Mamiko Tsukui

Diagnosis of elevated-type early gastric cancers by the optimal band imaging system

BACKGROUND The endoscopic diagnosis of an elevated-type early gastric cancer is often difficult. The optimal band imaging (OBI) system can reconstruct the best spectral images decomposed from ordinary endoscopic images with free selection of 3 wavelengths and provide unmagnified images with high light intensity as well as magnified images. OBJECTIVE To evaluate whether the OBI system facilitates detection of the demarcation lines between an elevated-type early gastric cancer and surrounding tissue and thus is more helpful for performing endoscopic therapy. DESIGN A prospective study. SETTING Jichi Medical University, Japan. PATIENTS Seventy-five patients, 81 lesions with an elevated-type early gastric cancer. MAIN OUTCOME MEASUREMENTS A comparison between OBI images and conventional endoscopic images in the identification of the demarcation lines of an elevated-type early gastric cancer without magnification and the rate of success in identifying the abnormal surface structure of cancer by using low-magnified OBI images. RESULTS Demarcation lines were easily identified in OBI images, even without magnification, because such cancers could be clearly distinguished from the surrounding whitish atrophic mucosa. Inexperienced endoscopists could determine demarcation lines with significantly greater accuracy with unmagnified OBI images than with conventional images. With 40-fold magnification, irregular microstructural or nonstructural patterns were also found within cancer lesions in all cases studied but in none of the cases in the surrounding noncancerous mucosa. CONCLUSIONS The new contrast images obtained with the OBI system enable better determination of the demarcation lines of elevated-type early gastric cancers, and this system may be useful for performing endoscopic therapy of this type of cancer as a new endoscopic modality.

Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer‐promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein‐coupled receptor for short‐chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT‐PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short‐chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. (Cancer Sci 2009)

NEWLY DEVELOPED OPTIMAL BAND IMAGING SYSTEM FOR THE DIAGNOSIS OF EARLY GASTRIC CANCER

Background:  Magnifying narrow band imaging system is useful for the diagnosis of early gastric cancer. However, it is difficult for the operator of the scope to maintain the correct distance between the tip of the endoscope and the gastric mucosa for appropriate visualization. The newly developed optimal band imaging system can reconstruct good spectral images derived from ordinary endoscopic images and enhance the mucosal surface without magnification as well as with low magnification. This imaging technique is based on narrowing the bandwidth of the conventional image arithmetically, using spectral estimation technology.

Identification of the transforming activity of Indian hedgehog by retroviral expression screening

To identify novel cancer‐promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non‐cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ. (Cancer Sci 2009)

Short-Term Results of Laparoscopic Radiofrequency Ablation Using a Multipolar System for Localized Hepatocellular Carcinoma

Background and Aim: Multipolar radiofrequency ablation (RFA) is feasible for the treatment of hepatocellular carcinoma (HCC) for which a large ablative area is planned, and it imposes a light physical burden on patients. Multipolar RFA via the percutaneous approach is performed in the majority of cases, but the efficacy of multipolar RFA with a laparoscopic approach has rarely been studied. This study aimed to evaluate the efficacy and safety of multipolar laparoscopic RFA (LRA) for localized HCC over the short term. Methods: From January 2014 to January 2016, 77 consecutive patients with 130 HCCs treated by multipolar LRA were assessed. One to three bipolar needle applicators were inserted under laparoscopic ultrasonography guidance, regardless of tumor location. We intended to achieve parallel insertions and no-touch ablation as much as possible. Results: The median size of the main tumor was 22 mm (range, 10-42 mm). The median follow-up time was 13.6 months (range, 3.1-24.8 months). In all cases, a sufficient ablative area was obtained as planned, without thermal injury of adjacent organs. During the follow-up period, all patients were alive with no local tumor progression, while intrahepatic recurrence distant from the primary site occurred in 7 patients. The 2-year local tumor progression-free survival rate and overall cancer-free survival rate were 100 and 81.6%, respectively. There were no procedural major complications caused prolonging the hospitalization, and all patients were discharged without subjective symptoms 4-7 days after LRA. Conclusions: Multipolar LRA was efficacious in the treatment of localized HCCs by safely achieving a good ablative area.

The rendezvous technique involving insertion of a guidewire in a percutaneous transhepatic gallbladder drainage tube for biliary access in a case of difficult biliary cannulation

Endoscopic retrograde cholangiopancreatography (ERCP) is a diagnostic method and treatment approach for biliary diseases. However, biliary cannulation can be difficult in some cases. We performed ERCP in a 97-year-old woman with abdominal pain resulting from acute cholangitis caused by choledocholithiasis and observed difficult biliary cannulation. Eventually, the patient was successfully treated with the rendezvous technique. We could not cannulate the biliary duct during ERCP twice. Therefore, we placed a percutaneous transhepatic gallbladder drainage (PTGBD) tube without intrahepatic dilation. The rendezvous technique was performed using the PTGBD tube. The patient did not experience pancreatitis or perforation.

No Regional Disparities in Sofosbuvir Plus Ribavirin Therapy for HCV Genotype 2 Infection in Tochigi Prefecture and its Vicinity

Objective Regional disparities were observed in the outcomes of interferon (IFN)-based therapy for chronic hepatitis C virus (HCV) infection in a Japanese nationwide study. However, whether or not these regional disparities are observed in the outcomes of direct-acting antiviral drugs, including sofosbuvir (SOF) plus ribavirin (RBV) therapy, remains unclear. Methods We conducted a multicenter study to assess the efficacy of SOF plus RBV therapy for HCV genotype 2 infection in Tochigi Prefecture and its vicinity, in which IFN-based therapy yielded a low sustained virologic response (SVR) rate. In addition, we divided Tochigi Prefecture into six regions to examine regional disparities in the SVR. Patients We enrolled patients with chronic HCV genotype 2 infection. Results Of the 583 patients enrolled, 569 (97.6%) completed the treatment, and 566 (97.1%) also complied with post-treatment follow-up for 12 weeks. The overall SVR12 rate was 96.1% by per protocol and 93.7% by intention-to-treat analyses. No marked differences were observed in the SVR12 between subjects ≥65 and <65 years of age. Although large gaps were observed in the characteristics of patients and accessibility to medical resources, there was no significant difference in the SVR12 rate among the six regions in Tochigi Prefecture. Conclusion SOF plus RBV therapy was effective for HCV genotype 2 infection in an area where IFN-based therapy had previously shown unsatisfactory results. In addition, no regional disparities in the SVR12 were observed in Tochigi Prefecture.

A 79-year-old Woman with Acute Hepatitis B Caused by the Infection of Subgenotype D1 Hepatitis B Virus in Japan: A Case Study

A 79-year-old Japanese woman was diagnosed with acute hepatitis B based on laboratory tests showing positivity for IgM-class antibody against hepatitis B virus (HBV) core and hepatitis B surface antigen (HBsAg) as well as elevated transaminases. A phylogenetic analysis revealed that the HBV strain obtained from the patient belonged to genotype D/subgenotype D1, similar to strains circulating in foreign countries but different from those in Japan. The clinical course was favorable. HBsAg became negative within 10 weeks after the onset. To our knowledge, this is the first report of acute hepatitis B caused by subgenotype D1 HBV in Japan.