Perforation of small intestinal during hematologic recovery in an elderly man after induction therapy for acute lymphoblastic leukemia L3

A 67-year-old man with a 7-month history of dilated cardiomyopathy was admitted to our hospital because of general fatigue, shortness of breath, and anemia on laboratory examination. Increased blasts were observed in the bone marrow. The blasts were characterized by large cells with abundant, intensely basophilic, vacuolated cytoplasm, round nuclei, and prominent nucleoli. Chromosome analysis revealed a nonrandom t(8;22)(q24;q11) chromosomal abnormality, and surface-marker analysis disclosed a positive immunophenotype for CD10, CD19, CD20, CD38, HLA-DR, FMC7, and IgM-lambda. These findings yielded a diagnosis of L3 acute lymphoblastic leukemia. The patient was treated with chemotherapeutic agents. On the 39th hospital day, during hematologic recovery after induction therapy, abdominal pain developed. Abdominal X-ray films disclosed ileus with dilatation of the small bowel and Kerckring's folds. Conservative treatment was begun but the patient died. At autopsy, intestinal perforations were observed at a site 55 cm proximal to the ileocecal junction. A specimen of perforated tissue revealed a diffuse infiltration of leukemic cells through the small bowel wall. However, bone marrow specimens showed no signs of aggravation of leukemia.     

Application of liver transplantation for familial amyloid polyneuropathy combined with Crohn's disease.

We describe the case of a 31-year-old Japanese man with familial amyloid polyneuropathy combined with Crohn's disease, who underwent living-related orthotopic liver transplantation. Although he had a 2-year history of alternating constipation/diarrhea, his bowel symptoms exacerbated severely during the period he was in our ward for pretransplant evaluation. Small bowel barium examination and gastroduodenal endoscopy showed typical features of Crohn's disease. He was diagnosed as having active Crohn's disease, and the scheduled living-related orthotopic liver transplantation was postponed. After controlling the active disease with conservative therapy for two months, he underwent living-related orthotopic liver transplantation using a graft of the left lobe from his father. Postoperative medication consisted of azathioprine, aminosalicylates, tacrolimus and steroids. His postoperative course was uneventful, and he was discharged from hospital on the 25th postoperative day. Pre- and postoperative transplant management of patients with Crohn's disease is also discussed, because it influences the clinical course of inflammatory bowel diseases.     

32-jähriger Patient mit Durchfall und akutem Nierenversagen

A 32-year-old male patient presented in the emergency department of our hospital with acute vomiting and diarrhoea. He reported occasional non-severe diarrhoea over several years in the past. Furthermore, at the time of presentation the patient had had anuria for several days. A prerenal and postrenal origin of the renal failure was excluded. A renal biopsy was performed and histopathological examination displayed findings consistent with a haemolytic-uraemic syndrome but no signs of glomerulonephritis. MRI examination of the small bowel revealed inflammatory alterations typical for Crohn's disease, even without histological verification. We describe haemolytic-waemic syndrome as manifestation of Crohn's disease for the first time.     

The value of dynamic ultrasound scanning in Crohn's disease

In a prospective, blinded study we investigated 30 patients with Crohn's disease (CD) and 27 normal controls by means of dynamic grey-scale ultrasound scan. Within a few weeks the patients were also examined by radiography of the small bowel. Of the 30 patients, 21 had CD lesion of the small bowel as judged by radiography. A target lesion at the ultrasound scan indicating thickened bowel wall was seen in 15 CD patients, of which 14 showed radiographic signs of CD in the ileum and/or right side of the large bowel, whereas one had normal radiographic findings. Seven patients out of 15 without sonographic changes had radiographic signs of CD. The patients with discrepancy between the two examinations could not be clinically characterized as an entity. None of the 27 normal controls showed signs of intestinal disease at the ultrasound examination. We conclude that dynamic grey-scale ultrasound examination is a new tool in depicting the CD lesion, but it does not seem to be able to replace the radiographic examination. However, it may find a place in the follow-up study of patients with known CD, thereby avoiding repeated radiographic examinations. Furthermore, the possibility of diagnosing abscesses and fistulae by sonography is well known and has relevance in CD.     

Granulocytic sarcoma of the jejunum: a rare cause of small bowel obstruction

We report the case of a 40-yr-old man presenting with symptoms of small bowel obstruction. Small bowel x-rays revealed a stricture of the mid-jejunum. Push enteroscopy found a polypoid mass at 1 meter of the ligament of Treitz. Histopathological examination of the biopsy and surgical specimens showed a diffuse infiltrate of the mucosa made of medium to large cells, which were stained on immunohistochemistery by the leucocyte marker CD45 and the histiocyte/monocyte marker CD68 but were negative for the B and T cell markers. Cytological examination of the ascitic fluid revealed many myelobasts with cytoplasmic Auer rods and positive myeloperoxidase staining. There was no evidence of blood or bone marrow involvement suggestive of acute leukemia or myeloproliferative disorders. These findings were consistent with the diagnosis of preleukemic granulocytic sarcoma (or chloroma). Chemotherapy led to complete remission, but 21 months later the patient developed an acute myeloid leukemia. He died from arpergillus pneumonitis, 10 months after bone marrow allograft. Preleukemic granulocytic sarcoma of the small bowel is a rare condition and its diagnosis is usually not easy, requiring histochemical or immunohistochemical studies. Most cases have progressed to acute myeloid leukemia.     

Acute myelocytic leukemia (M0) in an elderly patient with relapsed granulocytic sarcoma (M7) of bone during the second period of complete remission 5 years after onset]

A 75-year-old man was admitted because of right knee joint pain in December 1999. He had suffered from acute myelocytic leukemia (AML: M0) in November 1994 and achieved the first complete remission (CR) then. His AML relapsed in August 1996, but fortunately he achieved a second CR. Radiographical bone examination revealed osteolytic lesions in his right knee and bone scintigraphy showed uptake in the right knee and the middle part of the left femur. MRI also revealed a low attenuation signal in the left femur. He had no abnormal findings in peripheral blood or bone marrow. Histological examination of the biopsied bone tissue showed a diffuse proliferation of round cells with medium-sized or large nuclei. These cells were histochemistrically negative for myeloperoxidase and naphtol-ASD-chloroacetate esterase, and were also negative for lysozyme, cytokeratin 7, 9, 20, EMA, CEA, CD3, CD79a on immunohistochemistry, but were positive for CD43, CD56. In immunophenotypic analysis of these cells by flow cytometry, CD7, CD13, CD33, CD41, CD56 were revealed to be strongly positive. On the basis of these findings we diagnosed these tumors as granulocytic sarcomas (GS), extramedullary recurrence of AML M7. Although radiation (36Gy) to these tumors brought a temporary relief of the pain, he died of systemic relapse of AML in February 2001. When presented CD7+ AML M0 had been diagnosed, but GS cells were also positive for CD 56 and CD41. Although CD56 had not been examined initially, he might have been had myeloid/NK cell precursor acute leukemia and CD41 might be acquired later in the course of the disease. It is known that AML M0, M7 and myeloid/NK cell precursor acute leukemia have poor prognoses, nevertheless he survived for 6 years. It may be that intensive and repeated chemotherapy for AML can obtain excellent outcome in the elderly cases in good systemic condition and with favourable prognostic factors.     

A case of pulmonary tuberculosis case with pancytopenia accompanied to bone marrow gelatinous transformation]

A 45-year-old man did not visit a doctor in spite of his complains, cough and sputum lasting, for six months, and he finally could not eat without beer, and as a result, he lost his body weight and currently 52 kg. He became unconsciousness, was carried to a hospital, and was referred to our hospital. His sputum examination for acid fast bacilli was smear positive, Gaffky 6, for M. tuberculosis. His chest roentogenogram revealed large cavitary lesions in bilateral lung fields. On blood examination, WBC was 1100/microL, RBC was 256 x 10(4)/microL, and PLT was 13.4 x 10(4)/microL. Total protein was 4.7 g/dl, albumin was 1.9 mg/dl, and total cholesterol was 65 mg/dl. We tried to aspirate bone marrow from his sternum, but it was impossible. Hence we did biopsy of his ilium. The pathology of his bone marrow revealed gelatinous transformation. It was thought that the marked delay in visiting a doctor caused general consumption and loss of apetite, thus led to gelatinous transformation and finally pancytopenia.     

De novo CD5-positive diffuse large B-cell lymphoma with leukemic dissemination diagnosed by immunohistochemical examinations of bone marrow clot sections

A 61-year-old male visited his doctor in October 2000 because of a high fever. Laboratory examination revealed leukocytosis with blast-like cells and thrombocytopenia. He was referred and admitted to our hospital in November 2000. Although he had mild splenomegaly, he had no lymphadenopathy on the first admission. The white blood cell count was 10,520/microliter with 45% blast-like cells and the platelet count was 51 x 10(3)/microliters. Bone marrow aspiration revealed 82% blast-like cells, which were positive for CD5, CD10, CD13, CD19, and CD20. Immunohistochemistry of the bone marrow clot sections revealed blast-like cells were positive for CD5, but negative for TdT, CD23 and cyclin D1. We diagnosed the patient as having de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) with leukemic dissemination. He obtained a complete remission after two courses of CHOP therapy. The third chemotherapy was postponed because of strangulation of the intestine. He relapsed and died in spite of the third chemotherapy. CD5-positive DLBCL is one of the established disease entities that requires an appropriate therapy regimen because it is characterized by elderly onset, extranodal involvement, and a poorer prognosis.     

Gluten tolerance in adult patients with celiac disease 20 years after diagnosis?

BACKGROUND AND OBJECTIVE: Celiac disease (CD) is believed to be a permanent intolerance to gluten. A number of patients, however, discontinue the gluten-free diet (GFD) without developing symptoms or signs. The aim of our study was to investigate whether CD patients are capable of developing tolerance to gluten. METHODS: All 77 adult patients from our hospital known to have biopsy-proven CD for more than 10 years were invited to participate. We investigated symptoms, gluten consumption, antibodies for CD and other autoimmunity, human leukocyte antigen (HLA)-typing, bone mineral density, and performed small bowel biopsies. Tolerance was defined as no immunological or histological signs of CD while consuming gluten. RESULTS: Sixty-six patients accepted participation, but after review of the diagnostic biopsies 53 were found to have true CD. Twenty-three percent of patients had a gluten-containing diet, 15% admitted gluten transgression and 62% followed the GFD. Patients on a GFD had significantly more osteoporosis. Normal small bowel mucosa was found in four of eight on gluten-containing diet and in four of four with gluten transgression. Two patients were considered to have developed tolerance to gluten. One of them was HLA-DQ2/DQ8 negative. CONCLUSION: Development of tolerance to gluten seems possible in some patients with CD. Further follow-up will show whether this tolerance is permanent or only a long-term return to latency. This feature may be associated with genetic characteristics, especially with HLA genotypes that differ from DQ2 or DQ8. More insight into the mechanisms of the development of gluten tolerance may help to distinguish those CD patients that might not require life-long GFD.     

A unique case of collagenous colitis presenting as protein-losing enteropathy successfully treated with prednisolone

A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa, and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon, particularly in the ascending portion, was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy （PLE） without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.     

Improvement with interferon-alpha therapy and splenectomy in hairy cell leukemia of European-American type]

A 61-year-old man was admitted to our hospital in April 18, 1988, with dyspnea and gingival bleeding. Physical examination revealed marked splenomegaly, and peripheral blood showed severe pancytopenia with 38% abnormal mononuclear cells. The abnormal cells were characterized by a hairy appearance under a phase contrast microscopy, and strong tartrate-resistant acid phosphatase activity. These cells reacted with CD19, CD25 and CD11c monoclonal antibodies by the immunostaining method. Bone marrow aspiration failed and bone marrow biopsy revealed diffuse proliferation of hairy cells (HC) with moderate fibrosis. In addition, the staining pattern of HC peroxidase is similar to that found in megakaryocyte series. He was diagnosed as HCL of the European-American type based on these findings. Interferon (IFN)-alpha was administered at a daily dosage of 3 x 10(6) IU by intramuscular injection. Although splenomegaly and hematological conditions improved gradually, he received splenectomy because of his incomplete hematological improvement. Normalization of peripheral blood cell counts and a marked decrease of HC in bone marrow were obtained. Tubuloreticular structure and tubular confronting cisternae were seen in peripheral mononuclear cells during IFN therapy.     

Idiopathic CD4+ T lymphocytopenia disclosed by the onset of empyema thoracis

A 56-year-old man was admitted to our hospital in December 1996 due to empyema thoracis. A laboratory examination revealed lymphocytopenia and CD4+ T lymphocytopenia (<300 cells/ microl). No evidence for a human immunodeficiency virus (HIV) infection was found. No malignant, hematological or autoimmune disease was detected. We thus diagnosed this case as being idiopathic CD4+ T lymphocytopenia (ICL). During his hospital treatment, he was affected with cytomegaloviral retinitis and cured by therapy. His subsequent treatment went well without a recurrence of severe infection although a low CD4+ T lymphocyte count continued after the recovery from empyema thoracis.     

A rare cause of refractory ascites in a child: familial Mediterranean fever

Familial Mediterranean fever (FMF) is hereditary episodic febrile syndrome characterized by acute attacks of fever and serosal inflammation, generally lasting 1–3 days and resolves spontaneously. Apart from abdominal pain, patients may present with variety of abdominal manifestations such as acute peritonitis, mechanical intestinal obstruction, diarrhea, bowel infarction, amyloidosis and small amounts of peritoneal fluid during the acute attacks. A 6-year-old boy was admitted with massive ascites. After extensive laboratory investigations, no causative agent could be identified. On subsequent days, he developed fever and skin eruptions. Acute-phase reactants were increased. A second tomography revealed cystic fluid collection near the anterior side of spleen that invades the stomach. An exploratory was performed and histopathological examination of the all resected specimens revealed mix inflammatory cell infiltrate associated with severe myofibroblast proliferation suggesting chronic inflammatory process on the mesenteric region. A diagnosis of FMF was suspected based on the clinical, laboratory and histopathological findings, and a trial of colchicine therapy initiated. Ascites and other serosal inflammations improved within 1 week without any recurrence during the next 12-month period on colchicine treatment. Atypical presentations of FMF have been increasingly reported. Pediatricians should keep FMF in mind in the differential diagnosis of massive ascites especially in regions where hereditary inflammatory disease are common.     

HIV associated cytomegalovirus colitis as a mimic of inflammatory bowel disease.

Cytomegalovirus (CMV) colitis may cause symptoms and signs identical to those of idiopathic inflammatory bowel disease. Although difficult to diagnose with certainty, the histological finding of cytomegalovirus inclusions in tissue from a case of suspected inflammatory bowel disease is strongly suggestive. CMV colitis is an entity almost entirely confined to cases of severe immunosuppression. The case of a 79 year old widower who was admitted to hospital with symptoms suggestive of inflammatory bowel disease is presented. Despite medical treatment his condition worsened and he developed toxic dilatation of the colon requiring colectomy. Histological examination showed a mild superficial pancolitis, with focal severe inflammation, deep fissuring ulceration, and pseudopolyposis. Abundant CMV inclusions were seen in cells associated with the ulcerating inflammatory tissue. A diagnosis of indeterminate colitis with CMV was made. The patient's condition worsened after surgery and he died a few days later despite intensive treatment, including antiviral chemotherapy directed against CMV. After death HIV serology was found to be positive. Regardless of the age and perceived lifestyle of the patient, a diagnosis of CMV colitis in someone not known to be immunosuppressed raises the possibility of HIV infection.     

Clinical examination versus neurophysiological examination in the diagnosis of diabetic polyneuropathy.

Several methods have been used to diagnose diabetic polyneuropathy and to quantitate the degree of affection of peripheral nerves. Using a newly developed scoring system we compared bedside clinical examination with neurophysiological examination in a group of 78 diabetic patients. Individual scores for clinical examination were significantly correlated with scores for neurophysiological examination (r = 0.7, p < 0.0005). All 78 patients had at least one clinical symptom or sign of polyneuropathy. Clinical examination indicated polyneuropathy in three patients with neuropathic complaints, while neurophysiological examination in these patients showed no abnormalities. In 12 out of 14 patients with normal neurophysiological sensory nerve function, clinical examination showed at least one abnormal sensory modality. Comparing the four different sensory modalities, light touch sense and pinprick sense indicated polyneuropathy better than vibration or position senses. An abnormal Hoffmann reflex of the soleus muscle was always associated with a decreased or absent ankle jerk. The scoring system for the clinical examination proved useful for diagnosing and quantitating the severity of diabetic polyneuropathy. Clinical sensory deficits could not be inferred from the results of neurophysiological testing of sensory nerve function. Pinprick sense, light touch sense, and ankle jerks were the most important parameters in the clinical diagnosis of diabetic polyneuropathy.     

Gastrocolic fistula - a rare cause of cachexia and polyneuropathy

Gastrocolic fistula is a rare clinical disorder which in the past most often occurred after gastric surgery or carcinoma of the gastrointestinal tract. However, during the last decade an increasing number of cases after benign gastric ulcers have been described. Most common symptoms have been weight loss, abdominal pain, diarrhea and copremesis. A 49-year-old cachectic patient presented with a 2-year history of abdominal discomfort and diarrhea. He reported a weight loss of 32 kg during this period and was finally unable to move because of exhaustion. Furthermore, he suffered of burning paresthesia of the legs and the abdomen. His medical history included a Billroth II operation because of recurrent ulcer disease in 1987. Barium enema revealed a gastrocolic fistula which caused small bowel bacterial overgrowth with villous atrophy and malabsorption and development of polyneuropathy. The fistula was surgically resected, and postoperatively, the patient improved and regained his weight. Gastrocolic fistula is a rare cause of diarrhea and should be considered in clinical practice. Barium enema is superior to endoscopy in detecting gastrocolic fistula.     

Rheumatoid vasculitis with multiple intestinal ulcerations: report of a case]

Rheumatoid vasculitis is a relatively uncommon complication of rheumatoid arthritis (RA). It shows wide variety of extra-articular features including skin and neurologic involvement, but rarely shows gastrointestinal involvement. We describe a 79-old-man of rheumatoid vasculitis manifesting as small bowel multiple ulcerations accompanied by perforation of the descending colon diverticulum. The patient was admitted to our hospital with rectal bleeding and severe anemia. He had had rheumatoid arthritis for more than 10 years with treatment of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose prednisone. Upper endoscopy or colonoscopy revealed no evidence of bleeding. Suddenly he developed cramping abdominal pain, and emergency operation was performed. Segments of the descending colon and small bowel were resected to reveal perforation of the descending diverticulum and severe multiple ulcer of small bowel. The pathological examination showed multiple ulcerations of the small intestine was caused by vasculitis.     

Primary splenic lymphoma with hypoplastic bone marrow

A 44-year-old man was admitted because of persistent fever and pancytopenia. Because his bone marrow was hypoplastic and the karyotype of his marrow cells was normal, he was given a diagnosis of aplastic anemia, and treated with glucocorticoids and granulocyte colony-stimulating factor. Splenomegaly was later found and a splenectomy performed: pathological findings on resected tissue specimens disclosed non-Hodgkin's lymphoma, B-cell diffuse large. The patient was transferred to our hospital, where a bone marrow biopsy revealed lymphoma cells infiltrating his hypoplastic marrow. Complex chromosomal abnormalities were detected in marrow cells, but no lymphadenopathy was observed. A diagnosis of primary splenic lymphoma with infiltration of lymphoma cells into bone marrow was made, and chemotherapy was accordingly started. After multiple cycles of chemotherapy, the patient's marrow recovered to a normal state and his karyotype abnormalities disappeared. Six months later, pancytopenia reappeared and lymphoma cells were again detected in the patient's bone marrow. We reasoned that the hypoplastic state of his bone marrow was associated with the lymphoma, and that cytokines, including interferon-gamma, may have been responsible for this association.     

An Autopsy Case of Ki-1 Lymphoma Associated with Hepatic Failure

A 62-year-old man was admitted to our hospital because of severe jaundice and fever. Physical examination demonstrated hepatosplenomegaly. The laboratory data revealed elevated serum bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase, and the reduced hepaplastin test (Normotest). Computed tomography showed hepatosplenomegaly and swelling of the paraaortic lymph nodes. Although he was treated with antibiotics and steroids, he died of hepatic failure 22 days after admission. At autopsy, his liver weighed 1910 grams, and a histological examination of the liver revealed marked infiltration of CD30 (Ki-1) positive lymphoma cells. He was diagnosed as having non-Hodgkin lymphoma, large cell anaplastic type, Ki-1 lymphoma. We herein report our findings of this very rare case of Ki-1 lymphoma associated with hepatic failure.     

A CASE OF INDETERMINATE COLITIS UNDERGOING SUBTOTAL COLECTOMY

The nomenclature inflammatory bowel disease (IBD) generally defines ulcerative colitis (UC) and Crohn's disease (CD). However, we sometimes find patients who cannot be diagnosed as UC or CD, because of the presence of both characteristics. These cases have been reported as indeterminate colitis (IC) since the first report in 1978. In our department, we have experienced IBD since 1993 (366 cases of CD), but only three cases were diagnosed as IC. Of the three, we report here the clinical and pathological features of a patient who was followed up since the diagnosis. The case was a 19‐year‐old Japanese woman without any particular past history. In December 1997, she was admitted to our hospital complaining of abdominal pain, high fever, diarrhea and fresh blood in the stool. Based on the findings of various tests, we made a diagnosis of IC, and started to treat her with prednisolone intravenous injection (i.v) at a dose of 40 mg per day. Because symptoms and signs of inflammation relapsed frequently, it was judged that there was a relative indication for surgical operation. She underwent subtotal colectomy with end‐to‐end ileorectal anastomosis on 6 January 2002. On the histopathological examination of surgical specimens, several characteristics of both UC and CD were observed. Therefore, we finally diagnosed this case as IC. After operation, she has not experienced a relapse so far and maintained fair physical condition.