[A case of lung metastasis from colon cancer treated successfully with combined chemotherapy of CPT-11 and 5'-DFUR].

The patient was a 52-year-old woman who had sigmoid colon cancer with liver metastasis and multiple lung metastases. Resection of curability B was performed, and alternating adjuvant chemotherapy consisting of hepatic artery injection of 5-FU and systemic administration of CPT-11 was performed. Lung recurrence was found and no antitumor effect of chemotherapy was observed, so the CPT-11 which had been administered every other week was given every week in a dose of 60 mg/body, half of the original dose. Moreover, 5'-DFUR was administered in a dose of 800 mg/day every day. As a result, lung metastasis tumors were reduced markedly. Adverse events such as nausea, vomiting and depilation were mitigated, and no other toxicity was observed. The patient could thus be treated extremely safely in the outpatient clinic. This was considered to be a valuable case suggestive of the significance of combination chemotherapy of CPT-11 and 5'-DFUR and the importance of appropriate administration of CPT-11.

Circular stapling procedure for mucosal prolapse of the rectum associated with outlet obstruction.

The aim of this study was designed to investigate the outcome from using the new circular stapling device in the surgical treatment for mucosal prolapse of the rectum associated with outlet obstruction. The treatment consisted of resection of the mucosal prolapse through a transverse incision and resecting a suitable part of the mucosa between the rectum and the anal canal, using an HCS33 circular stapler. Eleven patients successfully underwent this operation without morbidity or mortality, and were assessed clinically and by rectoanal manometry and defecography pre- and post-operation. The mean operating time was 39 (range 22-49) min. The postoperative proctalgia and complications were mild, and the patients were discharged at 4 days after the operation. The pre-operative constipation was improved, and the patient's satisfaction was increased at one month after operation in comparison with the preoperative level. Rectoanal function test at 6 months after the operation demonstrated normalization of the maximum resting and squeezing pressures of the anal canal and rectal compliance to the normal levels. No patient has had recurrence of symptoms during the follow-up period. Our data suggest that this procedure may be a useful surgical treatment, as it causes little postoperative complication and enables early discharge of the patients. However, long-term outcomes of recurrence, continence, and constipation need to be evaluated in a more extended follow-up.

Adult colonic intussusception: a case report.

Intussusception accounts for almost all cases of intestinal obstruction in children. In contrast, intussusception in adults is relatively rare. An 86-year-old Japanese female with rectal bleeding came to our hospital via ambulance. At first, colonoscopy findings revealed the sigmoid colon cancer. Ultrasonography showed a hypoechoic mass with a multiple concentric ring sign. Computed tomography showed a round fluid-filled cystic structure. Colon contrast studies demonstrated stenosis in the rectosigmoid colon. A laparotomy was performed. The sigmoid colon was intussuscepted to the rectosigmoid colon. We employed both rectosigmoid and sigmoid colon resection. The resected specimen showed that the disease was advanced sigmoid colon cancer with ulcer formation due to an ischemic change. Tumor was 4.5 cm x 2.0 cm in size. The disease was histopathologically diagnosed as advanced sigmoid colon cancer, well-differentiated adenocarcinoma. We report here a case of adult intussusception due to the sigmoid colon cancer.

[Relationship between the anti-metastatic effect of UFT and in vitro chemosensitivity to 5-FU in metastatic tumors from orthotopic implanted colon cancer in nude rats].

We have investigated the correlation between the in vitro chemosensitivity to 5-FU, measured using the collagen gel droplet embedded culture drug sensitivity test (CD-DST), and the anti-tumor effect of UFT, a prodrug of 5-FU, in metastatic tumors from orthotopic implanted colon cancer in nude rats. Human colon cancer cells (KM12SM) were injected into the cecal wall of the nude rats. Five weeks later, the implanted cecal tumors were removed. Oral UFT (a daily dose of 30 mg/kg) was administered postoperatively for four weeks. After the UFT administration period, the lung and lymph nodes were analyzed macroscopically and microscopically. In vitro chemosensitivity to 5-FU in the lung and lymph node metastases was tested using CD-DST, and the enzymatic activities of thymidine synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in the lung and lymph node metastases were measured. A daily administration of UFT produced an inhibitory effect on lung metastasis compared with the control group. However, there was no difference in the frequency of lymph node metastasis. The inhibition rate produced by 5-FU in CD-DST was significantly higher for lung metastases than for lymph node metastases. There was no difference in the TS and DPD activities between the metastatic tumoral tissues. These results suggest that the organ specificity of the anti-tumor effects of UFT on colon metastases may be determined by CD-DST of 5-FU for individual tumors. The TS and DPD activity in the tumoral tissues may not affect the organ specificity of the anti-tumor effect of UFT on colon metastases.

Total mesorectal excision, lateral lymphadenectomy and autonomic nerve preservation for lower rectal cancer: significance in the long-term follow-up study.

We clarify the significance of total mesorectal excision (TME), lateral lymphadenectomy (LLA), and of autonomic nerve preservation (ANP) compared to conventional surgery (CVS), for lower rectal cancer. All 458 patients curatively resected between 1962 and 1997 were retrospectively investigated. In Period I from 1962-1974, when CVS only was performed, in Period II from 1975-1984, TME or TME + LLA was performed, and in Period III from 1985-1997, TME + ANP, TME + ANP + LLA, or TME + LLA was performed. In Dukes A + B disease, there was no significant difference among the three periods, regardless of operation methods. In Dukes C disease, in Period I, CVS (42 patients: pts) had a local recurrence (LR) rate of 45.2% and 5-year disease-free survival (5YDFS) rate of 33.3%. In Period II, TME + LLA (82 pts) had a lower LR rate of 26.8% (p = 0.0628) and higher 5YDFS 51.0% (p < 0.05) vs CVS. In Period III, TME + ANP (12 pts) had LR 25.0% and 5YDFS 55.6%, TME + ANP + LLA (45 pts) had LR 13.3% (p < 0.005, vs CVS) and 5YDFS 56.1% (p < 0.01, vs CVS), and TME + LLA (18 pts) had LR 16.7% (p < 0.05, vs CVS) and 5YDFS 20.8%. Also, CVS had the lowest curability rate 64.8% and the highest mortality rate 7.2%. TME and/or LLA was significant for reducing LR and improving survival in patients with Dukes C lower rectal cancer, compared to CVS. ANP was beneficial with LLA. TME + ANP was suitable for Dukes A or B disease.

Growth hormone directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats.

Growth hormone (GH) is known to interact with adipose tissue and to induce lipolysis. Adipocytes produce leptin which regulates appetite and energy expenditure. In order to elucidate the role of GH in leptin production, we studied the effect of GH on leptin gene expression and body fat in fatty Zucker rats, a model of obesity with resistance to both leptin and insulin. Recombinant human GH administered subcutaneously at 0.5 mg/kg per day (low dose) as well as at 1.65 mg/kg per day (high dose) reduced leptin mRNA levels in epididymal fat tissue but not in subcutaneous fat tissue after 7 days. GH administration only at the high dose reduced percentage body fat. Insulin-like growth factor-I infusion (200 microg/kg per day) did not change percentage body fat or leptin mRNA levels in epididymal fat. These observations suggest that GH directly interacts with adipose tissue and reduces leptin gene expression in visceral fat tissue.

Oncostatin M: a new potent inhibitor of iodine metabolism inhibits thyroid peroxidase gene expression but not DNA synthesis in porcine thyroid cells in culture.

The functions of thyroid cells are regulated by a number of cytokines and growth factors in addition to TSH. Recent studies have revealed that several cytokines including interleukin (IL)-6 are involved in thyroid dysfunction. Oncostatin M (OSM) is a glycoprotein belonging to the same family of cytokines as IL-6, to which it is related by sequence and structural homology and the use of the signal-transducing receptor component gp130. We, therefore, studied the effect of OSM on iodide uptake and DNA synthesis by porcine thyroid cells in culture. OSM increased c-fos and c-jun mRNA levels but did not stimulate DNA synthesis. OSM inhibited iodide uptake stimulated by TSH; while IL-6 also inhibited iodide uptake, it was only about one-tenth as potent. IL-6 had about the same potency as OSM when it was added with soluble IL-6 receptor. OSM had no effect on cAMP production but inhibited iodide uptake stimulated by 8-bromo-cAMP and forskolin. These findings suggest that OSM exerts its inhibitory effects at the post-cAMP production step(s). OSM also inhibited thyroid peroxidase mRNA levels but had little effect on thyroglobulin mRNA levels. Investigations of the signal transduction system showed that gp130 and leukemia inhibitory factor (LIF) receptor beta subunit mRNA were detectable in porcine thyroid cells by reverse transcription (RT)-polymerase chain reaction (PCR). Together with the report that serum OSM and IL-6 concentrations are elevated to the same levels in patients with sepsis, these results suggest that OSM may contribute to the thyroid dysfunction in this condition.

[Successful neoadjuvant chemotherapy in a patient with advanced gastric cancer with periaortic lymph node metastasis].

We described a case of advanced gastric cancer accompanied by metastasis to the periaortic lymph node. Two cycles of the neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. 5-FU (800mg/body/day) was administered as a continuous intravenous infusion for five days, and CDDP (10mg/body/day) was given as an intravenous infusion for an hour on days 1-5. The FP therapy resulted in a significant effect in the metastatic periaortic lymph node. Then, total gastrectomy with combined resection of spleen was done. Histological examination of the resected specimen revealed the histological effect showing Grade 3 in the primary site and Grade 2 in the periaortic lymph node. The patient is alive with no evidence of recurrence 13 months after operation. Thus, FP therapy is thought to be effective against advanced gastric cancer.

Effects of transforming growth factor alpha (TGF-alpha) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells.

Transforming growth factor alpha (TGF-alpha) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-alpha has similar effects using porcine thyroid cells in culture. Recombinant human TGF-alpha dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-alpha is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-alpha, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-alpha again was approximately 50% that of EGF. Transforming growth factor alpha did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-alpha. Thus, we conclude that TGF-alpha inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-alpha mRNA in porcine thyroid cells. These observations suggest that TGF-alpha acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells.

Interaction of endothelin-1 with porcine thyroid cells in culture: a possible autocrine factor regulating iodine metabolism.

Although endothelins were originally discovered as peptides with vasoconstrictor activity, recent studies have indicated a number of endothelin (ET)-induced hormonal functions in various tissues. We have studied the interaction of endothelins with porcine thyroid cells in culture. Specific binding of 125I-labelled ET-1 was demonstrated in porcine thyroid cells. The binding was displaced equally by unlabelled ET-1 and ET-2, but receptor affinity for ET-3 was lower than that for ET-1 and -2. Scatchard analysis of the data revealed a single class of high-affinity ET-1 receptors with a Kd of 0.45 nmol/l and a binding capacity of 2100 sites/cell. SDS-PAGE and autoradiography of 125I-labelled ET-1 cross-linked with thyroid cell membranes demonstrated ET-1 binding sites with an apparent molecular weight of 50 kDa. These results indicated that ET-1 receptors in thyroid cells are type A ET receptors. In association with the presence of ET-1 receptors, porcine thyroid cells responded to ET-1 and ET-2 with an increase in c-fos mRNA expression. Although ET-1 did not affect DNA synthesis stimulated by either EGF or IGF-I, it dose-dependently inhibited TSH-induced iodide uptake and also inhibited iodide uptake stimulated by forskolin and 8-bromo-cAMP. ET-1 had no effect on TSH-stimulated cAMP production. Thus, ET-1 inhibited TSH-induced iodine metabolism by acting at the steps distal to cAMP production. In agreement with a recent report, immunoreactive ET-1 was detected in medium conditioned by porcine thyroid cells. Antibody to ET-1 was found to increase TSH-induced iodide uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-dimensional control of optical spatial coherence by acoustooptic interactions.

A method is described for 2-D control of spatial coherence by use of multiple, crossing ultrasonic waves. If all the ultrasonic waves differ in frequency from one another, the coherence modification factor results as a product of the individual modification factor formed by each ultrasonic wave itself. Two arrangements are discussed in detail together with experimental results: one with the ultrasonic waves propagating in orthogonal directions, the other with the waves propagating in three symmetric directions. The coherence modification factor obtained from either arrangement varies periodically in space but is almost uniform in the azimuthal direction if the two-point separation concerned is taken in a linear dimension a little larger than half of one ultrasonic wavelength.