Junichiro Nakamura

The cost-effectiveness of the new protocol reflecting rapid virologic response to peginterferon α-2b and ribavirin for chronic hepatitis C

Objective Recent studies have reported the effectiveness of shorter courses of treatment with peginterferon &agr;-2b plus ribavirin for patients with chronic hepatitis C, who achieved a rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV-) RNA at week 4. The aim of this study was to evaluate the cost-effectiveness of the new protocol for treatment, from the perspective of RVR. Methods A cost-effectiveness analysis based on the rate of sustained virologic response was performed. A Markov cohort model of hepatitis C was constructed to demonstrate the clinical states on the basis of the assigned transition probabilities over 30 years. The treatment strategies were classified into five subgroups taking into consideration the viral genotypes, viral load, and RVR. The lifetime costs and quality-adjusted life years (QALYs) were compared between the new and standard protocols for treatment. Results Genotype 1-infected patients in the new protocol for treatment compared with the standard one could prolong QALYs by 0.33 and reduce lifetime cost by &U20AC; 5993. Genotype 2 or 3-infected patients in the new protocol for treatment compared with the standard one could prolong QALYs by 0.02 and reduce lifetime cost by &U20AC;2851. Conclusion Treatment strategies that consider viral load and RVR for patients with a low viral load infected with genotype 1 and those infected with genotype 2 or 3 are more cost-effective compared with the standard protocol for treatment.

A Fatal Aortoesophageal Fistula Caused by Critical Combination of Double Aortic Arch and Nasogastric Tube Insertion for Superior Mesenteric Artery Syndrome.

Double aortic arch (DAA) is a rare vascular congenital abnormality. Since a vascular ring surrounds bronchus and esophagus, any oral or nasal intubation can physically cause fatal aortoesophageal fistula (AEF). We report herein the first case of association of DAA and superior mesenteric artery (SMA) syndrome and the second case of AEF caused by nasogastric intubation in an adult with DAA. A 19-year-old woman visited our hospital for nausea and vomiting. She was diagnosed with SMA syndrome by computed tomography (CT). Nasogastric intubation relieved her symptoms in 4 days. Extramural compression with top ulceration was found in esophagogastroduodenoscopy on the 5th hospital day. She suddenly showed massive hematemesis on the 12th hospital day. AEF was found by CT. Soon, she died despite of intensive care. Retrospective interview disclosed the fact that DAA was pointed out in her childhood. We conclude that intubation must be avoided in DAA and a detailed clinical interview about DAA is mandatory to avoid AEF.

Hepatocellular carcinoma, with portal thrombus after viral eradication, disappeared by 5-fluorouracil and interferon.

Hepatocarcinogenesis after a sustained virological response (SVR) in type C chronic hepatitis and cirrhosis is an important issue in endemic areas; hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) therapy is especially very hard. We herein report a first case in which combination therapy with interferon-α and continuous intra-arterial infusion of 5-fluorouracil (designated as FAIT) provided a complete response in HCC with PVTT after SVR. Therefore, we think that FAIT is a good option to treat HCC with or without PVTT, even after SVR.

Laparoscopic peritoneal biopsy can be crucial for diagnosis of tuberculous peritonitis

A 28-year-old woman was admitted to a nearby hospital because of low-grade fever and lower abdominal pain, where ascites and slightly elevated serum CA125 level were found. Both acid-fast stain (AFS) and polymerase chain reaction (PCR) failed to detect Mycobacterium tuberculosis in her ascitic fluid, sputum, and gastric juice. She was referred to our division under suspicion of tuberculous peritonitis or ovarian carcinoma. Finally, diagnostic laparoscopy was carried out, showing yellowish-white small nodules disseminated on her whole peritoneum with thin fibrous adhesions. Peritoneal biopsy of these nodules showed epithelioid cell granulomas without caseous necrosis. AFS and PCR again failed to show any evidence of Mycobacterium tuberculosis in these biopsied samples. Based on the laparoscopic findings, however, we thought that she suffered from tuberculous peritonitis. Antituberculous therapy was started and she improved soon. Later, Mycobacterium tuberculosis was demonstrated in the 4-week culture of a peritoneal biopsy specimen. We conclude that laparoscopy may be the only way to detect Mycobacterium tuberculosis in tuberculous peritonitis whenever doubtful but no direct evidence is obtained.

Programs for calculating the statistical powers of detecting susceptibility genes in case–control studies based on multistage designs

Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs. Results: We developed programs for a multistage case–control association study using R language. In our programs, input parameters include numbers of samples and candidate loci, genome-wide false positive rate and proportions of samples and loci to be selected at the k-th stage (k=1,…, n). The programs output statistical powers, PPVs and numbers of typings in arbitrary n-stage designs. The programs can contribute to prior simulations under various conditions in planning a genome-wide association study. Availability: The R programs are freely available for academic users and can be downloaded from http://www.med.niigata-u.ac.jp/eng/resources/informatics/gwa.html Contact: nktmr@m12.alpha-net.ne.jp Supplementary information: Supplementary data are available at Bioinformatics online.

TTF-1 is useful for primary site determination in duodenal metastasis

We report here on a case of duodenal metastasis from primary lung adenocarcinoma. A 69-year old man was diagnosed with primary lung adenocarcinoma. Four courses of combined chemotherapy with carboplatin and paclitaxel associated with irradiation of 60 Gy shrunk the lung tumor. However, soon after,the para-aortic lymph node became swollen. Esophagogastroduodenoscopy revealed three duodenal tumors. Differential diagnosis between malignant lymphoma and metastatic duodenal cancer was endoscopically difficult. The histology of biopsied specimens was poorly differentiated adenocarcinoma. Immunohistochemical analysis revealed a positive reaction for thyroid transcription factor-1 (TTF-1). Thus, we concluded that these were metastatic duodenal tumors from lung adenocarcinoma. Two courses of gemcitabine led to a complete remission in this duodenal metastasis and para-aortic lymph node swelling with only scarring remaining in computed tomography. He is now on the continuous generalized chemotherapy. In conclusion, duodenal metastasis from primary lung adenocarcinoma is rare and hard to diagnose. In such an instance, TTF-1 immunostaining is crucial to obtain the correct diagnosis.

Thyroid Metastasis of Gastric Cancer: A Rare Occasion With Poor Prognosis

A 68-year-old man was diagnosed as having advanced gastric cancer. Computed tomography showed a thyroid tumor with trachea deviation. This tumor exhibited mosaic echogenecity in ultrasonography. Signet-ring cell carcinoma was found by means of fine needle aspiration biopsy. This tumor gradually became swollen and the thyroid hormone levels in blood were increased without any clinical symptom. Shortly, he died from his illness in the 29th hospital day. Autopsy disclosed that the left lobe of the thyroid gland was highly invaded by malignant cells and that lymphogenic rather than angiogenic metastasis was highly probable. Thyroid metastasis of gastric cancer is extremely rare. The prognosis is very poor. Ultrasonography is a very useful modality especially when coupled with recently developed fine needle aspiration biopsy in differential diagnosis of thyroid tumors once malignancy is suspected. Therapeutic strategy largely depends on the nature of primary malignant tumor. If the tumor is slowly progressive such as renal cell carcinoma and breast cancer, extirpation of thyroid tumors may extend life expectancy. In conclusion, the metastatic thyroid tumor of gastric cancer is rare and shows poor prognosis. Fine needle aspiration biopsy under ultrasonography is strongly recommended as a useful diagnostic tool.

Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes

AbstractA two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.

S1870 Clinical Significance of Cd38-Positive Plasma Cells Surrounding Interlobular Bile Ducts in Primary Biliary Cirrhosis (PBC)

Background/Aims: There has been increased interest in the potential role of B cells and antimitochondrial antibodies in PBC. Indeed a new paradigm in PBC includes the potential of B cells to act as both regulatory elements and as components of the inflammasone induced by apoptosis of biliary cells. We submit that a rigorous dissection of the inflammatory infiltrate in PBC will provide further insight on these issues. Materials and Methods: We took advantage of well-characterized Mabs to CD3, CD4, CD8, CD20, CD38, CD56, CD68, and pan-keratin antigens, and immunohistochemistry (IHC), to study the distribution of liver infiltrating CD38-positive plasma cells in 26 consecutive patients with PBC (AMA positive in 20 and negative in 6), all of whom had detailed staged clinical data. All data was “blindly” evaluated. We simultaneously studied 10 ageand gender-matched patients with chronic hepatitis C as a control. Results: Noteworthy within the IHC data was the presence of an intense coronal arrangement (CR) of CD38-positive cells around interlobular bile ducts, generally in specimens with chronic non-suppurative destractive cholangitis (CNSDC). In contrast, CD20-positive B lymphocytes (precursor cells of plasma cells) were found scattered and/or aggregated within the lymphoplasmocytic infiltration. Such CD20positive B cells also occasionally formed follicle-like aggregations but importantly were not observed in the proximity of CNSDC. PBC patients with CR demonstrated significantly higher titers of AMA (119.5±16.1 vs. 59.7±17.1, p=0.018) and lower levels of total cholesterol (TC) (195.1±9.0 vs. 223.6±9.6, p=0.04) than those without CR. Interestingly the CR correlated with titer of AMA (r=0.46), IgM (r=0.32), the presence of CNSDC (r=0.32) and inversely with age (r=-0.37), γ-GTP (r=-0.38) and TC (r=-0.41). In contrast, CD4and CD8-positive T lymphocyte infiltration was noted either in proximity of, or within the degenerated cholangioepithelium, suggesting the participation of these cells in the destructive processes of interlobular bile ducts. No CR was found in control subjects. Conclusion: The presence of CD38+ plasma cells surrounding biliary epithelium has clinical and serologic significance; further it correlates with disease progression exemplified by TC decrease and the development of florid duct lesions. These data further highlight the functional significance of B cells/ plasma cells; it also reflects a multilineage loss of tolerance in PBC. We submit that study of B cells in PBC should go beyond simple measurement of AMA titer and include rigorous phenotypical and functional dissection of the liver specific B cell lineage populations.