Search

AIM To determine the usefulness of assigning narrow-band imaging (NBI) scores for predicting tumor grade and invasion depth in colorectal tumors. METHODS A total of 161 colorectal lesions were analyzed from 138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa (SM) invasion were determined histopathologically. Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions. Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores. RESULTS NBI findings that correlated with a high tumor grade were associated with the “regular/irregular” (P < 0.0001) surface patterns and the “avascular area” pattern (P = 0.0600). The vascular patterns of “disrupted vessels” (P = 0.0714) and “thick vessels” (P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 μm. In our model, a total NBI-finding score ≥ 1 was indicative of a high tumor grade (sensitivity: 0.97; specificity: 0.24), and a total NBI-finding score ≥ 9 (sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 μm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 μm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology. CONCLUSION Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.

A 27-year-old woman with Crohn's disease, who had sustained clinical remission for two years following treatment with mesalazine and nutrition therapy, was admitted to our hospital complaining of dry cough, mild dysphagia, and slight fever. A computed tomography of the chest demonstrated an increase in the thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and edematous mucosa with whitish granular lesions in the trachea and main carina. Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was treated with 40mg/day prednisolone. Her symptoms improved immediately. However, dry cough recurred two months after prednisolone treatment, and further treatment with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's disease is rare, with only 13 cases having been reported. Tracheal involvement should be considered in Crohn's disease patients with respiratory symptoms.

In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater.

In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans . In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

The deep-seated mycosis occurred in immunocompromized patients. Normally, the deep-seated mycosis became sever infection because of the defects of host defense or the adverse effects of antifungal agents. The major factors of the reason on the severity of the deep-seated mycosis depends on the pathogenesity and the drug resistance for antifungal agents in infected fungi. The clinical factors related with hosts defenses are important to the other reason on the severity. We investigated that the multiple drug resistant (MDR) mechanism may be one of the major roles plays in the azole resistant Candida albicans strains isolated form the patients with oropharyngeal candidiasis infected HIV. We analyzed which clinical factors are related with the prognosis of the patients with pulmonary cryptococcosis and aspergilloma. The titer of cryptococcal capsular antigen was earlier improve in the patient without underline disease than in the patients with underline diseases diagnosed pulmonary cryptococcosis. CRP was higher in the death cases in the patients with pulmonary aspergilloma, compared with alive cases.

We compared the specificities and sensitivities of four tests used for the serodiagnosis of candidemia in 39 patients with candidemia, including 10 patients with superficial Candida colonization, 10 patients with deep mycosis, and 20 healthy subjects. The results obtained by the dot immunoblotting assay for detecting the enolase antigen (48 kDa) were compared with those of assays for detecting mannan antigen, heat-labile antigen (a threshold titer of four times), and beta-glucan (> or = 60 pg/ml). Enolase antigen was detected in 28 (71.8%) patients with candidemia, while 30 (76.9%), 10 (25.6%), and 27 (84.4%) patients were positive for the heat-labile antigen by the Cand-Tec assay, the mannan antigen by the Pastorex Candida assay, and beta-glucan by the limulus test, respectively. Ten patients with superficial Candida colonization, 5 patients with invasive pulmonary aspergillosis, 5 patients with cryptococcosis, and 20 healthy subjects were negative for both enolase antigen and mannan antigen. Two patients with superficial Candida colonization, one patient with invasive pulmonary aspergillosis, and two patients with cryptococcosis were positive by the Cand-Tec assay. The beta-glucan concentration was more than 60 pg/ml in all patients with invasive pulmonary aspergillosis; however, it was less than 10 pg/ml in all patients with cryptococcosis. The specificity of enolase antigen in the serodiagnosis of candidemia was 100%, but the sensitivity was 71.8%. The specificity and sensitivity of Cand-Tec, the assay for mannan antigen, and the assay for beta-glucan were 76.9 and 87.5%, 25.6 and 100%, and 84.4 and 87.5%, respectively. Our results demonstrated that antigen detection tests are useful for the diagnosis of candidemia; however, none is satisfactory for the serodiagnosis of candidemia. We suggest that a combination of two assays may increase the accuracy of diagnosis of candidiasis.

BALB/cマウスにC. albicans 7N株1.0×106CFUを静注した場合,無処置群は2ヶ月間全例生存したが,抗TNFα抗体投与群では生存率の低下が認められた.これに対し,抗γIFN抗体投与群では全例が生存し,生存率に差を認めなかった.C. albicans 7N株1.5×106CFUを静注した場合,無処置群は5日までに,全例が死亡した.抗γIFN抗体投与群では明らかに生存率の改善が認められたが,抗TNFα抗体投与群ではさらに生存率が低下した.C. albicans 7N浮遊液を飲水させ,腸管内に定着していることを確認したSCIDマウスに抗TNFα抗体,抗γIFN抗体,cyclophosphamide(5mg 2回)を静注したが,いずれでも全身性のカンジダ症への進展は病理学的にも,菌学的にも認められなかった.1.0×106CFUを投与した全身性カンジダ感染症モデルに,IL-12 0.1μgを腹腔内に連日2週間投与したが,生存率の変化は認められなかった.1.5×106CFUを感染させた致死的全身性カンジダ感染症モデルでは,無処理群が4日目までしか生存しなかったのに対して,予防的に感染前日にIL-12 0.1μgを1回のみ腹腔内投与した群では,6日まで生存した.

Cryptococcosis is one of the serious deep-seated mycoses in immunocompromised patients, especially those with AIDS. Cryptococcus neoformans ordinarily lives in natural environments such as soil and reproduces in pigeon excreta. It spreads in the air and infects human by inhalation. We isolated C. neoformans from pigeon excreta in hospitals, private houses, parks in Nagasaki from October to December in 1994. C. neoformans was isolated from 4 of 8 samples (50%) of pigeon excreta and the isolation rate increased to 80% (4/5) if they were weathered excreta. Two patients with pulmonary cryptococcosis occurred in the last two years in the area where C. neoformans was isolated during that period. Epidemiological studies of clinical isolates and environmental isolates are important to determine its origin of infection and the route of transmission.

This study evaluated combination therapy with miconazole and flucytosine for treating deep seated mycosis. Both mycological and clinical efficacy against candidemia and pulmonary cryptococcosis were satisfactory: All four isolatedCandida spp. were eradicated and all four patients with candidemia were cured, while six of nine patients with pulmonary cryptococcosis exhibited clinical improvement. The efficacy of combination therapy appeared to be low against aspergillosis, since only one of two patients with invasive pulmonary aspergillosis and two of five patients with pulmonary aspergilloma exhibited clinical improvement. Nevertheless, the clinical efficacy against aspergillosis was higher than that obtained with monotherapy in our previous study. Adverse reactions were observed in 36% (13 of 36) and abnormal laboratory findings in 22% (8 of 36) of patients treated with combination therapy; these rates were higher than those reported for monotherapy. These increases were not due to changes in serum concentrations of the two drugs due to simultaneous administration. The findings of this study suggest that combination therapy with miconazole and flucytosine may be an alternative therapy for refractory mycoses for carefully chosen patients.

The in vitro and in vivo antifungal activities of liposomal amphotericin B (L-AMPH) and amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, were compared with those of conventional amphotericin B (Fungizone, AMPH). The acute intravenous toxicity was markedly lower in BALB/c mice; 50% lethal doses (LD50s) were 2.75 mg/kg in AMPH, 32.9 mg/kg in L-AMPH and75 mg/kg in ABLC. In vitro antifungal activities against Candida albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei were evaluated by the agar plate dilution method. The activities were unchanged against C. albicans, but MICs increased more than four fold in 18 of the 20 strains other than C. albicans in L-AMPH and in 9 of the 20 in ABLC. L-AMPH and ABLC were as efficacious as AMPH in the treatment of mice infected with C. albicans, and at a dose of 0.5 and 1.0 mg/kg of body weight, ABLC was more efficacious on survival A ten-times larger dose (10 mg/kg) of L-AMPH and ABLC was administered to mice with 100% survival, suggesting improved tolerability as compared to amphotericin B.

各種抗真菌剤の併用効果について,基礎的ならびに臨床的検討を行った.その結果,臨床分離カンジダ属に対する試験管内併用効果ではamphotericin B (AMPH)とfluconazole(FLCZ)の組合せにおいて相乗効果を認めた.またCryptococcus neoformansについてはflucytosine(5-FC)とFLCZ, Aspergillus fumigatusに対してはAMPHとmiconazole(MCZ)の組合せにおいて相乗効果を示す株が最も多かった.臨床的検討では抗真菌剤の単剤投与が無効であった肺クリプトコックス症3例にFLCZと5-FCの併用投与を行った結果,全例ともに優れた臨床効果を認めた.また,深在性真菌症20例にてMCZと5-FCの併用投与の臨床的効果を検討した結果,有効率は7/20例(35%),真菌学的効果は6/13例(46%)であった.副作用は10/20例(50%)に認められ,消化器症状が多く認められた.

In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater.

We evaluated the usefulness of PCR and antigen detection for the diagnosis of pulmonary aspergillosis. Forty-four serum samples from patients with pulmonary aspergillosis (33 with pulmonary aspergilloma, 4 with allergic bronchopulmonary aspergillosis, 4 with invasive pulmonary aspergillosis, and 3 with aspergillus pyothorax) were used in this study. PCR detection of Aspergillus DNA in serum samples was successful in 39 patients. Galactomannan antigen was detected by sandwich enzyme-linked immunosorbent assay in 25 patients and by latex agglutination test in 13 patients. Detection of Aspergillus DNA in serum samples by nested PCR had the highest sensitivity of the three methods tested for the diagnosis of pulmonary aspergillosis.

Basic and clinical evaluation of lysis centrifugation using Isolator 10 was performed and compared with culture bottle methods. Blood, which was inoculated with C. albicans, C. tropicalis or C. parapsilosis, was cultured using lysis centrifugation or culture bottle method. The culture duration of C. albicans and C. parapsilosis by lysis centrifugation was shorter than that by the culture bottle (BHI release). C. albicans, C. parapsilosis and C. tropicalis became culture-positive within 1 or 2 days after culture by lysis centrifugation. C. albicans and C. parapsilosis became positive 4 days and C. tropicalis 6-8 days after culture by the culture bottle (BHI super). Clinical evaluation of both blood culture method as performed from April 1990 to March 1994. Sixty samples (4.4%) were positive out of 1370 samples. Twenty eight samples (7.2%) were positive out of 389 samples, which were examined by both methods. Twenty two samples were positive by both methods and the rest of the 6 samples was positive only by Lysis centrifugation.