Joar Svanvik

Systematic review of cholecystostomy as a treatment option in acute cholecystitis

OBJECTIVES Percutaneous cholecystostomy (PC) is an established low-mortality treatment option for elderly and critically ill patients with acute cholecystitis. The primary aim of this review is to find out if there is any evidence in the literature to recommend PC rather than cholecystectomy for acute cholecystitis in the elderly population. METHODS In April 2007, a systematic electronic database search was performed on the subject of PC and cholecystectomy in the elderly population. After exclusions, 53 studies remained, comprising 1918 patients. Three papers described randomized controlled trials (RCTs), but none compared the outcomes of PC and cholecystectomy. A total of 19 papers on mortality after cholecystectomy in patients aged >65 years were identified. RESULTS Successful intervention was seen in 85.6% of patients with acute cholecystitis. A total of 40% of patients treated with PC were later cholecystectomized, with a mortality rate of 1.96%. Procedure mortality was 0.36%, but 30-day mortality rates were 15.4 % in patients treated with PC and 4.5% in those treated with acute cholecystectomy (P < 0.001). CONCLUSIONS There are no controlled studies evaluating the outcome of PC vs. cholecystectomy and the papers reviewed are of evidence grade C. It is not possible to make definitive recommendations regarding treatment by PC or cholecystectomy in elderly or critically ill patients with acute cholecystitis. Low mortality rates after cholecystectomy in elderly patients with acute cholecystitis have been reported in recent years and therefore we believe it is time to launch an RCT to address this issue.

Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival

Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour‐associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF‐β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM‐stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

Enteric nervous system

It is becoming increasingly evident that the nerves of mucosal surfaces may play an important role both during physiological and pathophysiological circumstances. This has, of course, been known for a long time with regard to the skin with its triple reponse. However, research performed during the last decade has shown that this is also true for mucosal membranes. In bronchial asthma, for example, nerves may play an important role in its pathophysiology, explaining the bronchial constriction, hypersecretion, and tissue edema associated with this disease (1). The mucosal lining of the gastrointestinal tract, including the biliary tract, is provided with an extensive nervous supply, the enteric nervous system (ENS). Although known for more than a century, its function has only recently been studied in any detail. This review will deal with our present knowledge of the physiology and pathophysiology of the ENS in the intestines and the gallbladder. The review is divided into two parts, the first being devoted to the intestines and a following one to the gallbladder.It is becoming increasingly evident that the nerves of mucosal surfaces may play an important role both during physiological and pathophysiological circumstances. This has, of course, been known for a long time with regard to the skin with its triple reponse. However, research performed during the last decade has shown that this is also true for mucosal membranes. In bronchial asthma, for example, nerves may play an important role in its pathophysiology, explaining the bronchial constriction, hypersecretion, and tissue edema associated with this disease (1). The mucosal lining of the gastrointestinal tract, including the biliary tract, is provided with an extensive nervous supply, the enteric nervous system (ENS). Although known for more than a century, its function has only recently been studied in any detail. This review will deal with our present knowledge of the physiology and pathophysiology of the ENS in the intestines and the gallbladder. The review is divided into two parts, the first being devoted to the intestines and a following one to the gallbladder.

Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163‐positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163‐negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 × 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X‐rays inducing fusion. In CD163‐positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin‐dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki‐67 non significant (NS). It is concluded that primary rectal cancers may express CD‐163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

Expression of Macrophage Antigens by Tumor Cells

Macrophages are a heterogeneous cell population of the myeloid linage derived from monocytes. These cells show two different polarization states, M1 and M2 macrophages in response to different micro environmental signals. Tumor associated macrophages (TAM) represent the M2 type and promote tumor progression. These cells express antigens that more or less are specific for macrophages like: CD14, CD68, MAC387, CD163, and DAP12. In a series of recent studies it is shown that cancer cells may express these antigens and CD163, MAC387 and DAP12 may be expressed by e.g. breast cancer cells. Thus, 48% of the breast cancers expressed CD163 that is a scavenger receptor normally expressed by macrophages alone. The corresponding figure for rectal cancer is 31%. The expression of CD163 is correlated to early distant recurrence in breast cancer and local recurrence in rectal cancer and reduced survival time in both conditions. Expression of macrophage antigens in breast- and colorectal-cancers may have a prognostic relevance in clinical praxis. One explanation to these findings is that resemblance with macrophages may indicate a more invasive phenotype due to genetic exchange between the primary tumor cells and associated macrophages. This is further supported by the finding that expression of DAP12, a macrophage fusion receptor, in breast cancer is associated with an advanced tumor grade and higher rates of skeletal and liver metastases and overall shorter distant recurrence free survival. Another explanation to the changed phenotype is a genetic exchange between the cells by exosome-mediated transfer.

Effects of Intravenous Vasoactive Intestinal Peptide (VIP) on Gallbladder Function in the Cat

The influence of vasoactive intestinal peptide (VIP) on the concentrating mechanism and the motility in the feline gallbladder has been studied in vivo. A perfusion technique made possible a simultaneous study of the motility and of the net transport of water and electrolytes across the gallbladder wall. It was found that an intravenous infusion of VIP relaxes the gallbladder and induces a net fluid secretion into its lumen. The net absorption of chloride ions was markedly reduced, whereas the net transport of sodium, potassium, and bicarbonate was reversed from an absorption into a secretion. Owing to the presence of VIP-containing nerve fibers in the gallbladder wall, a physiological significance for the secretory gallbladder response to VIP is suggested.

Identification of Helicobacter pylori DNA in Human Cholesterol Gallstones

Background: The gallbladder mucosa secretes hydrogen ions and is covered by mucus. The environmental conditions for bacterial colonization are similar to those in the stomach. Gallbladder stones often contain DNA from enteric bacteria, but no compelling evidence demonstrates that Helicobacter spp. have been present. The aim of this study was to establish bacterial DNA profiles in cholesterol gallstones with special reference to Helicobacter pylori. Methods: Cholesterol gallstones from 20 patients were subjected to polymerase chain reaction, bacterial profiling by temporal temperature gradient gel electrophoresis, automated DNA sequencing, and Southern blot analysis using a Helicobacter sp. specific primer. A nested ureI- PCR assay was used to discriminate between gastric and non-gastric H. pylori. Results: TTGE, partial 16S rDNA sequencing, and hybridization analysis revealed the presence of DNA presumably representing a mixed bacterial flora in cholesterol gallstones, including H. pylori in the gallstone centres in 11 out of 20 patients. In three cases, the ureI -PCR assay revealed non-gastric H. pylori. Conclusions: These data support the presence of DNA from a mixed bacterial population, including H. pylori in cholesterol gallstones, reflecting either that H. pylori is an indigenous part of a flora in the stone-containing gallbladder or, alternatively, that H. pylori colonization in the biliary tract predisposes to cholesterol gallstone formation.

Reflex regulation of flow resistance in the feline sphincter of Oddi by hydrostatic pressure in the biliary tract

Despite wide variations in bile secretion and biliary tract capacitance, the pressure in the bile ducts is fairly constant. Recent studies have demonstrated that both inhibitory and excitatory nerves regulate the activity of the sphincter of Oddi. In the present study, it was consistently found that the resistance by the choledochoduodenal junction to a constant flow, within the physiologic range of hepatic bile output, is reduced when the hydrostatic pressure in the gallbladder and bile ducts is increased from 0 to 10, 0 to 15, and 0 to 20 cmH2O. This response was eliminated by tetrodotoxin or infiltration of the junction between the common bile duct and the cystic duct by mepivacaine, a local anesthetic. The results suggest a homeostatic mechanism during the interprandial periods, when the activity of the sphincter of Oddi is regulated by the distending pressure in the biliary tract. This reflex regulation is mediated by modulation of the activity of inhibitory nerves running along the common bile duct.

An Experimental Method for Studying In Vivo Gallbladder Absorption

A perfusion technique has been developed for the study of net absorption in the gallbaldder of the cat. The lumen of the gallbladder in situ with intact blood vessels and nerves is perfused at a constant rate with bile or a solution of known composition. Differences in volume input and output from the gallbladder are measured with a volume transducer, which in the absence of changes in gallbladder volume reflects net water absorption. By adding polyethylene glycol to the perfusate, net water absorption rate can be calculated from the changes in concentration of this test substance regardless of gallbladder motility. A combined use of these two methods makes possible a concomitant estimation of net water absorption and changes in gallbladder volume. The technique was tested and used for the study of net water absorption from bile, saline and isotonic mannitol solution in the gallbladder lumen.

Use of a virtual reality, real-time, simulation model for the training of urologists in transurethral resection of the prostate

Objective There is a growing need to develop surgical skills outside the operating theatre. In this study we describe the development of a virtual reality training system for practising transurethral resection of the prostate (TURP). Material and methods A face validity study was performed using a questionnaire sent to 28 experienced urologists to find out the ideal characteristics of a simulated TURP. Based on the comments a simulator was constructed and a content validity study was then performed in which nine experienced urologists tested the simulator and answered a second questionnaire. After corrections to the simulator, a basic construct validity test was performed. Results We have developed a computer-based simulator based on the requirements listed by 17 urologists. It consists of a modified resectoscope connected to a haptic device and supported by a frame. The software provides a virtual view of the prostatic lumen and resectoscope tip, a haptic rendering that generates force feedback and a simulation module that computes the information from the haptic device, resectoscope fluid tap and handle and the foot pedals. The software also simulates bleeding, absorption of irrigation fluid and pressure gradients. Variables are measured and presented in a result file after each “operation”. Nine experienced urologists performed a content validity study and changes were made accordingly. A basic construct validity test performed by seven inexperienced students showed a significant improvement in performance after they each performed six simulated procedures. Conclusion We have developed a simulator that may be used to practise TURP and which meets most of the demands raised in a face validity study. A basic construct validity test showed improved performance after repeated practice in the simulated environment.