Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non-invasive NAFLD tests. We aimed to review current evidence for common non-invasive tests for NAFLD-related fibrosis in obesity. METHODS: We systematically searched for studies assessing the diagnostic accuracy of 11 biomarker panels and elastography techniques for NAFLD-related fibrosis in obesity. Meta-analyses were performed where possible. RESULTS: Thirty-eight studies were identified assessing the selected tests in obese populations. Simple biomarker panels (e.g. NAFLD fibrosis score) were the most validated. Evidence showed better accuracy of complex biomarker panels (NAFLD fibrosis score: summary receiver operator characteristic [SROC] 0.795-0.813 vs. enhanced liver fibrosis: SROC 0.962); however, these were poorly validated in obesity. Elastography techniques were better studied and had high diagnostic accuracy (transient elastography: SROC 0.859; magnetic resonance elastography: SROC 0.965) but were limited by BMI-dependent failure. Limited evidence was found to validate the accuracy of any test in exclusively obese populations. CONCLUSION: In obese subjects, complex biomarker panels and elastography have been reasonable to good accuracy for NAFLD-related fibrosis; however, these methods have not been well validated. Further study in this high-risk population is needed.

The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis.

There have been numerous case reports of severe adverse events including deaths following chronic licorice ingestion. The aim of the present study was to evaluate the effect of chronic ingestion of licorice on blood pressure, plasma potassium, plasma renin activity and plasma aldosterone. A search of MEDLINE, PubMed, EMBASE, CENTRAL, DARE, CINAHL and Current Contents Connect was performed from inception through to 26 April 2017. Trials that included a treatment group ingesting a product containing at least 100 mg of glycyrrhizic acid daily were selected. Pooled mean changes from baseline with 95% confidence intervals were calculated for diastolic blood pressure, systolic blood pressure, plasma potassium, plasma renin activity and plasma aldosterone using a random effects model. An assessment of dose-response was also undertaken. A total of 18 studies (n=337) were included in the meta-analysis. There was a statistically significant increase in mean systolic blood pressure (5.45 mm Hg, 95% CI 3.51-7.39) and diastolic blood pressure (3.19 mm Hg, 95% CI 0.10-6.29) after chronic ingestion of a product containing glycyrrhizic acid. Plasma potassium (-0.33 mmol l-1, 95% CI -0.42 to 0.23), plasma renin activity (-0.82 ngml-1 per hour, 95% CI -1.27 to -0.37) and plasma aldosterone (-173.24 pmol l-1, 95% CI -231.65 to -114.83) were all significantly decreased. A significant correlation was noted between daily dose of glycyrrhizic acid and systolic blood pressure (r2=0.55) and diastolic blood pressure (r2=0.65), but not for the other outcome measures. Hence, chronic licorice ingestion is associated with an increase in blood pressure and a drop in plasma potassium, even at modest doses. This is of particular relevance for individuals with existing cardiovascular disease.

The Effect of Physical Exercise on Frail Older Persons: A Systematic Review.

Physical exercise is one of the most effective non-pharmacological interventions aimed to improve mobility and independence in older persons. The effect of physical exercise and the most effective type of exercise in frail older persons remain undefined. This systematic review examines the effectiveness of physical exercise on frail older persons. Seven databases were search for randomized control trials which assessed the effect of exercise on participants who were identified as being frail using specific and validated criteria. Nine articles were reviewed from eight studies, from which seven used a validated definition of frailty. Based on the articles analyzed in our systematic review, the evidence suggests that exercise has a positive effect on various measures used to determine frailty including cognition, physical functioning, and psychological wellbeing. Some studies revealed that exercise may prevent or delay the onset of frailty which can enhance quality of life in older adults. Despite the evidence for exercise interventions in frail older adults, it appears that there is no clear guidance regarding the most effective program variables. The reviewed studies were generally long in duration (≥6 months) with sessions lasting around 60 minutes performed three or more times per week, including multicomponent exercises. In conclusion, although exercise interventions appear to be effective in managing the various components of frailty and preventing/delaying the onset of frailty, the most effective exercise program in this population remains unidentified.

HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study.

BACKGROUND: Several studies have evaluated the prognostic value of HER2 in oesophageal cancer, but the prognostic influence of HER2 overexpression in oesophageal cancer remains uncertain. The aim of this study was to assess the incidence of HER2 positivity and relationship with clinicopathological features in patients with oesophageal cancer. DESIGN: The study cohort consisted of 269 patients diagnosed with oesophageal carcinoma in a single institution. HER2 expression was analysed by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival analysis was assessed using Hazard models. RESULTS: HER2 expression was IHC3+ in 14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases. SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among 27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of 125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95% CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71-20.00). There was no significant difference in survival between the (HER2 +ve, 14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence rate of 9.9% was found among patients with oesophageal cancer and no correlation with survival was detected overall.

Internal versus external fixation of the anterior component in unstable fractures of the pelvic ring: pooled results from a systematic review.

PURPOSE: Improving reduction of the pelvic ring improves long-term functional outcomes for patients. It has been demonstrated that posterior internal fixation is necessary to adequately control fractures to the posterior ring and there is evidence that supplementing this with fixation of the anterior ring improves stability. It is accepted that internal fixation provides greater stability than external fixation of the anterior ring but long-term differences in radiographic and functional outcomes have not yet been quantified. METHODS: A search of electronic databases, reference lists and review articles from 1989 to 2015 yielded 18 studies (n = 884) that met our inclusion criteria. We included studies that discussed pelvic ring injuries in adults, reported functional or radiological outcomes or complications by anterior ring intervention and exceeded 14 patients. We excluded biomechanical and cadaver studies. RESULTS: Internal fixation of the anterior pelvic ring had better functional and radiographic outcomes. Residual displacement of >10 mm was less common with internal fixation (ER 0.12, 95 % CI 0.06-0.24) than external fixation (ER 0.31, 95 % CI 0.11-0.62). Unsatisfactory outcomes also occurred at a lower rate (ER 0.09, 95 % CI 0.03-0.22) compared to external fixation (ER 0.32, 95 % CI 0.18-0.50). Losses of reduction (ER 0.02, 95 % CI 0.01-0.04 versus ER 0.07, 95 % CI 0.02-0.21), malunions (ER 0.03, 95 % CI 0.01-0.08 versus ER 0.07, 95 % CI 0.02-0.21) and delayed/non-unions (ER 0.02, 95 % CI 0.01-0.05 versus ER 0.04, 95 % CI 0.02-0.07). CONCLUSIONS: Internal fixation of the anterior pelvic ring as supplementary fixation for unstable injuries to the pelvic ring appears to result in better radiographic and functional outcomes as well as fewer complications. However, data that separated outcomes and complications in relation to interventions of the anterior pelvic ring were limited. More studies looking specifically at outcomes in relation to the type of anterior ring intervention are needed.

Role of decompressive hemicraniectomy in extensive middle cerebral artery strokes: a meta-analysis of randomised trials.

BACKGROUND: Prognosis for patients with 'malignant' or space-occupying oedema post middle cerebral artery infarct remains poor despite maximal medical therapy delivered in the intensive care setting. AIM: We performed a meta-analysis to evaluate the value of surgical decompression versus medical management alone in patients suffering from malignant middle cerebral artery infarct. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct and Web of Science. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The overall OR for mRS 6 (death) at 6 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.19 (95% CI: 0.10-0.37). The frequency of patients with mRS 2, 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 3.29 (95% CI: 1.76-6.13). The overall OR for mRS 6 (death) at 12 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.17 (95% CI: 0.10-0.29). The frequency of patients with mRS 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 4.43 (95% CI: 2.27-8.66). In the long run it was also observed that the number of patients with a mRS score of 2 was significantly higher in the decompressive surgery cohort an OR of 4.51 (95% CI: 1.06-19.24). CONCLUSIONS: Our results imply that surgical intervention decreased mortality of patients with fatal middle cerebral artery infarct at the expense of increasing the proportion suffering from substantial disability at the conclusion of follow up.

Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis.

BACKGROUND: Vitamin B12 (cobalamin) deficiency can result in irreversible structural brain changes if not treated appropriately. Long-term use of acid-lowering agents (ALA) has been linked to vitamin B12 deficiency, but results are inconsistent. AIM: To evaluate the association between prolonged ALA use and vitamin B12 deficiency by performing a meta-analysis. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents, Cochrane Library, Google Scholar, Science Direct and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio and 95% confidence interval (95% CI). RESULTS: Of the articles reviewed, four case-control studies (4254 cases and 19,228 controls) and one observational study met full criteria for analysis. The long-term ALA use was significantly associated with development of vitamin B12 deficiency (hazard ratio 1.83, 95% CI: 1.36-2.46, P-value 0.00). CONCLUSION: Chronic use of ALA is a risk factor for developing vitamin B12 deficiency. Judicious prescribing of ALA and regular monitoring of vitamin B12 in patients who are inevitably on long-term ALA therapy are recommended.

Streptococcus bovis infection and colorectal neoplasia: a meta-analysis.

AIM: A meta-analysis was conducted to determine the risk associated with Streptococcus bovis infection and the occurrence of colorectal neoplasia (CRN). The level of risk remains unknown. METHOD: We conducted a search of MEDLINE, PubMed and EMBASE up to January 2014. We used a random-effects model to analyse the data. RESULTS: We identified 48 studies concerning three main topics: S. bovis septicaemia, S. bovis endocarditis and S. bovis faecal carriage. The total sample sizes were 1729, 807 and 1145, respectively; the 48 studies included 9 case-control studies and 39 case series. Overall, the presence of S. bovis infection was found to be significantly associated with the presence of CRN. Streptococcus bovis endocarditis showed the strongest association in analyses of case-control studies and case series (OR 14.54, 95% CI 5.66-37.35, test for heterogeneity I2 = 43.53; event rate of 0.53, 95% CI 0.45-0.61, test for heterogeneity I2 = 53.50). Similarly, S. bovis septicaemia was also associated with a high level of concurrence with CRN (OR 7.48, 95% CI 3.10-18.06, test for heterogeneity I(2) = 43.32; event rate 0.49, 95% CI 0.42-0.56, test for heterogeneity I2 = 69.97). Patients with CRN were found to have a higher incidence of S. bovis in faeces upon stool culture (OR 2.52, 95% CI 1.14-5.58, test for heterogeneity I2 = 69.17). CONCLUSION: The meta-analysis showed a statistically significant association between the presence of S. bovis endocarditis or S. bovis septicaemia and CRN. Furthermore, there is a statistically significant increase in likelihood of finding S. bovis in the stool of individuals with CRN.

Folate intake and the risk of prostate cancer: a systematic review and meta-analysis.

There is conflicting evidence regarding the role of folate on the risk of developing prostate cancer. We performed a systematic review and quantitative meta-analysis of folate blood levels and folate intake, and the risk of prostate cancer. Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 11 October 2013, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of prostate cancer. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a random effects model. The dietary folate meta-analysis comprising 11 studies with 15 336 cases and a total sample size of 146 782 found no statistically significant association with prostate cancer, with an OR of 0.97 (95% CI 0.89-1.06). The total folate meta-analysis comprising of 5 studies with 7114 cases and a total sample size of 93 781 also found no statistically significant association with prostate cancer, with an OR of 0.99 (95% CI 0.82-1.19). The blood folate meta-analysis comprising of seven studies with 6122 cases and a total sample size of 10 232 found an increased risk of prostate cancer with high blood folate levels, with an OR of 1.43 (95% CI 1.06-1.93). There was significant heterogeneity (I(2)=79.5%, P<0.01). Removal of an outlier study removed the heterogeneity (I(2)=0.0%, P=0.54) and the association remained significant with an OR of 1.14 (95% CI 1.02-1.28). Dietary and total folate intake do not appear to be significantly associated with the risk of prostate cancer. High blood folate levels are associated with an increased risk of prostate cancer. These conclusions are limited by the predominance of included studies originating from developed countries with mostly Caucasian populations. Further research in populations with a high prevalence of non-Caucasian backgrounds is needed.

Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis.

SUMMARY: The oncogenic potential of human papillomaviruses (HPV) is well known in the context of cervical carcinoma; however, their role in the development of oesophageal squamous cell carcinoma (OSCC) is less clear. We aimed to determine the extent of the association between HPV infection and OSCC. A comprehensive literature search found 132 studies addressing HPV and OSCC in human cases, and a meta-analysis was performed using a random-effects model. There was evidence of an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2·69, 95% confidence interval (CI) 2·05-3·54]. The prevalence of HPV in OSCC was found to be 24·8%. There was an increased risk associated with HPV-16 infection (OR 2·35, 95% CI 1·73-3·19). Subgroup analyses showed geographical variance, with Asia (OR 2·94, 95% CI 2·16-4·00), and particularly China (OR 2·85, 95% CI 2·05-3·96) being high-risk areas. Our results confirm an increase in HPV infection in OSCC cases.

Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer.

BACKGROUND: Carcinoma of the gall-bladder is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. An association of chronic typhoid carriage and carcinoma of the gall-bladder has been reported. AIM: To clarify whether chronic Salmonella typhi carrier state is associated with carcinoma of the gall-bladder. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents, Cochrane library, Google Scholar, Science Direct and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Of the articles selected, only 17 studies met full criteria for analysis. The overall OR for chronic S. typhi carrier state was 4.28(95% CI: 1.84-9.96). Most of the studies were from South Asia especially India and China. When a subgroup analysis was performed according to region, a significant association was observed in South-East Asia (OR: 4.13, 95% CI: 2.87-5.94, P value <0.01). Chronic S. typhi carrier state was associated with carcinoma of the gall-bladder based on detection methods of S. typhi antibody levels (OR: 3.52, 95% CI: 2.48-5.00, P value <0.01) and even more so on culture (OR: 4.14, 95% CI: 2.41-7.12, P value <0.01). The association was prominent in controls without gallstones (OR: 5.86, 95% CI: 3.84-8.95, P value <0.01) when compared with controls with gallstones (OR: 2.71, 95% CI: 1.92-3.83, P value <0.01). CONCLUSIONS: Chronic S. typhi carrier state is an important risk factor among patients with carcinoma of the gall-bladder. Given the high risk associated with this carrier state, management options should include either elective cholecystectomy or careful monitoring using ultrasound.

Systematic review with meta-analysis: clinical manifestations and management of autoimmune hepatitis in the elderly.

BACKGROUND: Autoimmune hepatitis is an uncommon chronic progressive inflammatory disease of the liver, characterised by hypergammaglobulianemia, circulating autoantibodies, and interface hepatitis histologically. It is traditionally thought to be a disease of young women. However, recent epidemiological and retrospective studies suggest that it might be a disease predominantly of older women. Studies of AIH in elderly patients have been fairly limited. AIM: To investigate the differences in the clinical presentations and the management of AIH in the elderly and the younger patients. METHODS: We conducted a search on MEDLINE (from 1946), PubMed (1946) and EMBASE (1949) through to November 2013 using the terms 'autoimmune hepatitis in the elderly', and the combinations of 'Autoimmune hepatitis' AND the following terms: 'elderly', 'aging', 'older patients', and 'older'. The reference lists of relevant articles were also searched for appropriate studies. RESULTS: A total of 1063 patients were identified with AIH in 10 retrospective studies. The definition of 'elderly' ranged from 60 to 65 years; 264 elderly and 592 younger patients were included for analysis. Elderly, 24.8%, were more likely to present asymptomatically, cirrhotic at presentation and HLA-DR4-positive. They are less likely to be HLA-DR3-positive and to relapse after treatment withdrawal after complete remission. CONCLUSIONS: AIH is an important differential in elderly patients with cirrhosis or abnormal LFTs. Elderly are more likely to be cirrhotic and asymptomatic at presentation. Glucocorticoids use should be readily considered in the elderly patients as the current evidence suggests that they respond well to the therapy, with less relapse after treatment withdrawal.

Is complete lymph node dissection after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary? A meta-analysis.

BACKGROUND: The current recommendation for patients with cutaneous melanoma and a positive sentinel lymph node (SLN) biopsy is a complete lymph node dissection (CLND). However, metastatic melanoma is not present in approximately 80% of CLND specimens. A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive in patients with melanoma. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. The search identified 54 relevant articles reporting the frequency of NSN metastases in melanoma. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). FINDINGS: The pooled estimates that were found to be significantly associated with the high likelihood of NSN metastases were: ulceration (OR: 1.88, 95% CI: 1.53-2.31), satellitosis (OR: 3.25, 95% CI: 1.86-5.66), neurotropism (OR: 2.51, 95% CI: 1.39-4.53), >1 positive SLN (OR: 1.77, 95% CI: 1.2-2.62), Starz 3 (old) (OR: 1.83, 95% CI: 0.89-3.76), Angiolymphatic invasion (OR: 2.46, 95% CI: 1.34-4.54), extensive location (OR: 2.22, 95% CI: 1.74-2.81), macrometastases >2 mm (OR: 1.95, 95% CI: 1.61-2.35), extranodal extension (OR: 3.38, 95% CI: 1.79-6.40) and capsular involvement (OR: 3.16, 95% CI: 1.37-7.27). There were 3 characteristics not associated with NSN metastases: subcapsular location (OR: 0.51, 95% CI: 0.38-0.67), Rotterdam Criteria <0.1 mm (OR: 0.29, 95% CI: 0.17-0.50) and Starz I (new) (OR: 0.44, 95% CI: 0.22-0.91). Other variables including gender, Breslow thickness 2-4 mm and extremity as primary site were found to be equivocal. INTERPRETATION: This meta-analysis provides evidence that patients with low SLN tumor burden could probably be spared the morbidity associated with CLND. We identified 9 factors predictive of non-SLN metastases that should be recorded and evaluated routinely in SLN databases. However, further studies are needed to confirm the standard criteria for not performing CLND.

Maté consumption and the risk of esophageal squamous cell carcinoma: a meta-analysis.

Maté, a tea-like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta-analysis on the subject has been performed to date. A meta-analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever- vs. never-drinkers), as well as for the dose-dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66-3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33-5.73 vs. OR 1.84, 95% CI 1.12-3.00). Heterogeneity was observed in the ever versus never and the high-consumption analyses but not in the low-consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.

Meta-analysis: Barrett's oesophagus and the risk of colonic tumours.

BACKGROUND: Barrett's oesophagus (BO) is a premalignant condition associated with oesophageal adenocarcinoma. Although speculation exists, it is currently unclear if BO is associated with an increased risk of colonic tumours. AIM: To conduct a meta-analysis of studies reporting the prevalence of colonic tumours in patients with BO vs. controls and thus quantify the risk of colonic tumours associated with BO. METHODS: A search was conducted through Medline, PubMed, Embase, and Current Contents Connect to 7 October 2012. We calculated pooled odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model for the risk of all colonic tumours associated with BO, as well as for the subgroups of colorectal cancer (CRC) and benign adenomatous tumours. RESULTS: In total, 11 studies, with 2580 BO cases, met our inclusion criteria. BO was associated with an increased risk of any colonic tumours (OR: 1.96; 95% CI: 1.56-2.46). BO was associated with an increased risk of benign adenomatous tumours (OR: 1.69; 95% CI: 1.20-2.39), as well as an increased risk of CRC (OR: 1.90; 95% CI: 1.35-2.67). No statistically significant heterogeneity was observed. Publication bias was not present. CONCLUSIONS: Barrett's oesophagus was associated with an increased risk of both benign adenomatous colonic tumours and colorectal cancer. Barrett's oesophagus had a stronger association with colorectal cancer than with benign colonic tumours. Further prospective cohort studies are needed to confirm the relationship.

Meta-analysis: oral bisphosphonates and the risk of oesophageal cancer.

BACKGROUND: Bisphoshonates, which are used in the treatment and prevention of osteoporosis, have recently been implicated in the development of oesophageal cancer; however, studies report conflicting data. AIM: To conduct a meta-analysis of studies reporting on the association between bisphosphonates and oesophageal cancer to quantify the relationship. METHODS: A search was conducted through Medline, PubMed, Embase and Current Contents Connect to 2 August 2012. We calculated pooled odds ratios and 95% CIs using a random effects model for the risk of oesophageal cancer associated with exposure to bisphosphonates, as well as for the different periods of exposure. RESULTS: Seven studies, with 19 700 oesophageal cancer cases, met our inclusion criteria. We found a positive relationship between exposure to bisphosphonates and oesophageal cancer, with an odds ratio (OR) of 1.74 with a 95% CI of 1.19-2.55. Heterogeneity was observed (I(2 ) = 85%, P < 0.001). Publication bias was not present. An increased risk of oesophageal cancer was also found in the group exposed to bisphosphonates for a longer period of time, compared with the group who experienced a shorter period of exposure (OR 2.32; 95% CI 1.57-3.43 vs. OR 1.35; 95% CI 0.77-2.39). An increased risk was associated with exposure to Etidronate (OR 1.58; 95% CI 1.12-2.24), but not to Aledronate. CONCLUSIONS: Exposure to bisphosphonates may be associated with an increased risk of oesophageal cancer. More studies are needed to confirm the relationship.

Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy.

BACKGROUND: Coeliac disease has been associated with an increased risk of mortality and malignancy. However, the strength of this association is conflicting among different studies. AIM: To perform a systematic review and quantitative meta-analysis to determine the risk of all-cause mortality, any malignancy and lymphoid malignancy in coeliac disease patients. METHODS: Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 4 January 2012, with no language restrictions. From 8698 citations identified, a total of 17 studies met our inclusion criteria. RESULTS: The all-cause mortality meta-analysis showed an increased risk for all-cause mortality in coeliac patients [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.19-1.30]. A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of all-cause mortality (OR 1.16; 95% CI 1.02-1.31). The non-Hodgkin lymphoma (NHL) meta-analysis showed an increased risk for NHL in coeliac patients (OR 2.61; 95% CI 2.04-3.33). A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of NHL (OR 2.55; 95% CI 1.02-6.36). The T-cell non-Hodgkin lymphoma (TNHL) meta-analysis showed an increased risk of TNHL (OR 15.84; 95% CI 7.85-31.94). The any malignancy meta-analysis showed no increased risk (OR 1.07; 95% CI 0.89-1.29). CONCLUSIONS: Patients with coeliac disease are at an increased risk of mortality and non-Hodgkin lymphoma, particularly T-cell non-Hodgkin lymphoma; they do not have an increased risk of any malignancy overall. Serologically defined patients with coeliac disease have an elevated risk of mortality and non-Hodgkin lymphoma.