Endoscopic ultrasound-guided drainage of abdominal fluid collections after pancreatic surgery: Efficacy and long-term follow-up.

BACKGROUND/PURPOSE: Endoscopic ultrasound-guided drainage (EUS-GD) of postoperative abdominal fluid collections (POFC) following pancreatic surgery is used as an alternative or complement to percutaneous drainage (PD) procedure. The present single-center retrospective study evaluates its efficacy and safety. METHOD: We included consecutive cases with POFC treated by EUS-GD between September 2009 and November 2014 in our department. Technical success, long-term clinical success, recurrence rate and need for surgery were analyzed. RESULTS: 24 procedures in 20 patients (95 % after pancreatic resection) were assessed. Indications for surgery included tumors/lesions located in the pancreas (15/20), chronic pancreatitis (3/20) and duodenal adenoma not completely resectable endoscopically (2/20). EUS-GD was performed within a median of 30 days (IQR: 8.25) for a median fluid collection size of 72.5 mm (IQR: 46.25), requiring a mean of 1.2 sessions with placement of a mean of 2.1 plastic stents (7 Fr/10 Fr) per patient for a mean of 89 days (IQR: 127). Microbiology of aspirated fluid revealed positive cultures in 13 patients, mostly polymicrobial, isolated positive for fungal and 3 multidrug-resistant gram negative (MRGN) in 4 cases. An additional transpapillary drainage was inserted in 1/20 patients. 4/20 patients received PD, mostly before EUS-GD. Technical and clinical success was achieved in 20/20 (100 %) and 18/20 (90 %) patients, respectively, while 2 patients required re-operation. During follow-up (median 630 days after stent removal, range: 45 - 2160), recurrence occurred in 1/18 (5.5 %) patient that was referred for surgery. No death or severe adverse events were noted. CONCLUSION: EUS-GD is an effective, minimally invasive and safe method for therapy of POFC after pancreatic surgery offering long-term remission in about 95 % of cases.

Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO study with biomarker and serum programme.

BACKGROUND: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study. PATIENTS AND METHODS: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0-2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks+1-week rest followed by once 3-weeks+1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were prospectively stained for sorafenib targets and potential biomarkers. Serum samples (first two cycles) were measured for vascular endothelial growth factors (VEGFs), vascular endothelial growth factor receptor 2 (VEGFR-2) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gemcitabine plus sorafenib was generally well tolerated. Four and three patients achieved partial responses in the sorafenib and placebo groups, respectively. There was no difference in the primary end-point, median progression-free survival (PFS) for gemcitabine plus sorafenib versus gemcitabine plus placebo (3.0 versus 4.9 months, P=0.859), and no difference for median overall survival (OS) (8.4 versus 11.2 months, P=0.775). Patients with liver metastasis after resection of primary BTC survived longer with sorafenib (P=0.019) compared to placebo. Patients who developed hand-foot syndrome (HFS) showed longer PFS and OS than patients without HFS. Two sorafenib targets, VEGFR-2 and c-kit, were not expressed in BTC samples. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage. Absence of PDGFRß expression correlated with longer PFS. CONCLUSION: The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients. Biomarker subgroup analysis suggested that some patients might benefit from combined treatment.

[Klatskin tumors: rational diagnostics and staging]. / Klatskin-Tumoren: rationale Diagnostik und Staging.

Klatskin tumors continue to be a challenge for diagnostic assessment and staging due to their longitudinal tumor growth along the perihilar bile ducts. Therefore the rate of non-resectable tumors remains relatively stable despite modern imaging and endoscopic techniques. This article reviews the current diagnostic methods for preoperative staging and the significance for predicting resectability.

Terlipressin in 30 patients with hepatorenal syndrome: results of a retrospective study.

Terlipressin is known to improve renal function in patients with liver cirrhosis and hepatorenal syndrome (HRS). This study investigated effects of duration and dose of terlipressin therapy and predictive factors for positive response to treatment. The clinical charts of 30 consecutive patients with HRS who received terlipressin and albumin based on a determined therapeutic scheme, were retrospectively studied. In 25 (66 %) of 38 treatment episodes complete response was achieved (Kaplan-Meier survival method). Predictive for positive response to treatment were duration of treatment and cumulative terlipressin dosis (p < 0.01, 95 % CI 0.31 - 0.59 and p < 0.01, 95 % CI 0.93 - 0.98, respectively) as well as a low level of serum creatinine and MELD score at inclusion (p = 0.01, 95 % CI 0.3 - 9.85 and p < 0.01, 95 % CI 0.87 - 0.98 respectively) and HRS type II (p = 0.04, 95 % CI 1.04 - 9.93). The median duration of therapy was 6 days +/- 4.9 (SD) vs. 8 days +/- 6.3 in the nonresponder group. The median dose of terlipressin in the responder group was 3.9 mg +/- 1.3 per day vs. 3.4 mg +/- 1.4 in the nonresponder group (p = n. s.). The probability that complete response was obtained at day 17 of treatment was 84 % (95 % CI 0.64 - 0.96), whereas at day 7 it was just 52 % (95 % CI 0.36 - 0.7). In conclusion, these data confirm that terlipressin plus albumin is effective in two-thirds of patients with HRS. Prolongation of treatment beyond 7 days up to 20 days is capable of increasing the response rates. Whether outcome can be predicted depending on parameters like type of HRS and base-level of serum creatinine needs to be confirmed in further studies, especially with regard on the previously revised criteria of HRS.

[Recurrent gastrointestinal bleeding and aortic valve stenosis (Heyde syndrome): need for valve replacement?]. / Rezidivierende gastrointestinale Blutungen bei Aortenklappenstenose (Heyde-Syndrom): Indikation zum Aortenklappenersatz?

UNLABELLED: Angiodysplasia are common in patients over the age of 60. Heyde syndrome describes the coincidence of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia. We describe one characteristic case of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia which subsided after replacement with an aortic valve bioprosthesis. We review the current literature and discuss the actual explanation approaches for this phenomenon. CONCLUSION: There seems to be a clear indication for valve replacement in the case of aortic valve-stenosis and gastrointestinal bleeding due to angiodysplasia.

[Combined simulation training: a new concept and workshop is useful for crisis management in gastrointestinal endoscopy]. / Kombiniertes Simulationstraining: Ein neues Kurskonzept trainiert und verbessert das Krisenmanagement der gastroenterologischen Endoskopie.

INTRODUCTION: Crisis management as well as realistic emergency situations can be trained in the new developed simulation workshop "Gastrointestinal Endoscopy and Crisis Resource Management" by combining a full-scale simulator and the Erlanger Endoscopy Trainer. The aim of the current study was to evaluate the efficiency of the newly developed simulation workshop. METHODS: Endoscopists with more than 12 months experience can train their endoscopic skills and crisis resource management with the help of different simulators. In addition, two different scenarios (GI bleeding with significant blood loss and sedation overdoses) embedded in a realistic surrounding (emergency room) have to be managed by the participants. Vital parameters, endoscopic skills, as well as personal interactions were recorded and graded. RESULTS: 100 participants took part in the newly developed workshop (between June and December 2003). The participants showed a significantly better endoscopic performance and a significantly better crisis management after the standardized training program. CONCLUSIONS: Simulation training plays an essential role in aviation and minimizes the risk for human errors. In the current study it is clearly shown that simulation training is also useful in gastrointestinal endoscopy. The newly developed workshop may thus be of crucial importance to improve personal crisis management. Simulation also leads to an improvement of endoscopic and emergency skills. Accordingly, simulation training should be recommended or offered as an education option in gastrointestinal endoscopy.

Prospective comparison of cardiopulmonary events during minilaparoscopy and colonoscopy under conscious sedation.

BACKGROUND AND STUDY AIMS: Cardiorespiratory parameters were examined throughout diagnostic minilaparoscopy procedures. The same parameters were analyzed during colonoscopy, and the data were compared. PATIENTS AND METHODS: Sixty-five consecutive unselected patients undergoing minilaparoscopy (group 1: ASA I, n = 34; group 2: ASA II/III, n = 31) and 61 consecutive unselected patients undergoing colonoscopy (group 3: ASA I, n = 31; group 4: ASA II/III, n = 30) were included. Oxygen saturation (Sao (2)), heart rate (HR) and mean arterial pressure (RRm) were measured continuously, and 12-lead electrocardiography (ECG) recordings were made at specific times during each procedure. RESULTS: Minor differences were observed, particularly after premedication, probably due to different dosage regimens and timing in the two examination techniques. After premedication, testing for differences from baseline values showed a minor decrease in Sao (2) and RRm in the minilaparoscopy groups in comparison with the colonoscopy groups (median Sao (2), group 1: 99.9 % +/- 0 vs. group 3 : 100 % -1, P = 0.0078; median RRm, group 1: 99.5 - 4 mm Hg vs. group 3 : 96 -16 mm Hg, P = 0.046, and median RRm, group 2 : 110 + 1 mm Hg vs. group 4 : 101 -13.5 mm Hg, P = 0.0007). HR increased in minilaparoscopy in comparison with colonoscopy (median HR: group 2 : 77 + 4 beats/min vs. group 4 : 75.5 +/- 0 beats/min; P = 0.01). Comparison of defined relevant pathological changes in Sao (2), RRm, HR, and ECG showed no significant differences. DISCUSSION: These data indicate that diagnostic minilaparoscopy under conscious sedation is only associated with limited risk in patients with compensated cardiopulmonary diseases. This is probably due to the low insufflation pressure used.

Current practice in managing patients on anticoagulants and/or antiplatelet agents around the time of gastrointestinal endoscopy -- a nation-wide survey in Germany.

Anticoagulants and antiplatelet agents are widely used in the prophylaxis and management of thromboembolic and cardiovascular diseases. Gastrointestinal bleeding is a well-known complication of these agents. Modification of anticoagulant and antiplatelet therapy is often required in patients undergoing surgical procedures and specific recommendations for the perioperative period have been issued. Fewer data exist with regard to the use of these agents around the time of endoscopic procedures. A survey of the American Society for Gastrointestinal Endoscopy (ASGE), performed several years ago, showed a wide variation between endoscopists in the management of anticoagulants and antiplatelet agents in the periendoscopic period. Subsequently, guidelines have been proposed by the ASGE as well as the German Society for Gastroenterology (DGVS). The aim of this study was to investigate the current practices among German endoscopists regarding the use of these medications in patients undergoing endoscopic procedures and to assess their adherence to published guidelines. Our data demonstrate that, in spite of the dissemination of guidelines, there is still a wide variation in the periendoscopic management of patients who are at increased risk for bleeding due to anticoagulants, especially in patients taking antiplatelet agents.

Minilaparoscopy in the diagnosis of peritoneal tumor spread: prospective controlled comparison with computed tomography.

BACKGROUND: Early diagnosis of peritoneal spread in malignant disease prevents unnecessary laparotomies. Minimally invasive laparoscopy with the patient under conscious sedation is a new, easily feasible diagnostic technique. This study compares prospective and controlled diagnostic minilaparoscopy with computed tomography (CT) scan for the diagnosis of peritoneal metastases. METHODS: In this study, 56 patients with malignant disease were prospectively investigated with diagnostic minilaparoscopy and CT scan. RESULTS: The study criteria were fulfilled by 54 patients. Minilaparoscopy detected peritoneal carcinosis in 28 of 54 cases, whereas CT detected the disease in 14 of 54 cases. For 36 patients, the diagnosis could be verified by histologic examination of peritoneal biopsies or laparotomy. In this group, minilaparoscopy detected peritoneal carcinosis in 25 of 36 cases, whereas CT detected the disease in 12 of 36 cases. CONCLUSIONS: Minilaparoscopy was more sensitive than CT in detecting peritoneal carcinosis (100% vs 47.8%; p < 0.01). Considering its low grade of invasiveness and superior sensitivity, minilaparoscopy should be regarded as the procedure of choice for the early detection of peritoneal carcinosis.

Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child-Pugh A and macronodular disease.

BACKGROUND AND STUDY AIMS: The diagnosis of cirrhosis has prognostic and therapeutic implications, but early forms are difficult to diagnose. Laparoscopy with histology has been reported to be superior to histology alone, but is often considered to be too invasive. This study aimed to assess whether minilaparoscopy offers similarly high sensitivity coupled with only minor invasiveness. PATIENTS AND METHODS: Minilaparoscopy with biopsy was performed in 226 consecutive patients with chronic liver disease. Cirrhosis was diagnosed macroscopically primarily on the basis of nodularity in a nontumorous liver. A histological diagnosis using the modified Knodell score was made without knowledge of the macroscopic assessment. RESULTS: Biopsies from 22 patients were inadequate for histological assessment, and 16 of these were considered to be cirrhotic from macroscopic observation. Out of 204 liver biopsies, 94 (46 %) were macroscopically identified as cirrhotic; 68/204 (33 %) showed stage 5 or 6 fibrosis (incomplete or complete cirrhosis). Histological understaging occurred mainly in patients who were otherwise diagnosed as having early Child-Pugh A cirrhosis, macroscopically incomplete cirrhosis and macronodular cirrhosis; 4/204 (2 %) of patients with cirrhosis histologically were understaged macroscopically. CONCLUSIONS: Macroscopic evaluation during minilaparoscopy increases the sensitivity of detection of liver cirrhosis, compared with biopsy alone, by more than 30 %. Because of its minimal invasiveness, minilaparoscopy combined with biopsy is recommended as a superior method for the staging of chronic liver disease.

Minilaparoscopy-guided spleen biopsy in systemic disease with splenomegaly of unknown origin.

With the advent of a minimally invasive laparoscopy technique, the advantages of diagnostic laparoscopy are being rediscovered. We report here on four patients with systemic disease of unknown origin and splenomegaly, in whom minilaparoscopy-guided splenic biopsy yielded a definitive diagnosis. Four patients with unclear systemic disease were studied using diagnostic minilaparoscopy and guided spleen biopsy, after failure of diagnostic work-up. Minilaparoscopic spleen biopsy revealed the diagnosis of a B-cell non-Hodgkin's lymphoma in two cases. In one patient, who had a history of Still's disease, the spleen biopsy showed granulocytic infiltration in the spleen typical of an acute episode of Still's disease. One patient with a known immunodeficiency syndrome (stage C III) showed multiple hypodense lesions in the spleen. Biopsy allowed a diagnosis of mycobacterial infection, with identification of Mycobacterium tuberculosis. No major complications occurred in any of the four cases; post-biopsy bleeding was observed in three of the four, but was easily managed by argon plasma coagulation or application of fibrin glue, or both. We recommend the use of spleen biopsy as a diagnostic tool in splenopathy of unknown origin if previous diagnostic methods have failed to yield a definitive diagnosis.

[Safety and value of minilaparoscopy in high risk patients]. / Sicherheit und Wertigkeit der Minilaparoskopie bei Hochrisikopatienten.

INTRODUCTION: Coagulopathies and thrombocytopenia may constitute contraindications for percutaneous liver biopsy. We investigated the safety and value of visually guided liver biopsy using minilaparoscopy in patients with coagulation disorders. PATIENTS AND METHODS: We studied 50 patients requiring a liver biopsy, but whose risk of severe bleeding complications was considered too high for the following reasons: INR > 1.5 (40%), platelets 50/nl (36%) or both (18%), other coagulopathies (6%). Indications for liver biopsy were: Hepatopathy of unknown etiology (38%), fulminant liver failure (18%), virus induced hepatitis (6%) and evaluation for liver transplantation (38%). Patients underwent minimally invasive diagnostic laparoscopy and liver biopsies were obtained with a Silverman or Menghini needle. Bleeding was stopped or prevented by coagulation with the argon beamer or a monopolar probe or application of fibrin glue. RESULTS: Macroscopical assessment of the liver was possible in all patients. A liver biopsy was performed in 47/50. 46/47 biopsy specimens were large enough to allow reliable histological evaluation. The diagnostic procedure had major therapeutic consequences in 35/40 patients. No relevant bleeding from the liver biopsy site occurred. CONCLUSION: We demonstrated that laparoscopically guided liver biopsy is safe even in patients with a very high risk of bleeding complications because of coagulation disorders. It is therefore an attractive and preferable alternative to transjugular liver biopsy.

Cellular and humoral immune responses against autoreactive T cells in multiple sclerosis patients after T cell vaccination.

Myelin basic protein (MBP)-reactive T cells may play an important role in the autoimmune pathogenesis of multiple sclerosis (MS). MBP-reactive T cells can be specifically targeted by T cell vaccination, a procedure whereby MS patients are immunized with attenuated autologous MBP reactive T cells. T cell vaccination induces immune responses to the vaccine cells together with a depletion of MBP reactive T cells. Forty-nine MS patients were treated with T cell vaccination in an extended phase I trial to study the safety, immune responses and clinical effects of T cell vaccination. In the present paper the immune responses towards the vaccine cells were characterized. Substantial long-term in vitro proliferative responses were observed in all treated patients. Some patients, immunized with different clones, displayed distinct proliferative reactivity against the various vaccine clones, suggesting unequal immunogenic properties of these clones. Reactive TCRalphabeta(+), CD8(+)and CD4(+)T cells, and to a lesser extent, gammadelta T cells and NK cells were observed to in vitro stimulation with the vaccine cells. A small fraction only of CD8(+)T cells expressed cytolytic and inhibitory anti-clonotypic reactivity against the vaccine cells. Stimulation with the vaccine clones predominantly induced expression of pro-inflammatory cytokines in these mixed cultures, although one vaccine clone consistently induced production of IL-4. CD4(+)T cells are the major cytokine-producing cells in these anti-vaccine lines. We could not detect upregulated antibody responses to the vaccine cells in most patients, although a temporary antibody response was observed in one patient. In conclusion, immunization with attenuated autoreactive T cells induces a complex cellular response specifically targeted at the vaccine cells, but no antibody responses. These data provide further insights into the mechanisms of T cell vaccination and improve our understanding of the complex regulatory networks of autoreactive T cells.

[Ascorbic acid and cancer of the duodenum. An experimental study (author's transl)]. / Vitamin C und Dünndarmkrebs. Eine experimentelle Studie.

This study applies to the agency of vitamin C on chemical carcinogenesis in the small intestine of rats. Administration of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in drinking water produced tumors of the small intestine after 18 weeks in more than 90%. The induction of tumors could not be suppressed by a large amount (2-3%) of sodium ascorbate in food, but the depth of tumor infiltration was restricted. Cancer developed in 29 of 36 rats receiving ENNG only. In 25 animals of this group growth of tumor corresponded to a P4 stage. In 24 of 35 animals, additionally receiving vitamin C, P4 stage was observed in only 13 cases. Pathological changes in the small intestine could not be observed after the sole administration of vitamin C.