Endoscopic mucosal resection for early esophageal cancer and esophageal dysplasia.

BACKGROUND/AIMS: Advances in diagnostic technology have led to increased detection of early esophageal cancer, which is suitable for endoscopic treatment. We performed endoscopic esophageal mucosal resection of such cancer and dysplasia using the endoscopic esophageal mucosal resection tube and evaluated the clinical benefit of this technique. METHODOLOGY: Twenty-nine patients with esophageal mucosal cancer (27 cases with 33 lesions) or dysplasia (2 cases with 2 lesions) diagnosed between September 1992 and March 1998 were assessed endoscopically for the depth and extent of invasion by double staining with toluidine blue and iodine. Endoscopic ultrasonography was also performed to assess the depth of invasion in 22 cases with 22 lesions. RESULTS: The 35 esophageal lesions comprised 27 esophageal carcinomas and 8 areas of dysplasia. Twenty of the 35 lesions were resected en bloc and 15 were resected piecemeal. Subsequent surgery was performed for 5 cases with 7 lesions out of 10 cases with 15 lesions that were histopathologically diagnosed as m3 or more invasive. No recurrence has been detected in 24 evaluable cases (including 1 who died of another disease, 2 in whom surgery could not be performed due to complications, and 3 who refused subsequent surgery). No patients died of esophageal cancer after a mean follow-up period of 30.9 +/- 18.9 months. The 4-year survival rate was 100% in the m2 or less invasive group of 19 cases with 20 lesions, 75% in the m3 or higher invasive group of 5 cases with 8 lesions and 100% in the surgery group of 5 cases with 7 lesions (NS). No serious complications occurred except for 1 patient. Circumferential mucosal resection was done in this patient, resulting in esophageal stenosis, which responded to esophageal dilation. CONCLUSIONS: Esophageal mucosal resection using the endoscopic esophageal mucosal resection tube is safe and beneficial for early esophageal cancer and dysplasia.

Bleeding Meckel's diverticulum in an adult.

Bleeding Meckel's diverticulum tends to be a complication of ectopic gastric mucosa. It has been known that the gastric acid and digestive fluid produced from the ectopic gastric mucosa cause peptic ulcer, which leads to bleeding. When the ectopic gastric mucosa is entirely formed by the pyloric gland, however, ulcer formation may result from factors other than gastric acid and digestive fluid. This is a report of an adult case of bleeding Meckel's diverticulum with ectopic gastric mucosa in whom mechanical stimulation was suggested as a cause of the erosion and ulceration, resulting in bleeding.

[The examination of usefulness of the disposable pump in case of cancer pain relaxation and the economic problem].

Recently, an increasing number of cancer patients being taken care of at home has been able to use morphine to treat their pain by themselves. The most suitable administration method for individual patients-oral, intravenous, subcutaneous or depository--is being investigated. When oral intake becomes difficult, the subcutaneous via of administration is best option because it is the less dangerous and easier to use compared with the other two options. These are also thought to be less useful because it is difficult to judge the exact dosage. The use of pumps might be an economic problem to some patients. We will examine this problem.

Endoscopic injection sclerotherapy with ligation versus endoscopic injection sclerotherapy alone in the management of esophageal varices: a prospective randomized trial.

BACKGROUND/AIMS: Endoscopic injection sclerotherapy with ligation is a technique by which endoscopic injection sclerotherapy is first carried out for a target esophageal varix using an endoscope equipped with a device for endoscopic variceal ligation, and subsequently, endoscopic variceal ligation is performed for the varix together with the injection site of the sclerosing agent. The aim of this prospective, randomized trial was to compare endoscopic injection sclerotherapy with ligation with endoscopic injection sclerotherapy techniques in utility for patients with esophageal varices. METHODOLOGY: Twenty-four patients with esophageal varices who were to undergo either an elective treatment of bleeding esophageal varices or a prophylactic treatment of non-bleeding esophageal varices underwent endoscopic injection sclerotherapy with ligation (n = 12) or without ligation (n = 12). The patients were followed for a mean of 19.9 +/- 8.1 months in the endoscopic injection sclerotherapy with ligation (EISL) group and 19.5 +/- 5.4 months in the Endoscopic injection sclerotherapy (EIS) group. RESULTS: The red color sign disappeared in 10 patients in the EISL group and 3 in the EIS group (P = 0.004) after initial treatment. The length of time required for initial treatment was 16.3 +/- 4.7 min for the EISL group and 27.2 +/- 6.2 min for the EIS group (P = 0.0003). For treatment-related complications, no significant difference was noted between the 2 groups and no serious complication were noted in the 2 groups. The total quantity of ethanolamine oleate used to attain the endpoint was 17.3 +/- 7.9 mL for the EISL group and 25.2 +/- 9.7 mL for the EIS group (P < 0.05). The cumulative non-relapse rate for 2 years following attainment of the endpoint [F1, RC(-)] was 81.5% for the EISL group and 47.5% for the EIS group, producing no significant difference between the 2 groups. The cumulative non-bleeding and survival rates were 100% in the 2 groups. CONCLUSIONS: Endoscopic injection sclerotherapy with ligation is more useful for esophageal varices than endoscopic injection sclerotherapy alone.

Endoscopic management of gastric varices using a detachable snare and simultaneous endoscopic sclerotherapy and O-ring ligation.

BACKGROUND: Cyanoacrylate injection is highly effective and is regarded as the treatment of choice in bleeding gastric varices in Europe, but intravenous injection of cyanoacrylate is not allowed in the USA and Japan because it may cause embolisms in other organs. Accordingly, we developed a new endoscopic combined treatment of endoscopic management of gastric varices using a detachable snare (EVLs) and simultaneous endoscopic sclerotherapy and O-ring ligation (EISL) (i.e. EVLs + EISL), and we prospectively evaluated its efficacy and safety. METHODS: Gastric varices were ligated with the loop of a detachable snare that opened to a diameter of 4 cm (EVLs). Then the residual varices around the ligated portion were sclerosed by ethanolamine oleate and the injected vessel was ligated using a pneumo-activated EVL device (EISL). The EVLs + EISL was performed in 35 patients: on an emergency basis in eight patients, on an elective basis in six patients and as primary prophylaxis in 21 patients. Liver function was classified as Child-Pugh class A in 12 patients, class B in 12 patients and class C in 11 patients. RESULTS: Endoscopic disappearance of gastric varices was obtained in 97.1% of the patients and they regressed in all patients. Haemostasis was achieved in all eight emergency cases. The 2-year cumulative non-recurrence rate was 85%, the 2-year cumulative non-bleeding rate was 92% and the 2-year cumulative survival was 80%. No patients died of bleeding from gastric varices. There were no serious short-term complications, such as haemorrhage, gastro-oesophageal perforation, ileus, or renal impairment. CONCLUSION: Combined EVLs + EISL appears to be a useful treatment for gastric varices due to its safety and good clinical outcome.

Three-dimensional endoscopic ultrasonography of lesions of the upper gastrointestinal tract using a radial-linear switchable thin ultrasound probe.

BACKGROUND: The objective of three-dimensional (3-D) endoscopic ultrasonography (EUS) is to recognize lesions stereoscopically. METHODS AND RESULTS: We investigated a total of 43 lesions in the upper gastrointestinal (GI) tract by regenerating 3-D images in eight cases of oesophageal cancer, two cases of oesophageal submucosal tumour, two oesophageal varices, two cases of achalasia, 27 gastric cancers, one gastric carcinoid, and one duodenal submucosal tumour. Using a prototype system (Fujinon, Omiya, Japan), we reconstructed 3-D images from conventional EUS images taken by a thin ultrasound probe (Sonoprobe, SP-701, Fujinon) having a radial-linear scanning mode. The basic 3-D images could be obtained in a short period during EUS performed using the conventional thin-ultrasound probe. The acceptable quality level of the reconstructed 3-D images was 37% (57% in the oesophagus, 25% in the stomach and 100% in the duodenum). Deterioration of 3-D images was due to a wobbling of linear scanning mainly caused by peristalsis of the GI tract, cardiac impulses, and respiration. CONCLUSIONS: Our study has proved that the simple and speedy 3-D display system built using the existing linear-radial switchable probe is easily applicable to clinical cases.

Injection sclerotherapy for gastric varices using N-butyl-2-cyanoacrylate and ethanolamine oleate.

BACKGROUND/AIMS: Tissue adhesive agents, such as the cyanoacrylates, have been used as an alternative to conventional sclerotherapy to treat gastric varices, but the long-term efficacy of this approach has not been determined. We evaluated the efficacy and long-term outcome of injection sclerotherapy with n-butyl-2-cyanoacrylate and ethanolamine oleate in 16 patients with gastric varices. METHODOLOGY: We evaluated the effect of injection sclerotherapy in 16 Japanese patients with gastric varices. Injection sclerotherapy was performed on an emergency basis in 6 patients, an elective basis in 5 patients, and as prophylaxis in 5 patients. RESULTS: No bleeding was observed in the 7 patients in whom gastric varices disappeared during the 51 month follow-up period. The non-bleeding rate after treatment was significantly higher in this group than in the 9 patients in whom gastric varices did not disappear (p<0.05). Acute bleeding was stopped in 5 (83.3%) of 6 patients. The single failure was a patient in whom the sclerosant could not be injected into the gastric varices. No serious complications, such as emboli in other organs, were observed. CONCLUSION: The results suggest that this therapy is a safe and useful treatment for gastric varices and that the goal of injection sclerotherapy should be the disappearance of gastric varices.

Distribution of inducible nitric oxide synthase in ulcerative colitis.

OBJECTIVE: To investigate reports that the biosynthesis of nitric oxide (NO) is increased in the colonic mucosa of patients with active ulcerative colitis (UC), which suggests that serum NOx levels may be an important indicator of UC activity. METHODS: To determine the role of NO within the colon, we purchased polyclonal antibodies against human-inducible NO synthase (iNOS). We then examined the distribution of iNOS-reactive cells in UC colon tissues. RESULTS: In specimens from 12 UC patients, iNOS-positive neutrophils and macrophages were observed at the base of the ulcer but not in distant areas in the active stage. iNOS expression in colon mucosa was virtually absent during the inactive stage of UC and within the colon of patients with non-UC colitis. CONCLUSIONS: We conclude that NO in colonic mucosa may play a potential role in the pathogenesis of UC.

Therapeutic results of endoscopic variceal ligation for acute bleeding of oesophageal and gastric varices.

Endoscopic variceal ligation (EVL) using 'O' rings is widely accepted as a treatment of oesophageal varices that is at least as effective as endoscopic injection sclerotherapy but which produces fewer complications. Endoscopic variceal ligation using detachable snares has attracted attention as a safe and easy method of endoscopic treatment for gastric varices. Nineteen patients with acute bleeding from oesophageal or gastric varices were treated in the present study. Of these, 14 patients were treated with EVL using 'O' rings and five patients were treated with EVL using detachable snares and the treatment results were evaluated. Haemostasis was achieved in all patients. No serious complications of the procedures were observed. However, recurrences and rebleeding were observed in some patients during the maximum follow-up period of 24 months. Endoscopic variceal ligation using 'O' rings and detachable snares is useful for achieving haemostasis in cases of acute bleeding from oesophageal or gastric varices. However, additional endoscopic sclerotherapy may be needed to eliminate the variceal feeding vessels to further improve the long-term prognosis of these patients.

Efficacy of disinfectants against biofilm cells of Pseudomonas aeruginosa.

The effect of disinfectants on biofilm cells of Pseudomonas aeruginosa were evaluated. Biofilm cells of P. aeruginosa were eradicated by 0.4 to 0.5% chlorhexidine and 2% glutaral within 1 min, by 0.3% chlorhexidine, 0.5% benzalkonium chloride, 0.1% sodium hypochlorite, and 0.1% titratable I2 providone-iodine within 10 min, and by 0.2% chlorhexidine, 0.1% benzalkonium chloride, and 0.01% sodium hypochlorite within 30 min. However, 0.1% chlorhexidine and 0.1 to 0.5% alkyldiaminoethyl glycine were ineffective for eradication even after 1 h. Eradication of biofilm cells of P. aeruginosa by disinfectants required much longer time than that of planktonic cells in suspensions. The bactericidal effect of disinfectants against biofilm cells was found to be considerably enhanced by increasing the concentrations of the disinfectants.

[Spontaneous fracture and osteoporosis following renal transplantation].

The recovery of renal osteodystrophy can be achieved by renal transplantation but secondary bone changes appear after transplantation due to immunological reaction and immunosuppressive drugs. Very few cases of spontaneous fracture and osteoporosis have been documented among patients after renal transplantation. This was investigated from roentgenologic, histologic, biochemical, and immunological viewpoints in 180 transplant patients treated at Hyogo Prefectural Nishinomiya Hospital. The following conclusions were obtained. (1) Among 180 patients, spontaneous fractures occurred in 22%. (2) Pathogenesis of the fracture of transplant patient was found to be related to steroid induced osteoporosis and not to renal osteodystrophy. (3) There was no relation between spontaneous fracture and OKT4/OKT8 ratio.

Ultrastructural evidence for estradiol synthesis in the ovary of persistent-estrous rats exposed to continuous illumination.

The relation between sex hormone levels in blood and ultrastructural changes of ovarian follicles was examined in persistent-estrous rats exposed to continuous illumination (LL) for 100 days. Plasma LH showed a tonic level secretory pattern, and circulating estradiol and estrone concentrations were relatively high, while both levels of FSH and progesterone were low. Various stages of growing and degenerating follicles were observed in the ovary of the LL-exposed rats. The early stage of antral follicle did not seem to possess the ability of steroidogenesis. Theca cells around mature antral follicles contained prominent Golgi apparatuses, plenty of smooth endoplasmic reticulum (ER), abundant free ribosomes and many round-mitochondria. A few newly formed lipid droplets were seen in some of theca cells. Granulosa cells contained much distended rough ER, well-developed mitochondria, several lipid droplets and microfilaments. The theca cells of abnormal follicles with hyperplastic and infolded layers of granulosa cells contained many lipid droplets. However, the development of the smooth ER became hindered with increasing lipid droplets in the theca cell. On the other hand, granulosa cells of abnormal follicles contained greater numbers of lipid droplets than those of antral mature follicles, and were equipped with well-developed cytoplasmic organelles as were those of mature antral follicles. Theca interna cells of abnormal follicles may be more involved in the secretion of androgen, which has already been accumulated in the lipid droplets, than the cells involved in the active synthesis of the hormone, while the granulosa cells may convert its androgen to estrogen. The present findings suggest that both follicles of mature and abnormal types in the LL-exposed rat retain enough capacity of estradiol production and participate in the continued elevation of circulating estradiol, probably resulting in the stimulation of the theca cells by the tonic level of LH and of the granulosa cells by the levels of FSH, which are lower than the basal values during the normal 4-day estrous cycle.

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

Clearance of materials from breakdown of uterine collagen in mice during postpartum involution.

The collagen content of the mouse uterus increases during pregnancy and rapidly decreases to the level of nulliparous mice within a few days post partum. Most of the hydroxyproline in the uterine collagen had disappeared by day 3 post partum. During postpartum involution the hydroxyproline concentration in both the serum and blood clot was not higher than in nulliparous mice. The total hydroxyproline content in the liver, spleen and thymus was significantly increased during postpartum involution. These results indicate that materials derived from the breakdown of uterine collagen are rapidly removed from the blood stream by reticuloendothelial clearance.

Dissociation of estrous cycle and activity rhythm in rats.

When rats were kept in continuous light there was a time-lag between the onset of activity arrhythmia and that of persistent estrus. When animals showing both arrhythmias in continuous light were kept under a LD 21:3 photoperiod, the activity rhythm returned to normal but the estrous cycle did not.

Influence of pinealectomy on circadian patterns of plasma luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the male rat.

The effect of pinealectomy on the circadian periodicity in plasma gonadotropins (LH and FSH), testosterone (T) and dihydrotestosterone (DHT) was investigated in adult male rats maintained under conditions of 12 h light/12 h dark (light on 06:00-18:00 h). Animals were killed at 3 hour intervals over 24 hours by decapitation. Plasma concentrations of LH, T and DTH (but not FSH) were found to exhibit significant circadian variations as determined by analysis of variance. No distinct LH or T nadir was recorded but peaks were observed at 09:00 h. Peak DHT values were recorded near the middle of the dark period. Pinealectomy resulted in an altered daily LH and T rhythmicity, and also in an abolished DHT rhythmicity. The fact that there was no significant increase in mean gonadotropin levels at 50 days after pinealectomy suggests that the pineal regulates the timing of gonadotropin secretion rather than the quantity. Since pinealectomy was found to abolish the circadian rhythm of DHT but not of T, we deduced that the pineal may also be responsible for the rhythmic conversion of T to DHT.

Direct effect of melatonin on the accessory sexual organs in pinealectomized male rats kept in constant darkness.

Pinealectomized and sham-pinealectomized male rats were subcutaneously implanted with 2 cm silicone elastomer capsules filled with testosterone or dihydrotestosterone (DHT) and placed in constant darkness (DD) for 50 days. The data revealed that the sham-pinealectomized group treated with testosterone differed from the pinealectomized group, having lower weights of accessory sexual organs and levator ani muscle. Pinealectomy had no effect on organ and muscle weights of DHT-treated animals. Exposure of male rats to DD resulted in a marked decrease in weights of ventral prostate, seminal vesicle, coagulating gland and levator ani muscle and a decrease in plasma DHT levels. However there was no significant reduction in plasma LH, FSH or testosterone. Pinealectomy of the rats exposed to DD resulted in restoration of both DHT levels and accessory sex organ weights. Melatonin implants in pinealectomized males led to an increase in both testosterone and DHT levels, accompanied by a decrease in sexual organ weights. The data indicate that the anti-gonadal effect of the pineal gland cannot be completely mediated by melatonin and that melatonin and some unknown factors can act at the tissue level to reduce the size and function of the affected sexual organs.

Development of Harderian gland during metamorphosis in anurans.

Development of Harderian gland of larvae of Rana japonica, Bufo bufo japonicus, and Xenopus laevis was studied. In the adult animals, well-developed Harderian glands were invariably present in the orbit. In Rana and Bufo, the gland first appeared at late prometamorphic stage and in Xenopus it appeared around climax stage. In thyroidectomized tadpoles of Bufo and Rana, the Harderian gland was induced by thyroxine. In hypophysectomized tadpoles of Bufo the gland developed when they were treated with thyroxine or TSH.

Influences of some endocrine glands and of hormone replacement on the porphyrins of the Harderian glands of mice.

There are marked sex differences in the Harderian gland of the C3H/He strain of mice. Female (but not male) glands contain large amounts of porphyrin, which are readily visible as solid depositions within the lumina. The histology and porphyrin content of the Harderian gland were examined in intact and in pregnant mice and in mice subjected to combinations of adrenalectomy, gonadectomy and administration of sex steroid hormones. In male mice, castration approximately doubled the amount of porphyrin in the Harderian gland. Castration plus adrenalectomy increased the levels over 30-fold, to levels similar to those found in female mice, although adrenalectomy alone produced no significant effect. Administration of testosterone to the male mice which had been castrated and adrenalectomized prevented the increases while progesterone treatment produced further increases in porphyrins. In intact females, the amount of porphyrin varied with the phase of the oestrous cycle; being lowest during metoestrus and highest during dioestrus. In ovariectomized-adrenalectomized females, the effects of administered sex hormones on the amount of porphyrin in the gland were the same as in males. In pregnant mice, the level was no significantly different from that in intact oestrous animals.