Pathogenesis of tropical sprue A pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake.

Background & objectives: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). Methods: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). Results: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m2) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. Interpretation & conclusions: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS.

Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption.

Background & objectives: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. Methods: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. Results: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm3, P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. Interpretation & conclusions: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD.

Chronic diarrhea and malabsorption due to hypogammaglobulinemia: a report on twelve patients.

Hypogammaglobulinemic sprue (HGS), which may predispose to infection, is uncommon. Twelve patients (all men; median age 29 years, 15–50) with HGS (4%) of 296 with chronic small bowel diarrhea and malabsorption syndrome (MAS) during a 10-year period were analyzed. Treatment of HGS was delayed due to misdiagnosis as intestinal tuberculosis (n=7) and diarrhea-predominant irritable bowel syndrome (n=1). All had diarrhea and weight loss (median loss 12 Kg). Associated conditions were clubbing, bronchiectasis, and seizure (2 patients each), and hypothyroidism (n=1). Laboratory parameters were urinary D-xylose median 0.46 g/5 g/5 h (range 0.2–1.6; normal ≥1), fecal fat 11.9 g/day (3.8–16.7; normal ≤7 g), serum IgA, IgG, and IgM: 23.5 mg/dL (17–114; normal 90–450), 584 mg/dL (145–1051; normal 800–1800), and 23 (0–40.3; normal 60–280). IgA, IgG, and IgM were low in 10, 10, and 11, respectively. Duodenal biopsy was normal in 6 patients and showed partial villous atrophy in 6 and nodular lymphoid hyperplasia in two. Associated infections were giardiasis (n=1), disseminated strongyloidiasis (1), small intestinal bacterial overgrowth (3), septicemia (2), and septic arthritis (1). Two patients died of sepsis, five are well on immunoglobulin and specific antiinfective treatment, and five are lost to follow up. Approximately 4% patients with MAS have hypogammaglobulinemia, which is often associated with infection and is diagnosed late.

Patients with Helicobacter pylori infection have less severe gastroesophageal reflux disease: a study using endoscopy, 24-hour gastric and esophageal pH metry.

Background and aim The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion. Methods Patients with GERD (n=123), who were not on acid-suppressive drugs, and had not received anti-H. pylori therapy, underwent gastroduodenoscopy and tests for H. pylori detection. Esophageal manometry, 24-h pH metry, serum pepsinogen-I (PG-I), PG-II and gastrin-17 ELISA were done in all these patients. Univariate and multivariate analyses were performed to assess independent predictors for erosive esophagitis (EE). Results Of 123 patients (mean age 40.5 [13.1] years, 85 [69.1%] men), 59 (47.9%) had H. pylori infection. EE was more common in H. pylori non-infected than infected (49 vs. 32, p<0.001). Among patients older than 40 years, absence of H. pylori was associated with lower esophageal pH and longer reflux (p=0.02 and p<0.001, respectively). PG-I/PG-II ratio was lower in H. pylori infected subjects (p <0.001). In patients with higher LA grade of esophagitis, elevated PG-I levels and PG-I/PG-II ratio were associated with more acidic stomach (p=0.04 and p=0.01, respectively). Multivariate analyses showed low gastrin-17 (p=0.016), higher age (p=0.013), hiatus hernia (p=0.004) and absence of H. pylori (p=0.03) were independent predictors for risk of EE. Conclusion H. pylori infection is associated with less acidic stomach and less severe GERD. Low gastrin-17, higher age, hiatus hernia and absence of H. pylori were the best predictors for EE risk.

Manometric and symptomatic spectrum of motor dysphagia in a tertiary referral center in northern India.

Background We studied the spectrum of motor dysphagia in a northern Indian tertiary referral center. Methods In this retrospective study, consecutive patients with motor dysphagia referred to the Gastrointestinal Pathophysiology and Motility Laboratory from 2002 to 2007 were evaluated clinically and with eight-channel water-perfusion manometry. Causes of dysphagia were diagnosed using standard criteria. Results Of 250 patients (age 41.3 [15.0] years, 146 men), 193 (77%) had achalasia cardia (AC) and 57 (23%) had other causes (11, 4.4%: diffuse esophageal spasm [DES]; 9, 3.6%: hypertensive lower esophageal sphincter [Hy LES]); manometry was normal in 37 patients. Twenty-seven patients (14%) had vigorous AC. Duration of dysphagia at presentation was longer in those with AC and Hy LES than in normal manometry (NM) (21 months [1–180] vs. 6 [1–360], p = 0.000; 24 months [7–48] vs. 6 [1–360], p = 0.015). Regurgitation and bolus obstruction were more frequent in those with AC than in NM (89/154, 57.79% vs. 3/27, 11.11%, p = 0.000001). Heartburn was less frequent in patients with AC than in others (AC: 4/146, 2.73% vs. normal: 4/27, 14.8% [p = 0.02] and others: 3/15, 20% [p = 0.018]). Chest pain was reported by 74/135 (54.8%) classic and 12/19 (63.2%) vigorous AC (p = NS). Patients with NM had lower LES pressure than those with classic AC, Hy LES and vigorous AC (p < 0.0001 in each case). Patients with DES had lower LES pressure than in classic AC, Hy LES and vigorous AC (p = 0.043, p < 0.0001, and p = 0.002, respectively). Patients with classic AC had lower LES pressure than in Hy LES and vigorous AC (p = 0.024, p = 0.001, respectively). Conclusion Classic AC was the commonest cause of motor dysphagia in our center. AC was associated with higher LES pressure, longer duration of dysphagia, frequent regurgitation and bolus obstruction.

Manometric spectrum of fecal incontinence in a tertiary care center in northern India.

Background: Since, there is scanty data on manometric spectrum of fecal incontinence (FI) from India, ano-rectal manometry (ARM) parameters of patients with FI attending a tertiary care hospital were analyzed retrospectively. Methods: Data on 140 consecutive patients with FI (age 44.8 + 17.4 y, 89 male) referred for ARM were analyzed and interpreted according to standard criteria. Results: Low resting pressure (mainly due to internal sphincter; <40mmHg) and squeeze pressure (mainly due to external sphincter; <60 mmHg) were found in 88/140 (63%) and 44/140 (31.4%) patients, respectively. Low squeeze pressure indicating external sphincter defect was more commonly found in female than male [23/51 (45.1%) vs. 21/89 (23.6%), p=0.013] though other parameters on ARM were comparable among the two genders. Conclusion: Parameters of ano-rectal functions were abnormal in varying combinations on ARM in a large proportion of patients with FI attending a tertiary care center and females more often had low squeeze pressure indicating external sphincter defect than males though anal resting pressure, length of the high pressure zone and tolerability to intra-rectal balloon distension were comparable.

Esophageal function tests in clinical practice: A review.

Diseases of esophagus are common in gastroenterology practice. Improvement in diagnosis and better understanding in pathophysiology of these diseases have been possible recently due to advancement in technology. Advancement made in the field of computer softwares is another key development aiding further improvement in these instruments. In this article, we review techniques, interpretation and clinical utility of various tests of esophageal function with special reference to manometry, ambulatory pH and impedance monitoring. Esophageal manometry is simple to perform. Recent, availability of commercial user-friendly software has made analysis of recorded data easy. High resolution spatio-temporal manometry is advancement over conventional manometry. Manometry is a useful tool for diagnosis, followup and research in esophageal motility disorders. Ambulatory 24-h pH metry and impedance monitoring are also easily analyzed by commercially available software. 24-h impedance combined with pH-metry is currently considered as the gold standard for diagnosis of gastroesophageal reflux disease (GERD). All patients with GERD may not require these investigations, but those with atypical symptoms, those refractory to medical treatment and requiring surgery do. Esophageal transit study is useful in understanding functional correlates of abnormalities in manometry and is particularly useful during follow up studies and in research.

Lactose hydrogen breath test versus lactose tolerance test in the tropics: Does positive lactose tolerance test reflect more severe lactose malabsorption.

Background: We compared the lactose hydrogen breath (lactose HBT) and lactose tolerance tests (LTT) in their ability to diagnose lactose malabsorption (LM). Methods: Fasting and post-lactose (50 g) breath hydrogen and blood sugar were tested in patients with irritable bowel syndrome (IBS). Persistent rise in breath hydrogen by 20 ppm and failure of blood sugar to rise by >20 mg/dL above basal level, were considered positive lactose HBT and LTT, respectively. Symptoms of diarrhoea, bloating, abdominal pain and flatulence were noted. Results: Of 203 patients, 11 demonstrated high basal breath hydrogen and hence, 192 (age 37±14 years, 134 male) were included in the study. 125 (65%) and 137 (71%) were lactose HBT and LTT positive, respectively. 102/125 lactose HBT positive patients were LTT positive and 35/67 lactose HBT negative patients were LTT positive. 62/192 (32%) developed symptoms following lactose ingestion, which tended to be more in the LTT positive (49/137, 36% vs. 13/55, 24% p=0.07) but not in the lactose HBT positive patients (44/125, 35% vs. 18/ 67, 27% p=0.2). Peak breath hydrogen was higher (38±37 vs. 66±43; p<0.01) in LTT positive than negative patients. Peak level of breath hydrogen inversely correlated (58±43 vs. 10±23; p<0.001) with change in blood glucose following lactose ingestion. Conclusions: Positive LTT is associated with a higher breath hydrogen score than negative LTT. There was a trend towards more frequent symptom development following lactose load in LTT positive but not in lactose HBT positive patients. LTT is an easy and efficient test for diagnosis of LM.

Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump inhibitor therapy.

We report the case of a patient with gastroesophageal reflux disease who developed gastric atrophy and intestinal metaplasia (IM) while on 20-year treatment with proton pump inhibitors. This is perhaps the first report in human beings. A 74-year-old man, who presented with heartburn, showed abnormally high gastric pH (average 6.57) on 24-hour dual channel pH-metry even after discontinuing acid suppressive drugs for one month. No significant esophageal acid exposure was noted, which may be related to an impairment of the acid secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h period 0.3%). Upper gastrointestinal endoscopy was normal except for the prominent submucosal vessels in the body and fundus suggesting gastric atrophy. Histopathological examination of multiple biopsies from the body and antrum of stomach showed signs of gastric atrophy and IM. Rapid urease test and histopathology of gastric biopsies were negative for Helicobacter pylori. Anti-H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti-secretory drugs and only prokinetics were prescribed following which his symptoms markedly improved. On follow-up, in April 2007, he developed symptoms of peripheral neuropathy; serum vitamin 812 level was low. He responded to parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and a half years showed persistently high gastric pH (average pH 6.76). The patient remained well after discontinuing proton pump inhibitors and continuing prokinetics and vitamin B12 injections.

Antroduodenal manometry: experience from a tertiary care center.

BACKGROUND: Though antroduodenal manometry (ADM) is an important research tool, experience on its clinical utility is scanty. METHODS: All ADM performed as a clinical service, using an 8-channel water perfusion system were retrospectively analyzed. Impact on clinical management was classified as: (1) new diagnosis made, (2) change in management (new drug, decision regarding surgical treatment), (3) further special investigation done, (4) referral to another specialty. RESULTS: ADM was successful in 32/33 (97%) patients (age 30 years [range 8-71]); 6 patients were < 12 years old. Clinical impression before ADM was: chronic intestinal pseudo-obstruction (CIPO) in 16 (50%), suspected gastroparesis in 11 (34.3%), dyspepsia in 5 (15.6%). Consequent to ADM in patients with CIPO, a new diagnosis was made in two (intestinal neuronal dysplasia and celiac disease), new drugs were started in five, surgery was performed in three and specific referral was sought in three. ADM confirmed gastroparesis in 9 of 11 patients. A new diagnosis was made in three patients, new drugs were started in three, and three were referred. In five dyspeptic patients, ADM was normal and no therapy was suggested. Overall, eleven patients with CIPO and four with gastroparesis benefited after ADM. CONCLUSION: ADM was found useful in CIPO and gastroparesis, helped in decision making regarding surgery; however in nonspecific indications its utility was limited.

Colonic transit study by radio-opaque markers to investigate constipation: validation of a new protocol for a population with rapid gut transit.

BACKGROUND: Constipation is a common problem, which may be due to slow transit or faecal evacuation disorders. Though the screening test of colonic transit study using radio-opaque markers given at 0, 24 and 48 hours followed by abdominal X-ray at 72 hours is a good protocol in the West, it is not suitable for Indians who have a rapid gut transit. METHODS: Nine patients with adult Hirschsprung disease, 11 with chronic intestinal pseudo-obstruction diagnosed using standard investigations and 11 healthy subjects were evaluated by colonic transit study using radio-opaque markers (SGmark), 20 each at O, 12 and 24 hours followed by an abdominal X-ray at 36 and 60 hours. The cut-off was determined by using receiver operating characteristic (ROC) curves, and sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were determined. RESULTS: The total number of markers retained in the abdomen and those in the right segment at 36 hours in patients with Hirschsprung disease and chronic intestinal pseudo-obstruction was higher than that in healthy subjects though the number in the left and rectosigmoid segments were comparable. The abdominal X-ray at 60 hours, total number of markers and number in all segments were higher in patients with Hirschsprung disease and chronic intestinal pseudoobstruction than in healthy subjects. The best cut-off by ROC curves at 36 and 60 hours was 30 and 14 markers, respectively. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy and area under the ROC curve at 36 hours were 90%, 82%, 90%, 82%, 87% and 0.9, respectively; the corresponding values at 60 hours were 95%, 100%, 100%, 92%, 97% and 0.99, respectively. CONCLUSION: Using the proposed protocol, the colonic transit study is able to distinguish patients with specific motility disorders causing constipation such as Hirschsprung disease and chronic intestinal pseudo-obstruction from healthy subjects with reasonable sensitivity and specificity, and shows that an abdominal X-ray at 60 hours is better than one at 36 hours.

Malabsorption syndrome due to various causes is associated with antroduodenal hypomotility.

BACKGROUND: Patients with celiac disease who present with symptoms of gastrointestinal hypomotility have abnormal antroduodenal manometry. There are no data on antroduodenal manometry in malabsorption syndrome (MAS) due to causes other than celiac disease. METHODS: Fasting, post-prandial and post-octreotide antroduodenal motility parameters were compared in 18 untreated patients with MAS presenting with chronic diarrhea (tropical sprue 10, small bowel bacterial overgrowth 3, celiac disease 2, common variable immunodeficiency 1, AIDS with isosporidiasis and bacterial overgrowth 1, giardiasis 1) and 8 healthy subjects. RESULTS: Number of patients with MAS and controls having spontaneous migratory motor complexes (MMC) during fasting was comparable (11/18 vs 7/8; p=ns). Fasting contraction amplitude was weaker in MAS than in controls in the gastric antrum (median 42 [range 17-90] vs 80 [31-120] mmHg; p=0.001), proximal duodenum (50 [18-125] vs 72 [48-107]; p=0.013) and distal duodenum (45 [20-81] vs 76 [51-98]; p=0.001). In the fed state too, contraction amplitudes were weaker in patients with MAS in the antrum (32 [15-110] vs 76 [61-103] mmHg, p=0.002), proximal duodenum (57 [20-177] vs 73 [56-113]; p=0.07) and distal duodenum (45 [24-87] vs 75 [66-97]; p<0.0001). Patients with MAS had lower fasting and post-prandial antral and duodenal motility indices than healthy subjects. Intravenous octreotide induced MMC in all patients and controls. CONCLUSIONS: MAS due to various causes is associated with antroduodenal hypomotility typical of myopathic disorders.

Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO), which may result from intestinal stasis, is common in malabsorption syndrome (MAS). Quantitative culture of upper gut aspirate is used as a gold standard for the diagnosis of SIBO. Studies on diagnosis of SIBO using non-invasive hydrogen breath tests are contradictory. METHODS: 83 patients (age 35 [14-70] y; 50 men) with MAS due to various causes were investigated for SIBO using quantitative culture of upper gut aspirate obtained using a special endoscopic catheter and glucose and lactulose hydrogen breath tests (GHBT, LHBT). Sustained elevation in breath hydrogen of 12 ppm above basal and two separate peaks (one due to SIBO and the other from colon) were diagnostic of SIBO in GHBT and LHBT, respectively. Oro-cecal transit time (OCTT) was estimated using LHBT in 71 patients. RESULTS: Thirty two of 81 (39.5%) patients with MAS had SIBO on culture (>or= 10(5) CFU/mL). Using aspirate culture as the gold standard, sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of GHBT to diagnose SIBO were 44%, 80%, 62%, 67% and 65%, respectively; the corresponding values for LHBT were 31%, 86%, 62%, 54% and 55%, respectively. OCTT in patients with SIBO diagnosed on GHBT and/or aspirate culture (n=58) was longer than in those without (170 [60-250] vs. 120 [50-290] min, p=0.02); of others, 7 were hydrogen non-producers and in 6 OCTT could not be assessed due to sustained early peak because of SIBO. CONCLUSIONS: GHBT and LHBT are highly specific but insensitive for diagnosis of SIBO in MAS; OCTT is longer in patients with MAS and SIBO than in those without.

Cholangiocarcinoma presenting with severe gastroparesis and pseudoachalasia.

Tumor-associated gastroparesis, though reported in association with various malignancies, is rare in patients with cholangiocarcinoma. We report a 55-year-old woman who presented with dysphagia and recurrent vomiting. Esophagogastroduodenoscopy revealed dilated stomach and excess residue without organic obstruction. 99mTc sulfur colloid solid gastric emptying study, radio-opaque marker gut transit study, and esophageal manometry showed features suggestive of gastroparesis and achalasia cardia; electrogastrography revealed bradygastria. Cholangiocarcinoma was detected on CT scan performed after the patient developed jaundice two months later. The lesion was deemed surgically unresectable. She died four months later.

Etiological spectrum of sporadic malabsorption syndrome in northern Indian adults at a tertiary hospital.

BACKGROUND: The etiology of malabsorption syndrome (MAS) may differ in different geographical regions. Limited data are available on the etiological spectrum of MAS among Indian adults. METHODS: Ninety-nine consecutive adult patients with MAS (urine d-xylose <1 g/5 g/5 h with or without increased fecal fat (> or =7 g/24 h) were evaluated for cause of MAS using standard criteria. Past medical records were examined to know the nature of treatment received. RESULTS: The etiology of MAS was: tropical sprue 39, celiac disease 9, Crohn's disease 9, giardiasis 8, small intestinal bacterial overgrowth in absence of another cause of MAS 8, panhypogammaglobulinemia 2 (one with strongyloidiasis), intestinal lymphangiectasia 1, intestinal tuberculosis 4, idiopathic 15, acquired immunodeficiency syndrome 2, and amyloidosis 2. Twenty-eight patients had received anti-tubercular treatment earlier. CONCLUSIONS: Tropical sprue, celiac disease and Crohn's disease are common causes of MAS in Indian adults. Inappropriate anti-tubercular treatment is common in them and needs to be discouraged.