Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors – a single center experience

OBJECTIVE:

To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib.

METHODS:

Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing.

RESULTS:

We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months.

CONCLUSIONS:

Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.     

Low educational level but not low income impairs the achievement of cytogenetic remission in chronic myeloid leukemia patients treated with imatinib in Brazil

OBJECTIVES:

In Brazil, imatinib mesylate is supplied as the first-line therapy for chronic myeloid leukemia in the chronic phase through the public universal healthcare program, Sistema Único de Saúde (SUS). We studied the socio-demographic factors that influenced therapy success in a population in the northeast region of Brazil.

METHODS:

Patients with chronic myeloid leukemia from the state of Piauí were treated in only one reference center. Diagnosis was based on WHO 2008 criteria. Risk was assessed by Sokal, Hasford and EUTOS scores. Patients received 400 mg imatinib daily. We studied the influence of the following factors on the achievement of complete cytogenetic response within one year of treatment: age, clinical risk category, time interval between diagnosis and the start of imatinib treatment, geographic distance from the patient''s home to the hospital, years of formal education and monthly income.

RESULTS:

Among 103 patients studied, the median age was 42 years; 65% of the patients had 2-9 years of formal education, and the median monthly income was approximately 100 US$. Imatinib was started in the first year after diagnosis (early chronic phase) in 69 patients. After 12 months of treatment, 68 patients had a complete cytogenetic response. The Hasford score, delay to start imatinib and years of formal education influenced the attainment of a complete cytogenetic response, whereas income and the distance from the home to the healthcare facility did not.

CONCLUSION:

Patients require additional healthcare information to better understand the importance of long-term oral anticancer treatment and to improve their compliance with the treatment.     

Tuberculosis of the head and neck – epidemiological and clinical presentation

Introduction

The aim of our retrospective study was to review the clinical and epidemiological presentation of head and neck tuberculosis.

Material and methods

We analyzed the history of 73 patients with head and neck tuberculosis hospitalized in the Department of Otolaryngology, Medical University of Warsaw, between 1983 and 2009.

Results

We found that 26 (35.6%) patients presented with lymph node tuberculosis, 20 (27.4%) with laryngeal tuberculosis, 10 (13.7%) with oropharyngeal tuberculosis, 9 (12.3%) with salivary gland tuberculosis, 3 (4.1%) with tuberculosis of paranasal sinuses, 3 (4.1%) with aural tuberculosis, and 2 (2.7%) with skin tuberculosis in the head and neck region. Within the group of patients with lymph node tuberculosis in 15 cases there were infected lymph nodes of the 2^nd and 3^rd cervical region and in 11 infected lymph nodes of the 1^st cervical region. In 5 cases of laryngeal tuberculosis there was detected coexistence of cancer. Oropharyngeal tuberculosis in 7 cases was localized in tonsils, where in 1 case coexisting cancer was diagnosed. Chest X-ray was performed in all cases and pulmonary tuberculosis was identified in 26 (35.6%) cases.

Conclusions

We conclude that tuberculosis still remains a problem and must be taken into consideration in the diagnostic process. The coincidence of tuberculosis and cancer is remarkable in the head and neck region.     

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND:

To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome.

MATERIALS/METHODS:

We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35).

RESULTS:

We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups.

DISCUSSION:

The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process.     

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES:

The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival.

METHODS:

We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles.

RESULTS:

Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4×10⁹/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%.

CONCLUSION:

T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.     

Development and evaluation of a brief self-completed family history screening tool for common chronic disease prevention in primary care

Background

Family history is an important risk factor for many common chronic diseases, but it remains underutilised for diagnostic assessment and disease prevention in routine primary care.

Aim

To develop and validate a brief self-completed family history questionnaire (FHQ) for systematic primary care assessment for family history of diabetes, ischaemic heart disease, breast cancer, and colorectal cancer.

Design and setting

Two-stage diagnostic validation study in 10 general practices in eastern England.

Method

Participants aged 18–50 years were identified via random sampling from electronic searches of general practice records. Participants completed a FHQ then had a three-generational ‘gold standard’ pedigree taken, to determine disease risk category. In stage 1, the FHQ comprised 12 items; in stage 2 the shorter 6-item FHQ was validated against the same ‘gold standard’.

Results

There were 1147 participants (stage 1: 618; stage 2: 529). Overall, 32% were at increased risk of one or more marker conditions (diabetes 18.9%, ischaemic heart disease 13.3%, breast cancer 6.2%, colorectal cancer 2.2%). The shorter 6-item FHQ performed very well for all four conditions: pooled data from both stages show diabetes, sensitivity = 98%, specificity = 94%; ischaemic heart disease, sensitivity = 93%, specificity = 81%; breast cancer, sensitivity = 81%, specificity = 83%; colorectal cancer, sensitivity = 96%, specificity = 88%, with an area under the receiver operating characteristic curve of 0.90 for males and 0.89 for females.

Conclusion

This brief self-completed FHQ shows good diagnostic accuracy for identifying people at higher risk of four common chronic diseases. It could be used in routine primary care to identify patients who would be most likely to benefit from a more detailed pedigree and risk assessment, and consequent management strategies.     

Lymphoreticular diseases in Nigerians

Background

The lymphoreticular system plays a major role in both the innate and adaptive immune responses. This study reviews retrospectively cases of lymphoreticular diseases seen at a tertiary institution in Nigeria.

Materials and Methods

This is a retrospective study in which biopsies from the bone marrow, spleen, lymph nodes and extranodal lymphoid tissues reported within a period of 16 years were reviewed with respect to age, sex and pathological diagnosis. Statistical analysis was performed for differences in proportion using Chi square by SPSS version 12.

Results

Nine hundred and forty four cases comprising 559 biopsies from lymph nodes and extranodal lymphoid tissues, 272 bone marrow biopsies and 113 spleen biopsies were studied. Non Hodgkin''s lymphoma (NHL) and tuberculosis were the most common lesions in lymph nodes and extranodal lymphoid tissues. The axillary and cervical nodes accounted for most cases of metastasis. Breast cancer accounted for the majority of metastasis to lymph nodes.The most common pathological changes in bone marrow were NHL and reactive hyperplasia. Patients with chronic lymphocytic leukaemia (CLL) had the highest mean age, which was significantly higher than in those with NHL (p=.001, 95% confidence interval −27.91 to −7.76). The most common finding in the spleen was splenic rupture and haemoperitoneum from road traffic accident.

Conclusion

NHL and tuberculosis should be high on the list of differential diagnosis of lymphadenopathy in Nigerians. Whereas trauma from RTA was the major reason for splenectomy in Nigerians, in the elderly splenic biopsy would likely show CLL.     

Assessments of the associations of thrombus localization with accompanying disorders,risk factors,D-dimer levels,and the red cell distribution width in pulmonary embolism

OBJECTIVE:

Pulmonary embolisms occur as a wide spectrum ranging from clinically asymptomatic thrombi to massive thrombi that lead to cardiogenic shock. The purpose of this study was to determine the associations of thrombus localization with risk factors, accompanying disorders, D-dimer levels and the red blood cell distribution width in patients with pulmonary embolism.

MATERIAL AND METHODS:

In 148 patients diagnosed with pulmonary embolism, the presence and anatomical localization of the thrombus were assessed via computed tomographic pulmonary angiography. The accompanying disorders, risk factors, serum D-dimer levels, and red blood cell distribution width of the patients were retrospectively evaluated. ClinicalTrials.gov: NCT02388841.

RESULTS:

The mean age of the patients was 54±16.0 years, and 48 patients were ≥65 years of age. The most frequent accompanying disorders were chronic obstructive pulmonary disease (22%) and malignancy (10.1%), and the most frequent risk factors were recent operation (14.1%) and immobilization (18.2%). Thrombi were most frequently observed in the right pulmonary artery (37.8%). In 31% of the patients, the thrombus was localized to the main pulmonary arteries. Immobile patients exhibited a higher proportion of thrombi in the main pulmonary arteries than mobile patients. The mean D-dimer level and the mean red blood cell distribution width in the patients with thrombi in the main pulmonary arteries were higher than those in the patients with thrombi in more distal pulmonary arterial branches.

CONCLUSION:

Significant associations of proximally localized thrombi with immobilization, the D-dimer levels, and the red blood cell distribution width were observed.     

The reduction of serum aminotransferase levels is proportional to the decline of the glomerular filtration rate in patients with chronic kidney disease

OBJECTIVE:

This study sought to determine the serum aminotransferase levels of patients with predialysis chronic kidney disease and establish their relationships with serum creatinine levels and glomerular filtration rate.

METHODS:

Patients with chronic kidney disease were evaluated between September 2011 and May 2012. Aminotransferase and creatinine serum levels were measured using an automated kinetic method, and glomerular filtration rates were estimated using the Cockroft-Gault and Modification of Diet in Renal Disease formulas to classify patients into chronic kidney disease stages.

RESULTS:

Exactly 142 patients were evaluated (mean age: 64±16 years). The mean creatinine serum level and glomerular filtration rate were 3.3±1.2 mg/dL and 29.1±13 mL/min/1.73 m², respectively. Patients were distributed according to their chronic kidney disease stages as follows: 3 (2.1%) patients were Stage 2; 54 (38%) were Stage 3; 70 (49.3%) were Stage 4; and 15 (10.5%) were Stage 5. The mean aspartate aminotransferase and alanine aminotransferase serum levels showed a reduction in proportion to the increase in creatinine levels (p=0.001 and p=0.05, respectively) and the decrease in glomerular filtration rate (p=0.007 and p=0.028, respectively). Alanine aminotransferase and aspartate aminotransferase serum levels tended to be higher among patients classified as stage 2 or 3 compared with those classified as stage 4 or 5 (p=0.08 and p=0.06, respectively).

CONCLUSIONS:

The aspartate aminotransferase and alanine aminotransferase serum levels of patients with predialysis chronic kidney disease decreased in proportion to the progression of the disease; they were negatively correlated with creatinine levels and directly correlated with glomerular filtration rate.     

Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases

OBJECTIVES:

Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival.

METHODS:

We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed.

RESULTS:

The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had “pure fibrolamellar hepatocellular carcinoma,” whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having “mixed fibrolamellar hepatocellular carcinoma.” The median overall survival was 36 months. The presence of “mixed fibrolamellar hepatocellular carcinoma” and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery.

CONCLUSION:

Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival.     

Incidence and mortality trends of leukemia and lymphoma in Croatia, 1988-2009

Aim

To investigate the time trends of leukemia and lymphoma in Croatia from 1988-2009, compare them with trends in other populations, and identify possible changes.

Methods

The data sources were the Croatian National Cancer Registry for incidence data, Croatian Bureau of Statistics for the numbers of deaths, and United Nations population estimates. Joinpoint regression analysis using the age-standardized rates was used to analyze incidence and mortality trends.

Results

Acute lymphoblastic leukemia and chronic lymphocytic leukemia incidence did not significantly change. Acute myeloid leukemia incidence significantly increased in women, with estimated annual percentage change (EAPC) of 2.6% during the whole period, and in men since 1998, with EAPC of 3.2%. Chronic myeloid leukemia incidence significantly decreased in women (EAPC -3.7%) and remained stable in men. Mortality rates were stable for both lymphoid and myeloid leukemia in both sexes. Hodgkin lymphoma non-significantly increased in incidence and significantly decreased in mortality (EAPCs of -5.6% in men and -3.7% in women). Non-Hodgkin lymphoma significantly increased in incidence in women (EAPC 3.2%) and non-significantly in men and in mortality in both men (EAPC 1.6%) and women (EAPC 1.8%).

Conclusion

While Croatia had similar leukemia and lymphoma incidence trends as the other countries, the mortality trends were less favorable than in Western Europe. The lack of declines of leukemia incidence and non-Hodgkin lymphoma mortality could be attributed to late introduction of optimal therapies. As currently the most up-to-date diagnostics and treatments are available and covered by health insurance, we expect more favorable trends in the future.Leukemias and lymphomas contribute 5% to the overall cancer incidence in Croatia (1). They comprise disease entities diverse in etiology, incidence, prognosis, and treatment. The four major leukemia subtypes include acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), while lymphomas include Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).Estimated 5-year relative survival for patients diagnosed between 2000 and 2002 in Europe, according to EUROCARE-4 results, is 43.4% for the overall group of leukemias. CLL has the highest 5-year survival rate (70.2%), followed by CML (37.2%), ALL (28.8%), and AML (15.8%). Five-year survival rates for lymphomas were 81.9% for HL and 53.6% for NHL (2).Recognized environmental risk factors for leukemia are exposure to ionising radiation (3-5), chemicals such as benzene (6), pesticides (7), chemotherapy (8), cigarette smoking (9), genetic disorders (10,11), family history in case of CLL (12), infection with HTLV-I (13), socio-economic status (14), and obesity (15). However, those risk factors could explain only a minority of cases, and leukemia etiology remains largely unknown. Environmental risk factors for NHL are exposure to pesticides, solvents (16,17) and HIV infection (18), while those for HL include HIV (19) and Epstein-Barr virus infection (20).The last decades brought significant improvements in diagnosis and treatment of leukemias and lymphomas. The aim of our study was to investigate the time trends of leukemia and lymphoma in Croatia from 1988-2009, compare them with trends in other populations, and identify possible changes.     

Implication of Early Lymphocyte Recovery after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Leukemia

Purpose

The repopulating lymphocytes after allogeneic hematopoietic stem cell transplantation have an important role not only on the prevention of serious infections in the early transplantation period, but also on the killing of residual leukemic cells by graft-versus-leukemia effect. The aim of this study was to analyze the impact of lymphocyte recovery after allogeneic stem cell transplantation in children with hematologic malignancies.

Materials and Methods

We evaluated 69 children transplanted for acute lymphoblastic leukemia (ALL) (n=34), acute myeloid leukemia (AML) (n=26), chronic leukemia (n=7) and juvenile myelomonocytic leukemia (n=2) between 1996 and 2008 at the Chonnam National University Hospital, Korea. The patients were grouped based on absolute lymphocyte counts (ALC) <500/µL or ≥500/µL at D+21 and D+30 after transplant.

Results

Patients with a High ALC at D+21 and D+30 had a faster neutrophil and platelet engraftment. The High at D+30 group had a better 5 year overall survival (71% vs. 53%, p=0.043) and event-free survival (72% vs. 53%, p=0.065) than the Low at D+30 group. The incidence of grade II-IV acute and chronic graft-versus-host disease (GVHD), and relapse rate did not differ by the ALC counts. However, the Low at D+30 group had a significantly increased risk for transplant-related mortality (p=0.019). The univariate analysis showed that the factors associated with decreased survival were a Low ALC at D+30, patients with high risk ALL, and grade II-IV aGVHD in patients with ALL and AML.

Conclusion

Early posttransplant serial lymphocyte measurement would be a simple but useful method for predicting transplant outcomes.     

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES:

The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis.

METHODS:

We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10±68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism.

RESULTS:

Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto''s thyroiditis who had received a lower ¹³¹I cumulative dose and did not present lymph node metastases.

CONCLUSIONS:

We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.     

Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes

INTRODUCTION:

Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia.

OBJECTIVE:

To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients.

METHODS:

Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression.

RESULTS:

In the genes studied, no mutations were detected in the patients at the time of diagnosis. One patient with chronic myelomonocytic leukemia was heterozygous for a Janus kinase 2 mutation after disease progression.

CONCLUSIONS:

These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.     

Clinical features of bladder cancer in primary care

Background

Bladder cancer accounts for over 150 000 deaths worldwide. No screening is available, so diagnosis depends on investigations of symptoms. Of these, only visible haematuria has been studied in primary care.

Aim

To identify and quantify the features of bladder cancer in primary care.

Design and setting

Case-control study, using electronic medical records from UK primary care.

Method

Participants were 4915 patients aged ≥40 years, diagnosed with bladder cancer January 2000 to December 2009, and 21 718 age, sex, and practice-matched controls, were selected from the General Practice Research Database, UK. All clinical features independently associated with bladder cancer using conditional logistic regression were identified, and their positive predictive values for bladder cancer, singly and in combination, were estimated.

Results

Cases consulted their GP more frequently than controls before diagnosis: median 15 consultations (interquartile range 9–22) versus 8 (4–15): P<0.001. Seven features were independently associated with bladder cancer: visible haematuria, odds ratio 34 (95% confidence interval [CI] = 29 to 41), dysuria 4.1 (95% CI = 3.4 to 5.0), urinary tract infection 2.2 (95% CI = 2.0 to 2.5), raised white blood cell count 2.1 (95% CI = 1.6 to 2.8), abdominal pain 2.0 (95% CI = 1.6 to 2.4), constipation 1.5 (95% CI = 1.2 to 1.9), raised inflammatory markers 1.5 (95% CI = 1.2 to 1.9), and raised creatinine 1.3 (95% CI = 1.2 to 1.4). The positive predictive value for visible haematuria in patients aged ≥60 years was PPV of 3.9% (95% CI = 2.2 to 3.2).

Conclusion

Visible haematuria is the commonest and most powerful predictor of bladder cancer in primary care, and warrants investigation. Most other previously reported features of bladder cancer were associated with the disease, but with low predictive values. There is a need for improved diagnostic methods, for those patients whose bladder cancer presents without visible haematuria.     

Efficacy of levofloxacin,amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers

OBJECTIVES:

The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication.

METHODS:

Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days.

RESULTS:

A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints.

CONCLUSIONS:

Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen.     

Local anesthesia with epinephrine is safe and effective for oral surgery in patients with type 2 diabetes mellitus and coronary disease: a prospective randomized study

OBJECTIVE:

To investigate the variations in blood glucose levels, hemodynamic effects and patient anxiety scores during tooth extraction in patients with type 2 diabetes mellitus T2DM and coronary disease under local anesthesia with 2% lidocaine with or without epinephrine.

STUDY DESIGN:

This is a prospective randomized study of 70 patients with T2DM with coronary disease who underwent oral surgery. The study was double blind with respect to the glycemia measurements. Blood glucose levels were continuously monitored for 24 hours using the MiniMed Continuous Glucose Monitoring System. Patients were randomized into two groups: 35 patients received 5.4 mL of 2% lidocaine, and 35 patients received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Hemodynamic parameters (blood pressure and heart rate) and anxiety levels were also evaluated.

RESULTS:

There was no difference in blood glucose levels between the groups at each time point evaluated. Surprisingly, both groups demonstrated a significant decrease in blood glucose levels over time. The groups showed no significant differences in hemodynamic and anxiety status parameters.

CONCLUSION:

The administration of 5.4 mL of 2% lidocaine with epinephrine neither caused hyperglycemia nor had any significant impact on hemodynamic or anxiety parameters. However, lower blood glucose levels were observed. This is the first report using continuous blood glucose monitoring to show the benefits and lack of side effects of local anesthesia with epinephrine in patients with type 2 diabetes mellitus and coronary disease.     

Arch height and maximum rearfoot eversion during jogging in 2 static neutral positions

Context:

Clinically, lowering of the medial longitudinal arch is believed to be closely related to rearfoot eversion. However, the relationship between arch height and rearfoot eversion during gait is unclear.

Objectives:

(1) To examine the influence of 2 reference positions (weight-bearing neutral position [WBNP] and subtalar neutral position [STNP]) on maximum rearfoot eversion, tibial internal rotation, knee flexion, knee internal rotation, and dorsiflexion-plantar flexion of ankle joint measures during jogging and (2) to compare the relationships among static arch height, navicular drop, and the 2 maximum rearfoot eversion measures.

Design:

Crossover study.

Setting:

Gait laboratory.

Patients or Other Participants:

Thirty-three volunteers between 18 and 40 years of age.

Intervention(s):

Each participant stood on the treadmill in 2 static positions: WBNP and STNP. Kinematic data were obtained using a 10-camera motion analysis system (120 Hz) when participants jogged at 2.65 m/s on the treadmill in bare feet.

Main Outcome Measure(s):

Rearfoot and shank angular kinematics, navicular drop, and static arch height.

Results:

Maximum rearfoot eversion was greater (WBNP: 4.03° ± 2.58°, STNP: 10.91° ± 5.34°) when STNP was the static reference (P < .001). A strong correlation was seen between maximum STNP eversion and navicular drop (r = 0.842) but not between WBNP and navicular drop (r = 0.216). Differences were noted in dorsiflexion and knee kinematics during gait between the static references; however, the effect sizes were low, and the mean differences were smaller than 2°, which was less than 5% of total excursion during gait.

Conclusions:

Using STNP rather than WBNP as the reference position affects estimates of frontal-plane rearfoot movement but not other ankle or knee motions in jogging.     

Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study

OBJECTIVE:

Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China.

METHODS:

The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search.

RESULTS:

Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001).

CONCLUSIONS:

Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found.     

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES:

Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid.

METHODS:

Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis.

RESULTS:

Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups.

CONCLUSIONS:

Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange.