Endoscopic diagnosis of follicular lymphoma with small-bowel involvement using video capsule endoscopy and double-balloon endoscopy: a case series.

The aims of this study were to compare the detection rates of gastrointestinal follicular lymphoma lesions by video capsule endoscopy (VCE) and double-balloon endoscopy (DBE), and to determine the pathologic diagnostic yields of DBE-directed biopsies. A total of 27 consecutive patients were enrolled. No significant difference in detection rates was observed in 12 patients who underwent total enteroscopy at both VCE and DBE. Pathologic diagnostic yields stratified by location were 91 % in the proximal duodenum at esophagogastroduodenoscopy, 88 % in the jejunum at antegrade DBE, 52 % in the ileum at retrograde DBE, and 57 % in the terminal ileum at colonoscopy. VCE and DBE were helpful in determining treatment in 44 % of patients.

Significance of collagenous and mucinous spherulosis in breast cytology specimens.

OBJECTIVE: Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. METHODS: A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou-stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. RESULTS: We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. CONCLUSIONS: Cytological evidence of spherulosis is a good indicator of intraductal papilloma.

EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology.

OBJECTIVE: Extracellular matrix metalloproteinase inducer (EMMPRIN) and its induced matrix metalloproteinases (MMPs) play a crucial role in tumour progression, invasion and metastasis. EMMPRIN expression has been demonstrated in several tumours, but its expression profile in thyroid cancer remains unclear. METHODS: We evaluated the expression profile of EMMPRIN at various stages of differentiation of thyroid carcinoma, including 20 cases of well-differentiated papillary carcinoma (WDPC), 15 cases of papillary carcinoma with a poorly differentiated carcinoma component (PC/PDC) and four cases with an undifferentiated carcinoma (UDC) component, using paraffin-embedded sections for immunohistochemical stains. Also, we used 32 fine needle aspiration cytology and imprint smears from the same cases for immunocytochemical stains. The staining results were evaluated with a scoring system. RESULTS: Immunohistochemical staining showed that EMMPRIN expression was absent or weak in almost all WDPC specimens, whereas it was moderate or strong in PDC and UDC components. In tumours that showed a gradual morphological transformation from WDPC to PDC components, the expression of EMMPRIN was progressively stronger from the areas of WDPC to those of PDC. WDPC, PC/PDC and UDC had expression scores of 4.9, 45.0 and 245.7, respectively. Results of immunocytochemical staining showed almost the same staining profile as those of immunohistochemical staining. The cytological atypia of EMMPRIN-positive cells was greater than that of negative cells. CONCLUSION: These results indicated that EMMPRIN expression correlates significantly with the degree of dedifferentiation of thyroid carcinoma. This study demonstrates the feasibility of expression of EMMPRIN using fine needle aspiration samples. Therefore, immunocytochemical analysis of EMMPRIN may be a novel aid to evaluate the differentiation of thyroid carcinoma.

Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma.

OBJECTIVE: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. METHODS: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. RESULTS: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP. CONCLUSIONS: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.

Regulation of splicing by MBNL and CELF family of RNA-binding protein.

Myotonic Dystrophy (DM), the most common form of adult-onset muscular dystrophy, comprises at least 2 subtypes, DM1 and DM2. DM1 is caused by the expansion of a CTG repeat located in the 3' untranslated region of the DM protein kinase (DMPK) gene. Recently, the expansion of a CCTG tetranucleotide repeat located in the first intron of the ZNF9 gene was identified as the mutation responsible for DM2. Since both DM1 and DM2 are caused by the expansion of repetitive sequences, some common factors that interact with these sequences might be involved in the pathogenesis of DM. MBNL1 is a candidate for such factors and is thought to be sequestered by the expanded forms of DM transcripts.

Hemolytic uremic syndrome following autologous peripheral blood stem cell transplantation in a patient with malignant lymphoma.

Hemolytic uremic syndrome (HUS) has been reported in patients receiving bone marrow transplantation. However, only a few cases of HUS following autologous peripheral blood stem cell transplantation (PBSCT) have been reported. We present a case of HUS developing after autologous PBSCT in a 40-year-old man with non-Hodgkin's lymphoma. It appears that the chemotherapeutic agents administered during the conditioning regimen for PBSCT may have played an important role in the development of HUS in our patient. In the present case, the combination therapy of vincristine, methylprednisolone, and ticlopidine hydrochloride was effective.

Immunohistochemical study on VEGF expression in endometrial carcinoma--comparison with p53 expression, angiogenesis, and tumor histologic grade.

OBJECTIVE: Vascular endothelial growth factor (VEGF)--that activates endothelial cell growth--has been considered to induce angiogenesis, which is indispensable to tumor-genesis and progression. In this study, an immunohistochemical analysis was carried out to clarify the correlation of VEGF expression with angiogenesis, p53 expression--of which the wild-type is considered to suppress VEGF expression--and histologic grade in endometrial carcinoma. STUDY DESIGN: Immunohistochemical staining for detecting VEGF protein, factor VIII-related antigen of endothelial cells, and p53 protein was performed by the labeled streptavidin-biotin method on the formalin-fixed and paraffin-embedded tumor tissue of 104 patients with endometrial (endometrioid) carcinoma, including 69 with well-differentiated, 25 with moderately differentiated, and ten with poorly differentiated adenocarcinoma. RESULTS: The labeling index of p53 expression was 19.9+/-28.8% in the high VEGF group, whereas in the low VEGF group it was 12.2+/-17.0%, showing that VEGF expression was significantly correlated with p53 expression (P<0.05). VEGF expression, however, was not correlated with either the number of microvessels in the tumor area or tumor histologic grade. CONCLUSION: VEGF expression was not a single specific indicator of angiogenesis in endometrial carcinoma, whereas it was significantly correlated with p53 expression.

Interaction of 6-p-toluidinylnaphthalene-2-sulfonate with beta-cyclodextrin.

The interaction of 6-p-toluidinylnaphthalene-2-sulfonate (TNS) with beta-cyclodextrin was investigated in 0.1 M phosphate buffer at pH 7.4 by fluorescence spectroscopy. Using the fluorescence enhancement of TNS in the presence of beta-cyclodextrin, the thermodynamic parameters for the formation of two kinds of the inclusion complex (molar ratio of beta-cyclodextrin to TNS = 1:1 and 2:1) were determined as follows: delta G degree 1 (1:1 complex) = -20.0 kJ mol-1 at 25 degrees C, delta H degree 1 = -19.6 kJ mol-1, delta S degree 1 = -1.7 J mol-1 K-1, delta G degree 2 (2:1 complex) at 25 degrees C = -6.14 kJ mol-1, delta H degree 2 = -2.80 kJ mol-1, delta S degree 2 = 16.7 J mol-1 K-1. From the thermodynamic parameters, the main driving force for the 1:1 inclusion complex formation was considered to be the van der Waals-London dispersion force, while the contribution of the hydrophobic interaction was small. Also, the hydrogen bonding was suggested to contribute to the inclusion complex formation. The main driving force for the 2:1 inclusion complex formation was the hydrophobic interaction. Also, from the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structure was determined and discussed in connection with the thermodynamic parameters.

Immunocytochemistry of collagenase expression in transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate the usefulness of collagenase immunocytochemistry as well as its immunohistochemistry in assessing the correlation with prognostic factors in transitional cell carcinoma (TCC) of the urinary bladder. STUDY DESIGN: We investigated the expression of collagenase in catheterized urine and histologic specimens from 38 patients with TCC and 20 cases with benign lesions of the urinary tract. RESULTS: Thirteen (34.2%) and 17 (44.7%) patients with TCC showed positive expression of collagenase on cytologic and histologic specimens, respectively, whereas in no cases with benign lesions was such expression found (P < .01). Invasive and nonpapillary TCC had higher positive rates than noninvasive and papillary TCC. Grade 3 TCC was positive at a higher rate than was grade 2, whereas there were no positive cases with grade 1. Collagenase expression did not correlate significantly with stage. CONCLUSION: Collagenase expression in urinary TCC correlated well with tumor growth pattern, pathologic grade and invasiveness of the carcinoma; all are known to be prognostic factors. The application of collagenase immunostaining to urinary cytology is very useful for assessing prognosis in TCC.

Usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma.

OBJECTIVE: To evaluate the usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma. STUDY DESIGN: A total of 210 patients with ovarian carcinoma were investigated by endometrial aspiration cytology. RESULTS: Fifty-five of 210 patients (26.2%) had positive endometrial aspiration cytology. The positive rates of endometrial cytology were 3.9% in stage I, 23.8% in stage II, 36.5% in stage III and 53.3% in stage IV. When classified by histologic type, the positive rates of endometrial cytology in patients with serous adenocarcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma, undifferentiated carcinoma and yolk sac tumor were 38.9%, 11.8%, 21.1%, 16.7% and 16.7%, respectively. One hundred twenty-eight of 210 patients (61.0%) were positive on peritoneal cytology, and 54 of these 128 cases (42.2%) were also positive on endometrial cytology. The positive rates of endometrial cytology were especially high in patients with serous adenocarcinoma (51.2%) and those with clear cell adenocarcinoma (40.0%) among those who were positive on peritoneal cytology. Of 74 patients who were negative on peritoneal cytology, only one (1.4%) with mucinous adenocarcinoma had positive endometrial cytology. Hysterectomy was performed on 130 patients, and the positive rate of endometrial cytology was 100% in 4 patients with endometrial invasion and 15.9% in 126 cases without invasion. CONCLUSION: Endometrial aspiration cytology can detect ovarian carcinoma cells not only in patients with endometrial involvement but also in patients with positive peritoneal cytology. Endometrial aspiration cytology appears to be useful for the preoperative diagnosis of ovarian carcinoma.

[Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF].

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.

[Detection of DNA specific for Aspergillus species in serum samples from two patients with invasive pulmonary aspergillosis].

We investigated the possible presence of DNA specific for Aspergillus species in serum samples of two patients who were strongly suspected for invasive pulmonary aspergillosis (IPA) by a nested polymerase chain reaction (PCR) method. Both patients were diagnosed as having acute myelogenous leukemia and treated with induction chemotherapy. During chemotherapy-induced granulocytopenia, they complained of high fever, and the chest X-rays indicated infiltration shadows in their lungs. They were treated with antibiotics intravenously, but no clinical improvement was observed. As the results of the nested PCR were positive at the acute stage of infection, amphotericin B i.v. and granulocyte colony stimulating factor s.c. administrations were started in both cases. In case 1, the infectious disease improved and the nested PCR results turned negative after treatment. In case 2, in spite of the progression of the disease, the nested PCR results turned negative during treatment. Although we consider this method very useful for the diagnosis of IPA, further prospective evaluation with a large clinical population sample is required.

[Effects of thyrotropin-releasing hormone (TRH) on status epilepticus in rats].

Recent studies have demonstrated that intramuscular administration of thyrotropin-releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db-cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of liposome-entrapped lidocaine on limbic status epilepticus in rats].

Liposomes (LIPO), which are concentric lipid layers alternating with aqueous compartments, have been suggested as a potential carrier for various drugs. In the previous studies, we have demonstrated that anticonvulsant drugs such as valproic acid, phenytoin, and DN-1417 (an analog of thyrotropin-releasing hormone) entrapped into LIPO exert more prominent therapeutic efficacy than parent drugs. In the present study, we examined the comparative effects of Lidocaine (LDCA) which acts as a proconvulsant as well as an anticonvulsant, and LIPO-entrapped LDCA (LDCA-L) on limbic status epilepticus originating in the amygdala (AM) of rats. LDCA (LDCA hydrochloride) was dissolved in distilled water as a vehicle at a concentration of 2.5 mg/ml or 10 mg/ml. LIPO and LDCA-L were prepared from L-alpha-phosphatidylcholine, cholesterol, and stearylamine. Status epilepticus was induced by intra-AM injection of combined dibutyryl (db)-cAMP-200 micrograms/ethylene diaminetetraacetic acid (EDTA)-67.2 micrograms through the implanted cannula. The animals were divided into 4 groups which received vehicle (n = 6), LIPO (n = 5), LDCA (n = 9), and LDCA-L (n = 10). LDCA group was subdivided into 5 mg/kg (n = 4) and 20 mg/kg (n = 5) groups. LDCA-L group was treated with 5mg/kg (n = 4) or 20mg/kg (n = 6). All drugs were intravenously given at a volume of 2ml/kg via teflon tube previously inserted into cervical vein 30 min after db-cAMP/EDTA injection. Vehicle or LIPO alone did not alter the pattern of electroclinical ictal responses produced by intra-AM injection of db-cAMP/EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thrombotic thrombocytopenic purpura (TTP) in which plasmapheresis was ineffective but vincristine slow infusion therapy was effective with long-term remission].

A 38-year old female patient with thrombotic thrombocytopenic purpura (TTP) did not respond to plasmapheresis and treatment with corticosteroids and antiplatelet agents but did respond to subsequent high-dose gamma-globulin therapy and vincristine slow infusion therapy. Remission, thought to be due to vincristine, was achieved. The administration schedule of vincristine was 1 or 2 mg once a week by intravenous drip infusion over a period of 6 to 8 hr. Improvement tended to be seen after the 6th administration, and remission was achieved after the 12th administration (total dose: 15 mg), and continues to the time of this writing. In this case, it was thought that vincristine inhibited a certain excessive reaction in the process of PAIgG-related platelet consumption. We conclude that vincristine should be administered at least 5 to 6 times, and the therapeutic method should be established based on the experience in a larger number of clinical cases.

[Efficacy of combination with granisetron and methylprednisolone for nausea, vomiting and appetite loss in remission induction chemotherapy of acute myeloid leukemia--a randomized comparative trial between granisetron alone and granisetron plus methylprednisolone].

The prevention of nausea, vomiting and appetite loss induced by remission induction chemotherapy for acute myeloid leukemia was compared by randomization between granisetron alone and combination with granisetron plus methylprednisolone. Granisetron was administered at 40 micrograms/kg during chemotherapy, and methylprednisolone was administered concomitantly at 125 mg/body for 3 days or more in the combination group. The single and combination groups comprised 14 and 13 patients, respectively, and there was no significant difference between the background of both groups. To evaluate the effect they were scored according to 4 grades, and evaluated every 24 hours from the start of chemotherapy to 5 days after its completion. The complete inhibition rate of vomiting was as high as 71.4% and 92.3% in the single and combination groups, respectively, showing no significant difference. The grade of vomiting was mild in both groups. Nausea was noted in 71.4% and 46.2%, respectively, and the inhibitory effect tended to be higher in the combination group. Appetite loss developed in 92.9% and 41.7%, respectively, and the prevention effect was clearly higher in the combination group. The prevention effects on nausea 7, 8 and 10 days after the start of chemotherapy, on appetite loss 2-10 days after it, and 2-5 days after its completion, were higher in the combination group. Granisetron revealed an excellent inhibitory effect on vomiting induced by remission induction chemotherapy for acute myeloid leukemia, but combination with granisetron and methylprednisolone was considered useful for nausea in the latter half of the treatment period and for appetite loss during the whole period.

Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease.

BACKGROUND: The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. AIM: To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease. METHODS: Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays. RESULTS: Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively). CONCLUSION: The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.