Decrease of CA 19–9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19–9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients. Forty-three consecutive patients (median age 61 years, range 39–76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index ≥ 60 were treated with gemcitabine in a dose of 1000 mg m−2weekly × 7 followed by 1 week of rest during the first cycle and thereafter 1000 mg m−2weekly × 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19–9 could be performed. Patients with a decrease of > 20% of the baseline CA 19–9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease ≤ 20% (n = 11) (268 vs 110 days;P< 0.001). The response of CA 19–9 was the strongest independent predictor of survival (P< 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19–9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer. Serial measurements of CA 19–9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated. © 2000 Cancer Research Campaig

Jejunal Amyloidoma - a rare cause of gastrointestinal bleeding

We report a case of localized amyloid tumor of the jejunum which presented with abdominal pain and gastrointestinal bleeding. We reviewed the pathophysiologic process that precipitates bleeding in this rare tumor. We also examined the documented radiologic and endoscopic features of amyloidosis of the small bowel in the light of our reported case. All with a view to add to the growing evidence on this rare tumor which will facilitate accurate diagnosis and management

A Novel ABO Gene Variant Leads to Discrepant Results in Forward/Reverse and Molecular Blood Grouping

BACKGROUND: Discrepant results in antigen and reverse ABO blood typing are often caused by a variant ABO gene. Molecular analysis can help to characterize such variants. Here, we describe the identification of a novel ABO gene variant in a patient with aberrant ABO phenotype and discrepant genotyping results. METHODS: A patient with discrepant results in automated forward and reverse ABO phenotyping was further investigated by serological (gel and tube technique) and molecular (commercial and inhouse PCR-SSP, DNA sequencing) methods. A PCR-SSP system was established to screen the novel mutation in 1,820 blood donors. RESULTS: Standard serological tests confirmed blood group O, however, only anti-B isoagglutinins were present. A monoclonal anti-AB antibody detected very weak agglutination in gel technique. Standard ABO genotyping using PCR-SSP led to discrepant results (O1/O1 or O1/A) depending on the test system used. ABO exon re-sequencing identified a novel missense mutation in exon 6 at position 248A>G (Asp83Gly) in the binding region of PCR-SSP primers for the detection of 261G alleles. Blood donors with regular ABO blood groups were all negative for the 248G allele designated Aw34. CONCLUSION: The novel ABO gene variant Aw34 is associated with very weak A antigen expression and absent anti-A isoagglutinins. The mutation is located in exon 6 close to the O1-specific 261G deletion in the binding region of PCR-SSP primers. Presumably, depending on the primer concentration used in commercial ABO genotyping kits, the mutation could lead to a false-negative reaction

Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori eradication: two case reports

<p>Abstract</p> <p>Introduction</p> <p><it>Helicobacter pylori </it>infection is a major cause of gastric ulcers, and <it>Helicobacter pylori </it>eradication drastically reduces ulcer recurrence. It has been reported, however, that severe physical stress is closely associated with gastric ulceration even in <it>Helicobacter pylori </it>-negative patients.</p> <p>Case presentation</p> <p>We report the cases of a 47-year-old Japanese man and a 69-year-old Japanese man who developed psychological stress-induced hemorrhagic gastric ulcers, in both of whom <it>Helicobacter pylori </it>had been successfully eradicated.</p> <p>Conclusion</p> <p>Our cases strongly suggest that not only physical but also psychological stress is still an important pathogenic factor for peptic ulceration and accordingly that physicians should pay attention to the possible presence of psychological stress in the management of patients with peptic ulcers.</p

Molecular characterization of Miraflores peach variety and relatives using SSRs

The definitive version is published in: http://www.sciencedirect.com/science/journal/03044238Some traditional peach varieties, originated from the region of Aragón (Spain), were analysed by SSRs (Simple Sequence Repeats). The aim of this research was to characterize 19 clones related to ‘Miraflores’ variety, with unknown pedigrees, to assess their genetic diversity and to elucidate their possible relationships with 10 traditional peach varieties. Twenty SSR primer pairs with high levels of polymorphism, which have been previously developed for peach, were used in this study. A total of 46 alleles were obtained for all the microsatellites studied, ranging from one to six alleles per locus, with a mean value of 2.3 alleles per locus. Fourteen SSRs were polymorphic in the set of varieties studied and permitted to distinguish 16 different genotypes out of the 30 initially studied, although fourteen ‘Miraflores’ clones showed identical gel profiles. The genetic distance matrix was used to construct Neighbor joining cluster and to perform principal coordinate analysis which allowed the arrangement of all the genotypes according to their genetic relationships. The genetic relationships among these traditional peach varieties, and in particular among ‘Miraflores’ clones are discussed. The obtained results confirm that microsatellite markers are very useful for these purposes.We are thankful to T.N. Zhebentyayeva and G.L. Reighard for helpful comments on the manuscript. This research was funded by CICYT (Comisión Interministerial de Ciencia y Tecnología, AGL2002-04219 and AGL 2005-05533), INIA (Instituto Nacional de Investigación y Tecnología Agraria y Alimentación, RF03-014-C2), Bilateral Spain-France (HF03-273) and DGA (A28, A44) projects and co-funded by the European Regional Development Fund. M. Bouhadida was supported by a fellowship from the AECI (Agencia Española de Cooperación Internacional) of the Spanish Ministry of Foreign Affairs.Peer reviewe

The fate of Böhler's angle in conservatively-treated displaced intra-articular calcaneal fractures

Purpose: Although the predictive value of Böhler's angle on outcome remains subject of debate, the initial angle at the time of trauma still guides treatment. Changes in Böhler's angle during follow-up are frequently reported following surgical treatment of displaced intra-articular calcaneal fractures (DIACF). The aim of the present study was to determine the changes in Böhler's angle as a measure of secondary fracture displacement following conservative management of DIACF. Methods: Thirty-eight patients with a total of 44 displaced intra-articular calcaneal fractures treated conservatively with a minimum of two lateral radiographs during follow-up were analysed. Böhler's angle at different follow-up times was measured by three observers. The change in angle was compared with the angle at trauma, and influence of trauma mechanism and common calcaneal fracture classifications were determined. Results: The results showed a significant decline over time of the Böhler's angle in conservatively-treated patients of more than 11° on average at a mean follow-up of 29.2 weeks. This decrease was not related to gender, the initial angle, or the Essex-Lopresti or Sanders classification. A statistically significantly higher decrease was detected in high energetic trauma compared with low energetic trauma. Conclusion: The conservative treatment of displaced intra-articular calcaneal fractures is still a viable option, yet a significant secondary displacement in time should be taken into account, as reflected in a decrease of Böhler's angle of 11° up to one year following trauma

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease

Limiting esophageal temperature in radiofrequency ablation of left atrial tachyarrhythmias results in low incidence of thermal esophageal lesions

<p>Abstract</p> <p>Background</p> <p>Atrio-esophageal fistula formation following radiofrequency ablation of left atrial tachyarrhythmias is a rare but devastating complication. Esophageal injuries are believed to be precursors of fistula formation and reported to occur in up to 47% of patients. This study investigates the incidence of esophageal lesions when real time esophageal temperature monitoring and temperature limitation is used.</p> <p>Methods</p> <p>184 consecutive patients underwent open irrigated radiofrequency ablation of left atrial tachyarrhythmias. An esophageal temperature probe consisting of three independent thermocouples was used for temperature monitoring. A temperature limit of 40°C was defined to interrupt energy delivery. All patients underwent esophageal endoscopy the next day.</p> <p>Results</p> <p>Endoscopy revealed ulcer formation in 3/184 patients (1.6%). No patient developed atrio-esophageal fistula. Patient and disease characteristics had no influence on ulcer formation. The temperature threshold of 40°C was reached in 157/184 patients. A temperature overshoot after cessation of energy delivery was observed frequently. The mean maximal temperature was 40.8°C. Using a multiple regression analysis creating a box lesion that implies superior- and inferior lines at the posterior wall connecting the right and left encircling was an independent predictor of temperature. Six month follow-up showed an overall success rate of 78% documented as sinus rhythm in seven-day holter ECG.</p> <p>Conclusion</p> <p>Limitation of esophageal temperature to 40°C is associated with the lowest incidence of esophageal lesion formation published so far. This approach may contribute to increase the safety profile of radiofrequency ablation in the left atrium.</p

Outcomes of early switching from intravenous to oral antibiotics on medical wards

OBJECTIVES: To evaluate outcomes following implementation of a checklist with criteria for switching from intravenous (iv) to oral antibiotics on unselected patients on two general medical wards. METHODS: During a 12 month intervention study, a printed checklist of criteria for switching on the third day of iv treatment was placed in the medical charts. The decision to switch was left to the discretion of the attending physician. Outcome parameters of a 4 month control phase before intervention were compared with the equivalent 4 month period during the intervention phase to control for seasonal confounding (before-after study; April to July of 2006 and 2007, respectively): 250 episodes (215 patients) during the intervention period were compared with the control group of 176 episodes (162 patients). The main outcome measure was the duration of iv therapy. Additionally, safety, adherence to the checklist, reasons against switching patients and antibiotic cost were analysed during the whole year of the intervention (n = 698 episodes). RESULTS: In 38% (246/646) of episodes of continued iv antibiotic therapy, patients met all criteria for switching to oral antibiotics on the third day, and 151/246 (61.4%) were switched. The number of days of iv antibiotic treatment were reduced by 19% (95% confidence interval 9%-29%, P = 0.001; 6.0-5.0 days in median) with no increase in complications. The main reasons against switching were persisting fever (41%, n = 187) and absence of clinical improvement (41%, n = 185). CONCLUSIONS: On general medical wards, a checklist with bedside criteria for switching to oral antibiotics can shorten the duration of iv therapy without any negative effect on treatment outcome. The criteria were successfully applied to all patients on the wards, independently of the indication (empirical or directed treatment), the type of (presumed) infection, the underlying disease or the group of antibiotics being used

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program

Abstract Background In this article, we describe the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. Discussion The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. Summary The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align) to achieve these improvements, and at what cost