Lack of association between gestational age adjusted TSH percentiles and neurodevelopmental outcomes among preterm infants.

BACKGROUND: Limited evidence exists on whether subclinical hypothyroidism suggested by mildly elevated TSH levels affect neurodevelopment and growth in preterm infants. The objective of this study was to determine the association between gestational age adjusted TSH percentiles and neurodevelopmental outcomes among preterm infants. METHODS: Univariate linear regression analysis was conducted to determine, in infants born less than thirty-two weeks gestational age, the correlation between the TSH percentile on the last newborn screen and neurodevelopmental assessment scores and growth outcomes at eighteen to twenty-two months of corrected age. RESULTS: Seventy-four patients were enrolled in the study with a mean gestational age of 28.8 weeks. There was no correlation between the last TSH percentile value and Bayley-III cognitive composite score or other neurodevelopmental or growth outcomes. CONCLUSION: In a cohort of preterm infants, higher TSH percentiles suggesting potential subclinical hypothyroidism did not predict any adverse effect on neurodevelopmental or growth outcomes.

Ex vivo peripheral blood mononuclear cell response to R848 in children after supplementation with the probiotic Lactobacillus acidophilus NCFM/Bifidobacterium lactis Bi-07.

Several studies have demonstrated a decrease in upper respiratory infection (URI) frequency and severity in subjects taking probiotic supplements. We hypothesised beneficial effects of probiotics on viral URI in children are due to modulation of inflammatory innate immune responses. We tested this hypothesis, providing children with a probiotic combination of Lactobacillus acidophilus/Bidfidobacterium animalis ssp. lactis Bi-07 (NCFM/Bi-07) and measuring levels of cytokines in response to stimulation of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 7/8 agonist resiquimod (R848). In this open label study, 21 (2 dropouts) children received probiotic containing 5×109 cfu each of NCFM/(Bi-07) daily for 30 days. Whole blood was taken from each subject at study entry and 30 days for culture of PBMCs. PBMCs stimulated with resiquimod (R848) or unstimulated were incubated and a panel of immune markers was measured. There was a significant decrease in the net (stimulated-null) level of myeloid progenitor inhibitory factor 1 (MPIF-1) (mean decrease 0.1 ng/ml, 95% confidence interval 0.01-0.24, P=0.032) following probiotic supplementation. The change in immune marker levels after supplementation, when analysed together with respect to expected inflammatory/anti-inflammatory effects, was increased for interleukin (IL)-10 and decreased for MPIF-1, IL-8, interferon gamma induced protein 10, macrophage inflammatory protein 3 alpha (MIP-3α) and E-selectin (P=0.01). Adverse events were mild. In conclusion, supplementation with this probiotic combination was safe and resulted in significant modulation of PBMC limited immune response to TLR7/8 agonist R848 and in levels of MPIF-1 and MIP-3α. The anti-inflammatory effect may be one mechanism by which probiotics modulate the immune system however further study is needed.

Regulation of systemic tissue injury by coagulation inhibitors in B6.MRL/lpr autoimmune mice.

Impaired fibrinolysis and complement activation in Systemic Lupus Erythematosus contributes to disease amplification including increased risk of thrombosis and tissue Ischemia/Reperfusion (IR) injury. Previous work has demonstrated complement is a key regulator of tissue injury. In these studies inhibitors had varying efficacies in attenuating injury at primary versus systemic sites, such as lung. In this study the role of coagulation factors in tissue injury and complement function was evaluated. Tissue Factor Pathway Inhibitor (TFPI), an extrinsic pathway inhibitor, and Anti-Thrombin III, the downstream common pathway inhibitor, were utilized in this study. TFPI was more effective in attenuated primary intestinal tissue injury. However both attenuated systemic lung injury. However, ATIII treatment resulting in enhanced degradation of C3 split products in lung tissue compared to TFPI. This work delineates the influence of specific early and late coagulation pathway components during initial tissue injury versus later distal systemic tissue injury mechanism.

c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine.

BACKGROUND: KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c-kit mutations. HYPOTHESIS/OBJECTIVES: To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c-kit mutated MCT would have a better response to TOC than VBL. ANIMALS: Eighty-eight client-owned dogs with macroscopic MCT. METHODS: Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m2 weekly × 4 then EOW) by KIT localization and c-kit mutation status using an adaptive randomization scheme. RESULTS: Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c-kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62-3.92]; P = 0.28). Median progression-free survival (PFS) for dogs receiving VBL was 78 days (7-1,521) and for TOC 95.5 (14-990); hazard ratio (HR) = 1.34 [0.72-2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10-1,521) for the VBL group and 159 (20-990) for the TOC group; HR = 0.80 ([0.45-1.41]; P = 0.44). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c-kit mutations was not different between treatment groups in this population of dogs, c-kit mutation status did not predict treatment response.

FBXO10 deficiency and BTK activation upregulate BCL2 expression in mantle cell lymphoma.

Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathways is critical to enhance the efficacy of ibrutinib. Here, we focus on the BCL2 anti-apoptotic pathway. In a tissue microarray of 62 MCL samples, BCL2 expression positively correlated with BTK expression. Increased levels of BCL2 were shown to be due to a defect in protein degradation because of no or little expression of the E3 ubiquitin ligase FBXO10, as well as transcriptional upregulation through BTK-mediated canonical nuclear factor-κB activation. RNA-seq analysis confirmed that a set of anti-apoptotic genes (for example, BCL2, BCL-XL and DAD1) was downregulated by BTK short hairpin RNA. The downregulated genes also included those that are critical for B-cell growth and proliferation, such as BCL6, MYC, PIK3CA and BAFF-R. Targeting BCL2 by the specific inhibitor ABT-199 synergized with ibrutinib in inhibiting growth of both ibrutinib-sensitive and -resistant cancer cells in vitro and in vivo. These results suggest co-targeting of BTK and BCL2 as a new therapeutic strategy in MCL, especially for patients with primary resistance to ibrutinib.

Pulse oximetry screening for critical congenital heart disease in the neonatal intensive care unit.

OBJECTIVE: Pulse oximetry screening (POS) is an effective tool to detect critical congenital heart disease (CCHD) in asymptomatic term infants, but its value in the neonatal intensive care unit (NICU) requires further clarification. STUDY DESIGN: A retrospective review of 1005 babies without previously diagnosed CCHD admitted to a level III NICU was performed to assess the risk for missed CCHD and performance of POS. RESULT: Of the 1005 NICU patients, 812 had documented POS and none failed POS. In 812 patients, 547 had delayed POS because of the use of supplemental oxygen. In 259/812 patients, POS was delayed until the baby was >2 weeks old. CCHD was excluded by echocardiography, irrespective of POS, in 287/1005 patients. CONCLUSION: POS can be performed in the NICU with minimal adverse effects. However, in many NICU patients CCHD is confirmed or excluded before POS, and POS will frequently be performed after CCHD would have been expected to become symptomatic.

Assessment of adherence with oral anticancer agents in oncology clinical trials: A systematic review.

BACKGROUND: Despite recommendations for adherence reporting in clinical trials involving an oral anticancer agent, the frequency and methods of adherence reporting are inconsistent. The purpose of this systematic review is to determine the frequency and type of adherence measures used in oncology and hematology clinical trials of oral anticancer agents and their association with study characteristics including quality, cancer type, stage and treatment type. DESIGN: PubMed was searched of all randomized controlled clinical trials assessing self-administered pharmacological interventions in patients with cancer and published over two years, between 1 January 2011 and 31 December 2012 were evaluated. RESULTS: We identified 70 publications in the PubMed database, comprising 45,118 total patients. Adherence reporting was present in 14 of 70 trials (20%); quantitative reporting was present in three of 70 trials (4%). Method of adherence assessment varied and included medication count, medication diaries and patient self-report. There was no association between adherence reporting and study quality or other study characteristics, although there was a trend towards increased reporting in breast cancer studies, with 46% of the studies reporting adherence (p = 0.0621). In a preliminary analysis, hematology studies (mean Jadad score 2.19 ± 1.47) were found to have significantly lower quality when compared to non-hematology trials (mean Jadad score 3.39 ± 1.37, p = 0.0034). CONCLUSION: This systematic review demonstrates adherence reporting in clinical trials of oral anticancer agents is infrequent. When reported, adherence was not associated with overall study quality or other study characteristics. Given the potential effects of non-adherence on study power and validity, adherence reporting should be encouraged in oncology and hematology clinical trials.

Diagnostic accuracy of pre-treatment biopsy for grading soft tissue sarcomas in dogs.

Histologic grade is an important prognostic factor for both local recurrence and metastatic potential with canine soft tissue sarcoma (STS). Pre-treatment biopsy with identification of tumour grade may aid in prognostication and determination of surgical margins necessary for local control. The purpose of this study was to evaluate the grading accuracy of various pre-treatment biopsy techniques (wedge, punch, needle-core) for STS in dogs. Medical records of 68 dogs diagnosed with a STS via pre-treatment biopsy and confirmed by excisional biopsy were evaluated. The concordance in grade between excisional and pre-treatment biopsies was 59%. Of the 41% that lacked concordance, 29% of pre-treatment biopsies underestimated and 12% overestimated grade. The method of pre-treatment biopsy did not significantly effect grade concordance. Based on these data, needle-core biopsy appears to be similar in accuracy compared to open biopsy, however, grading determined by pre-treatment biopsy in general should be interpreted with caution.

Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor.

BACKGROUND AND PURPOSE: The cyclin-dependent kinase CDK9 is an important therapeutic target but currently available inhibitors exhibit low specificity and/or narrow therapeutic windows. Here we have used a new highly specific CDK9 inhibitor, LDC000067 to interrogate gene control mechanisms mediated by CDK9. EXPERIMENTAL APPROACH: The selectivity of LDC000067 was established in functional kinase assays. Functions of CDK9 in gene expression were assessed with in vitro transcription experiments, single gene analyses and genome-wide expression profiling. Cultures of mouse embryonic stem cells, HeLa cells, several cancer cell lines, along with cells from patients with acute myelogenous leukaemia were also used to investigate cellular responses to LDC000067. KEY RESULTS: The selectivity of LDC000067 for CDK9 over other CDKs exceeded that of the known inhibitors flavopiridol and DRB. LDC000067 inhibited in vitro transcription in an ATP-competitive and dose-dependent manner. Gene expression profiling of cells treated with LDC000067 demonstrated a selective reduction of short-lived mRNAs, including important regulators of proliferation and apoptosis. Analysis of de novo RNA synthesis suggested a wide ranging positive role of CDK9. At the molecular and cellular level, LDC000067 reproduced effects characteristic of CDK9 inhibition such as enhanced pausing of RNA polymerase II on genes and, most importantly, induction of apoptosis in cancer cells. CONCLUSIONS AND IMPLICATIONS: Our study provides a framework for the mechanistic understanding of cellular responses to CDK9 inhibition. LDC000067 represents a promising lead for the development of clinically useful, highly specific CDK9 inhibitors.

Predicting water intake by yearling feedlot steers.

Data from 4 separate beef cattle feedlot experiments, which were conducted at the Southeast Colorado Research Center (SECRC) in Lamar, CO, in 2001, 2003, 2004, and 2007, were utilized in a retrospective longitudinal study investigating possible relationships between daily water consumption (WC), DMI, and weather variables. The data set consisted of 8,209 records from 2001, 2003, 2004, and 2007, with pen based daily WC (L•animal(-1)) and DMI measurements and calculated daily steer BW from April to October in each year. Daily weather data were obtained from the weather station located at Lamar Municipal Airport located approximately 1.9 km from SECRC. Data collected consisted of daily high, low, and mean temperature; high, low, and mean humidity; high, low, and mean sea level pressure; mean wind speed; total precipitation; and average daily wind direction (cosine of radians from due north). Univariate analysis demonstrated that the continuous variables of BW, humidity, and sea level pressure were negatively related (P < 0.0001), whereas DMI, temperature the previous day, daily temperature, change in temperature from the previous day, average wind speed, and the temperature-humidity index (THI) were positively related (P < 0.001) to daily WC. There was a trend (P < 0.06) for the cosine of wind direction (1 = due north and -1 = due south) to be negatively related to WC. The multivariate, parsimonious model predicting average daily WC included (P < 0.05) average humidity, average humidity squared, high temperature squared, high humidity squared, low temperature, low temperature squared, low humidity, average sea level pressure, average wind speed, average daily BW, high sea level pressure, low sea level pressure, high humidity, and low humidity. The generalized R(2) of the parsimonious multivariate model was 0.32. These results indicate that BW and numerous weather factors are related to WC by yearling feedlot steers. Dry matter intake had minimal impact on WC for yearling feedlot steers consuming steam-flaked corn-based high concentrate diets from mid-spring to early fall.

Class II major histocompatibility complex expression and cell size independently predict survival in canine B-cell lymphoma.

BACKGROUND: Class II major histocompatibility complex (MHC) is an independent predictor of outcome in human B-cell lymphoma. We assessed class II expression together with other markers for their impact on prognosis in canine B-cell lymphoma. HYPOTHESIS: Low class II MHC expression, large cell size, and expression of CD34 will predict a poorer outcome in canine B-cell lymphoma. Expression of CD5 and CD21 on tumor cells also may be associated with outcome. ANIMALS: One hundred and sixty dogs with cytologically confirmed lymphoma. METHODS: Patient signalment, treatment type, and flow cytometry characteristics were analyzed for their influence on outcome. A multivariable predictive model of survival was generated using 2/3 of the patients and validated on the remaining 1/3 of the dataset. RESULTS: Class II MHC expression had a negative association with mortality and relapse. Treatment type also influenced relapse and mortality, whereas cell size and patient age was only associated with mortality. CD34, CD21, and CD5 expression was not associated with disease outcome. The constructed model performed variably in predicting the validation group's outcome at the 6-month time point. CONCLUSIONS AND CLINICAL IMPORTANCE: Low levels of class II MHC expression on B-cell lymphoma predict a poor outcome, as in human B-cell lymphoma. This finding has implications for the use of dogs to model human lymphomas. Class II expression, cell size, treatment, and age can be combined to predict mortality with a high level of specificity.

Effectiveness and Safety of PRECISE APC for the treatment of bleeding gastrointestinal angiodysplasia--a retrospective evaluation.

BACKGROUND: APC is a thermal coagulation technique that uses ionized argon to transmit high-frequency electrical current, contact-free, to tissue. Precise APC is one of the new modes and is characterized by a small and distinctive energy input, higher reproducibility of tissue effects which is almost independent of the probe distance. The aim of the study was the evaluation of precise APC in patients with bleeding angiodysplasia's in the cecum or the small bowel. AIM/METHODS: Patients (pts.) with bleeding angiodysplasia of the cecum or small bowel were prospectively enrolled. Effectivity and safety of APC was assessed by evaluating the local coagulation effect, number of rebleedings and transfusions and complications (perforation, infection). RESULTS: There were 50 males and 44 females, median age 65.5 ± 8.5 years. 58 pts. (62 %) had lesions in the small bowel, 28 pts. (30 %) lesions in the cecum and 8 pts. (8 %) lesions in small bowel and cecum. All 234 visible lesions in 94 pts. were coagulated successfully. There was no perforation, active bleeding and tissue carbonization after the procedure. Re-bleeding was recognized in 18 pts. (19 %) after a mean follow-up of 6.1 months and new lesions in the same area were seen in 15 / 18 pts (16 %). CONCLUSION: In a historical comparison to forced or pulsed APC, precise APC may be a more appropriate option for the treatment of bleeding angiodysplasia's in critical locations like the cecum or small bowel. The coagulation effect seems to be comparable and due to its better depth control we assume a better safety, especially in preventing perforations.

Increased monocyte chemotactic protein-1 concentration and monocyte count independently associate with a poor prognosis in dogs with lymphoma.

Overexpression of the chemokine monocyte chemotactic protein-1 (MCP-1) has been associated with a poor prognosis in many human cancers. Increased MCP-1 concentrations may promote tumour progression by increasing mobilization of myeloid derived suppressor cells such as immature monocytes and neutrophils. We hypothesized that increased numbers of peripheral neutrophils or monocytes and increased MCP-1 concentrations would predict a worse outcome in dogs with multicentric lymphoma. In this retrospective study involving 26 client-owned dogs diagnosed with lymphoma, we show that peripheral neutrophil and monocyte counts as well as serum MCP-1 concentrations were significantly elevated relative to healthy control animals, and that such increases were associated with a decreased disease-free interval in dogs treated with chemotherapy based on cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP). To our knowledge, this is the first study showing that pretreatment evaluation of monocyte and neutrophil counts can provide important prognostic information in dogs with lymphoma. The mechanisms underlying these observations remain to be determined.

Effectivity of current sterility methods for transgastric NOTES procedures: results of a randomized porcine study.

BACKGROUND AND AIM: Natural-orifice transluminal endoscopic surgery (NOTES) is an emerging transluminal technique in which interventions are carried out by entering the abdominal cavity via a natural orifice such as the stomach. Infection is a potential risk of the procedure, and the potential pathogens are different from those encountered with skin incisions. Currently, available data regarding prophylactic anti-infective treatment are limited. We compared the effectiveness of topical antimicrobial lavage of mouth and stomach and proton pump inhibitor therapy with gastric cleansing with sterile saline solution in preventing NOTES-related contamination and infection. METHODS: A randomized survival swine study was performed. Eight pigs underwent preparation with intravenously administered proton pump inhibitors, mouth and gastric lavage (chlorhexidine), and gastric irrigation (diluted neomycin), plus single-shot intravenous antibiotics. Control group (n = 8) underwent gastric cleansing with sterile saline solution. Peritoneal biopsy, multiple smears, and dilutions for cultures were taken and incubated. The swine were sacrificed after 14 days. Bacterial load was expressed in colony-forming units (CFU). RESULTS: One pig died due to gallbladder perforation after 3 days, 2/15 swine presented minor clinical signs of infection in the 14-day follow-up (all 3 pigs were in the control group). Mean C-reactive protein levels were 5.7 +/- 2.4 g/dL (therapy group) and 12.2 +/- 3.8 g/dL (control) ( P = 0.17). Bacterial growth was seen in 1/8 swine (therapy group) and 6/8 swine (control group) ( P = 0.002). Bacterial load was 282 CFU/mL (therapy) vs. 3.2 x 10 (5) CFU/mL (control) ( P = 0.023) in the follow-up. CONCLUSION: The use of intravenous antibiotics in addition to topical antimicrobial lavage of mouth and stomach and treatment with proton pump inhibitors decreased the peritoneal bacterial load to almost zero and this was associated with a significantly lower peritoneal infection rate compared with saline-only lavage.

Endoscopic resection of "giant" colorectal lesions: long-term outcome and safety.

BACKGROUND: Today, endoscopic resection is a standard procedure for the resection of colonic polyps. Before the establishment of endoscopic techniques, the surgical approach was a clearly preferred method for removal of polyps with a size larger than three centimeters. The safety and effectiveness concerning endoscopic resections of colorectal polyps also with a size of more than 3 cm have been demonstrated in numerous studies. PATIENTS AND METHODS: Data from 165 patients (age: 68 +/- 10.4 years) harboring 167 polyps with a minimum diameter of 3 cm were retrospectively evaluated. Objects of interest were macroscopic morphology and histopathology of the polyps, their localization in the colon, the modality of endoscopic resection and follow-up. In those cases with macroscopic signs of malignancy the patients were excluded. RESULTS: Successful endoscopic resections were obtained in 72.5 %. Therefrom, resection in the piecemeal-technique was necessary in 73.6 %. Recurrence polyps after endoscopic complete resections occurred in 26.3 % after a mean follow-up of 16 +/- 12.5 months. We registered a complication rate of 19.2 %. Relevant bleeding and perforation were registered as early complications in 18.6 %. We observed no intervention-related mortality. CONCLUSION: Endoscopic mucosal resection is a safe and efficient method even for removing giant colorectal polyps. Controls are recommended at defined intervals for detecting polyp recurrence.

Fragmentation of bile duct stones: a prospective systematic in vitro evaluation of argon plasma coagulation, cryotechnology, and water-jet technology.

BACKGROUND AND STUDY AIM: Choledocholithiasis is a common disease in the West. Lithotripsy by mechanical methods using baskets and by laser or electrohydraulic methods varies in effectiveness. With argon plasma coagulation (APC), high temperatures are used for devitalization and fragmentation; cryogenic techniques use the selective controlled application of freeze-thaw cycles to devitalize pathological tissue; and the dissecting water jet exploits the high pressure action of a thin laminar jet. We aimed to assess the feasibility and effectiveness of APC, cryotechnology, and the dissecting water jet as options for the fragmentation of bile duct stones. METHODS: In an in vitro feasibility study, we evaluated the fragmentation of 120 bile duct stones treated with the three methods. Primary measures were assessment of the fragmentation rate, fragmentation effect, and energy application for each technology. RESULTS: Fragmentation was seen in only 10 % of stones treated cryogenically using liquid nitrogen. APC at a power setting of 30 - 50 W fragmented all the cholesterol stones, but results with hard pigment stones were unsatisfactory even at high energies of a 100 W setting and long application time. Using the water jet, all 40 stones (100 %) were cracked effectively and completely with a pressure of 10 - 50 bar. CONCLUSION: In this feasibility study, the first of its kind, only the water-jet device demonstrated efficient fragmentation of large bile duct stones in vitro. APC and cryotechnology are not suitable for the treatment of bile duct stones; the fragmentation rate with these methods was inadequate.

A phase I study of an oral simulated FOLFOX with high dose capecitabine.

BACKGROUND: A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU. METHODS: Schedule A included oxaliplatin 100 mg/m(2), 5FU 400 mg/m(2), and LV 20 mg/m(2) (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h x 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule. RESULTS: 36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered. CONCLUSION: Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m(2)/dose or 2,250 mg/m(2)/dose in the absence of bolus 5FU/LV.

Pain sensation and neuromuscular stimulation during argon plasma coagulation in gastrointestinal endoscopy.

BACKGROUND: Argon plasma coagulation (APC) is a thermal coagulation technique that uses ionized argon for contact-free transmission of high-frequency electrical current to tissue. Prospective data on complications with the new APC-2 (VIO) system are lacking. METHODS: A prospective trial was conducted with 152 patients treated for various gastrointestinal diseases using three modes of the APC-2. The study aimed to assess complications, focusing on the pain and neuromuscular stimulation (NMS) experienced during and after treatment. Patients reported pain and NMS using a scale ranging from 0 to 10 and were interviewed for symptoms such as tingling, paresthesia, muscle pain, and cramping or twitching. The endoscopists also graded NMS using a separate questionnaire. RESULTS: A total of 85 males and 67 females (median age, 66 years) were enrolled in the study. All APC therapies were completed successfully. Two peri-interventional perforations were recorded. Of the 152 patients, 26 (17%) reported pain sensation during or after APC. The median pain sensation reported by the patients on the standardized scale was 3.7. The findings showed NMS in 14 (9.2%) of the 152 patients. Significantly more NMS events were seen with pulsed APC than with forced or precise APC. Additional risk factors for NMS were gender (female) and type of sedation (combination midazolam and pethidine). No complications were noted among patients with intracardiac defibrillators or cardiac pacemakers. CONCLUSIONS: According to the findings, APC may be associated with minor complications such as pain sensation and NMS. These complications were rarely seen, but occurred more often with pulsed APC than with forced or precise APC. Physicians should be aware of these complications.

Prospective nonrandomized comparison of two modes of argon beamer (APC) tumor desobstruction: effectiveness of the new pulsed APC versus forced APC.

BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has become an established noncontact method of tumor palliation in a variety of locations. The present prospective study evaluated a new APC system (APC-2) using amplified power settings and different application modes, such as intermittent energy delivery (pulsed APC) in comparison with the conventional technique (forced APC). PATIENTS AND METHODS: A total of 100 patients with esophageal, gastric, or rectal tumors were alternately (but not randomized) enrolled and treated with either pulsed APC (n = 46) or forced APC (n = 54). Parameters to assess the palliative effect were: amount of lumen restoration ((1/3), (2/3), complete), objective planimetry, stenosis length, treatment time, and number of APC sessions. RESULTS: Overall response rate was similar in both groups (pulsed 83 %, forced 87 %), the same was found in the subgroups with different amounts of lumen restoration and for the other objective parameters. However, the tumor debulking effect was achieved in a significantly shorter median treatment time with forced compared with pulsed APC (13.6 vs. 18.2 minutes, P = 0.03), with a similar number of treatment sessions in both groups. Complications also occurred with similar frequency in both groups. CONCLUSIONS: There was no significant difference in overall local tumor response between the two modes of APC application. However, data from this nonrandomized study suggest a faster achievement of response with forced APC. A combination of both modes may be superior.

[Space-occupying lesions in the liver: incidence of adenocarcinoma metastases of unknown primary site]. / Unklare hepatische Raumforderungen: Häufigkeit von Adenokarzinom-Metastasen eines unbekannten Primärtumors.

BACKGROUND AND OBJECTIVE: The diagnostic approach to newly detected space-occupying lesions in the liver can be difficult and a histogenetic classification of the primary tumor is impossible in some cases. Such cases of metastatic disease without a detectable primary tumor are classified as cancer of unknown primary site (CUP). The incidence of this diagnosis depends on the clinical and histochemical methods used. It was the main aim of this study to analyze the true incidence of adenocarcinoma metastases of the liver with an unknown primary cancer after application of a standardized protocol of clinical and immunhistochemical diagnostic tests and a long-term follow-up. PATIENTS AND METHODS: Between January 2000 and January 2003 127 consecutive patients underwent diagnostic ultrasound-guided biopsy of a space-occupying lesion in the liver. Based on the histopathology and immunochemistry a well defined and individually adapted diagnostic algorithm was employed (endoscopy, imaging). RESULTS: 44 females and 83 males, median age 66.8 years, were enrolled into the study. Primary tumors of the liver were found in 21 cases and non-hepatocellular tumors (metastases) were documented in 106 patients, 82 of the latter (77%) had metastases of an adenocarcinoma. The further diagnostic approach was based on histochemistry, immunhistochemistry and imaging techniques, making possible a full diagnosis of primary tumor in a further 59 (72%) cases. Thus the incidence of an adenocarcinoma of the liver of unknown primary site was 23 of 127 cases (18%). CONCLUSIONS: Although there is a wide variety of modern diagnostic methods today, the histogenetic classification of hepatic metastases is not always possible. However, in the last few years diagnostic advances have occurred based on modern immunhistochemical methods. This immunhistochemical definition has made it possible to avoid an oppressive "overdiagnosis" and offer patients early and appropriate therapeutic options.