Clinical study of primary carcinoma of the fallopian tube: experience with 14 cases

Between 1950 and 1986, 14 cases of primary carcinoma of the fallopian tube were treated and diagnosed at the Cancer Institute Hospital. These cases constituted 0.13% of the total number of gynecologic malignancies at the hospital during the period. The clinical/pathological findings and prognoses were described. Of the 14 cases, the average age was 56.0 years. The most frequent symptom was atypical genital bleeding, seen in 11 cases (79%). Massive watery discharge was seen in four cases (29%). In preoperative cytologic examination of vaginal smears, six cases (43%) were positive for cancer. All cases underwent operation as therapy. Postoperative irradiation, adjuvant chemotherapy, and/or second-or third- look operation was also used. Histopathologically, all materials were found to be adenocarcinoma. Four cases were well differentiated, seven were moderately differentiated, and three were poorly differentiated. Two patients with stage III and IV cancers died of the disease. Nine patients were still alive at the end of this study. The five-year survival rate was 57% (4/7). In stage I cancers, the five-year survival rate was 80% (4/5). The prognosis of stage I cancer patients was estimated as rather good.     

Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.     

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)     

Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease

Collapsin response mediating protein-2 (CRMP2) has been identified as an intracellular protein mediating Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling. In In vitro kinase assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3beta did not induce any phosphorylation of CRMP2. Phosphorylation by GSK3beta was exclusively observed in Cdk5-phosphorylated CRMP2, but barely in CRMP2T509A. These results indicate that Cdk5 primarily phosphorylates CRMP2 at Ser522 and GSK3beta secondarily phosphorylates at Thr509. The dual-phosphorylated CRMP2, but not non-phosphorylated or single-phosphorylated CRMP2, is recognized with the antibody 3F4, which is highly reactive with the neurofibrillary tangles of Alzheimer's disease. 3F4 recognized the CRMP2 in the wild-type but not cdk5-/- mouse embryonic brain lysates. The phosphorylation of CRMP2 at Ser522 caused reduction of its affinity to tubulin. In dorsal root ganglion neurones, Sema3A stimulation enhanced the levels of the phosphorylated form of CRMP2 detected by 3F4. Over-expression of CRMP2 mutant substituting either Ser522 or Thr509 to Ala attenuates Sema3A-induced growth cone collapse response. These results suggest that the sequential phosphorylation of CRMP is an important process of Sema3A signalling and the same mechanism may have some relevance to the pathological aggregation of the microtubule-associated proteins.     

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.     

Metal ions induce bone-resorbing cytokine production through the redox pathway in synoviocytes and bone marrow macrophages

To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl(2), CoCl(2), CrCl(3) or Fe(2)(SO(4))(3) at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor kappaB (NF-kappaB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (*OH), which accounts for PDTC-blockade of metal ion-induced NF-kappaB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.     

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.