A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01)
Osamu ItanoYusuke TakemuraNorihiro KishidaEiji TamagawaHiroharu ShinozakiKen‐ichi IkedaHidejiro UrakamiShigenori EiShigeo HayatsuKeiichi SuzukiTadayuki SakuragawaMasatsugu IshiiMasaya ShitoKoichi AiuraHiroto FujisakiKiminori TakanoJunichi MatsuiTakuya MinagawaMasahiro ShinodaMinoru KitagoYuta AbeHiroshi YagiGo OshimaShutaro HoriYuko Kitagawa
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Abstract Background: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. Methods: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m 2 /day orally twice daily on days 1–28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). Results: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. Conclusions : One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. Trial registration : UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347)Keywords:
Gallbladder Cancer
Adjuvant Therapy
Clinical endpoint
Intrahepatic Cholangiocarcinoma
Adjuvants are a critical component for vaccines, especially for a poorly immunogenic antigen, such as nicotine. However, the impact of adjuvant release rate from a vaccine formulation on its immunogenicity has not been well illustrated. In this study, we fabricated a series of hybrid-nanoparticle-based nicotine vaccines to study the impact of adjuvant release rate on their immunological efficacy. It was found that the nanovaccine with a medium or slow adjuvant release rate induced a significantly higher anti-nicotine antibody titer than that with a fast release rate. Furthermore, the medium and slow adjuvant release rates resulted in a significantly lower brain nicotine concentration than the fast release rate after nicotine challenge. All findings suggest that adjuvant release rate affects the immunological efficacy of nanoparticle-based nicotine vaccines, providing a potential strategy to rationally designing vaccine formulations against psychoactive drugs or even other antigens. The hybrid-nanoparticle-based nicotine vaccine with an optimized adjuvant release rate can be a promising next-generation immunotherapeutic candidate against nicotine.
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Esophageal motility disorder
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Intrahepatic Cholangiocarcinoma
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Intrahepatic Cholangiocarcinoma
Adjuvant Therapy
Neoadjuvant Therapy
Targeted Therapy
Adjuvant radiotherapy
Intrahepatic bile ducts
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Adenomyomatosis (ADM) of the gallbladder is a condition characterized by the proliferation of Rokitansky-Aschoff sinus (RAS), in which the epithelium of the gallbladder extends into the muscular layer, causing a thickening of the gallbladder wall. Although ADM is generally considered not to be a precancerous lesion of gallbladder cancer, there are some reports of cases of gallbladder cancer from ADM. Therefore, the relationship between ADM and gallbladder cancer remains controversial. We herein report a case of early-stage gallbladder cancer, BilIN3 (high grade), arising from ADM that was positive for ALDH1A1, an important marker of stem cells and cancer stem cells.
Adenomyomatosis
Gallbladder Cancer
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Electrostatic interactions and phosphate exchange are the most important mechanisms for the adsorption of antigens onto aluminum-containing adjuvant. But the immunogenicity of the final vaccine is not proportional to the amount and the adsorption strength of antigens onto aluminum-containing adjuvant. The stability of aluminum adjuvant would be decreased while it is stored in room temperature. However, it does not affect immune enhancement activity. Usually, aluminum adjuvant should avoid exposure to elevated temperature in long time, and buffer salts such as phosphate could be used to protect vaccines containing aluminum adjuvant. Now the new formulation of aluminum-adjuvanted vaccine dry powder can increase the stability of vaccines. This review describes recent studies on the interaction between aluminum adjuvant and antigens, the stability of vaccines containing aluminum adjuvant and the development tendency of aluminum adjuvant.
Vaccine adjuvant
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Objective To investigate the clinical value of contrast-enhanced ultrasound(CEUS) in the diagnosis of gallbladder cancer.Methods Twenty patients with gallbladder cancer and thirty-seven patients with benign gallbladder disease underwent conventional ultrasound and real-time CEUS.The enhancement patterns including types of time-intensity curve,centripetal fill-in,homogeneity and intensity of enhancement were analyzed.Results The focus and gallbladder wall in gallbladder cancers were enhanced at the same time,hepatic artery phase was mainly highly enhanced,hepatic portal vein phase was mairdy lowly enhanced.The percentages of those lesions that exhibited hyper-enhancement or iso-enhancement in the early phase and turned to hypo-enhancement within 35 s after contrast agent administration were 95.0%(19 /20) in gallbladder cancers and 16.2%(6 /37) in benign lesions(P = 0.000).Inhomogeneous enhancement was found 80.0%(16 /20) in gallbladder cancers and 23.3%(7 /30) in benign lesions (P =0.000).Destruction of the integrality of gallbladder wall was found 85.0%(17/20) in gallbladder cancers and none(0.0%,0 /37) in benign lesions(P = 0.000).The diagnose accordance rate、sensitivity and specificity of benign and malignant gallbladder diseases by CEUS was were 92.98% 、95.00% and91.83%,respectively.Conclusion CEUS can improve the diagnosis rates of gallbladder cancer and the ability of differentiating diagnosis between benign and malignant gallbladder diseases compared with conventional ultrasound.
Contrast-enhanced ultrasound
Gallbladder Cancer
Gallbladder disease
Adenomyomatosis
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Gallbladder cancer (GBC) has a high incidence in certain geographical regions. Morphologically, GBC presents as a mass replacing the gallbladder, a polypoidal lesion, or wall thickening. The incidence of preoperative diagnosis of wall thickening type of GBC is less well studied. The patterns of mural involvement and extramural spread are not well described in the literature. Additionally, wall thickening in the gallbladder does not always indicate malignancy and can be secondary to inflammatory or benign gallbladder diseases and extracholecystic causes and systemic pathologies. Objective reporting of gallbladder wall thickening will help us appreciate GBC's early features. In this review, we illustrate the imaging patterns of wall thickening type of GBC.
Gallbladder Cancer
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The similarity of gallbladder cancer and benign gallbladder lesions brings challenges to diagnosing gallbladder cancer (GBC). This study investigated whether a convolutional neural network (CNN) could adequately differentiate GBC from benign gallbladder diseases, and whether information from adjacent liver parenchyma could improve its performance.Consecutive patients referred to our hospital with suspicious gallbladder lesions with histopathological diagnosis confirmation and available contrast-enhanced portal venous phase CT scans were retrospectively selected. A CT-based CNN was trained once on gallbladder only and once on gallbladder including a 2 cm adjacent liver parenchyma. The best-performing classifier was combined with the diagnostic results based on radiological visual analysis.A total of 127 patients were included in the study: 83 patients with benign gallbladder lesions and 44 with gallbladder cancer. The CNN trained on the gallbladder including adjacent liver parenchyma achieved the best performance with an AUC of 0.81 (95% CI 0.71-0.92), being >10% better than the CNN trained on only the gallbladder (p = 0.09). Combining the CNN with radiological visual interpretation did not improve the differentiation between GBC and benign gallbladder diseases.The CT-based CNN shows promising ability to differentiate gallbladder cancer from benign gallbladder lesions. In addition, the liver parenchyma adjacent to the gallbladder seems to provide additional information, thereby improving the CNN's performance for gallbladder lesion characterization. However, these findings should be confirmed in larger multicenter studies.
Gallbladder Cancer
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Vaccine adjuvant
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