2
response, suppressing the Th 2 response (4, 5). Similarly, the activation of the Th 1 response has been clearly demonstrated in celiac disease in response to gliadin (1, 2). On this basis, it is possible to hypothesize that the impairment of the Th 1 /Th 2 balance exerted by ribavirin might activate celiac disease in predisposed subjects. These data suggest that anti-endomysium antibodies should be sought prior to in- terferon-ribavirin treatment, not only in naive patients, but also in relapsers. In this setting, the physician must be particularly alert because he/she may be easily deceived by the absence of side effects during the previous interferon course. Luigi E. Adinolfi Emanuele Durante Mangoni Augusto Andreana Department of Internal Medicine Second University of Naples Naples, Italy REFERENCES 1. Nilsen EM, Jahnsen FL, Lundin KE, et al. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology 1998; 115:551– 63. 2. Hansson T, Dannaeus A, Klareskog L. Cytokine-producing cells in peripheral blood of children with coeliac disease secrete cytokines with a type 1 profile. Clin Exp Immunol 1999;116: 246 –50. 3. Bardella MT, Marino R, Meroni PL. Celiac disease during interferon treatment. Ann Intern Med 1999;131:157– 8. 4. Hultgren C, Milich D, Weiland O, et al. The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses. J Gen Virol 1998;79:2381–91. 5. Tam RC, Pai B, Bard J, et al. Ribavirin polarizes human T cell responses towards a type 1 cytokine profile. J Hepatol 1999; 30:376 – 82. Reprint requests and correspondence: Dr. Luigi E. Adinolfi, Seconda Universita ` di Napoli, Istituto di Terapia Medica, Via Cotugno 1, c/o Ospedale Gesu ` e Maria, 80135 Napoli, Italy. Received Sep. 18, 2000; accepted Sep. 25, 2000. Recidivant Midgut Neuroendocrine Tumor in a Celiac Patient TO THE EDITOR: Celiac disease is thought to be a pre- malignant disease (1–3). Intestinal lymphoma and adeno- carcinoma of ileum have been frequently associated with untreated celiac disease (3–5). Only two cases of malignant carcinoid tumor complicating celiac disease were reported some years ago (6, 7). Carcinoid tumors are among the most common tumors of the small bowel (8, 9). Here is reported the case of a 65-yr-old male admitted to hospital for an abdominal mass in June 2000. Our patient was born in 1934 and at the age of 5 was hospitalized because of growth failure. In 1970 (age 36), he was hospi- talized for occasional postprandial flushing, occasional raise in arterial blood pressure, and raise of urinary 5-HIA ex- cretion and underwent surgery for a neuroendocrine tumor of terminal ileum (excision end resection of 10 cm of ileum). In 1995, his daughter was diagnosed with symptom- atic celiac disease. In 1998 following a short period of diarrhea, he was diagnosed with celiac disease on the basis of the presence of antiendomysial antibodies in serum and villous atrophy at jejunal biopsy. Laboratory analyses and physical examination were negative, with the exception of marked dental enamel dysplasia. The patient initiated glu- ten-free diet with complete recovery from diarrhea. In June 2000 during a follow-up visit for celiac disease, a lower abdominal mass was appreciated at physical exam- ination. The patient referred also a raise in blood pressure that required treatment in the last 5 months and rare episodes of face flushing. On admission, his hematological laboratory tests were normal, 5-HIA urinary excretion was 124 mg/124 h (reference range 10 mg/24 h), serum neuron specific enolase 11 ng/ml (range 0 –12.5), serum EMA and antitissue transglutaminase antibodies were negative. Perendoscopic jejunal biopsy showed normal mucosal architecture. Peptide receptor scintigraphy with 111 In-DTPA-D-phe1- octreotide localized a positive abdominal mass in paraum- belicar area and a diffuse positivity in the pelvic area. Tomography of the abdomen confirmed the presence of an ileum-related mass. No suspected focal areas were found in the liver. No lymph node enlargement was detected. During surgery, the abdominal mass was resected and at liver exploration a number of small methastatic lesions were visible, one of which was excised. The capsulated abdom- inal mass (9 3 5 3 3 cm) was localized in the mesentery near the intestinal anastomosis of the previous operation. Other small nodules were located in the omentum and along the intestinal loops. The biopsy showed a small cell neoplasm, chromogra- nine-positive, NSE-positive, synaptophisin-positive, and fo- cal cytocheratin-positive (9, 10). Similar aspects were found at liver biopsy. After recovery from surgery, the patient initiated therapy with long-acting somatostatin analogues, still ongoing. This is the third case known of neuroendocrine tumor of ileum associated with celiac disease. In our patient, the diagnosis of celiac disease was made 28 yr after that of neuroendocrine tumor. His clinical history (growth failure, dental enamel dysplasia), however, suggests that celiac dis- ease was present in childhood in a subclinical form. The case is noticeable because of the rare disease association, already reported in literature (6, 7) and because of the recidivation of tumor occurred after a long period of time (11). Gluten in the diet of celiac people also may stimulate 608 Letters to the Editor AJG – Vol. 96, No. 2, 2001

Recidivant midgut neuroendocrine tumor in a celiac patient

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response, suppressing the Th2 response (4, 5). Similarly, theactivation of the Th1 response has been clearly demonstratedin celiac disease in response to gliadin (1, 2). On this basis,it is possible to hypothesize that the impairment of theTh1/Th2 balance exerted by ribavirin might activate celiacdisease in predisposed subjects. These data suggest thatanti-endomysium antibodies should be sought prior to in-terferon-ribavirin treatment, not only in naive patients, butalso in relapsers. In this setting, the physician must beparticularly alert because he/she may be easily deceived bythe absence of side effects during the previous interferoncourse.

Luigi E. AdinolfiEmanuele Durante Mangoni

Augusto AndreanaDepartment of Internal Medicine

Second University of NaplesNaples, Italy

REFERENCES

1. Nilsen EM, Jahnsen FL, Lundin KE, et al. Gluten induces anintestinal cytokine response strongly dominated by interferongamma in patients with celiac disease. Gastroenterology 1998;115:551–63.

2. Hansson T, Dannaeus A, Klareskog L. Cytokine-producingcells in peripheral blood of children with coeliac disease secretecytokines with a type 1 profile. Clin Exp Immunol 1999;116:246–50.

3. Bardella MT, Marino R, Meroni PL. Celiac disease duringinterferon treatment. Ann Intern Med 1999;131:157–8.

4. Hultgren C, Milich D, Weiland O, et al. The antiviral compoundribavirin modulates the T helper (Th) 1/Th2 subset balance inhepatitis B and C virus-specific immune responses. J Gen Virol1998;79:2381–91.

5. Tam RC, Pai B, Bard J, et al. Ribavirin polarizes human T cellresponses towards a type 1 cytokine profile. J Hepatol 1999;30:376–82.

Reprint requests and correspondence:Dr. Luigi E. Adinolfi,Seconda Universita` di Napoli, Istituto di Terapia Medica, ViaCotugno 1, c/o Ospedale Gesu` e Maria, 80135 Napoli, Italy.

Received Sep. 18, 2000; accepted Sep. 25, 2000.

Recidivant Midgut NeuroendocrineTumor in a Celiac PatientTO THE EDITOR: Celiac disease is thought to be a pre-malignant disease (1–3). Intestinal lymphoma and adeno-carcinoma of ileum have been frequently associated withuntreated celiac disease (3–5). Only two cases of malignantcarcinoid tumor complicating celiac disease were reportedsome years ago (6, 7). Carcinoid tumors are among the mostcommon tumors of the small bowel (8, 9).

Here is reported the case of a 65-yr-old male admitted to

hospital for an abdominal mass in June 2000. Our patientwas born in 1934 and at the age of 5 was hospitalizedbecause of growth failure. In 1970 (age 36), he was hospi-talized for occasional postprandial flushing, occasional raisein arterial blood pressure, and raise of urinary 5-HIA ex-cretion and underwent surgery for a neuroendocrine tumorof terminal ileum (excision end resection of 10 cm ofileum). In 1995, his daughter was diagnosed with symptom-atic celiac disease. In 1998 following a short period ofdiarrhea, he was diagnosed with celiac disease on the basisof the presence of antiendomysial antibodies in serum andvillous atrophy at jejunal biopsy. Laboratory analyses andphysical examination were negative, with the exception ofmarked dental enamel dysplasia. The patient initiated glu-ten-free diet with complete recovery from diarrhea.

In June 2000 during a follow-up visit for celiac disease,a lower abdominal mass was appreciated at physical exam-ination. The patient referred also a raise in blood pressurethat required treatment in the last 5 months and rare episodesof face flushing. On admission, his hematological laboratorytests were normal, 5-HIA urinary excretion was 124 mg/124h (reference range 10 mg/24 h), serum neuron specificenolase 11 ng/ml (range 0–12.5), serum EMA and antitissuetransglutaminase antibodies were negative. Perendoscopicjejunal biopsy showed normal mucosal architecture.

Peptide receptor scintigraphy with 111 In-DTPA-D-phe1-octreotide localized a positive abdominal mass in paraum-belicar area and a diffuse positivity in the pelvic area.Tomography of the abdomen confirmed the presence of anileum-related mass. No suspected focal areas were found inthe liver. No lymph node enlargement was detected.

During surgery, the abdominal mass was resected and atliver exploration a number of small methastatic lesions werevisible, one of which was excised. The capsulated abdom-inal mass (93 5 3 3 cm) was localized in the mesenterynear the intestinal anastomosis of the previous operation.Other small nodules were located in the omentum and alongthe intestinal loops.

The biopsy showed a small cell neoplasm, chromogra-nine-positive, NSE-positive, synaptophisin-positive, and fo-cal cytocheratin-positive (9, 10). Similar aspects were foundat liver biopsy. After recovery from surgery, the patientinitiated therapy with long-acting somatostatin analogues,still ongoing.

This is the third case known of neuroendocrine tumor ofileum associated with celiac disease. In our patient, thediagnosis of celiac disease was made 28 yr after that ofneuroendocrine tumor. His clinical history (growth failure,dental enamel dysplasia), however, suggests that celiac dis-ease was present in childhood in a subclinical form. Thecase is noticeable because of the rare disease association,already reported in literature (6, 7) and because of therecidivation of tumor occurred after a long period of time(11). Gluten in the diet of celiac people also may stimulate

608 Letters to the Editor AJG – Vol. 96, No. 2, 2001

Page 2: Recidivant midgut neuroendocrine tumor in a celiac patient

proliferation and activity of enterochromaffin cells, asproved by the data of increased number of enterochromaffincells and increased cell levels of 5-HT in celiac mucosa(12). The prolonged stimulation may trigger cell dysplasiaand cancer transformation. Neuroendocrine tumors of theileum are considered rare, but it is possible that a trueassociation with the more common celiac disease exists,such as for adenocarcinoma of jejunum/ileum (4, 5). Thequestion to be answered is if the association between car-cinoid and celiac disease is greater than that expected bychance alone. To answer this question, it would be necessaryto prospectively test for celiac disease all patients affectedby neuroendocrine tumors of the gut.

Roberto SottileFrancesco Percopo

Vincenzo PersicoSurgery

Carolina CiacciGastroenterology

Federico II University of NapoliNapoli, Italy

REFERENCES

1. Selby WS, Gallagher ND. Malignancy in a 19-year experienceof adult celiac disease. Dig Dis Sci 1979;24:684–8.

2. Cooper BT, Holmes GK, Ferguson R, et al. Celiac disease andmalignancy. Medicine (Baltimore) 1980;59:249–61.

3. Cooper BT, Holmes GK, Cooke WT. Lymphoma risk in celiacdisease of later life. Digestion 1982;29:17–23.

4. Petreshock EP, Pessah M, Menachemie E. Adenocarcinoma ofjejunum associated with non tropical sprue. Dig Dis Sci 1975;20:796–802.

5. Holmes GK, Dunn GI, Lochel R, et al. Adenocarcinoma of theupper small bowel complicating celiac disease. Gut 1980;211:1010–6.

6. Hallert C, Norrby K. Malignant carcinoid tumor complicatingceliac disease. Acta Med Scand 1983;213:313–6.

7. Gardner GW, Van Patter T, Murray D. Atypical carcinoidtumor of the small bowel complicating celiac disease. Cancer1985;56:2716–22.

8. Luca IC. Endocrine diffuse system—histological and func-tional aspects interrelated with the tumoral pathology. RevMed Chir Soc Med Nat Iasi 1998;102:152–6.

9. Nicholson SA, Ryan MR. A review of cytologic findings inneuroendocrine carcinomas including carcinoid tumors withhistologic correlation. Cancer Cytopathology 2000;90:148–61.

10. Ruby SG. Protocol for the examination of specimens frompatients with carcinomas of the small intestine, including thosewith focal endocrine differentiation, exclusive of carcinoidtumors, lymphomas, and stromal tumors (sarcomas): A basisfor checklists. Cancer Committee, American College of Pa-thologists. Arch Pathol Lab Med 2000;124:46–50.

11. Angeletti S, Annibale B, Marignani M, et al. Natural history ofintestinal carcinoids. Ital J Gastroenterol Hepatol 1999;31(suppl 2):S108–10.

12. Challacombe DN, Robertson K. Enterochromaffin cells andceliac disease. Lancet 1976;1:370–1.

Reprint requests and correspondence:Carolina Ciacci, M.D.,Gastroenterology, Federico II University of Napoli, Via Pansini 5,80131 Napoli, Italy.

Received Sep. 15, 2000; accepted Sep. 25, 2000.

Portal Venous Gas Associated WithNonocclusive Mesenteric InfarctionTO THE EDITOR: Portal venous gas has occasionally beenseen in severe intestinal ischemia and has been associatedwith a high mortality (1, 2). Nonocclusive mesenteric in-farction, comprising about one-fourth of intestinal infarc-tion, may result from diminished arterial perfusion causedby a low cardiac output (3). With extensive infarction, it hasalso been associated with a poor prognosis. We report a caseof portal venous gas associated with nonocclusive mesen-teric infarction, who survived after surgery.

An 83-yr-old Japanese woman, who had been hospital-ized for congestive heart failure due to mitral valve regur-gitation during the previous 9 months, was transferred to ourhospital with shock. Twelve h before admission, she hadsevere abdominal pain and bloody diarrhea. The conditiondeteriorated gradually, with increasing abdominal disten-sion, loss of peristalsis, profuse bloody diarrhea, and shock.On arrival, physical examination revealed a distended ab-domen with muscular resistance. Laboratory data were ar-terial pH 7.16, serum urea nitrogen 74.8 mg/dl, creatinine3.2 mg/dl, blood glucose 295 mg/dl, white cell count 7100/ml, hemoglobin 14.1 g/dl, and platelet count 89000/ml. CTscan of abdomen revealed large collection of portal venousgas (Fig. 1A) and dilated loops of intestine with pneuma-tosis (Fig. 1B). The patient was treated withi.v. fluids andsodium bicarbonate before laparotomy. Hypotension per-sisted despite aggressive volume resuscitation, and dopa-mine was given to maintain blood pressure. Exploratorylaparotomy revealed bloody ascites and necrotic intestinefrom proximal jejunum to splenic flexure. Surprisingly,there was a pulsated blood flow in superior mesenteric arteryat laparotomy. The necrotic intestine was resected, andjejunostomy and colostomy were created. Histologic exam-ination revealed extensive mucosal inflammation and necro-sis with areas of pneumatosis, coagulative necrosis withsevere congestion beneath the necrotic epithelium, andtransmural necrosis in some areas. Moreover, histologicfindings included the presence of copious Gram-positiverods with the characteristic appearance of clostridial species.The patient was managed with parenteral hyperalimentationand was gradually getting better after laparotomy. On day32, however, she died of pulmonary embolism despite at-tempted cardiopulmonary resuscitation.

Portal venous gas has been associated with mucosal dis-ruption due to ischemia and passage of intraluminal gas intomesenteric venous system (1, 2). However, the histologicfinding in the intestinal wall of numerous large Gram-

609AJG – February, 2001 Letters to the Editor