Resolution of bone, cutaneous, and muscular involvement after haploidentical hematopoietic stem cell transplantation followed by post-transplant cyclophosphamide in adult T-cell leukemia/lymphoma.

Haploidentical hematopoietic stem cell transplantation followed by post-transplant cyclophosphamide provides a well-tolerated and potentially curable treatment for chemorefractory acute-type adult T-cell leukemia/lymphoma.

A unique subtype of diffuse large B-cell lymphoma primarily involving the bone marrow, spleen, and liver, defined by fluorodeoxyglucose-positron emission tomography combined with computed tomography.

We describe 10 cases of diffuse large B-cell lymphoma (DLBCL) confined to the bone marrow (BM), spleen, and liver, as evidenced by the uniformly increased uptake of fluorodeoxyglucose (FDG) on positron emission tomography combined with computed tomography (PET/CT). Ages ranged from 56 to 87. All, but one patient presented with 'B' symptoms, a poor performance status, and hepatosplenomegaly. All patients showed cytopenia and elevated lactate dehydrogenase levels and were classified into the high-risk category of the International Prognostic Index scoring. BM infiltration was diffuse, interstitial/intrasinusoidal, or mixed, and all showed the nongerminal center B immunophenotype. Five patients had a rearrangement involving 3q27/BCL6, while six had increased copies of MYC, BCL2, or BCL6. All patients were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, leading to complete responses in six out of eight evaluable patients. We propose BM, spleen, and liver-type DLBCL, which is defined by the findings of FDG-PET/CT.

[Indication and contraindication of radioiodine therapy for Graves' disease].

All patients with Graves' disease are potential candidates for radioiodine therapy with I-131 except during pregnancy and breast feeding. In addition, for those who wish to have babies, at least 6 months of contraception should be observed after administration of I-131 in a therapeutic dose. On top of its famous role as the last resort after severe adverse reaction to antithyroid drugs or at relapse after surgery, this method is also very suitable for subjects who prefer a safe and sure way of cure from hyperthyroidism rather than a prolonged and sometimes unpredictable drug regimen, and for those who wish to reduce their goiter size. Moreover, under exceptional circumstances, children can be treated with radioiodine. Patients with thyroid-associated ophthalmopathy should be followed up closely after I-131 therapy to rule out aggravation of their eye disease.

Delayed initial radioactive iodine therapy resulted in poor survival in patients with metastatic differentiated thyroid carcinoma: a retrospective statistical analysis of 198 cases.

UNLABELLED: To elucidate the prognostic role of (131)I radioactive iodine therapy (RIT), we conducted a retrospective cohort study analyzing the clinical factors that affect survival of postoperative patients with differentiated thyroid carcinoma (DTC). METHODS: We included 198 DTC patients with extrathyroidal extension who received total or near-total thyroidectomy and then RIT in our hospital from January 1997 to June 2009: patients with lymph node metastases only (n = 47), lung metastases without bone metastases (n = 105), or bone metastases and other distant metastases (lung, liver, brain, and skin) (n = 46). Hemithyroidectomy or subtotal thyroidectomy had been performed before total or near-total thyroidectomy in 59 patients. Disease-specific survival after initial RIT was statistically evaluated using relevant clinical parameters, including age at initial RIT, pathology, sex, therapeutic history before initial RIT, pre- and posttherapeutic serum thyroglobulin ("prethyroglobulin" and "postthyroglobulin," respectively) at initial RIT, thyroglobulin under thyroid-stimulating hormone stimulation at initial RIT ("peak thyroglobulin"), grade of uptake at scintigraphy, extent of metastasis, and number of total RITs. RESULTS: During follow-up after initial RIT (average, 5.37 y), 24 patients died from DTC (11 male patients and 13 female). The most common reasons for death were respiratory failure due to lung metastases (n = 11) and uncontrollable brain metastases (n = 6). Univariate analysis showed that disease-specific survival was related to the following factors: extent of metastasis, age at initial RIT (<45 y), prethyroglobulin (<125 ng/mL), peak thyroglobulin (<1,000 ng/mL), and interval from total thyroidectomy to initial RIT (<180 d). A past history of hemithyroidectomy or subtotal thyroidectomy was not related to disease-specific survival. Multivariate analysis showed 3 factors to be independent prognostic factors--grade of (131)I uptake at whole-body scintigraphy, extent of metastasis, and interval to RIT (P ≤ 0.001, 0.010, and 0.005, respectively)--and also showed that risk of death in patients with an interval over 180 d was 4.22 times higher than in those with an interval within 180 d. Kaplan-Meier analysis revealed that a shorter interval (180, 365, or 1,000 d) had prognostic value even in the subgroups 45 y or older, with lung metastases, and with bone metastases or more. CONCLUSION: The present study suggests that delaying initial RIT until more than 180 d after total thyroidectomy may result in poor survival for DTC patients.

[Radioiodine therapy for thyroid cancer].

Radioiodine therapy is indicated in patients after total thyroidectomy for differentiated thyroid cancer, either as ablation of remnant thyroid tissue or to treat distant metastasis, most commonly to lung and bone. Surveillance after treatment includes thyroglobulin measurement, neck ultrasonography, chest CT, scintigraphy with radiothallium or diagnostic dose radioiodine, and possibly FDG-PET. Minor but frequent side effects involve organs with physiological iodine uptake, namely the salivary glands and stomach. Uncommon but serious ones are aggravation of spinal paralysis in cases with large vertebral metastasis and myelosuppression in those with extensive skeletal lesions. Despite clear therapeutic effects in some subjects, proving prolonged survival with this therapy in the group of patients with known metastasis as a whole is an elusive goal due to too good prognosis. One the other hand, a prospective analysis of a large case series did show beneficial effect of the radio-ablation. Empirical treatment is still debatable in subjects with elevated serum thyroglobulin level and negative whole body radioiodine scan. In the near future recombinant human TSH will obviate the need for intentional hypothyroidism in preparation for diagnostic scan and therapy with radioiodine.

[Radiation therapy for Graves' ophthalmopathy].

External irradiation for thyroid eye disease has been employed for more than three decades. Destruction of infiltrating lymphocytes in the retroorbital tissue may account for its beneficial effects. Using high voltage X-ray generated from linear accelerator, usually a total dose of 20 Gy is delivered to both orbits in 2 Gy daily fractions. This therapy is devoid of grave side effects and can be done on outpatient bases, alone or in combination with glucocorticoid regimen. Its reported effectiveness lies between 50-70%. However, results of recent randomized controlled trials on its effects were controversial. As monotherapy, while in some studies the authors observed improvement in eye movement and/or diplopia, in another one there was no significant difference in changes of objective indices between irradiated and sham-irradiated eyes. Moreover, another controlled trial on combined therapy has failed to detect additional benefit of orbital radiation on high-dose intravenous steroid pulse treatment. To ascertain its true effectiveness and indication, multicenter trials with large number of subjects seems necessary.

[Guidelines for radio-iodine (131I) therapy in Graves' disease and thyroid cancer].

Radio-iodine (131I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine.

Comparison of whole-body 18F-FDG PET, 99mTc-MIBI SPET, and post-therapeutic 131I-Na scintigraphy in the detection of metastatic thyroid cancer.

UNLABELLED: The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile ((99m)Tc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of (99m)Tc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38-72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following (131)I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and (99m)Tc-MIBI SPET WBS at an interval of less than 1 week, followed by (131)I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. (131)I WBS was performed 3-5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, (201)Tl and (131)I scans). FDG-PET, (99m)Tc-MIBI SPET and post-therapeutic (131)I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and (99m)Tc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 (131)I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten (131)I-negative lesions, respectively. Three of the five (131)I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with (99m)Tc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive (99m)Tc-MIBI SPET alone). IN CONCLUSION: (a) even using whole-body SPET, FDG PET is superior to (99m)Tc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.

Effect of iodine restriction on thyroid function in patients with primary hypothyroidism.

Dietary iodine intake in Japan varies from as little as 0.1 mg/day to as much as 20 mg/day. The present study was undertaken to assess the frequency of iodine-induced reversible hypothyroidism in patients diagnosed as having primary hypothyroidism, and to clarify the clinical backgrounds responsible for the spontaneous recovery of thyroid functions. Thirty-three consecutive hypothyroid patients (25 women and eight men) with a median age of 52 years (range, 21-77 years) without a history of destructive thyroiditis within 1 year were asked to refrain from taking any iodine-containing drugs and foods such as seaweed products for 1-2 months. The median serum thyrotropin (TSH) level, which was initially 21.9 mU/L (range, 5.4-285 mU/L), was reduced to 5.3 mU/L (range, 0.9-52.3 mU/L) after iodine restriction. Twenty-one patients (63.6%) showed a decrease in serum TSH by >50% and to <10 mU/L. Eleven patients (33.3%) became euthyroid with TSH levels within the normal range (0.3-3.9 mU/L). The ratios of TSH after iodine restriction to TSH before iodine restriction (aTSH/bTSH) did not correlate significantly with titers of anti-thyroid peroxidase antibody and anti-thyroglobulin antibody or echogenicity on ultrasonography, but correlated inversely with (99m)Tc uptake (r = 0.600, p < 0.001). Serum non-hormonal iodine levels, although not correlated significantly with aTSH/bTSH values, were significantly higher in the 21 patients with reversible hypothyroidism than in the remaining 12 patients. TSH binding inhibitor immunoglobulin was negative in all except one weakly positive case. In conclusion, (1) primary hypothyroidism was recovered following iodine restriction in more than half of the patients, and (2) the reversibility of hypothyroidism was not significantly associated with Hashimoto's thyroiditis but with increased (99m)Tc uptake and elevated non-hormonal iodine levels.

Seasonal variation in relapse rate of graves' disease after thionamide drug treatment.

OBJECTIVE: Controversy abounds on the issue of seasonal variation in new onset of Graves' disease, partly due to the difficulty of precisely dating the exact start of symptoms. To address the possible relationship between climatic changes and disease activity from a different perspective, we reviewed time of relapse during regular follow-up after successful drug treatment with thionamides. DESIGN: Retrospective analysis of a case series in a university clinic. PATIENTS AND MEASUREMENTS: We consecutively registered patients who experienced re-emergence of hyperthyroidism between 1992 and 2001 after successful antithyroid drug therapy. Excluded were subjects with superimposing painless thyroiditis, in postpartum, on immunomodulatory drugs, or off thionamides prematurely on their own volition. RESULTS: Fifty-two patients recurred 2 to 36 months after drug cessation. The frequency was higher in spring and summer (March to August) than in autumn and winter (September to February). With a new coated-tube radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected in sera from 87.5% of the reworsened patients. CONCLUSIONS: Graves' disease tends to relapse more frequently in spring and summer. Further clinical studies are warranted to clarify underlying mechanism (s) for this seasonal variation.

Chemo-radionuclide therapy for thyroid cancer: initial experimental study with cultured cells.

UNLABELLED: Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. METHODS: Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. RESULTS: Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 microg/ml for CDDP, 0.3 microg/ml for Dox, and 3 microg/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. CONCLUSION: In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible.

A patient with two thyroid papillary carcinomas demonstrating hot and cold lesions on 113I thyroid scintigraphy.

A 44-year-old euthyroid woman had two palpable nodules in the thyroid gland. 123I thyroid scintigraphy showed a hot nodule in the right lobe and a cold one in the left lobe. Total thyroidectomy was performed, and histopathologic examination revealed that both tumors contained papillary carcinoma. Thus, hot nodules on a thyroid scintigram with 123I do not necessarily preclude malignancy.

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.