The novel form of amyloidosis derived from EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) preferentially affects the lower gastrointestinal tract of elderly femalesa.

AIMS: To characterise the clinicopathological features of amyloidosis due to EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), a newly described amyloid type. METHODS AND RESULTS: We identified cases by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry typing database for specimens with the universal amyloid signature proteins, abundant EFEMP1 spectra and absence of other specific amyloid precursor proteins. We also developed an immunohistochemical stain for EFEMP1 applicable to formalin-fixed tissue sections and performed electron microscopy in one case. We identified 33 specimens from 32 patients with EFEMP1 amyloid. Most patients were female (91%) with a mean age of 75 years, and most specimens (94%) were from the bowel. EFEMP1 amyloid was incidentally identified in specimens biopsied/resected for a variety of clinical indications. In bowel specimens, EFEMP1 amyloid involved blood vessels and interstitium of the lamina propria, submucosa and/or muscularis propria. Although the EFEMP1 deposits were weakly to moderately Congo red-positive with absent to weak birefringence, they were strongly positive for EFEMP1 by immunohistochemistry, had the characteristic fibrillar ultrastructure of amyloid and were readily identified by mass spectrometry. CONCLUSIONS: EFEMP1 amyloid is a recently described novel amyloid type that predominantly affects the bowel of elderly females. Because EFEMP1 amyloid is only weakly Congo red-positive, it may be overlooked without a high index of suspicion. However, its characteristic microanatomical distribution is highlighted by immunohistochemistry and its identity is readily confirmed by mass spectrometry. Based on its distinctive features, we propose that EFEMP1 amyloidosis be considered a new amyloid type.

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well-differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas.

AIMS: Special AT-rich sequence-binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well-differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms. METHODS AND RESULTS: Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0-3+), with an H-score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well-differentiated neoplasms (P < 0.0001). Expression in lower GI tract NETs (median H-score of 255) was stronger than in other positive tumours (median H-score of 7) (P < 0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H-score of 300), 33% of lung NECs (median H-score of 23), and 60% of extrapulmonary visceral NECs (median H-score of 110), with stronger expression in Merkel cell carcinoma (P < 0.001). At an H-score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma. CONCLUSIONS: SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.

A Pathology Review of the Lower Gastrointestinal Tract in Relation to Ulcerative Colitis in Rats and Cynomolgus Macaques Treated With Ammonium Perfluorooctanoate.

Among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (PFOA), the gastrointestinal tract has not been identified as a target organ for PFOA-related toxicity in laboratory animals where the corresponding serum PFOA concentrations typically approach several orders of magnitude higher than the general human population. These lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend was observed for ulcerative colitis, an idiopathic chronic inflammatory condition of the gut, in a Mid-Ohio River community whose drinking water contained higher levels of PFOA. This study was conducted to perform a histological reevaluation of large intestine sections in laboratory animals from 2 long-term toxicological studies: one was with Sprague Dawley rats that received ammonium PFOA in their diet for 2 years and the other one was with cynomolgus macaques that received daily capsules of ammonium PFOA for 6 months. In both studies, there was a lack of histological evidence of treatment-related inflammatory lesions that was suggestive of the occurrence of ulcerative colitis in these laboratory animals even under the most rigorous treatment schedules. These findings do not offer support for the biological plausibility of the epidemiological associations reported.

Diagnostic utility of immunochemical fecal occult blood tests to detect lower gastrointestinal lesions in patients with chronic kidney disease.

PURPOSE: The immunochemical fecal occult blood test (iFOBT) is a useful method to screen for lower gastrointestinal (GI) bleeding-related lesions. However, few studies have investigated the diagnostic utility of iFOBT in chronic kidney disease (CKD). METHODS: We included 691 patients with nondialysis-dependent CKD stages 2-5 or those receiving dialysis. Bleeding-related lower GI lesions were identified by colonoscopy, and the diagnostic utility of iFOBT was evaluated. RESULTS: Bleeding-related lower GI lesions were found in 9.2% of 491 patients with CKD stage 2, 17.8% of 107 patients with CKD stage 3/4, and 25.8% of 93 patients with CKD stage 5/dialysis (p < 0.001). Compared with CKD stage 2, CKD stage 5/dialysis was independently associated with a 2.80-fold risk for bleeding-related lesions (p = 0.019). The iFOBT was positive in 92 (13.3%) patients and the area under the receiver operating curve (AUC) for a bleeding-related lesion was 0.64 (p < 0.001). The sensitivity of iFOBT increased as the CKD stage worsened (20.0 vs 52.6 vs 58.3%; p = 0.002). However, the specificity to detect bleeding-related lesions decreased with the severity of CKD stage (94.6 vs. 78.4 vs. 76.8%; p < 0.001). The AUC of iFOBT to detect adenoma or carcinoma was 0.54 (p = 0.046), and a similar pattern of sensitivity and specificity was observed between different CKD stages. CONCLUSIONS: The prevalence of bleeding-related lower GI lesions and the sensitivity of iFOBT to detect these GI lesions increased in advanced CKD. However, iFOBT should be used cautiously in these patients because its specificity decreased.

A prospective phase 2 clinical trial of a C5a complement inhibitor for acute GVHD with lower GI tract involvement.

Involvement of lower gastrointestinal tract (LGI) occurs in 60% of patients with graft-versus-host-disease (GVHD). Complement components C3 and C5 are involved in GVHD pathogenesis. In this phase 2a study, we evaluated the safety and efficacy of ALXN1007, a monoclonal antibody against C5a, in patients with newly diagnosed LGI acute GVHD receiving concomitant corticosteroid. Twenty-five patients were enrolled; one was excluded from the efficacy analysis based upon negative biopsy. Most patients (16/25, 64%) had acute leukemia; 52% (13/25) had an HLA-matched unrelated donor; and 68% (17/25) received myeloablative conditioning. Half the patients (12/24) had a high biomarker profile, Ann Arbor score 3; 42% (10/24) had high-risk GVHD per Minnesota classification. Day-28 overall response was 58% (13/24 complete response, 1/24 partial response), and 63% by Day-56 (all complete responses). Day-28 overall response was 50% (5/10) in Minnesota high-risk and 42% (5/12) in high-risk Ann Arbor patients, increasing to 58% (7/12) by Day-56. Non-relapse mortality at 6-months was 24% (95% CI 11-53). The most common treatment-related adverse event was infection (6/25, 24%). Neither baseline complement levels (except for C5), activity, nor inhibition of C5a with ALXN1007 correlated with GVHD severity or responses. Further studies are needed to evaluate the role of complement inhibition in GVHD treatment.

Does this patient have a severe upper gastrointestinal bleed?

CONTEXT: Emergency physicians must determine both the location and the severity of acute gastrointestinal bleeding (GIB) to optimize the diagnostic and therapeutic approaches. OBJECTIVES: To identify the historical features, symptoms, signs, bedside maneuvers, and basic laboratory test results that distinguish acute upper GIB (UGIB) from acute lower GIB (LGIB) and to risk stratify those patients with a UGIB least likely to have severe bleeding that necessitates an urgent intervention. DATA SOURCES: A structured search of MEDLINE (1966-September 2011) and reference lists from retrieved articles, review articles, and physical examination textbooks. STUDY SELECTION: High-quality studies were included of adult patients who were either admitted with GIB or evaluated in emergency departments with bedside evaluations and/or routine laboratory tests, and studies that did not include endoscopic findings in prediction models. The initial search yielded 2628 citations, of which 8 were retained that tested methods of identifying a UGIB and 18 that identified methods of determining the severity of UGIB. DATA EXTRACTION: One author abstracted the data (prevalence, sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality, with confirmation by another author. Data were combined using random effects measures. DATA SYNTHESIS: The majority of patients (N = 1776) had an acute UGIB (prevalence, 63%; 95% CI, 51%-73%). Several clinical factors increase the likelihood that a patient has a UGIB, including a patient-reported history of melena (LR range, 5.1-5.9), melenic stool on examination (LR, 25; 95% CI, 4-174), a nasogastric lavage with blood or coffee grounds (LR, 9.6; 95% CI, 4.0-23.0), and a serum urea nitrogen:creatinine ratio of more than 30 (summary LR, 7.5; 95% CI, 2.8-12.0). Conversely, the presence of blood clots in stool (LR, 0.05; 95% CI, 0.01-0.38) decreases the likelihood of a UGIB. Of the patients clinically diagnosed with acute UGIB, 36% (95% CI, 29%-44%) had severe bleeding. A nasogastric lavage with red blood (summary LR, 3.1; 95% CI, 1.2-14.0), tachycardia (LR, 4.9; 95% CI, 3.2-7.6), or a hemoglobin level of less than 8 g/dL (LR range, 4.5-6.2) increase the likelihood of a severe UGIB requiring urgent intervention. A Blatchford score of 0 (summary LR, 0.02; 95% CI, 0-0.05) decreases the likelihood that a UGIB requires urgent intervention. CONCLUSIONS: Melena, nasogastric lavage with blood or coffee grounds, or serum urea nitrogen:creatinine ratio of more than 30 increase the likelihood of a UGIB. Blood clots in the stool make a UGIB much less likely. The Blatchford clinical prediction score, which does not require nasogastric lavage, is very efficient for identifying patients who do not require urgent intervention.

Spectrum of colonoscopy findings in Ile-Ife Nigeria.

AIMS AND OBJECTIVES: Lower gastrointestinal (LGI) diseases are the leading causes of morbidity and mortality worldwide. Colonoscopy holds an important place in screening, diagnosing and treatment of these conditions. In Nigeria, as in many other developing countries, the facility for performing colonoscopy is rarely available. This prospective report seeks to evaluate the demographic data of patients presenting for colonoscopy, the pattern and validity of referral diagnosis versus colonoscopy findings in Ile-Ife, Nigeria. SUBJECTS AND METHODS: All patients who had colonoscopy procedure done in the Endoscopy Unit of Obafemi Awolowo University Teaching Hospital Complex between January 2007 and December 2011 were included in the study. RESULTS: During the study period, colonoscopy was carried out in 320 patients. One hundred and eighty two (56.9%) were males, while 138 (43.1%) were females. The median age was 59.5 years. Their ages ranged from 2-87 years. The most common indications were lower gastrointestinal bleeding and change in bowel habit which together accounted for 79.0%. No abnormality was seen in 93(29.1%) patients. Abnormal endoscopic findings included 66(20.6%) patients who had haemorrhoids, 50(15.6%) cases colorectal cancer, 33 (10.3%) patients had benign polyps and (30 (9.4%) patients had diverticular disease. Other findings were colitis, inflammatory bowel disease, rectovaginal fistula, vascular ectasia and extra luminal compression. Haemorrhoids, diverticulosis and polyps were the most common findings in patients presenting with lower gastrointestinal bleeding. CONCLUSION: This present report showed that colonoscopy is a cheap, safe and effective method of investigating lower gastrointestinal disease in Ile-Ife, Nigeria. When the indication is based on symptoms, the diagnostic yield could be as high as 90%. The common causes of lower gastrointestinal bleeding in Ile-Ife, Nigeria include haemorrhoids, diverticulosis and polyps.

Surgical oncology in the age of multimodality therapy for cancer of the upper and lower gastrointestinal tract.

INTRODUCTION: To date, all efforts to fight gastrointestinal cancer, regardless of its origin and entity, have resulted in complex therapeutic regimens involving a combination of systemic therapy, radiation therapy and surgery. It is generally accepted across all disciplines that not one, but the combination and the proper timing of all modalities result in the best oncologic outcome. AREAS COVERED: Here, we provide insight into the current and future value of multimodal therapeutic approaches for upper and lower gastrointestinal cancer. Various aspects of treatment as well as open questions regarding indication and timing of multimodal strategies are addressed in this review. EXPERT OPINION: In order to further improve the survival and quality of life of patients with gastrointestinal tumors in the future, scientifically proven multimodal therapy concepts are needed first and foremost. In addition, markers are pivotal to assign individual patients to a specific concept and to monitor the success of therapy. The main question is in which situation a neoadjuvant, perioperative or adjuvant radio-, chemo- or immunotherapy is superior. In fact, almost every curatively intended concept still contains surgical resection. Thus, improvement in surgical technique is also critical for multimodality concepts.

Mixed adenoneuroendocrine carcinoma (MANEC) of the lower gastrointestinal tract: A systematic review with Bayesian hierarchical survival analysis.

BACKGROUND: Mixed adeno-neuroendocrine carcinomas (MANEC) are a subgroup of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) described as mixed neoplasms containing dual neuroendocrine and non-neuroendocrine components. The aim of this study was to appraise the prevalence of MANEC in the lower gastrointestinal (GI) tract and provide reliable estimates of survival. METHOD: A systematic review was undertaken in accordance with PRISMA guidelines using PubMed, Embase, Cochrane Library of Systematic Review, Web of Science, and Scopus databases, and a Bayesian hierarchical survival pooled analysis was performed. RESULTS: Of 182 unique records identified, 71 studies reporting on 752 patients met the inclusion criteria. Mean age was 64.2 ± 13.6, with a male-to-female ratio of 1.25. Overall, 60.3% of MANEC were located in the appendix, 29.3% in the colon, and 10.4% in the anorectum. More than a quarter (29%) of patients had stage IV disease at diagnosis, with higher prevalence in appendiceal than colonic and anorectal primaries. More than 80% had a high-grade (G3) endocrine component. Of the 152 patients followed up for a median of 20 months (interquartile range limits, 16.5-32), median overall survival was 12.3 months (95% credible interval [95%CrI], 11.3-13.7), with a 1.12 [95%CrI, 0.67-1.83] age-adjusted hazard ratio between metastatic and non-metastatic MANEC. Stage IV disease at diagnosis was more prognostically unfavorable in cases of colonic compared to anorectal origin. CONCLUSION: MANEC is a clinically aggressive pathological entity. The results of this study provide new insights for the understanding of tumor location within the lower GI tract and its prognosis in terms of overall survival.

Lower Gastrointestinal Functional and Motility Disorders in Children.

Functional and motility gastrointestinal disorders are the most common complaints to the pediatric gastroenterologist. Disorders affecting the small intestine carry a significant morbidity and mortality due to the severe limitation of therapeutic interventions available and the complications associated with such interventions. Congenital colorectal disorders are rare but also carry significant morbidity and poor quality of life plus the social stigma associated with its complications. In this review, we summarize the clinical presentation, diagnostic evaluations, and the therapeutic interventions available for the most common and severe gastrointestinal functional and motility disorders of the small bowel, colon, and anorectum.

Mycophenolate pharmacokinetics and association with response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network.

There are limited data as to the effectiveness of mycophenolate mofetil (MMF) plus high-dose corticosteroids for the treatment of acute graft-versus-host disease (aGVHD), and even less data regarding the pharmacokinetic disposition and exposure-response relationship of MMF in individuals with GVHD. MMF pharmacokinetics were studied in a multicenter Blood and Marrow Transplant Clinical Trials Network randomized phase II trial evaluating the effectiveness of MMF as one of 4 agents added to corticosteroids as treatment of aGVHD. Thirty-two of the patients randomized to receive MMF underwent pharmacokinetic sampling in weeks 1 and 2 were studied. Mean age was 41 +/- 13.6 years. Twenty one (65.6%), 5 (15.6%), 6 (18.8%) patients had a complete response (CR), partial response (PR) or lesser response by day 28, respectively. Twenty-five (78.1%), 2 (6.3%), 5 (15.6%) patients had a CR, PR, or other response by day 56 to treatment, respectively. Mycophenolic acid (MPA) pharmacokinetic measurements from weeks 1 and 2 did not correlate with CR at either day 28 or day 56 (P > .07); however, if the mean of weeks 1 and 2 total MPA troughs was >0.5 microg/mL or that of an unbound trough was >0.015 microg/mL, then a significantly greater proportion achieved CR + PR at days 28 and 56. CR + PR at day 28 was observed in 19 of 19 patients (100%) with a mean total trough >0.5 mg/mL, but in only 7 of 13 (54%) with a mean total trough < or =0.5 microg/mL (P = .002). Similarly, CR + PR at day 28 was seen in 15 of 15 patients (100%) with an unbound trough concentration >0.015 microg/mL, but in only 11 of 17 (65%) with an unbound trough concentration < or =0.015 microg/mL (P = .02). There was no association between the pharmacokinetic measures and risk of infection by day 90 or overall survival (OS) at day 180 postrandomization. About one-half of subjects did not achieve the favorable MPA total and unbound trough concentrations. The current practice of MMF 1 gm twice daily dosing provides low plasma concentrations in many patients. Higher doses may improve the efficacy of MMF as aGVHD therapy.

Upper and lower gastrointestinal causes of iron deficiency anemia in elderly compared with adult outpatients.

AIM: In the elderly, prevalence of bleeding- and/or iron malabsorption-related gastrointestinal (GI) causes of iron deficiency anemia (IDA) has not been addressed yet. The aim of this study was to assess the occurrence of malabsorptive diseases and bleeding lesions of the upper and lower GI tract in early (65-74 year-old) and late (over 75 year-old) elderly group compared with adult (50-64 year-old) outpatients. METHODS: The study enrolled 136 consecutive adult (N.=31), early (N.=48) and late elderly (N.=57) IDA outpatients who were referred to the Gastroenterology Department for IDA evaluation and underwent gastroscopy/histology and colonoscopy. RESULTS: Bleeding lesions were significantly less frequent in adult patients than in elderly patients (29% vs. 49.5%, P=0.0252). The most common bleeding lesions were large hiatal hernia (14.7%) and colon cancer (12.5%). Iron malabsorption diseases (Hp-related pangastritis, atrophic body gastritis and celiac disease) were more frequent in the adult group than in the early elderly group (80.6% vs. 56.2%, P=0.0367). In elderly patients, the observed prevalence of bleeding and iron malabsorption IDA causes was similar, whereas in adult patients iron malabsoptive diseases were more frequently detected (P<0.0001). The occurrence of concomitant IDA causes was not different among the three age-groups. CONCLUSION: In the early and late elderly, almost half of GI IDA causes are related to bleeding lesions which are more frequently observed respect to the adult patients. Iron malabsorption diseases affect almost 60% of early and late elderly groups. As for adult patients, an accurate upper and lower endoscopical/histological evaluation diagnoses IDA causes in the vast majority of the elderly outpatients.

Radiation-induced damage in the lower gastrointestinal tract: Clinical presentation, diagnostic tests and treatment options.

Radiation therapy is an important ally when treating malignant lesions in the pelvic area, but it is not exempt of adverse events. There are some measures that can be taken to reduce the possibility of these effects, but some are non-modifiable factors related to previous treatments, location of the lesions or comorbidities. There is a wide variety of clinical presentations that can be of an acute or chronic onset that go from mild to severe forms or that can have a great impact in the quality of life. Medical available therapies as metronidazole, sucralfate, mesalizine or probiotics, can be of aid although some lack of solid evidence of efficacy. Endoscopic treatment can be performed with argon plasma coagulation, bipolar cautery, radiofrequency, laser therapy or dilation. Hyperbaric therapy can be applied in refractory cases and surgery must be reserved to selected patients due to its high morbidity and mortality.

Endoscopic full-thickness resection and its treatment alternatives in difficult-to-treat lesions of the lower gastrointestinal tract: a cost-effectiveness analysis.

OBJECTIVE: Endoscopic full-thickness resection (EFTR) has shown efficacy and safety in the colorectum. The aim of this analysis was to investigate whether EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives. DESIGN: Real data from the study cohort of the prospective, single-arm WALL RESECT study were used. A simulated comparison arm was created based on a survey that included suggested treatment alternatives to EFTR of the respective lesions. Treatment costs and reimbursement were calculated in euro according to the coding rules of 2017 and 2019 (EFTR). R0 resection rate was used as a measure of effectiveness. To assess cost-effectiveness, the average cost-effectiveness ratio (ACER) and the incremental cost-effectiveness ratio (ICER) were determined. Calculations were made both from the perspective of the care provider as well as of the payer. RESULTS: The cost per case was €2852.20 for the EFTR group, €1712 for the standard endoscopic resection (SER) group, €8895 for the surgical resection group and €5828 for the pooled alternative treatment to EFTR. From the perspective of the care provider, the ACER (mean cost per R0 resection) was €3708.98 for EFTR, €3115.10 for SER, €8924.05 for surgical treatment and €7169.30 for all pooled and weighted alternatives to EFTR. The ICER (additional cost per R0 resection compared with EFTR) was €5196.47 for SER, €26 533.13 for surgical resection and €67 768.62 for the pooled rate of alternatives. Results from the perspective of the payer were similar. CONCLUSION: EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives in the colorectum.

Virome biogeography in the lower gastrointestinal tract of rhesus macaques with chronic diarrhea.

The composition of gastrointestinal tract viromes has been associated with multiple diseases. Our understanding of virus communities in the GI tract is still very limited due to challenges in sampling from different GI sites. Here we defined the GI viromes of 15 rhesus macaques with chronic diarrhea. Luminal content samples from terminal ileum, proximal and distal colon were collected at necropsy while samples from the rectum were collected antemortem using a fecal loop. The composition of and ecological parameters associated with the terminal ileum virome were distinct from the colon and rectum samples; these differences were driven by bacteriophages rather than eukaryotic viruses. The six contigs that were most discriminative of the viromes were distantly related to bacteriophages from three different families. Our analysis provides support for using fecal loop sampling of the rectum as a proxy of the colonic virome in humans.

The first in vivo application of synthetic polymers based on methacrylic acid as an aflatoxin sorbent in an animal model.

This study attempts to evaluate the potential aflatoxin binder activity of a molecularly imprinted polymer (TMU95) synthesized to target the aflatoxin B1 (AFB1) analog molecule in comparison to a commercial toxin binder (CTB). Adsorption experiments were carried out to assess the ability to bind to AFB1 at various pH values. The strength of binding was investigated by the chemisorption index. The isothermal analysis was used to determine the maximum adsorption capacity values. The ability of TMU95 and CTB to adsorb essential minerals was evaluated and the obtained data suggested that CTB would significantly reduce availability of them compared to TMU95. The in vivo efficacy of TMU95 as an aflatoxin (AF) binder in duckling exposed to aflatoxin-contaminated feed from 4 to 18 days of age in comparison to the CTB was also assessed. TMU95 and CTB were effective in reducing the adverse effects caused by AFs on feed conversion ratio of duckling (p ≤ 0.01), and also showed a minor reduction of injuries caused by AFs on visceral organs enlargement (p ≤ 0.01). It was concluded that TMU95 could absorb AFB1 in vitro efficiently and had beneficial health effects that could alleviate some of the toxic effects of AFs on growing duckling performance similar to CTB.

Radionuclide evaluation of the lower gastrointestinal tract.

This review outlines the technical aspects and diagnostic performance parameters of nuclear medicine procedures used on patients with disorders of the lower gastrointestinal tract, with the exclusion of techniques using tumor-seeking radiopharmaceuticals. Chronic disorders of the lower gastrointestinal tract often reduce the quality of life because of discomfort from constipation or diarrhea. Five classes of radionuclide procedures are used to characterize these disorders: transit scintigraphy, searches for ectopic gastric mucosa in Meckel's diverticulum, scintigraphy of active inflammatory bowel disease, scintigraphic defecography, and scintigraphy to detect sites of gastrointestinal bleeding. Protocols for these procedures and their relative merit in patient management are discussed, with special emphasis on their potential for semiquantitative assessment of the pathophysiologic parameter investigated. Quantitation is particularly relevant for prognostic purposes and for monitoring the efficacy of therapy.

Diagnostic evaluation of patients presenting with bleeding per rectum by colonoscopy.

BACKGROUND: Rectal bleeding is a manifestation of lower gastrointestinal bleed, which means bleeding from a site distal to ligament of Treitz. Annual incidence of this problem has been estimated to be 20% and mortality as 11%. Patients complaining of haematochezia are suspected of having lower GI bleeding and proctosigmoidoscopy followed by colonoscopy is the examination of choice for diagnosis and treatment. Previous evidence suggested that in our country, frequencies of different aetiologies of lower GI bleed are different from the West. This study validated the previous findings. The Objective of this study was to determine the causes of rectal bleeding in adult patients at Military Hospital, Rawalpindi. METHODS: One hundred and five adult patients with visible rectal bleed, irrespective of their gender were selected by non-probability convenient sampling from general medical OPD and general medical wards. Patients with suspected upper GI source of bleeding; haemorrhoidal bleed and acute infectious diarrhoea were excluded from the study. All patients were subjected to fibre-optic colonoscopy after necessary preparation and findings were recorded. Biopsies taken from suspected lesions were clinically indicated. Diagnosis was based on colonoscopic and histopathologic findings. RESULTS: A total of 105 patients (77 male and 28 female) with mean age 41.04 yrs were part of the study. Colonoscopy showed abnormal findings in 85 (84%) patients. The commonest diagnosis was ulcerative colitis, which was found in 48 (46%) patients. It was followed by colorectal carcinoma, 11 (10%) patients, and non-specific colitis, 9 (8%) patients. Other less frequent findings were colonic diverticuli, 7 (6%) patients, solitary rectal ulcer, 5 (4%) patients, colonic polyps in 3 (2.5%) patients and one case each of telangiectasia and Crohn's disease. CONCLUSION: Colonoscopy has very high diagnostic yield and would be recommended in the workup of patients presenting with bleeding per rectum. Ulcerative colitis was the leading cause of bleeding per rectum in this study; while infrequent findings of Crohn's disease, polyps and diverticuli indicate that these are uncommon in this region.

Sexually transmitted infections of the lower gastrointestinal tract.

The World Health Organization estimates that there is greater than one million new cases of sexually transmitted infections (STIs) every day. In many countries, STIs are at an unprecedented high, including the USA, where nearly 20 million new cases were reported in 2016. Although morbidity associated with STIs is usually seen in the context of genitourinary disease, these pathogens may also affect the gastrointestinal tract and cause anal pain, abdominal pain, or diarrhea. It is important to recognize patterns of injury associated with these pathogens, especially those that may mimic other gastrointestinal diseases, such as idiopathic inflammatory bowel disease (IBD). This review focuses upon STIs of the lower gastrointestinal tract, organized by the most common site of involvement: the anus, rectum, and colon.