Route to diagnosis of colorectal cancer and association with survival within the context of a bowel screening programme.

OBJECTIVES: Bowel cancer screening has been introduced to improve colorectal cancer outcomes; however, a significant proportion of cases continue to present with TNM Stage III-IV disease and/or emergently. This study analyses the prior interaction with screening of patients diagnosed with colorectal cancer and factors associated with non-screening diagnosis. STUDY DESIGN: This was a retrospective observational study. METHODS: All patients diagnosed with colorectal cancer in the West of Scotland from 2011 to 2014 were identified. Through data linkage to the Scottish Bowel Cancer Screening Programme, we analysed patient interaction with screening within 2 years before cancer diagnosis. RESULTS: In total, 6549 patients were diagnosed with colorectal cancer, 1217 (19%) via screening. Screening participation was associated with earlier TNM stage, reduced emergency presentations and improved 3-year survival (all P < 0.001). Failure to diagnose through screening was predominantly due to non-invitation (37%), non-return of screening test (29%) or negative test (13%). Three hundred fifty-one patients were below screening age, 79% of whom were aged 40-49 years and 2035 patients were above screening age. Factors associated with non-return of screening test included age, sex, SIMD (all P < 0.001) and raised Charlson score (P = 0.030). Factors associated with negative screening result included sex, anaemia, differentiation, right-sided tumours and venous invasion (P < 0.001). CONCLUSION: Within Scotland, <20% of colorectal cancer is diagnosed through screening despite the existence of a population screening programme. Measures must be taken to improve screening participation including encouragement of those of routine screening age and those age ≥75 years in good health to participate in screening with consideration given to extending screening to under 50s. A significant false-negative rate of testing was observed in the present study and this requires further investigation within a population undergoing screening through faecal immunochemical testing.

An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS).

OBJECTIVES: Colorectal polyp cancers present clinicians with a treatment dilemma. Decisions regarding whether to offer segmental resection or endoscopic surveillance are often taken without reference to good quality evidence. The aim of this study was to develop a treatment algorithm for patients with screen-detected polyp cancers. DESIGN: This national cohort study included all patients with a polyp cancer identified through the Scottish Bowel Screening Programme between 2000 and 2012. Multivariate regression analysis was used to assess the impact of clinical, endoscopic and pathological variables on the rate of adverse events (residual tumour in patients undergoing segmental resection or cancer-related death or disease recurrence in any patient). These data were used to develop a clinically relevant treatment algorithm. RESULTS: 485 patients with polyp cancers were included. 186/485 (38%) underwent segmental resection and residual tumour was identified in 41/186 (22%). The only factor associated with an increased risk of residual tumour in the bowel wall was incomplete excision of the original polyp (OR 5.61, p=0.001), while only lymphovascular invasion was associated with an increased risk of lymph node metastases (OR 5.95, p=0.002). When patients undergoing segmental resection or endoscopic surveillance were considered together, the risk of adverse events was significantly higher in patients with incomplete excision (OR 10.23, p<0.001) or lymphovascular invasion (OR 2.65, p=0.023). CONCLUSION: A policy of surveillance is adequate for the majority of patients with screen-detected colorectal polyp cancers. Consideration of segmental resection should be reserved for those with incomplete excision or evidence of lymphovascular invasion.

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients

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A comparison of tumour and host prognostic factors in screen-detected vs nonscreen-detected colorectal cancer: a contemporaneous study.

AIM: In addition to TNM stage there are adverse tumour and host factors, such as venous invasion and the presence of an elevated systemic inflammatory response (SIR), that influence the outcome in colorectal cancer. The present study aimed to examine how these factors varied in screen-detected (SD) and nonscreen-detected (NSD) tumours. METHOD: Prospectively maintained databases of the prevalence round of a biennial population faecal occult blood test screening programme and a regional cancer audit database were analysed. Interval cancers (INT) were defined as cancers identified within 2 years of a negative screening test. RESULTS: Of the 395 097 people invited, 204 535 (52%) responded, 6159 (3%) tested positive and 421 (9%) had cancer detected. A further 708 NSD patients were identified [468 (65%) nonresponders, 182 (25%) INT cancers and 58 (10%) who did not attend or did not have cancer diagnosed at colonoscopy]. Comparing SD and NSD patients, SD patients were more likely to be male, and have a tumour with a lower TNM stage (both P < 0.05). On stage-by-stage analysis, SD patients had less evidence of an elevated SIR (P < 0.05). Both the presence of venous invasion (P = 0.761) and an elevated SIR (P = 0.059) were similar in those with INT cancers and in those that arose in nonresponders. CONCLUSION: Independent of TNM stage, SD tumours have more favourable host prognostic factors than NSD tumours. There is no evidence that INT cancers are biologically more aggressive than those that develop in the rest of the population and are hence likely to be due to limitations of screening in its current format.

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland.

BACKGROUND: Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. METHODS: Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. RESULTS: In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P⩽0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P⩽0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P⩽0.001). CONCLUSIONS: Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer.

Flexible sigmoidoscopy following a positive faecal occult blood test within a bowel screening programme may reduce the detection of neoplasia.

AIM: Colorectal cancer screening using the faecal occult blood test (FOBt) detects a disproportionate number of left-sided tumours. This study aims to examine the theoretical impact on neoplasia detection rates of a sigmoidoscopy-first protocol in FOBt-positive patients undergoing colonoscopy. METHOD: From retrieved endoscopy/pathology reports, pathology up to and including the splenic flexure was assumed detectable by sigmoidoscopy. High-risk polyps prompting subsequent colonoscopy were classed as three or more polyps, one polyp of ≥ 1 cm, villous or tubulovillous components or the presence of high-grade dysplasia. RESULTS: Between April 2009 and April 2011, 4631 patients underwent colonoscopy as a result of a positive FOBt in Greater Glasgow and Clyde. Cancer was detected in 398 (9%) and adenomas were detected in 1985 (47%) of which 1323 (67%) were deemed significant according to British Society of Gastroenterology guidelines. Applying the flexible sigmoidoscopy-first model, cancer would have been detected in 329 (8%) patients and adenomas in 1640 (39%), of which 1140 (70%) would have been significant. In total, 1546 (37%) patients would have required subsequent colonoscopy, following which 21 patients would have a new diagnosis of cancer. The positive predictive values (PPVs) for neoplasia (47 vs 57%, P < 0.001), significant neoplasia (35 vs 41%, P < 0.001) and cancer (8 vs 9%, P = 0.007) were all lower in the sigmoidoscopy-first model. CONCLUSION: A significant reduction in the detection of both adenomas and cancers would be seen if the sigmoidoscopy-first protocol were to be used following a positive FOBt. Furthermore, a significant proportion of patients would be subjected to two procedures, with considerable implications for both the patient and cost.

The impact of aspirin, statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme.

BACKGROUND: There is increasing evidence that aspirin, statins and ACE-inhibitors can reduce the incidence of colorectal cancer. The aim of the present study was to assess the impact of these medications on an individual's risk of advanced neoplasia in a colorectal cancer screening programme. METHODS: A prospectively maintained database of the first round of screening in our geographical area was analysed. The outcome measure was advanced neoplasia (cancer or intermediate or high risk adenomata). RESULTS: Of the 4188 individuals who underwent colonoscopy following a positive occult blood stool test, colorectal pathology was present in 3043(73%). Of the 3043 patients with colorectal pathology, 1704(56%) had advanced neoplasia. Patients with advanced neoplasia were more likely to be older (OR 1.38; 95% CI 1.19-1.59) and male (OR 1.66; 95% CI 1.43-1.94) (both P<0.001). In contrast, those on aspirin (OR 0.68; 95% CI 0.56-0.83), statins (OR 0.65; 95% CI 0.55-0.78) or ACE inhibitors (OR 0.71; 95% CI 0.57-0.89) were less likely to have advanced neoplasia at colonoscopy (all P<0.05). CONCLUSION: In patients undergoing colonoscopy following a positive occult blood stool test with documented evidence of aspirin, statin or ACE-inhibitor usage, advanced neoplasia is less likely, suggesting that the usage of these medications may have a chemopreventative effect.

Treatment outcome, mortality and their predictors among HIV-associated tuberculosis patients.

The risk of death is significantly higher in HIV-infected patients with tuberculosis (TB). This study aims to evaluate the impact of demographic, clinical and laboratory characteristics on the treatment outcome and mortality of TB/HIV co-infected patients in a tertiary TB centre in Iran. In total, 111 patients were recruited from 2004 to 2007. Mycobacteriological studies and demographic, clinical, and laboratory data from all patients were analysed and predictors of unsuccessful outcomes as well as mortality were determined. The mean age for all 111 TB-HIV patients was 38 ± 9 years (range 22-70) and 107 (96.3%) were men; 104 (93.7%) had a history of drug abuse and 96 (86.4%) had a history of imprisonment. The method of HIV transmission was intravenous drug use in 88 (79.3%). Twenty-three (20.7%) had a history of Category 1 (CAT I) TB treatment and six (5.4%) Category 2 (CAT II) treatment. Combination antiretroviral therapy (cART) was given to 48 (43.2%). No significant associations were found between treatment outcomes or mortality and gender, smoking, drug and alcohol abuse, imprisonment, method of transmission, history of CAT I and CAT II treatments, CD4 counts or adverse effects (P > 0.05). Administration of cART led to significantly better outcomes (P < 0.001). Lower serum albumin levels and low body weight were significantly associated with mortality.

Drug resistance pattern and outcome of treatment in recurrent episodes of tuberculosis.

Patterns of drug resistance in recurrent cases of tuberculosis may be different than in those without a history of treatment. In this retrospective study, the drug resistance pattern and outcome of treatment with DOTS category I (CAT I) regimen was compared in 63 recurrent cases and 872 new cases of pulmonary tuberculosis from April 2003 to January 2008 at the National Research Institute of Tuberculosis and Lung Disease in Tehran, Islamic Republic of Iran. Resistance to isoniazid and ethambutol was significantly more common in recurrent cases, but there were no differences in rates of resistance to rifampin, pyrazinamide, streptomycin or the rate of multi-drug resistant strains. Resistance to streptomycin was the most common. No significant differences in treatment outcome and deaths were found between the 2 groups. Due to the low frequency of multi-drug resistance in the recurrent cases, a CAT I regimen may be suitable for empirical therapy before drug sensitivity results become available.

IL-2-inducible T-cell kinase deficiency with pulmonary manifestations due to disseminated Epstein-Barr virus infection.

IL-2-inducible T-cell kinase (ITK) deficiency is a rare inherited immunodeficiency disease characterized by homozygous mutations in the ITK gene and the inability to control Epstein-Barr virus (EBV) infection leading to EBV-associated lymphoproliferative disorders of B cell origin. Many aspects of its clinical presentation and immunologic phenotype are still unclear to clinicians. We report on a 14-year-old female patient with complaints of an 8-month history of cough and fever. Imaging studies revealed diffuse pulmonary nodules and mediastinal lymphadenopathy. Transbronchial lung biopsy showed nonmalignant polyclonal B cell proliferation. High titers of EBV DNA were detected by PCR analysis in bronchoalveolar lavage fluid, bone marrow, and blood. Genomic analysis revealed a homozygous single base pair deletion in exon 5 of the ITK gene (c.468delT) in this patient. Treatment with rituximab (anti-CD20 mab) resulted in complete clinical remission with resolution of pulmonary lesions and a negative EBV titer in serum. All patients with EBV-associated lymphoproliferative disorders should be analyzed for mutations in ITK.

Drug resistance pattern and outcome of treatment in recurrent episodes of tuberculosis

Patterns of drug resistance in recurrent cases of tuberculosis may be different than in those without a history of treatment. In this retrospective study, the drug resistance pattern and outcome of treatment with DOTS category I [CAT I] regimen was compared in 63 recurrent cases and 872 new cases of pulmonary tuberculosis from April 2003 to January 2008 at the National Research Institute of Tuberculosis and Lung Disease in Tehran, Islamic Republic of Iran. Resistance to isoniazid and ethambutol was significantly more common in recurrent cases, but there were no differences in rates of resistance to rifampin, pyrazinamide, streptomycin or the rate of multi-drug resistant strains. Resistance to streptomycin was the most common. No significant differences in treatment outcome and deaths were found between the 2 groups. Due to the low frequency of multi-drug resistance in the recurrent cases, a CAT I regimen may be suitable for empirical therapy before drug sensitivity results become available

Standardised second-line treatment of multidrug-resistant tuberculosis during pregnancy.

We describe the efficacy and outcome of standardised second-line anti-tuberculosis (TB) medications during pregnancy. Treatment outcomes of five pregnant women with documented multidrug-resistant TB (MDR-TB) referred to the National Research Institute of Tuberculosis and Lung Diseases from 2003 to 2009 were analysed in two categories, maternal and neonatal. Patients became pregnant during treatment for MDR-TB without any changes in their anti-tuberculosis regimen. None of them had any adverse effects during pregnancy and delivery. No adverse effects were observed in mothers or neonates. The treatment of MDR-TB during pregnancy with a standardised second-line regimen in this study population was safe, with an acceptable rate of treatment success.

Human infections due to Mycobacterium lentiflavum: first report in Iran.

Non-tuberculosis mycobacteria (NTM), as certain species of mycobacteria, can affect human in several ways. In the preceding years, the rate of NTM detection has risen in both immunocompromised and immunocompetent patients. On the other hand, several reports have debated the possibility of co-infection of both Mycobcateriu tuberculosis (MTB) and NTM in individuals that puts the role of NTM in disease manifestations under question. Moreover, it is now proven that some of the cases that are identified as anti-TB treatment failure or suspected for drug resistance are actually NTM.

First-line antituberculosis drug resistance prevalence and its pattern among HIV-infected patients in the national referral tuberculosis centre, Iran.

The objective of this study was to determine the drug resistance prevalence and its pattern among tuberculosis (TB)-HIV patients in Iran. In this retrospective study, all admitted TB/HIV patients presenting to our tertiary centre during 2005-2007 were considered. After confirmation for TB-HIV, first-line DST was performed for culture-positive patients. The drug resistance patterns and the treatment outcomes were analysed. Of the total 92 TB/HIV patients, 27 were culture negative, and DST were available in 65. Intravenous drug abuse was seen in 59 (90.8%). Thirty-seven (57%) were 'sensitive' cases and 28 (43%) were 'any drug resistance' cases. Twenty-one (32.3%) were mono-drug, three (4.6%) poly-drug and four (6.1%) were multidrug-resistant TB patients. Previous anti-TB medication was significantly associated with any drug resistance (P = 0.041; 95% confidence interval =0.086-0.984); however, having any drug resistance did not affect the treatment outcome (P = 0.56). Streptomycin showed the highest resistance rate (27%) followed by isoniazid (20%), pyrazinamide (9.8%), rifampin (9.2%) and ethambutol (3%). Drug resistance to antitubercular agents in TB-HIV co-infected patients in Iran is high compared with other reports. Drug resistance is higher among those who have had prior anti-TB medication.

Drug abuse profile - patient delay, diagnosis delay and drug resistance pattern - among addict patients with tuberculosis.

Socioeconomic problems limit the access of drug users to health-care services. This descriptive cross-sectional study was carried out by making use of the medical records of new case tuberculosis (TB) patients hospitalized at Masih Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006. Demographic and personal characteristics of the patients and type of disease were collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men with just three women drug users. The mean age of the drug users group was 43.04 +/- 13.81 years. The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and all three, opium, heroin and crack, in two (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000) against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug susceptibility tests were performed for 515 patients with positive cultures. One hundred and thirty-three (14.1%) were found to have 'any resistance' to anti-TB drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%) of the individuals who showed resistance to first-line agents were drug users. There was no significant relation between drug resistance and drug use (P = 0.4). In conclusion, it seems that active case finding for TB and HIV in addict cases must be contained in harm reduction packages. Moreover, the manifestations of the disease should be considered seriously regardless of attributing them to drug use.

Comparison of the effectiveness of 2 treatment regimens in patients with isoniazid-resistant tuberculosis.

We compared the effectiveness of 2 treatment regimens for isoniazid-resistant tuberculosis (TB) in 42 patients attending a TB referral centre in the Islamic Republic of Iran. The patients were divided into 2 treatment groups: 26 received the 6-month standard HRZE treatment and 16 received a modified treatment of RZE for 6 months. There were no significant differences in age or sex of the groups. With the standard method of treatment, 21 (80.8%) patients were cured, 4 (15.4%) resulted in treatment failure, and 1 (3.8%) died. In the modified treatment group, 16 (100%) patients were cured, These differences were not statistically significantly different (P = 0.194).

Comparison of the effectiveness of 2 treatment regimens in patients with isoniazid-resistant tuberculosis

We compared the effectiveness of 2 treatment regimens for isoniazid-resistant tuberculosis [TB] in 42 patients attending a TB referral centre in the Islamic Republic of Iran. The patients were divided into 2 treatment groups: 26 received the 6-month standard HRZE treatment and 16 received a modified treatment of RZE for 6 months. There were no significant differences in age or sex of the groups. With the standard method of treatment, 21 [80.8%] patients were cured, 4 [15.4%] resulted in treatment failure, and 1 [3.8%] died. In the modified treatment group, 16 [100%] patients were cured. These differences were not statistically significantly different [P = 0.194]