal zone infarct due to hemodynamically significant stenotic lesion. In patients with a larger deep infarct on CT, further investigation of the arteries in the carotid-axis and heart is important for determination of therapeutic indication.     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers.

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible nitinol stent

In order to treat fistulated esophageal cancer using a flexible stent, a covered flexible stent was constructed by wrapping a nitinol stent with a thin sheet of Gore-Tex, preserving the stents original advantages of flexibility and a low-profile introducer system. This stent was used to perform standard radiotherapy in a case of fistulated esophageal cancer.