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1.
Shoichiro Hikami Atsushi Shiozaki Maki Kitagawa-Juge Daisuke Ichikawa Toshiyuki Kosuga Hirotaka Konishi Shuhei Komatsu Hitoshi Fujiwara Kazuma Okamoto Eigo Otsuji 《Digestive diseases and sciences》2017,62(3):652-659
Background
The inhibitor of apoptosis protein (IAP) family are reported to play important roles in cancer cells evading apoptosis. However, the significance of their expression in human esophageal squamous cell carcinoma (ESCC) cells remains uncertain.Aims
The present study aimed to investigate the role of the IAP family members in tumor necrosis factor-α (TNF-α)-induced apoptosis of human ESCC cells.Methods
Five human ESCC cell lines were pretreated with TNF-α, cycloheximide (CHX, protein synthesis inhibitor), epoxomicin (proteasome inhibitor). Apoptosis assay and protein study with Western blot testing were conducted. Knockdown experiments with IAP siRNA were conducted, and the effect on cell apoptosis was analyzed.Results
Significant apoptosis was induced in five ESCC cell lines by TNF-α plus CHX stimulation, but not when treated with TNF-α or CHX alone. The protein expression levels of cIAP1 and XIAP were decreased by treatment with TNF-α in the presence of CHX, and the degree of cIAP1 and XIAP expression decrease was correlated with sensitivity to TNF-α plus CHX-induced apoptosis. Epoxomicin suppressed TNF-α plus CHX-induced degradation of survivin, cIAP1, and XIAP, in addition to apoptosis. A caspase inhibitor (z-VAD-fmk) suppressed TNF-α plus CHX-induced apoptosis, but did not suppress degradation of survivin, cIAP1, and XIAP. Furthermore, cIAP1 or XIAP siRNA transfected cells underwent apoptosis in response to treatment with TNF-α alone. Double knockdown of both genes resulted in further increased apoptosis.Conclusion
cIAP1 and XIAP play an essential role in the resistance of ESCC cells against apoptosis.2.
Lingling Chen Sujie Ni Mei Li Chaoyan Shen Zhipeng Lin Yu Ouyang Fei Xia Li Liang Wenyan Jiang Runzhou Ni Jianguo Zhang 《Digestive diseases and sciences》2017,62(2):387-395
Background
BCCIP was originally identified as a BRCA2 interacting protein in humans and Ustilago maydis. It had low expression in some human cancer tissues. However, recent research indicated that many caretaker genes are also necessary for cell viability and their expression could contribute to tumor progression.Aim
To characterize whether BCCIP is a caretaker gene in esophageal squamous cell carcinoma (ESCC).Methods
Western blotting and immunohistochemistry were used to measure the expression of BCCIP β. In vitro studies were used to verify the effects of BCCIP β in Eca109 cells.Results
Expression of BCCIP β was notably higher in tumor tissues of ESCC and Eca 109 cells. Meanwhile, the immunohistochemistry stain revealed that BCCIP β was positively correlated with clinical pathologic variables such as tumor size and tumor grade, as well as Ki-67, and prompted poor prognosis. In vitro studies such as starvation and refeeding assay along with BCCIP β-shRNA transfection assay demonstrated that BCCIP β expression promoted proliferation of ESCC cells. In addition, BCCIP β downregulation by silencing RNA significantly decreased the rate of colony formation, alleviated cellular apoptosis and increased the chemosensitivity of cisplatin.Conclusions
This research first put forward that BCCIP β is an oncogene in human ESCC and contributes to the poor outcome of the deadly disease.3.
Koji Kono Kousaku Mimura Reo Yamada Daisuke Ujiie Suguru Hayase Takeshi Tada Hiroyuki Hanayama Aung Kyi Thar Min Masahiko Shibata Tomoyuki Momma Zenichirou Saze Shinji Ohki 《Esophagus》2018,15(1):1-9
Background
Immunotherapy has become a promising treatment strategy for cancer. Immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types including esophageal squamous cell carcinoma (ESCC). There are several clinical trials using anti-PD1 mAb for ESCC in early phases and the results are currently promising.Results and Conclusions
In this review, recent advances in cancer immunotherapy for ESCC are discussed with particular focus on immune checkpoint inhibitors and cancer vaccine.4.
Xue Hu Jingjing Ma Vikash Vikash Jiao Li Dandan Wu Ya Liu Jixiang Zhang Weiguo Dong 《Digestive diseases and sciences》2018,63(1):126-134
Background
Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC).Aims
To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo.Methods
The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis.Results
TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP.Conclusions
TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.5.
6.
Youichi Kumagai Kaiyo Takubo Kenro Kawada Morihiro Higashi Toru Ishiguro Jun Sobajima Minoru Fukuchi Keiichiro Ishibashi Erito Mochiki Junko Aida Tatsuyuki Kawano Hideyuki Ishida 《Esophagus》2016,13(2):200-207
Background
Use of an endocytoscopy system (ECS) makes it possible to omit biopsy histology for esophageal squamous cell carcinoma (ESCC). However, for differential diagnosis of ESCC, the endocytoscopic characteristics of esophagitis should be clarified.Methods
We examined the morphology of surface cells in 20 cases of gastroesophageal reflux disease (GERD) (Grade M: 6 cases, A: 5 cases, B: 1 cases, C: 4 cases, D: 4 cases), five cases of candida esophagitis, and one case of eosinophilic esophagitis. One endoscopist classified the lesions using the modified type classification, and one pathologist judged the endocytoscopy images as “neoplastic”, “borderline”, or “non-neoplastic”.Results
All cases of Grade M, A, and B GERD were classified as “type 1 or 2” by the endoscopist. However, 3/8 Grade C and D GERD lesions that had been diagnosed as regenerative squamous epithelium from biopsy histology were diagnosed as Type 3. All Grade M, A, and B cases were interpreted by the pathologist as “non-neoplastic”, whereas 4/8 Grade C and D GERD lesions, including three cases of regenerating epithelium, were diagnosed as “borderline” on the basis of ECS images. In 80 % of candida esophagitis cases, hyphae were visualized as white areas. Eosinophilic esophagitis showed a slight increase of cell density with marked infiltration of inflammatory cells.Conclusion
Some cases of severe GERD cannot be clearly distinguished from esophageal squamous cell carcinoma (ESCC) using ECS, and therefore at present, cases of ESCC coexisting with severe GERD should not be diagnosed by ECS alone and probably require biopsy. (UMIN000007627).7.
Ning Liu Yuan-Yuan Sun Xiao-Wen Zhang Sheng Chen Ye Wang Zhao-Xiong Zhang Shao-Wei Song Guang-Bin Qiu Wei-Neng Fu 《Digestive diseases and sciences》2015,60(7):2000-2008
Background
miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not.Aims
We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis.Methods
miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively.Results
Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3′UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects.Conclusions
It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.8.
Hiroshi Okamoto Yusuke Taniyama Tadashi Sakurai Takahiro Heishi Jin Teshima Chiaki Sato Shota Maruyama Ken Ito Yu Onodera Takuro Konno-Kumagai Hirotaka Ishida Takashi Kamei 《Esophagus》2018,15(4):281-285
Background
Recently, definitive chemoradiotherapy (dCRT) has become one of the essential treatment strategies for esophageal squamous cell carcinoma (ESCC) and has been especially gaining prevalence for cervical ESCC to preserve the larynx. Our department recently introduced dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for treating advanced cervical ESCC. This study aims to assess the safety and outcomes of DCF-R in patients with advanced cervical ESCC.Methods
We retrospectively assessed 11 patients with advanced cervical ESCC (clinical stage: II–IV, including T4b and/or M1 lymph node) who received DCF-R as the first-line treatment between December 2010 and February 2015.Results
Our patient cohort comprised 8 males and 3 females (median age 68 years; range 54–76 years). The pretreatment clinical stage included stage II (1), stage III (7), and stage IV (3) cases [including 3 patients with T4b (2 trachea and 1 thyroid) and 3 patients with M1 lymph node]. We attained complete response (CR) in 10 patients and stable disease in 1 patient. Of 10 patients with CR, 5 experienced recurrence and 5 continued exhibiting CR. Furthermore, grade 3 or more adverse events included leucopenia (91%), neutropenia (91%), febrile neutropenia (45%), and pharyngeal pain (55%). While the 2-year overall survival rate was 72%, the 2-year recurrent-free survival rate was 64%, respectively.Conclusions
DCF-R treatment for advanced cervical esophageal cancer could be completed by the careful administration; although a strong blood toxicity might occur, this treatment may provide the chance to obtain favorable prognosis with larynx preservation.9.
10.
Giovanni B. Gaeta Massimo Puoti Nicola Coppola Teresa Santantonio Raffaele Bruno Antonio Chirianni Massimo Galli 《Infection》2018,46(2):183-188
Aim
This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).Methods
This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.Results
Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.Conclusions
Early treatment with DAA should be offered when available.11.
Yasuo Hamamoto Masanori Nojima Yu Aoki Takeshi Suzuki Kenta Kawasaki Kenro Hirata Yasutaka Sukawa Akira Kasuga Hirofumi Kawakubo Hiroya Takeuchi Koji Murakami Hiromasa Takaishi Takanori Kanai Yuko Kitagawa 《Esophagus》2017,14(4):324-332
Background
Identifying clinical resectability of locally advanced esophageal squamous cell carcinoma (ESCC) is important, although inter-evaluator heterogeneity (IEH) could exist, especially in borderline resectable (BLR) cases. To investigate the extent of heterogeneity, we conducted clinical diagnostic imaging questionnaires.Materials and methods
Five cases with clinical T3 or T4 cases, which were treated with neo-adjuvant triplet chemotherapy followed by surgery, were selected as the model. These cases were divided into two groups: curative resected cases (#1–#3) and non-curative resected cases (#4 and #5). Only imaging slides were shown without any information about patient characteristics or clinical course. The evaluators consisted of surgeons (staff and non-staff), medical oncologists, and an imaging radiologist; a total of 25 medical staff answered the questionnaire. Two questions (1: clinical T stage before chemotherapy, 2: resectability after chemotherapy) were answered. Occupational differences were assessed by comparing the results to the imaging radiologist.Results
IEH was observed for clinical diagnosis before chemotherapy in one case (clinical T4: 52%, clinical T3: 48%). In the other cases, most evaluators diagnosed them as clinical T4, with 76–88% agreement. IEH for clinical resectability after chemotherapy was relatively small. Occupational IEH was observed in both before and after chemotherapy.Conclusion
IEH in decisions about treating BLR cases in ESCC should be considered in clinical practice. Multi-disciplinary teams are essential to overcome this problem.12.
Background
For patients with postoperative lymph node (LN) recurrent esophageal cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains controversial. We assessed the clinical outcomes and prognostic factors related to involved-field CRT for postoperative solitary LN recurrence of esophageal squamous cell carcinoma (ESCC).Methods
We retrospectively evaluated 21 patients who had received curative resection, with LN recurrence of ESCC. Patients received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60 Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals, and prognostic factors. We defined elective nodal failure (ENF) as recurrence in a regional LN without involved-field failure.Results
The median follow-up duration was 32 months (range, 4–106 months). Nine patients experienced failure—4 (19%) within involved-field and 5 (24%) with distant metastasis. No patients had ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was 78%. In the univariate analysis of OS, two factors, the maximal diameter of the metastatic LN?<?25 mm and the absence of serum p53 antibodies (s-p53-Abs), were associated with a significantly better prognosis (p?=?0.025 and p?=?0.01, respectively).Conclusions
Involved-field CRT for postoperative solitary LN recurrence of ESCC did not cause ENF and was without severe toxicities. Two factors, a length of the metastatic LN?<?25 mm and the absence of s-p53-Abs may improve the treatment outcome. Involved-field CRT is a treatment option worthy of consideration for postoperative solitary LN recurrence of ESCC.13.
Lena M. Biehl Rebeca Cruz Aguilar Fedja Farowski Werner Hahn Angela Nowag Hilmar Wisplinghoff Maria J. G. T. Vehreschild 《Infection》2018,46(6):871-874
Purpose
We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.Methods
FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.Results
The patient remained without symptoms after FMT.Conclusions
Underlying mechanisms of action need to be addressed in depth by future research.14.
15.
J. Daryl Thornton Catherine Sullivan Jeffrey M. Albert Maria Cedeño Bridget Patrick Julie Pencak Kristine A. Wong Margaret D. Allen Linda Kimble Heather Mekesa Gordon Bowen Ashwini R. Sehgal 《Journal of general internal medicine》2016,31(8):832-839
BACKGROUND
Low organ donation rates remain a major barrier to organ transplantation.OBJECTIVE
We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.DESIGN
This was a randomized controlled trial between February 2013 and May 2014.SETTING
The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.PATIENTS
The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.INTERVENTIONS
Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.MAIN MEASURES
The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.KEY RESULTS
Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).LIMITATION
How the observed increases in organ donation consent might translate into a greater organ supply is unclear.CONCLUSION
Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT0169713716.
BACKGROUND
Educating medical students about health disparities may be one step in diminishing the disparities in health among different populations. According to adult learning theory, learners’ opinions are vital to the development of future curricula.DESIGN
Qualitative research using focus group methodology.OBJECTIVES
Our objectives were to explore the content that learners value in a health disparities curriculum and how they would want such a curriculum to be taught.PARTICIPANTS
Study participants were first year medical students with an interest in health disparities (n?=?17).APPROACH
Semi-structured interviews consisting of 12 predetermined questions, with follow-up and clarifying questions arising from the discussion. Using grounded theory, codes were initially developed by the team of investigators, applied, and validated through an iterative process.MAIN RESULTS
The students perceived negative attitudes towards health disparities education as a potential barrier towards the development of a health disparities curriculum and proposed possible solutions. These solutions centered around the learning environment and skill building to combat health disparities.CONCLUSIONS
While many of the students’ opinions were corroborated in the literature, the most striking differences were their opinions on how to develop good attitudes among the student body. Given the impact of the provider on health disparities, how to develop such attitudes is an important area for further research.17.
Purpose
To determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection.Methods
Prospective observational study in a tertiary referral hospital in Malawi.Results
Predictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68–0.78)], increasing to 0.77 (95% CI 0.72–0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value.Conclusion
qSOFA is a simple tool that can aid risk stratification in resource-limited settings.18.
M. G. Pramateftakis P. Hatzigianni D. Kanellos G. Vrakas Th. Tsachalis I. Mantzoros I. Kanellos C. Lazaridis 《Techniques in coloproctology》2010,14(1):63-64
Aim
In this study, we present our patients with metachronous colorectal cancer.Patients and methods
In the period between 1990 and 2009, 670 patients with colorectal cancer were treated.Results
Metachronous cancer was developed in 4 (0.6%) patients. The time interval between index and metachronous cancer was 28 months to 22 years (mean 146 months).Conclusion
Metachronous colorectal cancer is a potential risk that proves the necessity of postoperative colonoscopic control of all patients with colorectal cancer.19.
Background
Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.Objectives
The psychosocial support given by self-help associations in different phases is evaluated.Materials and methods
Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.Results
On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.Conclusions
The removal of barriers and development of effective structures are overdue.20.
Grant R. Martsolf Ryan Kandrack Robert A. Gabbay Mark W. Friedberg 《Journal of general internal medicine》2016,31(7):723-731