Comprehensive diagnostic ability of endocytoscopy compared with biopsy for colorectal neoplasms: a prospective randomized noninferiority trial.

BACKGROUND AND STUDY AIMS: Endocytoscopy enables observation at 450-fold magnification during gastrointestinal endoscopy, allowing on-site "optical biopsy." We compared the accuracies of endocytoscopy and standard biopsy for the diagnosis of colorectal neoplasms. PATIENTS AND METHODS: We performed a randomized, controlled, open-label trial of patients with colorectal lesions (≥ 5 mm) detected during colonoscopy in a tertiary referral center. We randomly assigned the 203 detected lesions of 170 eligible patients to either the endocytoscopy or standard biopsy group. An on-site endoscopist assessed the histopathology of the endocytoscopy group lesions according to the endocytoscopic findings, whereas a pathologist later assessed standard biopsy group lesions by microscopic examination of the biopsy specimens. We calculated the diagnostic accuracies in both groups with reference to the final histopathology of the resected specimens. The primary endpoint was to determine whether the diagnostic accuracy of endocytoscopy for neoplastic lesions was noninferior to that of standard biopsy (with a predefined noninferiority margin of 10%). Analyses were by intention-to-treat and per-protocol. The study is registered, number UMIN000003923. RESULTS: Overall, 102 lesions in the endocytoscopy group and 101 in the standard biopsy group were available for primary outcome analysis. There were no complications. The diagnostic accuracy of endocytoscopy for the discrimination of neoplastic lesions was 94.1% (95% confidence interval 87.6% to 97.8%), whereas that of standard biopsy was 96.0% (90.2% to 98.9%), which is within the noninferiority margin (absolute difference -1.9%, -8.6% to +5.0%). CONCLUSIONS: Endocytoscopy is noninferior to standard biopsy for the discrimination of neoplastic lesions. With its advantage of providing an on-site diagnosis, endocytoscopy could provide a novel alternative to standard biopsy in routine colonoscopy.

Recent advancement of observing living cells in the esophagus using CM double staining: endocytoscopic atypia classification.

Magnification endoscopy enables in vivo evaluation of gastrointestinal mucosa. Furthermore, endocytoscopy (ECS) with ultra-high magnification enables in vivo observation of cellular atypia during routine endoscopic examination. The purpose of this study is to clarify the efficacy of ECS and endocytoscopic atypia (ECA) classification in various types of benign and malignant pathology in the esophagus. Consecutive 110 patients, who underwent ECS in our institution from March 2003 to December 2009, were included in this study. One hundred and forty-six esophageal lesions were classified according to ECA classification, and these endocytoscopic images were compared with histological images. We categorized endocytoscopic images into five categories according to size and uniformity of nuclei, number of cells and regularity of cellular arrangement. Eighty-one out of 89 ECA-1 to ECA-3 lesions (91.0%) corresponded to Vienna categories 1 to 3. Seventy-one out of 84 ECA-4 or ECA-5 lesions (91.2%) corresponded to Vienna category 4 or 5. Overall accuracy of ECS was 91.3%, providing images similar to conventional hematoxylin and eosin staining. In addition, with ECS, we can take an 'optical biopsy' even in patients with cardiovascular disease without interrupting anticoagulant therapy. A newly designed single charge-coupled device endocytoscope allows observation of target tissue noninvasibly from regular magnification to ultra-high magnification. The development of ECS has opened the door to in vivo cellular imaging, enabling endoscopic diagnosis of tissue cytological atypia during routine endoscopic examination.

Diagnosis of colorectal lesions with a novel endocytoscopic classification - a pilot study.

BACKGROUND AND STUDY AIMS: Recent advances in endocytoscopy have enabled in vivo evaluation not on ly of structural atypia, but also of cellular atypia with observation of lumens and nuclei in the surface layer of the mucosa. The aim of this prospective pilot study was to evaluate the usefulness of our novel endocytoscopic classification in colorectal lesions. PATIENTS AND METHODS: A total of 206 consecutive patients were enrolled in the study and underwent endocytoscopic examination. Endocytoscopic images were stored electronically and two endoscopists blinded to the findings at live examination assigned them diagnoses using the endocytoscopic (EC) classification. The endocytoscopic diagnosis was then compared to the final histopathological diagnosis. RESULTS: In all, 196 patients with 213 specimens were available for analysis. All normal mucosae were classified as EC1a and all hyperplastic polyps as EC1b. Dysplasias were mainly classified as EC2, while massively invasive submucosal cancers (SMm) or worse, which have the possibility of metastasis, were mainly EC3b. Assuming that an EC1b classification was diagnostic of hyperplastic polyps, we were able to differentiate nonneoplastic from neoplastic lesions with a sensitivity of 100 % and a specificity of 100 % (P < 0.05). Assuming that an EC3b classification was diagnostic of SMm or worse, we were able to differentiate "SMm or worse" from other neoplastic lesions (dysplasias and slightly invasive submucosal cancers) with a sensitivity of 90.1 % and a specificity of 99.2 % (P < 0.05). CONCLUSIONS: The endocytoscopic classification was particularly useful for differentiating between neoplastic and nonneoplastic lesions and between "SMm or worse" and other neoplastic lesions, which in the case of colorectal neoplasms would help to determine treatment.

Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial.

BACKGROUND AND STUDY AIMS: A newly designed magnifying endoscope featuring an endocytoscopy function provided by ultrahigh magnification was evaluated in a pilot study in patients with various types of benign and malignant pathology in the esophagus. PATIENTS AND METHODS: Seventy-five consecutive patients were included in the study from 15 March to 21 December 2005. Twenty-nine patients with specific esophageal lesions that had been detected by regular or narrow-band imaging, or both, were further evaluated using endocytoscopy, followed by tissue biopsy or resection. During the endocytoscopic examinations, the esophageal mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final histopathological diagnoses based on biopsies or resected specimens were as follows: category 1 in the Vienna classification, n = 4; category 2, n = 6; category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic diagnoses were compared with the histopathological diagnoses. RESULTS: Clear endocytoscopic images were obtained in all cases. In definitely malignant lesions, the cell nuclei had an enlarged and irregularly arranged appearance (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5) was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3 %. The overall accuracy of endocytoscopy for differentiating between nonmalignant tissue (categories 1 - 3 in the Vienna classification) and malignant tissue (categories 4 and 5) was 82 %. CONCLUSIONS: These preliminary results suggest that incorporating endocytoscopy facilities into a standard endoscope may be helpful in characterizing tissue in a variety of esophageal lesions. The potential clinical impact of this method in relation to other gastrointestinal organs requires further study.

Induction of graft-versus-host disease and a graft-versus-leukemia effect using ubenimex in a patient with infantile leukemia relapsing after an unrelated cord blood transplant.

A 20-month-old boy with infantile leukemia was treated with total body irradiation, etoposide, cyclophosphamide and unrelated cord blood transplantation with a one-antigen mismatch. He relapsed on day 100 and achieved remission after ubenimex administration, and also developed chronic graft-versus-host disease of the skin. He remained in remission for 22 months with repeated courses of ubenimex. Ubenimex may be an alternative to donor lymphocyte transfusion and may be useful for the treatment of a patient who has relapsed after cord blood transplantation.

Neurosarcoidosis without systemic sarcoidosis--case report.

A 20-year-old male presented with symptoms of isolated neurosarcoidosis including epilepsy. Magnetic resonance imaging disclosed multiple enhanced right temporal and frontal lesions. Cerebrospinal fluid examination identified mild lymphocytic pleocytosis, and histological examination of a stereotactic brain biopsy specimen demonstrated noncaseating granulomas, so fungal or other inflammatory or granulomatous diseases were excluded. The diagnosis was cerebral sarcoidosis, despite the absence of systemic manifestations. Corticosteroid therapy improved his neurological state and radiological findings. Neurosarcoidosis is a well-recognized occurrence in systemic sarcoidosis, but diagnosis may be difficult in the absence of extracerebral manifestations.

Histomorphometric characteristics and cellular kinetics of colorectal polyps with epithelial serrated proliferation adjacent to carcinoma.

Four cases of colorectal polyps with epithelial serrated proliferation (CP-ESP) with malignant transformation were studied. In CP-ESP adjacent to carcinoma, if the nuclear size in the surface layer was significantly smaller than those in the bottom and the middle layers of the crypts, the specimen was defined as zone formation positive. If there was no significant difference among the layers, the specimen was defined as zone formation negative. Cell kinetics were evaluated using Ki-67 immunostaining. The CP-ESP regions of cases 1 and 2 showed zone formation with inferior and lateral glandular branching, and were qualitatively hyperplastic on cell kinetics. Cases 3 and 4 showed inferior and lateral glandular branching with no zone formation, and were kinetically neoplastic (adenoma). The histogenesis of hyperplastic polyps with atypia (cases 1 and 2) involves the hyperplastic polyp-carcinoma sequence. In contrast, the development of tubulovillous adenoma or serrated adenoma (cases 3 and 4) may involve the tubulovillous adenoma-carcinoma or serrated adenoma-carcinoma sequence.

Successful treatment of disseminated Fusarium infection in an infant with leukemia.

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.

Effect of combined high-frequency oscillatory ventilation on rabbit alveolar type-2 cells.

The effects on lung tissue of high-frequency oscillatory ventilation combined with intermittent mandatory ventilation (HFO-IMV) were compared with those of conventional mechanical ventilation (CMV) by matching the mean tracheal pressure. Pulmonary alveolar type-2 cells and subcellular organelles from rabbit lung were morphometrically examined by electron microscopy. The volume and surface densities of lamellar bodies in alveolar type-2 cells from the animals ventilated with HFO-IMV were decreased significantly compared with those from the animals either ventilated with CMV or breathing spontaneously (control group). The cell surface to volume ratio in the HFO-IMV group showed a significant increase compared with the CMV groups, whereas other variables showed no differences between the three groups. These results suggest that the secretion of surfactant from alveolar type-2 cells was enhanced in HFO-IMV-treated animals compared with CMV-treated and control groups.

Effect of rapid-rate ventilation on the experimental diseased lung caused by meconium aspiration.

We compared rapid-rate ventilation using a conventional ventilator with slow-rate ventilation in the normal lung of 7 newborn pigs and in the diseased lung model instilled with 25% meconium solution into the trachea. The flow rate (7.5 1/min) and inspiratory:expiratory ratio (1:3) were kept constant during the experiments by using a constant-flow and time-cycled ventilator; the only change in settings was the rate. Transthoracic electrical impedance at end-expiration increased in the normal and in the diseased lung. Both mean intratracheal pressure and end-expiratory esophageal pressure increased significantly (p less than 0.05) in both models upon changing to rapid-rate ventilation. Following the increase in ventilatory rates from an initial frequency of 37.5 breaths/min to a rapid rate of 150 breaths/min, there was a significant rise in both PaO2 and PaCO2 in the normal and diseased lung models. Although rapid-rate ventilation was maintained for 1 h, the improvement in oxygenation progressively deteriorated and PaCO2 also increased further. This rise in PaCO2 returned to the control levels by decreasing ventilation to the initial rate of 37.5/min. This study demonstrates that rapid-rate ventilation using a constant-flow and time-cycled ventilator is inferior to slow-rate ventilation in the diseased lung model.

Plasma cortisol levels in paediatric anaesthesia.

We measured plasma cortisol levels during surgery in seven neonates within ten days after birth and in 14 infants ranging in age from three months to 11 months. The 14 infants were divided into two groups; Group I included eight infants in whom general anaesthesia was maintained with oxygen, nitrous oxide and a muscle relaxant, Group II, six infants in whom general anaesthesia was maintained with oxygen, nitrous oxide, halothane and a muscle relaxant. In the neonates, the changes in mean plasma cortisol levels during anaesthesia were not statistically significant. In both Group I and Group II infants, the mean cortisol levels gradually rose during anaesthesia, but the initial rise in plasma cortisol levels was suppressed in the patients who received halothane.