When is total thyroidectomy indicated as a treatment of “follicular carcinoma”?

Clinicopathologic studies were performed to establish rational criteria for total thyroidectomy as a treatment of follicular carcinoma. During the 4-year period from 1981 to 1984, total thyroidectomy was carried out on 23 patients in whom unequivocal vascular invasion and/or obvious extracapsular extension were disclosed on pathological study of the primary thyroid lesion. Although occult metastatic lesions were detected postoperatively in 5 patients, no distant metastases have been found in 12. Distant metastasis was clinically manifest on admission in the other 6 patients. The degree of vascular invasion at the primary lesion was not correlated with the occurrence of distant metastasis. However, 10 of the 15 patients with tumors characterized by a thick fibrous capsule had distant metastases, while all but 1 of 8 patients with a thin capsule showed no metastasis. Apparent capsular invasion seemed to increase the relative risk of distant metastasis. On the other hand, solid clusters of tumor cells containing a variable number of small follicles, which characterize Langhans' wuchernde Struma, were found in 6 patients, and 5 of them showed distant metastases. Thus, total thyroidectomy should be considered when (a) distant metastases are clinically apparent, (b) the primary lesion has a thick fibrous capsule with or without obvious capsular invasion, or (c) solid clusters of tumor cells are demonstrated microscopically.

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Resumen Se realizaron estudios clinicopatológicos con el propósito de establecer criterios racionales para la tiroidectomía total en el tratamiento del carcinoma folicular. En el curso de un perfodo de 4 anos entre 1981 y 1984, se realizó tiroidectomía total en 23 pacientes en quienes se halló inequívoca invasión vascular y/o obvia extension extracapsular en el examen histopatológico de la lesión tiroidea primaria. Aunque postoperatoriamente se detectaron lesiones metastáticas ocultas en 5 pacientes, no se encontraron metástasis distantes en 12. Metástasis distantes eran clínicamente manifiestas en el momenta de la admisión en los otros 6 pacientes. El grado de invasión vascular en la lesión primaria no apareció correlacionado con la ocurrencia de metástasis distantes. Sin embargo, 10 de los 15 pacientes con tumores caracterizados por una cápsula gruesa y fibrosa tenían metástasis distantes, mientras solo 1 de 8 pacientes con tumores de cápsula fina mostró metástasis. La invasión capsular aparente parece incrementar el riesgo relativo de metástasis distantes. Por otra parte, agrupaciones sólidas de células tumorales con presencia de números variables de folículos pequeños, que caracterizan al wuchernde Struma de Langhans, fueron encontrados en 6 pacientes, 5 de los cuales mostraron metastasis distantes. Por lo tanto, se debe considerar la tiroidectomía total cuando: (a) haya metástasis distantes clínicamente aparentes, (b) la lesión primaria tenga una gruesa cápsula fibrosa con o sin invasión capsular obvia, y (c) se demuestren microscópicamente agrupaciones sólidas de células tumorales.

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Résumé Une étude clinicopathologique a été menée pour déterminer les critères de thyroïdectomie totale comme traitement dans le cancer folliculaire de la thyroïde. Pendant 4 ans, de 1981 à 1984, 23 patients ont subi une thyroïdectomie totale pour envahissement vasculaire non équivoque et/ou extension extracapsulaire évidente découverte sur la pièce d'exérèse initiale. Cinq patients avaient des métastases occultes découvertes dans la période postopératoire, 6 avaient des métastases cliniquement évidentes, alors que 12 ne présentaient aucun signe de métastase à distance. Le degré d'envahissement vasculaire de la lésion primitive n'était pas corrélé avec la survenue de métastases à distance. Cependant, 10 des 15 patients à tumeurs caractérisées par un épaississement de la capsule fibreuse avaient des métastases à distance, alors que 7 des 8 patients avec une capsule mince n'avaient pas de métastases. L'envahissement capsulaire était associé à un plus grand risque de métastases à distance. Des amas solides de cellules tumorales contenant de petits follicules, le wuckernde struma de Langhans, étaient retrouvés dans 6 cas, dont 5 avaient des métastases à distance. Ainsi, la thyroïdectomie totale est préconisée lorsque (a) des métastases à distance sont cliniquement évidentes, (b) la lésion primitive possède une capsule fibreuse épaisse avec ou sans envahissement évident, et (c) on met en évidence des cellules tumorales en amas microscopiquement.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.     

Combination of radio-chemotherapy for curing of childhood hematologic tumors: preventive approaches and problems on CNS involvement

The CNS has often been classified as a "drug sanctuary" as most anticancer drugs do not achieve effective penetration of the blood-brain barrier. With more effective systemic chemotherapy program, the incidence of CNS involvement in leukemia has increased. The strategy for treatment of leukemia is that one achieves by destruction of all leukemia cells including CNS. Between 1972 and 1978, 153 children with ALL were treated with multiple methods of CNS-prophylaxis and were analyzed in relation to treatment regimens, age, sex and initial hematologic status. Patients received CNS-prophylaxis; Group I: three doses of intrathecal methotrexate (MTX) and hydrocortisone (HDC), Group II: same as in Group I followed by cyclic MTX and HDC, Group III: same as in Group I plus 2,400 cGy of cranial irradiation. CNS leukemia terminated complete remission in 25 of 153 patients (16.3%). The cumulative incidence of CNS leukemia at 4-year calculated by the Kaplan-Meier Method was 40.5% in Group I, 26.9% in Group II, and 14.5% in Group III. We concluded that the combination of cranial irradiation and intrathecal MTX and HDC was highly efficacious. The efficacy of high-dose MTX with CF rescue therapy for CNS-prophylaxis was evaluated in 62 children with ALL between 1978 and 1980 (protocol 787 study), and was demonstrated to be same as cranial irradiation in standard risk of ALL. In protocol 811 study (1981-1984), the dosage of cranial radiation has been reduced from 2,400 cGy to 1,800 cGy without loss of efficacy for CNS-prophylaxis. Although CNS-leukemia was no longer an unmanageable clinical problem, and the prospects for cure of ALL appeared good, there remained question as to the toxic effects of intensive treatment on the CNS. Successful prevention of these complications will depend in large part on an understanding of their causes.     

Radial flap: a valuable fasciocutaneous flap for intra-oral reconstruction

The radial forearm flap, or the forearm flap, is called "Chinese flap" for its development of the chinese doctors, and is originally designed for the correction to the post-burn contraction of the face and neck. The radial forearm flap is one of the fasciocutaneous flap, supplied by the radial artery, and transferred as a single-stage reconstruction micro-surgically. In oral and maxillofacial region, the deltopectral flap (D-P flap) and the pectralis major myocutaneous flap (P-M-M-C flap) are mainly used for the reconstruction. These flaps, however, are sometimes too bulky and limited to transfer, and more require two-stage operations. On the other hand, as the forearm flap being thin and pliable, some doctors use this flap micro-surgically at single-stage free flap reconstruction. Before two years, we have begun to transfer the radial forearm flap for the intra-oral reconstruction. The operation method is as follows. Design and Elevation of the Radial Forearm Flap 1. Using the ultrasonic doppler flow meter, the radial artery and the subcutaneous forearm veins are marked on the skin. 2. The flap is designed 20% larger according to the pattern to be reconstructed, with the distal section of the radial artery as an axis on the forearm and the median vein of forearm inclusively. 3. Before the operation, Allen test must be performed in order to determine whether the hand will survive without a radial arterial in-put. 4. The operation is performed with a arm tourniquet. The margin of the flap are incised down to the deep fascia, isolating and preserving the proximal subcutaneous veins as required.(ABSTRACT TRUNCATED AT 250 WORDS)     

Porcine TCR CD3zeta-chain and eta-chain

Complete porcine CD3ζ-chain cDNA sequence was obtained for the first time, and its genomic nucleotide sequence was investigated from exon 2 down to CD3η-chain exon 8. The sequence of porcine CD3ζ-chain showed homologous amino acid sequence with human and murine counterparts, in contrast to CD3η-chain exon 8 with diversity among animals previously investigated. CD3η-chain peptide is an alternative splice form of CD3ζ-chain exon 7 splicing to CD3η-chain exon 8 instead of CD3ζ-chain exon 8. The genomic sequences revealed that the splice acceptor sequences of CD3η-chain exon 8 of all animals investigated to be completely uniform. Further, CD3η-chain exon 8 amino acid sequences retained the unique characters of having high proline (Pro) and positively charged amino acid content except for rats and mice. Although the biological role of CD3η-chain remains to be enigmatic, these evidences suggests the evolutional pressure to maintain its sequence.     

Relationship between glucose transporter and changes in the absorptive system in small intestinal absorptive cells during the weaning process

In the present study, we investigated the changes in the localization of the glucose transporter GLUT2 and the fructose transporter GLUT5 in small intestinal absorptive cells during postnatal development, especially during the weaning period, using immunohistochemistry and confocal laser scanning microscopy. In the jejunum, GLUT2 was observed within the apical and basolateral membrane domain of absorptive cells, especially in the middle part of the villi. In the suckling rat ileum, GLUT2 was found within the apical and basolateral membrane domain of absorptive cells, but after 18 or 19 days after birth, GLUT2 was found mainly within the apical membrane domain. GLUT5 was observed within the apical membrane domain of absorptive cells in the suckling rat jejunum. In the 18- or 19-day-old rat jejunum, GLUT5 was localized within the apical and basolateral membrane domain of absorptive cells in the lower part of the villi, but after weaning, GLUT5 was found within the apical and basolateral membrane domain of absorptive cells throughout the entire villi. In the suckling rat ileum, there was little GLUT5 in the absorptive cells. In the 18- or 19-day-old rat ileum, GLUT5 was localized within the apical membrane domain of absorptive cells in the lower part of the villi, but after weaning, GLUT5 was observed mainly within the apical membrane domain of absorptive cells throughout the entire villi. These results suggest that the localization of glucose transporters corresponds with a shift from neonatal-suckling to weaned absorptive cells during postnatal development.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.     

GATA3 abnormalities and the phenotypic spectrum of HDR syndrome

We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.


Keywords: GATA3; HDR syndrome; phenotypic spectrum; mutation analysis     

A novel human B-lymphocyte antigen shared with lymphoid dendritic cells: characterization by monoclonal antibody.

A novel cell-surface antigen (L25) expressed on human B cells was identified using a B cell-reactive monoclonal antibody (TB1-4D5). This L25 antigen was expressed on most B-lineage cells but not other cell types including thymocytes, T cells, granulocytes and monocytes. Thus, L25 existed on the majority of normal B cells present in the blood and lymphoid tissues, on cultured cell lines derived from normal and malignant B cells, and on neoplastic cells isolated from patients with B cell-derived malignancies. Though L25 was persistently expressed on B cells until 7 days after their activation with pokeweed mitogen (PWM), neither normal nor neoplastic plasma cells expressed L25. Moreover, L25 was present on cultured as well as freshly isolated leukaemic cells with common acute lymphatic leukaemia (CALL) antigen, which have been thought to correspond to the early B-cell ontogeny. Besides pan-B cell reactivity of TB1-4D5 antibody, it apparently cross-reacted with so-called dendritic or interdigitating cells located in the thymic-dependent areas of peripheral lymphoid organs, which have been presumably ascribed to those associated with accessory-cell function. Functional studies showed that anti-L25 (TB1-4D5) antibody had inhibitory effect on induction of immunoglobulin synthesis by PWM-stimulated B cells.     

Inherited partial duplication of chromosome No. 15

A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented.