Gastric cancer in Connecticut: outlook for improved survival.
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Biomedical subjects
Publications and source records attributed to W E Longo.
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Early gastric cancer (EGC) is characterized by tumor invasion limited to the submucosa, with or without regional lymph node involvement, and five-year survival rates in excess of 90%. Although infrequently reported in the United States, EGC represents 35% of gastric cancers in Japan. A retrospective analysis of all patients with gastric cancer (1972 through 1985) was performed to determine the frequency and most efficacious diagnostic modalities in this group of patients. Early gastric cancer was identified in 6% (17/302) of all these patients and in 28% (17/61) of patients undergoing curative resection. A review of presenting historical, physical, laboratory, radiologic, and endoscopic findings identified fiberoptic endoscopy as the most sensitive diagnostic procedure. Increased use of endoscopy in patients with persistent nonspecific gastrointestinal tract complaints may increase the number of patients seen with EGC.
It is rare for pneumatosis cystoides intestinalis to give rise to abdominal pain. We report a patient with signs and symptoms of a perforated viscous in whom abdominal exploration was negative, but in whom biopsy of various intraabdominal cystic structures revealed only pneumatosis cystoides intestinalis.
This is the 14th case report of squamous cell carcinoma in situ developing in perianal condyloma acuminata. A 72-year-old nonhomosexual man suffered this lesion 11 months after his condyloma was first fulgurated. The lesion was excised locally. He received no local or systemic chemotherapy. Random biopsies on several occasions since that time have not shown any evidence of local recurrence. Squamous-cell carcinoma in situ in perianal condyloma must be distinguished from Bowen's disease and extramammary Paget's disease of the perianal skin, both of which have associated skin rashes. Although Bowen's disease and extramammary Paget's disease frequently are associated with either local or distant malignancies, no such association has been found for squamous cell carcinoma in situ in condyloma unless the patient also has the acquired immunodeficiency syndrome (AIDS). Since this lesion is a premalignant lesion like Bowen's disease and extramammary Paget's disease, squamous cell carcinoma in situ in condyloma is treated by local excision. If the margins are free of tumor, the resection is curative. No local or systemic recurrence of this condition has been reported following adequate local resection. Patients with condyloma acuminata should undergo treatment to eliminate all of the warts. When the condylomata recur, or when the patient has AIDS, the lesions should be examined histologically for evidence of premalignant or malignant degeneration.
We report an adenocarcinoma arising in an ileostomy after colectomy for ulcerative colitis and discuss the treatment of a localized recurrence.
A method has been developed for preparing unique hydrophilic HSA/MS. Important aspects of this synthesis include addition of the cross-linking agent (glutaraldehyde) in the organic phase and use of concentrated polymer solutions as dispersion media. The polymer solutions afford excellent steric stabilization of aqueous albumin microdispersions for microsphere synthesis. Steric stabilization of dispersions by polymer solutions was shown to be a function of polymer concentration and molecular weight. The HSA/MS prepared by this method are hydrophilic and easily dispersed in a variety of aqueous media without surfactants. Chemical modifications are easily accomplished using available reactive aldehyde groups remaining after cross-linking. Although hydrophilicity of the microspheres is advantageous for many drug delivery applications, in some instances (such as the use of MS in adjuvant immunotherapy or vaccine preparations) some hydrophobicity may be desirable. For this purpose, surface modifications to produce controlled hydrophobicity is easily achieved by covalent coupling with appropriate reagents (e.g., fatty amines). Adriamycin was bound to HSA/MS by both physical association (to 18 wt%) and covalent binding (also to 18 wt%). In vitro release of drug was measured for the MS using a dynamic flow method. Two distinct release mechanisms could be achieved depending on the type of drug bonding used: slow by hydrolytic degradation of covalent bonds and fast by release of physically adsorbed drug. This new and versatile synthesis of hydrophilic HSA/MS opens up many new opportunities for producing chemically modified MS containing high concentrations of therapeutic agents. Use for immunodiagnostic and adjuvant compositions is also suggested.(ABSTRACT TRUNCATED AT 250 WORDS)
A new method for preparing glutaraldehyde cross-linked human serum albumin microspheres has been developed. Important aspects of this method include addition of glutaraldehyde in the organic phase and use of concentrated solutions of hydrophobic polymers (polymethylmethacrylate) or hydrophilic polymers (polyoxyethylene-polyoxypropylene block copolymer) as dispersion media. Uniform, round, solid, 3-150-microns hydrophilic microspheres were readily prepared by this process. The average size of microspheres was a function of dispersion time and energy input. Surface properties were altered by chemical modification using either 2-aminoethanol or aminoacetic acid to quench residual aldehyde groups. Optical and scanning electron microscopy and electronic particle size characterization indicate that the process is versatile in producing solid microspheres in a wide size range. Albumin microspheres of this type are readily dispersed in aqueous media for injection, without the need for surfactants.
Using a combination of ultraviolet-visible absorption, 1H NMR and ESR techniques we have established that N(1) of the imidazole and N(1) of the pyrimidine residues of bleomycin A2 bind to Cu(II) and Zn(II). The observations coupled with the earlier results that the alpha-amino group of the alpha-amino carboxamide function and the carbamoyl moiety are also Cu(II)-ligating groups makes it possible to reconstruct the detailed geometry and stereochemistry of the metal binding site of bleomycin A2.
The possible activation of immunologic defenses against tumor by local ultrasonic irradiation was investigated. Sonication of one tumor of a dual implant destroyed that tumor only with no contralateral effect. Injection of tumor cells previously sonicated in vivo did not induced immunity to subsequent challenge with live cells. Immunofluorescent staining of host kidneys for antibody complexes was negative. It was concluded that sonication was only effective when directly applied to the tumor.
Local sonic irradiation was applied to subcutaneously implanted Furth-Columbia rat Wilms' tumor. The weight and the rate of tritiated thymidine uptake were measured in host organs distal to the application field. Kidney and spleen weights were inhibited by the Wilms' tumor, and sonication of the tumor removed all or part of this inhibition. Liver weight was increased after sonication of tumor-bearing rats but not in nontumor-bearing rats. This may have been a response to tumor-specific substances released into the circulation by sonic destruction of tumor tissue. The adrenals enlarged as a response to the stresses of both tumor-bearing and of sonication. Animals were implanted on both sides with the Wilms' tumor and on without any break in the growth curve while the sonicated right tumor was inhibited. These data suggest that the therapeutic effect of ultrasound is due solely to local factors and that systemic sequelae of some irradiation are unrelated to tumor inhibition.
Exposure of 300 adult, male Wistar-Furth rats bearing subcutaneous implants of Wilms tumor to a vertically oriented planar ultrasound beam consistently resulted in a marked decrease in the growth rates of the tumors with an increase in the survival times of the treated animals. Grossly, the local effects consisted of a flattening of the tumors with clean excavation of their bases. Histologically, a line of demarcation was demonstrated between the sonicated (or destroyed) and non-sonicated portions of the same rat Wilms tumors. The sonicated portions exhibited a complete loss of the normal spatial relationship between the tumor epithelium and its surrounding mesenchyme. Ghost residuals of portions of individual cytoplasmic cell borders and nuclei with condensed chromatin patterns still could be discerned. Electron microscopy demonstrated a marked destruction of the nuclear and cytoplasmic cellular membranes with a migration of destroyed condensed chromatin material into the surrounding cytoplasm.
Ultrasonic irradiation was employed by direct administration to the skin overlying subcutaneously implanted Furth-Columbia rat Wilms' tumors. Treated tumors were flattened and excavated and demonstrated no stigmata of hemorrhage or infection. There was a marked decrease in growth rate of the tumors with an increase in survival time of the host. Histologic assessment with the light microscope exhibited a sharp line of demarcation between the necrosed sonicated portion of tumor and the viable intact nonsonicated area of tumor. A blackened area of skin, which was not histologically similar to a burn, was interposed betwwen the site of application of the ultrasound and the necrosed tumor.
Subcutaneous neck emphysema has been reported infrequently following colonoscopic perforation and only a single case of pneumopericardium has been previously reported. The successful management of these patients in the literature has largely been non-operative. We report a case of colonoscopic perforation which presented with subcutaneous neck emphysema, pneumopericardium, and pneumoperitoneum that required operative intervention.
Eicosanoids are involved in gallbladder inflammation, epithelial water transport, and mucous secretion. Phospholipase Asubscript2 enzymes liberate arachidonic acid from membrane phospholipids for the synthesis of eicosanoids. The purpose of this study was to determine the effect of selective cytoplasmic and secretory phospholipase A2 inhibitors on basal and stimulated arachidonic acid and prostaglandin E2 release in gallbladder cells. Western immunoblotting was employed to evaluate both cytosolic and secretory phospholipase A2 enzymes in human gallbladder cells. Cells were incubated for 22 hours with (3)H-labeled arachidonic acid. Arachidonic acid and prostaglandin E2 release was then measured in the supernate after 2 hours of exposure to human interleukin-1beta, alone or after pretreatment for 1 hour with the inhibitors. Unstimulated gallbladder cells express both 85 kDa cytosolic and 14 kDa secretory phospholipase A2++. The 85 kDa phospholipase A2 was induced by interleukin-1beta, whereas there was no apparent change in secretory phospholipase A2 enzyme concentrations. Both the secretory phospholipase A2 inhibitor p-bromophenylacyl bromide and the cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone decreased basal and interleukin-1beta-stimulated arachidonic acid release. In contrast, only inhibition of cytosolic phospholipase A2 led to a decrease in interleukin-1beta-stimulated prostaglandin E2 release. Basal and interleukin-1beta-stimulated arachidonic acid release appears to be the result of the activity of both cytosolic and secretory phospholipase A2. Interleukin-1beta-stimulated prostaglandin E2 release appears to be dependent on the activity of cytosolic phospholipase A2.