Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease.

BACKGROUND & AIMS: Patients with celiac disease (CD) who do not improve or exhibit villous atrophy on a gluten-free diet may have type 1 refractory CD (RCD) with a polyclonal mucosal T-cell infiltrate, or type 2 RCD with a monoclonal infiltrate, also termed cryptic T-cell lymphoma. Both conditions are difficult to treat. Here we describe the effects of a nonimmunogenic elemental diet on clinical symptoms and mucosal immunopathology in type 1 RCD. METHODS: Ten CD patients on a strict gluten-free diet were diagnosed with type 1 RCD after extensive clinical evaluation in a tertiary referral hospital. A 4-week amino-acid-based liquid elemental diet regimen was given with no other treatment, except in 1 patient who also received methotrexate. Duodenal biopsy specimens were obtained before and after treatment for histologic assessment, immunophenotyping of intraepithelial lymphocytes, T-cell receptor clonality, mucosal interleukin (IL)-15 expression, flow-cytometric analysis of interferon (IFN)-gamma-secreting T cells, and whole biopsy specimen IFN-gamma messenger RNA determination. RESULTS: Nine patients completed the treatment; however, 1 patient did not tolerate the diet. Histologic improvement and reduced epithelial IL-15 were seen in 8 patients, whereas IFN-gamma-secreting mucosal T cells and IFN-gamma messenger RNA levels decreased in 4 and 7 patients, respectively. Clinical improvement was noted in 6 patients, with 1 patient showing normalization of hypoalbuminemia. Three patients could discontinue their total parenteral nutrition. CONCLUSIONS: Persistent mucosal IFN-gamma and IL-15 production often occurs in type 1 RCD despite conventional treatment. Elemental diet is a therapeutic option that can provide long-term immunopathologic and clinical improvement of this difficult condition.     

The management of complicated celiac disease

Refractory celiac disease (RCD) is being defined as persisting or recurring villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (IELs) in spite of a strict gluten-free diet (GFD) for >12 months or when severe persisting symptoms necessitate intervention independent of the duration of the GFD. RCD may not respond primarily or secondarily to GFD. All other causes of malabsorption must be excluded and additional features supporting the diagnosis of CD must be looked for, including the presence of antibodies in the untreated state and the presence of celiac-related HLA-DQ markers. In contrast to patients with a high percentage of aberrant T-cells, patients with RCD I seem to profit from an immunosuppressive treatment. RCD II is usually resistant to medical therapies. Response to corticosteroid treatment does not exclude underlying enteropathy-associated T-cell lymphoma. Cladribine seems to have a role, although it is less than optimal in the treatment of these patients. It may be considered, however, as the only treatment thus far studied that showed significant reduction of aberrant T cells, seems to be well tolerated, and may have beneficial long-term effects in a subgroup of patients showing significant reduction of the aberrant T-cell population. Autologous stem cell transplantation (ASCT) seems promising in those patients with persisting high percentages of aberrant T cells. The first group of patients treated with ASCT showed improvement in the small intestinal histology, together with an impressive clinical improvement. However, it remains to be proven if this therapy delays or prevents lymphoma development.     

Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease

BACKGROUND & AIMS: Plasma citrulline, a nonprotein amino acid produced by enterocytes, was suggested as a marker of remnant enterocyte mass in patients with short bowel. Our objective was to evaluate citrulline as a marker of severity and extent of villous atrophy in patients without intestinal resection. METHODS: Forty-two patients with celiac disease and 10 patients with non-celiac villous atrophy disease were studied by plasma postabsorptive citrulline and biological dosages, biopsies of proximal (duodenojejunal) small bowel and distal ileum (n = 25), or measurement of vitamin B(12) absorption (n = 4). Nine patients were reevaluated after following a gluten-free diet for 1 year. Controls were 51 healthy subjects and 10 severely malnourished patients with anorexia nervosa with no intestinal mucosal abnormalities. RESULTS: Plasma citrulline concentration was lower (P < 0.001) in patients with villous atrophy (24 +/- 13 micromol/L) than in healthy subjects (40 +/- 10 micromol/L) and patients with anorexia nervosa (39 +/- 9 micromol/L). Three thresholds were individualized: <10 micromol/L for patients with diffuse total villous atrophy (n = 10), 10-20 micromol/L for patients with proximal-only total villous atrophy (n = 12), and 20-30 micromol/L for patients with partial villous atrophy (n = 10). Plasma citrulline concentration was correlated to the severity and extent of villous atrophy (r = 0.81; P < 0.001) and to albuminemia (r = 0.47; P < 0.01). Receiver operating characteristic curves indicated that plasma citrulline concentration was the best biological variable to predict villous atrophy. Following a 1-year gluten-free diet, plasma citrulline concentration increased in histologically responsive (n = 6) but not in unresponsive (n = 3) patients. CONCLUSIONS: In patient villous atrophy diseases, plasma citrulline concentration may prove to be a simple and reliable marker of reduced enterocyte mass.     

Autologous hematopoietic stem cell transplantation in refractory celiac disease with aberrant T cells

Autologous hematopoietic stem cell transplantation (ASCT) is an increasingly accepted treatment for refractory autoimmune diseases. Refractory celiac disease with aberrant T cells (RCD type II) is unresponsive to available therapies and carries a high risk of transition into enteropathy associated T-cell lymphoma (EATL). This study reports on the feasibility, safety, and efficacy of ASCT in patients with RCD type II. Thirteen patients with RCD type II were evaluated. Seven patients (4 men, 3 women, mean age 61.5 years [range, 51-69 years]) underwent transplantation. After conditioning with fludarabine and melphalan, ASCT was performed. Patients were monitored for response, adverse effects, and hematopoietic reconstitution. All 7 patients completed the mobilization and leukapheresis procedures successfully and subsequently underwent conditioning and transplantation. Engraftment occurred in all patients. No major nonhematologic toxicity or transplantation-related mortality was observed. There was a significant reduction in the aberrant T cells in duodenal biopsies associated with improvement in clinical well-being and normalization of hematologic and biochemical markers (mean follow-up, 15.5 months; range, 7-30 months). One patient died 8 months after transplantation from progressive neuroceliac disease. These preliminary results showed that high-dose chemotherapy followed by ASCT seems feasible and safe and might result in long-term improvement of patients with RCD type II whose condition did not respond promptly to available drugs.     

Collagenous colitis associated with small intestinal villous atrophy.

Two patients diagnosed as having small intestinal hyperplastic villous atrophy and being treated with a gluten free diet were investigated because of persistent watery diarrhoea. Both were found to have collagenous colitis. Previous reports of this condition have emphasised the presence of normal small intestinal mucosal architecture and the association of collagenous colitis with intestinal villous atrophy has not previously been reported. Both cases responded to oral steroid therapy, but not to other previously recommended treatment regimens.     

Refractory coeliac disease

A small proportion of coeliac disease (CD) patients fail to improve after a gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a malabsorption syndrome defined by persisting villous atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific therapies like antibiotics in tropical sprue and giardiasis and immune globulin substitution in common variable immunodeficiency, while other malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal T-cell lymphomas in a subgroup of RCD. Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and parenteral nutrition has to be applied in some of these cases. First results with more aggressive chemotherapies and use of cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.     

Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery

OBJECTIVE: Although serum IgA-class endomysial antibody (EmA) has high sensitivity for villous atrophy (VA) in patients with untreated celiac disease, few studies have attempted to correlate EmA seroconversion with histological recovery after starting a gluten-free diet. We prospectively studied changes in EmA status and in duodenal histology of seropositive patients after dietary treatment. METHODS: Patients with VA and EmA had repeat EmA testing at 3, 6, and 12 months after starting gluten-free diet, plus assessment of dietary compliance by dietitians and follow-up duodenal biopsy at 12 months. VA before and after treatment was classified as partial (P), subtotal (ST), and total (T). RESULTS: Of 77 patients with newly diagnosed VA and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with T or STVA and 16 of 20 (80%) with PVA. Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months. However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only three (33%) of 10 patients with persisting ST or TVA and two (9%) of 22 with PVA remained EmA positive. Four of the five patients with persisting EmA had poor dietary compliance. CONCLUSIONS: EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance. Although there are no clear guidelines regarding the need for follow-up biopsy, EmA seroconversion cannot substitute. The apparent association between dietary compliance and seroconversion suggests that gluten intake may determine whether untreated celiac patients are EmA positive or negative for a given degree of small bowel damage.     

醋酸钙联合低钙透析液在老年高钙高磷腹膜透析患者中的应用

目的 探讨醋酸钙联合低钙透析液治疗对并发高钙和高磷血症老年腹膜透析患者钙磷代谢状况的影响.方法 选择行CAPD治疗6m以上、病情稳定且伴有高钙、高磷血症的老年患者20例,随机分为对照组（使用含钙1.5 mmol/L透析液＋饮食控制）和治疗组（使用含钙1.25 mmol/L透析液＋醋酸钙＋饮食控制）,每组10例,分别观察治疗前、治疗后1、3和6个月的血钙、血磷、钙磷乘积、iPTH和相关不良反应.结果 ①共18人完成该临床研究,其中对照组有1人因出现腹透相关性腹膜炎退出研究;试验组有1人因无法耐受服用醋酸钙后出现的恶心、反酸症状而退出试验.②醋酸钙联合低钙透析液治疗组在治疗后第3个月时血钙、血磷及钙磷乘积水平明显降低,血iPTH浓度明显升高,与对照组相比均有统计学差异（P＜0.05）;至第6个月时血钙、血磷及钙磷乘积水平趋于稳定.③两组患者在研究期间除治疗组1人出现肌肉痉挛外,其余患者未见明显不良反应.结论 醋酸钙联合低钙透析液对于合并高钙血症和高磷血症的老年腹膜透析患者具有较好的治疗效果.     

Wheat starch-containing gluten-free flour products in the treatment of coeliac disease and dermatitis herpetiformis. A long-term follow-up study

BACKGROUND: We investigated whether wheat starch-based gluten-free products are safe in the treatment of gluten intolerance. METHODS: The study involved 41 children and adults with coeliac disease and 11 adults with dermatitis herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start of a gluten-free diet and 27 non-coeliac patients with dyspepsia were investigated for comparison. Daily dietary gluten and wheat starch intake were calculated. Small-bowel mucosal villous architecture, CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty of 52 long-term-treated patients adhered to a strict wheat starch-based diet and 6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the 46 patients on a strict diet the villous architecture, enterocyte height, and density of alphabeta+ intraepithelial lymphocytes were similar to those in non-coeliac subjects and better than in short-term-treated coeliac patients. The density of gammadelta(+)cells was higher, but they seemed to decrease over time with the gluten-free diet. Wheat starch-based gluten-free flour products did not cause aberrant upregulation of mucosal HLA-DR. The mucosal integrity was not dependent on the daily intake of wheat starch in all patients on a strict diet, whereas two of the six patients with dietary lapses had villous atrophy and positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were not harmful in the treatment of coeliac disease and dermatitis herpetiformis.     

Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.     

Can villous atrophy be induced by chronic alcohol consumption?

A 43-year-old man presented with loose stools, abdominal pain and a weight loss of 15 kg. Investigations revealed a pancreatic insufficiency and an enteropathy with villous atrophy. Coeliaki was suspected. In spite of treatment with a gluten-free diet in hospital the patient did not improve and the villous atrophy remained unchanged. Other causes than coeliaki to villous atrophy were ruled out. The patient had a heavy consumption of alcohol and after prolonged abstinence the patient gained weight, the pain disappeared and the stools were normalized. The jejunal biopsy was now normal. This case report raises the possibility that enteropathy and villous atrophy may be causally related to alcohol overconsumption.     

Hydrogen concentration in expired air analyzed with a new hydrogen sensor, plasma glucose rise, and symptoms of lactose intolerance after oral administration of 100 gram lactose

A rapid breath hydrogen analyzer to detect lactose malabsorption is described. After ingestion of a lactose solution the patient expires into a mouthpiece attached to a hydrogen sensor at 30-min intervals for 3 1/2 h. The hydrogen of the expired air causes a voltage change that can be transformed into ppm from a calibration curve. A tolerance test with a load of 100 g lactose was performed in 43 consecutive patients with various gastrointestinal disturbances, referred to the laboratory for the commonly used lactose tolerance test based on plasma glucose measurements. Eleven patients developed symptoms of lactose intolerance during the test. Biopsy specimens from the distal duodenum or proximal jejunum showed partial villous atrophy in one, in whom celiac disease with lactose intolerance was diagnosed; the other 10 had normal specimens. In nine of them lactose intolerance was diagnosed and confirmed by observation for months on a lactose-poor diet. The 10th patient (H.P.L.) did not improve on such a diet. He also showed pronounced symptoms of intolerance during a test with monosaccharides (glucose + galactose). His intestinal disease remained undiagnosed. The 11 patients with symptoms of intolerance and 3 patients without symptoms during the lactose load showed a flat plasma glucose curve after drinking the lactose solution--that is, a maximum rise of the glucose concentration of 1.5 mmol/l. One of the symptom-free patients dropped out and could not be observed, another did not improve on a lactose-poor diet, and the third noticed a favorable effect of the diet on stool consistency but not on other abdominal symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Celiac disease onset after pegylated interferon and ribavirin treatment of chronic hepatitis C

AIM: Report of a case of a woman patient who developed celiac disease after pegylated interferon alpha-2a and ribavirin use for chronic hepatitis C. PATIENT AND METHOD: A 34-year-old woman with chronic hepatitis C, genotype 3, receiving pegylated interferon alpha-2a and ribavirin for 6 months, developed progressive malaise and anemia 6 months after the end of treatment. RESULT: Additional investigation revealed duodenal villous atrophy and positivity for anti-endomysium and anti-gliadin antibodies. Celiac disease diagnosis was performed and symptoms and laboratory abnormalities improved after gluten-free diet. CONCLUSION: Celiac disease must be ruled out in patients with malabsorption complaints in or after interferon (or pegylated interferon) therapy. Screening for celiac disease with detection of anti-endomysium antibodies would be done in susceptible patients.     

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-γ prior to initiation of interferon-α treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-α treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-γ (1 MIU/day) was administered daily for 14 days followed by natural IFN-α (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-α treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-γ administration, and tended to return to the pretreatment level after the start of IFN-α administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-γ prior to the initiation of IFN-α treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.     

Jejunal villous atrophy with morbid obesity: death after jejunoileal bypass.

A 49-year-old woman with morbid obesity was found to have subtotal villous atrophy in an operative jejunal biopsy, taken when a jejunoileal bypass was created. After the operation, the patient developed marked weight loss, vomiting, hepatic failure, and a bizarre mental state with sudden losses of consciousness. Six months after the first operation the bypass was reversed but the patient developed hepatorenal failure and died one week after the second operation. The histological features of several biopsies of jejunum were typical of a gluten sensitive enteropathy. This, previously subclinical, small bowel disease may have contributed to her hepatic failure and death by interfering with jejunoileal adaptation. In the absence of any of the other, rarer, causes of villous atrophy, this woman appears to have had coeliac disease.     

Serum antibodies to gliadin and small-intestinal morphology in dermatitis herpetiformis. A controlled clinical study of the effect of treatment with a gluten-free diet

Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay in 41 patients with dermatitis herpetiformis before treatment with a gluten-free diet. Increased gliadin antibody levels were found more frequently in patients with subtotal villous atrophy (9 out of 17 patients, or 53%; p less than 0.05) than in patients with partial villous atrophy (2 out of 13 patients, or 15%) or normal villous appearance (2 out of 10 patients, or 20%). The gliadin antibody levels were negatively correlated with the urinary xylose excretion (r = -0.40, p less than 0.02 for the IgA class and r = -0.64, p less than 0.001 for the IgG class). Intestinal morphology improved and mean gliadin antibody levels of the IgA and IgG classes decreased during treatment with a gluten-free diet for 16-36 months (mean, 20 months) (p less than 0.005, n = 26), whereas no significant changes of the gliadin antibody levels or the small-intestinal morphology were observed in the other 15 patients, who continued on a non-restricted diet for 17-35 months (mean, 20 months). Thus, gliadin antibody levels in sera from patients with dermatitis herpetiformis seem to be correlated with the severity of the intestinal disease. However, all patients with villous atrophy are not detected by determination of serum gliadin antibodies.     

Refractory celiac disease: an unusual disease in a Chinese patient

Celiac disease (CD) is an autoimmune disease characterized by mucosal inflammation and villous atrophy of the small bowel upon exposure to ingested gluten. Although common in developed countries, it is extremely rare in the Chinese population. Refractory celiac disease (RCD) is a rare complication of CD with poor prognosis. Patients may die of severe malabsorption or development of enteropathy-associated T-cell lymphoma. We report a case of RCD in a Chinese woman who required steroid therapy in addition to a gluten-free diet to induce disease remission. The possibility of CD in Chinese patients should not be overlooked.     

Refractory celiac disease

Celiac disease (CD) is a small intestinal inflammatory disorder characterized by an immune-mediated enteropathy triggered by the ingestion of wheat gluten or related rye and barley proteins in genetically predisposed individuals carrying the human leukocyte antigens (HLA)-DQ2 or-DQ8. Nonresponsive CD (NRCD) is a clinical diagnosis defined by the persistence of signs, symptoms, and/or laboratory abnormalities typical of CD despite adherence to a gluten-free diet for at least 6 months. One cause for NRCD is refractory CD (RCD), defined as the persistence of severe villous atrophy on small intestinal biopsy despite strict gluten withdrawal for at least 6 months with no evidence of other pathology. Although rare, RCD should be suspected in individuals with an established diagnosis of CD who fail to respond primarily or secondarily to a strict gluten-free diet, particularly if they manifest significant weight loss. A thorough evaluation must be performed to distinguish RCD from other causes of NRCD. RCD may be categorized into type I or type II. Type I RCD has a more favorable prognosis compared with type II and can often be managed with nutritional supplementation and possibly low level immunosuppressive therapy. Type II RCD carries a poor prognosis and is more likely to progress to life-threatening malnutrition or intestinal T-cell lymphoma. Immunosuppressive agents and, more recently, autologous stem cell transplant have been used to treat type II RCD.     

Local Excision of Large Rectal Villous Adenomas

PURPOSE: Transanal excision of rectal villous adenomas is a widely used surgical technique, because it is a one-step procedure, requiring no sophisticated instrumentation, and allowing complete histologic analysis of the excised tumor. Therefore, it ranks alongside radical surgery and palliative destructive procedures, but its results are highly variable in the published series. This discrepancy may be explained by the variable completeness of tumor excision because of potential dissection difficulties. Because intraoperative exposure may be a major limiting factor, one of us (JF) has developed a tractable cutaneomucous flap procedure to lower the rectal tumor to the anal verge, where control of the dissection line is easier. This retrospective review of consecutive patients operated on during ten-year period reports long-term results after transanal excision for large rectal villous adenomas with the tractable flap technique. PATIENTS: From 1978 to 1988, 207 consecutive patients (100 males), mean age 68 (range, 24-90) years, were operated on for an apparently benign villous rectal adenoma. Twenty-one patients (10 percent) were referred after failure of previous treatments: 11 endoscopic, 8 surgical, 1 laser, 1 radiotherapy. Mean distance of lower tumor edge from anal margin was 5.6 (range, 0-13) cm and was <10 cm in 82 percent. RESULTS: Three patients (1.5 percent), including one with a Tis carcinoma, underwent a secondary treatment for immediate gross failure of resection: one further local excision and two palliative laser destructions. Immediate postoperative course was uneventful for 96 percent; there was one death from perineal gangrenous infection, four cases of hemorrhage, and three urinary retentions. Subsequently one case of transient fecal incontinence and 11 medically managed stenoses were noted. Mean size of resected tumor was 5.4 (range, 1-17) cm. Deep excision margins concerned the rectal muscular layers in 199 patients (96 percent) and perirectal fat in 8 (4 percent). Specimen margins were negative for cancer in 175 (85 percent) and positive or unknown in 32 cases. Histologic evaluation demonstrated in situ cancer in 28 (14 percent) and invasive carcinoma in 9 (4 percent). In three patients (1 percent), two abdominoperineal resections were immediately performed (one T2 with a mucinous contingent, one T3) and one adjuvant radiotherapy (one undifferentiated T2). Four patients (2 percent) did not return for postoperative evaluation. For the remaining 198 patients, mean follow-up was 74 +/- 34 (median, 75; range, 1-168) months. Forty-four died from unrelated causes. Recurrence occurred in seven (3.6 percent) and was malignant in two, who subsequently died. Specific recurrence-free probability was 99.5 percent at one year, 96 percent at five years, and 95 percent at ten years. A lesion size >6 cm (10 vs. 1 percent for smaller tumors) and the presence of an invasive carcinoma (20 vs. 3 percent without invasive carcinoma) were significantly associated with an increased probability of recurrence at five years. CONCLUSION: Providing that adequate intraoperative exposure is obtained and advanced malignant tumors receive immediate secondary treatment, transanal resection of clinically benign, large rectal villous adenomas is safe and effective. It is an alternative to rectal resection, which exposes the patient to potentially adverse effects, and also to destructive procedures, which preclude any histologic evaluation of the tumor.     

Enteropathy-associated T-cell lymphoma: a diagnostic challenge

Diagnosis of refractory celiac disease (CD) is based on exclusion of other disorders, persistence of malabsorptive symptoms and villous atrophy, despite a strict gluten-free diet for at least 6-12 months. Detection of alterations in the intraepithelial lymphocyte population is crucial for diagnosis. A subgroup of patients with refractory CD may develop severe complications such as enteropathy-associated T cell lymphoma (EATL). We present the case of a patient with longstanding silent CD who developed EALT, highlighting the challenge posed by the diagnosis and treatment of this entity.