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Immune checkpoint inhibitors (ICIs) may induce persistent immune-related adverse events (irAEs). We investigated persistent irAEs and implications on patients' lives compared to non-ICI-induced autoimmune diseases (AIs).The multicentre, cross-sectional study comprised 200 patients with cancer ≥12 weeks after ICI cessation (ICI-patients) and 2705 patients with AIs (AI-patients), recruited in German outpatient clinics and support groups. The prevalence of persistent irAEs subdivided in long-term (12 weeks to 12 months) and chronic irAEs (≥12 months) since ICI discontinuation, health-related quality of life (HRQoL) using the EuroQol 5D-5L (EQ-Index/VAS score), and burden of autoimmune symptoms and respective therapies were assessed.Long-term/chronic irAEs occurred in 51.9%/35.5% of outpatient ICI-patients, including arthralgia (16.7%/16.1%), myalgia (13.0%/14.0%), hypothyroidism (11.1%/10.8%), xerostomia (7.4%/8.6%), vitiligo (13.0%/7.5%) and hypophysitis (9.3%/7.5%). ICI-patients with long-term/chronic irAEs reported clinically significantly reduced HRQoL compared to ICI-patients without long-term/chronic irAEs (EQ-Index score: 0.767/0.752 versus 0.920/0.923, p 0.001/0.001; EQ-VAS score: 52.2/52.0 versus 63.6/74.7, p =/ 0.040/0.001). Multiple linear regression analyses confirmed clinically significant reductions in HRQoL scores by chronic irAEs (EQ-Index/VAS score: -0.163/-23.4, p 0.001/0.001). HRQoL, burden of autoimmune symptoms and burden of respective therapies in ICI-patients with chronic irAEs were similar to AI-patients with non-exacerbated AIs. Patients with chronic irAEs felt inadequately informed about side-effects compared to patients without chronic irAEs (p 0.001).Persistent irAEs impose a significant burden on patients after ICI cessation. Especially in early tumour stages, risk-benefit ratios must be carefully evaluated, and patients need to be informed about potential long-term sequelae.

To investigate the perioperative management and outcome of patients undergoing abdominal surgery with additional vascular (comorbid) alterations for internal quality assurance of the clinical results.Over a defined study period all consecutive cases of the aforementioned profile were documented and retrospectively analyzed as part of an ongoing prospective monocentric observational study to reflect the daily surgical practice.Over 10 years (from January 1999 to December 2008), a total of 113 cases were registered. Pancreas resection including vascular reconstruction showed the highest percentage (30.1%). Within the target patient groups, similar outcome data were found compared with international reports. An exception was in the case of mesenteric ischemia, where open surgery was more frequently used in comparison to the study situation (included together were patients treated by surgery and interventions). The majority of vascular alterations during the postoperative course and iatrogenic lesions occurred following pancreas resection. In the therapeutic profile there are two particularly important measures, namely open surgery on one hand and image-guided radiology as well as endoscopy on the other hand. The majority of patients with a rare visceral artery aneurysm (considerable potential for rupture or erosion) were more frequently treated with image-guided interventional radiology versus open surgery. This conforms to the current well-established sequential patient (individual), results, and, in particular, risk-adapted staged treatment approach.Additional vascular surgical treatment of problematic situations during abdominal surgery or in emergency cases is not daily routine; however, it is a challenging field including a considerable potential for complications (morbidity) and definitely mortality. This requires an experienced surgeon with high expertise, if possible in a center for vascular medicine.

Novel slim and shapely sp3-rich nitrogen containing heterocyclic ring systems are sought-after platforms for the expansion of molecular diversity in lead discovery. The present work describes the synthesis and characterization of a series of derivatives of hitherto unknown 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines 2. This approach was guided by a computational study, aiming at an optimization of previously reported [1,2,4]triazolo[1,2-a]pyridazine-1-thiones 1 known to inhibit the inducible nitric oxide synthase (iNOS). The title compounds are accessible by methylation of compounds 1 under mild conditions. The products were biologically evaluated by the same cell-based assay as applied for previous products of type 1 using RINm5F cells, which were stimulated to produce NO on the influence of proinflammatory cytokines IL-1β and IFN-γ. Compounds 2 did not display the anticipated improved iNOS inhibitory activity in the selected assay but contribute to SAR in the field. In addition, an unprecedented formation of side-products 3 via oxidation has been investigated. The novel scaffolds represent attractive starting points for the construction of diverse molecules which differ considerably from known compounds based on flat and lipophilic aromatic scaffolds.

Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6–3.79) for all evaluable patients and 8.4 months (95% CI: 0–18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08–9.31) and 9.4 months (95% CI: 4.82–13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24–15.35) versus 2.7 months (95% CI: 1.03–4.36; P = 0.002), and 9.8 months (95% CI: 3.23–16.37) versus 4.4 months (95% CI: 3.14–5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of

Nonadherence may cause severe health problems in heart transplant (HTx) recipients.The present study aimed to investigate adherence to prescribed medication and recommended lifestyle habits in post-HTx patients and to assess associations between adherence, quality of life (QOL), and psychological well-being.A questionnaire package was sent to all HTx patients from our clinic (n = 858) to answer questions anonymously on medication adherence, dietary recommendations (avoidance of raw animal products and ice cream), pet keeping (risk of zoonosis), anxiety and depression, QOL, and posttraumatic stress disorders.Of the contacted patients, 524 (61%) responded and 505 fulfilled the inclusion criteria (age ≥18 years and ability to understand German). Of the study participants, 72.4% reported taking their medications very correctly, 72.2% stated consuming alcohol less often than once a week, 58.3% performed physical exercise at least once a week, one-third reported eating nonrecommended foods, 22.1% stated pet keeping, and 4.3% reported smoking. Adherence to prescribed medication was positively associated with age ( P.001) and mental QOL ( P = .015) but was unrelated to eating nonrecommended foods ( P.05). Depressiveness correlated inversely with physical QOL ( r = -0.232; P.01) and mental QOL ( r = -0.411; P.01). Stress disorders and minor stressful events were reported by 7.8% and 46.6%, respectively. Stress disorders correlated inversely with mental QOL ( r = -0.282; P.01) and physical QOL ( r = -0.422; P.01).Many HTx patients adhere to prescribed medications and health advice. Nevertheless, nonadherence is a problem, especially in younger HTx patients, indicating the need for a nonadherence crisis intervention program for long-term HTx patients.

Purpose: The purpose of this study was to find out whether pneumothorax detection and exclusion is superior in expiratory digital chest radiography. Materials and Methods: 131 patients with pneumothorax with paired inspiratory and expiratory chest radiographs were analyzed regarding localization and size of pneumothorax. Sensitivity, specificity, negative (npv) and positive predictive value (ppv) as well as the positive (LR+) and negative likelihood ratio (LR-) were determined in a blinded randomized interobserver study with 116 patients. The evaluation was performed by three board-certified radiologists. Results: In 131 patients, there were 139 pneumothoraces, 135 (97.1 %) were located apical, 88 (63.3 %) lateral and 33 (23.7 %) basal. Sensitivity was 99 % for inspiratory and 97 % for expiratory radiographs. The interobserver study yielded a mean sensitivity of 86.1 %/86.1 %, specificity of 97.3 %/93.4 %, npv of 88.7 %/88.5 % and ppv of 96.7 %/92.1 % for inspiration/expiration. For inspiratory radiographs the LR+/LR- were 40.2/0.14 and for expiration 13.9 and 0.15. McNemar-Test showed no significant difference for the detection of pneumothoraces in in-/exspiration. Conclusion: Inspiratory and expiratory digital radiographs are equally suitable for pneumothorax detection. Inspiratory radiographs are recommended as the initial examination of choice for pneumothorax detection, an additional expiratory radiograph is only recommended in doubtful cases. Key Points: • Basal pneumothoraces during inspiration demonstrate a greater width than during expiration. • There is statistically no difference between inspiration/expiration for the diagnosis of pneumothorax. • An image taken during inspiration is recommended to confirm or rule out a pneumothorax. Citation Format: • Thomsen L, Natho O, Feigen U et al. Value of Digital Radiography in Expiration in Detection of Pneumothorax. Fortschr Rontgenstr 2014; 186: 267 – 273

Objectives Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Materials and methods Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90–99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. Results In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90–99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. Conclusions In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

Lymphoid hyperplasia of the intestine has been associated with multiple diseases and symptoms. This study was undertaken to analyze the number and topographical distribution of the lymphoid follicles. A total of 302 adult consecutive patients were enrolled when they underwent elective colonoscopy. Standardized pictures from terminal ileum and colon were taken using video colonoscopes. In each picture, the number, size, and mucosal elevation of lymphoid follicles were analyzed in relation to histological and immunological findings and medical history. Lymphoid hyperplasia was found to be most extensive in the terminal ileum and cecum. Patients with untreated gastrointestinally mediated allergy (GMA) showed the highest number of lymphoid follicles per visible field in the terminal ileum ( P < 0.001) and cecum ( P = 0.003) vs. the control group. Patients with infectious colitis also showed a high number of lymphoid follicles per endoscopic visible field in the transverse colon ( P = 0.020). The presence of lymphoid hyperplasia is a frequent finding during colonoscopy. It may indicate an enhanced immunological mucosal response to antigenic stimulation such as GMA or infection.

To investigate the relationship of strictures of the common bile duct (CBD) with pain in patients with chronic pancreatitis (CP) and jaundice.A total of 61 patients with CBD strictures caused by CP of alcoholic etiology were treated by endoscopic stent insertion for 1 year with scheduled stent exchanges. Pain was assessed using a visual analogue scale, and analgesic medication was recorded prior to and after endoscopic treatment.Endoscopic drainage was successful in all cases, with complete resolution of jaundice during the 1-year follow-up period. Prior to the endoscopic stent insertion, pain scores were 6.8 +/- 6.3. Following stent therapy pain scores were 7.7 +/- 7.7. Pain scores, the number of patients requiring analgesics, the required amount of analgesics, and the type of analgesic medication did not change following treatment of CBD stricture.Successful endoscopic drainage of biliary obstruction has no influence on pain pattern in patients with CP. CBD obstruction does not cause pain in patients with CP.

Reduced pulmonary diffusion capacity is a hallmark of COPD, although the relative contribution of the subcomponents of pulmonary diffusion--membranous component (Dm) and capillary volume (Vc)--is unknown. These components can be measured with the method of NO single-breath diffusion (DLNO). In a prospective study, pulmonary function tests including spirometry, body plethysmography and single-breath measurements of diffusion capacity with CO and NO were performed in 183 patients with COPD of varying severity. There was a severity-dependent decrease in DLCO. Furthermore, Dm as well as Vc was positively correlated with the severity of COPD measured by FEV1. In all stages of COPD, reduction of Vc was more pronounced than constriction of Dm. In patients with most severe COPD, the preponderance of the reduction of Vc was significantly more marked than in milder stages.We conclude that Dm as well as Vc contributes to the reduction of DLCO in COPD, with a predominance of Vc at all stages of COPD. This confirms the idea that the loss of pulmonary capillaries in COPD is functionally relevant.

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.

HISTORY AND INTERVENTION: A 52-year-old female patient underwent open abdominothoracic cardia and esophageal resection with gastric transposition because of histologically diagnosed Barrett metaplasia with "high-grade" intraepithelial neoplasia (HGIEN) and parts of an invasive adenocarcinoma. The anastomotic insufficiency on the 10th postoperative day including an esophagobronchial fistula prompted to a subsequent surgical re-intervention with suture of the fistula, lavage and additional drainage, an endoscopic stenting of the fistula from esophageal site, as well as repeated (n = 22) bronchoscopic applications of fibrin glue (1-3 ml each) into the lumen of the fistula after each bronchoscopic lavage of the fistula until the complete closure was achieved. The changeful clinical course of 77 days on the surgical ICU was characterized by secondary complications such as pneumonia, mediastinitis and respiratory insufficiency with long-term artificial respiration and creation of a percutaneous dilatation tracheotomy.The application of fibrin glue can be considered a promising, minimally invasive therapeutic option in the management of postoperative fistula after esophageal resection, which requires expertise in decision-making and the finding-specific approach, in particular, if indicated inital steps of the sequential complication management such as surgical re-intervention and conventional endoscopic measures (stenting, Endo-VAC[-sponge]) do not provide great therapeutic potential any more due to the prolonged postoperative time course and the unfavorable local findings. In the presented case, modes of an assisted artificial respiration with low pressure and short phases of apnoe after fibrin glue application were the crucial predictions for an initial and favorable adhesion of this glue and finally for a successful sealing resulting in a sufficient closure of the fistula.

The square of ultrasound transmission velocity in a material is related to the modulus of elasticity, which is known to be an indicator of stability in bone. The aim of our study was to use ultrasound transmission velocity to obtain information about the material properties of bone tissue, keeping other factors possibly influencing ultrasound transmission as constant as possible. Apparent phalangeal ultrasound transmission velocity (APU) measured in 54 isolated, fresh pig phalanges was shown to be independent of bone mineral density (BMD) measured by SPA. Fastest sound transmission led exclusively through cortical bone so that intertrabecular connectivity in spongious bone could not influence the result. In humans APU was measured in the mediolateral direction at the midphalanx of the middle finger. In 53 healthy subjects (15–81 years old; 27 women, 26 men), there was a decrease of APU with age (r=−0.30, p

Obstruction of bile flow following pancreatoduodenectomy can be caused by stenosis of the hepaticojejunostomy created at the time of surgery, obstruction of the bile-draining jejunal loop, stones or, very rarely, ingested foreign bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or the once popular side-to-side-choledochduodenostomy, the creation of a hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling intestinal content such as ingested foreign bodies or food fibers to migrate into the bile duct. We report on the case of a patient developing biliary tract obstruction due to fibrous material in the common hepatic duct 15 years after pancreatoduodenectomy. In addition, an overview of the literature on the rare phenomenon of foreign body-associated obstructive jaundice is given.

Knowledge on potentially pathogenic microbes including characteristics of their antibiotic resistance in septic patients as well as on the ward- and department-specific microbial spectrum can be considered essential for an efficient initiation of an adequate antimicrobial treatment, which turns out to become pivotal for patient outcome. Permanent changes in microbial patterns and antibiotic resistance can only be identified by a continuous investigation of various microbiological specimens.Based on the retrospective evaluation of prospectively collected data on microbiological investigations of the surgical ICU in 1996, 2002, 2004 and 2005, the short- and long-term changes by trend of microbial spectrum and antibiotic resistance following reorganisation and restructuring of the University Hospital from the more traditional pavillon-based system to a multidisciplinary complex building in 2003 were investigated.Twice a week, routine microbiological testing of blood and urinary cultures as well as swabs from wound areas and endotracheal swabs were initiated in septic patients (suspect, manifestation) or in case of their clinical impairment. The microbial spectrum was sub-divided according to Gram-staining (Gram-positive/ -negative), various species and fungi with descriptive absolute and relative data values. -Various groups and time periods were statistically compared using χ² test as appropriate. P values0.05 were considered statistically significant.In total (n (Total) = 4 899), microbiological testing resulted in the detection of microbes in 699 and 833 blood and urinary cultures (14.3 % and 17 %, respectively) as well as 1 232 wound swabs (25.1 %) together with 2 135 samples from the endotracheal sites (43.6 %). During the short- (2002 vs. 2004) and long-term analyses (1996 vs. 2005), the proportion of Gram-positive microbes increased. Al-though Gram-positive bacteria can be considered the most frequent microbes for bacteriemia, there was a shift onto urinary and wound infections as well as pneumonias through the observation period. Despite the decreasing incidence of Enterococcus and the consistent proportion of MRSA, the increase of resistant Enterococcus strains (0 % vs. 43.2 %; P0.05) is critical. However, in the Gram-negative microbial spectrum there was an increase of the bacteraemia rate but a fall of the detection rate in wound and endotracheal swabs. In parallel, an increase of the detection rate of E. coli in blood (6.5 % vs. 45.5 %; P0.05) and endotracheal swabs (9.2 % vs. 16.2 %; P0.05) is associated with an increase of multiresistant Enterobacteriaceae strains (0 % vs. 30.7 %; P0.05). The portion of multiresistant strains of Pseudomonas with 31 % stayed the same through the 10-year time period. While Candida-based colonisation showed a decreased incidence (25 % vs. 15 %; P0.05) during the whole investigation period, there was a relative rise in the frequency of candidemia.ICU relocation from the pavillon-based system to a new complex clinic building was not associated with any significant alteration of the microbial spectrum on the surgical ICU. Increasing incidences of resistant Enterococcus and Gram-negative problematic microbes may indicate a general spread of multi-resistant microbes under the steady selecting pressure of a not always adequately initiated antibiotic / antimicrobial therapeutic regimen and underline the required but specific and selected microbiological screening.

worldwide, orthotopic heart transplantation (HTx)remains an accepted therapeutic option in the treatment ofheart failure. As cardiac transplantation evolved, malignantdisorders in the postoperative course became a seriouscomplication after solid organ transplantation. With im-proved survival, the first reports on postoperative lympho-proliferative disorders

Under inflammatory conditions, the pleiotropic cytokine interleukin-10 (IL-10) is released in many tissues. It mediates anti-inflammatory effects in particular by inhibiting the release of T helper type 1 (Th1) cytokines. In contrast, we show here that NK cell cytotoxicity against autologous macrophages is elevated if both cell types are cultured with IL-10. The expression of most activatory NK receptors is increased after culture in the presence of IL-10. On the other hand, macrophages cultured in the presence of IL-10 show elevated expression of the NKG2D ligands major histocompatibility complex (MHC) class 1-like molecules (MIC) - A and - B, as well as UL-16 binding proteins (ULBP) - ULBP-1, ULBP-2 and ULBP-3. By masking the interaction of NK cells with macrophages through interruption of the NKG2D receptor with its ligands, we could reverse the IL-10-induced lysis of macrophages. Our data therefore reveal that IL-10 may exert a novel immunomodulatory role by stimulating NKG2D ligand expression on macrophages, thereby rendering them susceptible to NK cell elimination. This suggests that NK cells would delete macrophages and potentially other immature antigen-presenting cells (APC) or their precursors under inflammatory conditions as a feedback mechanism to shut off uncontrolled immune responses.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

Retroperitoneal soft-tissue sarcomas (RSTS) represent a rare and heterogeneous class of diseases for which the clinical management is still largely non-standardised. Based on a selective review of recent publications, it was the purpose of the present review article to summarize the current concepts of disease classification, diagnostics and surgical as well as multimodal therapy for these tumors.A clinically based empirical review derived from a literature search focusing on publications from the past 5 years was carried out.Due to the paucity of randomised-controlled trials, therapy for RSTS is largely based on personal experience, retrospectively gathered data and historical controls. Pre-therapeutic planning requires precise information on the localisation, extension, and texture of the tumor through cross-sectional imaging (CT, MRI) as well as histological diagnosis through percutaneous or open biopsy. Complete tumor resection is crucial. Recent studies have confirmed the importance of microscopically negative resection margins which has subsequently led to a trend towards more radical resection. Chemotherapy does not play a role in the adjuvant setting except in clinical trials; however, radiotherapy has been controversely debated in adjuvant RSTS therapy. Efforts to limit radiation toxicity include modern techniques as well as a strategy of using pre-resection radiotherapy instead of postoperative radiation. Surgery is also the treatment of choice for locally recurrent RSTS and pulmonary metastases. The prognosis of RSTS depends on the quality of surgical care and several disease-specific factors (histological type, grading).The clinical management of RSTS is complex and can only partly be considered as evidence-based. Due to the required level of experience in the treatment of these tumor lesions and the involvement of several subspecialties, pre-therapeutic planning, treatment and follow-up should be limited to high-volume surgical centres. In order to achieve microscopically negative resection margins, multivisceral resections are a valuable option after thorough consideration of the risks and benefits. Adjuvant radiotherapy needs to be decided upon on an individual basis, taking into account patient- and tumor-specific factors as well as resection status.

This study was a pre-planned country-specific secondary analysis of results in Germany from a multinational multicenter observational study to retrospectively evaluate clinical outcomes with caspofungin in patients with probable and proven invasive fungal infection following solid organ transplantation (SOT).Data were retrospectively collected on a single episode of invasive fungal infection (IFI) in patients who had a SOT between January 2004 and June 2007. Effectiveness was reported as the proportion of patients who received at least five doses of caspofungin with a favorable (complete or partial) response. Safety was assessed for patients who received at least one dose of caspofungin. Descriptive statistics were employed for all evaluations.A total of 41 SOT patients (27 male, 14 female; median age 56 years, median APACHE II score at start of caspofungin therapy 23) were enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and liver (46%). Prevalent risk factors for IFI at baseline were use of central venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients, 90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of SOT procedure5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in 34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy for IFI, in most cases because they were refractory to prior antifungal drugs. Immunosuppressants were administered with caspofungin in 39 out of 41 patients (95%). In subjects with at least 5 doses of caspofungin (modified intention to treat population) the favorable response rate at the end of caspofungin therapy was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%), 86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with combination therapy. No (serious) adverse events or drug interactions related to treatment with caspofungin were reported. The overall survival rate was 79% (26 out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin treatment.Caspofungin was found to be an effective treatment of probable and proven invasive fungal infections in patients following SOT in Germany.

M. Winkler, J. Pratschke, U. Schulz, S. Zheng, M. Zhang, W. Li, M. Lu, D. Sgarabotto, G. Sganga, P. Kaskel, S. Chandwani, L. Ma, J. Petrovic, M. Shivaprakash. Caspofungin for post solid organ transplant invasive fungal disease: results of a retrospective observational study. Transpl Infect Dis 2010: 12: 230–237. All rights reserved Objective This study was designed to determine clinical outcomes with caspofungin in patients with proven or probable invasive fungal infection (IFI) after a solid organ transplant (SOT) procedure. Methods In this retrospective observational study, data were collected for a single episode of IFI in patients with an SOT between January 2004 and June 2007. Response was determined by the investigator as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT). The primary effectiveness population was the proportion of patients who received ≥5 doses of caspofungin (modified all-patients-treated population). Safety was assessed for patients who received ≥1 dose of caspofungin. Results A total 81 of patients from 13 sites in China, Germany, Italy, and the United Kingdom were enrolled, including 49 (60%) liver, 22 (27%) heart, 5 (6%) lung, 2 (2%) kidney, 2 (2%) liver and kidney, and 1 (1%) pancreas and kidney recipients. Candidiasis was diagnosed in 64/81 patients (79%) and aspergillosis in 22/81 patients (27%). Most patients received caspofungin monotherapy (75%). Caspofungin was given as first-line therapy to 59 (73%) patients. The overall favorable response at EOCT was 87% (58/67; 95% confidence interval [CI]: 76%, 94%), with favorable responses in 88% (43/49; 95% CI: 75%, 95%) of patients receiving caspofungin monotherapy and 83% (15/18; 95% CI: 59%, 96%) of patients receiving combination therapy with caspofungin (modified all-patients-treated population). Response by type of SOT was as follows: liver 87% (39/45), heart 93% (14/15), kidney 100% (5/5), and lung 50% (2/4). An overall survival rate (all-patients-treated) of 69% (56/81; 95% CI: 59%, 79%) was observed at 7 days post EOCT. No serious drug-related adverse events were reported. Conclusion In this study, caspofungin was effective and well tolerated in the treatment of IFIs involving SOT recipients.

A high-performance liquid chromatographic method for the determination of low concentrations in serum of apovincaminic acid, the main metabolite of vinpocetine, is reported. The assay includes a two-step ion-pair extraction with tetrabutylammonium as counter ion. Recovery is ca. 40%. Separation is performed on a narrow-range 5 microns particle size octadecylsilane modified silica packing. Heptanesulphonic acid is the pairing ion in the eluent, and the ultraviolet detection wavelength is 224 nm. Yohimbine serves as the internal standard. The assay is fast, accurate and sensitive quantifying at least 5 ng/ml apovincaminic acid in serum. The method was applied to the analysis of serum samples from aged subjects, treated with a 20-mg dose of vinpocetine.

At the Heart Center North Rhine-Westfalia, Germany, more than 1,500 adult cardiac transplantations and more than 100 pediatric cardiac transplantations have been performed since the transplant program was initiated in 1989. Each year, we take care of 800 cardiac transplant recipients and 1,700 patients with heart failure who are in a long-term program for cardiac transplantation or on the Eurotransplant waiting list for cardiac transplantation. We have experience with ventricular assist device implantation as bridge to transplant in more than 300 patients. In total, our clinical know-how with cardiac transplant recipients is based on 10,800 patient-years of observation. In 2006, we transplanted the first donor heart worldwide with the Organ Care System, a technology capable of maintaining human organs in a functioning state ex-vivo. Usually, our transplant recipients have more preoperative risk factors than cardiac transplant recipients at other German heart centers. Our postoperative patient care is individualized with respect to immunosuppression and the performance of myocardial biopsies and coronary angiography. Since 1989, we have performed 31 cardiac retransplantations.

Metacarpophalangeal flexion of the thumb is known to be highly variable. To obtain normative values, active metacarpophalangeal flexion of the thumb was measured bilaterally in healthy Caucasian adults (female n = 403; male n = 366) in a standardized manner. Independent of gender, inter-individual variation was high, ranging between 16 degrees and 90 degrees and showing a continuous decrease with increasing age. Women showed a bigger range of motion than men but in both range of motion was higher on the left thumb (mean 1.4 degrees in women and mean 1.1 degrees in men). No influence of hand dominance was observed. Thus, the healthy contralateral side should be used as parameter of comparison.

Based on hypothesis that calcific tendonitis of the supraspinatus tendon (CTSSP) could be associated with glenohumeral imbalance, glenohumeral stress distribution was analyzed.26 patient shoulders with CTSSP, unsuccessfully treated by non-operative measures, were examined. A group of 26 macroscopically normal shoulder specimens served as controls. Analysis of glenohumeral stress distribution was indirect evaluating glenoid subchondral bone mineralization by computed tomography osteoabsorptiometry. Density distribution of glenoid subchondral bone mineralization and the position of the two most frequent density maxima were analyzed.Patterns of subchondral mineralization and position of the anterior density maximum were significantly different between both groups. CTSSP mostly presented with a monocentric, anteriorly increased mineralization indicative for a regional increase of stress. The inferior shift of the anterior density maximum demonstrates a parallel shift of glenohumeral stress distribution.Mineralization patterns indicate that glenohumeral stress distribution is not physiologic in CTSSP. Moreover, it is comparable with glenohumeral stress distribution as observed in atraumatic antero-inferior glenohumeral instability. Relevance of this observation should be proven for etiology of CTSSP.

Awake craniotomy in tumor and epilepsy surgery or for the implantation of electrodes for deep brain stimulation requires specific anesthesiological strategies. Propofol allows for quick emergence and has little effect on the respiratory function of the usually spontaneously breathing patient. Pain control may be instituted by hemiscalp block for trepanation or local infiltration for deep brain electrode implantation. In addition, low dose remifentanil is recommended for trepanation (i.e. tumor or epilepsy surgery). The airway may be secured by an ordinary Magill tube placed transnasally with its tip underneath the epiglottis. To protect the patient against vomiting an adequate antiemetic prophylaxis is required.

Stereotactic body radiotherapy (SBRT) is a high dose radiotherapy, the radiation dose is applicated one-time or in a few fractions exactly to the tumor or metastases under maximal separation from the normal tissue. Because of this a major expenditure of medical and technical efforts are necessary, a detailed description of the proceedings is following in the methodic part of this article. Indications of SBRT are especially medical irresectable lung tumors of early stages, primary liver/biliary tumors and pulmonary or liver metastases if there is an oncological benefit for the patients. The side effects are moderate, the local tumor control rate is between 78 to 100 %. Depending on the primary tumor the overall survival is prolonged statistically significant. In the Klinikum Krefeld indications of SBRT vs chemotherapy, LITT or resection are discussed by an interdisciplinary conference of gastroenterologists/oncologists, radiologists, radiooncologists and surgeons. An example of LITT will be shown also.

We report on a case of a 19-year-old female patient with acute promyelocytic leukemia suffering from febrile monarthitis of the right knee during neutropenia after consolidation chemotherapy caused by Geotrichum capitatum. Apparently this infection occurred due to a hematological reactivation since the patient had already developed Geotrichum capitatum fungemia during induction therapy. Under antimycotic therapy with voriconazole, flucytosine, and caspofungin as well as after two arthroscopic synovectomies with cleansing of the right knee, the infection could be controlled and the full clinical function of the knee joint could be preserved.

The aim of this investigation was the quantification of leukocyte/lymphocyte populations in the peripheral blood of ENT-carcinoma patients before and long after therapy. PROBANDS AND METHOD: PBL T-lymphocytes and NK-cells were examined in 346 patients and 31 controls using flow cytometry. In 248 participants additional populations of leukocytes, monocytes, granulocytes, lymphocytes in toto, CD4+- and CD8+-lymphocytes, CD4+8+-lymphocytes, B-lymphocytes, activated T-lymphocytes, NK-cells and CD3+56+-T-lymphocytes were studied.We demonstrated a long-term reduction in T-lymphocytes (CD4+-lymphocytes) in patients more than 10 years after receiving therapy, caused mainly, but not solely, by radio/chemotherapy. We also showed a long-term, significant increase in NK-cells after more than 10 years in patients following therapy without renewed carcinoma in comparison to controls, patients prior to therapy or patients with a recurrence of carcinoma.Due to long-term deficits in CD4+-lymphocytes, and considering the possible protective effect of NK-cells in treated patients, an immune-supportive therapy is recommended.

Spontaneous or postoperative hemorrhage into the abdominal cavity due to inflammatory vessel arrosion represents an uncommon but menacing situation. According to the literature, such hemorrhage is associated with a lethality of nearly 2%. Therapeutical options include reoperation and interventional radiological techniques such as endovascular catheter techniques with stent graft implantation or the embolization of vessels. We report on the management of seven cases with hemorrhage either from the gastroduodenal artery ( n=5) following pancreatic surgery for pancreatic carcinoma, liposarcoma, and chronic pancreatitis or from the common hepatic artery ( n=1) and the superior mesenteric artery ( n=1) following chronic pancreatitis. The present article describes our experiences with stent graft implantation (hemobahn prosthesis) in four cases. Based on these experiences, we see the advantages of stent grafts in primary hemostasis without any contact to infected tissue and the preservation of regular perfusion. However, further clinical data are required focussing on indication, technical success rates, stent-related complications, and long-term outcome.

The most frequently reported adverse events associated with acetylsalicylic acid intake are minor gastrointestinal complaints. Galenic modifications, such as buffered formulations with or without ascorbic acid, may improve the benefit-risk ratio by decreasing the local mucosal side-effects of acetylsalicylic acid.To assess endoscopically-proven gastrointestinal lesions and the amount of gastric microbleeding of four different buffered and plain acetylsalicylic acid formulations, one containing paracetamol.A randomized, four-fold cross-over study was performed in 17 healthy subjects who underwent serial oesophago-gastro-duodenoscopy before and after each course of 4-day dosing. Gastric aspirates were collected for the determination of haemoglobin concentrations to detect microbleeding.Buffered acetylsalicylic acid plus ascorbic acid yielded the lowest Lanza score, the lowest increase in the number of mucosal petechiae and the lowest increase in the amount of gastric microbleeding. Subjects receiving acetylsalicylic acid plus paracetamol plus caffeine showed the highest Lanza score of all treatments, and a considerably greater sum of petechiae in the oesophagus, stomach and duodenum compared with those receiving buffered acetylsalicylic acid plus ascorbic acid.The trial confirms that buffering of acetylsalicylic acid improves local gastric tolerability. Acetylsalicylic acid in combination with ascorbic acid shows significantly fewer gastric lesions and the lowest increase in gastric microbleeding compared with the other tested formulations.

Despite obvious clinical symptoms, dynamic, palmar instability of the ulnar head remains a diagnostic and therapeutic problem. This is demonstrated by a case of chronic, palmar instability of the ulnar head after a tear of the triangular fibrocartilage complex (TFCC). A concomitant, minimal dorsal angulation of the radius after a fracture in childhood and a general capsulo-ligamentous laxity possibly were predisposing factors. Aspects of diagnostic and therapeutic options are discussed. In our case, due to secondary arthrosis, an arthrodesis of the distal radioulnar joint combined with a stabilization of the TFCC was opted for. Although the patient is painfree and mobile, she complains of a loss of power in supination. This salvage procedure probably could have been avoided by an earlier diagnosis.

The radiological morphology of calcified deposits in calcifying tendinitis of the shoulder is classified according to Patte and Goutallier and according to Mole et al. The results of these classifications influence the choice of therapeutic procedures. In this study, the intraoberserver reproducibility and interobserver reliability of these classifications were determined. Plain anteroposterior radiographs of shoulders from 100 patients with symptomatic calcified deposits of the rotator cuff were classified according to the criteria of Patte and Goutallier as well as to the criteria of Mole et al, by six independent observers, twice within four months. The kappa values of intraoberserver reproducibility and interobserver reliability were calculated. Classification of Patte and Goutallier: intraoberserver reproducibility, mean kappa value 0.458 (standard deviation 0.098); interobserver reliability, mean kappa values 0.4 (first test) and 0.354 (second test). Classification of Mole et al: intraoberserver reproducibility, mean kappa value 0.402 (standard deviation 0.092); interobserver reliability, mean kappa values 0.239 (first test) and 0.191 (second test). Both classifications demonstrated a satisfactory to sufficient intraobserver reproducibility. The classification of Patte and Goutallier showed a satisfactory interobserver reliability, whereas the classification of Mole et al had a satisfactory to insufficient interobserver reliability. Studies dealing with both classifications should therefore be interpreted carefully.

Obstructive jaundice is a common clinical sign in patients with pancreatic cancer. 52% of all patients with a potentially resectable pancreatic cancer suffer from painless obstructive jaundice. There are no prospective studies showing a beneficial effect of preoperative drainage in patients with resectable pancreatic cancer. Morbidity (53%) and mortality (15%) in patients without preoperative biliary drainage are not significantly different from those who had endoscopic drainage preoperatively (morbidity 41%; mortality 15%). However, there are some logistic reasons for preoperative drainage, especially if surgery is delayed. In cases of nonresectable pancreatic cancer endoscopic drainage for palliation of obstructive jaundice is the method of choice. The decision between metallic and plastic stents for palliation is based on expected survival time and quality of life. Implantation of metal stents is the method of choice in patients with life expectancy exceeding six months. Scheduled three months exchange of plastic stents is recommended to avoid complications. After a six months interval about 70% of patients with scheduled exchange are without symptoms, compared to about 40% of patients who had exchange of plastic stents on demand. Scheduled three months exchange of plastic stents leeds to a patency rate of plastic stents comparable to those of metallic stents.

To determine the intraobserver reproducibility and interobserver reliability of DePalma and Kruper's classification of calcific tendinitis of the rotator cuff. The result of this classification influences the choice of therapeutic procedures in patients with symptomatic calcific tendinitis.Plain anteroposterior radiographs of shoulders from 100 patients with symptomatic calcified deposits of the rotator cuff were classified according to the criteria of DePalma and Kruper by 6 independent observers at 2 different time points within 4 months. The kappa values of intraobserver reproducibility and interobserver reliability were calculated.Kappa values of intraobserver reproducibility had a mean of 0.487 (SD 0.094); kappa values of interobserver reliability were 0.234 for the first test and 0.273 for the second test.Determination of intraobserver reproducibility gave satisfactory to sufficient results and interobserver reliability was satisfactory for both tests indicating that studies based on the classification of DePalma and Kruper should be interpreted cautiously.

The roentgenologic morphology of symptomatic calcified deposits of the rotator cuff can be classified according Gärtner. This classification influences therapeutic procedures and prognosis of clinical outcome in these patients. In the present study intraoberserver-reproducibility and interobserver-reliability of Gärtner's classification were tested.Plane radiographs of 100 patients with calcifications of the supraspinatus tendon were classified according the criteria of Gärtner by 6 independent observers twice within 4 months. Intraoberserver-reproducibility and interobserver-reliability were calculated by means of Cohen's kappa-index.kappa-values of intraoberserver-reproducibility had a mean of 0.4208 (SD 0.1299), kappa-values of interobserver-reliability were 0.490 for the first and 0.474 for the second classification.Determination of intraoberserver-reproducibility gave insufficient to satisfactory results, interobserver-reliability was sufficient. The clinical use of Gärtner's classification to plan therapeutic procedures or to determine clinical prognosis in patients with calcifying tendinitis can be recommended only with limitations.

Ogilvie's syndrome (acute colonic pseudo-obstruction) is a rare clinical disease characterized by segmental distension of the proximal colon caused by a paralysis without mechanic obstruction. It may be a sequel of underlying neurological, medical or surgical disease. Risk factors are respiratory decompensation, electrolyte disturbances and different drugs. A special kind is the primary idiopathic pseudoobstruction with a high risk of perforation or necrosis. Especially elderly patients (70 years) with cardiovascular or neurologic diseases and accordant drugs are concerned. Clinical symptoms are progressive abdominal distension and abdominal pain like an acute abdomen. The differential diagnosis of a mechanic ileus is important for further treatment. This case report should draw attention to this rare disease.

The sublabral foramen is considered to be a clinically asymptomatic, isolated variant of the anterior-superior capsulo-labral-complex. It may be observed during shoulder arthroscopy and may implicate problems in differential diagnosis of traumatic lesions. In an anatomic study on 89 macroscopically healthy shoulder specimens the age distribution and the incidence in relation to the varying shape of the glenoid as feasible factors of influence for a sublabral foramen (SF) were analyzed in order to elucidate the unknown pathogenesis of SF. In addition histologic sections of three SF samples were obtained. Mean age of the specimens with a sublabral foramen [n=20; 69 (37-84) years] was significantly higher (p=0.04) compared to samples without a sublabral foramen [n=69; 59 (18-94) years]. An increased incidence of a sublabral foramen in relation to a distinct shape of the glenoid could not be established although a prevalence of a glenoid with anterior notch was observed. The results indicate an age-related development of the sublabral foramen,thus in younger patients with an anterior-superior capsulolabral displacement local signs of trauma and involvement of the biceps anchor should be controlled before definitive diagnosis.

Open surgical removal of calcifications in chronic courses of calcifying tendinitis of the shoulder can be combined with acromioplasty. Independent of the surgical procedure not all patients achieve satisfactory surgical results. The aim of the study was to investigate whether preoperatively known epidemiologic, social, clinical and radiologic factors or intraoperative findings might influence the therapeutic outcome.Following diagnostic arthroscopy, open removal of the calcifications was done as an isolated procedure (group A, n = 12) or combined with open acromioplasty (group/B, n = 24). Follow-up was 33 months for both groups.Clinical outcomes were comparable in both groups (Group A, 74.9 points; Group B 73.4 points, Constant-Murley score) and independent of gender, age, profession, duration of anamnesis, hospital-stay period, follow-up period, dominance of arm, preoperative Constant-Murley score, calcification morphology and size and acromial type. 20 patients in total achieved a clinical outcome of/= 75 points (Constant-Murley score). 12 of these demonstrated lesions of the rotator cuff and joint cartilage combined with synovialitis. In 6 patients an adverse preoperative Constant-Murley score or the wish to receive a pension was recorded.Both surgical procedures lead to overall good and satisfactory clinical results. Below average clinical outcomes are associated with pathologic findings of the glenohumeral joints, adverse preoperative clinical situation or the wish to receive a pension.

Extracorporeal shockwave application (ESWA) is in clinical use to promote disintegration of symptomatic calcifications of the rotator cuff of the shoulder. However, disintegration of roentgenologically comparable calcifications of the rotator cuff is not always successfull. It is known from urologic stone lithotripsy that the susceptibility for disintegration of stone-like concrements depends on their mineral content. Therefore, in the present investigation the relative contents of calcium and phosphorus in rotator cuff calcifications were determined.39 surgically removed rotator cuff calcifications were analyzed by means of atomic emission spectrometry.The relative content of calcium of the rotator cuff calcifications was found to be 22.3 % +/- 5.7 % (mean +/- SD; 6.8 % - 32.4 %), that of phosphorus as 10.5 % +/- 2.4 % (2.7 % - 14.4 %). The data neither depend on the gender of the patients nor on their age at the time point of surgical removal of the rotator cuff calcifications.Roentgenologically comparable calcifications of the rotator cuff demonstrated distinct individual differences concerning the relative contents of calcium and phosphorus. The present results may serve as the first indication that the susceptibility of rotator cuff calcifications for disintegration may depend on their relative contents of calcium and phosphorus.

Leukemic cells proliferate under the influence of cytokines. In particular, the colony-stimulating factors stimulate the growth and proliferation of myeloid leukemia cells. Under normal conditions, tumor necrosis factor-alpha (TNF-alpha) is produced by activated monocytes, whereas interleukin- 10 (IL-10) is produced by several cell types like monocytes and lymphocytes. The autocrine production of cytokines by leukemic cells may have a pathogenic role in the progression of leukemia or may be an epiphenomenon. In this study, we investigated the expression of TNF-alpha and IL-10 in human leukemic cells by RT-PCR and by a cytoplasmic protein assay. Most cases of acute myelogenous leukemia (AML) (7/8 cases) and all cases of acute lymphoblastic leukemia (ALL) (n = 2), chronic myelogenous leukemia (CML) (n = 5), both in chronic phase and during blast crisis, expressed the mRNA for TNF-alpha and IL-10. A patient whose blasts were positive for IL-10 and negative for TNF-alpha, had high circulating levels of IL-10 and failed to respond to donor lymphocyte infusions. Using a cytoplasmic protein assay, generally low levels of cytoplasmic TNF-alpha and IL-10 were found which increased in case of TNF-alpha following stimulation with lipopolysaccharide. Taken together, our data show that most leukemic cells express the mRNA for a proinflammatory cytokine (TNF-alpha) and an immunosuppressive cytokine (IL-10). More work is necessary to determine under which conditions these cytokines actually paralyze the immune system and thereby permit the progression of leukemia.

Hepato-biliary cystadenomas are rare intrahepatic cystic tumours. The correct preoperative diagnosis of this lesion is difficult.We report four cases of hepato-biliary cystadenoma treated in our department from January 1995 to December 1999.The symptoms were unspecific. Preoperative computed tomography showed signs of an echinococcal cystic lesion in two patients, but there were no antibodies against an echinoccocal species in the serum. We performed a complete resection of the cystic tumour in three patients and a subtotal resection of a hepato-biliary cystadenoma in one, because of involvement of the hepatic portal structures. We did not find a malignant transformation to a hepato-biliary cystadenocarcinoma.Complete excision of a cystadenoma with a wide margin of normal liver tissue is the treatment of choice, because several reports have described malignant transformation of this kind of tumour. Taking a rapidly frozen section during the operation is an important step in the treatment of cystic liver lesions. A cystic liver lesion with several walls and a elevated CA 19-9 can predict a mucinous cystadenoma or cystadenocarcinoma.

Isolated pancreatic metastases from renal-cell carcinomas (RCC) are extremely rare. Only 96 cases of clinically diagnosed renal-cell carcinoma metastatic to the pancreas have been reported in the world literature, and 70 of the patients (including ours) underwent a definitive surgical resection. In many cases the time between the nephrectomy and diagnosis of metachronous metastases is reported to exceed 10 years. Therefore, the initial diagnosis may be overlooked when there is a prolonged disease-free interval. When it does occur simultaneously or metachronously, aggressive surgical resection, when possible, seems to be the most effective treatment for this metastatic lesion. Surgical resection can provide long-term survival in selected cases. We present the case of a 69-year-old woman in whom two pancreatic metastases were treated by a left-sided subtotal pancreatectomy with splenectomy, 12 years after radical nephrectomy for a RCC. The patient simultaneously presented with both a mass in the body of the pancreas and a right-sided colon cancer. Thus, the diagnosis of pancreatic metastasis of colon cancer was suspected initially. Both tumors were radically resected, and histological examination revealed two pancreatic metastases from the previous RCC. In the world literature this report represents the eighth case of multiple pancreatic metastases due to RCC. It illustrates a rare indication of pancreatic resection because of pancreatic metastasis. The need for prolonged follow-up of patients is emphasized. The few reports on surgically treated pancreatic metastases from RCC are reviewed after the presentation of this case.

Stromal tumors of the gut (GISTs) have rarely been analyzed for genetic alterations. This study aimed at determining telomerase activity and the expression of the telomerase subunits human telomerase reverse transcriptase (hTRT) and human telomerase RNA (hTR) in GISTs and extragastrointestinal neurogenic or myogenic sarcomas. Telomerase activity was investigated using the telomeric repeat amplification protocol assay in 21 GISTs, recurrences and liver metastases from 16 patients, and in 22 leiomyosarcomas and 21 malignant peripheral nerve sheath tumors (MPNSTs), which served as reference tumors. Expression of hTRT and hTR mRNA was investigated using reverse transcription-PCR. Thirteen GISTs were localized in the stomach and three in the small intestine. Two tumors were benign. In one case, the biological behavior was uncertain. In 67% of GISTs, high telomerase activity was found, whereas high activity was noted in only 18% of leiomyosarcomas and in 48% of MPNSTs. There was no activity in two benign and two malignant GISTs. In one malignant tumor of the small intestine, the primary tumor showed no activity at first but a marked activity in its recurrence. In the tumor with uncertain behavior, telomerase activity and hTRT expression were only weak. In all GISTs showing telomerase activity, the catalytic subunit hTRT was expressed. All GISTs and extragastrointestinal sarcomas expressed hTR. In comparison with leiomyosarcomas and MPNSTs, malignant GISTs showed a higher telomerase activity, which, however, was not seen in benign GISTs. It is possible that telomerase activity occurs during the progression of malignant GISTs. There was a correlation between telomerase activity and the expression of hTRT.

Differential display is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa that may precede the development of gastric cancer. Using the differential display technique, we identified a cDNA fragment, encoding metallothionein (MT) IIa mRNA. We performed immunohistochemical analysis using a monoclonal antibody directed against human MT and tissues obtained from 34 patients with gastric cancer and 20 healthy individuals to determine the expression and localization of MT in gastric cancer and its associated premalignant lesions and to correlate our findings with histomorphological features and Helicobacter pylori status. In addition, MT expression was assessed in gastric tissues obtained from patients with gastric cancer and first-degree relatives of patients with gastric cancers and healthy individuals using reverse transcription-PCR analysis. Northern blot analysis confirmed the overexpression of MT IIa in gastric cancer. In the normal gastric tissues, no MT immunoreactivity was observed at the superficial gastric epithelium toward the top of gastric glands. However, MT immunoreactivity was detected at the foveolar neck of the gastric glands. Immunohistochemical analysis revealed an intense MT immunoreactivity in gastric cancer cells, independent of tumor stage, grade of differentiation, or tumor type. Furthermore, areas of dysplasia and intestinal metaplasia also exhibited intense MT immunoreactivity. Reverse transcription-PCR analysis of gastric biopsies obtained from first-degree relatives of patients with gastric cancer revealed the frequent expression of MT Ia in this high-risk group as compared with healthy subjects (P0.01). The overexpression of MT in gastric cancer and the expression of MT in intestinal metaplasia and dysplasia, as well as the expression of MT in the gastric mucosa of first-degree relatives of patients with gastric cancer, point to a role for MT in the early process of malignant transformation of the gastric mucosa.

By means of 3 cases with infield soft tissue carcinomas after radiotherapy for breast cancer, symptoms and therapy are described. Consequences for treatment planning and patient's information before radiotherapy for breast cancer are discussed.Three of 1,025 patients with breast cancer irradiated from 1984 to 1997 suffered from infield secondary soft tissue sarcomas. The latency periods were 61, 49 and 59 months. Two patients had been treated with breast-conserving therapy (computerized planning, 50 Gy to reference point, 5 times 2 Gy/week, 5-MV photons), 1 patient received a local boost dose of 15 Gy (10-MeV electrons), patient 3 radiotherapy of the thoracic wall and regional lymph nodes after mastectomy using 12-MeV electrons (thoracic wall) and 5-MV photons (lymph node areas) to 50 Gy, 5 times 2 Gy/week. No adjuvant chemotherapy was given. All sarcomas were very extensive, all patients died from local progression and/or distant failure after 17, 13 and 12 months.The incidence of spontaneous sarcomas of the breast is about 0.06%, after operation and radiotherapy 0.09 to 0.45%. No correlations to radiotherapy technique and no risk factors were found. Radiation dose could play a role, but there are very sparse data about this.Secondary soft tissue sarcomas are very rare, but familiar complications of radiotherapy. Only early diagnosis leads to a chance for cure. Because of unclear correlations to the treatment parameters and rareness of this event, in our opinion no regular information to the patient receiving radiotherapy for breast cancer is mandatory.