Non-operative management of acute cholecystitis in the elderly.

BACKGROUND: Although cholecystectomy is the standard therapy for acute cholecystitis (AC), operative morbidity in the elderly may be high owing to medical co-morbidities and decreased physiological reserve. Outcomes of AC in the elderly have not been fully defined with regard to operative and long-term non-operative management. METHODS: Patients aged 65 years or over admitted to a tertiary care centre with a diagnosis of AC between January 2000 and December 2009 were reviewed retrospectively. Patient data, operative and postoperative details were obtained. To determine cholecystectomy rates in the non-operative group, medical records were reviewed, and patients and families were interviewed. RESULTS: A total of 290 patients underwent cholecystectomy during the index admission, of whom 59 (20·3 per cent) required conversion to open operation. Fifty-eight of these patients experienced 98 complications, including acute respiratory failure (27), pneumonia (18), myocardial infarction (16) and sepsis (15). Some 185 patients had non-operative treatment, of whom 67 underwent percutaneous cholecystostomy. Forty-four patients subsequently had elective cholecystectomy, with a complication rate of 23 per cent. One hundred and twenty-six patients were discharged without a plan for cholecystectomy; the rate of recurrent AC was 4 per cent among the two-thirds of patients followed to within 15 months of death. No deaths or major complications occurred among those with recurrent AC. CONCLUSION: Despite selection of the best elderly candidates for cholecystectomy, postoperative morbidity was significant. Medical management, with interval cholecystectomy only for recurrent AC, may be appropriate in selected patients.

Crocidolite asbestos fibers in smoke from original Kent cigarettes.

The original version of the Kent Micronite cigarette filter used crocidolite, a form of asbestos, from 1952 until at least mid-1956. Cigarettes from intact, unopened packs of the brand from this period were examined. One filter contained approximately 10 mg of crocidolite. Crocidolite structures were found in the mainstream smoke from the first two puffs of each cigarette smoked. At the observed rates of asbestos release, a person smoking a pack of these cigarettes each day would take in more than 131 million crocidolite structures longer than 5 microns in 1 year. These observations suggest that people who smoked the original version of this cigarette should be warned of their possible substantial exposure to crocidolite during the 1950s.

A spectroscopic investigation of the metal binding site of bleomycin A2. The Cu(II) and Zn(II) derivatives.

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.

Geographic variation in patient surveillance after colon cancer surgery.

PURPOSE: Considerable variation among surgeons exists in the current practice of patient surveillance after colon cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS: Profiles of hypothetical patients and a detailed questionnaire based on the profiles were mailed to 2,733 members of two national surgical societies. The influence of the geographic location of the respondents on practice patterns were assessed in two ways. Repeated-measures analysis of variance was used to compare the practice patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis was used to determine whether these patterns differed by MSA population size. RESULTS: Seven of nine commonly used surveillance modalities were ordered significantly more frequently with increasing tumor-node-metastasis (TNM) stage and significantly less frequently with year postsurgery among the 995 respondents with assessable responses, but MSA population size and geographic location of physicians generally had no effect on documented practice variability. The remaining two modalities (bone scan and computed tomography [CT]) were used so infrequently as to preclude meaningful analysis. CONCLUSION: Surveillance after potentially curative colon cancer surgery for otherwise healthy patients is not significantly affected by the geographic location of the surgeon who performs the surveillance testing and only modestly affected by the population size of the MSA in which he/she practices. These data should help in the design of prospective trials of this topic.

Primary signet-ring cell carcinoma mimicking segmental Crohn's colitis.

Primary signet-ring cell carcinoma of the colon is a rare entity with a dismal prognosis, mainly due to a delay in diagnosis. Here, we present a case of a 30-year-old Filipino woman who presented with symptoms mimicking inflammatory bowel disease. A barium enema and colonoscopy demonstrated a stricture in the rectosigmoid region. A biopsy revealed granulomatous changes indicative of inflammatory bowel disease. Despite initial improvement of her symptoms on total parenteral nutrition and steroids, the patient relapsed several weeks later with recurrent left lower quadrant pain. A subsequent biopsy revealed poorly differentiated signet-ring cell carcinoma of the colon. She was treated surgically with a left hemi-colectomy and primary repair. A high degree of suspicion is necessary to correctly diagnose these, often young, patients with primary signet-ring cell carcinoma early and have a positive impact on survival. The literature on primary signet-ring cell carcinoma is reviewed.

The surgical management of elderly cancer patients; recommendations of the SIOG surgical task force.

Although cancer in the elderly is extremely common, few health professionals in oncology are familiar with caring for series of oncogeriatric patients. Surgery is at present the first choice, but is frequently delivered suboptimally: under-treatment is justified by concerns about unsustainable toxicity, whilst over-treatment is explained by the lack of knowledge in optimising preoperative risk assessment. This article summarises the point of view of the Surgical Task Force @ SIOG (International Society for Geriatric Oncology), pointing out differences from, and similarities to, the younger cohorts of cancer patients, and highlighting the latest updates and trends specifically related to senior cancer patients.

Hydrophilic albumin microspheres.

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)

Mineral fiber content of lung tissue in patients with environmental exposures: household contacts vs. building occupants.

Analysis of tissue mineral fiber content in patients with environmental exposures has seldom been reported in the past. Our studies of six household contacts of asbestos workers indicate that these individuals often have pulmonary asbestos concentrations similar to some occupationally exposed individuals. In contrast, our studies of four occupants of buildings with asbestos-containing materials indicate that these individuals often have pulmonary asbestos burdens indistinguishable from the general nonoccupationally exposed population. However, one such building occupant exposed for many years and who later developed pleural mesothelioma was studied in detail, and it was concluded that her exposure as a teacher's aide in a school building containing acoustical plaster was the likely cause of her mesothelioma.

Treatment of Crohn's colitis. Segmental or total colectomy?

In our institution, segmental Crohn's colitis has been treated with segmental colectomy rather than more extensive resection. The purpose of this study was to review the rate of recurrence following surgical treatment of Crohn's colitis using this approach. From 1974 through 1984, 37 patients with Crohn's disease limited to the colon or rectum underwent resection. Average time of follow-up was 5.5 years. There were recurrences in 13 (62%) of 21 patients treated by segmental colectomy and four (67%) of six patients treated by total abdominal colectomy and small-bowel recurrences in two (20%) of ten patients treated by proctocolectomy. Intestinal continuity was maintained in 17 (81%) of the 21 patients treated by segmental resection. Although recurrence is likely, segmental colectomy improves the quality of life by delaying the need for a stoma and by preserving functioning bowel.

Role of endoscopy in the diagnosis of early gastric cancer.

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.

Clostridium difficile toxins influence hepatocyte protein synthesis through the interleukin 1 receptor.

HYPOTHESIS: Clostridium difficile toxins require interleukin 1 (IL-1) production or a functioning IL-1 receptor to elicit acute-phase protein production by murine hepatocytes. DESIGN: Experimental study. SETTING: Research laboratory at the DVA Medical Center, St Louis, Mo. CELLS STUDIED: Hepatocytes prepared from normal mice, from knockout mice deficient in IL-1 production due to loss of IL-1 converting enzyme, or from knockout mice deficient in the IL-1 p80 receptor. INTERVENTIONS: Cells were treated with lipopolysaccharide, a crude C difficile toxin extract, or purified C difficile toxins A or B for 24 hours in vitro, then radiolabeled with (35)S methionine. Newly synthesized acute-phase proteins were identified by electrophoresis and autoradiography. MAIN OUTCOME MEASURES: Synthesis of a 23-kd acute-phase protein in response to the various stimuli. RESULTS: Lipopolysaccharide, C difficile culture extract, and purified toxins A and B stimulated the synthesis of the 23-kd acute-phase protein by hepatocytes from normal mice and by hepatocytes from knockout mice deficient in the IL-1 converting enzyme. However, hepatocytes from knockout mice deficient in the IL-1 p80 receptor failed to produce this acute-phase protein when treated with the C difficile toxins, although they responded fully to lipopolysaccharide. CONCLUSIONS: Stimulation of acute-phase protein synthesis by C difficile toxins does not require IL-1 production, but does require a functioning IL-1 p80 receptor. This suggests that some of the actions of these toxins are mediated by this receptor.

Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2.

Acute cholecystitis is associated with increased gallbladder prostanoid formation and the inflammatory changes and prostanoid increases can be inhibited by nonsteroidal anti-inflammatory agents. Recent information indicates that prostanoids are produced by two cyclooxygenase (COX) enzymes, COX-1 and COX-2. The purpose of this study was to determine the COX enzymatic pathway in gallbladder mucosal cells involved in the production of prostanoids stimulated by inflammatory agents. Human gallbladder mucosal cells were isolated from cholecystectomy specimens and maintained in cell culture and studied in comparison with cells from a well differentiated gallbladder mucosal carcinoma cell line. COX enzymes were evaluated by Western immunoblotting and prostanoids were measured by ELISA. Unstimulated and stimulated cells were exposed to specific COX-1 and COX-2 inhibitors. In both normal and transformed cells constitutive COX-1 was evident and in gallbladder cancer cells lysophosphatidyl choline (LPC) induced the formation of constitutive COX-1 enzyme. While not detected in unstimulated normal mucosal cells and cancer cells, COX-2 protein was induced by both lipopolysaccharide (LPS) and LPC. Unstimulated gallbladder mucosal cells and cancer cells produced prostaglandin E2 (PGE2) and prostacyclin (6-keto prostaglandin F1alpha, 6-keto PGF1alpha) continuously. In freshly isolated normal gallbladder mucosal cells, continuously produced 6 keto PGF1alpha was inhibited by both COX-1 and COX-2 inhibitors while PGE2 levels were not affected. Both LPS and LPC stimulated PGE2 and 6 keto PGF1alpha formation were blocked by COX-2 inhibitors in freshly isolated, normal human gallbladder mucosal cells and in the gallbladder cancer cells. The prostanoid response of gallbladder cells stimulated by proinflammatory agents is inhibited by COX-2 inhibitors suggesting that these agents may be effective in treating the pain and inflammation of gallbladder disease.

Platelet-activating factor mediates trinitrobenzene induced colitis.

Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.

Interaction of ultrasound with neoplastic tissue. Local effect on subcutaneously implanted Furth-Columbia rat Wilms' tumor.

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.

Role of chronic catheterization in the development of bladder cancer in patients with spinal cord injury.

OBJECTIVES: Patients with spinal cord injury (SCI) and chronic indwelling catheters are known to be at increased risk of bladder malignancy. "Decatheterization" by clean intermittent catheterization, external condom catheterization, or spontaneous voiding is thought to reduce the risk by decreasing the chronic mucosal irritation and rate of infection. We examined two Department of Veterans Affairs (DVA) data bases to test this theory. METHODS: A population-based retrospective analysis of invasive treatments for carcinoma of the bladder in all DVA hospitals was conducted using computerized inpatient files from fiscal years 1988 to 1992. RESULTS: One hundred thirty patients with bladder malignancy were identified from a pool of 33,565 patients with SCI (0.39%). All 130 patients underwent either radical cystectomy (n = 63, 48%) or transurethral resection of bladder tumor (n = 67, 52%). The 30-day perioperative mortality and overall 5-year survival rates were 2 (1.5%) and 49 (38%) of 130, respectively. Of the 130 patients analyzed, 42 (32%) had adequate data available regarding tumor pathologic findings and method of bladder management for analysis. The average age at diagnosis was 57.3 years. The histologic finding was transitional cell carcinoma in 23 (55%), squamous cell carcinoma in 14 (33%), and adenocarcinoma in 4 (10%) of 42. Bladder management was an indwelling urethral catheter in 18 (43%), suprapubic catheter in 8 (19%), clean intermittent catheterization in 8 (19%), and condom catheter in 6 (14%) of 42 patients. Squamous cell carcinoma was more common in patients with indwelling urethral catheters and suprapubic tubes (11 of 26, 42%) than in those using clean intermittent catheterization, condom catheterization, or spontaneous voiding (3 of 16, 19%). CONCLUSIONS: Bladder cancer was diagnosed in approximately 0.39% of this large SCI population during a 5-year period. Most cancers (55%) were transitional cell carcinomas. Squamous cell carcinoma was more common in patients with SCI and indwelling catheters than those without chronic catheterization. These data continue to suggest that avoidance of indwelling catheters, when feasible, is the preferred method of bladder management in patients with SCI.

Interaction of ultrasound with neoplastic tissue. II. Systemic effects after local sonic irradiation.

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.

Effect of platelet-activating factor and its antagonists on colonic dysmotility and tissue levels of colonic neuropeptides.

We investigated whether platelet-activating factor (PAF) alters colonic tissue levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides that regulate colonic motility. Left colons were harvested from NZ White Rabbits and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 x 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and decreased the force of colonic contractions. Pretreatment with WEB-2170 or alprazolam decreased concentrations of both tissue neuropeptides, and decreased the force of colonic contractions and minute motility index. These results suggest that both VIP and substance P are stimulated by PAF and may participate in colonic dysmotility during inflammatory states.

Outcomes after detection of metastatic carcinoma of the colon and rectum in a national hospital system.

BACKGROUND: Selected institutions have reported good results with resection for metastatic carcinoma of the colon and rectum, but the number of patients and the expenses required to identify the resectable metastases are unknown. STUDY DESIGN: A retrospective survival analysis was performed using computerized files of the United States Department of Veterans Affairs hospitals from 1988 to 1992, complete through December 1994. Survival was calculated from diagnosis or resection until death. Patients without a death record were assumed to be alive. RESULTS: In all, 22,715 patients underwent colectomy for carcinoma, and 12,150 presented with metastatic carcinoma of the colon and rectum, of which 6,607 had hepatic and 2,659 had pulmonary metastases. Only 2,040 patients with hepatic (and 514 with pulmonary metastases had no prior or other metastatic sites. Of the patients with hepatic metastases, 887 had a computed tomography (CT) scan or liver biopsy, or both, for diagnosis; 133 hepatic and 76 pulmonary resections were done. The projected five-year survival rate after hepatic resection was 26 percent, mean survival was 31 months, and the 30-day mortality rate was 4 percent. After pulmonary resection, results were similar: 36 percent, 38 months, and 3 percent, respectively. The 887 patients with hepatic metastases documented by CT scan or biopsy results has a mean survival of 11 months, and less than 2 percent were alive or unavailable for follow-up examination at analysis. Estimated surveillance costs alone averaged $1.3 million per life saved by resection, or $203,000 per year of added life. CONCLUSIONS: Resection of isolated colorectal metastases produced 70 five-year survivors (hepatic, n=42, pulmonary, n=28) and accounted for 446 additional years of patient life over that expected without resection.

How practice patterns in colon cancer patient follow-up are affected by surgeon age.

BACKGROUND: Strategies for the follow-up of colon cancer patients after potentially curative treatment are known to vary widely. The optimal regimen remains unknown. We investigated whether the date of completion of formal surgical training affects choice of surveillance strategy. METHODS: The 1070 members of the Society of Surgical Oncology (SSO) and the 1663 members of the American Society of Colon and Rectal Surgeons (ASCRS) were surveyed using a detailed questionnaire to measure how these surgical experts deal with colon cancer follow-up. Subjects were asked how they use nine specific follow-up modalities during years 1-5 following primary treatment for patients with colon cancer (TNM Stages I-III). Repeated-measures analysis of variance was used to compare practice patterns by TNM stage and year post-surgery, as well as by the year in which the surgeon's formal surgery training was completed. RESULTS: Evaluable responses were received from 349 SSO members (33%) and 646 ASCRS members (39%). Few significant differences in follow-up practices were noted by training period, but follow-up for most of the nine modalities was highly correlated with TNM stage and year post-surgery, as expected. CONCLUSIONS: This analysis indicates that the post-treatment surveillance practice patterns of surgeons caring for patients with colon cancer do not vary substantially with practitioner age. The data provide credible evidence that postgraduate education is effective in homogenizing practitioner behaviour.

Role of cytosolic phospholipase A2 in cytokine-stimulated prostaglandin release by human gallbladder cells.

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.