Routine endoscopy using a magnifying endoscope for gastric cancer diagnosis

BACKGROUND AND STUDY AIMS: It has been reported that the fine mucosal patterns of the gastric pits can be observed with magnification and this may assist in preliminary evaluation prior to histological diagnosis. The aim of this prospective study was to clarify the relationship between the fine mucosal patterns of gastric lesions and histological findings, and also to evaluate the usefulness of magnifying endoscopy during routine endoscopy. PATIENTS AND METHODS: A recently developed magnifying video endoscope, which enables magnification up to 80 times, was used for gastrointestinal endoscopy in 318 patients between January 2000 and January 2001, at the National Shikoku Cancer Center. In total, 232 lesions were detected. However, patients diagnosed by conventional endoscopy as having advanced gastric cancer, malignant lymphoma, or submucosal tumor were excluded from the study. The endoscopic findings for 211 lesions included in this study were compared with the histological findings. RESULTS: Coarse and irregular mucosal patterns were observed in elevated-type cancers by magnifying endoscopy, and in depressed-type cancers there was a finer pit pattern than in the surrounding mucosa, destruction or disappearance of the mucosal microstructure, and abnormal capillary vessels. The magnifying endoscopy results were closely related to the mucosal microstructure observed by dissecting microscopy and to the histological features. The rate of presumptive diagnosis of small gastric cancers was significantly higher when a magnifying endoscope was used compared with conventional endoscopy. In this study, the sensitivity and specificity of magnifying endoscopy as a diagnostic method were 96.0% and 95.5%, respectively. CONCLUSIONS: The fine mucosal patterns and the features of capillary vessels, which were identified with the magnifying endoscope, correlated well with the pathological diagnosis. Magnifying endoscopy will be very useful in predicting the histological diagnosis during routine endoscopic procedures.     

Clinical roles of serum autoantibody against neuron-specific enolase in glaucoma patients

In our recent papers, we found the presence of serum autoantibody against neuron specific enolase (NSE) in some glaucoma patients and suggested that this antibody might have significant roles in pathogenesis of glaucomatous optic neuropathy. In order to evaluate further the clinical roles of serum autoantibody against NSE in glaucoma, serum autoantibody against NSE was examined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) in 4 patients with ocular hypertension (OH) and 242 patients with glaucoma (normal tension glaucoma [NTG], 73 cases; primary open angle glaucoma [POAG], 169 cases), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. The titers of anti-NSE antibody showed a regular decreasing pattern with deteriorating visual field losses and glaucoma stages in POAG, especially early and late stages. However, no systematic pattern was observed in NTG. Although maximum and mean intraocular pressures (IOP)s and progression of visual field losses showed no correlation with the levels of serum anti-NSE antibody titers in either POAG or NTG, the anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. The present observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG.     

Area between the hepatic and heart curves of 99mTc-galactosyl-human serum albumin scintigraphy represents liver function and disease progression for preoperative evaluation in hepatocellular carcinoma patients

Background/purpose

We developed software to calculate the pixels of interest in the area between the hepatic and heart curves (ABC) of ^99mTc-galactosyl human serum albumin (GSA) scintigraphy. The aim of this study was to examine the accuracy of the ABC to evaluate liver function before hepatectomy.

Methods

Between January 2005 and December 2010, 205 consecutive patients who underwent initial hepatectomy were enrolled in this study. The ABC was calculated using original computer software. The area under the receiver operating characteristic curve (AUC) was calculated for evaluation of Child–Pugh score grade B (Child B), pathological chronic hepatitis (CH), and liver cirrhosis (LC).

Results

The AUC of any indicator for Child B was more than 0.900 except bilirubin. The AUC of ABC for CH and LC (AUC 0.734 each) was comparable to those of HH15 (clearance index; AUC 0.704 and 0.700, respectively) and LHL15 (receptor index; AUC 0.703 and 0.706, respectively) in multiple receiver operating characteristic comparison.

Conclusions

We have developed a novel liver function indicator, the ABC, to count radioactivity in sequence. The ABC reflects liver function according to pathological deterioration of the liver. Although the ABC gave no significant advantage compared to HH15 and LHL15, it improved the AUC evaluation by 0.028–0.034.     

Response of Human Insulinoma Cells to Extracellular Calcium Is Different from Normal B Cells

The preoperative determination of thelocalization of a small insulinoma is sometimesdifficult using routine imaging techniques. We have usedthe selective arterial calcium injection (SACI) test todetermine the location of the tumor preoperatively. Thepathophysiologic basis of the SACI test is based on theresponsiveness of insulinomas to calcium injected intothe feeding artery. In this study, we demonstrated the in vitro response of the insulinoma cellsto the extracellular calcium challenge by usingprimary-cultured insulinoma cells. Human insulinomacells were obtained from three patients. MIN6 cells(normal pancreatic B cells) were used as a control;their insulin response to various stimuli resembles thatof normal B cells. The insulin secretory dynamics inresponse to extracellular calcium were observed using a perfusion system. Second, the change ofthe concentration of cytosolic free calcium([Ca²⁺]_i) was monitored byfluorometry using fura-2/AM. When the concentration ofextracellular calcium ([Ca²⁺]_o) was changed from 2.54 mM to 10 mM, insulinsecretion from the insulinoma cells was markedlyincreased within 6 min (10- to 18-fold at maximum), andrapidly returned to the basal level; at the same time, [Ca²⁺]_i was immediatelyelevated and reached a peak within 1 min. In contrast,in the MIN6 cells, the insulin secretion and [Ca2+]iwere not significantly changed when[Ca²⁺]_o was switched to 10 mM. The results of these in vitro experiments agreedwith the clinical results of the SACI test. The positiveresponse of the insulinoma to the SACI test is probablydue to the different response of insulinoma cells to the extracellular calcium challengecompared with normal B cells. The role of[Ca²⁺]_i may be important in themechanism underlying the SACI test.     

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.     

Recurrent cellulitis due to Helicobacter cinaedi after chemotherapy for malignant lymphoma

A 62-year-old man with diffuse large B-cell lymphoma received five courses of R-CHOP chemotherapy. The patient developed cellulitis in the bilateral lower extremities without fever, and blood culture yielded Helicobacter cinaedi after five-day culture. Although the response to tazobactam/piperacillin (TAZ/PIPC) was prompt, cellulitis recurred immediately after discontinuation of the drug. Even after two months of treatment with PIPC plus amikacin followed by amoxicillin, it recurred again soon after stopping the antibiotics. H. cinaedi reportedly causes bacteremia and cellulitis in immunocompromised patients mostly in patients with acquired immunodeficiency syndrome. Only sporadic cases have been reported in association with hematological malignancies. Physicians should be aware of H. cinaedi as one of the causative pathogens of bacteremia and cellulitis in patients with hematological malignancies. Longer incubation period of blood culture is needed to detect the microbe and long-term use of antimicrobials is required to prevent recurrent cellulitis.     

A case of fulminant amoebic colitis with an abscess in the abdominal cavity rescued by conservative management

A 75-year-old man was admitted because of watery diarrhea, hematochezia and right lower abdominal pain. Many deep undermining colonic ulcers were found by colonoscopy, and we detected trophozoite amoeba pathologically. Metronidazole was administered orally from 3 days after admission. However, since CT demonstrated a huge abscess in the abdominal cavity, we performed percutaneous drainage from 17 days after admission. On day 157, the patient was discharged, because the colonic ulcers had almost healed, and trophozoite amoebas were not recognized pathologically.     

Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anti-cluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4(+) T-cell allostimulatory capacity. CD27(+) memory B cells and, more specifically, CD27(+) IgM(+) B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. CONCLUSION: Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population.     

Peutz-jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas

The unusual occurrence of an “inside-out” appendix reported here is a case of complete intussusception of the appendix of a 45-year-old woman with Peutz-Jeghers syndrome in whom the diagnosis of intussusception was made preoperatively. At laparotomy, the lead point of intussusceptum was revealed to be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion in the pancreas, and subsequent distal pancreatectomy revealed a cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and two duodenal Peutz-Jeghers syndrome polyps were foundvia intraoperative endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal wedge resection was performed for the adjoining jejunal polyps. One of the two duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the first report of complete intussusception of the appendix caused by a Peutz-Jeghers syndrome polyp.     

Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin

Background

The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

Methods

A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.

Results

Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p????0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5???g/kg/week to 1?C3% with a dose of <1.5???g/kg/week (p????0.001), and at week 12 the rate had decreased from 44% with a dose of ??1.2???g/kg/week to 18% with a dose of <1.2???g/kg/week (p?=?0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54?C66% of patients given <1.2???g/kg/week (p????0.001), and these patients accounted for 64% of the non-responders.

Conclusions

The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.