Microbiological analysis of fluids in postsurgical gastroesophageal intrathoracic leaks obtained by endoscopy: a new way to optimize antibiotic therapy.

BACKGROUND/AIMS: Postsurgical gastroesophageal intrathoracic leakage is a potentially life-threatening condition that is frequently accompanied by mediastinitis and subsequent sepsis. Aspiration of fluids from intrathoracic leaks during endoscopy for microbiological analysis is rarely performed in clinical routine. The aim was to evaluate the role of routine microbiological analysis of intrathoracic leaks via endoscopy and its impact on antibiotic therapy. METHODS: This is a prospective, observational single-center study. Seventeen consecutive patients who presented for endoscopic treatment of intrathoracic leaks were included. Concomitantly, fluids from intrathoracic leaks during endoscopic intervention and blood cultures were obtained and a microbiological analysis was performed. RESULTS: Bacteria and/or fungi were detected by culture of fluid aspirated from intrathoracic leaks in 88% cases, but in none of the blood cultures. In 15 patients, microbial colonization of the leakage was detected despite previous empiric antibiotic therapy; treatment had to be adjusted in all patients according to the observed antibiotic susceptibility profile. CONCLUSIONS: The microbiological colonization of postsurgical gastroesophageal intrathoracic leaks in patients is frequent. Only the direct microbiological analysis of fluids from intrathoracic leaks, but not of blood cultures, is effective for optimizing an antibiotic therapy in such patients.

Endoscopic closure of esophageal intrathoracic leaks: stent versus endoscopic vacuum-assisted closure, a retrospective analysis.

BACKGROUND AND STUDY AIM: Placement of covered self-expanding metal or plastic stents (SEMS or SEPS) is an established method for managing intrathoracic leaks. Recently, endoscopic vacuum-assisted closure (EVAC) has been described as a new effective treatment option. Our aim was to compare stent placement with EVAC for nonsurgical closure of intrathoracic anastomotic leaks. PATIENTS AND METHODS: In a retrospective analysis we were able to identify 39 patients who were treated with SEMS or SEPS and 32 patients who were treated with EVAC for intrathoracic leakage. In addition to successful fistula closure, we analyzed hospital mortality, number of endoscopic interventions, incidence of stenoses, and duration of hospitalization. RESULTS: In a multivariate analysis, successful wound closure was independently associated with EVAC therapy (hazard ratio 2.997, 95 % confidence interval [95 %CI] 1.568 - 5.729; P = 0.001). The overall closure rate was significantly higher in the EVAC group (84.4 %) compared with the SEMS/SEPS group (53.8 %). No difference was found for hospitalization and hospital mortality. We found significantly more strictures in the stent group (28.2 % vs. 9.4 % with EVAC, P < 0,05). CONCLUSIONS: EVAC is an effective endoscopic treatment option for intrathoracic leaks and showed higher effectiveness than stent placement in our cohort.

[Endoscopic vacuum-assisted closure]. / Endoskopische Vakuumschwammtherapie.

Anastomotic leakage in the upper and lower intestinal tract is associated with high morbidity and mortality. Within the last 10 years endoscopic treatment options have been accepted as sufficient treatment option of these surgical complications. Endoscopic vacuum assisted closure (E-VAC) is a new innovative endoscopic therapeutic option in this field. E-VAC transfers the positive effects of vacuum assisted closure (VAC) on infected cutaneous wounds to infected cavities that can only be reached endoscopically. A sponge connected to a drainage tube is endoscopically placed in the leakage and a continuous vacuum is applied. Sponge and vacuum allow removal of infected fluids and promote granulation of the leakage. This results in clean wound grounds and finally allows wound closure. Meanwhile the method was also successfully used in the treatment of necrotic pancreatitis.

Secondary sclerosing cholangitis in critically ill patients: model of end-stage liver disease score and renal function predict outcome.

Secondary sclerosing cholangitis in critically ill patients (SSC - CIP) is an underdiagnosed emerging disease. The aim of this study was to characterize clinical features and prognostic factors for mortality in SSC - CIP. This retrospective study included 54 patients who were diagnosed via endoscopic retrograde cholangiopancreatography (ERCP) after cardiothoracic surgery (n = 21), sepsis (n = 13), polytrauma (n = 11), and others (n = 9). In total, 33 patients who either died (n = 27) or needed liver transplantation (n = 6) were compared with surviving patients (n = 21). The model for end-stage liver disease (MELD) score and need for renal replacement therapy were independent risk factors for mortality. Compared with ERCP, accuracy was 30% for ultrasound and 36 % for liver biopsies. As a result of microbiological bile analysis, 28 % of patients required a change in antibiotic treatment. SSC - CIP is frequently a fatal disease. ERCP should be considered in selected patients to establish the diagnosis and hence provide useful clinical information.

Combination of conservative and interventional therapy strategies for intra- and extrahepatic cholangiocellular carcinoma: a retrospective survival analysis.

Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival.

Measurement of IgG4 in bile: a new approach for the diagnosis of IgG4-associated cholangiopathy.

BACKGROUND AND STUDY AIMS: Immunoglobulin G4 (IgG4)-associated cholangitis (IAC) is difficult to diagnose because on cholangiography the associated biliary tract strictures cannot be differentiated from cholangiocarcinoma or primary sclerosing cholangitis (PSC). Serum IgG4 levels show a low sensitivity and specificity and are unreliable, particularly in patients with related diseases such as PSC. As IAC takes place at the biliary epithelium, we hypothesized that IgG4 measurement in bile may have higher sensitivity compared with serum. METHODS: Bile and serum samples were collected during cholangiography in 67 patients, including 23 patients with PSC, 25 with cholangiocarcinoma, 14 with choledocholithiasis, and five with IAC. IgG4 was measured in both bile and serum. RESULTS: Bile IgG4 levels were markedly elevated in patients with IAC compared with patients with other biliary disorders. Whereas elevated serum IgG4 levels were found both in patients with PSC and IAC, biliary IgG4 levels were only increased in patients with IAC. CONCLUSIONS: The study demonstrates that bile IgG4 measurement is possible and may help to distinguish IAC from other diseases.

Peripapillary duodenal varices as a rare cause of severe bleeding in a patient with no other signs of portal hypertension--successful endoscopic treatment with cyanoacrylate injection.

Duodenal varices (DVs) are a rare cause of upper gastrointestinal bleeding and rather suspected in patients with portal hypertension. Bleeding DVs are difficult to manage and often fatal due to delayed diagnosis. We report on a 71-year-old patient with massive upper gastrointestinal haemorrhage, who did not show any clinical signs of portal hypertension; however, he had a history of duodenal segmental resection 8 years before. The source of bleeding could not be detected with different imaging methods such as angiography and computed tomography. Upper gastrointestinal endoscopy finally revealed DVs, which were located just adjacent to the papilla. After endoscopic injection therapy with n-butyl 2-cyanoacrylate the bleeding stopped immediately and the patient soon stabilised. Despite the peripapillar localisation no signs of pancreatitis or cholestasis occurred; during 10-month follow-up a marked regression of the varices without further signs of variceal bleeding was observed.

[Endoscopic palliation of esophageal and bronchial carcinomas]. / Endoskopische Palliation bei Osophagus- und Bronchialkarzinomen.

Luminal obstruction from tumor growth can in relation to bronchial carcinoma lead to airway and/or esophageal obstruction in breathlessness or swallowing difficulties respectively. Self-expanding stents have become an established method of restoring luminal patency in both the esophagus and central airways, leading to significant symptomatic improvement. Due to anatomical constraints particularly in processes around the tracheal carina, stent implantation within the bronchial system often poses greater difficulty than within the esophagus. Technical difficulties do however arise in the esophagus, specifically in relation to stenotic high-cervical tumors, as well as distal stenosis. In this regard, advances in stent development have resulted in significantly improved outcomes with modern stents. In high-cervical esophageal tumors as well as locally invasive tumors with evidence of tracheobronchial fistulae a shared interdisciplinary care between the gastroenterology and pulmonary teams is necessary for a satisfactory outcome.

[CMV-enterocolitis as a cause for repeated intestinal intussusceptions in an adult patient after liver transplantation?]. / CMV-Enterokolitis bei einer erwachsenen lebertransplantierten Patientin als Ursache rezidivierender Invaginationen?

Intestinal intussusception in the adult is often idiopathic but also known to be associated with chronic inflammatory bowel disease, coeliac disease, tumours or previous abdominal operations. A 22-year-old women after liver transplantation due to Crigler Najar Syndrome suffered from repeated episodes of abdominal pain. The diagnosis of repeated self-limited intestinal intussusceptions was made by computed tomography and ultrasonography. A laparoscopy revealed no cause for the intussusceptions. During a new episode of abdominal pain caused again by an intussusception a colonoscopy was performed that showed aspects of a discreet colitis. In the biopsies CMV was detected by qualitative PCR, while blood tests for CMV pp65 antigen were negative. A therapy with gancyclovir was initiated which lead to remission of the patient's symptoms. A colonoscopy six weeks later showed a completely normal colon, while in the biopsies CMV was not detectable. After a follow-up of one year the patient has not suffered from any further episodes. This case demonstrates the role of chronic intestinal CMV infection as a possible causative factor for repeated intussusceptions in immunosuppressed patients. Whenever possible a PCR for CMV in colon biopsies should be carried out to detect an intestinal CMV infection because as shown in our case results for immunohistopathology and CMV pp65 can be negative despite a chronic infection.

[Splenosis--important differential diagnosis in splenectomized patients presenting with abdominal masses of unknown origin]. / Splenose -- eine wichtige Differenzialdiagnose unklarer abdomineller Raumforderungen bei splenektomierten Patienten.

A 40-year-old female patient was admitted for work-up of multiple abdominal masses. The lymphoma-mimicking tumors were detected accidentally during an ultrasound course. The past medical history was unremarkable besides a status post-traumatic splenic rupture and splenectomy. The patient was asymptomatic, especially there were no complaints of fever, night sweats or weight loss. Laboratory tests did not show pathological results. Ultrasound of the abdomen revealed multiple hypoechoic mesenterial and peritoneal enlarged tumors as well as a subhepatic mass (30 x 20 mm). Transmission computed tomography (CT) showed a normal chest, excluded abnormal thoracal masses and confirmed the multiple abdominal nodules. Microparticles were trapped only by tissue with phagocytosis function as cells of the reticulohistiocytary system in liver and spleen. Uptake of (99 m)Tc-labeled microparticles is specific for splenic tissue. All abdominal masses were detectable by single photon emission computed tomography (SPECT) after intravenous administration of this radiotracer. Ultrasound-guided biopsy proved the presence of spleen tissue with follicular hyperplasia. In conclusion, we report a case of post-traumatic splenosis. In 16 - 67 % of patients who experienced traumatic splenic rupture autotransplanted spleen tissue can be detected. Splenosis therefore is an important differential diagnosis of abdominal masses in splenectomized patients.

[Molecular therapy in gastroenterology and hepatology]. / Molekulare Therapie in der Gastroenterologie und Hepatologie.

During recent years, molecular techniques have significantly impacted our understanding and therapeutic concepts in gastrointestinal and liver disease. In a number of diseases, diagnostic work-up includes molecular data that supplements the phenotypical evaluation. This includes monogenic diseases as well as the identification of genetic risk factors (e. g. NOD2/CARD15 mutation in Crohn's disease) and viral disease. Attempts to replace liver transplantation in hereditary liver disease by targeted molecular interventions (e. g. via viral vectors) are still experimental, but the associated techniques have improved considerably. The molecular identification of therapeutic targets was followed by the development of specifically tailored therapeutics. These agents are mainly used in the treatment of chronic inflammatory bowel disease and gastrointestinal tumors.

[Transcutaneous perianal ultrasound (PAUS) for the imaging of fistulas and abscesses in Crohn's disease]. / Aktuelle Sonographie: Transkutaner, perianaler Ultraschall (PAUS) zur Diagnostik von Fisteln und Abszessen bei M. Crohn.

Pelvic MRI and transanal ultrasound constitute the gold standard for the imaging of perianal inflammatory lesions in Crohn's disease. Perianal ultrasound (PAUS), however, is rarely considered in recent literature. In contrast to the established methods, perianal ultrasound represents an easy, cost-effective and at the same time sensitive method for the imaging of perianal abscesses and fistulas. This article illustrates the performance of perianal ultrasound and shows typical images of pathological findings such as abscesses and fistulas. PAUS is especially useful for acute diagnostics to rule out perianal abscesses and for follow-up evaluation of fistula treatment. For example, complications such as abscesses can be detected in a timely manner.

Malignant lymphoma accompanied by renal cell carcinoma - a not so rare coincidence?

We report a case of a patient who presented with a left sided inguinal swelling. Ultrasound examination clearly revealed a bilateral inguinal lymphoma. In addition, a renal cell carcinoma was diagnosed through ultrasound. The differences in texture between lymph nodes and renal tumour as well as the even concentric swelling of the lymph node sinus permitted a clear cut differentiation between the two entities. CT could not provide this clear distinction. Despite some controversy several case reports as well as a few retrospective studies showed an increased coincidence of renal cell carcinoma and malignant lymphoma. However, a pathophysiological connection has not yet been discovered. This report presents another case of synchronous appearance of renal cell carcinoma and malignant lymphoma and demonstrate the relevance of ultrasound in the discrimination between the two clinical entities. It is essential for physicians performing either sonography and/or CT to be aware of this coincidence to avoid misdiagnosis of lymphadenopathy in patients with renal cell carcinoma as metastasis and, vice versa, renal tumours in lymphoma patients as renal manifestation of the lymphoma.

Simulation of abdomen sonography. Evaluation of a new ultrasound simulator.

AIM: We developed and evaluated a simulator for the sonography of the abdomen in order to improve the teaching quality in sonography training. METHOD: Eleven medicine residents who had received 4 to 12 months full time sonography training performed ultrasound examinations of the right upper quadrant in 5 consecutive patients and in 5 simulator cases. The correctness of their findings and the time required for the examinations were measured. The subjective confidence in their findings and the handling of the ultrasound machines were rated on a visual analogue scale. RESULTS: During patient ultrasound examination 75 % (SEM 9%) of all pathologic findings were recognized by the residents, whereas 71 % (SEM 8%) of the pathologies of the simulator cases were found. This minimal difference was not significant in the paired, two sided t-test (p = 0.15). Severe pathologies did not escape detection. The time required for patient examination(10.57 min, SEM 3.25 min) was not significantly different (p = 0.53) to the time required for the simulator cases (9.59 min, SEM 2.98 min). The subjective confidence in the sonographic findings did not differ significantly (p = 0.39) between the real patient situation (68%, SEM 6%) and the simulation (64%, SEM 12 %). Only the handling of the ultrasound machines was judged to be significantly better (p=0.008) than the simulator (74%,SEM 7% vs. 61 %, SEM 12%). CONCLUSION: In this first direct crossover comparison between real patient sonography and simulator based scanning we proved that the simulator we developed simulates the real patient examination reliably and reproducibly.

An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide.

EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is associated with exposure to a foreign antigen that is often derived from medication, insect venom or food. We report here that, after self-tolerance to myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case a myelin peptide. "Horror autotoxicus", which was initially described by Ehrlich, may not only include autoimmunity to self, it may also encompass immediate hypersensitivity to self, which leads to shock and rapid death.

Roles of mast cells and basophils in innate and acquired immunity.

There have been several recent advances in knowledge about mast cells and basophils in immune responses, of which some are particularly important: a role has been found for heparin in the storage of certain proteases and other mediators in mast cell cytoplasmic granules; an important role for mast cells in the development of several chronic aspects of an asthma model in mice has been discovered; and a new approach has been developed, based on the generation of mast cells from embryonic stem cells in vitro, to investigate mast cell function in vitro or in vivo.

In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo.

An important goal of tissue engineering is to achieve reconstitution of specific functionally active cell types by transplantation of differentiated cell populations derived from normal or genetically altered embryonic stem cells in vitro. We find that mast cells derived in vitro from wild-type or genetically manipulated embryonic stem cells can survive and orchestrate immunologically specific IgE-dependent reactions after transplantation into mast cell-deficient Kit(W)/Kit(W-v) mice. These findings define a unique approach for analyzing the effects of mutations of any genes that are expressed in mast cells, including embryonic lethal mutations, in vitro or in vivo.

Mast cells and basophils in acquired immunity.

In this review we describe the basic biology of mast cells and basophils and discuss their proposed effector and immunoregulatory roles in acquired immunity, particularly the IgE-associated immune responses. While mast cells and basophils share a number of similarities, they also differ in many aspects of natural history and function. Both mast cells and basophils express the high affinity receptor for immunoglobulin E (Fc epsilon RI) on their surface and can be activated to secrete diverse preformed, lipid and cytokine mediators after crosslinking of Fc epsilon RI-bound IgE with bi- or multivalent antigen. Thus, both cell types can represent important effector cells, as well as potential immunoregulatory cells, in IgE-mediated acquired immunity. However, mature mast cells are long-term residents of vascularized tissues, whereas basophils are granulocytic leukocytes that circulate in mature form and must be recruited into tissues that are sites of inflammatory or immune responses. The similarities and differences in the natural history, mediator content and other features of mast cells and basophils not only strongly indicate that these cells represent distinct hematopoietic lineages that can express complementary or overlapping functions, but also offer insights into the specific roles of these cells in acute, 'late phase' and chronic aspects of adaptive or pathological IgE-associated acquired immune responses.

Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.

BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined. METHODS: Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.