Makoto Sawafuji

Frequency of transmission of human parvovirus B19 infection by fibrin sealant used during thoracic surgery

BACKGROUND Fibrin sealant is used in many kinds of surgical procedures. Although pasteurization is insufficient to remove human parvovirus (HPV) B19 from this plasma-derived product, the frequency of HPV B19 infection transmitted by its use has never been known. METHODS Blood samples of 85 patients more than 20 years of age who had undergone pulmonary resection with fibrin sealant were obtained before and 12, 24, and 48 weeks after surgery. Anti-HPV B19 antibody IgG (HPV B19 IgG) and HPV B19 DNA were detected with these samples. RESULTS In 56 (65.9%) of 85 patients, blood samples obtained before operation were positive for HPV B19 IgG. In these 56 patients, blood samples obtained 12 to 48 weeks after surgery were all negative for HPV B19 DNA by polymerase chain reaction (PCR). In 6 (20.7%) of 29 patients whose blood samples were negative for HPV B19 IgG before surgery, blood samples obtained 12 to 48 weeks after surgery were positive for HPV B19 DNA by PCR and also positive for HPV B19 IgG. In 5 of these 6 patients reticulocyte counts decreased to less than 10 x 10(9)/l 12 to 20 days after surgery. CONCLUSIONS Epidemiologic evidence suggests that more than 20% uninfected persons were subsequently infected with HPV B19 by use of fibrin sealant during surgery.

Mediastinal lymph nodes in patients with non-small cell lung cancer: preliminary experience with diffusion-weighted MR imaging.

Objectives The purpose of our study was to describe our preliminary experience of evaluating mediastinal lymph node metastases with diffusion-weighted magnetic resonance (MR) imaging in patients with non-small cell lung cancer. Materials and Methods Forty-two consecutive patients with non-small cell lung cancer underwent preoperative diffusion-weighted MR imaging using a non-breath-hold short inversion time inversion recovery-echo planar imaging sequence with a high b value of 1000 s/mm2. An experienced thoracic radiologist prospectively evaluated each study for mediastinal lymph node metastases on a per-patient basis. On diffusion-weighted MR imaging, mediastinal lymph node metastasis was defined as a focus of low signal intensity at the site of a visible lymph node on corresponding T2-weighted image. The MR results were correlated with histopathologic findings. Results Diffusion-weighted MR imaging demonstrated mediastinal lymph node metastasis in 4 (80%) of 5 patients with pathologically proven metastasis and accurately identified 36 (97%) of 37 patients without mediastinal lymph node metastasis. Thus, 40 (95%) of 42 patients were accurately diagnosed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of diffusion-weighted MR imaging for mediastinal lymph node metastasis were 80%, 97%, 80%, 97%, and 95%, respectively. Conclusions Our preliminary results show that diffusion-weighted MR imaging has a high negative predictive value for excluding mediastinal lymph node metastases from non-small cell lung cancer and has the potential to be a reliable alternative non-invasive imaging method for the preoperative staging of mediastinal lymph node in patients with non-small cell lung cancer.

Staple-line reinforcement with a new type of polyglycolic acid felt

Although various materials have been used for reinforcement in lung-volume-reduction surgery to buttress pulmonary staple-line, absorbable materials are not available for use in thoracoscopic surgery. Moreover, even nonabsorbable types of reinforcements have been used only for lung volume reduction surgery. However, elderly patients with spontaneous pneumothorax secondary to emphysematous lung are well treated with staple-line reinforcement. The authors developed a new type of polyglycolic acid felt to buttress staple-line. This felt is absorbable, easier to cut with a stapler knife than is the conventional polyglycolic acid felt, and inexpensive enough to use for various types of thoracic surgeries for emphysematous lungs in Japan, and it can be attached to staplers with a small amount of fibrin glue. These strips were used to reinforce pulmonary staple lines for resection of emphysematous lungs in 14 patients: pulmonary emphysema (n = 1), bilateral giant bullae (n = 1), ipsilateral giant bullae (n = 6), spontaneous pneumothorax with multiple bullae in an emphysematous lung (n = 5), and lung cancer in a patient with pulmonary emphysema (n = 1). There were no air leaks during surgery. Air leaks were noted in three patients after surgery. In two patients, the air leaks stopped within 2 weeks. In one patient, the air leak was found to originate from an untouched lobe during reoperation. No infection or allergic reaction developed in a patient during a mean follow-up of 12 months (range, 1 to 24 months).

Neutrophil depletion attenuates interleukin-8 production in mild-overstretch ventilated normal rabbit lung

ObjectiveAcute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear. DesignTo assess the contribution of neutrophils, we compared the effects of noninjurious large tidal volume (Vt) ventilation on lungs in normal and neutrophil-depleted animals. SettingResearch animal laboratory. SubjectsTwenty-six male Japanese white rabbits. InterventionsAnimals were mechanically ventilated for 4 hrs with one of the three following protocols: large Vt (20 mL/kg), small Vt (8 mL/kg), and large Vt (20 mL/kg) with neutrophil depletion achieved by a single dose of vinblastine injection (0.75 mg/kg) intravenously 4 days before the experiment. Measurements and Main ResultsLarge Vt ventilation produced alveolar neutrophil influx compared with low Vt (p = .002) without evidence of edema or increased epithelial permeability. The neutrophil influx was accompanied by increases in interleukin-8 in bronchoalveolar lavage fluid (p = .04). Immunohistochemistry of large Vt lungs showed increased interleukin-8 staining in bronchial epithelial cells, alveolar epithelium, alveolar macrophages, and smooth muscles of pulmonary vessels. Neutrophil depletion attenuated the interleukin-8 increase in the lung. Large Vt did not increase plasma interleukin-8 or tumor necrosis factor-&agr; in plasma and bronchoalveolar lavage fluid. No expression of p-selectin or intercellular adhesion molecule-1 was observed. ConclusionsCyclic overstretching of normal rabbit lungs with noninjurious large Vt produced neutrophil influx and interleukin-8 increase in bronchoalveolar lavage fluid. Production of pulmonary interleukin-8 by lung overstretch might require the interaction between resident lung cells and migrated neutrophils. This study suggests that large Vt ventilation potentiates the predisposed, subclinical lung injury, such as nosocomial pneumonia or aspiration of gastric contents.

Radiation therapy for roentogenographically occult lung cancer by external beam irradiation and endobronchial high dose rate brachytherapy.

PURPOSE We investigated the clinical usefulness of radiation therapy by external beam irradiation and endobronchial brachytherapy for the treatment of roentogenographically occult lung cancer. PATIENTS AND METHODS From 1995 to 1996, five patients were treated with radiation therapy. We analyzed their treatment outcomes. The follow-up period varied from 3.0 to 3.8 years or until death. External beam radiation (40 Gy/20 fractions/4 weeks) was delivered to the tumor site alone, and not prophylactically given to the mediastinum. Endobronchial brachytherapy using high dose rate iridium (Ir)-192 was concurrently administered principally to a total dose of 18 Gy on the bronchial mucosa in three weekly fractions of 6 Gy each. RESULTS Complete remission was obtained in all patients. Two patients died of intercurrent diseases at 12 and 21 months without any evidence of recurrence. The disease has been also controlled in the other three cases. With the above doses, three small tumors < 1 cm were controlled without adverse effect. In two tumors, the dose reference points were set 2-7 mm beneath the mucosa, and larger doses were administered by brachytherapy. An applicator acting as a spacer was not used in these cases. The tumors were controlled, although the irradiated bronchi showed severe stenosis in 6 months following the treatment. However, the patients were asymptomatic and did not need further intervention. CONCLUSION External beam irradiation combined with endobronchial brachytherapy was useful for the treatment of roentogenographically occult lung cancer as an alternative to surgery. Further investigation is needed to determine the optimal doses of radiation therapy.

F-18 FDG PET imaging in a patient with granulocyte colony stimulating factor producing pulmonary pleomorphic carcinoma.

We studied the diffusely increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) in the vertebrae of a 74-year-old man with granulocyte colony stimulating factor (G-CSF) producing pulmonary pleomorphic carcinoma. The PET findings were due to bone marrow hyperplasia induced by G-CSF and indicate that we should be careful in differentiating these findings from bone metastases and complications with hematological disease. The Tc-99m HMDP bone scan was normal. PET image in another patient with lung cancer after treatment by rhG-CSF resembles that of the described case. PET imaging in a patient with G-CSF producing carcinoma is probably rare.

Effects of initial passage of endotoxin through the liver on the extent of acute lung injury in a rat model

ABSTRACT We hypothesized that the extent of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is modified with its initial passage through the liver. We tested this hypothesis by administering LPS, 5 mg/kg, or saline to 120 male Wistar rats via the portal vein (PV) or the inferior vena cava (IVC) over 1 h. Four experimental groups of rats were administered saline into the PV, saline into the IVC, LPS into the PV (LPS-PV group), and LPS into the IVC (LPS-IVC group), respectively. At 15 and 30 min after onset of 51Chromium-LPS infusion, the &ggr; counts in the liver were higher in the LPS-PV group than that in the LPS-IVC group. The ratio of 125Iodine-albumin counts in lung tissue to that in plasma per unit of weight (as an assessment of pulmonary microvascular permeability) at 240 min after onset of LPS stimulation, the accumulation of polymorphonuclear cell (assessed by myeloperoxidase activity) and the concentration of tumor necrosis factor &agr; in the lung at 60 and 240 min after onset of LPS infusion, were higher in the LPS-IVC group than in the LPS-PV group. Significant differences in several factors indicative of inflammation and in the extent of LPS-induced ALI were observed after the onset of LPS infusion, depending on whether it was delivered via the PV or the IVC. These observations suggest that the entrapping of LPS during its initial passage through the hepatic circulation may attenuate LPS-induced ALI within 4 h of initiation of LPS stimulation.

Attenuation by intravenous 2-chloroadenosine of acute lung injury induced by live Escherichia coli or latex particles added to endotoxin in the neutropenic state

Although neutrophil depletion can reduce the level of acute lung injury (ALI) induced by Escherichia coli endotoxin, that induced by live E coli cannot be attenuated even in neutropenia. This suggests that live E coli cause ALI by way of an mechanism independent of circulating neutrophil. Tumor necrosis factor-alpha (TNF-alpha), which is released from monocytes and macrophages, is a proinflammatory cytokine that is recognized as a central mediator of several forms of inflammation. In this controlled experimental study, we examined the effects of an adenosine-receptor agonist, 2-chloroadenosine (2CA), that has suppressive effects on various cell types and TNF-alpha, on endotoxin plus latex particles, and on ALI induced by live E coli in the neutropenic state. We studied 42 guinea pigs rendered neutropenic by means of intraperitoneal cyclophosphamide administration. Experimental groups consisted of (1) a saline-solution control group; (2) an endotoxin (0.2 mg/kg)-treated group; (3) a group treated with endotoxin plus 2CA (10 micro g/kg); (4) a group treated with latex (2 x 10(9)/kg); (5) a group exposed to endotoxin and latex; (6) a group exposed to endotoxin, latex, and 2CA; (7) a group exposed to E coli (2 x 10(9)/kg); and (8) a group exposed to E coli and 2CA. The injection of endotoxin alone in neutropenic animals did not increase the indexes of ALI (lung tissue/plasma ratio [T/P] and lung wet weight/dry weight ratio [W/D], calculated with the use of iodine 125-labeled albumin). In contrast, these indexes were increased in the endotoxin-and-latex groups compared with those of the control group. ALI in the endotoxin-and-latex group was attenuated by intravenous 2CA. The intravenous injection of live E coli also caused increases in T/P, W/D, and plasma TNF-alpha, but thse were limited by 2CA. In summary, ALI induced by latex particles added to endotoxin and live E coli in the neutropenic state was attenuated by 2CA, suggesting a partial contribution of various cell types or humoral mediators as a neutrophil-independent pathway in its pathogenesis.

Experimental tracheal replacement using the esophagus and an expandable metallic stent.

An experimental study was conducted to investigate whether a segment of autogenous esophagus with its lumen supported by an expandable metallic stent (EMS) could be successfully used as a tracheal substitute. Seven rings of the cervical trachea were circumferentially removed and reconstructed by interposing a pedicled segment of the esophagus with an EMS in six mongrel dogs. The interposed esophagus was observed endoscopically at various stages after the operation. By 1 month, the EMS was found to be buried under the esophageal mucosa, and the lumen was patent. The dogs died 5, 17, 61, 92, 210, and 478 days after the operation, but the cause of death could not be determined by postmortem examination and no respiratory tract complications were detected. The results of this study indicated that a segment of the esophagus with its lumen supported by an EMS could work as a reliable tracheal substitute, though its practical use is not clinically feasible. Nevertheless, we conclude that some autogenous material other than the esophagus with its lumen supported by an EMS could provide a feasible method for tracheal replacement.

Enhanced expression of telomerase activity in thymoma and thymic carcinoma tissues: A clinicopathologic study

Telomerase is a nucleoprotein complex that caps the physical termini of all eukaryotic chromosomes. Because most malignant cells and reproductive cells have telomerase activity, which elongates telomeric DNA, telomerase may play important roles in unlimited cell division acquisition of the malignant phenotype. The current study examined the relation of telomerase activity in thymoma and thymic carcinoma with the clinicopathologic features of these lesions.