Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma.

This study was designed to investigate the relationship between Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy and outcome of treatment in patients with non-Hodgkin's lymphoma (NHL). Forty-five patients with NHL were studied with Tc-99m-MIBI before any treatment. Images of the lesions were obtained at 20 min and 2 h after radionuclide administration. Visual semi-quantitative interpretation was performed for Tc-99m-MIBI (grade 0-4) scintigraphy. Patients underwent 3-5 cycles of CHOP chemotherapy with/without involved field radiotherapy for large tumors. Their responses to treatment were evaluated at the end of chemotherapy and during the follow-up period. Forty of 45 patients (89%) showed abnormal uptake of Tc-99m-MIBI. There was no correlation between intensity of MIBI accumulation and response to chemotherapy. However, patients with negative or decreased MIBI activity 2 h after radionuclide administration showed worse response to chemotherapy compared to those with continued MIBI activity. MIBI activity could not predict the development of relapse in the follow-up study. In this study, the number of patients was small and we could not reach definite conclusions. However, we think that MIBI scintigraphy is not valuable for predicting the chemotherapy outcome in patients with NHL.

Normalized spleen/liver ratios on 111In-labelled platelet scintigraphy to predict the outcome of partial splenic embolization in patients with idiopathic thrombocytopenic purpura.

In this study, we examined the use of 111In-labelled platelet imaging to predict the outcome of partial splenic embolization (PSE) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-eight patients with a clinical diagnosis of ITP underwent 111In-labelled platelet scintigraphy. Twenty-four patients with intractable ITP underwent PSE after 111In-labelled platelet scintigraphy. The conventional spleen/liver ratio at 1 h and 192 h and the normalized spleen/liver ratio [(spleen uptake at 192 h/liver uptake at 192 h)/(spleen uptake at 1 h/liver uptake at 1 h)] were compared between responders and non-responders to PSE. Patients with ITP showed a significant reduction in platelet counts, increased platelet associated IgG, decreased platelet survival, and an increased conventional spleen/liver ratio at 192 h. No significant difference was found between patients who had and who had not undergone previous medical treatment. A significant difference was observed in the mean conventional spleen/liver ratio at 192 h between responders and non-responders, but there was substantial overlap among individuals. The mean normalized spleen/liver ratio was significantly higher in responders than non-responders; there was less overlap between the two groups with the normalized spleen/liver ratio than the conventional spleen/liver ratio. The therapeutic outcome of PSE is predicted more accurately using a normalized spleen/liver uptake ratio of 111In-labelled platelets in patients with idiopathic thrombocytopenic purpura than a conventional splenic/hepatic uptake ratio on delayed images.

[Bleomycin, adriamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma: long-term survival rate and complications].

This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival.

[A case with nasopharyngeal carcinoma extending into the cavernous sinus].

Nasopharyngeal carcinoma is seen frequently in South China, but it is rare in Japan as well as in Western countries. We reported a rare case with intracranial extension at the initial presentation. This 25-year-old Japanese female showed left abducens palsy. MRI revealed an intracavernous mass with homogeneous enhancement connected with the lesion around the epipharynx through the parapharyngeal space. The mass enlarged gradually, followed by left trigeminal palsy. An elevation of the titer of serum EBV Ig-G was noted. She was operated on via the subtemporal approach, which revealed an intracavernous tumor, connected with the infratemporal fossa mass via the enlarged foramen ovale. Histological examination of the surgical specimen revealed lymphoepithelioma. Local irradiation of 60Co of 63 Gy was performed on the cavernous and parapharyngeal tumors and they decreased in size remarkably. However, metastasis to the upper right neck lymph node occurred, and it was removed. Additional irradiation of 45 Gy was performed on her neck. Chemotherapy was not able to be carried out due to leucocytopenia. At present, 2 years after onset, no regrowth of the tumor has been seen. At initial presentation, intracranial extension of nasopharyngeal carcinoma is very rare. Remission may be obtained by a combination of surgery and irradiation even in cases with metastasis.

Indium-111 labelled lymphocytes: isotope distribution and cell division.

Since lymphocytes continue to proliferate and divide in vivo, it is important to determine the fate of a radionulide following lymphocyte labelling. Using the mixed lymphocyte reaction (MLR), we induced indium-111 labelled lymphocytes from a specific in-bred rat strain (AS) to divide and then observed the subsequent 111In distribution between cells and supernatant. L10 and L12.4 cells, which are allospecific CD4+ T lymphocytes from the AS rat, were stimulated in the MLR by antigen-presenting cells from the August rat, a different strain. We labelled L10 or L12.4 lymphocytes on day 0, the first day of the stimulation cycle, and continued to culture the lymphocytes in vitro. The proliferation of the cells was estimated according to their increase in number. The distribution of 111In between cell and supernatant fractions and between viable and dead (but intact) cells was measured in the cell suspension each day after labelling. The metabolic activity of 111In-labelled lymphocytes was compared with control cells by measuring their uptake of fluorine-18 fluorodeoxyglucose ([18F]FDG). 111In-labelled lymphocytes showed a poor proliferative response compared with control cells 24-48 h after labelling but increased in number after this time. From 24 to 72 h, about 70% of 111In was in the supernatant but only about 5%-10% was associated with intact dead cells. These dead cells tended to retain their 111In, losing less than 30% per day, suggesting that 111In in the supernatant was the result of active elimination from viable cells. Moreover, 24 h after culture, considerably more 111In was associated with viable than with dead lymphocytes, although over the next few days this distribution reversed. 111In-labelled lymphocytes took up more [18F]FDG than control cells at 24 h but not at 0 or 72-96 h; the maximum [18F]FDG uptake coincided with the greatest reduction in cell number. Furthermore, [18F]FDG uptake correlated with the initial 111In burden in lymphocytes labelled with 111In 24 h previously. The results are consistent with active elimination of 111In by 111In-labelled lymphocytes. The energy requirements for this are diverted away from cell division, thereby increasing the probability of cell death. As lymphocytes become 111In deplete, they recover their capacity to proliferate and their risk of death decreases. These findings have important implications for 111In-labelled lymphocyte scintigraphy, suggesting that cells remaining viable immediately after labelling will either subsequently die or alternatively eliminate the label.

Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.

Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.

[Tumor imaging in nuclear medicine].

Tumor imaging in nuclear medicine has been improved by imaging instruments and newly developed radiopharmaceuticals. One of the imaging developments is a SPECT system using three-detector system. Its each detector rotates 120 degrees when SPECT projection data are acquired and we can save the scanning time and get a high resolution image which is less than 10 mm FWHM. About radiopharmaceuticals 99mTc MDP and 57Ga-citrate are used most commonly for detecting early metastatic lesions in the body. 201Tl chloride and 99mTc MIBI as used for cardiac imaging are also used for tumor detection. 111In-DTPA-D-Phe-octreotide are developed for detection of somatostatin receptor and will be used for many kinds of tumor such as small cell lung cancer, meningioma, malignant lymphoma and gastrointestinal hormone producing tumor.

[111In-labeled leukocyte scintigraphy in patients with inflammation of unknown focus].

This study evaluates the usefulness of 111In-labeled leukocyte scintigraphy to localize inflammatory foci that cannot be determined by clinical symptoms and other imaging studies. Patients with persistent fever following abdominal surgery (n = 20), suspected post-traumatic osteomyelitis associated with multiple fractures (n = 5), and fever of unknown origin (n = 22) were recruited. In all patients, the exact location of inflammatory foci could not be determined by clinical symptoms and conventional imaging studies. In patients with post-surgical fever, leukocyte scintigraphy localized responsible foci in 65% of patients and provided clinically useful information for the treatment. In patients with multiple fractures, the location of osteomyelitis was diagnosed confidently in only one case (20%). In patients with fever of unknown origin, responsible foci were detected in 18% of patients. Although in those patients positive leukocyte studies provided clinically useful information, overall usefulness seemed to be limited. Leukocyte scintigraphy is able to detect inflammatory foci in patients with post-surgical fever, but less likely to localize responsible foci for post-traumatic osteomyelitis or fever of unknown origin when patients have been examined carefully by clinical symptoms and conventional imaging studies.

Myelodysplastic syndrome associated with erythrophagocytosis by blasts and myeloid cells.

A 63-year-old man with refractory anemia with excess of blasts in transformation exhibited erythroid hyperplasia, dyserythropoiesis, a del(20q) abnormality, susceptibility to bacterial infections, and a relatively short survival. Phagocytosis of erythrocytes by blast cells was observed. Erythrophagocytosis was also seen in myeloid cells, including promyelocytes, myelocytes, metamyelocytes and neutrophils. Neither the monocytes nor the macrophages showed erythrophagocytosis. This is the first report of erythrophagocytosis by blasts and myeloid cells in a patient with myelodysplastic syndrome.

[Reversion to chronic phase of chronic myelogenous leukemia in blast crisis with small-dose daunorubicin and oral prednisolone].

In December 1993, a 76-year-old Japanese male presented with general fatigue. Peripheral blood (PB) examination indicated marked leukocytosis (WBC count, 19.8 x 10(4)/microliter; leukemic blast differential, 89.5%). Leukemic blasts were positive for CD33, and negative for lymphoid antigens, with 2% of the blasts being positive for myeloperoxidase staining. On admission, chromosome analysis of leukemic cells in PB showed 45, X,-Y, t (9;22) [12/15]/46, XY, t (9;22) [3/15]. Southern blot analysis of the DNA from PB showed a rearrangement at the M-BCR region and germline configurations of both TCR beta and IgH chain genes. The patient was diagnosed as Philadelphia-positive chronic myelogenous leukemia (CML) in blast crisis. We commenced treatment with daunorubicin (DNR; 20 mg/day x 1 IV) and daily prednisolone (PSL; 60 mg/day PO). Leukemic blasts disappeared rapidly from PB, while the promyelocytes showed a transient increase, peaked 7 days after the start of therapy, and then disappeared. Myelocytes and metamyelocytes also showed transient increases. Without a period of severe myelosuppression, the patient reverted to the chronic phase of CML and karyotypic analysis of bone marrow cells showed 45, X,-Y, t (9;22) [33/35]/46, XY, [2/35]. Consolidation chemotherapy with DNR and BHAC was started, but the patient's condition deteriorated due to bacterial infection and he died of hepatic failure on March 1994. In this case, reversion to the chronic phase of CML in blast crisis may be accomplished by the cytodifferentiating effects of small-dose DNR and oral PSL to the leukemic blasts.

Synchronous fluctuation of interleukin-6 and platelet count in cyclic thrombocytopenia and thrombocytosis.

We describe a case of cyclic thrombocytopenia and thrombocytosis, whose cytokine levels, granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6) in plasma, fluctuated in synchrony with platelet count. The levels of the two cytokines correlated significantly with the platelet count for 11 observations over an 8-month period (r = 0.79, p < 0.01 for GM-CSF and r = 0.87, p < 0.001 for IL-6). No inverse relationship between platelet-associated immunoglobulin G (PAIgG) and platelet count was observed (r = 0.39, p > 0.20). These findings suggest that the fluctuation of platelet count in this case may result from an aberration of the cytokine network regulating megakaryopoiesis and platelet formation.

[Evaluation of hilar 67Ga-citrate uptake in bronchogenic carcinoma].

We evaluated hilar uptake on 67Ga-citrate scintigraphy and correlated with hilar lymph node metastases in one-hundred seventeen cases (two-hundred thirty four hila) of bronchogenic carcinoma. Hilar uptake was classified into three grades independently on anterior and posterior chest views: no uptake (grade 0), uptake equal to that in the thoracic vertebrae (grade 1), uptake higher than that in the thoracic vertebrae (grade 2). If a summed grade of anterior and posterior view was larger than 3, hilar uptake was considered as positive. In forty-four cases (forty-nine hila) with hilar lymph node metastases, positive hilar uptake was found in ten cases (eleven hila), resulting in sensitivity of 22% based on cases and 23% based on hila. In seventy-three cases (one-hundred forty-six hila) without hilar lymph node metastases, positive hilar uptake was found in six cases (ten hila), resulting in specificity of 91% based on cases and 93% based on hila. In comparison to scintigraphic findings of unilaterally positive hilar uptake, findings of bilaterally positive hilar uptake showed significantly lower accuracy in determining presence of hilar lymph node metastases. No definite correlation between hilar uptake and histopathology or 67Ga-citrate uptake in a primary tumor was observed. The results indicate that usefulness of 67Ga-citrate scintigraphy is limited when evaluating hilar lymph node metastases in bronchogenic carcinoma.

[Giant plasmacytoma of the skull which appeared in the clinical course of multiple myeloma--a case report].

A 51-year-old woman with large plasmacytoma occurring from the temporal bone is presented. She has a history of multiple myeloma for 9 years. She manifested marked swelling in the left temporal area with tenderness. Neurological examination revealed no abnormality. She showed monoclonal free light chain (lambda type) in the serum and urine, and had multiple osteolytic lesions in her general bones. T1 WI of MRI exhibited a huge mass showing slightly high intensity in the left middle fossa and infratemporal fossa, and a part of the mass protruded into the extracranial space. The mass was markedly enhanced by Gd-DTPA. Angiography showed a hypervascular mass supplied by the external carotid artery. Biopsy disclosed plasmacytoma. She underwent local irradiation of 30 Gy and chemotherapy of Ranimustine (100 mg) and Cyclophosphamide (400 mg). The tumor reduced its size, and tenderness in her temporal area disappeared.

Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with proliferative activity.

To evaluate the relationship between PET using 18F-fluorodeoxyglucose (FDG) and pathological findings and to compare indices obtained by FDG-PET, FDG-PET was performed in 23 patients with untreated malignant lymphoma. Three indices obtained by FDG-PET, tumor-to-normal contrast ratio (TCR), distribution absorption ratio (DAR), k1k2/(k2 + k3), correlated with proliferative activity which was pathologically estimated both by mitotic count and by proportion of cells in all phases of the cell cycle. The relationship did not significantly change according to which of the three indices was chosen. FDG-PET, which shows the proliferative activity of tumors, is considered to be a useful method for managing tumors.

Change of cerebral glucose metabolism by antineoplastic drug.

To estimate change of cerebral glucose metabolism by anticancer drugs, positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) was performed in 11 patients with malignancies who did not show neurological symptoms. In a patient treated with intravenous high-dose methotrexate (HD-MTX) and intrathecal MTX, apparent decrease of glucose metabolism was observed. HD-MTX and intrathecal MTX may cause cerebral glucose metabolism disorder primarily. Cerebral glucose metabolism was also mildly reduced by chemotherapy with drugs other than MTX and by radiotherapy outside the brain, with a corresponding change of blood data. It may reflect a psychosomatic change in whole body.

The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis.

Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma.

[Triple malignancy including bladder carcinoma, prostate carcinoma and malignant lymphoma: a case report].

A 70-year-old man was admitted to our hospital with the complaint of lower abdominal mass. Previously, he had received partial cystectomy and radiation of 38 Gy for bladder transitional cell carcinoma and transurethral resection of prostate and diethylstilbestrol administration for prostatic adenocarcinoma. The third tumor was located between the bladder and lower abdominal wall with inguinal lymph node swelling. Biopsy specimen revealed malignant lymphoma. After 2 courses of combination chemotherapy consisting of vincristine, prednisolone and procarbazine, complete remission was achieved. We discuss about multiple malignancies including urological organs.

[Ceftriaxone as a single agent in empirical therapy of infection in patients with hematologic disorders. Hanshin Infection Study Group].

For seventy episodes of infection in hematologic disorders mostly during the phase of severe granulocytopenia, a trial was designed to evaluate the efficacy of a new third-generation cephalosporin, ceftriaxone (CTRX). The regimen consisted mainly of drip infusion of CTRX 2 g every 12 hours. The overall response rate achieved was 54.3 percent. Two episodes of an outpatient with malignant lymphoma were effectively treated by CTRX at a dose of 2-4 g once a day, reflecting its long biological half-life. Gastrointestinal symptoms, hypersensitivity reactions and elevation of hepatic enzyme levels occurred rarely (6.4 and 5.1 percent of the patients, respectively), and these abnormalities were mild and reversible. Thus, CTRX may be recommended as an effective monotherapy in the treatment of infections in immunocompromised patients with hematologic disorders.