Biomedical subjects
Publications and source records attributed to T Goya.
The five year survival rate of lung cancer patients is only 10% in Japan. The staging system of c-TNM is more important than p-TNM when deciding treatment modality for lung cancer. Compared to other solid cancers, neoadjuvant therapy in lung cancer treatment has a more important position. A clinical protocol study should be carried out with the idea of "intent to treat" and medical oncology will play a more important role in the treatment of lung cancer.
A 19-year-old woman with dermatofibrosarcoma protuberans (DFSP) of the breastis described. She presented with a tumor of the left breast with redness and swelling. She had noticed a small tumor five years previously, but it had begun togrow rapidly three months previously. Mammography, ultrasonography and aspiration biopsy cytology demonstrated an apparently benign tumor of the breast preoperatively. Wide excision was performed to confirm the diagnosis. Histologically, the tumor was composed of a uniform population of fibroblasts in a distinct storiform pattern. DFSP was diagnosed in the skin over the breast. This lesion ordinarily originates from the dermis in the trunk and proximal extremities. It is important to diagnose a soft tissue lesion accurately when it occurs in the breast.
Recent findings suggest that hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on vascular endothelial growth factor (VEGF) expression of c-Met/HGF receptor-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of VEGF proteins accompanying increased transcription of VEGF mRNA in a dose-dependent fashion. Since malignant gliomas frequently co-express HGF/SF and its receptor, these results suggest that HGF/SF could act as an indirect angiogenic factor through autocrine induction of VEGF expression and secretion in malignant gliomas.
We herein report a case of Epstein-Barr virus (EBV)-associated T-cell lymphoma that developed within a month after a kidney transplantation. The recipient was a 37-year-old man who had evidence of a previous EBV infection. Cyclosporine, methylprednisolone, and azathioprine were used for immunosuppression, and acute rejection was treated with high-dose methylprednisolone. The lactate dehydrogenase level started to increase on day 24 and thereafter peaked on day 37 while also demonstrating progressive jaundice and a bleeding tendency. A transplant nephrectomy was done on day 37; however, the patient could not recover and eventually died of respiratory failure as a result of diffuse pulmonary edema. A pathological examination of the resected kidney revealed a diffuse proliferation of large atypical lymphoid cells in the parenchyma. Immunohistochemically, the tumor cells were positive for CD45 and T-cell marker, CD45RO, but negative for B-cell markers. EBV-encoded RNA was demonstrated within the neoplastic cells by in situ hybridization.
Expression of hepatocyte growth factor (HGF) and c-met, a proto-oncogene that encodes a receptor for HGF, was examined in 45 cases of human primary intracranial tumors by means of RT-PCR. In gliomas, HGF and c-met mRNAs were preferentially expressed in high-grade tumors. Co-expression of both genes was observed in glioblastomas (6/15) and in one anaplastic astrocytoma (1/5) but not in low-grade astrocytomas (0/3). By contrast, the c-met gene was consistently expressed in meningiomas (12/14) and schwannomas (8/8). The presence of c-Met protein was confirmed in the tumor cells of glioblastoma, meningioma and schwannoma by immunohistochemical staining. Moreover, all of the schwannoma cases co-expressed the HGF gene. These observations suggest that HGF/c-met expression is somehow related to the disease progression in gliomas, whereas c-Met protein might have an important fundamental biological role in meningioma and schwannoma. Moreover, since all of the schwannoma cases concomitantly expressed the ligand (HGF) and the receptor (c-met) genes, HGF may act in an autocrine fashion in schwannoma.
We designed a protocol of 3-dimensional phase contrast (3D-PC-) magnetic resonance angiography (MRA), which was performed in the axial plane to assess the circle of Willis and in the coronal plane to assess the arteries of the head and neck, for screening of the intra- and extracranial arterial occlusive diseases. We evaluated the accuracy of 3D-PC-MRA comparing it with intraarterial angiography. In 52 consecutive patients presenting with clinical suspicion of a stroke, common carotid bifurcation (CCB), petrous segment of internal carotid artery (C5 segment), carotid siphon, middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA), and basilar artery (BA) were evaluated. Both examinations were blindly graded as normal, mild (0-29% stenosis), moderate (30-69% stenosis), severe (70-99% stenosis), or occluded. In the two readers experienced and inexperienced in MR interpretation, Spearman rank correlations between the two techniques were 0.917/0.866 (CCB), 0.803/0.758 (C5 segment), 0.837/0.702 (carotid siphon), 0.841/0.787 (MCA), 0.899/0.886 (PCA), 0.935/0.889 (VA), and 0.932/0.900 (BA), respectively (p < 0.0001). 3D-PC-MRA and intraarterial angiography had a good overall agreement, suggesting its use as a primary screening technique for intra- and extracranial arterial occlusive diseases, although the diagnostic accuracy of MRA was relatively poor in the C5 segment, carotid siphon, and MCA presumably due to phase dispersion.
A 73-year-old man was admitted because of right frontal headache and gradual loss of right visual acuity, which had been occurring for 1 year. He had been treated with corticosteroids under the diagnosis of retrobulbar optic neuritis at a nearby clinic. Magnetic resonance imaging (MRI) revealed a nodular lesion at the tuberculum sellae, which showed isointensity on T1-weighted images, iso- to low-intensity on T2-weighted images, and heterogeneous enhancement with Gd-DTPA. Meningioma was diagnosed, and surgery was performed but was limited to biopsy because of intraoperative detection of purulent inflammation of the nodule. Histologic examination revealed aspergillosis in a portion of the meningotheliomatous meningioma. The patient died of meningoencephalitis about 1 month after surgery in spite of extensive treatment with antifungal agents. MRI findings of meningioma and aspergillosis are similar, thus making preoperative diagnosis difficult. However, this case provides evidence that aspergillosis should be included in the differential diagnosis when a skull-base meningioma-like nodule is noted if sinusitis is revealed in the sphenoid sinus.
Technetium-99m sestamibi (MIBI) is thought to be passively taken up by metabolically active tumour cells and effluxed from them by P-glycoprotein (Pgp). This 170-kDa membrane-bound protein, encoded by the MDR-1 gene, acts as an energy-dependent efflux pump for several antineoplastic agents, resulting in multidrug resistance. For this reason, it is of interest whether the tumour's response to chemotherapy can be predicted by MIBI single-photon emission tomography (SPET). In this study, MIBI SPET was compared with thallium-201 (Tl) SPET using magnetic resonance imaging as a guide in 16 patients with untreated brain tumours [ten glioblastomas (GBs), two anaplastic astrocytomas (AAs), two low-grade gliomas (LGASs) and two metastatic brain tumours) and in four patients who had received treatment for with brain tumours (two GBs, two AAs). In addition, we investigated the expression of the MDR-1 gene and its product Pgp in the same patients, and compared the results with MIBI SPET findings. MIBI, as well as Tl, was highly accumulated and retained in the enhanced region of malignant gliomas. In addition, MIBI SPET yielded sharp and well-contrasted images, and the margin of the tumour was more clearly defined than with Tl SPET due to a good signal-to-noise ratio. Follow-up MIBI SPET in patients who had received therapy showed marked uptake in a patient with malignant transformation, who deteriorated clinically. Patients with no uptake on MIBI SPET showed no sign of recurrence. Semiquantitative analysis of untreated patients showed a relationship between the early uptake index (UI, ratio of average count/pixel in the lesion to that in the contralateral area on early images) and the degree of malignancy (early UI = 1.08+/-0.06 in LGASs, 4.10+/-0.84 in AAs, 5.71+/-3.47 in GBs, and 7.52+/-1.52 in metastatic brain tumours). The retention index (RI, ratio of delayed to early UI) of MIBI was significantly lower than that of Tl in metastatic brain tumours (P<0.05), but not in malignant gliomas. Histological and biological investigation of gliomas showed that the MDR-1 gene and its product Pgp were expressed only in normal endothelial cells and not in tumour cells or proliferating endothelial cells; Pgp tended to decrease as the degree of malignancy rose. Hence, the presence of Pgp and the grade of malignancy were inversely related in gliomas. By contrast, immunohistochemical study showed strong accumulation of Pgp in metastatic brain tumour cells. These histopathological findings and MIBI SPET findings are compatible with experimental data; MIBI was washed out by Pgp. The main cause of chemoresistance is probably not an increasing drug efflux by Pgp in gliomas. Thus, MIBI SPET is useful for detecting the active lesions, but may not be useful for predicting the response to chemotherapy in gliomas.
PURPOSE: This study was conducted to determine whether there was any relationship between the adverse toxicity of combination chemotherapy and clinical values including age, sex, creatinine clearance (Ccr), body surface area and relative body weight. METHODS: Cisplatin at a dose of 80 mg/m2 on day 1 and etoposide at a dose of 100 mg/m2 on days 1, 2 and 3 were given to 42 consecutive patients with solid tumors. All patients had normal major organ function and received uniform hydration therapy. RESULTS: Body Mass Index as a measure of relative body weight was inversely correlated with the percentage decrease in white blood cells (P = 0.0681) and platelet count (P = 0.0115). Body surface area was also inversely correlated with leukopenia (P = 0.0171) and thrombocytopenia (P = 0.0058). In contrast, age, sex and Ccr had no significant relationship with adverse toxicity. CONCLUSIONS: It is concluded that dose adjustment of combination chemotherapy with cisplatin and etoposide according to age or ideal body weight is not appropriate and that a conventional dose modification method based solely on body surface area is probably not sufficient to reduce interpatient variability of cancer chemotherapy. A pharmacokinetic and pharmacodynamic study of combination chemotherapy is warranted to establish the ideal dose modification method.
Irinotecan chloride (CPT-11) is a new semi-synthetic camptothecin analogue which has encouraging antitumor activity against various malignancies. The major and unique toxicity of CPT-11 is diarrhea. Cardiovascular toxicity is rare and has not been found in clinical trials performed in Japan except for a very few cases of insignificant tachycardiac arrhythmia. We report a case of a 69-year-old man with recurrent colon cancer who suffered from bradycardia induced by infusion of CPT-11. Other toxicities including hematological toxicity and diarrhea were mild. Pharmacokinetic analysis using a limited sampling model revealed that the occurrence of bradycardia did not correlate with the excess of drug exposure. Although all of the cholinergic actions reported in the literature were mild, cardiotoxicity may come to be a clinically significant problem. If the events were examined more thoroughly, the cholinergic effect may be discovered more frequently. To administer CPT-11 safely needs meticulous monitoring not only for hematological toxicity and diarrhea but also for other cholinergic actions including bradycardia.
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We reviewed 546 operative cases in haemodialysis patients during the past 8 years between June 1990 and May 1998. The average age of the 257 male and the 289 female patients was 57.1 years. The average period of haemodialysis was 14 years and 4 months. We discussed the etiology, pathological focus, frequency, symptoms, problems and operative indications. Carpal tunnel syndrome occurred most frequently, occupying 289 cases. Short-term postoperative results were positive in the initial case within 6 months after the occurrence of the first symptoms. Because no effective method preventing recurrence existed, synovectomy was used as much as possible in the initial operation. Surgical treatment was used for amyloid arthropathy in 15 shoulders. It was effective in cases resistant to any conservative treatment. For the knee joint, the arthroscopic synovectomy was performed in 8 cases, and total knee replacement in 6 cases. The results of the total knee replacement cases were good. However, recurrences were observed in 40% of the synovectomy cases. In the hip joint, the curettage and bone grafting were performed in 7 hips of 6 patients. All bone grafts were consolidated and there was no case of postoperative pathological fracture. In some cases with destructive spondyloarthropathy, the vertebrae involved spontaneously fused without severe kyphotic deformity. A case with mild pain and without neurological deficit can be treated conservatively. A case with severe pain, instability, and myelopathy indicates operative measures must be taken. Attention must be paid for a possible collapse of the grafted bone after the cervical level two anterior fusion. Haemodialysis patients are vulnerable to infection. This diagnosis is difficult to distinguish due to the weakened state of the immune system. Rigorous attention is required to prevent and detect infection in cases using artificial joints or instrumentation. The treatment of bone and joint disturbances from dialysis-related amyloidosis has become surgical due to the advancement of dialysis control. However, it remains one of the more conservative treatments. Determining the cause and establishing a method of treatment are desired as early as possible.
We studied the hemodynamic effects of delayed initiation (6 h postburn) of antioxidant therapy with high-dose vitamin C in second-degree thermal injuries. Seventy percent body surface area burns were produced by subxiphoid immersion of 12 guinea pigs into 100 degrees C water for 3 s. The animals were resuscitated with Ringer's lactate solution (R/L) according to the Parkland formula (4 ml/kg/% burn during the first 24 h) from 6 h postburn, after which the resuscitation fluid volume was reduced to 25% of the Parkland formula volume. Animals were divided into two groups. The vitamin C group (n = 6) received R/L to which vitamin C (340 mg/kg/24 h) was added after 6 h postburn. The control group (n = 6) received R/L only. Both groups received identical resuscitation volumes. Heart rates, mean arterial blood pressure, cardiac output, hematocrit level, and water content of burned and unburned tissue were measured before injury and at intervals thereafter. No animals died. There were no significant differences in heart rates or blood pressures between the two groups throughout the 24-h study period. The vitamin C group showed significantly (P < 0.05) lower hematocrits 8 and 24 h postburn, and higher cardiac outputs after 7 h postburn. At 24 h postburn, the burned skin in the vitamin C group had a significantly (P < 0.05) lower water content (73.1 +/- 1.1) than that of the control group (76.0 +/- 0.8). In conclusion, delayed initiation of high-dose vitamin C therapy beginning 6 h postburn with 25% of the Parkland formula volume significantly reduced edema formation in burned tissue, while maintaining stable hemodynamics.
Dialysis-related amyloidosis (DRA) predominantly occurs in the osteoarticular structures. However, according to studies in the increasing number of long-term hemodialysis patients, DRA has also been systemically found to appear in the other tissues and organs as well. In this study, we investigated lingual amyloidosis in relation to systemic DRA. A total of 472 patients were studied who were on regular hemodialysis for more than 10 years, including 103 patients for more than 20 years. Eight of these patients (7 males and 1 female, mean age 59 +/- 8 years, range 46 to 68 years) developed lingual amyloidosis, seemingly as a result of beta2-microglobulin (beta2m) deposits. All patients demonstrating lingual amyloidosis had been treated with regular hemodialysis for more than 20 years (mean HD duration 23.6 +/- 1.4 years), and its morbidity was 7.8% in the 103 patients and 20% (6 patients) in the 30 patients treated for more than 23 years with hemodialysis. Hemodialysis (HD) duration with bioincompatible unsubstituted cellulose membranes in the 8 patients was longer than that in the control group without lingual amyloidosis (P < 0.05). Lingual amyloid nodules were whitish-yellow in color and varied in size, at least over 1 mm in diameter. Their consistency was firmer than the intact tongue. The location of the amyloid nodules could be classified into two types: (1) diffuse type (diffusely distributed over the tongue), and (2) lateral type (localized only in the lateral side of the tongue). Five of the eight patients with lingual amyloidosis complained of functional disturbances in the tongue, such as abnormal taste, or difficulty in mobility and articulation. No macroglossia was observed in any of these cases. It was thus concluded that DRA of the tongue is a very rare complication, occurring in the late stage of long-term hemodialysis patients, that disturbs their quality of life.
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