S Dattagupta

Potential of magnetic resonance spectroscopic imaging in predicting absence of prostate cancer in men with serum prostate-specific antigen between 4 and 10 ng/ml: a follow-up study.

OBJECTIVES Screening for prostate cancer using serum prostate-specific antigen (PSA) determination has a positive predictive value of only 30% to 42% for a PSA level between 4 and 10 ng/mL. Magnetic resonance spectroscopic imaging (MRSI), which identifies cancer on the basis of changes in cellular metabolite levels, might be able to identify patients with noncancerous PSA elevation and help avoid unnecessary biopsies. We tested this hypothesis by evaluating the incidence of prostate cancer in men with a PSA level of 4 to 10 ng/mL and a negative MRSI study. METHODS A total of 155 men underwent a three-dimensional proton MRSI of the prostate before transrectal ultrasound-guided biopsy for clinical indications. MRSI was performed using an endorectal coil on a 1.5-T magnetic resonance scanner. Patients with no voxels positive for malignancy underwent standard sextant biopsy, and additional MRSI-targeted biopsies were obtained in men with suspicious or malignant voxels. Patients with a biopsy negative for cancer underwent repeat serum PSA estimation every 6 months for a minimum of 18 months. RESULTS Of the 155 men, 36 (mean PSA level of 6.47 ng/mL, range 4.25 to 9.9) had no malignant voxels on MRSI. None of them were positive for cancer on biopsy. Of these 36 men, 26 completed at least 18 months (mean 26.9, range 18 to 44) of follow-up. Four patients required repeat biopsies and one, with a persistently elevated PSA level was diagnosed with prostate cancer 29 months after the initial MRSI. CONCLUSIONS The results of our study have shown that prostate biopsy can be deferred in patients with an increased serum PSA of 4 to 10 ng/mL if their MRSI does not show any malignant voxels.

Therapeutic use of stem cells in congenital anomalies: A pilot study

Introduction: Stem cells with potential to transform into healthy cells and repair damaged cells may prove beneficial in various congenital malformations. Aim: To explore the use of stem cells in liver cirrhosis and meningomyelocele. Materials and Methods: During July 2005 to July 2006, stem cells were used in 27 patients; 12 with liver cirrhosis and 15 with meningomyelocele. Autologous stem cells were injected during definite surgery into hepatic artery and portal vein or hepatobiliary radicles for liver cirrhosis or spinal cord and caudal space for meningomyelocele. The pre-operative status of the patient served as control for that patient. Results: The patients with liver cirrhosis were between 1.5 and 9 months (mean 4.12 months). Liver cirrhosis was due to extra hepatic biliary atresia (EHBA); neonatal hepatitis and choledochal cyst in 8; 2 and 2 patients, respectively. About five patients expired due to late presentation and ongoing cirrhosis. Follow up results evaluated at 3-12 months (n=7) showed absence of cholangitis (4/7); yellow stools (5/7); decreased liver firmness (3/7); improved liver functions (6/7) and improved appetite (6/7). Hepatobiliary scan was excretory in 6/7 with improved uptake in 4/7. Histopathology repeated after stem cells demonstrated comparative improvement in fibrosis in three. The meningomyelocele patients were between 0 and 1 month; 1-5 months, and 1-4 years in 5; 8 and 2 cases, respectively. 5 had history of rupture. 3 had undergone meningocele repair in past with neurological deficits. Redo surgery for tethered cord was done in 1. Follow up (3-11 months) in 14 cases showed improved power in 4 (28%), dramatic recovery in 3 (22%), and status quo in 7 (50%). One patient is still under observation. Conclusion: Initial use of stem cells in EHBA and meningomyelocele has shown beneficial results. However, long-term evaluation with randomized-controlled trials is essential to draw further conclusions.

Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer.

Background/Aims Recent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance. Methods Between March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated. Results Twenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia. Conclusions Random biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease

Background As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. Methods A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. Results A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. Conclusions Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Evaluation of Xpert MTB/RIF assay performance in the diagnosis of abdominal tuberculosis

Background/Aims The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population. Methods Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohns disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay. Results Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively. Conclusions The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population.

CD4 + CD25 + FOXP3 + T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn’s disease

Background Distinguishing between Crohn’s Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker. Methods The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients. Results Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%. Conclusion Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.