BACKGROUND: Acute acalculous cholecystitis (AAC) is a serious complication of critical illness. We evaluated the underlying diseases, clinical and diagnostic features, severity of associated organ failures, and outcome of operatively treated AAC in a mixed ICU patient population. METHODS: The data of all ICU patients who had operatively confirmed AAC during their ICU stay between 1 January 2000 and 31 December 2001 were collected from the hospital records and the intensive care unit's data management system for predetermined variables. RESULTS: Thirty-nine (1%) out of 3984 patients underwent open cholecystectomy for AAC during the two-year period. Infection was the most common admission diagnosis, followed by cardiovascular surgery. The mean APACHE II score on admission was 25, and 64% of the patients had three or more failing organs on the day of cholecystectomy. The mean length of ICU stay before cholecystectomy was 8 days, and the mean total length of ICU stay was 19 days. Most patients (85%) received norepinephrine infusion, and 90% suffered respiratory failure before cholecystectomy. Hospital mortality was 44%. The non-survivors had higher Sequential Organ Failure Assessment (SOFA) scores on the day of cholecystectomy compared to the survivors (12.9 vs. 9.5, P = 0.007). CONCLUSION: Acute acalculous cholecystitis was associated with severe illness, infection, long ICU stay, and multiple organ failure. Mortality was related to the degree of organ failure. Prompt diagnosis and active treatment of AAC can be life-saving in these patients.
This study compares the localization of carbonic anhydrase isozymes (CA) I and II and that of IX and XII in normal large intestine and in colorectal tumors. Immunohistochemical studies were performed on 69 colorectal lesions. While the normal mucosa of the large intestine showed high expression for CA I and II, the intensity of the immunostaining for both isozymes decreased in benign lesions and was very weak in malignant tumors. The reciprocal pattern of expression observed for these cytoplasmic isozymes and transmembrane CA IX and XII in intestinal tissue specimens supports the suggestion that CA IX and XII may be functionally involved in tumor progression to malignancy and/or in invasion. By contrast, while CA I and II are prominent in normal colorectal mucosa, where they play a role in regulation of pH homeostasis and water and ion transport, loss of expression of these cytoplasmic isozymes consistently accompanies progression to malignant transformation.
Carbonic anhydrase isozyme XII is a recently discovered member of the alpha-carbonic anhydrase gene family with a suggested role in von Hippel-Lindau gene-mediated carcinogenesis. Increased expression of its mRNA has been observed in renal and lung carcinomas. This paper presents the localization of CA XII in the normal human gut and in colorectal tumors. Immunohistochemistry performed using a polyclonal antibody raised against truncated CA XII revealed prominent polarized staining for CA XII in the basolateral plasma membrane of the enterocytes of the normal large intestine, the reaction being most intense in the surface epithelial cuff region. Most colorectal tumors displayed abnormal expression of CA XII; the most dramatic change was observed in the deep parts of the adenomatous mucosa, where the positive immunoreaction clearly increased along with the grade of dysplasia. Adenomas with severe dysplasia and carcinomas showed an equal, diffuse staining pattern. The results indicate region-specific regulation of CA XII expression along the cranial-caudal axis of the human gut, whereas its diffuse expression in the most malignant tumors seems to correlate with their biological behavior.
Carbonic anhydrase isozyme XII (CA XII) is a novel membrane-associated protein with a potential role in von Hippel-Lindau carcinogenesis. Although Northern blotting has revealed positive signal for CA XII in normal human kidney, this is the first study to demonstrate its cellular and subcellular localization along the human nephron and collecting duct. Immunohistochemistry with a polyclonal antibody (PAb) raised against truncated CA XII revealed distinct staining in the basolateral plasma membrane of the epithelial cells in the thick ascending limb of Henle and distal convoluted tubules, and in the principal cells of the collecting ducts. A weak basolateral signal was also detected in the epithelium of the proximal convoluted tubules. In addition to the normal kidney specimens, this immunohistochemical study included 31 renal tumors. CA XII showed moderate or strong plasma membrane-associated expression in most oncocytomas and clear-cell carcinomas. The segmental, cellular, and subcellular distribution of CA XII along the human nephron and collecting duct suggests that it may be one of the key enzymes involved in normal renal physiology, particularly in the regulation of water homeostasis. High expression of CA XII in some renal carcinomas may contribute to its role in von Hippel-Lindau carcinogenesis.
Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes which are expressed in several epithelia and overexpressed in some carcinomas. They have recently been linked to von Hippel-Lindau gene-mediated carcinogenesis in that both isoenzymes are downregulated by the product of the wild-type von Hippel-Lindau tumour suppressor gene. This paper describes the localisation of CA IX and XII in the normal human pancreas and pancreatic tumours. Both isoenzymes showed positive reaction in the basolateral plasma membrane of the normal acinar and ductal epithelia. The hyperplastic ductal epithelium in tumour specimens generally showed an increased staining for CA IX. Of 29 malignant tumours of exocrine pancreas, 10 showed moderate or strong immunoreaction for CA IX. The signal for CA XII remained weak in most malignant lesions. The present results show that both CA IX and XII are unevenly expressed in the ductal and acinar compartments of the human pancreas. The expression of these isoenzymes in a relatively low number of malignant tumour specimens suggests that they have a limited value in diagnostic evaluation of pancreatic carcinoma. However, the increased expression of CA IX in hyperplastic ductal epithelium may contribute to the pancreatic tumourigenesis.
Carbonic anhydrase isoenzyme IX, MN/CA IX, is a recently discovered member of the carbonic anhydrase (CA) gene family with a suggested function in acid-base balance, intercellular communication, and cell proliferation. Increased expression of MN/CA IX has been observed with certain epithelial tumors. We investigated the expression of MN/CA IX in 69 colorectal neoplasms, consisting of 1 juvenile polyp, 8 hyperplastic polyps, 39 adenomatous lesions, 21 carcinomas, and 7 metastases. Tissue sections were immunostained with a monoclonal antibody specific to MN/CA IX. The proliferative activity of the tumor cells was evaluated by Ki-67 antigen immunoreactivity. The hyperplastic polyps showed a weak or moderate reaction for MN/CA IX only in the cryptal epithelium, as did the normal intestinal mucosa. The adenomas showed immunoreactivity mainly in the superficial part of the mucosa, whereas the distribution in the carcinomas and metastases was more diffuse. Comparative immunostaining of serial sections for Ki-67, a well established marker of cell proliferation, confirmed that MN/CA IX is expressed in areas with high proliferative capacity. Our results show abnormal MN/CA IX expression in colorectal neoplasms, suggesting its involvement in their pathogenesis. The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa.
Comment In: Am J Pathol. 1998 Jul;153(1):1-49665457
BACKGROUND: Acute acalculous cholecystitis (AAC) refers to cholecystitis without gallstones and is a serious complication of critical illness. We describe the time course of organ system dysfunction associated with cholecystectomy in critically ill patients with AAC. METHODS: The data of all intensive care unit (ICU) patients who had operatively confirmed AAC during their ICU stay between 2003 and 2004 were analyzed. Patients who also had other intra-abdominal pathologies were excluded. The Sequential Organ Failure Assessment (SOFA) scores were recorded 3 days before, on the day of operation and on the first, second, third and seventh post-operative day after cholecystectomy. The impact of open cholecystectomy on organ dysfunction was evaluated on the basis of the change in the total and individual organ SOFA scores. RESULTS: Twenty-four patients underwent open cholecystectomy for AAC with no other intra-abdominal pathology. Sepsis was the most common admission diagnosis, followed by cardiovascular surgery. The mean (standard deviation, SD) Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS) II and SOFA scores on admission were 24.7 (5.8), 44.3 (12.3) and 9.4 (3.2), respectively. The median (25th, 75th percentiles) total SOFA score 3 days before cholecystectomy was 7.5 (1.3, 8.0), which increased to 10.5 (8.3, 13.0) (P
BACKGROUND: The purpose of this trial was to measure the health-related quality of life (HRQL) of gastroesophageal reflux disease (GERD) patients waiting for an antireflux operation. METHODS: A total of 120 patients waiting for a laparoscopic fundoplication were sent questionnaires measuring their symptoms and quality of life. RESULTS: Ninety-five of the patients still needing an operation returned the questionaires and were included in the analysis. Thirty-one of 84 patients (37%) felt that the symptoms had worsened, and 51/90 (57%) were unsatisfied. Thirty percent suffered from throat or airway infections, 25% from swallowing difficulties, 48% from retrosternal pain, and 18% had asthma. The mean GERD HRQL score (0-45) was 21.7 (95% confidence interval, 19.7-23.7). Short Form-36 scores of this population were significantly worse when compared to patients with inguinal hernia or moderate asthma. CONCLUSIONS: Patients waiting for a fundoplication seem to have a significantly decreased health-related quality of life due to poor symptom control regardless of continuous medical treatment.
BACKGROUND/AIMS: Carbonic anhydrase isoenzyme IX (MN/CA IX) is a transmembrane protein with a suggested function in maintaining the acid-base balance and intercellular communication. Previous studies have demonstrated that MN/CA IX is expressed in the basolateral plasma membrane of normal biliary epithelial cells, but not in hepatocytes. This study was designed to examine the expression of MN/CA IX in hepatobiliary neoplasms and to elucidate its value as a marker for biliary differentiation. METHODS: Fifty-seven hepatobiliary lesions were immunostained for MN/CA IX using biotin-streptavidin complex method. Twenty samples containing normal biliary epithelium and five containing normal liver tissue were used as controls. RESULTS: In the biliary epithelial tumours, immunostaining for MN/CA IX was mainly localized at the basolateral surface of the epithelial cells, like in normal mucosa. All non-invasive dysplastic lesions and 57% of invasive lesions of gall-bladder expressed MN/CA IX. In liver, 78% of cholangiocellular malignant lesions showed a positive reaction for MN/CA IX, whereas only 33% of hepatocellular carcinomas showed a weak immunoreaction. CONCLUSIONS: Our results suggest that abnormal expression of MN/CA IX may be linked to malignant transformation of hepatobiliary cells. In addition, it seems to be a promising marker for biliary differentiation in hepatobiliary neoplasms.