Isolated Pulmonary Cryptococcosis Confused with Lung Tumor 5 Years After Kidney Transplantation: A Case Report.

BACKGROUND: In transplant recipients, due to the use of immunosuppressive therapy, it is occasionally difficult to distinguish between an infection and malignancy, especially in the case of a lung lesion. Here, we report a case of isolated pulmonary cryptococcosis after kidney transplantation that was difficult to distinguish from a lung tumor. CASE REPORT: A 52-year-old man underwent a kidney transplant from his mother when he was 44 years old. Immunosuppression was maintained with tacrolimus, methylprednisolone, and mycophenolate mofetil. His post-transplant course was uneventful and serum creatinine levels were maintained. Five years post-transplantation, a non-contrast computed tomography (CT) examination revealed a nodule measuring 3 mm in diameter in the middle lobe of the right lung. The nodule gradually increased to 12 mm in 2 years. Positron emission tomography/CT examination showed a maximum standardized uptake value of 0.5 for the nodule. Biochemical examination revealed no elevation in total leucocyte count and C-reactive protein levels. However, tumor markers were elevated: serum carcinoembryonic antigen, 5.9 ng/mL; pro-gastrin-releasing peptide, 84.6 pg/mL. Furthermore, the serum cryptococcus antigen was negative. Therefore, thoracoscopic partial lung resection was performed. Pathologically, a number of spherical fungi from the necrotic substance of the tumor were confirmed positive by periodic acid-Schiff and Grocott-Gomori staining. The patient was therefore diagnosed with pulmonary cryptococcosis. Two years later, the patient is alive and has shown no evidence of recurrence. CONCLUSIONS: In lung nodules after kidney transplantation, even if serum cryptococcus antigen is not identified, it is necessary to keep in mind the possibility of pulmonary cryptococcosis.

[Local advanced lung cancer invaded thoracic vertebral bodies with unruptured cerebral aneurysm].

A 57-year-old man presented with the chief complaint of left shoulder pain in June 2001, and paridrosis of left upper trunk and left upper limb in July 2001. Head magnetic resonance imaging (MRI) showed 8 mm sized unrupture aneurysm of left middle cerebral artery, and chest computed tomography (CT) showed the lung tumor invaded thoracic vertebral bodies. The local advanced lung carcinoma (cT4N0M0) and unrupture aneurysm of left middle cerebral artery was diagnosed. The prevented clipping of unrupture aneurysm was performed at 11th September 2001, and left upper lobectomy, hemivertebrectomy and reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS at 12th October 2001. The pathological findings revealed squamous cell carcinoma. The staging was pT4N0M0, IIIB. The postoperative course was uneventful. After the radiotherapy (50 Gy), chemotherapy (gemcitabine and vinorelbine) was performed. But the radiation pneumonia was occurred and chemotherapy was intermitted. The steroid was administrated due to the radiation pneumonia, and the complication was improved. He discharged at 17th April 2002 and had no recurrence. The prevented clipping of unrupture cerebral aneurysm and the reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS were useful for the radical operation of the local advanced lung cancer.

Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.

It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.

Role of the bcl-2/bax pathway in hepatocyte apoptosis during acute rejection after rat liver transplantation.

It is well established that hepatocytes undergo apoptotic cell death in the course of rejection of liver grafts. The present study was designed to investigate the role of the bcl-2/bax pathway in liver allograft tissue. Orthotopic liver transplantation was performed in three groups of rats: group 1, a syngeneic combination (Lewis to Lewis), group 2, an allogeneic combination (ACI to Lewis), and group 3, an allogeneic combination (ACI to Lewis) treated with 15-deoxyspergualin. The number of apoptotic cells identified by the TUNEL method in the grafted liver reflected the severity of acute rejection. In group 1, both bcl-2 mRNA and bax mRNA were expressed in trace amounts. In group 2, bcl-2 mRNA was slightly expressed while the expression of bax mRNA rose steadily. In group 3, bcl-2 mRNA expression levels remained similar to group 1, while bax expression levels exceeded those in group 1, but were less than in group 2. Expression of bcl-2 mRNA was stationary in comparison with expression of bax mRNA. Significantly higher levels of bax mRNA were expressed from day 4 in group 2 than in group 1 (on postoperative days 4, 6, and 8, P < 0.05, group 2 vs group 1). We also investigated bax protein and results consistent with the mRNA analysis data were obtained. These findings suggest that apoptotic cell death in liver allograft rejection is regulated, at least in part, by bax.

Expression of bcl-2 homologue mRNAs in rat liver allograft: rejection-induced cell apoptosis is associated with upregulation of bax and bcl-xs expression.

Apoptosis is considered to play an important role in rejection of organ transplants, although the precise mechanism has not been elucidated. In this study, we screened for the expression of bcl-2 homologues (bcl-2, bax, bcl-xl, and bcl-xs) and Fas ligand (FasL) by RT-PCR method in grafts during acute rejection in rats following liver transplantation. Both bax and bcl-xs (inducers of apoptosis) mRNA levels increased steadily in the allografted group from postoperative day (POD) 2 to 8, while no remarkable changes of bcl-2 and bcl-xl expression (inhibitors of apoptosis) were recognized. Significant induction of FasL gene expression was observed in the allografted group on POD 4 and expression gradually decreased thereafter, although minimal FasL mRNA expression was seen in isografts. Our results indicated, for the first time, that rejection-induced cell apoptosis is closely associated with upregulation of bax and bcl-xs expression besides FasL, but not with down-regulation of bcl-xl.