Biomedical subjects
Publications and source records attributed to K J Chang.
Linear array endosonography, with its capacity to perform EUS-guided FNA and EUS-guided injections, as well as color mapping and Doppler ultrasonography, is becoming an important instrument for the endosonographer. Familiarity with linear array anatomy, as introduced here, is the critical foundation on which these diagnostic and therapeutic procedures can be performed safely and effectively.
To evaluate the prognosis of patients with gastric stump cancer after previous distal gastrectomy for benign gastroduodenal disease, we compared 25 patients with resected gastric remnant cancer with 143 patients with primary cancer in the upper third of the stomach. The histopathological differences between gastric remnant cancer and primary cancer were not significant, except for esophageal invasion. The percentage of esophageal invasion in gastric remnant cancer is 16%, significantly lower than 56.6% in primary cancer. The overall 5-year survival rates were 46% and 25% for patients with resected remnant cancer (n = 25) and resected primary cancer (n = 143), respectively, and there was no statistical difference between the two groups. The 5-year survival rates for gastric remnant cancer with stage I or II and primary cancer with the same stages were 89% (n = 11) and 39% (n = 50), a statistically significant (p < 0.02) difference. On contrast, the 5-year survival rate for gastric remnant cancer with stage III or IV was 0%, which was significantly worse than 17% for primary cancer with the same stages (p < 0.05). The prognosis of gastric remnant cancer is better than that of primary cancer in the upper third of the stomach at its early stages, but it is worse at its late stages. An aggressive resection is recommended for gastric stump cancer.
The mitogen-activated protein (MAP) kinase of Chinese hamster ovary cells (CHO mu66 cell line) transfected to express mu-opioid receptors was markedly activated by mu agonists. The rank order of effectiveness of agonists was approximately the same as the rank order of their binding affinities to the mu receptor. The delta and kappa receptor-specific agonists cyclic[D-Pen2, D-Pen5]enkephalin and U69,593 showed a very weak stimulatory effect. The mu agonist-stimulated MAP kinase activity peaked at approximately 4-8 min and lasted almost 1 hr. The stimulatory effect of mu agonists was antagonized by the opioid receptor antagonist naltrexone and inhibited by pretreatment of cells with pertussis toxin. This opioid-induced activation of MAP kinase activity may have a role in the long term effects of opioids.
During the past 40 years (1951-1990), 7,663 patients with peptic ulcer disease underwent surgical treatment at the National Taiwan University Hospital. A great change in patient characteristics and operative procedures was noted between the last 10 years and the previous three decades. There were 7,105 patients (92.7%) between 1951 and 1980, an average of 237 patients per year. However, only 558 patients received surgery in the last 10 years, an average of 56 patients per year. The proportion of female patients increased from 9.5% in the earlier period to 20.4% in the last 10 years; the average age of patients also increased. In the earlier period, the indications for surgery were hemorrhage (38.4%), perforation (36.1%), intractable pain (16.4%) and stenosis (9.1%). Perforation (89.2%) was the most common indication for surgical treatment in the last 10 years. Hemorrhage (4.9%), pain (4.1%) and stenosis (1.8%) were less common. There was no significant difference in surgical morbidity between the two periods. Primary subtotal gastrectomy (SG) accounted for 75.4% of operations in the earlier period, but vagotomy became the main treatment in the last 10 years, including highly selective vagotomy (HSV) (31.9%), and truncal vagotomy with drainage procedure (TV + D) (31.0%). The surgical mortality in the earlier period was 1.3% for SG, 1.8% for TV + D and 16.1% for simple closure. There was no significant change in ulcer location between the two periods. The overall mortality rate was higher in the last 10 years (5.2%) than in the earlier 30 years (2.7%) (p < 0.001). In follow-up studies, the satisfactory rate after operation was similar among patients receiving SG (89.8%), HSV (90.3%) and TV + D (91.1%) between 1977 and 1990.
To compare the efficacy of the biofragmentable anastomotic ring (Valtrac-BAR, Davis and Geck, Medical Device Division, Danbury, CT, USA) with conventional anastomotic techniques, 30 patients who underwent colorectal surgery from August 1993 to March 1995 were retrospectively studied. The use of the BAR was also compared with conventional techniques including hand-sewn sutures in 30 patients and an end-to-end anastomosis (EEA) stapler in 24 patients. There were 17 men and 13 women in the BAR group with ages ranging from 37 to 80 years, 18 men and 12 women in the hand-sewn group with ages ranging from 41 to 82 years and 14 men and 10 women in the EEA group with ages ranging from 38 to 72 years. Surgical indications included: 25 colon cancers and five rectal cancers in the BAR group; 27 colon cancers and three rectal cancers in the hand-sewn group; and six colon cancers and 18 rectal cancers in the EEA group. There was no conversion to other anastomotic methods. Most of the patients tolerated a low-residual diet from the fifth post-operative day. No clinical leakage or stricture was noted. Only seven patients were aware of the passage of BAR fragments. The mean hospital stay was 14.1 days. There were no significant differences among these techniques in the return of bowel function, the incidence of surgical complications, including anastomotic leakage, or the length of hospitalization. BAR anastomosis was more time efficient than conventional techniques. Our results confirmed that BAR was an ideal sutureless alternative for anastomosis in colorectal surgery.
Our laboratory has previously shown that intracerebroventricular (i.c.v.) administration of beta-endorphin suppresses brain and liver ornithine decarboxylase activity (ODC; a growth regulatory enzyme) in preweanling rats. This investigation examined, in 6-day-old rats, the relative participation of brain mu-, delta- and epsilon-opioid receptors in beta-endorphin's ODC effects, by comparing tissue ODC responses to beta-endorphin given alone i.c.v. and in the presence of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-opioid receptor antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; delta-opioid receptor antagonist) or beta-endorphin-(1-27) (epsilon-opioid receptor antagonist). Administration of 0.5 microgram of beta-endorphin alone significantly decreased brain and liver ODC activity 4 h after injection, and the effect was completely blocked by coinjection of CTOP (0.075 micrograms) but not by ICI-174,864 (0.75 or 3.75 micrograms) or beta-endorphin-(1-27) (3.75 or 7.5 micrograms). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 microgram) or ICI-174,864 alone was accompanied by increased levels of basal ODC activity. The results obtained demonstrate that i.c.v. beta-endorphin downregulates ODC expression in central as well as in peripheral tissues by interacting with brain mu-opioid receptors, but not with delta- or epsilon-opioid receptors or mu/delta-opioid receptor complexes. Also, they indicate that endogenous opioid systems have a tonic inhibitory influence on ODC activity which is mediated, at least in part, by mu- and delta-opioid receptors.
The binding properties and pharmacological activities of H-Tyr(3'-I)-Tic-Phe-Phe-OH ([Tyr(3'-I)1]TIPP) were studied. Similar to the delta-opioid receptor antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3'-I)1]TIPP is a selective and potent ligand at delta-opioid receptors. The displacement curve of [3H]diprenorphine binding by [Tyr(3'-I)1]TIPP was shifted to the right in the presence of Na+ and 5'-guanylylimidodiphosphate, suggesting that it acted as a delta-opioid receptor agonist. [Tyr(3'-I)1]TIPP also behaved as a full agonist in the mouse vas deferens assay and its effect was both naloxone- and TIPP-reversible. These data show that monoiodination at the 3'-position of the N-terminal tyrosine aromatic ring of TIPP converted it from a potent and selective antagonist to a full agonist at delta-opioid receptors.
The synthetic delta-opioid receptor agonist BW373U86 (0.18-0.56 mg/kg s.c.) was studied in rhesus monkeys with a warm-water, tail-withdrawal assay, designed to detect bradykinin (0.1 microgram) and prostaglandin E2 (5-15.8 micrograms)-induced thermal allodynia. BW373U86 dose-dependently reversed bradykinin allodynia, but was ineffective against prostaglandin E2 allodynia. The BW373U86 dose-effect curve was shifted to the right by the delta-opioid receptor-selective antagonist naltrindole (1.0 mg/kg) but not by the mu-opioid receptor-selective antagonist quadazocine (0.1 mg/kg). The present findings add to the conditions in which delta-opioid receptor-mediated behavioral effects have been detected in primates, and suggest that delta-opioid agonists may be of therapeutic interest in the treatment of some types of hyperalgesic conditions.
The preoperative seropositivity of Helicobacter pylori was determined in 128 patients who had undergone gastrectomy for primary gastric adenocarcinoma during the past 5 years. The overall seroprevalence of H. pylori was 64 per cent. Gastric cancers positive for H. pylori were associated with tumours located in the lower third of the stomach which were of localized type (Borrmann I and II) (P < 0.05), but not with age, sex, blood type, tumour size, invasion depth, lymph node metastases, histological type, DNA ploidy or type of surgery. The cumulative 5-year survival curves after surgical resection were significantly better in patients who were positive for H. pylori. Multivariate analysis revealed that seropositivity for H. pylori was not an independent prognostic factor. Pathological tumour node metastasis staging was the only prognostic indicator. Better prognosis for those with H. pylori-seropositive gastric cancer may be attributed to the more advanced stage of H. pylori-seronegative gastric cancers. The potential role of H. pylori in gastric cancer carcinogenesis and its biological significance warrant further investigation.
Experiments were carried out at different times of hibernation to ascertain whether prostaglandin is produced by Rana ovarian follicles during gonadotropin- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced in vitro ovulation. Ovarian fragments were cultured in amphibian Ringer in the presence or absence of frog pituitary homogenate (FPH, 0.05 gland/ml) or TPA (1 or 10 microM). After various periods of culture, incidence of ovulation was determined and prostaglandin F2 alpha (PGF2 alpha) accumulated in culture medium was measured by radioimmunoassay. FPH and TPA increased PGF2 alpha levels in medium in a dose-dependent manner. The time course of PGF2 alpha secretion and ovulation by FPH or TPA treatment varied during the hibernation period. In early-hibernation, FPH stimulated neither PGF2 alpha secretion nor ovulation while TPA stimulated PGF2 alpha secretion, although it failed to induce ovulation. In mid-hibernation, FPH and TPA effectively stimulated PGF2 alpha secretion and ovulation, but both events took place several hours later than those observed in late-hibernation. Some fragments obtained in mid-hibernation and most obtained in late-hibernation spontaneously produced PGF2 alpha in vitro without FPH or TPA treatment and in some instances spontaneously ovulated. Furthermore, FPH or TPA increased PGF2 alpha levels further or accelerated the time course of secretion by such fragments. In late-hibernation, PGF2 alpha secretion induced with FPH or TPA increased simultaneously with or later than onset of ovulation. Exogenous cAMP (2.5 mM) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 100 microM), a PKC inactivator, markedly suppressed FPH- or TPA-stimulated PGF2 alpha secretion and ovulation in mid-hibernation. Indomethacin (IM, 5 micrograms/ml) strongly suppressed TPA- or FPH-stimulated PGF2 alpha production by fragments but its effect on ovulation varied among animals and at different times. IM suppressed ovulation of some ovarian fragments obtained in mid-hibernation, but failed to suppress hormone-induced ovulation in late-hibernation. Cycloheximide (5 micrograms/ml) and actinomycin D (1 microgram/ml) effectively suppressed FPH-stimulated PGF2 alpha production and ovulation, whereas actinomycin D reduced but failed to significantly suppress TPA-induced PGF2 alpha production in mid-hibernation. In general, effects of ovulation inhibitors exhibited strong seasonal variations and were less efficient as the breeding season approached. Taken together, the data suggest that elevated levels of PGF2 alpha are associated with spontaneous and hormone-induced ovulation, and PKC mediates gonadotropin induction of PGF2 alpha but not steroid synthesis in Rana ovaries.
Splenic abscess, with its rare incidence and various misleading clinical manifestations, usually is a diagnostic pitfall in the modern emergency department. The most frequently seen symptoms and signs are fever, abdominal pain and tenderness over left upper quadrant, splenomegaly, leucocytosis, and left lower chest abnormalities. Four cases were collected during the past five years. On admission, one patient manifested symptoms mimicking a perforated peptic ulcer and the other three patients presented clinical and roentgenographic signs suggestive, but non-specific, for splenic abscess. In two cases, the diagnosis was based on sonography followed by computed tomography (CT). In one case, the splenic abscess was only visualized by CT. They all survived after splenectomy and appropriate antibiotic therapy. Culturing disclosed the offending organisms to be Escherichia coli, Pseudomonas aeruginosa, a Salmonella species, and Streptococcus viridans. These nonspecific clinical pictures should be thoroughly investigated, and CT, the most sensitive diagnostic tool, should be used whenever splenic abscess is suspected. Early diagnosis and timely treatment reduce the morbidity and mortality associated with splenic abscess.
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Our institute serves as a centralized clinical laboratory for municipal and private hospitals in Taipei, a major international metropolis in the Asian region. Two key considerations leading to the development of our toxicology program are: a large number of foreign visitors and local residents returning from overseas trips may bring in chemicals which are less commonly seen in this region; and the lack of readily available assays for a large percentage of commonly used medicines, including prescription and over-the-counter drugs. Our toxicology screening program addresses the needs of both the Emergency Department Drug Screening and Drug of Abuse Screening. In Emergency Department Drug Screening, REMEDi HS is used as the general screening method. In Drug of Abuse Screening, the TDx is used for the initial screening of amphetamine-like substances and opiates, followed by REMEDi HS for the confirmation of positive samples. Emergency Department data collected at our institute over one year (September 1992 to August 1993) identified 57 different drugs in 713 samples. Opiates, narcotics and central stimulants accounted for 24% of the encountered drugs. Presently, there is no extensive reporting of misuse of benzodiazepines in this region. The detection of herbal ingredients like ephedrine and methylephedrine (from the Ma-Huang plant) in patient samples illustrates a large area often overlooked by western toxicology.
New vessel formation (angiogenesis) plays an important role in the metastasis of cancer cells. To investigate the correlation between tumor angiogenesis and metastatic potential in breast cancer, the microvessel counts of tumor specimens from 81 women with primary infiltrating ductal carcinomas were examined. Histologic parameters (nodal status, tumor size and tumor grade) and hormone receptor status were also analyzed. We found that axillary node metastasis correlated significantly with the microvessel counts per 200x field and with tumor size, but not with age, tumor grade or hormone receptor status. Tumors without axillary node involvement had a lower microvessel count, irrespective of age, tumor size, tumor grade or hormone receptor status. Logistic regression demonstrated that the microvessel count provided the most important estimate of the relative risk of metastasis. These results suggest that, in invasive breast carcinoma, angiogenesis is closely related to metastatic potential.
In this retrospective study, 652 patients who had curative resections for gastric cancer from 1977 to 1991 were reviewed to evaluate improvements in gastric cancer surgery and the influence of the extent of lymphadenectomy on survival. The patients were grouped into three time periods: 1977 to 1981, 1982 to 1986 and 1987 to 1991. The percentage of patients with early gastric cancer increased from 17.7% during 1977 to 1981, to 24.3% during 1987 to 1991. The average number of dissected lymph nodes was 7.5 +/- 8.1 during 1977 to 1981 and 16.4 +/- 10.3 during 1987 to 1991, when more radical lymphadenectomy was adopted. Total gastrectomies increased from 10.9% to 25.9% in the same time periods while combined visceral resections increased from 26.7% to 38.1%. Operative mortality decreased from 5.0% to 1.7%. The overall 5-year survival rate increased from 34.8% to 59.4%. In subgroup analysis, significant improvement of the 5-year survival rate was noted in the following groups: patients with stage I, II and III tumors but not stage IV; both proximal and distally located tumors; tumors with or without lymph node metastases; T1 and T2 but not in T3 and T4 (cancer invasion beyond the serosa). The decreased surgical mortality in recent years suggests that curative resection with extensive lymph node dissection can now be safely performed. Radical gastrectomy with extended lymphadenectomy may be adopted in gastric cancer resection for better control of regional disease.
The clinical and pathologic features of 34 phyllodes tumors in 33 women were analyzed. These included 20 benign tumors, 7 borderline malignant tumors and 7 malignant tumors. The median age of the patients at the time of diagnosis was 38 years. Patients with malignant tumors were older and had larger tumors. The tumor size varied from 1.6 cm to 40 cm. Local recurrence was evident in 4 of 21 patients who were followed-up, irrespective of their tumor type (one benign, two borderline malignant and one malignant). The recurrence rate was higher in younger patients. No single pathologic feature was found to have prognostic significance. Distant or regional lymph node metastasis and mortality due to the disease were not identified. Based on these results, wide excision with an adequate margin continues to be the appropriate initial surgical treatment.
Endoscopic ultrasound (EUS) has been established as an important modality for staging gastrointestinal malignancies. We have previously described the new technique of EUS-guided fine needle aspiration (FNA) in diagnosing submucosal and extraluminal tumors and lymph nodes. We now report the novel application of EUS and EUS-guided FNA in diagnosing malignant ascites and malignant pleural effusion in two patients with gastric carcinoma. In the first patient, CT did not detect any effusion or ascites. EUS-guided FNA diagnosed cytologically that both fluids were malignant, thereby precluding surgery. The second patient had a small pleural effusion on CT that was not detected on the chest x-ray. EUS-guided FNA made the cytological diagnosis of recurrent adenocarcinoma in the pleural fluid. These two cases demonstrate for the first time that EUS combined with EUS-guided FNA can be used for the diagnosis of malignant pleural or ascitic fluid in patients with gastrointestinal malignancies and might further extend the staging capabilities of EUS.