Correlations Between Small Airway Function,Ventilation Distribution,and Functional Exercise Capacity in COPD Patients

Background

Interest in using the nitrogen single-breath washout (N₂SBW) test to measure ventilation inhomogeneity and small airway function in COPD patients has grown in recent years. Our aim was to assess the correlation of the measures obtained by the N₂SBW test and other pulmonary function parameters with the six-minute walk distance (6MWD), the degree of dyspnea score, and health status in COPD patients.

Methods

In this cross-sectional study, 31 patients with COPD were subjected to the N₂SBW test, spirometry, whole-body plethysmography, carbon monoxide diffusing capacity measurement, the six-minute walk test, the modified Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).

Results

We found a strong correlation between the 6MWD and the phase III slope of the nitrogen single-breath washout (Phase III slope_N2SBW) (r = ?0.796; p = 0.0001). We found moderate correlations between the 6MWD and the residual volume (RV) (r = ?0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = ?0.600; p = 0.0004). We also found moderate correlations between the CAT score and Phase III slope_N2SBW (r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r = 0.603; p = 0.0003). There was a significant difference between the mMRC grades for the following variables: Phase III slope_N2SBW (p = 0.0001), RV (p = 0.0001), and smoking history (p = 0.008). Multivariate analysis showed that Phase III slope_N2SBW was the only independent predictor of the 6MWD (R ²  = 0.703; p = 0.0001), CAT score (R ²  = 0.586; p = 0.0001), and mMRC scale (relative risk = 1.14; p = 0.0001).

Conclusions

In patients with COPD, our findings suggest that the ventilation inhomogeneity impacts the functional exercise capacity, the degree of dyspnea, and health status.     

Impact of treatment satisfaction on quality of life of patients with acromegaly

Purpose

To evaluate satisfaction of acromegalic subjects with their medical treatment and its contribution to their quality of life.

Methods

This cross-sectional study included a total of 159 medications used in 133 subjects with acromegaly (controlled n = 84 and uncontrolled n = 49, female/male: 81/52). Subjects were asked to complete questionnaires on symptoms of depression (BDI) and satisfaction with the medical therapy they received for acromegaly (TSQM). Acromegaly cases also completed Acromegaly Quality of Life Questionnaire (AcroQoL).

Results

Subjects on pegvisomant therapy scored lower on convenience (p = 0.007). Cases on combination therapy had lower domain scores for effectiveness, convenience and global satisfaction in comparison to the cases on monotherapy (p = 0.01, p = 0.01 and p = 0.01, respectively). The time elapsed since diagnosis and the duration of medical therapy were positively correlated with effectiveness score (r = 0.2, p = 0.007 and r = 0.2, p = 0.04, respectively). The AcroQoL score was positively correlated with all domains of TSQM (for effectiveness r = 0.2, p = 0.01; for side effects r = 0.3, p = 0.001; for convenience r = 0.3, p = 0.004 and for global satisfaction r = 0.2, p = 0.01). In contrast, the BDI score was inversely correlated with all domains of TSQM (for effectiveness r = ?0.3, p = 0.001; for side effects r = ?0.2, p = 0.006; for convenience r = ?0.3, p < 0.001 and for global satisfaction r = ?0.3, p = 0.001).

Conclusion

In acromegaly, quality of life, status of depression and satisfaction of the subjects with their treatment are intercorrelated.     

Tumor diameter and Ki-67 expression in biopsy could be diagnostic markers discriminating from adenoma and early stage cancer in patients with ampullary tumors

Background

Ampullary early stage cancer (early CA) potentially harbors lymphovascular invasion; there are few data on markers that could differentiate adenoma and early CA.

Aim

To investigate those markers, we compared the tumor diameter and Ki-67 expression in endoscopy biopsy specimens of adenoma with those of early CA.

Methods

Patients on whom endoscopic papillectomy (EP) was performed (n = 35) with histopathologically proven adenomas and with low/high grade dysplasia and early CA were studied. We made pre-procedure evaluations of ampullary tumors by using endoscopic ultrasonography (EUS) and transpapillary intraductal ultrasonography. Tumor diameter was measured by EUS. Endoscopic biopsy using immunostaining of Ki-67 labeling index (LI) prior to EP were evaluated.

Results

The areas under the receiver-operating characteristic (AUROC) curves for tumor diameter and Ki-67 expression were 0.824 and 0.873, respectively. Cut-off values calculated based on AUROC data were 15 mm in tumor diameter and 32 cells/high-power field (HPF) in Ki-67. Early CA (n = 11) was diagnosed by using a cut-off value for tumor diameter in 8 out of 11 patients (sensitivity 72.7 %, specificity 66.7 %, accuracy 68.6 %). Significant infiltration of the major duodenal papilla by Ki-67 positive tumor cells (>31/HPF) was recognized in 8 of the 11 patients with early CA (sensitivity 100 %, specificity 54.2 %, accuracy 62.9 %).

Conclusions

Observation of tumor diameter and Ki-67 LI would be helpful for safety EP. EP should not be indicated for ampullary tumors more than 15 mm in diameter and/or Ki-67 LI 31/HPF.     

Biological characteristics of interval cancers: a role for biomarkers in the breast cancer screening

Introduction

In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes.

Materials and methods

We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2? and Ki67 <14 %, luminal B (HER2 negative) if ER/PR+, HER2? and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR?and HER2?, HER2 positive if ER/PR? and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables.

Results

Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112–11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709).

Conclusion

Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies.     

Soluble FGL2, a novel effector molecule of activated hepatic stellate cells,regulates T-cell function in cirrhotic patients with hepatocellular carcinoma

Purpose

To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC).

Methods

Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA.

Results

sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody.

Conclusion

sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.     

Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists

Objectives

Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters.

Methods

Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging.

Results

Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = ?0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change.

Conclusions

The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.     

Effect of Pronase Premedication on Narrow-Band Imaging Endoscopy in Patients with Precancerous Conditions of Stomach

Background

Narrow-band imaging (NBI) endoscopy improves the detection of intestinal metaplasia. However, strategies to improve the visibility and diagnostic performance of NBI should be sought, as endoscopic views are often obscured by the presence of mucus.

Aim

To compare the visibility and diagnostic performance of NBI endoscopy according to pronase premedication in patients with precancerous conditions of the stomach.

Methods

Consecutive outpatients with a previous diagnosis of precancerous condition of the stomach were invited to undergo a surveillance NBI endoscopy between June and December 2012. Enrolled subjects were randomly assigned to pronase or control groups before NBI endoscopy. The visibility score and diagnostic performance of NBI endoscopy were compared between the two groups.

Results

Patients’ endoscopic and histopathological characteristics were similar between the two groups. Visibility score in the proximal part of the stomach and satisfaction score of the endoscopist were significantly higher in the pronase group than in the control group (p = 0.014 and p = 0.034, respectively). The diagnostic performance of NBI endoscopy to detect intestinal metaplasia was not different in either group (both p > 0.1). However, the negative predictive value of NBI endoscopy was much improved over that of white light endoscopy only in the pronase group (p = 0.013).

Conclusion

Pronase premedication increased the visibility of the proximal part of the stomach and the satisfaction score during NBI endoscopy. Furthermore, negative predictive value of NBI endoscopy was much improved compared with that of white light endoscopy after pronase premedication.     

BCL-2, topoisomerase IIα, microvessel density and prognosis of early advanced breast cancer patients after adjuvant anthracycline-based chemotherapy

Purpose

The aim of this retrospective study was to investigate the effect of B cell lymphoma 2 (BCL-2) expression on disease-free survival (DFS) in 172 early breast cancer (BC) patients treated with anthracycline-based adjuvant chemotherapy. We have reanalysed follow-up data in these patient groups, and therefore, the relation between DFS and other tumour biological features [expression of oestrogen (ER) and progesterone (PgR) receptors, cytokeratin 5/6 (CK5/6), HER2, topoisomerase IIα (TOPOIIα), Ki-67, P53 and microvessel density (MVD)] studied previously (Biesaga et al. in Breast 20(4):338–350, 2011, doi:10.1016/j.breast.2011.03.002, Pathol Oncol Res 18(4): 949–960, 2012, doi:10.1007/s12253-012-9525-9) was also investigated.

Method

Tumour biological features were assessed immunohistochemically on paraffin-embedded sections obtained before treatment from 172 women with BC in stage T1–T2, N1–N2, M0.

Results

In univariate analysis, longer DFS was found for patients having tumours with BCL-2 positivity (P = 0.005), low grade (P = 0.001), ER (P = 0.017) and PgR (P = 0.045) positivity, CK5/6 negativity (P = 0.021), low TOPOIIα expression (P = 0.003) and high MVD (P = 0.000). In multivariate analysis, BCL-2, TOPOIIα and MVD were independent parameters indicating patient prognosis. All patients (n = 18) characterized by tumour BCL-2 positivity, low TOPOIIα expression and high MVD survived 80 months without any evidence of cancer disease, whereas DFS for all other patients was significantly (P = 0.022) lower (76.5 %).

Conclusion

Combination of three parameters: BCL-2 positivity, low topoisomerase IIα expression and high MVD, allows to identify subgroup of BC patients with very good prognosis after adjuvant anthracycline-based chemotherapy.     

Clindamycin–primaquine for pneumocystis jiroveci pneumonia in renal transplant patients

Background

Trimethoprim/sulfamethoxazole (TMP/SMX) is considered first-line therapy for pneumocystis jiroveci pneumonia (PCP) in renal transplant patients. Alternatives have not been formally studied. Clindamycin–primaquine (C–P) is effective in HIV-associated PCP, but data in renal transplant patients are lacking.

Patients and methods

Retrospective cohort study of 57 consecutive renal transplant patients who developed PCP and were treated with C–P (n = 23) or TMP/SMX (n = 34).

Results

A non-significantly higher failure rate was observed in patients on C–P due to lack of efficacy (30.4 versus 20.6 %, p = 0.545). The difference was more pronounced in severe PCP (60 versus 37.5 %, p = 0.611) and a significantly lower efficacy of C–P was seen when used as salvage therapy. The two patients who had received C–P after not responding to TMP/SMX failed this regimen, but all seven patients who had failed initial treatment with C–P and had been switched to TMP/SMX were cured (p = 0.028). No treatment-limiting adverse reactions were reported for patients on C–P while six patients (17.6 %) on TMP/SMX developed possibly related treatment-limiting toxicity (p = 0.071). However, in only two patients adverse events were definitely related to TMP/SMX (5.9 %).

Conclusions

Clindamycin–primaquine appears to be safe and well tolerated for treating PCP in renal transplant patients but is probably less effective than TMP/SMX, the standard regimen. However, our data indicates that C–P represents an acceptable alternative for patients with contraindications or treatment emergent toxicities during TMP/SMX use. Notably, TMP/SMX was also acceptably tolerated in most patients. TMP/SMX remains an effective salvage regimen in case of C–P failure.     

Evaluation of Endoscopic Transpapillary Brushing Cytology for the Diagnosis of Bile Duct Cancer Based on the Histopathologic Findings

Background and Aim

Diagnosis of the bile duct cancer still needs more accuracy. Studies on endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing cytology were carried to evaluate the role of the endoscopic transpapillary brushing cytology for the diagnosis of bile duct cancer.

Patients and Method

The study involved 76 consecutive patients who underwent ERCP-guided bile duct cytology for the diagnosis of bile duct cancer from 2008 to August 2012. Three types of cytological specimens were obtained using different sampling methods, i.e., bile aspiration cytology (BAC), brush tip cytology (BTC), and post brushing bile cytology (PBC), to investigate their diagnostic abilities, and comparatively studied with each macroscopic type of the surgically resected specimens.

Results

The cancer-positive rate was 67.1 % (BAC alone: 41.9 %), and the use of BTC and PBC in addition to BAC yielded a statistically significant increase of the cancer-positive rate (p = 0.0031). In 34 resected cases, the cancer-positive rate in relation to the macroscopic type was improved by the addition of BTC and PBC to BAC alone for the papillary (87.5 vs. 40.0 %, p = 0.071) and nodular (100 vs. 70.0 %, p = 0.0603) types, but not for the flat type (62.5 vs. 57.1 %; p = 0.7651).

Conclusion

The diagnostic ability of ERCP-guided brushing cytology could be improved by the addition of PBC. However, the cancer-positive rate was the lowest for the flat type of bile duct cancer.     

Intravenous Albumin Shortens the Duration of Hospitalization for Patients with Hypoalbuminemia and Bleeding Peptic Ulcers: A Pilot Study

Background

Patients with hypoalbuminemia have an increased risk of ulcer rebleeding and longer length of hospitalization.

Aims

This study aimed to test whether intravenous albumin can decrease the incidence of rebleeding or shorten the duration of hospitalization in patients with bleeding peptic ulcers and hypoalbuminemia.

Methods

Sixty-two patients with bleeding peptic ulcers and Rockall scores ≥6 were prospectively enrolled after having received endoscopic therapy. The enrolled patients were divided into a normal albumin group (serum albumin ≥3 g/dL, n = 39) or an intervention group (<3 g/dL, n = 23) to receive a 3-day course of omeprazole infusion and 25-day oral esomeprazole. Patients (n = 29) with bleeding ulcers and hypoalbuminemia who received the same dose of intravenous and oral omeprazole but did not receive albumin therapy were enrolled from a previous study as the control group. In the intervention group, patients received albumin infusion (10 g q8h) for 1 day (serum albumin levels 2.5–2.9 g/dL) and 2 days (<2.5 g/dL), respectively.

Results

The 28-day cumulative rebleeding rates were similar between the intervention group and the control group (39.1 vs. 42.3 %, p = 0.99). The intervention group had a shorter duration of hospitalization (9 vs. 15 days, p = 0.02) than cohort controls. The risk of rebleeding developed after discharge were similar (normal albumin group vs. intervention group vs. control group, 1/5 [20 %] vs. 2/9 [22.2 %] vs. 1/11 [9.1 %], p = 0.7).

Conclusions

Albumin administration shortens the duration of hospitalization for patients with peptic ulcer bleeding and hypoalbuminemia, but does not decrease the incidence of rebleeding.     

Biochemical and quality of life responses to octreotide-LAR in acromegaly

Objectives

AcroQoL is a questionnaire developed to assess quality of life in patients with acromegaly, covering physical and psychological dimensions. This study was designed to determine AcroQoL score changes and concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), before and after treatment with octreotide-LAR (oct-LAR) in acromegaly.

Methods

Retrospective observational study of 28 acromegalic patients with a mean age of 45 years (range 28–64), evaluated over a 4-year period, before and during treatment with oct-LAR in clinical practice conditions.

Results

Baseline AcroQoL score (53 ± 15) improved after oct-LAR treatment (70 ± 15) globally for the 28 patients (p < 0.001). Three patients in whom AcroQoL score did not improve over time had severe headaches, which did not disappear. In patients who normalized, both GH (<2.5 μg/L) and IGF-1, AcroQoL score increased on average by 22 points (p = 0.003); when GH and IGF-1 improved, but did not normalize, AcroQol score increased on average by 16 points (p = 0.008). In 6 patients with discordant results, AcroQol score tended to improve if IGF-1 normalized (n = 4, p = 0.066), but not if IGF-1 remained high.

Conclusion

Oct-LAR therapy in acromegaly improved quality of life scores in parallel to biochemical markers, except in patients with severe headaches. The AcroQoL questionnaire is an additional tool to establish therapeutic effectivity.     

Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for patients with metastatic colorectal cancer: Superior progression-free survival is restricted to patients with measurable tumors and objective tumor response—a retrospective study

Purpose

We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.

Methods

Between April 2005 and March 2012, patients (n = 158) diagnosed with metastatic colorectal cancer after at least four courses of first-line bevacizumab-based (n = 95) or cetuximab-based triplet (n = 63) were retrospectively analyzed. The KRAS genotypes were sequenced for all patients. The Kaplan–Meier method was used for survival analysis, and Cox proportional hazards models were used for univariate and multivariate analyses.

Results

Cetuximab-based triplet was associated with a higher objective response rate (66.0 vs. 47.2 %, p = 0.037) and a higher conversion rate to resectability (39.7 vs. 20.0 %, p = 0.007) compared to bevacizumab-based triplet. Compared with bevacizumab-based triplet, cetuximab-based triplet significantly increased progression-free survival in patients with measurable metastatic colorectal cancer who achieved objective tumor response (responders) (median 13.1 vs. 10.5 months, p = 0.023), but no significant increase was observed for overall survival. After adjustment for group differences in baseline characteristics and combined chemotherapy agents, cetuximab-based triplet remained an independent determinant of progression-free survival in responders as compared with bevacizumab-based triplet. KRAS mutation was not a prognostic factor in patients with metastatic colorectal cancer.

Conclusions

As compared with bevacizumab-based triplet, cetuximab-based triplet as the first-line treatment of metastatic colorectal cancer was associated with better progression-free survival in patients with measurable tumors who achieved objective tumor response to bio-chemotherapy.     

High IGF2 and FGFR3 are associated with tumour progression in undifferentiated pleomorphic sarcomas,but EGFR and FGFR3 mutations are a rare event

Aim

Pleomorphic undifferentiated sarcomas (formerly known as malignant fibrous histiocytomas) are recognised by the actual WHO classification as an undifferentiated, unclassifiable category of pleomorphic sarcomas which show no definable line of differentiation and are still a diagnosis of exclusion. Therefore, diagnostic, prognostic and therapeutic options of these tumours are urgently needed.

Methods

Three hundred and twenty-seven spindle cell tumours of a German consultation and reference centre of soft tissue tumours consisting of 200 undifferentiated pleomorphic sarcomas (UPS), 45 low-grade sarcomas (10 low-grade fibromyxoid sarcomas, 32 low-grade myofibroblastic sarcomas and three myxoinflammatory fibroblastic sarcomas) and 82 tumours of the fasciitis family were revisited. The specimens were analysed immunohistochemically with distinct markers including tyrosine kinases and expression correlated with clinicopathological parameters. Additionally, mutational analysis was performed on specimens with high expression of EGFR and FGFR3.

Results

At the protein level high IGF2 expression was observed in 86 %, FGFR3 (69 %), PDGFRA (62 %), PDGFRB (39 %), FGFR1 (8 %), EGFR (5 %), KDR/VEGFR2 (3 %), ALK (0 %) and high Ki67 (63 %) in UPS. High expressions of IGF2 and FGFR3 are significantly correlated with a higher grading (p = 0.023 and p = 0.016, respectively) and a high Ki67 index (p = 0.017 and p = 0.001, respectively). No mutations were found in the hot spots of tumour specimens with a high expression of EGFR gene (exons 18–21) and FGFR3 gene (exons 7, 10 and 15).

Conclusions

High expressions of IGF2 and FGFR3 are significantly associated with tumour progression, grading and Ki67 and might classify a subgroup of undifferentiated pleomorphic sarcoma. These markers might guide targeted therapies in these neoplasms.     

Serum alkaline phosphatase differentiates prostate-specific antigen flare from early disease progression after docetaxel chemotherapy in castration-resistant prostate cancer with bone metastasis

Purpose

A transient rise in prostate-specific antigen (PSA) after the initiation of chemotherapy, called as PSA flare, has been frequently reported in patients with castration-resistant prostate cancer (CRPC) but there has been no way to differentiate PSA rises in CRPC. We investigated whether bone-related serum markers differentiate PSA flare from progression in CRPC patients with bone metastasis.

Methods

We reviewed CRPC patients with bone metastasis who received systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP), calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow-up serum parameters after the first cycle of chemotherapy were included in statistical analyses.

Results

PSA increased in 38 patients (45.8 %) at the first evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or did not decrease to the stabilization level by the third evaluation in 22 (26.5 %) patients, while PSA decreased to the stabilization or response level by the third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The univariate analyses showed that no baseline parameters were associated with PSA flare, but the initial ALP decrease, changed ALP ratio, and median calcium level were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012, respectively). Multivariate logistic regression analysis showed that a change in the ALP level is an independent predictive factor for PSA flare (p = 0.017).

Conclusions

ALP is a useful biomarker to differentiate PSA flare from early PSA progression during docetaxel chemotherapy in CRPC patients with bone metastasis.     

Evaluation of fatty acid synthase expression in oesophageal mucosa of patients with oesophagitis, Barrett’s oesophagus and adenocarcinoma

Background and aim

To evaluate the expression of fatty acid synthase (FAS) in the oesophagitis–Barrett’s oesophagus–oesophageal adenocarcinoma sequence compared with p53 and Ki67 expressions, retained for a long time reliable markers of oesophageal cells biological behaviour.

Methods

In Barrett’s oesophagus, oesophagitis and oesophageal adenocarcinoma patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, p53 and Ki67. FAS expression was positive, when a strong granular cytoplasmic staining was observed in oesophageal cells. Ki67 and p53 was defined positive, when nuclear staining was clearly detected at 10× magnification.

Results

A mild expression of FAS was found in 39% of patients with oesophagitis. The amount of FAS expression increased up to 70% in Barrett’s oesophagus while this was present in all patients with oesophageal adenocarcinoma (p = 0.0001). In Barrett’s oesophagus, p53 was mildly or intensely expressed in 77% and in 15% of cases, respectively, and mildly or intensely expressed in 33% and 67% of patients with oesophageal adenocarcinoma, respectively, (p = 0.0001). Ki67 was mildly expressed in 17% of oesophagitis cases and was absent in the majority of cases. In Barrett’s oesophagus, a mild Ki67 expression was present in 46% of cases, and in oesophageal adenocarcinoma it was present prevalently in intense form (67%; p = 0.0001).

Conclusions

The over-expression of p53, Ki67 and FAS in otherwise similar morphological groups may be useful to stratify patients into selected prognostic subgroups in order to achieve better clinical approaches.     

Hospital Readmissions with Exacerbation of Obstructive Pulmonary Disease in Illicit Drug Smokers

Purpose

Patients with obstructive pulmonary disease (asthma or chronic obstructive pulmonary disease—COPD) who smoke illicit drugs are at an increased risk of hospital admissions. We compared hospital readmission rates due to exacerbations of obstructive pulmonary disease amongst patients who were current/ex-illicit drug smokers versus current/ex-tobacco smokers.

Methods

We reviewed all the admissions between January 2009 and September 2011 with a presumptive diagnosis of an ‘exacerbation of COPD’ retrospectively from our COPD admission database.

Results

There were 950 sequential hospital admissions in 709 patients over a 33-month period; 250 ex-tobacco smokers, 370 current tobacco smokers and 89 current/ex-illicit drug smokers. Recurrent hospital admission rates with exacerbation of obstructive pulmonary disease were higher in the illicit drug smokers compared with current/ex-tobacco smokers (1.00 versus 0.22/0.26, p < 0.001). Illicit drug smokers were younger [50 versus 72.9/69.9 (mean 71.2) years, p < 0.001] and had shorter length of hospital stay [7.44 versus 9.28/10.69 (mean 9.87) days, p = 0.038]. Illicit drug smokers with FEV₁ < 1 litre (L) had higher readmissions than ex/current tobacco smokers with FEV₁ < 1 L (p < 0.001). Admissions requiring non-invasive ventilation for type 2 respiratory failure were more common in illicit drug smokers (8.4 versus 3 %, p < 0.002).

Conclusion

We have shown that readmission rates in illicit drug smokers with FEV₁ < 1 L are higher than in tobacco smokers. Studies are needed to determine whether targeting these illicit drug users with an intensive community intervention package (to include early therapy, pulmonary rehabilitation) will reduce readmission rates in this often neglected population.     

A Novel Adenosine Precursor 2′,3′-Cyclic Adenosine Monophosphate Inhibits Formation of Post-surgical Adhesions

Background

Intraperitoneal adenosine reduces abdominal adhesions. However, because of the ultra-short half-life and low solubility of adenosine, optimal efficacy requires multiple dosing.

Aim

Here, we compared the ability of potential adenosine prodrugs to inhibit post-surgical abdominal adhesions after a single intraperitoneal dose.

Methods

Abdominal adhesions were induced in mice using an electric toothbrush to damage the cecum. Also, 20 μL of 95 % ethanol was applied to the cecum to cause chemically induced injury. After injury, mice received intraperitoneally either saline (n = 18) or near-solubility limit of adenosine (23 mmol/L; n = 12); 5′-adenosine monophosphate (75 mmol/L; n = 11); 3′-adenosine monophosphate (75 mmol/L; n = 12); 2′-adenosine monophosphate (75 mmol/L; n = 12); 3′,5′-cyclic adenosine monophosphate (75 mmol/L; n = 19); or 2′,3′-cyclic adenosine monophosphate (75 mmol/L; n = 20). After 2 weeks, adhesion formation was scored by an observer blinded to the treatments. In a second study, intraperitoneal adenosine levels were measured using tandem mass spectrometry for 3 h after instillation of 2′,3′-cyclic adenosine monophosphate (75 mmol/L) into the abdomen.

Results

The order of efficacy for attenuating adhesion formation was: 2′,3′-cyclic adenosine monophosphate > 3′,5′-cyclic adenosine monophosphate ≈ adenosine > 5′-adenosine monophosphate ≈ 3′-adenosine monophosphate ≈ 2′-adenosine monophosphate. The groups were compared using a one-factor analysis of variance, and the overall p value for differences between groups was p < 0.000001. Intraperitoneal administration of 2′,3′-cAMP yielded pharmacologically relevant levels of adenosine in the abdominal cavity for >3 h.

Conclusion

Administration of 2′,3′-cyclic adenosine monophosphate into the surgical field is a unique, convenient and effective method of preventing post-surgical adhesions by acting as an adenosine prodrug.     

Diastolic cardiac dysfunction is a predictor of dismal prognosis in patients with liver cirrhosis

Background and purpose

Left ventricular diastolic dysfunction (LVDD) constitutes the prominent characteristic of cirrhotic cardiomyopathy, but its relevance on the clinical course of cirrhotic patients has not been clearly defined. The aim of the study was to evaluate the relationship of LVDD with the severity and etiology of liver disease and to investigate whether it affects the outcome of cirrhotic patients.

Methods

Cardiac function of 45 cirrhotics was studied by a tissue Doppler imaging echocardiography. Diagnosis of LVDD was made according to the latest guidelines of the American Society of Echocardiography. All patients were followed up for a period of 2 years. Death or liver transplantation was the endpoint of the study.

Results

LVDD was found in 17 (38 %) of 45 patients. Its presence was not found to be associated with the etiology and stage of cirrhosis, but its severity was directly correlated with the Child-Pugh score. At the end of follow-up, 14 patients had died; 9 had LVDD (9/17, 53 %) and 5 had not (5/28, 18 %). Patients who died at the beginning of observation period had a higher Child-Pugh and MELD score, higher BNP, lower albumin and more prolonged QTc. On Kaplan-Meier analysis, patients with LVDD had statistically significantly worse prognosis compared to those without (p = 0.013, log rank: 5.495). Low albumin values (p = 0.003) and presence of LVDD (p = 0.017) were independent predictive factors of mortality.

Conclusions

LVDD is a common complication of cirrhosis. As its development seems to be related to a worse prognosis, patients with LVDD must be under a strict follow-up.