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.

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.

Renal cell carcinoma in patients with prior spinal cord injury.

INTRODUCTION: In patients with spinal cord injury (SCI), abdominal diseases such as renal carcinoma are often diagnosed and treated late in their course. METHODS: A population-based retrospective review of SCI patients receiving care for renal cell carcinoma (RCC) in all Department of Veterans Affairs (DVA) medical centers was conducted for fiscal years 1988 to 1998. RESULTS: Of 96 patients identified, 57 were evaluable and 27 met study criteria. The mean patient age was 59 (range, 41-79 years). The mean time between SCI and treatment for RCC was 25 years (range, 1-51 years). All patients were men; 22/27 (81%) had 1 or more comorbid conditions. RCC was an incidental finding on surveillance imaging studies in 81% (22/27) of the patients. All 27 patients were treated surgically, 74% (20/27) by radical nephrectomy and 26% (7/27) by partial nephrectomy. All tumors were renal cell adenocarcinomas. Pathological staging by the tumor, nodes, and metastasis system was possible in 25; 92% (23/25) of tumors were stage I and 8% (2/25) were stage II. Postoperative morbidity occurred in 56% (15/27), and death occurred in 7% (2/27). CONCLUSION: In SCI patients in the DVA system, diagnosis of RCC is usually the result of an incidental finding on surveillance imaging. Tumors are diagnosed at early stages and partial nephrectomy is often feasible. Many of the postoperative complications are related to the SCI, and may be preventable.

Idiopathic megarectum complicating pregnancy: report of a case.

Pregnancy often exacerbates constipation in young women with chronic constipation syndromes. The presence of the fetus presents a challenge in both the diagnosis and treatment of these syndromes. This study was conducted to report a rare case of idiopathic megarectum complicating a pregnancy. An aggressive polyethylene glycol (PEG) regimen allowed the patient to carry the child to term and to have a normal vaginal delivery. Successful proctocolectomy was performed with coloanal anastomosis 3 months postpartum. The patient has been free of constipation for 18 months without the need for cathartics or laxatives. All efforts to avoid operative intervention should be made in constipated patients during pregnancy. This principle holds true even in the setting of dilated large bowel. Idiopathic megarectum and the management of constipation in pregnancy are discussed.

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.

The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells.

Information suggests that the cyclooxygenase (COX) metabolites, the prostanoids, play a role in gall bladder physiology and disease. Non-steroidal anti-inflammatory drugs which inhibit COX enzymes have been shown in vivo and in vitro to alter the growth patterns of intestinal epithelial cells, and specific COX-2 inhibitors have been shown to decrease mitogenesis in intestinal epithelial cells. The present study was intended to evaluate the effect of specific COX inhibitors on the growth patterns of gall bladder cancer cells. Employing a human gall bladder cancer cell line, mitogenesis, apoptosis and prostaglandin E(2) (PGE(2)) formation were evaluated in response to serum and hepatocyte growth factor and transforming growth factor alpha stimulation in the presence and absence of specific COX-1 and -2 inhibitors. The effect of the mitogens on COX enzyme expression was also evaluated. Serum and the growth factors increased COX enzyme expression and mitogenesis, and decreased apoptosis as evaluated by the percentage of cells that were floating in culture media rather than attached. There was more DNA degradation in floating than in attached cells. The specific COX-2 inhibitor, but not the COX-1 inhibitor, decreased mitogenesis and increased gall bladder cell apoptosis as evaluated by the number of floating versus attached cells and the number of floating cells in the terminal phase of apoptosis or dead. The inhibition of mitogenesis and the increased apoptosis produced by the COX-2 inhibitor was associated with decreased PGE(2) production. The inhibition of replication of gall bladder cancer cells and the increase in apoptosis produced by the selective COX-2 inhibitor suggests that the COX enzymes and the prostanoids may play a role in the development of gall bladder cancer and that the COX-2 inhibitors may have a therapeutic role in the prevention of gall bladder neoplasms.

Risk factors for morbidity and mortality after colectomy for colon cancer.

PURPOSE: Comorbid conditions affect the risk of adverse outcomes after surgery, but the magnitude of risk has not previously been quantified using multivariate statistical methods and prospectively collected data. Identifying factors that predict results of surgical procedures would be valuable in assessing the quality of surgical care. This study was performed to define risk factors that predict adverse events after colectomy for cancer in Department of Veterans Affairs Medical Centers. METHODS: The National Veterans Affairs Surgical Quality Improvement Program contains prospectively collected and extensively validated data on more than 415,000 surgical operations. All patients undergoing colectomy for colon cancer from 1991 to 1995 who were registered in the National Veterans Affairs Surgical Quality Improvement Program database were selected for study. Independent variables examined included 68 preoperative and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting the 30-day mortality rate and 30-day morbidity rates for each of the ten most frequent complications. RESULTS: A total of 5,853 patients were identified; 4,711 (80 percent) underwent resection and primary anastomosis. One or more complications were observed in 1,639 of 5,853 (28 percent) patients. Prolonged ileus (439/5,853; 7.5 percent), pneumonia (364/5,853; 6.2 percent), failure to wean from the ventilator (334/5,853; 5.7 percent), and urinary tract infection (292/5,853; 5 percent) were the most frequent complications. The 30-day mortality rate was 5.7 percent (335/5,853). For most complications, 30-day in-hospital mortality rates were significantly higher for patients with a complication than for those without. Thirty-day mortality rates exceeded 50 percent if postoperative coma, cardiac arrest, a pre-existing vascular graft prosthesis that failed after colectomy, renal failure, pulmonary embolism, or progressive renal insufficiency occurred. Preoperative factors that predicted a high risk of 30-day mortality included ascites, serum sodium >145 mg/dl, "do not resuscitate" status before surgery, American Society of Anesthesiologists classes III and IV OR V, and low serum albumin. CONCLUSIONS: Mortality rates after colectomy in Veterans Affairs hospitals are comparable with those reported in other large studies. Ascites, hypernatremia, do not resuscitate status before surgery, and American Society of Anesthesiologists classes III and IV OR V were strongly predictive of perioperative death. Clinical trials to decrease the complication rate after colectomy for colon cancer should focus on these risk factors.

Sigmoid volvulus in Department of Veterans Affairs Medical Centers.

PURPOSE: Sigmoid volvulus is the third leading cause of large-bowel obstruction. The optimal management strategy remains controversial. This study was undertaken to evaluate the care of patients with sigmoid volvulus recently treated at Department of Veterans Affairs hospitals. METHODS: All patients with the International Classification of Diseases, Ninth Revision, Clinical Modification, Third Edition code for colonic volvulus during the period 1991 to 1995 were identified in the computerized national Department of Veterans Affairs database. Data on patient demographics, clinical course, and outcomes were analyzed. RESULTS: Two hundred twenty-eight patients had volvulus of the sigmoid colon and sufficient clinical data for evaluation. The mean age was 70; all were males. Endoscopic decompression was attempted in 189 of 228 (83 percent) patients and was successful in 154 of 189 (81 percent). Management included celiotomy in 178 of 228 (78 percent) patients. There were no intraoperative deaths. Twenty-five of 178 (14 percent) patients died within 30 days of surgery. The mortality rate was 24 percent for emergency operations (19/79), and 6 percent for elective procedures (6/99). Mortality was correlated with emergent surgery (P < 0.01) and necrotic colon (P < 0.05). Among those 50 patients managed by decompression alone, six (12 percent) died during the index admission. Ten of the remaining 44 (23 percent) patients eventually developed recurrent volvulus requiring further treatment, and 2 of 10 (20 percent) patients died. CONCLUSIONS: In this cohort sigmoid volvulus often presents as a surgical emergency. Initial endoscopic decompression resolves the acute obstruction in the majority of cases. Surgical intervention carries a substantial risk of mortality, particularly in the setting of emergent surgery or in the presence of necrotic colon.

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.

Clostridium difficile toxin: cytoskeletal changes and lactate dehydrogenase release in hepatocytes.

BACKGROUND: We have found that Clostridium difficile toxins can evoke hepatocyte acute-phase protein synthesis, and that this effect is dependent on a functioning interleukin-1 (IL-1) receptor. The present study was undertaken to determine if C. difficile toxicity, as determined by actin rearrangement and lactate dehydrogenase (LDH) release, also requires a functioning IL-1 receptor. METHODS: Primary hepatocyte cultures were prepared from normal mice, knockout mice deficient in the IL-1-converting enzyme (ICE), and knockout mice deficient in the IL-1 p80 receptor. Hepatocytes were treated for 24 h with C. difficile culture extract, purified C. difficile toxin A, or purified C. difficile toxin B. The actin cytoskeleton was examined using confocal microscopy, and LDH release was measured by spectrophotometric analysis. RESULTS: C. difficile culture extract, toxin A, and toxin B induced collapse of the actin cytoskeleton in hepatocytes from normal mice. Hepatocytes from both the ICE-deficient mice and the IL-1 p80 receptor-deficient mice demonstrated similar responses to both toxins. These toxins also induced significant LDH release in a concentration-dependent fashion in the normal hepatocytes and the ICE-deficient hepatocytes. However, no significant increase in LDH release was observed in hepatocytes from IL-1 p80 receptor-deficient mice. CONCLUSIONS: C. difficile toxins induce actin cytoskeletal collapse independent of IL-1 or the IL-1 receptor. In contrast, toxin-stimulated LDH release was dependent on the presence of the IL-1 receptor. Thus, separate pathways appear to mediate toxic effects as manifested by actin rearrangement and LDH release.

Role of cytoplasmic and secretory phospholipase A2 in intestinal epithelial cell prostaglandin E2 formation.

BACKGROUND: Prostanoid production is dependent on the enzymatic activity of phospholipase A2 enzymes to produce the precursor, arachidonic acid. Two principle phospholipase A2 enzymes play a major role in arachidonic acid production, 85kDa cytoplasmic phospholipase A2 (cPLA2) and 14kDa secretory phospholipase A2 (sPLA2). The purpose of this study was to determine the PLA2 enzyme involved in prostanoid formation in intestinal epithelial cells. METHODS: Employing a human and murine intestinal epithelial cell line, cells were exposed to the stimulants lipopolysaccharide (LPS), interleukin 1beta (IL-1) and calcium ionophore (Ca Ion) in the presence and absence of cPLA2 and sPLA2 inhibitors. The expression of both PLA2 enzymes and prostaglandin E2 (PGE2) formation were determined. RESULTS: Western blotting demonstrated that the cPLA2 enzyme was constitutively expressed in the human cell lines and not evidently increased by exposure to any of the stimulants. In murine cells the cPLA2 enzyme was also constitutively expressed and not induced by the stimulants evaluated. The sPLA2 enzyme was constitutively expressed in both cell lines and appeared to be induced by LPS and IL-1 in human enterocytes but not by Ca Ion. In murine enterocytes sPLA2 was induced by all three stimuli. PGE2 production by the human cell line was increased by LPS, IL-1 and Ca Ion. IL-1 and Ca Ion stimulated PGE2 formation was inhibited by the cPLA2 enzyme inhibitors while LPS stimulated PGE2 production was not inhibited by the cPLA2 inhibitor; but was inhibited by the sPLA2 enzyme inhibitor. Murine epithelial cells increased PGE2 formation in response to IL-1 and Ca Ion, but not LPS and the increased PGE2 was significantly decreased by cPLA2 enzyme inhibitors. CONCLUSIONS: The metabolic pathway of PGE2 formation is variable and the PLA2 enzyme involved in producing PGE2 is dependent on the stimulus and the cell line. In human intestinal epithelial cells, LPS production of PGE2 proceeds through a pathway associated with sPLA2 generated arachidonic acid while IL-1 stimulated PGE2 is produced by arachidonic acid generated by cPLA2. The physiologic significance of the various metabolic pathways of PGE2 formation is unknown.

Appendicitis in patients with previous spinal cord injury.

BACKGROUND: Acute abdominal emergencies are particularly dangerous in patients with impaired sensation. METHODS: Thirty patients with spinal cord injury who later developed appendicitis were identified in Department of Veterans Affairs computer files over a 5-year period; 26 were evaluable. RESULTS: The mean age was 55 years (range 27 to 79); all were males. Abdominal distention or discomfort was present in 16 of 26 (62%), while 2 of 26 (8%) presented in shock. A palpable right lower quadrant mass was present in 6 of 26 (23%). The mean initial white blood cell count was 18,000/mm3. Only 9 of 26 (35%) had the diagnosis of appendicitis made on admission. In 12 of 26, computed tomography was done; all correctly diagnosed appendicitis. The mean delay in diagnosis after hospitalization was 2 days (range 0 to 5). Perforated appendicitis was found at surgery in 24 of 26 (92%). Twenty-three of 26 (88%) underwent appendectomy; 3 of 26 (12%) underwent right colectomy. The 30-day mortality rate was 4%. Six of 26 (23%) developed a postoperative complication. The mean length of stay was 16 days. CONCLUSIONS: Acute appendicitis in spinal-cord-injured patients frequently presents late and complications are common. Computed tomography appears to be an excellent diagnostic modality. Some of the adverse outcomes which are related to preexisting spinal cord injury may be preventable with early intervention.