New strategies for diagnosis and management of celiac disease

Celiac disease is a gastrointestinal disorder characterized by inflammation, leading to injury to the mucosal lining of the small intestine. The inflammation occurs when gliadin, a protein found in such gluten-containing foods as wheat, rye, and barley, is ingested by genetically susceptible individuals. The mucosal damage and subsequent malabsorption of nutrients leads to various complications. Researchers estimate that more than 2 million people in the United States have celiac disease-a prevalence that is greater than was previously believed. Approximately 60,000 Americans are diagnosed annually with celiac disease. Until recently, diagnosis has been complicated by the fact that the indicators of celiac disease are nonspecific. However, because of the development of new, easy-to-administer serology tests, diagnosis has become much less complicated. After conducting a review of the literature, the authors recommend a serologic testing sequence for diagnosis of celiac disease and urge that adults and children with an assortment of symptoms be tested for this disease. Common signs and symptoms of celiac disease include anemia, arthralgia, fatigue, infertility, neuropathy, and weight loss, in addition to such gastrointestinal symptomatology as abdominal pain, anorexia, bloating, constipation, and diarrhea. The only treatment for patients with celiac disease remains a gluten-free diet.     

Subclinical celiac disease and crystal-induced kidney disease following kidney transplant

Decreased kidney function from kidney deposition of calcium oxalate has been described previously in inflammatory bowel disease and after jejuno-ileal and Roux-en-Y gastric bypass surgeries. Although celiac disease is the most prevalent bowel abnormality associated with intestinal malabsorption, its relationship to high kidney oxalate burden and decreased kidney function has not been established. We report a case of subclinical celiac disease and hyperoxaluria that presented with loss of kidney function as a result of high oxalate load in the absence of overt diarrhea, documented intestinal fat malabsorption, and nephrolithiasis. Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients. We propose that this entity should be suspected in patients with chronic kidney disease in which the cause of kidney damage has not been clearly established.     

胰十二指肠切除术后患者腹泻71例分析

目的分析胰十二指肠切除术后患者腹泻发生的原因及机制,并探讨治疗对策.方法以笔者近1年半内收治的159例胰十二指肠切除术患者为对象,分析术后腹泻发生的原因及不同的处理方法.结果全组有71例发生不同程度的腹泻,发生率为44.7%.其中22例为肠道细菌感染,4例出现真菌感染,感染发生率占腹泻患者的36.6%.针对不同的病因给予治疗后,64例腹泻有不同程度的缓解,有效率为90.1%;7例出现慢性腹泻,经一般治疗效果不明显者,加用口服胰酶片治疗,2周后腹泻较用药前有明显缓解. 结论腹泻在胰十二指肠切除术后患者中较多见,根据不同的病因进行相应处理多能治愈.     

Celiac trunk compression: angiographic phenomenon or cause of ischemic abdominal complaints?

Compression of the celiac trunk commonly occurs in young men and women as well. Most of the patients suffering from this rare disease derive from a large pool of people having diffuse and chronic abdominal complaints including epigastric pain, postprandial abdominal pain and diarrhea leading to weight loss. Aim of the study was the finding of true criteria which can guarantee a successful operative procedure. A major issue in preoperative assessment is color flow Duplex imaging of the celiac axis. The most important finding aside from clinical symptoms is a peak flow in the celiac axis of more than 200 cm/s during inspiration and expiration position of the diaphragm. In addition arteriography of the celiac axis and superior mesenteric artery (SMA) showing a steal phenomenon is essential. Because of the rareness of the disease "only" 15 patients were operated on including intraoperative balloon dilatation of the celiac trunk. 93 % had a long term follow up success. Normal values of peak flow velocity in the mesenteric arteries were determined in more than one hundred healthy persons and compared to findings in the literature which were nearly identical. As a result of the study it could be shown that a successful outcome of the operative procedure can be expected when certain essential criteria are observed: 1. peak flow velocity in the celiac trunk higher than 200 cm/s during in- and expiration 2. steal effect via pancreatic arcades from the superior mesenteric artery documented by Duplex ultrasound and arteriography 3. triad of symptoms: epigastric pain, postprandial pain and weight loss of more than 5 kg. Special emphasis is given to the possible occurrence of severe complications after liver transplantations and pancreatic surgery, if the diagnosis "median arcuate ligament compression" is not known.     

Bone loss in celiac disease is related to secondary hyperparathyroidism.

Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.     

Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control

Type 1 diabetes mellitus is associated with celiac disease, with a prevalence that varies between 0.6% and 16.4%, according to different studies. After a diagnosis of celiac disease is confirmed by small bowel biopsy, patients are advised to commence a gluten-free diet (GFD). This dietary restriction may be particularly difficult for the child with diabetes, but in Europe (and in Italy) many food stores have targeted this section of the market with better labeling of products and more availability of specific GFD products. Treatment with a GFD in symptomatic patients has been shown to improve the symptoms, signs and complications of celiac disease. However, the effects of a GFD on diabetic control are less well established. Initial reports of improved hypoglycemic control were based on children who were diagnosed with celiac disease associated with malabsorption, but there have subsequently been reports of improvement in patients with type 1 diabetes with subclinical celiac disease. There are other studies reporting no effect, improved control and an improvement of hypoglycemic episodes. Moreover, in this review we wish to focus on low glycemic index foods, often suggested in people with type 1 diabetes, since they might reduce postprandial glycemic excursion and enhance long-term glycemic control. In contrast, GFD may be rich in high glycemic index foods that can increase the risk of obesity, insulin resistance and cardiovascular disease, worsening the metabolic control of the child with diabetes. Hence, it is important to evaluate the impact of a GFD on metabolic control, growth and nutritional status in children with type 1 diabetes.     

Bone and celiac disease

Celiac disease is an intestinal disease due to an abnormal immuno-mediated response to gluten and other peptides from different cereals in genetically susceptible subjects. Several systemic alterations, including bone alterations, may be present in affected subjects. Once considered rare, it is now known to be quite frequent in both Europe and North America, as the recent availability of specific serological markers has drastically changed our perspective on its prevalence. The diagnosis of celiac disease may be very difficult because the clinical picture is highly variable and the characteristic intestinal signs and symptoms may be completely absent. Among the extra-intestinal alterations, bone mass decrease and bone metabolism derangement are frequently present and can be the only signs of an otherwise silent celiac disease. Clinical and epidemiological data are now plentiful but no conclusive data on the pathogenesis of bone involvement in celiac disease are available yet. Bone alterations were once thought to derive from calcium and vitamin D deficiency secondary to simple intestinal malabsorption, but now a more complex interaction between cytokines and local/systemic factors influencing bone formation and reabsorption is envisaged, Also, there is now substantial evidence supporting a lifelong gluten-free diet as the first-choice therapy for celiac disease, and as far as we know, this is the only effective measure to restore bone metabolism to an apparent normality. In the young, an early-started gluten-free diet can even lead to a satisfactory recovery of bone mass. In adults, however, there is no spontaneous recovery, and there are no conclusive data on the efficacy of standard therapies for osteoporosis in reducing the fracture risk. For these reasons, we feel that a review of the clinical findings on bone problems in celiac disease may be useful for both gastroenterologists and osteoporosis specialists.     

Diarrhées chroniques infectieuses et dysimmunitaires

Clinical background is an essential data to achieve diagnosis of chronic diarrhea from infectious or immune dysfunction etiology. In HIV patients when the immune deficiency is important, diarrhea can be related to opportunistic infection. This diarrhea may be due to parasitic or bacterial infection. In primary immunodeficiency disorders, villous atrophy may also explain chronic diarrhea. Giardiasis, responsible for diarrhea and malabsorption, should always be looked for, because immune competent patients are not spared. Some specific clinical data (surgery history, achlorhydria, diabetes, immune deficiency, etc.) may be relevant to diagnose gut microbial pullulation. Whipple disease, although rare, should be kept in mind as treatment is easy and prognosis without treatment is very poor.     

The histologic spectrum and clinical outcome of refractory and unclassified sprue

The vast majority of patients with celiac disease respond to a gluten-free diet; yet, a small number of refractory patients do not respond and have persistent malabsorption and residual mucosal abnormalities of the small intestine. The histologic features of refractory/unclassified sprue have been published as case reports, often without long-term follow up, and no clear histologic picture has emerged. We present the results of a long-term study of the clinical and histologic features of 10 patients with refractory/unclassified sprue. The histologic features of small bowel biopsies in this group of patients were compared with those of 10 patients with responsive celiac disease and with 10 patients without malabsorption who had normal duodenal biopsies. Five of the 10 refractory patients ultimately developed collagenous sprue as a distinct histologic marker of refractory disease. Additional distinctive findings found in small bowel biopsies in the refractory group were subcryptal chronic inflammation (10 of 10) and marked mucosal thinning in three patients. Other nonspecific findings included acute inflammation and gastric metaplasia. One patient with collagenous sprue developed a B-cell lymphoma of the ileum, and in general collagenous sprue was associated with a poor prognosis. Two of five patients died whereas two others require total parenteral nutrition for survival. Pathologists evaluating small bowel biopsies in the setting of malabsorption should be aware of the subtle histologic changes described here that may portend a refractory course.     

The Mayo clinic approach to the surgical treatment of adenocarcinoma of the pancreas.

Ductal carcinoma of the pancreas remains a challenging problem for gastrointestinal surgeons. Significant progress has been made in diagnosis, preoperative staging, and safety of surgery; however, long-term survival after resection is unusual, and cure is rare. That said, the authors maintain their aggressive posture regarding this disease, recognizing that resection offers the only potential for cure. The authors' approach such patients in the most efficient and least invasive manner possible, relying primarily on triple phase helical abdominal CT for clinical diagnosis and staging, reserving ERCP and EUS for diagnostic dilemmas. In fit candidates with potentially resectable lesions, the authors eschew pre- or intraoperative biopsy, angiography, or endoscopic stenting and use preliminary limited staging laparoscopy selectively. Surgical palliation is chosen for fit patients who, at exploration for potentially curative resection, are found to have occult distant metastases or locally unresectable disease. Radical pancreatoduodenectomy can be performed with a mortality rate of 3% or less, and although morbidity remains significant, most can be managed with conservative measures. Quality of life after pancreatoduodenectomy is good and, if not, is generally a manifestation of recurrence rather than physiologic alterations inherent to the procedure. Adjuvant chemoradiation is standard therapy after resection, recommended for those with locally unresectable disease but used selectively for those with distant metastasis. Survival after potentially curative resection has remained disappointing. Whether extended lymphadenectomy or neoadjuvant chemoradiation improves survival has not been determined. Clearly, methods for earlier diagnosis of pancreatic cancer and more effective adjuvant therapies are sorely needed.     

Celiac axis compression syndrome: factors predicting a favorable outcome

There is still considerable doubt about the existence of the celiac axis compression syndrome. Asymptomatic compression or narrowing of the celiac artery is common, and it is difficult to understand why some patients have significant symptoms while others have none. One major problem emerges from a study of the literature, in that there is no precise definition of the clinical features of a syndrome. Patients with all kinds of abdominal symptoms and varying psychiatric and medical backgrounds have been included in previous studies. It is not surprising, then, that there is no agreement on whether surgery is ever justified. We reported a small series of 11 patients whose clinical features have been carefully documented. Regression analysis of results suggests that good surgical results can be achieved in selected patients by decompression of the artery and restoration of the normal arterial lumen. Patients likely to benefit are those with epigastric pain related to food or hunger who do not have a galaxy of other unrelated symptoms. It is suggested that these factors be included in subsequent definitions of the celiac axis compression syndrome, so that some uniformity be introduced into the writing and thinking about this confusing problem.     

Celiac axis occlusion with replaced common hepatic artery and pancreatoduodenectomy

A rare case of intraductal papillary mucinous tumor of the pancreas associated with a replaced common hepatic artery and celiac axis occlusion, which was treated by pancreatoduodenectomy, is reported. In this patient, the celiac trunk was occluded at its root and the splenic and left gastric artery could be visualized serially via the enlarged collateral artery on superior mesenteric arteriography. At surgery, the collateral artery was carefully preserved and pancreatoduodenectomy was successfully performed without ischemia of the stomach, spleen, and remnant pancreas. Although celiac axis occlusion is an uncommon finding for patients undergoing pancreatoduodenectomy, we recommend performing celio-mesenteric angiography before pancreatoduodenectomy, and, at surgery, clamping of the gastroduodenal artery is required for patients with celiac axis occlusion.     

Isolated Whipple disease of the brain resembling a tumour

Introduction  Isolated Whipple disease of the central nervous system is a rare occurrence. Migratory arthralgias and gastrointestinal problems, including malabsorption, abdominal pain, diarrhea, and weight loss, are common presenting symptoms. Discussion  For those patients with systemic signs and symptoms of Whipple disease, 6% to 43% will have clinically manifested CNS involvement that may include alterations in personality, ataxia, and dementia. We report our experience with a patient, who was successfully treated for Whipple disease 12 years prior to presentation and had a magnetic resonance image of the brain that revealed two solitary lesions resembling a tumor upon presentation.     

Severe malabsorption due to refractory celiac disease complicated by extensive gastric heterotopia of the jejunum

Refractory celiac disease denotes that patients considered to have celiac disease fail to respond histologically to treatment with a gluten-free diet. Among several causes of nonresponsiveness, enteropathy-type T-cell lymphoma is most important because of its almost invariably rapid lethal outcome. We present the case of a 44-year-old patient with refractory celiac disease complicated by unusually severe malabsorption. Repeated duodenal biopsies disclosed normal and slightly shortened villi, focal crypt hypertrophy, and a moderate increase of intraepithelial lymphocytes consistent with celiac disease, but unable to explain the severe malabsorption. To rule out cryptic lymphoma, push enteroscopy was done providing 21 biopsies taken along the entire jejunum. Surprisingly, about 70% of the biopsies were composed of gastric glands covered by nonabsorptive-type, strongly periodic acid-Schiff-positive surface epithelium and showed a villous architecture. Alternating with the gastric mucosa, there were areas of flat mucosa with elongated crypts and occasional erosions. Irrespective of the type of surface epithelium, intraepithelial lymphocytes were increased with counts up to 80/100 epithelial cells. Despite harboring an aberrant immunophenotype, overt T-cell lymphoma was ruled out histologically and by lack of monoclonality, as tested by polymerase chain reaction. To the best of our knowledge, this is the first case of refractory celiac disease complicated by extensive jejunal gastric heterotopia, which might have contributed to the severe malabsorption.     

Autoimmune hypoparathyroidism in a 12-year-old girl with McKusick cartilage hair hypoplasia

McKusick type metaphyseal chondrodysplasia, or cartilage hair hypoplasia (CHH), is a rare autosomal recessive osteochondrodysplasia secondary to a mutation in the RMRP gene. In addition to the metaphyseal chondrodysplasia and the short-limb dwarfism, patients may present with a multisystemic disease, associating immune deficiency with recurrent infantile or childhood infections, hematological abnormalities, and gastrointestinal dysfunction. The probability of malignancy is increased in these patients, as are disimmune manifestations. We report on a 12-year-old girl with a new mutation of the RMRP gene and a severe multisystemic CHH (hematological and pulmonary lesions, severe immune deficiency, arthritis, pancreatic insufficiency, malabsorption, chronic diarrhea) receiving parenteral nutrition who presented with acute symptomatic hypocalcemia and hypercalciuria associated with the presence of autoantibodies directed against the calcium-sensor receptor. At the same time, there was an important escalation of diarrhea. Corticosteroids led to a progressive improvement of biological signs (hypocalcemia, hypoparathyroidism). By contrast, gastrointestinal symptoms and malabsorption did not improve. To our knowledge, this is the first report of autoimmune hypoparathyroidism in CHH.     

Arterial Reconstruction during Pancreatoduodenectomy in Patients with Celiac Axis Stenosis—Utility of Doppler Ultrasonography

Celiac axis stenosis is found at an incidence of 2%–24% in the general population. During pancreatoduodenectomy in patients with celiac axis stenosis, division of the gastroduodenal artery from the common hepatic artery may cause acute ischemia of the upper abdominal organs, such as the liver, stomach, or spleen. Under these circumstances, the clinical indications of arterial reconstruction remain controversial. Between 1994 and 2003, seven patients with celiac axis stenosis (n = 4) or occlusion (n = 3) underwent pancreatoduodenectomy at our hospital. Arterial reconstruction, including division of the median arcuate ligament, was conducted in two patients; the replaced right hepatic artery was preserved in one patient, and no vascular refinement was undertaken in the remaining four of the seven patients. In two of the four patients without arterial reconstruction or preservation, the serum levels of liver enzymes were markedly elevated (> 800 IU/l) on postoperative day 1, and these patients subsequently developed liver abscesses. Two patients who underwent arterial reconstruction and three patients who showed no decrease in intrahepatic arterial flow under Doppler ultrasonography after clamping of the gastroduodenal artery developed no ischemic complications. Although our experience is limited, when intraoperative Doppler ultrasonography indicates a decrease in the hepatic arterial signals, we believe that reconstruction of the hepatic artery will be necessary to minimize ischemic complications in the liver in patients with celiac axis stenosis.     

Pseudoaneurysm of the Dorsal Pancreatic Artery with Obstruction of the Celiac Axis After Pancreatoduodenectomy: Report of a Case

Pancreatoduodenectomy can be difficult in patients with obstruction of the celiac axis because of the development of collateral arteries around the head of the pancreas. Bleeding from a pseudoaneurysm is a rare and serious complication of pancreatoduodenectomy. We report a case of a pseudoaneurysm of an enlarged dorsal pancreatic artery, which formed as a result of obstruciton of the celiac axis after pancreatoduodenectomy. We assumed that a weakness in the wall of this dorsal pancreatic artery caused by the dissection led to the formation of the aneurysm. Although transcatheter arterial embolization (TAE) could not treat the aneurysm or stop bleeding from the aneurysm completely, it achieved transient hemostasis, whereby the patients condition improved, making laparotomy safe. This case demonstrates that the dissection of arteries that have developed around the head of the pancreas must be considered in patients with obstruction of the celiac axis.     

Association of adult celiac disease with surgical abdominal pain: a case-control study in patients referred to secondary care

BACKGROUND: Acute abdominal pain is the most common indication for surgical admission. Nonspecific abdominal pain (NSAP) may account for up to 40% of cases. There has been no published prospective study in which adult patients presenting with acute abdominal pain are investigated for celiac disease. AIMS: We aimed to assess the association of celiac disease with surgical abdominal pain. PATIENTS AND METHODS: A case-control study was undertaken involving 300 consecutive new unselected patients presenting with acute abdominal pain (in a university hospital) and healthy controls (age and sex matched) without abdominal pain (n = 300). Initial investigations for celiac disease were immunoglobulins, IgA/IgG anti-gliadin (AGA), and endomysial antibodies (EMA). Any patient with a positive IgA AGA, EMA, or only IgG AGA in the presence of IgA deficiency was offered a small bowel biopsy to confirm the diagnosis. RESULTS:: There were 33 patients with abdominal pain who had positive antibodies, of whom 9 had histologically confirmed celiac disease (6 EMA positive; 3 EMA negative). One antibody positive patient (EMA in isolation) declined duodenal biopsy and the remaining 23 had normal duodenal mucosa. Within the control group, there were 2 cases of celiac disease. Compared with matched controls the association of acute abdominal pain with celiac disease gave an odds ratio 4.6. (P = 0.068, 95% confidence interval, 1.11-19.05). When only considering NSAP the prevalence of celiac disease was highly significant at 10.5% (9 of 86, P = 0.006). Patients' symptoms improved on a gluten-free diet at 12- to 18-month follow-up. CONCLUSION: Celiac disease was diagnosed in 3% of patients who presented with unselected acute abdominal pain to secondary care. Targeting patients who have NSAP or celiac associated symptoms/diseases may improve the diagnostic yield.     

Operative therapy of gallbladder disease in patients with cystic fibrosis

We retrospectively studied 20 patients with cystic fibrosis who underwent surgery for gallbladder disease from 1973 to 1986. A long delay between the onset of symptoms and the diagnosis was noted (mean 7.4 months). This delay was attributed to masking of the symptoms of biliary disease by the malabsorption and pulmonary symptoms seen in this patient population. There was a notable lack of common bile duct disease in our patients as well as in those reported in the literature. This may have been due to a combination of factors: the increased viscosity of the mucus, the small caliber of the gallbladder and ductal system, and the hypotonicity of the gallbladder. We do not recommend routine intraoperative cholangiography in patients with cystic fibrosis and gallbladder disease. Cystic fibrosis is a disease with progressive pulmonary deterioration. Cholecystectomy can be performed in these patients with relative safety if careful preoperative and postoperative care is provided. We recommend early operative intervention in the patient with gallbladder disease and cystic fibrosis.     

Nephrolithiasis in a child with glucose-galactose malabsorption

Glucose-galactose malabsorption (GGM) is a rare autosomal recessive disorder of intestinal transport of glucose and galactose, leading to watery diarrhea, dehydration, failure to thrive, or early death. We report a female newborn with GGM, whose clinical diagnosis was confirmed by mutational analysis of the SGTL1 gene. Bilateral nephrolithiasis was discovered after an episode of hematuria. Metabolic causes of nephrolithiasis were not found. The most likely explanation for the development of nephrolithiasis is chronic diarrhea leading to dehydration and highly concentrated urine. High fluid intake and rigorous prevention of dehydration is therefore advised for these patients. Furthermore, life-long monitoring of their renal status, including regular ultrasound examinations, is warranted.