Toru Tani

Gastrointestinal tract perforation: CT diagnosis of presence, site, and cause

Gastrointestinal tract perforation is an emergent condition that requires prompt surgery. Diagnosis largely depends on imaging examinations, and correct diagnosis of the presence, level, and cause of perforation is essential for appropriate management and surgical planning. Plain radiography remains the first imaging study and may be followed by intraluminal contrast examination; however, the high clinical efficacy of computed tomographic examination in this field has been well recognized. The advent of spiral and multidetector-row computed tomographic scanners has enabled examination of the entire abdomen in a single breath-hold by using thin-slice sections that allow precise assessment of pathology in the alimentary tract. Extraluminal air that is too small to be detected by conventional radiography can be demonstrated by computed tomography. Indirect findings of bowel perforation such as phlegmon, abscess, peritoneal fluid, or an extraluminal foreign body can also be demonstrated. Gastrointestinal mural pathology and associated adjacent inflammation are precisely assessed with thin-section images and multiplanar reformations that aid in the assessment of the site and cause of perforation.

Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)-based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r(1) of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential.

The Relation Between Negative Emotional Suppression and Emotional Distress in Breast Cancer Diagnosis and Treatment

Our objective was to investigate differences in emotional distress between negative emotional suppression and expression patients in the progress of medical treatment, including the operation. We studied the differences in affective response between patients who suppress negative emotion and those who express negative emotion by using Profile of Mood States (McNair, Lorr, & Droppleman, 1971) at four sessions: (a) at the first visit to the clinic, (b) immediately after being told the diagnosis of breast cancer, (c) after the operation, and (d) at 3 months after discharge. Our results showed that emotional suppression patients tended to report more emotional distress (in particular, anxiety, depression, and anger) than did emotional expression patients on 3 sessions, the exception being after the operation. Also, patients who suppress anger and anxiety felt strong psychological distress. We suggest that it is essential to encourage suppressive patients to express both negative and positive emotion clearly and appropriately.

Differences in emotional distress between breast tumor patients with emotional inhibition and those with emotional expression

Abstract The differences in affective status between patients who restrain their negative emotion and those who express negative emotion after being given their breast cancer diagnosis were studied using the Profile of Mood States (POMS) at two sessions: (i) at the first visit to the outpatient surgery clinic, and (ii) immediately after being given the diagnosis of breast cancer. Eighty‐seven patients completed the POMS and the Courtauld Emotional Control Scale (CECS) at the first visit to the outpatient surgery clinic at Shiga University of Medical Science Hospital. They also completed the POMS immediately after being given the diagnosis of breast cancer. Breast cancer patients who restrain their negative emotion (n = 8) were highly anxious, depressed and confused after being given the diagnosis compared to breast cancer patients who express negative emotion (n = 8). Emotional distress in benign breast tumor patients was reduced after being given the diagnosis regardless of the trend of emotional inhibition. That is, emotional distress in patients who restrain their emotions was considerably increased compared with that of patients who expressed their emotions when they were faced with a life‐threatening disease. These results suggest that it may be therapeutic to advise breast cancer patients to express their negative emotion.

An initial clinical study on the efficacy of cisplatin-releasing gelatin microspheres for metastatic liver tumors

PURPOSE To evaluate the antitumor effect and side effects of cisplatin-releasing gelatin microspheres (Cis-GMSs) for metastatic liver tumors. METHODS Cis-GMSs that degraded over 14 days were employed. The subjects comprised a total of nine cases. Transcatheter hepatic artery embolization (TAE) using Cis-GMSs (Cis-GMSs-TAE) was performed 13 times in total. Six cases, each containing one to five tumors in a single segment to an entire lobe were treated by Cis-GMSs-TAE. In the remaining three cases with six or more metastatic liver tumors, the right and left lobes were treated by Cis-GMSs-TAE at a 2-week interval. RESULTS There were two complete response (CR), one partial response (PR) and six stable disease (SD) cases. The response rate was 33.3%. The average rate of reduction in tumor diameter was 32%. Disappearance of metastatic liver tumors was observed in only two of the nine cases. As for side effects and complications, post-embolization syndrome was observed in eight cases, but no severe complications such as cholangitis or liver abscess were observed. CONCLUSION Considering the mild side effects by Cis-GMSs-TAE, it is suggested that Cis-GMSs-TAE should be tried at least once as topical therapy for metastatic liver tumors when the response to systemic chemotherapy and other treatments is not satisfactory.

Late resistance to adenoviral p53-mediated apoptosis caused by decreased expression of Coxsackie-adenovirus receptors in human lung cancer cells

Adenovirus‐mediated wild‐type p53 gene transfer induces apoptosis in a variety of human cancer cells. Although clinical trials have demonstrated that a replication‐deficient recombinant adenovirus expressing the wild‐type p53 gene (Ad‐p53) is effective in suppressing growth of non‐small cell lung cancer (NSCLC), we often experienced late resistance to this treatment. To elucidate the mechanism of late resistance to Ad‐p53 in human lung cancer cells, we generated 5 different resistant variants from p53‐susceptible H1299 NSCLC cells by repeated infections with Ad‐p53. We first examined the transduction efficiency of adenoviral vector by Ad‐LacZ transduction followed by X‐gal staining in parental and 5 resistant H1299 cell lines. Their sensitivity to viral infection decreased in correlation with the magnitude of resistance, and Ad‐p53‐mediated tumor suppression could be restored by dose escalation of Ad‐p53 in the resistant variants. The expression of Coxsackie and adenovirus receptor (CAR) and αV integrins, which are cellular receptors for attachment and internalization of the virus, respectively, was next investigated in these cell lines. Flow cytometry revealed that αVβ3 and αVβ5 integrin expression was consistent, while p53‐resistant cell lines showed that diminished CAR expression correlated with the magnitude of the resistance. Our results demonstrated that decreased CAR expression could be one of the mechanisms of late resistance to Ad‐p53, which may have a significant impact on the outcome of adenovirus‐based cancer gene therapy.

New Method for the Detection of Bacterial Translocation Using Intestinal Permeability with Polyethylene Glycol 4000

Background: Currently, there is no method of accurately diagnosing bacterial translocation (BT) in humans. BT may be related to changes in intestinal permeability. In this study, we examined the correlation between intestinal permeability using polyethylene glycol (PEG) 4000 and BT. Materials and Methods: Under general anesthesia, laparotomy was done in rats, and PEG4000 was administered to the small intestine. We prepared models of invasive stimulation in which lipopolysaccharide (LPS) was intravenously administered, and a hemorrhagic shock model in which blood pressure was decreased to 30 mm Hg. Blood PEG4000 levels were measured. We also measured blood PEG levels in a model in which oxygen was administered to treat hemorrhagic shock. In all models, the presence or absence of BT development was evaluated. Results: In groups given LPS, mean blood PEG levels were significant higher than in the group treated with saline solution. In the hemorrhagic shock group, the mean PEG level was increased but was slightly inhibited by oxygen administration. In the LPS and hemorrhagic shock groups, the incidene of BT was significantly greater than in the control group. In the hemorrhagic shock group, the incidence of BT was 0% after oxygen administration. There was a correlation between the incidence of BT and changes in the intestinal permeability of PEG4000 (R2 = 0.824). Conclusions: LPS stimulation enhanced intestinal permeability in a dose-dependent manner. An increase in intestinal permeability was correlated with the incidence of BT. Blood PEG4000 levels correlated positively with the grade of invasion and the incidence of BT.

New Therapeutic Method Against Septic Shock — Removal of Endotoxin Using Extracorporeal Circulation

Polymyxin B has been shown to prevent endotoxin-induced mortality of mice and rabbits (9, 10), and to decrease the incidence of endotoxindisseminated intravascular coagulation (1). However, its use is limited only to oral or local administration because of its strong side effect on the central nervous system and the kidneys. Therefore, it cannot be used by intravenous injection for the therapy of endotoxemia. To solve problems, a new method of preparing polymyxin B by fixing it to an insoluble fiber was developed. We previously reported that polymyxin B would be covalently coupled to an insoluble fiber and could not be removed anymore by washing with isotonic saline (1, 3).

Relation of the Expression of Transcriptional Factor TFAP2B to That of Adipokines in Subcutaneous and Omental Adipose Tissues

To determine the potential role of the transcriptional factor‐activating enhancer‐binding protein‐2β (TFAP2B) in the regulation of expression of adipokines, adiponectin, leptin, and interleukin‐6 (IL‐6) in vivo, we quantified the mRNA expression levels of these adipokines and TFAP2B in visceral (omental) and abdominal subcutaneous adipose tissues of 66 individuals with variable degree of adiposity and studied their correlations with BMI and their plasma concentrations. We found that BMI correlated negatively with plasma adiponectin levels and positively with those of leptin. Adiponection mRNA expression in subcutaneous fat correlated negatively with BMI, whereas leptin mRNA levels in the omentum correlated with plasma leptin levels and BMI. In contrast, IL‐6 mRNA levels in subcutaneous and omental fat did not correlate with BMI. IL‐6 mRNA levels in the omental fat correlated with plasma IL‐6 levels. Whereas TFAP2B mRNA expression did not correlate with BMI, it correlated negatively with adiponectin expression in the subcutaneous adipose tissue. Furthermore, TFAP2B mRNA expression correlated negatively with leptin and positively with IL‐6 expression in both subcutaneous and omental adipose tissues. These relationships are consistent with our in vitro observations and indicate that TFAP2B seems to regulate the expression of various adipokines in vivo.

Cholangiocarcinoma in the distal bile duct: a probable etiologic association with choledocholithiasis.

Cholangiocarcinoma is a rare malignant disease, and recently the worldwide incidence of this malignancy has been gradually increasing. Overall, the annual incidence of cholangiocarcinoma is approximately 1.0 per 100,000 in the United States, 7.3 per 100,000 in Israel, 6.5 per 100,000 among American Indians, and 5.5 per 100,000 in Japan (1). Progress in diagnostic procedures such as endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP), and, recently, positron emission tomography (PET) scanning have probably contributed to the increase in the detection of early-stage cholangiocarcinoma, but this increase predated these technological advances. Cholangiocarcinoma is classified into three groups: intrahepatic, perihilar, and distal. The distal type is the second most common (27%), following the perihilar type (67%) (2). Cholangiocarcinoma is usually clinically silent, and unfortunately symptoms such as jaundice, abdominal pain, and weight loss usually emerge at an advanced stage that is beyond surgical excision. Surprisingly, about 50% of patients with extrahepatic cholangiocarcinomas are American Joint Committee of Cancer (AJCC) (3) TNM stage III upon presentation, and 10%–20% of them are found at stage IV (4). Therefore, curative surgical resections for extrahepatic cholangiocarcinoma are strikingly rare (only 22.5%), and the prognosis is bleak (5). However, the prognosis of patients with distal cholangiocarcinoma is more favorable than that of patients with